An introduction

Lung cancer is the leading cause of cancer mortality for men and women in the United States. While decreasing the risk for this cancer will occur through cessation of tobacco use, lung cancer will remain a major public health problem for decades to come even if all the national smoking cessation goals were met. This is because there are many former smokers and those who have been exposed to second hand smoke. Methods are needed to treat lung cancers and prevent them in the high- risk population of ex-smokers where genetic damage to the bronchial epithelium may have occurred. All-trans-retinoic acid (RA), a derivative of vitamin A, signals growth arrest and differentiation in tumor cell lines. It also causes complete remissions in acute promyelocytic leukemia. By altering gene expression of species involved in differentiation and by affecting regulatory molecules involved in cell cycle control via interactions with nuclear retinoid receptors (RARs and RXRs), RA has been shown to reverse aerodigestive tract preneoplasia in the clinic and cause growth suppression in preneoplastic cells. Further studies of the mechanisms engaged in these effects would be invaluable to overcome limitations involved in RA treatments by overcoming resistance to RA in lung carcinogenesis. To investigate RA resistance in the lung, we derived a resistant cell line designated as the BEAS-2B-R1 line from a RA sensitive bronchial epithelial cell line, BEAS-2B, by passage in 4 M RA cells. To determine the mechanism of resistance, the roles of the various retinoic acid receptors and the closely related rexinoid receptors were evaluated by Western analyses. Our findings point to suppression of the critical retinoid receptor, RAR, as the lesion responsible for retinoid resistance in human bronchial epithelial cells. preneoplasia in the clinic and cause growth suppression in preneoplastic cells. Further studies of the mechanisms engaged in these effects would be invaluable to overcome limitations involved in RA treatments by overcoming resistance to RA in lung carcinogenesis. To investigate RA resistance in the lung, we derived a resistant cell line designated as the BEAS-2B-R1 line from a RA sensitive bronchial epithelial cell line, BEAS-2B, by passage in 4 M RA cells. To determine the mechanism of resistance, the roles of the various retinoic acid receptors and the closely related rexinoid receptors were evaluated by Western analyses. Our findings point to suppression of the critical retinoid receptor, RAR, as the lesion responsible for retinoid resistance in human bronchial epithelial cells. e preneoplasia in the clinic and cause growth suppression in preneoplastic cells. Further studies of the mechanisms engaged in these effects would be invaluable to overcome limitations involved in RA treatments by overcoming resistance to RA in lung carcinogenesis. To investigate RA resistance in the lung, we derived a resistant cell line designated as the BEAS-2B-R1 line from a RA sensitive bronchial epithelial cell line, BEAS-2B, by passage in 4 M RA cells. To determine the mechanism of resistance, the roles of the various retinoic acid receptors and the closely related rexinoid receptors were evaluated by Western analyses. Our findings point to suppression of the critical retinoid receptor, RAR, as the lesion responsible for retinoid resistance in human bronchial epithelial cells.

Lung cancer is the leading cause of cancer mortality for men and women in the United States. While decreasing the risk for this cancer will occur through cessation of tobacco use, lung cancer will remain a major public health problem for decades to come even if all the national smoking cessation goals were met. This is because there are many former smokers and those who have been exposed to second hand smoke. Methods are needed to treat lung cancers and prevent them in the high- risk population of ex-smokers where genetic damage to the bronchial epithelium may have occurred. All-trans-retinoic acid (RA), a derivative of vitamin A, signals growth arrest and differentiation in tumor cell lines. It also causes complete remissions in acute promyelocytic leukemia. By altering gene expression of species involved in differentiation and by affecting regulatory molecules involved in cell cycle control via interactions with nuclear retinoid receptors (RARs and RXRs), RA has been shown to reverse aerodigestive tract preneoplasia in the clinic and cause growth suppression in preneoplastic cells. Further studies of the mechanisms engaged in these effects would be invaluable to overcome limitations involved in RA treatments by overcoming resistance to RA in lung carcinogenesis. To investigate RA resistance in the lung, we derived a resistant cell line designated as the BEAS-2B-R1 line from a RA sensitive bronchial epithelial cell line, BEAS-2B, by passage in 4 M RA cells. To determine the mechanism of resistance, the roles of the various retinoic acid receptors and the closely related rexinoid receptors were evaluated by Western analyses. Our findings point to suppression of the critical retinoid receptor, RAR, as the lesion responsible for retinoid resistance in human bronchial epithelial cells. preneoplasia in the clinic and cause growth suppression in preneoplastic cells. Further studies of the mechanisms engaged in these effects would be invaluable to overcome limitations involved in RA treatments by overcoming resistance to RA in lung carcinogenesis. To investigate RA resistance in the lung, we derived a resistant cell line designated as the BEAS-2B-R1 line from a RA sensitive bronchial epithelial cell line, BEAS-2B, by passage in 4 M RA cells. To determine the mechanism of resistance, the roles of the various retinoic acid receptors and the closely related rexinoid receptors were evaluated by Western analyses. Our findings point to suppression of the critical retinoid receptor, RAR, as the lesion responsible for retinoid resistance in human bronchial epithelial cells. e preneoplasia in the clinic and cause growth suppression in preneoplastic cells. Further studies of the mechanisms engaged in these effects would be invaluable to overcome limitations involved in RA treatments by overcoming resistance to RA in lung carcinogenesis. To investigate RA resistance in the lung, we derived a resistant cell line designated as the BEAS-2B-R1 line from a RA sensitive bronchial epithelial cell line, BEAS-2B, by passage in 4 M RA cells. To determine the mechanism of resistance, the roles of the various retinoic acid receptors and the closely related rexinoid receptors were evaluated by Western analyses. Our findings point to suppression of the critical retinoid receptor, RAR, as the lesion responsible for retinoid resistance in human bronchial epithelial cells.

Introduction: G-protein coupled receptors (GPCRs) translate outside information via specific ligands into inside signal transduction pathways that ultimately lead to a cellular response. Many GPCRs possess additional, allosteric binding sites that invite other ligands to affect its activity. Our visual pigment rhodopsin is a GPCR made up of the protein opsin and its ligand 11-cis-retinal, which acts as an inverse agonist to rhodopsin. We wanted to determine whether rhodopsin is subject to allosteric modulation with the ultimate goal of finding a therapy for retinal disorders that stem from genetic mutations in the phototransduction system. In rods and cones of the retina, K+ ions flows out of the inner segment while Na+ and Ca2+ flow into the outer segment, creating a closed electrical circuit called the dark current. Photon absorption closes ion channels in the outer segment plasma membrane, blocking Na+ and Ca2+ entry, which decreases the dark current. Thus, if drug affects any component of phototransduction, the cell’s response to light will change.

Introduction: G-protein coupled receptors (GPCRs) translate outside information via specific ligands into inside signal transduction pathways that ultimately lead to a cellular response. Many GPCRs possess additional, allosteric binding sites that invite other ligands to affect its activity. Our visual pigment rhodopsin is a GPCR made up of the protein opsin and its ligand 11-cis-retinal, which acts as an inverse agonist to rhodopsin. We wanted to determine whether rhodopsin is subject to allosteric modulation with the ultimate goal of finding a therapy for retinal disorders that stem from genetic mutations in the phototransduction system. In rods and cones of the retina, K+ ions flows out of the inner segment while Na+ and Ca2+ flow into the outer segment, creating a closed electrical circuit called the dark current. Photon absorption closes ion channels in the outer segment plasma membrane, blocking Na+ and Ca2+ entry, which decreases the dark current. Thus, if drug affects any component of phototransduction, the cell’s response to light will change.

INTRODUCTION Trends in laboratory animal use Annually many millions of animals are used worldwide, and steady increases in the use of genetically modified animals and several large scale chemical testing programs are Increasing laboratory animal use. Claims supporting laboratory animal use Biomedical research using laboratory animals is highly controversial. Advocates frequently claim such research Is vital for preventing, curing or alleviating human diseases (e.g., Brom 2002, Festing 2004a), that the greatest achievements of medicine have been possible only due to the use of animals (e.g., Pawlik 1998), and that the complexity of humans requires nothing less than the complexity of laboratory animals to effectively model during biomedical investigations (e.g., Kjellmer 2002). They even claim that medical progress would be "severely maimed by prohibition or severe curtailing of animal experiments," and that "catastrophic consequences would ensue" (Osswald 1992). The necessity of systematic reviews The premise that laboratory animal models are generally predictive of human outcomes is the basis for their widespread use In human toxicity testing, and In the safety and efficacy testing of putative chemotherapeutic agents and other clinical interventions. However, the numerous cases of discordance between human and laboratory animal outcomes suggest that this premise may well be incorrect, and that the utility of animal experiments for these purposes may not be assured. On the other hand, only small numbers of experiments are normally reviewed in such case studies, and their selection may be subject to bias. To provide more definitive conclusions, systematic reviews of the human clinical or toxicological utility of large numbers of animal experiments are necessary. Experiments included in such reviews are selected without bias, via randomisation or similarly methodical and impartial means. A growing number of such reviews and meta-analyses have been published, which collectively provide important insights into the human clinical and toxicological utility of animal models. Their identification and examination was the purpose of this review.

INTRODUCTION Trends in laboratory animal use Annually many millions of animals are used worldwide, and steady increases in the use of genetically modified animals and several large scale chemical testing programs are Increasing laboratory animal use. Claims supporting laboratory animal use Biomedical research using laboratory animals is highly controversial. Advocates frequently claim such research Is vital for preventing, curing or alleviating human diseases (e.g., Brom 2002, Festing 2004a), that the greatest achievements of medicine have been possible only due to the use of animals (e.g., Pawlik 1998), and that the complexity of humans requires nothing less than the complexity of laboratory animals to effectively model during biomedical investigations (e.g., Kjellmer 2002). They even claim that medical progress would be "severely maimed by prohibition or severe curtailing of animal experiments," and that "catastrophic consequences would ensue" (Osswald 1992). The necessity of systematic reviews The premise that laboratory animal models are generally predictive of human outcomes is the basis for their widespread use In human toxicity testing, and In the safety and efficacy testing of putative chemotherapeutic agents and other clinical interventions. However, the numerous cases of discordance between human and laboratory animal outcomes suggest that this premise may well be incorrect, and that the utility of animal experiments for these purposes may not be assured. On the other hand, only small numbers of experiments are normally reviewed in such case studies, and their selection may be subject to bias. To provide more definitive conclusions, systematic reviews of the human clinical or toxicological utility of large numbers of animal experiments are necessary. Experiments included in such reviews are selected without bias, via randomisation or similarly methodical and impartial means. A growing number of such reviews and meta-analyses have been published, which collectively provide important insights into the human clinical and toxicological utility of animal models. Their identification and examination was the purpose of this review.

Summary: We present a method for the integration of microarray datasets employing a fixed structure Bayesian network. We learn one set of network parameters per functional category, allowing us to focus on individual functions, data sets, and analysis techniques as desired. The outputs of these networks are integrated to produce a probability of functional relationship between any two genes. Motivation: Individual microarray data sets generally explore a particular experimental condition: response to heat shock, the cell cycle, iron transport , and various other cellular processes. When a biologist examines a gene with unknown function , though , it is not necessarily clear under which conditions it will respond. By combining many microarray data sets, it is possible to cover both many genes and many experimental conditions. This is not necessarily easy; simply concatenating data sets and finding correlation scores can be misleading, since related genes may not respond similarly under different conditions. We propose a method of predicting per-function and generalized relationships between gene pairs, the latter by integrating predictions from many functional categories. Our method also provides a means of detecting how well any one data set predicts functional relationships within a single functional category.

Summary: We present a method for the integration of microarray datasets employing a fixed structure Bayesian network. We learn one set of network parameters per functional category, allowing us to focus on individual functions, data sets, and analysis techniques as desired. The outputs of these networks are integrated to produce a probability of functional relationship between any two genes. Motivation: Individual microarray data sets generally explore a particular experimental condition: response to heat shock, the cell cycle, iron transport , and various other cellular processes. When a biologist examines a gene with unknown function , though , it is not necessarily clear under which conditions it will respond. By combining many microarray data sets, it is possible to cover both many genes and many experimental conditions. This is not necessarily easy; simply concatenating data sets and finding correlation scores can be misleading, since related genes may not respond similarly under different conditions. We propose a method of predicting per-function and generalized relationships between gene pairs, the latter by integrating predictions from many functional categories. Our method also provides a means of detecting how well any one data set predicts functional relationships within a single functional category.

Abstract This study relates patterns in sea otter resource selection to benthic habitat type and available sea otter prey quantity and quality in order to understand why otters frequent certain geographic areas over others. Findings suggest that hard bottom habitats and their associated prey communities are more heavily utilized by otters in the greater Kasitsna Bay area of Kachemak Bay, Alaska. Introduction The ability of sea otters to significantly reduce prey abundance, limit prey size, and consequently alter community structure has been well documented (Estes & Palmisano 1974, Estes et al. 1978). Much of this research, however, has focused on sea otter interactions with rocky habitats. Relatively little is known the otters ability to limit prey populations in soft-bott0m communities (K vitek et al. 1992) or how patterns in sea otter space use and foraging ecology respond to heterogeneous landscapes. In South Central Alaska, sea otters occupying the shallow broad shelf habitats of Kachemak Bay have equal access to both rocky and soft-bottom habitat types within their natural range. The proximity of different grain sizes in the bay provides a unique opportunity to relate known sea otter foraging activity to a particular substrate type and associated prey community. In this study, patterns in sea otter space use detected by telemetry and aerial observations will be described in terms of available habitat and prey. Biomass and energy per unit area will be used as currencies to compare the potential contribution of habitat types to sea otter diet. Understanding bow otters interact with a variety of available habitat types and prey fields in Kachemak Bay is critical to the monitoring and management of this species as it continues to stabilize in an ecologically, commercially, and recreationally important area in coastal Alaska.

Abstract This study relates patterns in sea otter resource selection to benthic habitat type and available sea otter prey quantity and quality in order to understand why otters frequent certain geographic areas over others. Findings suggest that hard bottom habitats and their associated prey communities are more heavily utilized by otters in the greater Kasitsna Bay area of Kachemak Bay, Alaska. Introduction The ability of sea otters to significantly reduce prey abundance, limit prey size, and consequently alter community structure has been well documented (Estes & Palmisano 1974, Estes et al. 1978). Much of this research, however, has focused on sea otter interactions with rocky habitats. Relatively little is known the otters ability to limit prey populations in soft-bott0m communities (K vitek et al. 1992) or how patterns in sea otter space use and foraging ecology respond to heterogeneous landscapes. In South Central Alaska, sea otters occupying the shallow broad shelf habitats of Kachemak Bay have equal access to both rocky and soft-bottom habitat types within their natural range. The proximity of different grain sizes in the bay provides a unique opportunity to relate known sea otter foraging activity to a particular substrate type and associated prey community. In this study, patterns in sea otter space use detected by telemetry and aerial observations will be described in terms of available habitat and prey. Biomass and energy per unit area will be used as currencies to compare the potential contribution of habitat types to sea otter diet. Understanding bow otters interact with a variety of available habitat types and prey fields in Kachemak Bay is critical to the monitoring and management of this species as it continues to stabilize in an ecologically, commercially, and recreationally important area in coastal Alaska.

Introduction Angiogenesis plays an important role in normal cyclical ovarian function. Relatively avascular preovulatory follicles develop into highly vascular corpus luteum. Vascular endothelial growth factor (VEGF) and Placental growth factor (PIGF) are known potent vascular mitogen factors with important functions in angiogenesis in many tissues.

Introduction Angiogenesis plays an important role in normal cyclical ovarian function. Relatively avascular preovulatory follicles develop into highly vascular corpus luteum. Vascular endothelial growth factor (VEGF) and Placental growth factor (PIGF) are known potent vascular mitogen factors with important functions in angiogenesis in many tissues.

Background • The independent pixel approximation (IPA) is known to have good accuracy for domain average fluxes in overcast cloud fields. • For broken clouds IPA may have significant errors in domain average fluxes due to net horizontal photon transport, such as cloud side leakage and cloud side illumination by the Sun. • Studies with simple cloud shapes have shown that size of the horizontal transport or "three-dimensional radiative" effect depends strongly on the cloud aspect ratio, cloud fraction, and solar zenith angle (SZA). • We hypothesize that the cloud thickness field and its relation to the optical depth field is the key to the three-dimensional radiative effect of broken clouds, since the IPA is exact in the limit of geometrically thin clouds. • We define the three dimensional radiative effect as the difference between the IPA and 30 domain averaged reflected or atmosphere absorbed fluxes. Overview: 1) Use many fair weather cumulus fields from a large eddy simulation model. 2) Generate approximate fields with different methods for cloud base height and thickness while keeping the original LWP and optical depth. 3) Calculate broadband domain average solar fluxes with a Monte Carlo model. 4) Compare the IPA-30 fluxes from the approximate and original fields.

Background • The independent pixel approximation (IPA) is known to have good accuracy for domain average fluxes in overcast cloud fields. • For broken clouds IPA may have significant errors in domain average fluxes due to net horizontal photon transport, such as cloud side leakage and cloud side illumination by the Sun. • Studies with simple cloud shapes have shown that size of the horizontal transport or "three-dimensional radiative" effect depends strongly on the cloud aspect ratio, cloud fraction, and solar zenith angle (SZA). • We hypothesize that the cloud thickness field and its relation to the optical depth field is the key to the three-dimensional radiative effect of broken clouds, since the IPA is exact in the limit of geometrically thin clouds. • We define the three dimensional radiative effect as the difference between the IPA and 30 domain averaged reflected or atmosphere absorbed fluxes. Overview: 1) Use many fair weather cumulus fields from a large eddy simulation model. 2) Generate approximate fields with different methods for cloud base height and thickness while keeping the original LWP and optical depth. 3) Calculate broadband domain average solar fluxes with a Monte Carlo model. 4) Compare the IPA-30 fluxes from the approximate and original fields.

INTRODUCTION Growth hormone-releasing hormone (GRF) and pituitary adenylate cyclase-activating polypeptide (PACAP) are two structurally related members of the glucagon superfamily that are involved in growth and development. Both hormones are produced in the brain and a variety of peripheral issues. For GRF, the primary function is to stimulate the release of growth hormone from the pituitary. For PACAP, the primary function is still unknown, but it can act as a neuromodulator, neurotrophic factor, smooth muscle relaxant and releasing factor in the pituitary, adrenal and pancreas. The physiological actions of GRF are mediated by the activation of a GRF specific 7-transmembrane G-protein coupled receptor. The physiological actions of PACAP are mediated by activation of two types of G-protein-coupled receptors. The first receptor type (PAC1) is PACAP specific and the second type (VPAC) is shared by a vasoactive intestinal peptide and PACAP. In mammals, three PACAP receptors have been isolated: PAC1, VPAC1 and VPAC2. In addition, nine isoforms of the PAC1 receptor have been found, including six isoforms involving the exclusion (short) or inclusion of three cassettes (hip, hop2, and hop2) alone or in combination in the 3rd intracellular loop.

INTRODUCTION Growth hormone-releasing hormone (GRF) and pituitary adenylate cyclase-activating polypeptide (PACAP) are two structurally related members of the glucagon superfamily that are involved in growth and development. Both hormones are produced in the brain and a variety of peripheral issues. For GRF, the primary function is to stimulate the release of growth hormone from the pituitary. For PACAP, the primary function is still unknown, but it can act as a neuromodulator, neurotrophic factor, smooth muscle relaxant and releasing factor in the pituitary, adrenal and pancreas. The physiological actions of GRF are mediated by the activation of a GRF specific 7-transmembrane G-protein coupled receptor. The physiological actions of PACAP are mediated by activation of two types of G-protein-coupled receptors. The first receptor type (PAC1) is PACAP specific and the second type (VPAC) is shared by a vasoactive intestinal peptide and PACAP. In mammals, three PACAP receptors have been isolated: PAC1, VPAC1 and VPAC2. In addition, nine isoforms of the PAC1 receptor have been found, including six isoforms involving the exclusion (short) or inclusion of three cassettes (hip, hop2, and hop2) alone or in combination in the 3rd intracellular loop.

Introduction Recent studies have suggested that soil respiration is the main determinant of carbon balance of terrestrial ecosystems (e.g. Valentini et al, 2001). To date, most soil respiration research has been based on surface flux data, which is the measurement of gas diffusion in response to a concentration gradient. However, surface fluxes of CO2 are a function of more than rootmicrobial production, but also the diffuse, advective, thermal and geochemical controls on CO2 transport and storage (Risk et al, 2002a and b). Using sampling of the subsurface CO2 concentrations at several depth intervals, we consider whether the temperature dependence of CO2 releases from soils would be better assessed using estimates of soil profile CO2 production rather than surface flux. We find that, unlike surface fluxes, subsurface CO2 production is closely regulated by soil temperature. In fact, a single regression between temperature and profile CO2 production can describe the relationship across the three land use types studied, meaning that soil respiration is more sensitive to the soil thermal regime than to the different ecosystem characteristics. We also found that relationships were improved further by using ‘soil heat content’ as opposed to a single soil temperature; the former better describes the energy available for subsurface biologic processes.

Introduction Recent studies have suggested that soil respiration is the main determinant of carbon balance of terrestrial ecosystems (e.g. Valentini et al, 2001). To date, most soil respiration research has been based on surface flux data, which is the measurement of gas diffusion in response to a concentration gradient. However, surface fluxes of CO2 are a function of more than rootmicrobial production, but also the diffuse, advective, thermal and geochemical controls on CO2 transport and storage (Risk et al, 2002a and b). Using sampling of the subsurface CO2 concentrations at several depth intervals, we consider whether the temperature dependence of CO2 releases from soils would be better assessed using estimates of soil profile CO2 production rather than surface flux. We find that, unlike surface fluxes, subsurface CO2 production is closely regulated by soil temperature. In fact, a single regression between temperature and profile CO2 production can describe the relationship across the three land use types studied, meaning that soil respiration is more sensitive to the soil thermal regime than to the different ecosystem characteristics. We also found that relationships were improved further by using ‘soil heat content’ as opposed to a single soil temperature; the former better describes the energy available for subsurface biologic processes.

The sun turns heavy matter into happy, chuckling, giggling, laughing light… which flies free into empty, open space —oh so happy to be free, to be light— Can you imagine it? Can you really? Ah, but a life of only 8 minutes —so short— before the light is caught by trees, and put to work. Trees use the energy in the light to grow, by changing air and water into new forms like wood and other parts of the tree. This is the story of light’s second life as parts of a tree and how we might use trees to power our cars.

The sun turns heavy matter into happy, chuckling, giggling, laughing light… which flies free into empty, open space —oh so happy to be free, to be light— Can you imagine it? Can you really? Ah, but a life of only 8 minutes —so short— before the light is caught by trees, and put to work. Trees use the energy in the light to grow, by changing air and water into new forms like wood and other parts of the tree. This is the story of light’s second life as parts of a tree and how we might use trees to power our cars.

Introduction The SSS Quality Management System (QMS) was developed by a cross-organization team directed by the SSS leadership group. The goal was to develop an SSS-wide approach to quality management that -aligned with RTT’s quality program -emphasized SSS-level quality standards -was bulk from the bottom up using best practices of each unit -included a workable governance plan for program monitoring and continuous improvement. In fall of 2006, a core Quality Committee was formed to lead this initiative. In summer of 2007, the committee, with the help of numerous quality representatives from across SSS, developed a beta version of the SSS QMS Quality Handbook and submitted it for review by all SSS staff. Following a 6-month review and comment period, the system was revised and expanded and officially launched in June 2008.

Introduction The SSS Quality Management System (QMS) was developed by a cross-organization team directed by the SSS leadership group. The goal was to develop an SSS-wide approach to quality management that -aligned with RTT’s quality program -emphasized SSS-level quality standards -was bulk from the bottom up using best practices of each unit -included a workable governance plan for program monitoring and continuous improvement. In fall of 2006, a core Quality Committee was formed to lead this initiative. In summer of 2007, the committee, with the help of numerous quality representatives from across SSS, developed a beta version of the SSS QMS Quality Handbook and submitted it for review by all SSS staff. Following a 6-month review and comment period, the system was revised and expanded and officially launched in June 2008.

Abstract Embryos of the african clawed frog, Xenopus laevis, are used in FETAX (frog embryo teratogenesis assay-Xenopus) to assess developmental toxicity of chemicals. Halogenated aromatic hydrocarbons, including 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), can be potent developmental and although assessments in X. laevis vary, some reports suggest that this species may also be relatively insensitive to TCDD. In other vertebrates, TCDD toxicity is mediated by the aryl hydrocarbon sensitivity and resistance in X. laevis, we have isolated cDNA sequences encoding AHR from 96 hour phylogenetic analysis demonstrates that both X. laevis AHRs are orthologs of mammalian AHR1; neither resmenles the AHR2 genes common to fish. The two proteins, AHR1 and AHR1, share 86% amino acid identity, suggesting that they evolved rather recently, perhaps coincident with the tetraploidization of acid identity, suggesting that they evolved rather recently, perhaps coincident with the tetraploidization of the Xenopus genome approximately 30 mya. FETAX is used as a model for predicting the developmental toxicity of materials to other vertebrates. An understanding of the molecular mechanisms underlying sensitivity differences to halogenated aromatic hydrocarbons should contribute to the development of this model for testing the toxicity of samples containing these compounds.

Abstract Embryos of the african clawed frog, Xenopus laevis, are used in FETAX (frog embryo teratogenesis assay-Xenopus) to assess developmental toxicity of chemicals. Halogenated aromatic hydrocarbons, including 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), can be potent developmental and although assessments in X. laevis vary, some reports suggest that this species may also be relatively insensitive to TCDD. In other vertebrates, TCDD toxicity is mediated by the aryl hydrocarbon sensitivity and resistance in X. laevis, we have isolated cDNA sequences encoding AHR from 96 hour phylogenetic analysis demonstrates that both X. laevis AHRs are orthologs of mammalian AHR1; neither resmenles the AHR2 genes common to fish. The two proteins, AHR1 and AHR1, share 86% amino acid identity, suggesting that they evolved rather recently, perhaps coincident with the tetraploidization of acid identity, suggesting that they evolved rather recently, perhaps coincident with the tetraploidization of the Xenopus genome approximately 30 mya. FETAX is used as a model for predicting the developmental toxicity of materials to other vertebrates. An understanding of the molecular mechanisms underlying sensitivity differences to halogenated aromatic hydrocarbons should contribute to the development of this model for testing the toxicity of samples containing these compounds.

Nothing like a nice stroll in the sun! But wait, who are those weird looking skeletons in the distance? And what’s wrong with them? My name is Fibrodysplasia Ossificans Progressiva. I’ve got a disease where my tendons turn to bone. My name is Achilles. I damaged the tendons in my legs with extreme exercise. My name is Bony Spur. Age made my tendons accumulate bony lumps in odd places. But how does this happen? Does anyone know? Actually, yes! Research is being undertaken to try to understand what happens when tendon turns to bone. A good model for studying the process behind this ossification is chicken, as their tendons naturally turn to bone when they age.

Nothing like a nice stroll in the sun! But wait, who are those weird looking skeletons in the distance? And what’s wrong with them? My name is Fibrodysplasia Ossificans Progressiva. I’ve got a disease where my tendons turn to bone. My name is Achilles. I damaged the tendons in my legs with extreme exercise. My name is Bony Spur. Age made my tendons accumulate bony lumps in odd places. But how does this happen? Does anyone know? Actually, yes! Research is being undertaken to try to understand what happens when tendon turns to bone. A good model for studying the process behind this ossification is chicken, as their tendons naturally turn to bone when they age.

Abstract Identification of novel drug targets in ovarian cancers has focused on expression of genes in the tyrosine kinase family. We have previously shown that the spleen tyrosine kinase (SYK) gene was expressed in 73% of 55 ovarian cancer specimens. Previous studies established the role of SYK in tumor progression. Among its many targets, SYK can bind microtubules and other molecules associated with the cytoskeleton. We found SYK to be expressed in 6 of 10 ovarian carcinoma cell lines. Because of the ability of SYK to bind into microtubules, we studied the relationship of SYK expression to cellular migration. We examined several ovarian cancer cell lines that variably express SYK to elucidate the potential effects of SYK on cell migration. Our results demonstrate that knockdown of SYK expression by siRNA resulted in a decreased capability of cells to migrate using a traditional wound scratch assay. The duration of this effect was dependent upon cell line used suggesting that additional protein targets may be involved in the migratory process. The potential effects of SYK expression on invasion are currently being investigated. We will evaluate potential upstream and downstream targets to elucidate the pathway(s) responsible for SYK effects and compare within the cell lines examined. Understanding the growth signals and proteins potentially responsible for invasion and metastasis in ovarian cancer cell lines and tumor samples may eventually lead to new therapeutic approached for ovarian cancers.

Abstract Identification of novel drug targets in ovarian cancers has focused on expression of genes in the tyrosine kinase family. We have previously shown that the spleen tyrosine kinase (SYK) gene was expressed in 73% of 55 ovarian cancer specimens. Previous studies established the role of SYK in tumor progression. Among its many targets, SYK can bind microtubules and other molecules associated with the cytoskeleton. We found SYK to be expressed in 6 of 10 ovarian carcinoma cell lines. Because of the ability of SYK to bind into microtubules, we studied the relationship of SYK expression to cellular migration. We examined several ovarian cancer cell lines that variably express SYK to elucidate the potential effects of SYK on cell migration. Our results demonstrate that knockdown of SYK expression by siRNA resulted in a decreased capability of cells to migrate using a traditional wound scratch assay. The duration of this effect was dependent upon cell line used suggesting that additional protein targets may be involved in the migratory process. The potential effects of SYK expression on invasion are currently being investigated. We will evaluate potential upstream and downstream targets to elucidate the pathway(s) responsible for SYK effects and compare within the cell lines examined. Understanding the growth signals and proteins potentially responsible for invasion and metastasis in ovarian cancer cell lines and tumor samples may eventually lead to new therapeutic approached for ovarian cancers.

Hey there! My name is Karen Howard, and I am a Masters student in the Bangia Lab. Now no one apoptose on me…all the information is still here, just presented more visually than you may be accustomed! Enjoy! ABSTRACT MHC Class I molecules are key in the anti-tumor and anti-viral responses of the immune system. MHC molecules are constitutively expressed on the surface of all nucleated cells, and require the assistance of multiple chaperones for correct folding, peptide loading and transport to the cell surface. Of the chaperones involved with the correct folding, TAP-Associated proteIN(tapasin) has been shown to be of utmost importance; downregulation or absence of tapasin results in the inability of the MHC heavy chain to associated with the TAP transporter to receive antigen. We know that cytokines may enhance antigen presentation by up-regulating the expression of genes involved with MHC Class I assembly and transport… BUT …little is known about how post-translational modifications regulate antigen presentation. We have discovered another level of MHC regulation involving the ribosome-associated Sec61 translocon complex of the endoplasmic reticulum (ER). Here, we show an interaction between tapasin and TRanslocon-Associated Protein Alpha (TRAPalpha), a ribosome-associated membrane protein (RAMP)in the ER membrane. Using biochemical fractionation to isolate ribosome-associated membrane proteins, we determined that TRAPalpha is required for tapasin and MHC heavy chain association with the translocon. I don’t really know how to read comics either, but apparently if you follow the arrows, you’ll be ok. (why do I always get the strange grad students?)

Hey there! My name is Karen Howard, and I am a Masters student in the Bangia Lab. Now no one apoptose on me…all the information is still here, just presented more visually than you may be accustomed! Enjoy! ABSTRACT MHC Class I molecules are key in the anti-tumor and anti-viral responses of the immune system. MHC molecules are constitutively expressed on the surface of all nucleated cells, and require the assistance of multiple chaperones for correct folding, peptide loading and transport to the cell surface. Of the chaperones involved with the correct folding, TAP-Associated proteIN(tapasin) has been shown to be of utmost importance; downregulation or absence of tapasin results in the inability of the MHC heavy chain to associated with the TAP transporter to receive antigen. We know that cytokines may enhance antigen presentation by up-regulating the expression of genes involved with MHC Class I assembly and transport… BUT …little is known about how post-translational modifications regulate antigen presentation. We have discovered another level of MHC regulation involving the ribosome-associated Sec61 translocon complex of the endoplasmic reticulum (ER). Here, we show an interaction between tapasin and TRanslocon-Associated Protein Alpha (TRAPalpha), a ribosome-associated membrane protein (RAMP)in the ER membrane. Using biochemical fractionation to isolate ribosome-associated membrane proteins, we determined that TRAPalpha is required for tapasin and MHC heavy chain association with the translocon. I don’t really know how to read comics either, but apparently if you follow the arrows, you’ll be ok. (why do I always get the strange grad students?)

Healthcare provision centres around providing the best available treatment for ‘Mrs Jones’. Research and evidence-based practice (EBP) are key underpinning components in achieving a best outcome and it is with these tools that we look to refine and develop our clinical practice. Full consideration however, needs to be given to the environment in which these approaches are both applied and delivered. Of the 1.3 million staff employed within the UK National Health Service, ‘medics’ – (whilst instigating the majority of treatment regimes in modern healthcare services), comprise less than 10% of the workforce. An ‘unseen-majority’ undertake the support and implementation of clinical objectives, and yet the differing levels of professionalism, academic development and comprehension, prohibits a standard approach to developing EBP. Unless research and education is adapted to meet a range of employment strata, there is little likelihood of an engaged and integrated approach to medicine and its paramedical disciplines. EBP serves to empower and equip staff at all levels. As such, any simplification of its approach should not be viewed as the ‘dilution’ of research science, but an inclusionist approach that promotes a broader subscription to the common healthcare ethic-we all want what is best for ‘Mrs Jones’.

Healthcare provision centres around providing the best available treatment for ‘Mrs Jones’. Research and evidence-based practice (EBP) are key underpinning components in achieving a best outcome and it is with these tools that we look to refine and develop our clinical practice. Full consideration however, needs to be given to the environment in which these approaches are both applied and delivered. Of the 1.3 million staff employed within the UK National Health Service, ‘medics’ – (whilst instigating the majority of treatment regimes in modern healthcare services), comprise less than 10% of the workforce. An ‘unseen-majority’ undertake the support and implementation of clinical objectives, and yet the differing levels of professionalism, academic development and comprehension, prohibits a standard approach to developing EBP. Unless research and education is adapted to meet a range of employment strata, there is little likelihood of an engaged and integrated approach to medicine and its paramedical disciplines. EBP serves to empower and equip staff at all levels. As such, any simplification of its approach should not be viewed as the ‘dilution’ of research science, but an inclusionist approach that promotes a broader subscription to the common healthcare ethic-we all want what is best for ‘Mrs Jones’.

Objective The proposed research addresses the outstanding need for an integrated approach to dissolve cellulosics, an abundant and renewable resource, as an essential step for their processing into fundamental understanding of cellulose-solvent molecular interactions, coupled with knowledge of the dissolution mechanism of semicrystalline cellulosic-solvent molecular interactions, can lead to the rational selection and optimization of solvent processing conditions for cellulosic biomass. In this project we consider the transport phenomena governing the dissolution of solid cellulose, e.g., solvent penetration, transformation from crystalline to amorphous domains, specimen swelling, and polymer chain untangling, and analyze the effect of various parameters on the kinetics of dissolution.

Objective The proposed research addresses the outstanding need for an integrated approach to dissolve cellulosics, an abundant and renewable resource, as an essential step for their processing into fundamental understanding of cellulose-solvent molecular interactions, coupled with knowledge of the dissolution mechanism of semicrystalline cellulosic-solvent molecular interactions, can lead to the rational selection and optimization of solvent processing conditions for cellulosic biomass. In this project we consider the transport phenomena governing the dissolution of solid cellulose, e.g., solvent penetration, transformation from crystalline to amorphous domains, specimen swelling, and polymer chain untangling, and analyze the effect of various parameters on the kinetics of dissolution.

Abstract Bioactivity networks derived from the CARLSBAD bioactivity database are multipartite in nature, in particular when evaluating the relationship between targets, pathways, compounds, and chemical patterns. Management and exploration of bioactivity knowledge demands high-level evaluations that are beyond network analytics. Here we introduce SmartGraph, an application that simplifies data analysis workflows into single-click tasks by utilizing novel, high-level bioactivity network concepts. The application provides means for effective data visualization and target-space navigation. SmartGraph serves as a front-end built on a back-end database that stores pre-processed information derived from CARLSBAD. This design allows for a quick-response, modular workflow execution that could potentially enhance early phase drug discovery, with respect to target prioritization, off-target analyses and drug repurposing.

Abstract Bioactivity networks derived from the CARLSBAD bioactivity database are multipartite in nature, in particular when evaluating the relationship between targets, pathways, compounds, and chemical patterns. Management and exploration of bioactivity knowledge demands high-level evaluations that are beyond network analytics. Here we introduce SmartGraph, an application that simplifies data analysis workflows into single-click tasks by utilizing novel, high-level bioactivity network concepts. The application provides means for effective data visualization and target-space navigation. SmartGraph serves as a front-end built on a back-end database that stores pre-processed information derived from CARLSBAD. This design allows for a quick-response, modular workflow execution that could potentially enhance early phase drug discovery, with respect to target prioritization, off-target analyses and drug repurposing.

Introduction The CQ Method The CQ method is a way to identify Y chromosome genes. The central parameter of the CQ method is the chromosome quotient (CQ), the ratio of female to male alignments to a selected reference sequence. Y chromosomes are present exclusively in males, so Y chromosome sequences can be accurately identified by their distinctive chromosome quotients.

Introduction The CQ Method The CQ method is a way to identify Y chromosome genes. The central parameter of the CQ method is the chromosome quotient (CQ), the ratio of female to male alignments to a selected reference sequence. Y chromosomes are present exclusively in males, so Y chromosome sequences can be accurately identified by their distinctive chromosome quotients.

Taxonomic Functional Transfer: TaFTan To understand the functional and metabolic activities of microbes and microbial communities, it is critical to link genes and proteins to their biological roles. This encompasses both their biochemical activities and the processes and pathways in which they are used by the cell. This problem is typically approached by transferring knowledge to newly sequenced genomes by relying on sequence similarity. This can be a difficult process involving sparse knowledge and the propagation of error, and even the best-studied organisms’ genomes are only partially characterized. To mitigate these issues, we have developed a data integration method leveraging all experimental results available from multiple model systems to identify potential functional roles for genes in a new organism.

Taxonomic Functional Transfer: TaFTan To understand the functional and metabolic activities of microbes and microbial communities, it is critical to link genes and proteins to their biological roles. This encompasses both their biochemical activities and the processes and pathways in which they are used by the cell. This problem is typically approached by transferring knowledge to newly sequenced genomes by relying on sequence similarity. This can be a difficult process involving sparse knowledge and the propagation of error, and even the best-studied organisms’ genomes are only partially characterized. To mitigate these issues, we have developed a data integration method leveraging all experimental results available from multiple model systems to identify potential functional roles for genes in a new organism.

History, Objectives This project has monitored the long-term retention and loss of Exxon Valdez oil (EVO) in Prince William Sound mussel beds since 1992. Most dense oiled mussel beds were not cleaned in 1998 and 1990 because aggressive techniques necessary to remove oil would have destroyed the beds. Natural rates of hydrocarbon loss were slower than anticipated and substantial quantities of EVO persisted in mussel bed sediments and overlying mussels. These contaminated beds remained a potential source of chronic hydrocarbon exposure for mussel consumers and other animals in the beds. To facilitate hydrocarbon loss, nine beds were restored in 1994 by manually removing mussels, replacing oiled sediments with clean sediments, and then replacing the mussels on the clean sediments. Concentrations in the replaced sediments remained low for the first year after restoration, and concentrations in mussels were at background levels in all but one bed. By 1996, however, there was evidence that oil was being reacquired from deeper sediments or surrounding areas. In 1999, we sampled sediments and mussels from 25 oiled mussel beds where concentrations of EVO in each bed were above baseline (52 part per million (ppm)) in 1995 or 1996 to monitor recovery and compare hydrocarbon loss in restored versus nonrestored beds.

History, Objectives This project has monitored the long-term retention and loss of Exxon Valdez oil (EVO) in Prince William Sound mussel beds since 1992. Most dense oiled mussel beds were not cleaned in 1998 and 1990 because aggressive techniques necessary to remove oil would have destroyed the beds. Natural rates of hydrocarbon loss were slower than anticipated and substantial quantities of EVO persisted in mussel bed sediments and overlying mussels. These contaminated beds remained a potential source of chronic hydrocarbon exposure for mussel consumers and other animals in the beds. To facilitate hydrocarbon loss, nine beds were restored in 1994 by manually removing mussels, replacing oiled sediments with clean sediments, and then replacing the mussels on the clean sediments. Concentrations in the replaced sediments remained low for the first year after restoration, and concentrations in mussels were at background levels in all but one bed. By 1996, however, there was evidence that oil was being reacquired from deeper sediments or surrounding areas. In 1999, we sampled sediments and mussels from 25 oiled mussel beds where concentrations of EVO in each bed were above baseline (52 part per million (ppm)) in 1995 or 1996 to monitor recovery and compare hydrocarbonloss in restored versus nonrestored beds.

Abstract At the University of Southern California, nineteen students from across the nation are brought together to study earthquake behavior at the Southern California Earthquake Center (SCEC). These students, coming from a wide range of academic interests, compose the intern class for the Undergraduate Studies in Earthquake Information Technology (UseIT). Each intern class is presented with a Grand Challenge – a task that can only be completed by combining each intern’s knowledge of computer science and earth science. It is the Media Team’s responsibility to document this collaboration and its development throughout the entirety of the internship. In order to accomplish this, the Media Team was in constant dialogue with each of the separate groups working on different aspects of the Grand Challenge. They collected multiple interviews with interns and supervisors each week and wrote the voice over narration for the documentary as the interviews were clipped. Shooting footage to be paired with the interviews in the documentary was a constant process, as was a logging and editing the footage filmed. As the Media Team experienced the internship, they decided UseIT would be best represented by having both a scientific documentary and more light-hearted intern experience video.

Abstract At the University of Southern California, nineteen students from across the nation are brought together to study earthquake behavior at the Southern California Earthquake Center (SCEC). These students, coming from a wide range of academic interests, compose the intern class for the Undergraduate Studies in Earthquake Information Technology (UseIT). Each intern class is presented with a Grand Challenge – a task that can only be completed by combining each intern’s knowledge of computer science and earth science. It is the Media Team’s responsibility to document this collaboration and its development throughout the entirety of the internship. In order to accomplish this, the Media Team was in constant dialogue with each of the separate groups working on different aspects of the Grand Challenge. They collected multiple interviews with interns and supervisors each week and wrote the voice over narration for the documentary as the interviews were clipped. Shooting footage to be paired with the interviews in the documentary was a constant process, as was a logging and editing the footage filmed. As the Media Team experienced the internship, they decided UseIT would be best represented by having both a scientific documentary and more light-hearted intern experience video.

Premise Benthic microalagae (microphytobenthos, MPB) production is generally considered not to be nutrient limited due to an inexhaustible supply of nutrients from the sediment.

Premise Benthic microalagae (microphytobenthos, MPB) production is generally considered not to be nutrient limited due to an inexhaustible supply of nutrients from the sediment.

INTRODUCTION The Priarie Pothole Region (PPR) is recognized as the most productive areas for waterfowl in North America. The productivity of the PPR relative to migratory birds is dependent upon abundant wetland and grassland resources from breeding habitat. For over 50 years, the U.S. Fish and Wildlife Service National Wildlife Refuge System (NWRS) has protected upland and wetland resources in the U.S. PPR by purchasing National Wildlife Refuges, and fee-title and perpetual easement Waterfowl Production Areas. In the PPR of North and South Dakota and northeastern Montana (hereafter R6 PPR), more than 0.5 million hectares of upland and nearly 0.5 million hectares of wetland habitat have been protected by the NWRS. Breeding waterfowl information is collected by the NWRS during the annual Four Square Mile Breeding Waterfowl Population and Habitat Survey (FSMS). In the PPR, this data has been used extensively to assess the biological outcomes for both breeding populations and production to evaluate conservation programs, and develop spatially explicit decision support tools for conservation delivery. Recent scenarios of potential temperature changes in the PPR presented by Johnson et al. (2005) predict a warmer, drier climate within the western and central portions of the PPR. Additional simulations that specifically address wetland hydro-period (Johnson et al. 2010), conclude that wetlands with temporary and seasonal water regimes will have shorter hydro-periods and as a result be too dry to support historic waterfowl population levels. Johnson et al. (2005, 2010) present concluded that conservation entities such as the NWRS should shift wetland and grassland conservation resources away from traditional areas, eastward in anticipation of projected climate changes. Some wildlife managers may accept these conclusions and argue for shifting funding from the current most productive areas of the PPR where valuable habitat remains to areas further east, where restoration of habitat is required. Others argue that it would take extreme differential changes in climate to render the western areas of the U.S PPR less productive than the far eastern areas where habitat loss is virtually complete due to conversion for other uses, and the cost is more expensive. We Examined the Potential Cost of Erring by Shifting Conservation Focus Away from the Current Productive Habitat s of the Central and Western PPR of North Dakota and South and northeast Montana, and toward eastern areas of North and South Dakota where most wetland and upland habitat has been converted to crop agriculture.

INTRODUCTION The Priarie Pothole Region (PPR) is recognized as the most productive areas for waterfowl in North America. The productivity of the PPR relative to migratory birds is dependent upon abundant wetland and grassland resources from breeding habitat. For over 50 years, the U.S. Fish and Wildlife Service National Wildlife Refuge System (NWRS) has protected upland and wetland resources in the U.S. PPR by purchasing National Wildlife Refuges, and fee-title and perpetual easement Waterfowl Production Areas. In the PPR of North and South Dakota and northeastern Montana (hereafter R6 PPR), more than 0.5 million hectares of upland and nearly 0.5 million hectares of wetland habitat have been protected by the NWRS. Breeding waterfowl information is collected by the NWRS during the annual Four Square Mile Breeding Waterfowl Population and Habitat Survey (FSMS). In the PPR, this data has been used extensively to assess the biological outcomes for both breeding populations and production to evaluate conservation programs, and develop spatially explicit decision support tools for conservation delivery. Recent scenarios of potential temperature changes in the PPR presented by Johnson et al. (2005) predict a warmer, drier climate within the western and central portions of the PPR. Additional simulations that specifically address wetland hydro-period (Johnson et al. 2010), conclude that wetlands with temporary and seasonal water regimes will have shorter hydro-periods and as a result be too dry to support historic waterfowl population levels. Johnson et al. (2005, 2010) present concluded that conservation entities such as the NWRS should shift wetland and grassland conservation resources away from traditional areas, eastward in anticipation of projected climate changes. Some wildlife managers may accept these conclusions and argue for shifting funding from the current most productive areas of the PPR where valuable habitat remains to areas further east, where restoration of habitat is required. Others argue that it would take extreme differential changes in climate to render the western areas of the U.S PPR less productive than the far eastern areas where habitat loss is virtually complete due to conversion for other uses, and the cost is more expensive. We Examined the Potential Cost of Erring by Shifting Conservation Focus Away from the Current Productive Habitat s of the Central and Western PPR of North Dakota and South and northeast Montana, and toward eastern areas of North and South Dakota where most wetland and upland habitat has been converted to crop agriculture.

Introduction Learning and memory are believed to involve in synapse changes. The cellular mechanisms for storing memory in the brain are not known. Long-term potentiation (LTP) (Bliss and Lomo, 1973; Bliss and Collinridge, 1993) represents unique physiological model for the search of structural corrleates of synaptic transmission. However, the structural basis of LTP expression still represents the subject of considerable debates (Muller et al., 2000; Sorra and Harris, 1998; Stewart et al., 2000; Toni et al. 1999, 2001). There is evidence for LTP remodeling occurring both at the pre- and posynaptic synaptic levels (Bliss and Collinridge, 1993), although last finding strongly argue for an important role played by postsynaptic receptors (Malenka and Nicoll, 1999). The most prominent role in postsynaptic mechanism of LTP plays the remodeling of dendritic spines and dendritic filopodia (Engert and Bonhoeffer, 1999; Fiala et al., 1998; Harris, 1999; Kirov and Harris 1999; Segal, 2001; Segal and Andersen, 2001; Sorra and Harris, 1998; Toni et al. 1999, 2001; Yuste and Bonhoeffer, 2001). The most part of the structural studies has been done in the dendate gyrus of the hippocampal formation in vivo and involved repeated stimulation of the performant path input. In this region the changes in synapse number and structure of dendritic spines have been reported to occur as early as 2-30 min after induction of LTP (Desmond and Levy, 1986a,b, 1998, 1990; Trommald and Hulleberg, 1997) and to have lasted for hours to days (Geinisman et al, 1991, 1994; Stewart et al., 2000). Remodeling of synapses in vivo showed experimental proofs regarding such natural biological models: in the course estrus of the rat (Wooley et al., 1990; Yankova et al., 2001), hibernation of ground squirrel (Popov and Bocharova, 1992; Popov et al., 1992), induced epilepsy after recurrent seizures in rat infancy (Jiang et al., 1998), in the course rat learning (Geinisman et al., 2001) and postnatal development of rat brain emerge or disappear depending on the age and activity of the neuron. Immature dendrites have more protrusions when the neurons have less synaptic activation, or when there is more local activation (Harris, 1999). In vitro synaptic activation of hippocampal neurons can induce outgrowth of dendritic filopodia and spines (Engert and Bonhoeffer, 2001). Conversely mature dendrite in vitro become increasingly spiny with reduction in synaptic activity (Kirov and Harris, 1999). These data show high lability of synaptic structure. However, real remodeling of both presynaptic and postsynaptic structure requires more intensive 3D reconstructions serial thin sections to understand synapse organization. So far, such studies are very rare. Postsynaptic density (PSD) is single marker for identification of synapses at ultrastructrual level. Knowledges about the density of synapses and fine details (volume, area, shape) of both PSDs and dendritic spines are very important in the search of morphological correlates of synaptic transmission. In last years there is a big progress for the study dendritic spines and presynaptic boutons using high resolution fluorescent microscopy (Engert and Bonhoeffer, 1999; Segal, 2001). Nevertheless, there are objective both limitations and difficulties for confocal microscopy usage: (i) it is possible to use only cultured neurons/organotypic cultures or surviving brain slices which must be places in artificial medium; (ii) in contrast to electron microscopy (EM) there is limitation for resolution that does not allow to estimate correct curvature of surface of small both spines and boutons; (iii)impossible to distinguish neighboring spines because of their overlapping; (iiii) the absence of control for penetration fluorescent dye and its interactions with cytosol ingredients that depends from functional state of nervous tissue. Usefulness of the confocal microscopy for synaptic details and for a study of the presynaptic elements was described previously (Harris, 1994; Moser et al., 1997). Single-section analysis are no recognized to be accurate because individual synapses might be identified incorrectly or missed and variability in synapse density, shape and size, including synapse orientation substantially influences the probability of viewing them on a random single sections (Braendgaard and Gundersen, 1986; Coggeshall and Lecan, 1996; Fiala and Harris, 2001; Harris, 1994) Advances in computer technology, particularly in personal computer hardware and software allow to use serial electron microscopic image registration for next stereoloical analysis and 3D reconstructuin of any synaptic organelles (for details see: Fiala and Harris, 2001). Fiala and Harris (2001) has developed new relatively simple software (IGL Trace) for unbiased reconstruction of synaptic structures usinf serial sections (for details see: “http://synapses. bu.edy/index.asp”). The phase of LTP which requires enhanced protein synthesis (both in vivo and in vitro) is believed to begin 2-5 h after induction of potentiation (Frey and Morris, 1997). This argues that more prominent structural changes, if any, are likely to occur after this period. Previously (Sorra and Harris, 1998) the stereological analysis including 3D reconstructions of various synapses showed that LTP did not cause and overall formation of new synapses at 2 hr post-tetanus in hippocampal area CA1 in vitro and this study supported the hypothesis that LTP could involve a redistribution of synaptic weights among existing synapses. Controversial data were observed by Toni et al. (2001) CA1 synapses using organotypic slice cultures. These authors showed the increase in the proportion of synapses with perforated PSDs and formation multiple spine buttons. However, the absence of quantitative stereological analysis of distributions and density of different categories synapses similar to Sorra and Harris (1998) does not allow to estimate the changes in number of synapses (density) after LTP induction to compare with confocal micrsopy data (Engert and Bonhoeffer, 1999; Korkotian and Segal, 2001). To understand better the functional implication of the different types of synapses observed after LTP induction we used both stereological analysis and 3D reconstructions of serial 70nm-thick sections according to methodology of Harris (1994). Hippocampus from left brain hemisphere was subjected to tetanic electrical stimulation while the hippocampal formation in right brain hemisphere was used as “control”. Besides, we used electrical stimulation without LTP as additional “control”.

Introduction Learning and memory are believed to involve in synapse changes. The cellular mechanisms for storing memory in the brain are not known. Long-term potentiation (LTP) (Bliss and Lomo, 1973; Bliss and Collinridge, 1993) represents unique physiological model for the search of structural corrleates of synaptic transmission. However, the structural basis of LTP expression still represents the subject of considerable debates (Muller et al., 2000; Sorra and Harris, 1998; Stewart et al., 2000; Toni et al. 1999, 2001). There is evidence for LTP remodeling occurring both at the pre- and posynaptic synaptic levels (Bliss and Collinridge, 1993), although last finding strongly argue for an important role played by postsynaptic receptors (Malenka and Nicoll, 1999). The most prominent role in postsynaptic mechanism of LTP plays the remodeling of dendritic spines and dendritic filopodia (Engert and Bonhoeffer, 1999; Fiala et al., 1998; Harris, 1999; Kirov and Harris 1999; Segal, 2001; Segal and Andersen, 2001; Sorra and Harris, 1998; Toni et al. 1999, 2001; Yuste and Bonhoeffer, 2001). The most part of the structural studies has been done in the dendate gyrus of the hippocampal formation in vivo and involved repeated stimulation of the performant path input. In this region the changes in synapse number and structure of dendritic spines have been reported to occur as early as 2-30 min after induction of LTP (Desmond and Levy, 1986a,b, 1998, 1990; Trommald and Hulleberg, 1997) and to have lasted for hours to days (Geinisman et al, 1991, 1994; Stewart et al., 2000). Remodeling of synapses in vivo showed experimental proofs regarding such natural biological models: in the course estrus of the rat (Wooley et al., 1990; Yankova et al., 2001), hibernation of ground squirrel (Popov and Bocharova, 1992; Popov et al., 1992), induced epilepsy after recurrent seizures in rat infancy (Jiang et al., 1998), in the course rat learning (Geinisman et al., 2001) and postnatal development of rat brain emerge or disappear depending on the age and activity of the neuron. Immature dendrites have more protrusions when the neurons have less synaptic activation, or when there is more local activation (Harris, 1999). In vitro synaptic activation of hippocampal neurons can induce outgrowth of dendritic filopodia and spines (Engert and Bonhoeffer, 2001). Conversely mature dendrite in vitro become increasingly spiny with reduction in synaptic activity (Kirov and Harris, 1999). These data show high lability of synaptic structure. However, real remodeling of both presynaptic and postsynaptic structure requires more intensive 3D reconstructions serial thin sections to understand synapse organization. So far, such studies are very rare. Postsynaptic density (PSD) is single marker for identification of synapses at ultrastructrual level. Knowledges about the density of synapses and fine details (volume, area, shape) of both PSDs and dendritic spines are very important in the search of morphological correlates of synaptic transmission. In last years there is a big progress for the study dendritic spines and presynaptic boutons using high resolution fluorescent microscopy (Engert and Bonhoeffer, 1999; Segal, 2001). Nevertheless, there are objective both limitations and difficulties for confocal microscopy usage: (i) it is possible to use only cultured neurons/organotypic cultures or surviving brain slices which must be places in artificial medium; (ii) in contrast to electron microscopy (EM) there is limitation for resolution that does not allow to estimate correct curvature of surface of small both spines and boutons; (iii)impossible to distinguish neighboring spines because of their overlapping; (iiii) the absence of control for penetration fluorescent dye and its interactions with cytosol ingredients that depends from functional state of nervous tissue. Usefulness of the confocal microscopy for synaptic details and for a study of the presynaptic elements was described previously (Harris, 1994; Moser et al., 1997). Single-section analysis are no recognized to be accurate because individual synapses might be identified incorrectly or missed and variability in synapse density, shape and size, including synapse orientation substantially influences the probability of viewing them on a random single sections (Braendgaard and Gundersen, 1986; Coggeshall and Lecan, 1996; Fiala and Harris, 2001; Harris, 1994) Advances in computer technology, particularly in personal computer hardware and software allow to use serial electron microscopic image registration for next stereoloical analysis and 3D reconstructuin of any synaptic organelles (for details see: Fiala and Harris, 2001). Fiala and Harris (2001) has developed new relatively simple software (IGL Trace) for unbiased reconstruction of synaptic structures usinf serial sections (for details see: “http://synapses. bu.edy/index.asp”). The phase of LTP which requires enhanced protein synthesis (both in vivo and in vitro) is believed to begin 2-5 h after induction of potentiation (Frey and Morris, 1997). This argues that more prominent structural changes, if any, are likely to occur after this period. Previously (Sorra and Harris, 1998) the stereological analysis including 3D reconstructions of various synapses showed that LTP did not cause and overall formation of new synapses at 2 hr post-tetanus in hippocampal area CA1 in vitro and this study supported the hypothesis that LTP could involve a redistribution of synaptic weights among existing synapses. Controversial data were observed by Toni et al. (2001) CA1 synapses using organotypic slice cultures. These authors showed the increase in the proportion of synapses with perforated PSDs and formation multiple spine buttons. However, the absence of quantitative stereological analysis of distributions and density of different categories synapses similar to Sorra and Harris (1998) does not allow to estimate the changes in number of synapses (density) after LTP induction to compare with confocal micrsopy data (Engert and Bonhoeffer, 1999; Korkotian and Segal, 2001). To understand better the functional implication of the different types of synapses observed after LTP induction we used both stereological analysis and 3D reconstructions of serial 70nm-thick sections according to methodology of Harris (1994). Hippocampus from left brain hemisphere was subjected to tetanic electrical stimulation while the hippocampal formation in right brain hemisphere was used as “control”. Besides, we used electrical stimulation without LTP as additional “control”.

Here, we present a new model of the actin filament (F-actin) that incorporates the global structure of a recently published model but also conserves internal stereochemistry. The improved quality of the model is apparent in a comparison made of the model with other recent F-actin models using molecular dynamics (MD) stimulation, monitoring a number of structural determinants. In addition, stimulations of the model are carried out in states with both ADP or ATP bound and local hydrogen-bonding differences characterized. The results point to the significance of a direct interaction of Gln137 with ATP for activation of ATPase activity after the G-to-F-actin transition. Introduction The atomic-detail structure of F-actin is still unknown. We propose a new model of F-actin, “Holmes 2010”, which was built using a straightforward approach in which priority was given to keeping the stereochemistry within the actin protomer intact while altering the position of the two actin domains to account for the global conformational change during the G-to-F-actin transition. A comparison is made of the structures and dynamics of Holmes 2010 with Oda 2009 and Holmes 2004 by subjecting them to MD stimulation. The nucleotide effects (ADP or ATP) on the conformation of the filament are also studied with a particular focus on the the G-to-F-actin ATPase activation

Here, we present a new model of the actin filament (F-actin) that incorporates the global structure of a recently published model but also conserves internal stereochemistry. The improved quality of the model is apparent in a comparison made of the model with other recent F-actin models using molecular dynamics (MD) stimulation, monitoring a number of structural determinants. In addition, stimulations of the model are carried out in states with both ADP or ATP bound and local hydrogen-bonding differences characterized. The results point to the significance of a direct interaction of Gln137 with ATP for activation of ATPase activity after the G-to-F-actin transition. Introduction The atomic-detail structure of F-actin is still unknown. We propose a new model of F-actin, “Holmes 2010”, which was built using a straightforward approach in which priority was given to keeping the stereochemistry within the actin protomer intact while altering the position of the two actin domains to account for the global conformational change during the G-to-F-actin transition. A comparison is made of the structures and dynamics of Holmes 2010 with Oda 2009 and Holmes 2004 by subjecting them to MD stimulation. The nucleotide effects (ADP or ATP) on the conformation of the filament are also studied with a particular focus on the the G-to-F-actin ATPase activation

Introduction: The goal of this study is to compare feeding patterns of larval and juvenile walleye Pollack (Theragara chalcogramma) and Pacific cod (Gadus macrocephalus). Poor recruitment success during warm years (e.g., 2001-2005) lead to reduced pollock biomass in the eastern Bering Sea (Ianelli et al. 2007). Feeding success, thus growth, during the first summer is an important prerequisite for overwinter survival and subsequent recruitment success (Sogard 1997; Sogard and Olla 2000). While age-0 pollock were ubiquitous and were collected at all stations over the entire eastern Bering Sea shelf from 1996-2000 (Duffy-Anderson et al. 2006). These observations suggest that larval and juvenile pollock cod may exploit similar prey fields, presenting a potential for dietary overlap and possible competition for prey resources.

Introduction: The goal of this study is to compare feeding patterns of larval and juvenile walleye Pollack (Theragara chalcogramma) and Pacific cod (Gadus macrocephalus). Poor recruitment success during warm years (e.g., 2001-2005) lead to reduced pollock biomass in the eastern Bering Sea (Ianelli et al. 2007). Feeding success, thus growth, during the first summer is an important prerequisite for overwinter survival and subsequent recruitment success (Sogard 1997; Sogard and Olla 2000). While age-0 pollock were ubiquitous and were collected at all stations over the entire eastern Bering Sea shelf from 1996-2000 (Duffy-Anderson et al. 2006). These observations suggest that larval and juvenile pollock cod may exploit similar prey fields, presenting a potential for dietary overlap and possible competition for prey resources.

Abstract Our experiment examined the role that two different phospholipases play in the development of Arabidopsis thaliana root apical meristem architecture. The phospholipases (PLC and PLD) both synthesize phosphatidic acid (PA), a lipid second messenger, but go about it differently. We were interested in whether the PA derived from either PLC of PLD is more important for proper meristem development. We observed that certain PLC and certain PLD treatments make a difference in transcription factor levels (and thus cell identity) and root architecture. However, certain doubts about the specificity of the treatments mean that we cannot necessarily attribute our observations to our proposed pathway. The data collected suggest many interesting future projects. Introduction The principal focus of the Herrera lab (Departamento de Ingeniería Genética, CINVESTA V-IPN) in Irapuato, Mexico, is how plants acquire phosphorous and use it efficiently. The lab uses Arabidopsis thaliana mutants and marker lines to study the physiological mechanisms by which plants obtain sufficient phosphorus (P) when P is scarce. Interestingly, the abdunance of phospholipids decreases during P-starvation, while the abdundance of other lipids increases. We hypothesize that phospholipids are broken down to phosphatidic acid (PA) during P-starvation to make phosphorus available for metabolic functions, and/or to trigger stress-response processes. PA can be derived from the phospholipase C (PLC) or phospholipase D (PLD) pathway (Fig 1, Fig 2). Our project examines the effect of manipulatin PA levels synthesized by different pathways on a group of mitotically inactive cells in the root apical meristem, called the quiescent center (QC) (Fig 5). Since this was a “fishing” experiment, rather than predicting which pathway will prove more important in conferring cell identity and organization, we hoped to disprove the null hypothesis: that the pathways are equally important. Central Questions - What adaptive responses occur in the root meristem as a result of changes in PA biosynthesis, specifically in the quiescent center (QC)? - Is the PA that functions as a lipid secondary messenger to the QC primarily derived from the PLC or the PLD pathway? Who Cares? - Findings will contribute to the general understanding of root meristem metabolism and function, and the effects of P-starvation on Arabidopsis roots. - Results may be useful for the creation of genetically engineered crops.

Abstract Our experiment examined the role that two different phospholipases play in the development of Arabidopsis thaliana root apical meristem architecture. The phospholipases (PLC and PLD) both synthesize phosphatidic acid (PA), a lipid second messenger, but go about it differently. We were interested in whether the PA derived from either PLC of PLD is more important for proper meristem development. We observed that certain PLC and certain PLD treatments make a difference in transcription factor levels (and thus cell identity) and root architecture. However, certain doubts about the specificity of the treatments mean that we cannot necessarily attribute our observations to our proposed pathway. The data collected suggest many interesting future projects. Introduction The principal focus of the Herrera lab (Departamento de Ingeniería Genética, CINVESTA V-IPN) in Irapuato, Mexico, is how plants acquire phosphorous and use it efficiently. The lab uses Arabidopsis thaliana mutants and marker lines to study the physiological mechanisms by which plants obtain sufficient phosphorus (P) when P is scarce. Interestingly, the abdunance of phospholipids decreases during P-starvation, while the abdundance of other lipids increases. We hypothesize that phospholipids are broken down to phosphatidic acid (PA) during P-starvation to make phosphorus available for metabolic functions, and/or to trigger stress-response processes. PA can be derived from the phospholipase C (PLC) or phospholipase D (PLD) pathway (Fig 1, Fig 2). Our project examines the effect of manipulatin PA levels synthesized by different pathways on a group of mitotically inactive cells in the root apical meristem, called the quiescent center (QC) (Fig 5). Since this was a “fishing” experiment, rather than predicting which pathway will prove more important in conferring cell identity and organization, we hoped to disprove the null hypothesis: that the pathways are equally important. Central Questions - What adaptive responses occur in the root meristem as a result of changes in PA biosynthesis, specifically in the quiescent center (QC)? - Is the PA that functions as a lipid secondary messenger to the QC primarily derived from the PLC or the PLD pathway? Who Cares? - Findings will contribute to the general understanding of root meristem metabolism and function, and the effects of P-starvation on Arabidopsis roots. - Results may be useful for the creation of genetically engineered crops.

1. Context There is growing recognition that an ethnically diverse higher education workforce positively affects the ability of institutions to deliver their core functions fully to an increasingly diverse student population. Evidence from the NUS (2011) highlights that BME students want a more representative workforce, diverse teaching practices & more BME role models. Many institutions have therefore demonstrated a strong policy commitment to race equality. However, research focused solely on the effects of ethnicity of staff in HEIs is limited. 2. Introduction Identity perspectives focus on professionals’ understanding of ‘who they are’ & the ways in which this influences, & is influenced by, what they do at work. This study investigates the identities of African & Asian British academics practicing within UK higher education.

1. Context There is growing recognition that an ethnically diverse higher education workforce positively affects the ability of institutions to deliver their core functions fully to an increasingly diverse student population. Evidence from the NUS (2011) highlights that BME students want a more representative workforce, diverse teaching practices & more BME role models. Many institutions have therefore demonstrated a strong policy commitment to race equality. However, research focused solely on the effects of ethnicity of staff in HEIs is limited. 2. Introduction Identity perspectives focus on professionals’ understanding of ‘who they are’ & the ways in which this influences, & is influenced by, what they do at work. This study investigates the identities of African & Asian British academics practicing within UK higher education.

Take Home Message CRACLe implements a novel algorithm for critical residue analysis to enable high-throughput prediction of protein-protein binding sites. Introduction The study of protein-protein interactions (PPIs) plays an important role in systems biology, particularly for understanding biological networks. Protein-protein interfaces are characterized by clusters of hot spots, i.e., amino acids that account for a significant portion of the binding free energy. Hot spots are highly conserved, and the mutation of one or more usually results in disruption of the interaction [1]. We have developed a novel algorithm to analyze protein-protein interactions based on Delaunay tessellation and an empirical statistical scoring function called Simplical Neighborhood Analysis of Protein Packing (SNAPP), implemented in a software called Critical Residue Analysis and Complementary Likelihood, or CRACLe. Herein, we focus on using CRACLe to (a) predict hot spot residues and (b) identify protein-protein binding sites. CRACLe predicted binding sites that are found at the target interface, i.e., a specific interface in the crystal structure, for more than 85% of 3545 proteins from protein-protein complexes in the Dockground data set [2] and 77% of 1099 proteins from protein-peptide complexes in the PepX data set[3].

Take Home Message CRACLe implements a novel algorithm for critical residue analysis to enable high-throughput prediction of protein-protein binding sites. Introduction The study of protein-protein interactions (PPIs) plays an important role in systems biology, particularly for understanding biological networks. Protein-protein interfaces are characterized by clusters of hot spots, i.e., amino acids that account for a significant portion of the binding free energy. Hot spots are highly conserved, and the mutation of one or more usually results in disruption of the interaction [1]. We have developed a novel algorithm to analyze protein-protein interactions based on Delaunay tessellation and an empirical statistical scoring function called Simplical Neighborhood Analysis of Protein Packing (SNAPP), implemented in a software called Critical Residue Analysis and Complementary Likelihood, or CRACLe. Herein, we focus on using CRACLe to (a) predict hot spot residues and (b) identify protein-protein binding sites. CRACLe predicted binding sites that are found at the target interface, i.e., a specific interface in the crystal structure, for more than 85% of 3545 proteins from protein-protein complexes in the Dockground data set [2] and 77% of 1099 proteins from protein-peptide complexes in the PepX data set[3].

Crystal packing determines the properties of the bulk material and in organic semiconductors it helps to determine the charge transfer. Pentacene is one of the most studied organic semiconductors and its electronic properties depend on its large p-conjugated system. While it shows good performance the packing and therefore charge transfer can be improved. Large numbers of polycyclic aromatic hydrocarbons assume a herringbone packing motif. The interactions that dominate are CC and CH between nearest neighbor molecules. Typically this results n 2D charge transport withing the stacked layers. Due to the large angle between the layers however this is not ideal for transport. The preference for a herringbone structure decreases with the lower numbers of CH interactions. So substitution offers a way to tune the interactions and create more favourable motifs for improved charge transfer. Winkler and Houk attempted the crystal structure prediction of four of them.

Crystal packing determines the properties of the bulk material and in organic semiconductors it helps to determine the charge transfer. Pentacene is one of the most studied organic semiconductors and its electronic properties depend on its large p-conjugated system. While it shows good performance the packing and therefore charge transfer can be improved. Large numbers of polycyclic aromatic hydrocarbons assume a herringbone packing motif. The interactions that dominate are CC and CH between nearest neighbor molecules. Typically this results n 2D charge transport withing the stacked layers. Due to the large angle between the layers however this is not ideal for transport. The preference for a herringbone structure decreases with the lower numbers of CH interactions. So substitution offers a way to tune the interactions and create more favourable motifs for improved charge transfer. Winkler and Houk attempted the crystal structure prediction of four of them.

The Maximum Clique Problem A clique in a graph is a set of vertices, where every pair of vertices in the set are adjacent. Finding a maximum clique is NP-hard. We can grow candidate cliques by recursively selecting a vertex for inclusion, and rejecting non-adjacent vertices. If we can coulour a graph using k colours, giving adjacent vertices different colours, then the graph cannot contain a clique with more than k vertices. This gives a branch and bound algorithm: a greedy colouring of the undecided vertices determines whether we might be able to beat the best clique found so far.

The Maximum Clique Problem A clique in a graph is a set of vertices, where every pair of vertices in the set are adjacent. Finding a maximum clique is NP-hard. We can grow candidate cliques by recursively selecting a vertex for inclusion, and rejecting non-adjacent vertices. If we can coulour a graph using k colours, giving adjacent vertices different colours, then the graph cannot contain a clique with more than k vertices. This gives a branch and bound algorithm: a greedy colouring of the undecided vertices determines whether we might be able to beat the best clique found so far.

Background Shotgun metagenomics is increasingly used not just to show patterns of change or statistically significant differences among samples, but as a culture-independent method to detect individual organisms of intense clinical, epidemiological, conservation, forensic or regulatory interest. Consequently, microbial ecologists must confirm the presence or absence of a pathogen or other taxon of interest, and may only have access to the sequence of data and not to the primary specimen. Confirming presence of a taxon in a given sample is also important for generating accurate niche reconstruction and testing hypotheses about nutrient cycling.

Background Shotgun metagenomics is increasingly used not just to show patterns of change or statistically significant differences among samples, but as a culture-independent method to detect individual organisms of intense clinical, epidemiological, conservation, forensic or regulatory interest. Consequently, microbial ecologists must confirm the presence or absence of a pathogen or other taxon of interest, and may only have access to the sequence of data and not to the primary specimen. Confirming presence of a taxon in a given sample is also important for generating accurate niche reconstruction and testing hypotheses about nutrient cycling.

1. Introduction The thorough non-destructive characterization of skin samples is a critical step in investigating dermatological diseases. The benefit to combine morphological and molecular information is investigated in this work. Asynchronous images are acquired and fused through digital image manipulation techniques. Optical coherence tomography (OCT) is a non-invasive optical imaging based on the measure echo delay of backscattered light. It provides depth information beneath the skin surface with micrometer resolution, while biochemical characterization is provided by Raman spectroscopy.

1. Introduction The thorough non-destructive characterization of skin samples is a critical step in investigating dermatological diseases. The benefit to combine morphological and molecular information is investigated in this work. Asynchronous images are acquired and fused through digital image manipulation techniques. Optical coherence tomography (OCT) is a non-invasive optical imaging based on the measure echo delay of backscattered light. It provides depth information beneath the skin surface with micrometer resolution, while biochemical characterization is provided by Raman spectroscopy.

Background Today, plants are used as botanical preparation or plant food supplements which have been suggested to impact positively on human health. German chamomile (GC) has been reported to show anti-inflammatory activity and sedative properties among other efficacies. However, its composition has not been properly established and reported, and information regarding possible compounds produced during the initial stages of metabolism in the body are scarce.

Background Today, plants are used as botanical preparation or plant food supplements which have been suggested to impact positively on human health. German chamomile (GC) has been reported to show anti-inflammatory activity and sedative properties among other efficacies. However, its composition has not been properly established and reported, and information regarding possible compounds produced during the initial stages of metabolism in the body are scarce.

Abstract Histone modification is important for epigenetic regulation of gene expression. Histone3-lysine27 N-methyltransferase EZH2 is part of a protein group called the polycomb repressive complex-2 (PRC2) and primarily plays a role in gene silencing by adding three methyl groups to H3K27, causing chromatin to condense and silencing the genes encoded in the condensed DNA. The role of EZH2 as to which genes are silenced and which are expressed in the developin lung is not clear. Using homologous recombination, mice were genetically engineered such that the promoter for signaling recombinase. Since developing lung epithelium cells express Shh, the expression of Cre recombinase combined with the insertion LoxP sites in the introns of Ezh2 led the removal of EZH2 from developing lung epithelium in this knock-out model. We report successful confirmation of the absence of the EZH2 protein in the lung epithelium in this knock-out model. We report successful confirmation of the absence of the EZH2 protein in the genotyping with PCR and analyzing phenotypes by fluorescent immuno-histochemistry. Mice homozygous for the removed Ezh2 alleles had phenotypically abnormal lung development during late gestation. Consequently, this mouse model may allow for further study of the role of EZH2 in lung development and its effects on gene expression. Introduction DNA is packaged around histones in the cell nucleus, and the way the DNA is packaged is important for gene expression. Histone expression is dynamic and can be changed by methylation of lysine residue of the histones. Methylation of H3K27 has been shown to be affiliated with gene silencing. EZH2 is important for maintaining cell fate and differentiation by silencing genes during development and is the main methyltransferase for H3K27. Mutations in EZH2 result in developmental problems such as Weaver syndrome.

Abstract Histone modification is important for epigenetic regulation of gene expression. Histone3-lysine27 N-methyltransferase EZH2 is part of a protein group called the polycomb repressive complex-2 (PRC2) and primarily plays a role in gene silencing by adding three methyl groups to H3K27, causing chromatin to condense and silencing the genes encoded in the condensed DNA. The role of EZH2 as to which genes are silenced and which are expressed in the developin lung is not clear. Using homologous recombination, mice were genetically engineered such that the promoter for signaling recombinase. Since developing lung epithelium cells express Shh, the expression of Cre recombinase combined with the insertion LoxP sites in the introns of Ezh2 led the removal of EZH2 from developing lung epithelium in this knock-out model. We report successful confirmation of the absence of the EZH2 protein in the lung epithelium in this knock-out model. We report successful confirmation of the absence of the EZH2 protein in the genotyping with PCR and analyzing phenotypes by fluorescent immuno-histochemistry. Mice homozygous for the removed Ezh2 alleles had phenotypically abnormal lung development during late gestation. Consequently, this mouse model may allow for further study of the role of EZH2 in lung development and its effects on gene expression. Introduction DNA is packaged around histones in the cell nucleus, and the way the DNA is packaged is important for gene expression. Histone expression is dynamic and can be changed by methylation of lysine residue of the histones. Methylation of H3K27 has been shown to be affiliated with gene silencing. EZH2 is important for maintaining cell fate and differentiation by silencing genes during development and is the main methyltransferase for H3K27. Mutations in EZH2 result in developmental problems such as Weaver syndrome.

Introduction Slow-wave sleep (SWS) (“deep sleep”) is involved in memory consolidation, parasympathetic (“rest and digest”) function, and recovery after sleep deprivation. Large population-based studies consistently demonstrate: 1. People lose SWS with as they age 2. Men tend to have less SWS than women of the same age The timing of this gender dimorphism is unclear.

Introduction Slow-wave sleep (SWS) (“deep sleep”) is involved in memory consolidation, parasympathetic (“rest and digest”) function, and recovery after sleep deprivation. Large population-based studies consistently demonstrate: 1. People lose SWS with as they age 2. Men tend to have less SWS than women of the same age The timing of this gender dimorphism is unclear.

A key barrier to converting woody biomass to biofuels through the sugar platform is the crystallinity of cellulose, which makes it recalcitrant to hydrolysis. Significant past research on cellulosic biofuels has focused on overcoming this recalcitrance and improving the conversion to glucose. Instead, we propose to convert this recalcitrant cellulose into nano-fibrillated cellulose in forms that can be used as high-performance polymer reinforcement for the thermoset and the injection molding industries. We will do this by 1. integrating the production of sugars for drop-in biofuels production with production of cellulose nanofibers, 2. optimizing conversion of the recalcitrant cellulose to high-performance polymer reinforcements, and 3. demonstrating effective use of the reinforcements in both thermoset and thermoplastic polymers.

A key barrier to converting woody biomass to biofuels through the sugar platform is the crystallinity of cellulose, which makes it recalcitrant to hydrolysis. Significant past research on cellulosic biofuels has focused on overcoming this recalcitrance and improving the conversion to glucose. Instead, we propose to convert this recalcitrant cellulose into nano-fibrillated cellulose in forms that can be used as high-performance polymer reinforcement for the thermoset and the injection molding industries. We will do this by 1. integrating the production of sugars for drop-in biofuels production with production of cellulose nanofibers, 2. optimizing conversion of the recalcitrant cellulose to high-performance polymer reinforcements, and 3. demonstrating effective use of the reinforcements in both thermoset and thermoplastic polymers.

Accelerating forest restoration Approximately 400 million acres of public and private forest land in the United States need restoration. Restoration typically means removing excess forest biomass. The estimated cost for one round of forest restoration is $69 billion, which is overwhelming compared to the $0.3 billion in the U.S. Forest Service is funded annually for restoration efforts. However, inaction is not an option. Accumulation of excess forest biomass fuels catastrophic wildfires and devastating loss in lives and property. The U.S. Forest Service typically spends over $3 billion annually fighting wildfires, and costs continue to rise. Faces with this staggering challenge, the U.S. Forest Service is pursuing advanced materials research in an effort to find market-based outlets for the excess forest biomass removed during restoration. The aim is to recoup some or all of the restoration costs and to accelerate forest restoration with the need for additional funding.

Accelerating forest restoration Approximately 400 million acres of public and private forest land in the United States need restoration. Restoration typically means removing excess forest biomass. The estimated cost for one round of forest restoration is $69 billion, which is overwhelming compared to the $0.3 billion in the U.S. Forest Service is funded annually for restoration efforts. However, inaction is not an option. Accumulation of excess forest biomass fuels catastrophic wildfires and devastating loss in lives and property. The U.S. Forest Service typically spends over $3 billion annually fighting wildfires, and costs continue to rise. Faces with this staggering challenge, the U.S. Forest Service is pursuing advanced materials research in an effort to find market-based outlets for the excess forest biomass removed during restoration. The aim is to recoup some or all of the restoration costs and to accelerate forest restoration with the need for additional funding.

Introduction Three primary hypothesis can explain the dearth of land crabs in the fossil record: 1) Land crabs have a low preservation potential and are removed from the system prior to fossilization (taphonomic hyphothesis) 2) Land crabs evolved more recently than their close relatives and therefore were not present to be incorporated into the fossil record (evolutionary hypothesis) 3) Land crab remains have been overlooked or misidentified (taxonomic hypothesis). This study focuses on the short-term, pre-burial processes and taphonomic biases affecting land crab remains.

Introduction Three primary hypothesis can explain the dearth of land crabs in the fossil record: 1) Land crabs have a low preservation potential and are removed from the system prior to fossilization (taphonomic hyphothesis) 2) Land crabs evolved more recently than their close relatives and therefore were not present to be incorporated into the fossil record (evolutionary hypothesis) 3) Land crab remains have been overlooked or misidentified (taxonomic hypothesis). This study focuses on the short-term, pre-burial processes and taphonomic biases affecting land crab remains.

Introduction Deep water coral reefs (300-100m) could shelter commercial fish stocks and provide coral larvae for recovering shallow reefs. Deep corals appear healthier than shallow corals, but depth has restricted their study. Current quantitative study methods involve scattering random points across images and visually identifying substrates. Montastrea annularis complex is a major reef building coral representing as much as 75% of the coral cover in some areas. Its dominance and smooth texture make it an ideal candidate for image processing. The goal of this research was to develop an algorithm to segment out colonies of the M. annularis complex and calculate percent coverage values

Introduction Deep water coral reefs (300-100m) could shelter commercial fish stocks and provide coral larvae for recovering shallow reefs. Deep corals appear healthier than shallow corals, but depth has restricted their study. Current quantitative study methods involve scattering random points across images and visually identifying substrates. Montastrea annularis complex is a major reef building coral representing as much as 75% of the coral cover in some areas. Its dominance and smooth texture make it an ideal candidate for image processing. The goal of this research was to develop an algorithm to segment out colonies of the M. annularis complex and calculate percent coverage values

BACKGROUND: Changes in spring phenology are visible and readily accessible measures of the ecological effects of climate change. While both monitoring and historical data have contributed to in depth studies of the timing of leaf out, flowering, and migratory bird arrivals in a few places, such as Concord, MA, complete long-term records of phenological events are rare. Aside from Henry David Thoreau and Aldo Leopold, few naturalists consistently noted these events and even fewer had their diaries archived. From 1940-1957, a hunting guide names L.S. Quackenbush in Northern Maine kept detailed journals with Thoreau-like attention to the dates of leaf out, the first flowers, and the earliest sightings of migratory birds each Spring. Quakenbush’s home, in the rural region of Aroostook County, Maine, has been traditionally neglected in climate change research due to its remote location and low population density. Here, we use Quackenbush’s notes to study the ecological effects of climate change in Northern Maine.

BACKGROUND: Changes in spring phenology are visible and readily accessible measures of the ecological effects of climate change. While both monitoring and historical data have contributed to in depth studies of the timing of leaf out, flowering, and migratory bird arrivals in a few places, such as Concord, MA, complete long-term records of phenological events are rare. Aside from Henry David Thoreau and Aldo Leopold, few naturalists consistently noted these events and even fewer had their diaries archived. From 1940-1957, a hunting guide names L.S. Quackenbush in Northern Maine kept detailed journals with Thoreau-like attention to the dates of leaf out, the first flowers, and the earliest sightings of migratory birds each Spring. Quakenbush’s home, in the rural region of Aroostook County, Maine, has been traditionally neglected in climate change research due to its remote location and low population density. Here, we use Quackenbush’s notes to study the ecological effects of climate change in Northern Maine.

INTRODUCTION Abstract To define new relevant therapeutic targets for hepatitis C treatment, we sought to identify cellular factors required for the entry of the Hepatitis C Virus (HCV) in the cell target. In this context, we analyzed the impact of individual gene extinctions by RNA interference on cell susceptibility to HCV infection. The cRNA library targeted 122 cellular genes involved in the trafficking and membrane remodeling. The functional test was based on the in vitro infection of Huh 7.6.1 cells by HCVpp (recombinant retrovirus pseudotyped with the HCV enveloped glycoproteins). Our results confirmed the use of clathrin dependant entry route and revealed the unexpected involvement of the phosphatidlylinositol 4-kinase, oatalytic, alpha (PI4KIlla). The partial extinction of the gene coding for this kinase efficiently protected hepatic cells from the infection by HCVpp or by HCVoo (complete recombinant viral particles produced in vitro). Further investigations on genes coding for the different members of the same kinase family (PI4Ks)and the use of an additional functional fact dedicated to the HCV replication stages allowed us to demonstrate that the presence of two kinases (PI4KIlla and B) in the host cell was required to support both HCV entry and replication. Those kinases represent very interesting potential therapeutic targets since they are implied in two different steps of the HCV life cycle.

INTRODUCTION Abstract To define new relevant therapeutic targets for hepatitis C treatment, we sought to identify cellular factors required for the entry of the Hepatitis C Virus (HCV) in the cell target. In this context, we analyzed the impact of individual gene extinctions by RNA interference on cell susceptibility to HCV infection. The cRNA library targeted 122 cellular genes involved in the trafficking and membrane remodeling. The functional test was based on the in vitro infection of Huh 7.6.1 cells by HCVpp (recombinant retrovirus pseudotyped with the HCV enveloped glycoproteins). Our results confirmed the use of clathrin dependant entry route and revealed the unexpected involvement of the phosphatidlylinositol 4-kinase, oatalytic, alpha (PI4KIlla). The partial extinction of the gene coding for this kinase efficiently protected hepatic cells from the infection by HCVpp or by HCVoo (complete recombinant viral particles produced in vitro). Further investigations on genes coding for the different members of the same kinase family (PI4Ks)and the use of an additional functional fact dedicated to the HCV replication stages allowed us to demonstrate that the presence of two kinases (PI4KIlla and B) in the host cell was required to support both HCV entry and replication. Those kinases represent very interesting potential therapeutic targets since they are implied in two different steps of the HCV life cycle.

Background Anytime an individual transitions from sedentary behaviour from sedentary behaviour to light activity (e.g. standing, walking) it is considered a break in their sedentary time. These breaks are associated with reduced cardiometabolic disease risk in adults, independent of total physical activity and sedentary time (1,2). However, these finding have yet to be replicated in children.

Background Anytime an individual transitions from sedentary behaviour from sedentary behaviour to light activity (e.g. standing, walking) it is considered a break in their sedentary time. These breaks are associated with reduced cardiometabolic disease risk in adults, independent of total physical activity and sedentary time (1,2). However, these finding have yet to be replicated in children.

The Problem The mysterious fruits of some trees are best explained when viewed in the megafauna filled world in which they evolved (Fig 1). Tree species like Joshua Tree, which produce fruit largely uneaten today, were among common foods of now-extinct megaherbivores. Since the Pleistocene megafaunal collapse, trees dependent upon these dispersers should have a reduced ability to track changing climates. We can test hypothesis using the percentage a species realizes of its bioclimatically potential range as a range as a proxy for dispersal during the Holocene. On this poster, we estimate potential ranges with MaxEnt for Joshua Tree and Honey Mesquite, two species thought to have been dispersed by the community of megaherbivores that lived in the arid American Southwest. Results are shown as maps below.

The Problem The mysterious fruits of some trees are best explained when viewed in the megafauna filled world in which they evolved (Fig 1). Tree species like Joshua Tree, which produce fruit largely uneaten today, were among common foods of now-extinct megaherbivores. Since the Pleistocene megafaunal collapse, trees dependent upon these dispersers should have a reduced ability to track changing climates. We can test hypothesis using the percentage a species realizes of its bioclimatically potential range as a range as a proxy for dispersal during the Holocene. On this poster, we estimate potential ranges with MaxEnt for Joshua Tree and Honey Mesquite, two species thought to have been dispersed by the community of megaherbivores that lived in the arid American Southwest. Results are shown as maps below.

1. Introduction Polypeptides have attracted widespread attention as building block of complex materials due to their ability to form higher-ordered structures such as -sheets. Still, the propensity of -sheet-forming peptides to form unprocessable aggregates in solution remains a critical issue towards the preparation od well-defined--sheet-assembled materials. By employing surface-initiated N-carboxyanhydride ring-opening polymerixation (SI-ROP), we recently reported a robust strategy to form well-defined peptide -sheet architectures with sponge-like morphology. Herein, we demonstrate the unique ability of the H-bonded microsponges in entrapping metal nanoparticles, proteins, drug molecules and biorelevant polymers via non-covalent interactions. This ability mimics the absorption/filtering ability of marine animals (e.g., sea sponges) and present a simple yet versatile approach towards the fabrication of functional materials for various applications.

1. Introduction Polypeptides have attracted widespread attention as building block of complex materials due to their ability to form higher-ordered structures such as -sheets. Still, the propensity of -sheet-forming peptides to form unprocessable aggregates in solution remains a critical issue towards the preparation od well-defined--sheet-assembled materials. By employing surface-initiated N-carboxyanhydride ring-opening polymerixation (SI-ROP), we recently reported a robust strategy to form well-defined peptide -sheet architectures with sponge-like morphology. Herein, we demonstrate the unique ability of the H-bonded microsponges in entrapping metal nanoparticles, proteins, drug molecules and biorelevant polymers via non-covalent interactions. This ability mimics the absorption/filtering ability of marine animals (e.g., sea sponges) and present a simple yet versatile approach towards the fabrication of functional materials for various applications.

Introduction Nephrology bloggers are rarely compensated and their writing is not usually considered part of academic production in regards to advancement. Without obvious advantages for the blogger, I thought that bloggers must thrive on internal enthusiasm and it may wane over time.

Introduction Nephrology bloggers are rarely compensated and their writing is not usually considered part of academic production in regards to advancement. Without obvious advantages for the blogger, I thought that bloggers must thrive on internal enthusiasm and it may wane over time.

Background Sexual reproduction is overwhelmingly common in nature but, despite its success, the costs of sex are substantial. These include: -The 2-fold cost of sex -The destruction of beneficial genetic associations One hypothesis, proposed by Muller (1964), predicts that genetic drift causes accumulation of deleterious linkage disequilibrium, leading to an irreversible fitness decline and eventual extinction in asexual populations. Sexual populations, however, are able to purge this disequilibrium via recombination. Recent computational investigations have supported this, finding that fitness of asexuals declined over time relative to the fitness of sexuals (Hartfield 2012). However, these models did not incorporate genetic interations. In this work, we have modeled population dynamics in both sexual and asexual populations of different sizes, thus varying strength of drift and amount of resultant deleterious linkage disequilibrium.

Background Sexual reproduction is overwhelmingly common in nature but, despite its success, the costs of sex are substantial. These include: -The 2-fold cost of sex -The destruction of beneficial genetic associations One hypothesis, proposed by Muller (1964), predicts that genetic drift causes accumulation of deleterious linkage disequilibrium, leading to an irreversible fitness decline and eventual extinction in asexual populations. Sexual populations, however, are able to purge this disequilibrium via recombination. Recent computational investigations have supported this, finding that fitness of asexuals declined over time relative to the fitness of sexuals (Hartfield 2012). However, these models did not incorporate genetic interations. In this work, we have modeled population dynamics in both sexual and asexual populations of different sizes, thus varying strength of drift and amount of resultant deleterious linkage disequilibrium.