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Full-Text Articles in Life Sciences

Winner's Curse Correction And Variable Thresholding Improve Performance Of Polygenic Risk Modeling Based On Genome-Wide Association Study Summary-Level Data, Jianxin Shi, Ju-Hyun Park, Jubao Duan, Sonja T. Berndt, Winton Moy, Kai Yu, Lei Song, William Wheeler, Xing Hua, Debra Silverman, Montserrat Garcia-Closas, Chao Agnes Hsiung, Jonine D. Figueroa, Victoria K. Cortessis, Nuria Malats, Margaret R. Karagas Dec 2016

Winner's Curse Correction And Variable Thresholding Improve Performance Of Polygenic Risk Modeling Based On Genome-Wide Association Study Summary-Level Data, Jianxin Shi, Ju-Hyun Park, Jubao Duan, Sonja T. Berndt, Winton Moy, Kai Yu, Lei Song, William Wheeler, Xing Hua, Debra Silverman, Montserrat Garcia-Closas, Chao Agnes Hsiung, Jonine D. Figueroa, Victoria K. Cortessis, Nuria Malats, Margaret R. Karagas

Dartmouth Scholarship

Recent heritability analyses have indicated that genome-wide association studies (GWAS) have the potential to improve genetic risk prediction for complex diseases based on polygenic risk score (PRS), a simple modelling technique that can be implemented using summary-level data from the discovery samples. We herein propose modifications to improve the performance of PRS. We introduce threshold-dependent winner’s-curse adjustments for marginal association coefficients that are used to weight the single-nucleotide polymorphisms (SNPs) in PRS. Further, as a way to incorporate external functional/annotation knowledge that could identify subsets of SNPs highly enriched for associations, we propose variable thresholds for SNPs selection. We applied …


Comparative Genetic Screens In Human Cells Reveal New Regulatory Mechanisms In Wnt Signaling, Andres M. Lebensohn, Ramin Dubey, Leif Neitzel, Ofelia Tacchelly-Benites Dec 2016

Comparative Genetic Screens In Human Cells Reveal New Regulatory Mechanisms In Wnt Signaling, Andres M. Lebensohn, Ramin Dubey, Leif Neitzel, Ofelia Tacchelly-Benites

Dartmouth Scholarship

The comprehensive understanding of cellular signaling pathways remains a challenge due to multiple layers of regulation that may become evident only when the pathway is probed at different levels or critical nodes are eliminated. To discover regulatory mechanisms in canonical WNT signaling, we conducted a systematic forward genetic analysis through reporter-based screens in haploid human cells. Comparison of screens for negative, attenuating and positive regulators of WNT signaling, mediators of R-spondin-dependent signaling and suppressors of constitutive signaling induced by loss of the tumor suppressor adenomatous polyposis coli or casein kinase 1α uncovered new regulatory features at most levels of the …


The Vibrio Cholerae Minor Pilin Tcpb Initiates Assembly And Retraction Of The Toxin-Coregulated Pilus, Dixon Ng, Tony Harn, Tuba Altindal, Subramania Kolappan, Jarrad Marles, Rajan Lala, Ingrid Spielman, Yang Gao, Caitlyn Hauke, Gabriela Kovacikova Dec 2016

The Vibrio Cholerae Minor Pilin Tcpb Initiates Assembly And Retraction Of The Toxin-Coregulated Pilus, Dixon Ng, Tony Harn, Tuba Altindal, Subramania Kolappan, Jarrad Marles, Rajan Lala, Ingrid Spielman, Yang Gao, Caitlyn Hauke, Gabriela Kovacikova

Dartmouth Scholarship

Type IV pilus (T4P) systems are complex molecular machines that polymerize major pilin proteins into thin filaments displayed on bacterial surfaces. Pilus functions require rapid extension and depolymerization of the pilus, powered by the assembly and retraction ATPases, respectively. A set of low abundance minor pilins influences pilus dynamics by unknown mechanisms. The Vibrio cholerae toxin-coregulated pilus (TCP) is among the simplest of the T4P systems, having a single minor pilin TcpB and lacking a retraction ATPase. Here we show that TcpB, like its homolog CofB, initiates pilus assembly. TcpB co-localizes with the pili but at extremely low levels, equivalent …


Biophysical And Functional Characterization Of Rhesus Macaque Igg Subclasses, Austin W. Boesch, Nana Yaw Osei-Owusu, Andrew R. Crowley, Thach H. Chu, Ying Chan, Joshua Weiner, Pranay Bharadwaj, Rufus Hards, Mark Adamo, Scott Gerber, Sarah Cocklin, Joern Schmitz, Adam Miles, Joshua Eckman, Aaron J. Belli, Keith Reimann, Margaret E. Ackerman Dec 2016

Biophysical And Functional Characterization Of Rhesus Macaque Igg Subclasses, Austin W. Boesch, Nana Yaw Osei-Owusu, Andrew R. Crowley, Thach H. Chu, Ying Chan, Joshua Weiner, Pranay Bharadwaj, Rufus Hards, Mark Adamo, Scott Gerber, Sarah Cocklin, Joern Schmitz, Adam Miles, Joshua Eckman, Aaron J. Belli, Keith Reimann, Margaret E. Ackerman

Dartmouth Scholarship

Antibodies raised in Indian rhesus macaques [Macaca mulatta (MM)] in many preclinical vaccine studies are often evaluated in vitro for titer, antigen-recognition breadth, neu- tralization potency, and/or effector function, and in vivo for potential associations with protection. However, despite reliance on this key animal model in translation of promising candidate vaccines for evaluation in first in man studies, little is known about the proper- ties of MM immunoglobulin G (IgG) subclasses and how they may compare to human IgG subclasses. Here, we evaluate the binding of MM IgG1, IgG2, IgG3, and IgG4 to human Fc gamma receptors (FcγR) and their …


Novel And Lost Forests In The Upper Midwestern United States, From New Estimates Of Settlement-Era Composition, Stem Density, And Biomass, Simon J. Goring, David J. Mladenoff, Charles V. Cogbill, Sydne Record, Christopher J. Paciorek, Stephen T. Jackson, Michael C. Dietze, Andria Dawson, Jaclyn Hatala Matthes, Jason S. Mclachlan, John W. Williams Dec 2016

Novel And Lost Forests In The Upper Midwestern United States, From New Estimates Of Settlement-Era Composition, Stem Density, And Biomass, Simon J. Goring, David J. Mladenoff, Charles V. Cogbill, Sydne Record, Christopher J. Paciorek, Stephen T. Jackson, Michael C. Dietze, Andria Dawson, Jaclyn Hatala Matthes, Jason S. Mclachlan, John W. Williams

Dartmouth Scholarship

EuroAmerican land-use and its legacies have transformed forest structure and composition across the United States (US). More accurate reconstructions of historical states are critical to understanding the processes governing past, current, and future forest dynamics. Here we present new gridded (8x8km) reconstructions of pre-settlement (1800s) forest composition and structure from the upper Midwestern US (Minnesota, Wisconsin, and most of Michigan), using 19th Century Public Land Survey System (PLSS), with estimates of relative composition, above-ground biomass, stem density, and basal area for 28 tree types. This mapping is more robust than past efforts, using spatially varying correction factors to accommodate sampling …


Characterization Of The Cytokinin-Responsive Transcriptome In Rice, Tracy Raines, Ivory C. Blakley, Yu-Chang Tsai, Jennifer M. Worthen, José M. Franco-Zorrilla, Roberto Solano, G. Eric Schaller Dec 2016

Characterization Of The Cytokinin-Responsive Transcriptome In Rice, Tracy Raines, Ivory C. Blakley, Yu-Chang Tsai, Jennifer M. Worthen, José M. Franco-Zorrilla, Roberto Solano, G. Eric Schaller

Dartmouth Scholarship

Cytokinin activates transcriptional cascades important for development and the responses to biotic and abiotic stresses. Most of what is known regarding cytokinin-regulated gene expression comes from studies of the dicotyledonous plant Arabidopsis thaliana. To expand the understanding of the cytokinin-regulated transcriptome, we employed RNA-Seq to analyze gene expression in response to cytokinin in roots and shoots of the monocotyledonous plant rice.


Calcium-Mediated Actin Reset (Caar) Mediates Acute Cell Adaptations, Pauline Wales, Christian Schuberth, Roland Aufschnaiter, Johannes Fels, Ireth Garcia-Aguilar, Annette Janning, Christopher D. Dlugos, Marco Schaefer-Herte, Christoph Klingner, Mike Waelte, Julian Kuhlmann, Ekaterina Menis, Hockaday Kang Hockaday Kang, Kerstin C. Maier, Wenya Hou, Antonella Russo, Henry N. Higgs Dec 2016

Calcium-Mediated Actin Reset (Caar) Mediates Acute Cell Adaptations, Pauline Wales, Christian Schuberth, Roland Aufschnaiter, Johannes Fels, Ireth Garcia-Aguilar, Annette Janning, Christopher D. Dlugos, Marco Schaefer-Herte, Christoph Klingner, Mike Waelte, Julian Kuhlmann, Ekaterina Menis, Hockaday Kang Hockaday Kang, Kerstin C. Maier, Wenya Hou, Antonella Russo, Henry N. Higgs

Dartmouth Scholarship

Actin has well established functions in cellular morphogenesis. However, it is not well understood how the various actin assemblies in a cell are kept in a dynamic equilibrium, in particular when cells have to respond to acute signals. Here, we characterize a rapid and transient actin reset in response to increased intracellular calcium levels. Within seconds of calcium influx, the formin INF2 stimulates filament polymerization at the endoplasmic reticulum (ER), while cortical actin is disassembled. The reaction is then reversed within a few minutes. This Calcium-mediated actin reset (CaAR) occurs in a wide range of mammalian cell types and in …


Tertiary Alphabet For The Observable Protein Structural Universe, Craig\ O. Mackenzie, Jianfu Zhou, Gevorg Grigoryan Nov 2016

Tertiary Alphabet For The Observable Protein Structural Universe, Craig\ O. Mackenzie, Jianfu Zhou, Gevorg Grigoryan

Dartmouth Scholarship

Here, we systematically decompose the known protein structural universe into its basic elements, which we dub tertiary structural motifs (TERMs). A TERM is a compact backbone fragment that captures the secondary, tertiary, and quaternary environments around a given residue, comprising one or more disjoint segments (three on average). We seek the set of universal TERMs that capture all structure in the Protein Data Bank (PDB), finding remarkable degeneracy. Only ∼600 TERMs are sufficient to describe 50% of the PDB at sub-Angstrom resolution. However, more rare geometries also exist, and the overall structural coverage grows logarithmically with the number of TERMs. …


Application Of Rnai-Induced Gene Expression Profiles For Prognostic Prediction In Breast Cancer, Yue Wang, Kenneth . M. K. Mark, Matthew H. Ung, Arminja Kettenbach, Todd Miller, Wei Xu, Wenqing Cheng Cheng, Tian Xia, Chao Cheng Oct 2016

Application Of Rnai-Induced Gene Expression Profiles For Prognostic Prediction In Breast Cancer, Yue Wang, Kenneth . M. K. Mark, Matthew H. Ung, Arminja Kettenbach, Todd Miller, Wei Xu, Wenqing Cheng Cheng, Tian Xia, Chao Cheng

Dartmouth Scholarship

Homologous recombination (HR) is the primary pathway for repairing double-strand DNA breaks implicating in the development of cancer. RNAi-based knockdowns of BRCA1 and RAD51 in this pathway have been performed to investigate the resulting transcriptomic profiles. Here we propose a computational framework to utilize these profiles to calculate a score, named RNA-Interference derived Proliferation Score (RIPS), which reflects cell proliferation ability in individual breast tumors. RIPS is predictive of breast cancer classes, prognosis, genome instability, and neoadjuvant chemosensitivity. This framework directly translates the readout of knockdown experiments into potential clinical applications and generates a robust biomarker in breast cancer.


A New Timepiece: An Epigenetic Mitotic Clock, Brock C. Christensen, Karl T. Kelsey Oct 2016

A New Timepiece: An Epigenetic Mitotic Clock, Brock C. Christensen, Karl T. Kelsey

Dartmouth Scholarship

A new mitotic clock and mathematical approach that incorporates DNA methylation biology common among human cell types provides a new tool for cancer epigenetics research.


Oxidative Stress In Oocytes During Midprophase Induces Premature Loss Of Cohesion And Chromosome Segregation Errors, Adrienne T. Perkins, Thomas M. Das, Lauren C. Panzera, Sharon E. Bickel Oct 2016

Oxidative Stress In Oocytes During Midprophase Induces Premature Loss Of Cohesion And Chromosome Segregation Errors, Adrienne T. Perkins, Thomas M. Das, Lauren C. Panzera, Sharon E. Bickel

Dartmouth Scholarship

In humans, errors in meiotic chromosome segregation that produce aneuploid gametes increase dramatically as women age, a phenomenon termed the "maternal age effect." During meiosis, cohesion between sister chromatids keeps recombinant homologs physically attached and premature loss of cohesion can lead to missegregation of homologs during meiosis I. A growing body of evidence suggests that meiotic cohesion deteriorates as oocytes age and contributes to the maternal age effect. One hallmark of aging cells is an increase in oxidative damage caused by reactive oxygen species (ROS). Therefore, increased oxidative damage in older oocytes may be one of the factors that leads …


Circnet: A Database Of Circular Rnas Derived From Transcriptome Sequencing Data, Yu-Chen Liu, Jian-Rong Li, Chuan-Hu Sun, Erik Andrews, Rou-Fang Chao, Feng-Mao Lin, Shun-Long Weng, Sheng-Da Hsu, Chieh-Chen Huang, Chao Cheng, Chun-Chi Liu, Hsien-Da Huang Oct 2016

Circnet: A Database Of Circular Rnas Derived From Transcriptome Sequencing Data, Yu-Chen Liu, Jian-Rong Li, Chuan-Hu Sun, Erik Andrews, Rou-Fang Chao, Feng-Mao Lin, Shun-Long Weng, Sheng-Da Hsu, Chieh-Chen Huang, Chao Cheng, Chun-Chi Liu, Hsien-Da Huang

Dartmouth Scholarship

Circular RNAs (circRNAs) represent a new type of regulatory noncoding RNA that only recently has been identified and cataloged. Emerging evidence indicates that circRNAs exert a new layer of post-transcriptional regulation of gene expression. In this study, we utilized transcriptome sequencing datasets to systematically identify the expression of circRNAs (including known and newly identified ones by our pipeline) in 464 RNA-seq samples, and then constructed the CircNet database (http://circnet.mbc.nctu.edu.tw/) that provides the following resources: (i) novel circRNAs, (ii) integrated miRNA-target networks, (iii) expression profiles of circRNA isoforms, (iv) genomic annotations of circRNA isoforms (e.g. 282 948 exon positions), …


Dissection Of Molecular Assembly Dynamics By Tracking Orientation And Position Of Single Molecules In Live Cells, Shalin B. Mehta, Molly Mcquilken, Patrick J. La Riviere, Patricia Occhipinti, Amitabh Verma, Rudolf Oldenbourg, Amy Gladfelter, Tomomi Tani Sep 2016

Dissection Of Molecular Assembly Dynamics By Tracking Orientation And Position Of Single Molecules In Live Cells, Shalin B. Mehta, Molly Mcquilken, Patrick J. La Riviere, Patricia Occhipinti, Amitabh Verma, Rudolf Oldenbourg, Amy Gladfelter, Tomomi Tani

Dartmouth Scholarship

Regulation of order, such as orientation and conformation, drives the function of most molecular assemblies in living cells but remains difficult to measure accurately through space and time. We built an instantaneous fluorescence polarization microscope, which simultaneously images position and orientation of fluorophores in living cells with single-molecule sensitivity and a time resolution of 100 ms. We developed image acquisition and analysis methods to track single particles that interact with higher-order assemblies of molecules. We tracked the fluctuations in position and orientation of molecules from the level of an ensemble of fluorophores down to single fluorophores. We tested our system …


Presence Of The Cyanotoxin Microcystin In Arctic Lakes Of Southwestern Greenland, Jessica Trout-Haney, Zachary Wood, Kathryn Cottingham Aug 2016

Presence Of The Cyanotoxin Microcystin In Arctic Lakes Of Southwestern Greenland, Jessica Trout-Haney, Zachary Wood, Kathryn Cottingham

Dartmouth Scholarship

Cyanobacteria and their toxins have received significant attention in eutrophic temperate and tropical systems where conspicuous blooms of certain planktonic taxa release toxins into fresh water, threatening its potability and safe use for recreation. Although toxigenic cyanobacteria are not confined to high nutrient environments, bloom-forming species, or planktonic taxa, these other situations are studied les often studied. For example, toxin production in picoplankton and benthic cyanobacteria—the predominant photoautotrophs found in polar lakes—is poorly understood. We quantified the occurrence of microcystin (MC, a hepatotoxic cyanotoxin) across 18 Arctic lakes in southwestern Greenland. All of the focal lakes contained detectable levels of …


The Importance Of Ambient Temperature To Growth And The Induction Of Flowering, C. R. Mcclung, Ping Lou, Victor Hermand, Jin A. Kim Aug 2016

The Importance Of Ambient Temperature To Growth And The Induction Of Flowering, C. R. Mcclung, Ping Lou, Victor Hermand, Jin A. Kim

Dartmouth Scholarship

Plant development is exquisitely sensitive to the environment. Light quantity, quality, and duration (photoperiod) have profound effects on vegetative morphology and flowering time. Recent studies have demonstrated that ambient temperature is a similarly potent stimulus influencing morphology and flowering. In Arabidopsis, ambient temperatures that are high, but not so high as to induce a heat stress response, confer morphological changes that resemble the shade avoidance syndrome. Similarly, these high but not stressful temperatures can accelerate flowering under short day conditions as effectively as exposure to long days. Photoperiodic flowering entails a series of external coincidences, in which environmental cycles of …


Belowground Rhizomes In Paleosols: The Hidden Half Of An Early Devonian Vascular Plant, Jinzhuang Xue, Zhenzhen Deng, Pu Huang, Kangjun Huang, Michael J. Benton, Ying Cui Aug 2016

Belowground Rhizomes In Paleosols: The Hidden Half Of An Early Devonian Vascular Plant, Jinzhuang Xue, Zhenzhen Deng, Pu Huang, Kangjun Huang, Michael J. Benton, Ying Cui

Dartmouth Scholarship

The colonization of terrestrial environments by rooted vascular plants had far-reaching impacts on the Earth system. However, the belowground structures of early vascular plants are rarely documented, and thus the plant−soil interactions in early terrestrial ecosystems are poorly understood. Here we report the earliest rooted paleosols (fossil soils) in Asia from Early Devonian deposits of Yunnan, China. Plant traces are extensive within the soil and occur as complex network-like structures, which are interpreted as representing long-lived, belowground rhizomes of the basal lycopsid Drepanophycus. The rhizomes produced large clones and helped the plant survive frequent sediment burial in well-drained soils …


Building From The Hiv Response Toward Universal Health Coverage, Jonathon Jay, Kent Buse, Marielle Hart, Robert Marten, Scott Kellerman, Morolake Odetoyinbo, Jonathan D. Quick, Timothy Evans, Peter Piot, Mark Dybul, Agnes Binagwaho Aug 2016

Building From The Hiv Response Toward Universal Health Coverage, Jonathon Jay, Kent Buse, Marielle Hart, Robert Marten, Scott Kellerman, Morolake Odetoyinbo, Jonathan D. Quick, Timothy Evans, Peter Piot, Mark Dybul, Agnes Binagwaho

Dartmouth Scholarship

Universal health coverage (UHC) has gained prominence as a global health priority. The UHC movement aims to increase access to quality, needed health services while reducing financial hardship from health spending, particularly in low- and middle- income countries.
As a policy agenda, UHC has been identified primarily with prepayment and risk-pool- ing programs. While financing policies provide important benefits, increasing access to health services will require broader reforms.
For lessons, the UHC movement should look to the global HIV response, which has confronted many of the same barriers to access in weak health systems. Considerable success on HIV has resulted …


Itar: A Web Server For Identifying Target Genes Of Transcription Factors Using Chip-Seq Or Chip-Chip Data, Chia-Chun Yang, Erik H. Andrews, Min-Hsuan Chen, Wan-Yu Wang Aug 2016

Itar: A Web Server For Identifying Target Genes Of Transcription Factors Using Chip-Seq Or Chip-Chip Data, Chia-Chun Yang, Erik H. Andrews, Min-Hsuan Chen, Wan-Yu Wang

Dartmouth Scholarship

Chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) or microarray hybridization (ChIP-chip) has been widely used to determine the genomic occupation of transcription factors (TFs). We have previously developed a probabilistic method, called TIP (Target Identification from Profiles), to identify TF target genes using ChIP-seq/ChIP-chip data. To achieve high specificity, TIP applies a conservative method to estimate significance of target genes, with the trade-off being a relatively low sensitivity of target gene identification compared to other methods. Additionally, TIP’s output does not render binding-peak locations or intensity, information highly useful for visualization and general experimental biological use, while the …


Field Estimates Of Parentage Reveal Sexually Antagonistic Selection On Body Size In A Population Of Anolis Lizards, Mary C. Duryea, Patrick Bergeron, Zachary Clare-Salzler, Ryan Calsbeek Aug 2016

Field Estimates Of Parentage Reveal Sexually Antagonistic Selection On Body Size In A Population Of Anolis Lizards, Mary C. Duryea, Patrick Bergeron, Zachary Clare-Salzler, Ryan Calsbeek

Dartmouth Scholarship

Sexual dimorphism evolves when selection favors different phenotypic optima between the sexes. Such sexually antagonistic selection creates intralocus sexual conflict when traits are genetically correlated between the sexes and have sex‐specific optima. Brown anoles are highly sexually dimorphic: Males are on average 30% longer than females and 150% heavier in our study population. Viability selection on body size is known to be sexually antagonistic, and directional selection favors large male size whereas stabilizing selection constrains females to remain small. We build on previous studies of viability selection by measuring sexually antagonistic selection using reproductive components of fitness over three generations …


Individual Differences In Response Of Dorsomedial Prefrontal Cortex Predict Daily Social Behavior, Katherine E. Powers, Robert S. Chavez, Todd F. Heatherton Jul 2016

Individual Differences In Response Of Dorsomedial Prefrontal Cortex Predict Daily Social Behavior, Katherine E. Powers, Robert S. Chavez, Todd F. Heatherton

Dartmouth Scholarship

The capacity to accurately infer the thoughts and intentions of other people is critical for effective social interaction, and neural activity in dorsomedial prefrontal cortex (dmPFC) has long been linked with the extent to which people engage in mental state attribution. In this study, we combined functional neuroimaging and experience sampling methodologies to test the predictive value of this neural response for daily social behaviors. We found that individuals who displayed greater activity in dmPFC when viewing social scenes spent more time around other people on a daily basis. These findings suggest a specific role for the neural mechanisms that …


A Face Versus Non-Face Context Influences Amygdala Responses To Masked Fearful Eye Whites, M. Justin Kim, Kimberly M. Solomon, Maital Neta, F. Caroline Davis, Jonathan A. Oler, Emily C. Mazzulla, Paul J. Whalen Jul 2016

A Face Versus Non-Face Context Influences Amygdala Responses To Masked Fearful Eye Whites, M. Justin Kim, Kimberly M. Solomon, Maital Neta, F. Caroline Davis, Jonathan A. Oler, Emily C. Mazzulla, Paul J. Whalen

Dartmouth Scholarship

The structure of the mask stimulus is crucial in backward masking studies and we recently demonstrated such an effect when masking faces. Specifically, we showed that activity of the amygdala is increased to fearful facial expressions masked with neutral faces and decreased to fearful expressions masked with a pattern mask—but critically both masked conditions discriminated fearful expressions from happy expressions. Given this finding, we sought to test whether masked fearful eye whites would produce a similar profile of amygdala response in a face vs non-face context. During functional magnetic resonance imaging scanning sessions, 30 participants viewed fearful or happy eye …


A Heavy Metal P-Type Atpase Oshma4 Prevents Copper Accumulation In Rice Grain, Xin-Yuan Huang, Fenglin Deng, Naoki Yamaji, Shannon R.M. Pinson, Miho Fujii-Kashino, John Danku, Alex Douglas, Mary Lou Guerinot, David Salt, Jian Feng Ma Jul 2016

A Heavy Metal P-Type Atpase Oshma4 Prevents Copper Accumulation In Rice Grain, Xin-Yuan Huang, Fenglin Deng, Naoki Yamaji, Shannon R.M. Pinson, Miho Fujii-Kashino, John Danku, Alex Douglas, Mary Lou Guerinot, David Salt, Jian Feng Ma

Dartmouth Scholarship

Rice is a major source of calories and mineral nutrients for over half the world's human population. However, little is known in rice about the genetic basis of variation in accumulation of copper (Cu), an essential but potentially toxic nutrient. Here we identify OsHMA4 as the likely causal gene of a quantitative trait locus controlling Cu accumulation in rice grain. We provide evidence that OsHMA4 functions to sequester Cu into root vacuoles, limiting Cu accumulation in the grain. The difference in grain Cu accumulation is most likely attributed to a single amino acid substitution that leads to different OsHMA4 transport …


A New Method For Ecoacoustics? Toward The Extraction And Evaluation Of Ecologically-Meaningful Soundscape Components Using Sparse Coding Methods, Alice Eldridge, Michael Casey, Paola Moscoso, Mika Peck Jun 2016

A New Method For Ecoacoustics? Toward The Extraction And Evaluation Of Ecologically-Meaningful Soundscape Components Using Sparse Coding Methods, Alice Eldridge, Michael Casey, Paola Moscoso, Mika Peck

Dartmouth Scholarship

Passive acoustic monitoring is emerging as a promising non-invasive proxy for ecological complexity with potential as a tool for remote assessment and monitoring (Sueur & Farina, 2015). Rather than attempting to recognise species-specific calls, either manually or automatically, there is a growing interest in evaluating the global acoustic environment. Positioned within the conceptual framework of ecoacoustics, a growing number of indices have been proposed which aim to capture community- level dynamics by (e.g., Pieretti, Farina & Morri, 2011; Farina, 2014; Sueur et al.,2008b) by providing statistical summaries of the frequency or time domain signal. Although promising, the ecological relevance and …


Microrna Mir-155 Is Necessary For Efficient Gammaherpesvirus Reactivation From Latency, But Not For Establishment Of Latency, Rebecca L. Crepeau, Peisheng Zhang, Edward J. Usherwood Jun 2016

Microrna Mir-155 Is Necessary For Efficient Gammaherpesvirus Reactivation From Latency, But Not For Establishment Of Latency, Rebecca L. Crepeau, Peisheng Zhang, Edward J. Usherwood

Dartmouth Scholarship

MicroRNA-155 (miR-155) has been shown to play significant roles in the immune response, including in the formation of germinal centers (GC) and the development and maturation of T follicular helper (Tfh) cells. There is in vitro evidence to support a critical role for cellular miR-155 and viral miR-155 homologs in the establishment of gammaherpesvirus latency in B cells. We sought to determine the contribution of miR-155 to the establishment and maintenance of latency in vivousing murine gammaherpesvirus (MHV-68) infection. MHV-68-infected mice deficient in miR-155 exhibited decreases in GC B cells and Tfh cells. However, the frequencies of spleen cells …


Alcohol Discrimination And Preferences In Two Species Of Nectar-Feeding Primate, Samuel R. Gochman, Michael B. Brown, Nathaniel J. Dominy Jun 2016

Alcohol Discrimination And Preferences In Two Species Of Nectar-Feeding Primate, Samuel R. Gochman, Michael B. Brown, Nathaniel J. Dominy

Dartmouth Scholarship

Recent reports suggest that dietary ethanol, or alcohol, is a supplemental source of calories for some primates. For example, slow lorises (Nycticebus coucang) consume fermented nectars with a mean alcohol concentration of 0.6% (range: 0.0–3.8%). A similar behaviour is hypothesized for aye-ayes (Daubentonia madagascariensis) based on a single point mutation (A294V) in the gene that encodes alcohol dehydrogenase class IV (ADH4), the first enzyme to catabolize alcohol during digestion. The mutation increases catalytic efficiency 40-fold and may confer a selective advantage to aye-ayes that consume the nectar of Ravenala madagascariensis. It is uncertain, however, whether alcohol exists in this nectar …


The Brain Imaging Data Structure, A Format For Organizing And Describing Outputs Of Neuroimaging Experiments, Krzysztof Gorgolewski, Tibor Auer, Vince Calhoun, R Cameron Craddock, Samir Das, Eugene Duff, Guillaume Flandin, Tristan Glatard, Yaroslav Halchenko Jun 2016

The Brain Imaging Data Structure, A Format For Organizing And Describing Outputs Of Neuroimaging Experiments, Krzysztof Gorgolewski, Tibor Auer, Vince Calhoun, R Cameron Craddock, Samir Das, Eugene Duff, Guillaume Flandin, Tristan Glatard, Yaroslav Halchenko

Dartmouth Scholarship

The development of magnetic resonance imaging (MRI) techniques has defined modern neuroimaging. Since its inception, tens of thousands of studies using techniques such as functional MRI and diffusion weighted imaging have allowed for the non-invasive study of the brain. Despite the fact that MRI is routinely used to obtain data for neuroscience research, there has been no widely adopted standard for organizing and describing the data collected in an imaging experiment. This renders sharing and reusing data (within or between labs) difficult if not impossible and unnecessarily complicates the application of automatic pipelines and quality assurance protocols. To solve this …


Effect Of A Ropy Exopolysaccharide-Producing Bifidobacterium Animalis Subsp. Lactis Strain Orally Administered On Dss-Induced Colitis Mice Model, Claudio Hidalgo-Cantabrana, Francesca Algieri, Alba Rodriguez-Nogales, Teresa Vezza, Pablo Martínez-Camblor Jun 2016

Effect Of A Ropy Exopolysaccharide-Producing Bifidobacterium Animalis Subsp. Lactis Strain Orally Administered On Dss-Induced Colitis Mice Model, Claudio Hidalgo-Cantabrana, Francesca Algieri, Alba Rodriguez-Nogales, Teresa Vezza, Pablo Martínez-Camblor

Dartmouth Scholarship

Exopolysaccharide (EPS)-producing bifidobacteria, particularly Bifidobacterium animalis subsp. lactis strains, are used in the functional food industry as promising probiotics with purported beneficial effects. We used three isogenic strains of B. animalis subsp. lactis, with different EPS producing phenotypes (mucoid-ropy and non-ropy), in order to determine their capability to survive the murine gastrointestinal tract transit, as well as to evaluate their role in improving clinical outcomes in a chemically-induced colitis model. The three strains were able to survive in the intestinal tract of C57BL/6J mice during the course of the intervention study. Furthermore, the disease activity index (DAI) of the animal …


Depression In Visual Impairment Trial (Depvit): A Randomized Clinical Trial Of Depression Treatments In People With Low Vision, Claire L. Nollett, Nathan Bray, Catey Bunce, Robin J. Casten, Rhiannon T. Edwards, Mark T. Hegel, Sarah Janikoun, Sandra E. Jumbe, Barbara Ryan, Julia Shearn Jun 2016

Depression In Visual Impairment Trial (Depvit): A Randomized Clinical Trial Of Depression Treatments In People With Low Vision, Claire L. Nollett, Nathan Bray, Catey Bunce, Robin J. Casten, Rhiannon T. Edwards, Mark T. Hegel, Sarah Janikoun, Sandra E. Jumbe, Barbara Ryan, Julia Shearn

Dartmouth Scholarship

Purpose: The purpose of this study was to compare two interventions for depression, problem solving treatment (PST) and referral to the patient's physician, with a waiting-list control group in people with sight loss and depressive symptoms.

Methods: This was an assessor-masked, exploratory, multicenter, randomized clinical trial, with concurrent economic analysis. Of 1008 consecutive attendees at 14 low-vision rehabilitation centers in Britain, 43% (n = 430) screened positive for depressive symptoms on the Geriatric Depression Scale and 85 of these attendees participated in the trial. Eligible participants were randomized in the ratio 1:1:1 to PST, referral to their physician, or …


The Pseudomonas Aeruginosa Efflux Pump Mexghi-Opmd Transports A Natural Phenazine That Controls Gene Expression And Biofilm Development, Hassan Sakhtah, Leslie Koyama, Yihan Zhang, Diana K. Morales, Blanche Fields, Alexa Price-Whelan, Deborah Hogan Jun 2016

The Pseudomonas Aeruginosa Efflux Pump Mexghi-Opmd Transports A Natural Phenazine That Controls Gene Expression And Biofilm Development, Hassan Sakhtah, Leslie Koyama, Yihan Zhang, Diana K. Morales, Blanche Fields, Alexa Price-Whelan, Deborah Hogan

Dartmouth Scholarship

Redox-cycling compounds, including endogenously produced phenazine antibiotics, induce expression of the efflux pump MexGHI-OpmD in the opportunistic pathogen Pseudomonas aeruginosa Previous studies of P. aeruginosa virulence, physiology, and biofilm development have focused on the blue phenazine pyocyanin and the yellow phenazine-1-carboxylic acid (PCA). In P. aeruginosa phenazine biosynthesis, conversion of PCA to pyocyanin is presumed to proceed through the intermediate 5-methylphenazine-1-carboxylate (5-Me-PCA), a reactive compound that has eluded detection in most laboratory samples. Here, we apply electrochemical methods to directly detect 5-Me-PCA and find that it is transported by MexGHI-OpmD in P. aeruginosa strain PA14 planktonic and biofilm cells. We …


Flow-Dependent Myosin Recruitment During Drosophila Cellularization Requires Zygotic Dunk Activity, Bing He, Adam Martin, Eric Wieschaus May 2016

Flow-Dependent Myosin Recruitment During Drosophila Cellularization Requires Zygotic Dunk Activity, Bing He, Adam Martin, Eric Wieschaus

Dartmouth Scholarship

Actomyosin contractility underlies force generation in morphogenesis ranging from cytokinesis to epithelial extension or invagination. In Drosophila, the cleavage of the syncytial blastoderm is initiated by an actomyosin network at the base of membrane furrows that invaginate from the surface of the embryo. It remains unclear how this network forms and how it affects tissue mechanics. Here, we show that during Drosophila cleavage, myosin recruitment to the cleavage furrows proceeds in temporally distinct phases of tension-driven cortical flow and direct recruitment, regulated by different zygotic genes. We identify the gene dunk, which we show is transiently transcribed when cellularization starts …