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Articles 1 - 15 of 15
Full-Text Articles in Biology
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
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 …
Tertiary Alphabet For The Observable Protein Structural Universe, Craig\ O. Mackenzie, Jianfu Zhou, Gevorg Grigoryan
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. …
A New Timepiece: An Epigenetic Mitotic Clock, Brock C. Christensen, Karl T. Kelsey
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
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 …
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
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 …
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
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 …
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
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
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 …
Alcohol Discrimination And Preferences In Two Species Of Nectar-Feeding Primate, Samuel R. Gochman, Michael B. Brown, Nathaniel J. Dominy
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 …
Elevational Variation In Body-Temperature Response To Immune Challenge In A Lizard, Francisco Javier Zamora-Camacho, Senda Reguera, Gregorio Moreno-Rueda
Elevational Variation In Body-Temperature Response To Immune Challenge In A Lizard, Francisco Javier Zamora-Camacho, Senda Reguera, Gregorio Moreno-Rueda
Dartmouth Scholarship
Immunocompetence benefits animal fitness by combating pathogens, but also entails some costs. One of its main components is fever, which in ectotherms involves two main types of costs: energy expenditure and predation risk. Whenever those costs of fever outweigh its benefits, ectotherms are expected not to develop fever, or even to show hypothermia, reducing costs of thermoregulation and diverting the energy saved to other components of the immune system. Environmental thermal quality, and therefore the thermoregulation cost/benefit balance, varies geographically. Hence, we hypothesize that, in alpine habitats, immune-challenged ectotherms should show no thermal response, given that (1) hypothermia would be …
Micron-Scale Plasma Membrane Curvature Is Recognized By The Septin Cytoskeleton, Andrew A. Bridges, Maximilian S. Jentzsch, Patrick W. Oakes, Patricia Occhipinti, Amy S. Gladfelter
Micron-Scale Plasma Membrane Curvature Is Recognized By The Septin Cytoskeleton, Andrew A. Bridges, Maximilian S. Jentzsch, Patrick W. Oakes, Patricia Occhipinti, Amy S. Gladfelter
Dartmouth Scholarship
Cells change shape in response to diverse environmental and developmental conditions, creating topologies with micron-scale features. Although individual proteins can sense nanometer-scale membrane curvature, it is unclear if a cell could also use nanometer-scale components to sense micron-scale contours, such as the cytokinetic furrow and base of neuronal branches. Septins are filament-forming proteins that serve as signaling platforms and are frequently associated with areas of the plasma membrane where there is micron-scale curvature, including the cytokinetic furrow and the base of cell protrusions. We report here that fungal and human septins are able to distinguish between different degrees of micron-scale …
The Fast-Evolving Phy-2 Gene Modulates Sexual Development In Response To Light In The Model Fungus Neurospora Crassa, Zheng Wang, Ning Li, Jigang Li, Jay C. Dunlap, Frances Trail, Jeffrey P. Townsend
The Fast-Evolving Phy-2 Gene Modulates Sexual Development In Response To Light In The Model Fungus Neurospora Crassa, Zheng Wang, Ning Li, Jigang Li, Jay C. Dunlap, Frances Trail, Jeffrey P. Townsend
Dartmouth Scholarship
Rapid responses to changes in incident light are critical to the guidance of behavior and development in most species. Phytochrome light receptors in particular play key roles in bacterial physiology and plant development, but their functions and regulation are less well understood in fungi. Nevertheless, genome-wide expression measurements provide key information that can guide experiments that reveal how genes respond to environmental signals and clarify their role in development. We performed functional genomic and phenotypic analyses of the two phytochromes in Neurospora crassa, a fungal model adapted to a postfire environment that experiences dramatically variable light conditions. Expression of phy-1 …
Experimenting With Sex: Four Approaches To The Genetics Of Sex Reversal Before 1950, Michael Dietrich
Experimenting With Sex: Four Approaches To The Genetics Of Sex Reversal Before 1950, Michael Dietrich
Dartmouth Scholarship
In the early twentieth century, Tatsuo Aida in Japan, jvind Winge in Denmark, Richard Goldschmidt in Germany, and Calvin Bridges in the United States all developed different experimental systems to study the genetics of sex reversal. These locally specific experimental systems grounded these experimenters' understanding of sex reversal as well as their interpretation of claims regarding experimental results and theories. The comparison of four researchers and their experimental systems reveals how those different systems mediated their understanding of genetic phenomena, and influenced their interpretations of sex reversal.
Evolutionary Escalation: The Bat–Moth Arms Race, John M. Ratcliffe
Evolutionary Escalation: The Bat–Moth Arms Race, John M. Ratcliffe
Dartmouth Scholarship
Echolocation in bats and high-frequency hearing in their insect prey make bats and insects an ideal system for studying the sensory ecology and neuroethology of predator–prey interactions. Here, we review the evolutionary history of bats and eared insects, focusing on the insect order Lepidoptera, and consider the evidence for antipredator adaptations and predator counter-adaptations. Ears evolved in a remarkable number of body locations across insects, with the original selection pressure for ears differing between groups. Although cause and effect are difficult to determine, correlations between hearing and life history strategies in moths provide evidence for how these two variables influence …
A Comprehensive Benchmarking Study Of Protocols And Sequencing Platforms For 16s Rrna Community Profiling, Rosalinda D’Amore, Umer Zeeshan Ijaz, Melanie Schirmer, John G. Kenny, Richard Gregory, Alistair C. Darby, Migun Shakya
A Comprehensive Benchmarking Study Of Protocols And Sequencing Platforms For 16s Rrna Community Profiling, Rosalinda D’Amore, Umer Zeeshan Ijaz, Melanie Schirmer, John G. Kenny, Richard Gregory, Alistair C. Darby, Migun Shakya
Dartmouth Scholarship
In the last 5 years, the rapid pace of innovations and improvements in sequencing technologies has completely changed the landscape of metagenomic and metagenetic experiments. Therefore, it is critical to benchmark the various methodologies for interrogating the composition of microbial communities, so that we can assess their strengths and limitations. The most common phylogenetic marker for microbial community diversity studies is the 16S ribosomal RNA gene and in the last 10 years the field has moved from sequencing a small number of amplicons and samples to more complex studies where thousands of samples and multiple different gene regions are interrogated. …