Open Access. Powered by Scholars. Published by Universities.®

Life Sciences Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 30 of 124

Full-Text Articles in Life Sciences

Enabling Precision Medicine Via Standard Communication Of Hts Provenance, Analysis, And Results, Gil Alterovitz, Dennis Dean, Carole Globe, Michael R. Crusoe, Stiam Soiland-Reyes, Amanda Bell, Anais Hayes, Anita Suresh, Anjan Purkkayastha, Charles H. King, Dan Taylor, Elaine Johanson, Elaine E. Thompson, Eric Donaldson, Hiroki Morizono, Hsinyi Tsang, Jeet K. Vora, Jeremy Goecks, Jianchao Yao, Jonas S. Almeida, Jonathon Keeney, Kanakadurga Addepalli, Konstantinos Krampis, Krista M. Smith, Lydia Guo, Mark Walderhaug, Marco Schito, Matthew Ezewudo, Nuria Guimera, Paul Walsh, Robel Kahsay, Srikanth Gottipati, Timothy C. Rodwell, Toby Bloom, Yuching Lai, Vahan Simonyan, Raja Mazumder Dec 2018

Enabling Precision Medicine Via Standard Communication Of Hts Provenance, Analysis, And Results, Gil Alterovitz, Dennis Dean, Carole Globe, Michael R. Crusoe, Stiam Soiland-Reyes, Amanda Bell, Anais Hayes, Anita Suresh, Anjan Purkkayastha, Charles H. King, Dan Taylor, Elaine Johanson, Elaine E. Thompson, Eric Donaldson, Hiroki Morizono, Hsinyi Tsang, Jeet K. Vora, Jeremy Goecks, Jianchao Yao, Jonas S. Almeida, Jonathon Keeney, Kanakadurga Addepalli, Konstantinos Krampis, Krista M. Smith, Lydia Guo, Mark Walderhaug, Marco Schito, Matthew Ezewudo, Nuria Guimera, Paul Walsh, Robel Kahsay, Srikanth Gottipati, Timothy C. Rodwell, Toby Bloom, Yuching Lai, Vahan Simonyan, Raja Mazumder

Publications and Research

A personalized approach based on a patient's or pathogen’s unique genomic sequence is the foundation of precision medicine. Genomic findings must be robust and reproducible, and experimental data capture should adhere to findable, accessible, interoperable, and reusable (FAIR) guiding principles. Moreover, effective precision medicine requires standardized reporting that extends beyond wet-lab procedures to computational methods. The BioCompute framework (https://w3id.org/biocompute/1.3.0) enables standardized reporting of genomic sequence data provenance, including provenance domain, usability domain, execution domain, verification kit, and error domain. This framework facilitates communication and promotes interoperability. Bioinformatics computation instances that employ the BioCompute framework are easily relayed, repeated …


The International Conference On Intelligent Biology And Medicine (Icibm) 2018: Bioinformatics Towards Translational Applications, Xiaoming Liu, Lei Xie, Zhijin Wu, Kai Wang, Zhongming Zhao, Jianhuan Ruan, Degui Zhi Dec 2018

The International Conference On Intelligent Biology And Medicine (Icibm) 2018: Bioinformatics Towards Translational Applications, Xiaoming Liu, Lei Xie, Zhijin Wu, Kai Wang, Zhongming Zhao, Jianhuan Ruan, Degui Zhi

Publications and Research

The 2018 International Conference on Intelligent Biology and Medicine (ICIBM 2018) was held on June 10–12, 2018, in Los Angeles, California, USA. The conference consisted of a total of eleven scientific sessions, four tutorials, one poster session, four keynote talks and four eminent scholar talks, which covered a wild range of aspects of bioinformatics, medical informatics, systems biology and intelligent computing. Here, we summarize nine research articles selected for publishing in BMC Bioinformatics.


A New Insight Into Underlying Disease Mechanism Through Semi-Parametric Latent Differential Network Model, Yong He, Jiadong Ji, Lei Xie, Xinsheng Zhang, Fuzhong Xue Dec 2018

A New Insight Into Underlying Disease Mechanism Through Semi-Parametric Latent Differential Network Model, Yong He, Jiadong Ji, Lei Xie, Xinsheng Zhang, Fuzhong Xue

Publications and Research

Background

In genomic studies, to investigate how the structure of a genetic network differs between two experiment conditions is a very interesting but challenging problem, especially in high-dimensional setting. Existing literatures mostly focus on differential network modelling for continuous data. However, in real application, we may encounter discrete data or mixed data, which urges us to propose a unified differential network modelling for various data types.

Results

We propose a unified latent Gaussian copula differential network model which provides deeper understanding of the unknown mechanism than that among the observed variables. Adaptive rank-based estimation approaches are proposed with the assumption …


Using Physical Contact Heterogeneity And Frequency To Characterize Dynamics Of Human Exposure To Nonhuman Primate Bodily Fluids In Central Africa, Victor Narat, Mamdou Kampo, Thibut Heyer, Stephanie Rupp, Philippe Ambata, Richard Njouom, Tamara Giles-Vernick Dec 2018

Using Physical Contact Heterogeneity And Frequency To Characterize Dynamics Of Human Exposure To Nonhuman Primate Bodily Fluids In Central Africa, Victor Narat, Mamdou Kampo, Thibut Heyer, Stephanie Rupp, Philippe Ambata, Richard Njouom, Tamara Giles-Vernick

Publications and Research

Emerging infectious diseases of zoonotic origin constitute a recurrent threat to global health. Nonhuman primates (NHPs) occupy an important place in zoonotic spillovers (pathogenic transmissions from animals to humans), serving as reservoirs or amplifiers of multiple neglected tropical diseases, including viral hemorrhagic fevers and arboviruses, parasites and bacteria, as well as retroviruses (simian foamy virus, PTLV) that are pathogenic in human beings. Hunting and butchering studies in Africa characterize at-risk human social groups, but overlook critical factors of contact heterogeneity and frequency, NHP species differences, and meat processing practices. In southeastern Cameroon, a region with a history of zoonotic emergence …


Effects Of Urbanization On The Foraging Ecology And Microbiota Of The Generalist Seabird Larus Argentatus, Matthew Fuirst, Richard R. Veit, Megan Hahn, Nolwenn Dheilly, Lesley H. Thorne Dec 2018

Effects Of Urbanization On The Foraging Ecology And Microbiota Of The Generalist Seabird Larus Argentatus, Matthew Fuirst, Richard R. Veit, Megan Hahn, Nolwenn Dheilly, Lesley H. Thorne

Publications and Research

Larus gull species have proven adaptable to urbanization and due to their generalist feeding behaviors, they provide useful opportunities to study how urban environments impact foraging behavior and host-associated microbiota. We evaluated how urbanization influenced the foraging behavior and microbiome characteristics of breeding herring gulls (Larus argentatus) at three different colonies on the east coast of the United States. Study colonies represented high, medium and low degrees of urbanization, respectively. At all colonies, gulls frequently foraged at landfills and in other urban environments, but both the use of urban environments and gull foraging metrics differed with the degree of urbanization. …


Gofish: A Versatile Nested Pcr Strategy For Environmental Dna Assays For Marine Vertebrates, Mark Y. Stoeckle, Mithun Das Mishu, Zachary Charlop-Powers Dec 2018

Gofish: A Versatile Nested Pcr Strategy For Environmental Dna Assays For Marine Vertebrates, Mark Y. Stoeckle, Mithun Das Mishu, Zachary Charlop-Powers

Publications and Research

Here we describe GoFish, a strategy for single-species environmental DNA (eDNA) presence/absence assays using nested PCR. The assays amplify a mitochondrial 12S rDNA segment with vertebrate metabarcoding primers, followed by nested PCR with M13-tailed, species-specific primers. Sanger sequencing confirms positives detected by gel electrophoresis. We first obtained 12S sequences from 77 fish specimens for 36 northwestern Atlantic taxa not well documented in GenBank. Using these and existing 12S records, we designed GoFish assays for 11 bony fish species common in the lower Hudson River estuary and tested seasonal abundance and habitat preference at two sites. Additional assays detected nine cartilaginous …


Investigating The Impact Of Oxidative Stress On Tetrahymena Thermophila Sirtuin,Thd 18, Emmanuel Dubuisson Dec 2018

Investigating The Impact Of Oxidative Stress On Tetrahymena Thermophila Sirtuin,Thd 18, Emmanuel Dubuisson

Publications and Research

Sirtuins are a family of enzymes that fulfill various important biological functions. Investigators have looked for the implication of Sirtuin genes in cell signaling mechanisms, in the formation and silencing of heterochromatin, in the regulation of ion channels, and in the modulation of the cellular redox reactions[2]. Different model organisms have been previously used to conduct these studies; among them, there are yeasts, nematodes, and fruit flies. Each one has made some valuable contribution into the vast body of knowledge related to this field.

However, gaps in the understanding of Sirtuins functions still remain to be filled. In this optic, …


Instances Of Influenza In The United States Visualized, Parth Patel Dec 2018

Instances Of Influenza In The United States Visualized, Parth Patel

Publications and Research

The Tycho Project collects large data sets related to healthcare and in particular, instances and geographical information of diseases. We look at the instance counts and locations of Influenza from 1919-1951 across the United States. We hope to find seasonal and geographical insight to the spread of the disease.


Immediate Neurophysiological Effects Of Transcranial Electrical Stimulation, Anli Liu, Mihály Vöröslakos, Gregory Kronberg, Simon Henin, Matthew R. Krause, Yu Huang, Alexander Opitz, Ashesh Mehta, Christopher C. Pack, Bart Krekelberg, Antal Berényi, Lucas C. Parra, Lucia Melloni, Orrin Devinsky, György Buzsáki Nov 2018

Immediate Neurophysiological Effects Of Transcranial Electrical Stimulation, Anli Liu, Mihály Vöröslakos, Gregory Kronberg, Simon Henin, Matthew R. Krause, Yu Huang, Alexander Opitz, Ashesh Mehta, Christopher C. Pack, Bart Krekelberg, Antal Berényi, Lucas C. Parra, Lucia Melloni, Orrin Devinsky, György Buzsáki

Publications and Research

Noninvasive brain stimulation techniques are used in experimental and clinical fields for their potential effects on brain network dynamics and behavior. Transcranial electrical stimulation (TES), including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), has gained popularity because of its convenience and potential as a chronic therapy. However, a mechanistic understanding of TES has lagged behind its widespread adoption. Here, we review data and modelling on the immediate neurophysiological effects of TES in vitro as well as in vivo in both humans and other animals. While it remains unclear how typical TES protocols affect neural activity, we …


Contextual Fear Memory Modulates Psd95 Phosphorylation, Ampar Subunits, Pkmζ And Pi3k Differentially Between Adult And Juvenile Rats, Roseanna M. Zanca, Shirley Sanay, Jorge A. Avila, Edgar Rodriguez, Harry N. Shair, Peter A. Serrano Nov 2018

Contextual Fear Memory Modulates Psd95 Phosphorylation, Ampar Subunits, Pkmζ And Pi3k Differentially Between Adult And Juvenile Rats, Roseanna M. Zanca, Shirley Sanay, Jorge A. Avila, Edgar Rodriguez, Harry N. Shair, Peter A. Serrano

Publications and Research

It is well known that young organisms do not maintain memories as long as adults, but the mechanisms for this ontogenetic difference are undetermined. Previous work has revealed that the α-amino-3-hydroxy-5-methyl-4isoxazolepropionic acidreceptor (AMPAr)subunits aretraffickedinto the synaptic membranefollowing memory retrieval in adults. Additionally, phosphorylated PSD-95-pS295 promotes AMPAr stabilization at the synapse. We investigated these plasticity related proteins as potential mediators in the differential contextual stress memory retrieval capabilities observed between adult and juvenile rats. Rats were assigned to either pedestal stress (1h) or no stress control (home cage). Each animal was placed alone in an open field for 5minat the base …


Identification And Characterization Of Early Photoreceptor Cis-Regulatory Elements And Their Relation To Onecut1, Nathalie Jean-Charles, Diego F. Buenaventura, Mark M. Emerson Nov 2018

Identification And Characterization Of Early Photoreceptor Cis-Regulatory Elements And Their Relation To Onecut1, Nathalie Jean-Charles, Diego F. Buenaventura, Mark M. Emerson

Publications and Research

Background: Cone and rod photoreceptors are two of the primary cell types affected in human retinal disease. Potential strategies to combat these diseases are the use of gene therapy to rescue compromised photoreceptors or to generate new functional photoreceptors to replace those lost in the diseased retina. Cis-regulatory elements specific to cones, rods, or both types of photoreceptors are critical components of successful implementation of these two strategies. The purpose of this study was to identify and characterize the cell type specificity and activity of cis-regulatory elements active in developing photoreceptors.

Methods: Cis-regulatory elements were introduced into the developing chicken …


Cryptic Diversity In The Mexican Highlands: Thousands Of Uce Loci Help Illuminate Phylogenetic Relationships, Species Limits And Divergence Times Of Montane Rattlesnakes (Viperidae: Crotalus ), Christopher Blair, Robert W. Bryson Jr, Charles W. Linkem, David Lazcano, John Klicka, John E. Mccormack Nov 2018

Cryptic Diversity In The Mexican Highlands: Thousands Of Uce Loci Help Illuminate Phylogenetic Relationships, Species Limits And Divergence Times Of Montane Rattlesnakes (Viperidae: Crotalus ), Christopher Blair, Robert W. Bryson Jr, Charles W. Linkem, David Lazcano, John Klicka, John E. Mccormack

Publications and Research

With the continued adoption of genome‐scale data in evolutionary biology comes the challenge of adequately harnessing the information to make accurate phylogenetic inferences. Coalescent‐based methods of species tree inference have become common, and concatenation has been shown in simulation to perform well, particularly when levels of incomplete lineage sorting are low. However, simulation conditions are often overly simplistic, leaving empiricists with uncertainty regarding analytical tools. We use a large ultraconserved element data set (>3,000 loci) from rattlesnakes of the Crotalus triseriatus group to delimit lineages and estimate species trees using concatenation and several coalescent‐based methods. Unpartitioned and partitioned maximum …


Il-24 Promotes Apoptosis Through Camp-Dependent Pka Pathways In Human Breast Cancer Cells, Leah Persaud, Jason Mighty, Xuelin Zhong, Ashleigh Francis, Marifer Mendez, Hilal Muharam, Stephen M. Redenti, Dibash Das, Bertal Huseyin Aktas, Moira Sauane Nov 2018

Il-24 Promotes Apoptosis Through Camp-Dependent Pka Pathways In Human Breast Cancer Cells, Leah Persaud, Jason Mighty, Xuelin Zhong, Ashleigh Francis, Marifer Mendez, Hilal Muharam, Stephen M. Redenti, Dibash Das, Bertal Huseyin Aktas, Moira Sauane

Publications and Research

Interleukin 24 (IL-24) is a tumor-suppressing protein, which inhibits angiogenesis and induces cancer cell-specific apoptosis. We have shown that IL-24 regulates apoptosis through phosphorylated eukaryotic initiation factor 2 alpha (eIF2α) during endoplasmic reticulum (ER) stress in cancer. Although multiple stresses converge on eIF2α phosphorylation, the cellular outcome is not always the same. In particular, ER stress-induced apoptosis is primarily regulated through the extent of eIF2α phosphorylation and activating transcription factor 4 (ATF4) action. Our studies show for the first time that cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) activation is required for IL-24-induced cell death in a variety of …


Association Of The Haptoglobin Gene Polymorphism With Cognitive Function And Decline In Elderly African American Adults With Type 2 Diabetes: Findings From The Action To Control Cardiovascular Risk In Diabetes–Memory In Diabetes (Accord-Mind) Study, Michael Beeri, Hung-Mo Lin, Mary Sano, Ramit Ravona-Springer, Xiaoyu Liu, Barbara B. Bendlin, Carey E. Gleason, Elizabeth Guerrero-Berroa, Laili Soleimani, Lenore J. Launer, Scott Ehrenberg, Orit Lache, Yaakov K. Seligman, Andrew P. Levy Nov 2018

Association Of The Haptoglobin Gene Polymorphism With Cognitive Function And Decline In Elderly African American Adults With Type 2 Diabetes: Findings From The Action To Control Cardiovascular Risk In Diabetes–Memory In Diabetes (Accord-Mind) Study, Michael Beeri, Hung-Mo Lin, Mary Sano, Ramit Ravona-Springer, Xiaoyu Liu, Barbara B. Bendlin, Carey E. Gleason, Elizabeth Guerrero-Berroa, Laili Soleimani, Lenore J. Launer, Scott Ehrenberg, Orit Lache, Yaakov K. Seligman, Andrew P. Levy

Publications and Research

IMPORTANCE African American individuals have higher dementia risk than individuals of white race/ethnicity. They also have higher rates of type 2 diabetes, which may contribute to this elevated risk. This study examined the association of the following 2 classes of alleles at the haptoglobin (Hp) locus that are associated with poor cognition, cardiovascular disease, and mortality: Hp 1-1 (associated with poor cognition and cerebrovascular disease) and Hp 2-1 and Hp 2-2 (associated with greater risk ofmyocardial infarction and mortality). An additional polymorphism in the promoter region of the Hp 2 allele, restricted to individuals of African descent, yields a fourth …


Local Adaptation In Mainland Anole Lizards: Integrating Population History And Genome–Environment Associations, Ivan Prates, Anna Penna, Miguel Trefaut Rodrigues, Ana Carolina Carnaval Nov 2018

Local Adaptation In Mainland Anole Lizards: Integrating Population History And Genome–Environment Associations, Ivan Prates, Anna Penna, Miguel Trefaut Rodrigues, Ana Carolina Carnaval

Publications and Research

Environmental gradients constrain physiological performance and thus species’ ranges, suggesting that species occurrence in diverse environments may be associated with local adaptation. Genome–environment association analyses (GEAA) have become central for studies of local adaptation, yet they are sensitive to the spatial orientation of historical range expansions relative to landscape gradients. To test whether potentially adaptive genotypes occur in varied climates in wide‐ranged species, we implemented GEAA on the basis of genomewide data from the anole lizards Anolis ortonii and Anolis punctatus, which expanded from Amazonia, presently dominated by warm and wet settings, into the cooler and less rainy Atlantic …


Pyronaridine Exerts Potent Cytotoxicity On Human Breast And Hematological Cancer Cells Through Induction Of Apoptosis, Paulina J. Villanueva, Alberto Martinez, Sarah T. Baca, Rebecca E. Dejesus, Manuel Larragoity, Lisett Contreras, Denisse A. Gutierrez, Armando Varela-Ramirez, Renato J. Aguilera Nov 2018

Pyronaridine Exerts Potent Cytotoxicity On Human Breast And Hematological Cancer Cells Through Induction Of Apoptosis, Paulina J. Villanueva, Alberto Martinez, Sarah T. Baca, Rebecca E. Dejesus, Manuel Larragoity, Lisett Contreras, Denisse A. Gutierrez, Armando Varela-Ramirez, Renato J. Aguilera

Publications and Research

The potent antimalarial drug pyronaridine (PND) was tested for its potential as an anticancer drug. After exposing cancerous (17) and non-cancerous (2) cells to PND for 72 hr, PND was found to exhibit consistent and potent cytotoxic activity at low micromolar (μM) concentrations that ranged from 1.6 μM to 9.4 μM. Moreover, PND exerted a significant selective cytotoxicity index (SCI) on five out of seven breast cancer cell lines tested, with favorable values of 2.5 to 4.4, as compared with the non-cancerous breast MCF-10A cell line. By using the same comparison, PND exhibited a significant SCI on three out of …


Microbial Diversity In Urban Environments: Concern For Antibiotic Resistance, Ality Aghedo, Mangala Tawde, Nazrul I. Khandaker Nov 2018

Microbial Diversity In Urban Environments: Concern For Antibiotic Resistance, Ality Aghedo, Mangala Tawde, Nazrul I. Khandaker

Publications and Research

We are almost oblivious to the presence of microorganisms in our daily lives, but they exist and come into contact with us all the time. While some bacteria are harmless, and even beneficial, other bacteria can cause infections. A common treatment to bacterial infections is antibiotics and the success of an antibiotic depends on the resistance of the bacteria to the antibiotic. We conducted experiments to identify the types of bacteria that can be found on surfaces or within soil environments that come into contact with a vast number of people on a daily basis and how this can affect …


Postmortem Toxicology Of New Synthetic Opiods, Marta Concheiro, Rachel Chesser, Justine Pardi, Gail Cooper Oct 2018

Postmortem Toxicology Of New Synthetic Opiods, Marta Concheiro, Rachel Chesser, Justine Pardi, Gail Cooper

Publications and Research

One hundred fifteen Americans die every day from opioid overdose. These overdose fatalities have been augmented by the increased availability of potent synthetic opioids, such as fentanyl and its derivatives. The death rate of synthetic opioids, other than methadone, increased by 72.2% from 2014 to 2015, and doubled from 2015 to 2016, situating the USA in the midst of an opioid overdose epidemic. The analytical identification of these opioids in postmortem samples and the correct toxicological data interpretation is critical to identify and implement preventive strategies. This article reviews the current knowledge of postmortem toxicology of synthetic opioids and the …


Manipulation Of Human Verticality Using High-Definition Transcranial Direct Current Stimulation, Taiza E. G. Santos, Diandra B. Favoretto, Iman Ghodratti Toostani, Diego C. Nascimento, Brunna P. Rimoli, Eduardo Bergonzoni, Tenysson Will Lemos, Dennis Quangvinh Truong, Alexandre C. B. Delbem, Bahador Makkiabadi, Renato Moraes, Francisco Louzada, Marom Bikson, Joao P. Leite, Dylan J. Edwards Oct 2018

Manipulation Of Human Verticality Using High-Definition Transcranial Direct Current Stimulation, Taiza E. G. Santos, Diandra B. Favoretto, Iman Ghodratti Toostani, Diego C. Nascimento, Brunna P. Rimoli, Eduardo Bergonzoni, Tenysson Will Lemos, Dennis Quangvinh Truong, Alexandre C. B. Delbem, Bahador Makkiabadi, Renato Moraes, Francisco Louzada, Marom Bikson, Joao P. Leite, Dylan J. Edwards

Publications and Research

Background: Using conventional tDCS over the temporo-parietal junction (TPJ) we previously reported that it is possible to manipulate subjective visual vertical (SVV) and postural control. We also demonstrated that high-definition tDCS (HD-tDCS) can achieve substantially greater cortical stimulation focality than conventional tDCS. However, it is critical to establish dose-response effects using well-defined protocols with relevance to clinically meaningful applications.

Objective: To conduct three pilot studies investigating polarity and intensity-dependent effects of HD-tDCS over the right TPJ on behavioral and physiological outcome measures in healthy subjects. We additionally aimed to establish the feasibility, safety, and tolerability of this stimulation protocol.

Methods: …


Hominoid Intraspecific Cranial Variation Mirrors Neutral Genetic Diversity, Julia M. Zichello, Karen L. Baab, Kieran P. Mcnulty, Christopher J. Raxworthy, Michael E. Steiper Oct 2018

Hominoid Intraspecific Cranial Variation Mirrors Neutral Genetic Diversity, Julia M. Zichello, Karen L. Baab, Kieran P. Mcnulty, Christopher J. Raxworthy, Michael E. Steiper

Publications and Research

Natural selection, developmental constraint, and plasticity have all been invoked as explanations for intraspecific cranial variation in humans and apes. However, global patterns of human cranial variation are congruent with patterns of genetic variation, demonstrating that population history has influenced cranial variation in humans. Here we show that this finding is not unique to Homo sapiens but is also broadly evident across extant ape species. Specifically, taxa that exhibit greater intraspecific cranial shape variation also exhibit greater genetic diversity at neutral autosomal loci. Thus, cranial shape variation within hominoid taxa reflects the population history of each species. Our results suggest …


Maternal Choline And Betaine Supplementation Modifies The Placental Response To Hyperglycemia In Mice And Human Trophoblasts, Khatia Nanobashvili, Chauntelle Jack-Roberts, Rachel Bretter, Naudia Jones, Kathleen Axen, Anjana Saxena, Kali Blain, Xinyin Jiang Oct 2018

Maternal Choline And Betaine Supplementation Modifies The Placental Response To Hyperglycemia In Mice And Human Trophoblasts, Khatia Nanobashvili, Chauntelle Jack-Roberts, Rachel Bretter, Naudia Jones, Kathleen Axen, Anjana Saxena, Kali Blain, Xinyin Jiang

Publications and Research

Gestational diabetes mellitus (GDM) is characterized by excessive placental fat and glucose transport, resulting in fetal overgrowth. Earlier we demonstrated that maternal choline supplementation normalizes fetal growth in GDM mice at mid-gestation. In this study, we further assess how choline and its oxidation product betaine influence determinants of placental nutrient transport in GDM mice and human trophoblasts. C57BL/6J mice were fed a high-fat (HF) diet 4 weeks prior to and during pregnancy to induce GDM or fed a control normal fat (NF) diet. The HF mice also received 25 mM choline, 85 mM betaine, or control drinking water. We observed …


Re-Thinking Alzheimer's Disease Therapeutic Targets Using Gene-Based Tests, Man Ki Kwok, Shi Lin Lin, C Mary Schooling Oct 2018

Re-Thinking Alzheimer's Disease Therapeutic Targets Using Gene-Based Tests, Man Ki Kwok, Shi Lin Lin, C Mary Schooling

Publications and Research

Background: Alzheimer's disease (AD) is a devastating condition with no known effective drug treatments. Existing drugs only alleviate symptoms. Given repeated expensive drug failures, we assessed systematically whether approved and investigational AD drugs are targeting products of genes strongly associated with AD and whether these genes are targeted by existing drugs for other indications which could be re-purposed.

Methods: We identified genes strongly associated with late-onset AD fromthe loci of genetic variants associated with AD at genome-wide-significance and from a gene-based test applied to the most extensively genotyped late-onset AD case (n=17,008)-control (n=37,154) study, the International Genomics of Alzheimer's Project. …


Unravelling The Structure Of Glycosyl Cations Via Cold-Ion Infrared Spectroscopy, Eike Mucha, Mateusz Marianski, Fei-Fei Xu, Daniel A. Thomas, Gerard Meijer, Gert Von Helden, Peter H. Seeberger, Kevin Pagel Oct 2018

Unravelling The Structure Of Glycosyl Cations Via Cold-Ion Infrared Spectroscopy, Eike Mucha, Mateusz Marianski, Fei-Fei Xu, Daniel A. Thomas, Gerard Meijer, Gert Von Helden, Peter H. Seeberger, Kevin Pagel

Publications and Research

Glycosyl cations are the key intermediates during the glycosylation reaction that covalently links building blocks during the synthetic assembly of carbohydrates. The exact structure of these ions remained elusive due to their transient and short-lived nature. Structural insights into the intermediate would improve our understanding of the reaction mechanism of glycosidic bond formation. Here, we report an in-depth structural analysis of glycosyl cations using a combination of cold-ion infrared spectroscopy and first-principles theory. Participating C2 protective groups form indeed a covalent bond with the anomeric carbon that leads to C1-bridged acetoxonium-type structures. The resulting bicyclic structure strongly distorts the ring, …


Hyperphosphorylation Of Tau Associates With Changes In Its Function Beyond Microtubule Stability, Alejandra D. Alonso, Leah S. Cohen, Christopher Corbo, Viktoriya Morozova, Abdeslem Elldrissi, Greg R. Phillips, Frida E. Kleiman Oct 2018

Hyperphosphorylation Of Tau Associates With Changes In Its Function Beyond Microtubule Stability, Alejandra D. Alonso, Leah S. Cohen, Christopher Corbo, Viktoriya Morozova, Abdeslem Elldrissi, Greg R. Phillips, Frida E. Kleiman

Publications and Research

Tau is a neuronal microtubule associated protein whose main biological functions are to promote microtubule self-assembly by tubulin and to stabilize those already formed. Tau also plays an important role as an axonal microtubule protein. Tau is an amazing protein that plays a key role in cognitive processes, however, deposits of abnormal forms of tau are associated with several neurodegenerative diseases, including Alzheimer disease (AD), the most prevalent, and Chronic Traumatic Encephalopathy (CTE) and Traumatic Brain Injury (TBI), the most recently associated to abnormal tau. Tau post-translational modifications (PTMs) are responsible for its gain of toxic function. Alonso et al. …


Season-Ahead Forecasting Of Water Storage And Irrigation Requirements – An Application To The Southwest Monsoon In India, Arun Ravindranath, Naresh Devineni, Upmanu Lall, Paulina Concha Larrauri Oct 2018

Season-Ahead Forecasting Of Water Storage And Irrigation Requirements – An Application To The Southwest Monsoon In India, Arun Ravindranath, Naresh Devineni, Upmanu Lall, Paulina Concha Larrauri

Publications and Research

Water risk management is a ubiquitous challenge faced by stakeholders in the water or agricultural sector. We present a methodological framework for forecasting water storage requirements and present an application of this methodology to risk assessment in India. The application focused on forecasting crop water stress for potatoes grown during the monsoon season in the Satara district of Maharashtra. Pre-season large-scale climate predictors used to forecast water stress were selected based on an exhaustive search method that evaluates for highest ranked probability skill score and lowest root-mean-squared error in a leave-one-out cross-validation mode. Adaptive forecasts were made in the years …


A Dexterous, Glove-Based Teleoperable Low-Power Soft Robotic Arm For Delicate Deep-Sea Biological Exploration, Brennan T. Phillips, Kaitlyn P. Becker, Shunichi Kurumaya, Kevin C. Galloway, Griffin Whittredge, Daniel M. Vogt, Clark B. Teeple, Michelle H. Rosen, Vincent A. Pieribone, David F. Gruber, Robert J. Wood Oct 2018

A Dexterous, Glove-Based Teleoperable Low-Power Soft Robotic Arm For Delicate Deep-Sea Biological Exploration, Brennan T. Phillips, Kaitlyn P. Becker, Shunichi Kurumaya, Kevin C. Galloway, Griffin Whittredge, Daniel M. Vogt, Clark B. Teeple, Michelle H. Rosen, Vincent A. Pieribone, David F. Gruber, Robert J. Wood

Publications and Research

Modern marine biologists seeking to study or interact with deep-sea organisms are confronted with few options beyond industrial robotic arms, claws, and suction samplers. This limits biological interactions to a subset of “rugged” and mostly immotile fauna. As the deep sea is one of the most biologically diverse and least studied ecosystems on the planet, there is much room for innovation in facilitating delicate interactions with a multitude of organisms. The biodiversity and physiology of shallow marine systems, such as coral reefs, are common study targets due to the easier nature of access; SCUBA diving allows for in situ delicate …


Developmental Transitions In Amygdala Pkc Isoforms And Ampa Receptor Expression Associated With Threat Memory In Infant Rats, Maya Opendak, Roseanna M. Zanca, Eben Anane, Peter Serrano, Regina M. Sullivan Oct 2018

Developmental Transitions In Amygdala Pkc Isoforms And Ampa Receptor Expression Associated With Threat Memory In Infant Rats, Maya Opendak, Roseanna M. Zanca, Eben Anane, Peter Serrano, Regina M. Sullivan

Publications and Research

Although infants learn and remember, they rapidly forget, a phenomenon known as infantile amnesia. While myriad mechanisms impact this rapid forgetting, the molecular events supporting memory maintenance have yet to be explored. To explore memory mechanisms across development, we used amygdala-dependent odor-shock conditioning and focused on mechanisms important in adult memory, the AMPA receptor subunits GluA1/2 and upstream protein kinases important for trafficking AMPAR, protein kinase M zeta (PKMζ) and iota/lambda (PKCι/λ). We use odor-shock conditioning in infant rats because it is late-developing (postnatal day, PN10) and can be modulated by corticosterone during a sensitive period in early life. Our …


Nanoparticles As Multimodal Photon Transducers Of Ionizing Radiation, Edwin C. Pratt, Travis M. Shaffer, Qize Zhang, Charles Michael Drain, Jan Grimm Sep 2018

Nanoparticles As Multimodal Photon Transducers Of Ionizing Radiation, Edwin C. Pratt, Travis M. Shaffer, Qize Zhang, Charles Michael Drain, Jan Grimm

Publications and Research

In biomedical imaging, nanoparticles combined with radionuclides that generate Cerenkov luminescence are used in diagnostic imaging, photon-induced therapies, and as activatable probes. In these applications, the nanoparticle is often viewed as a carrier inert to ionizing radiation from the radionuclide. However, certain phenomena such as enhanced nanoparticle luminescence and generation of reactive oxygen species cannot be explained by only Cerenkov luminescence interactions with nanoparticles. Herein, we report methods to examine the mechanisms of nanoparticle excitation by radionuclides, including interactions with Cerenkov luminescence, β particles, and γ radiation. We demonstrate that β scintillation contributes appreciably to excitation and reactivity in certain …


Able: Blockwise Site Frequency Spectrafor Inferring Complex Population Histories And Recombination, Champak R. Beeravolu, Michael J. Hickerson, Laurent A. F. Frantz, Konrad Lohse Sep 2018

Able: Blockwise Site Frequency Spectrafor Inferring Complex Population Histories And Recombination, Champak R. Beeravolu, Michael J. Hickerson, Laurent A. F. Frantz, Konrad Lohse

Publications and Research

We introduce ABLE (Approximate Blockwise Likelihood Estimation), a novel simulation-based composite likelihood method that uses the blockwise site frequency spectrum to jointly infer past demography and recombination. ABLE is explicitly designed for a wide variety of data from unphased diploid genomes to genome-wide multi-locus data (for example, RADSeq) and can also accommodate arbitrarily large samples. We use simulations to demonstrate the accuracy of this method to infer complex histories of divergence and gene flow and reanalyze whole genome data from two species of orangutan. ABLE is available for download at https://github.com/champost/ABLE.


The Role Of Proton Transport In Gating Current In A Voltage Gated Ion Channel, As Shown By Quantum Calculations, Alisher M. Kariev, Michael E. Green Sep 2018

The Role Of Proton Transport In Gating Current In A Voltage Gated Ion Channel, As Shown By Quantum Calculations, Alisher M. Kariev, Michael E. Green

Publications and Research

Over two-thirds of a century ago, Hodgkin and Huxley proposed the existence of voltage gated ion channels (VGIC) to carry Na+ and K+ ions across the cell membrane to create the nerve impulse, in response to depolarization of the membrane. The channels have multiple physiological roles, and play a central role in a wide variety of diseases when they malfunction. The first channel structure was found by MacKinnon and coworkers in 1998. Subsequently the structure of a number of VGIC was determined in the open (ion conducting) state. This type of channel consists of four voltage sensing domains …