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Full-Text Articles in Biology

Insights Into The Molecular Roles Of Foxr2 In The Pathology Of Primary Pediatric Brain Tumors, Rajendra Gharbaran Oct 2023

Insights Into The Molecular Roles Of Foxr2 In The Pathology Of Primary Pediatric Brain Tumors, Rajendra Gharbaran

Publications and Research

Forkhead box gene R2 (FOXR2) belongs to the family of FOX genes which codes for highly conserved transcription factors (TFs) with critical roles in biological processes ranging from development to organogenesis to metabolic and immune regulation to cellular homeostasis. A number of FOX genes are associated with cancer development and progression and poor prognosis. A growing body of evidence suggests that FOXR2 is an oncogene. Studies suggested important roles for FOXR2 in cancer cell growth, metastasis, and drug resistance. Recent studies showed that FOXR2 is overexpressed by a subset of newly identified entities of embryonal tumors. This review discusses the …


Exploration Of Dark Chemical Genomics Space Via Portal Learning: Applied To Targeting The Undruggable Genome And Covid-19 Anti-Infective Polypharmacology, Tian Cai, Li Xie, Muge Chen, Yang Liu, Di He, Shuo Zhang, Cameron Mura, Philip Boume, Lei Xie Dec 2021

Exploration Of Dark Chemical Genomics Space Via Portal Learning: Applied To Targeting The Undruggable Genome And Covid-19 Anti-Infective Polypharmacology, Tian Cai, Li Xie, Muge Chen, Yang Liu, Di He, Shuo Zhang, Cameron Mura, Philip Boume, Lei Xie

Publications and Research

Advances in biomedicine are largely fueled by exploring uncharted territories of human biology. Machine learning can both enable and accelerate discovery, but faces a fundamental hurdle when applied to unseen data with distributions that differ from previously observed ones—a common dilemma in scientific inquiry. We have developed a new deep learning framework, called Portal Learning , to explore dark chemical and biological space. Three key, novel components of our approach include: (i) end-to-end, step-wise transfer learning, in recognition of biology’s sequence-structure-function paradigm, (ii) out-of-cluster meta-learning, and (iii) stress model selection. Portal Learning provides a practical solution to the out-of-distribution (OOD) …


Taking A Closer Look On The Coronavirus, Alisha Barday, Janina Duran, Lisa Agranov May 2020

Taking A Closer Look On The Coronavirus, Alisha Barday, Janina Duran, Lisa Agranov

Publications and Research

No abstract provided.


Microrna-4719 And Microrna-6756-5p Correlate With Castration-Resistant Prostate Cancer Progression Through Interleukin-24 Regulation, Dibash K. Das, Leah Persaud, Moira Sauane Jan 2019

Microrna-4719 And Microrna-6756-5p Correlate With Castration-Resistant Prostate Cancer Progression Through Interleukin-24 Regulation, Dibash K. Das, Leah Persaud, Moira Sauane

Publications and Research

Prostate cancer (PCa) is the second leading cause of cancer death in the United States. The five-year survival rate for men diagnosed with localized PCa is nearly 100%, yet for those diagnosed with aggressive PCa, it is less than 30%. The pleiotropic cytokine Interleukin-24 (IL-24) has been shown to specifically kill PCa cells compared to normal cells when overexpressed in both in vitro and in vivo studies. Despite this, the mechanisms regulating IL-24 in PCa are not well understood. Since specific microRNAs (miRNAs) are dysregulated in PCa, we used miRNA target prediction algorithm tools to identify miR-4719 and miR-6556-5p as …


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 …


Market Integration Predicts Human Gut Microbiome Attributes Across A Gradient Of Economic Development, Keaton Stagaman, Tara J. Cepon-Robins, Melissa A. Liebert, Theresa E. Gildner, Samuel S. Urlacher, Felicia C. Madimenos, Karen Guillemin, J. Josh Snodgrass, Lawrence S. Sugiyama, Brendan J. M. Bohannan Feb 2018

Market Integration Predicts Human Gut Microbiome Attributes Across A Gradient Of Economic Development, Keaton Stagaman, Tara J. Cepon-Robins, Melissa A. Liebert, Theresa E. Gildner, Samuel S. Urlacher, Felicia C. Madimenos, Karen Guillemin, J. Josh Snodgrass, Lawrence S. Sugiyama, Brendan J. M. Bohannan

Publications and Research

Economic development is marked by dramatic increases in the incidence of microbiome-associated diseases, such as autoimmune diseases and metabolic syndromes, but the lifestyle changes that drive alterations in the human microbiome are not known. We measured market integration as a proxy for economically related lifestyle attributes, such as ownership of specific market goods that index degree of market integration and components of traditional and nontraditional (more modern) house structure and infrastructure, and profiled the fecal microbiomes of 213 participants from a contiguous, indigenous Ecuadorian population. Despite relatively modest differences in lifestyle across the population, greater economic development correlated with significantly …


Nlrp10 Enhances Cd4+ T-Cell-Mediated Ifnγ Response Via Regulation Of Dendritic Cell-Derived Il-12 Release, Maurizio Vacca, Julia Böhme, Lisa Zambetti, Hanif Javanmard Khameneh, Bhairav S. Paleja, Federica Laudisi, Adrian W. S. Ho, Kurt Neo, Keith Weng Kit Leong, Mardiana Marzuki, Bernett Lee, Michael Poidinger, Laura Santambrogio, Liana Tsenova, Francesca Zolezzi, Gennaro De Libero, Amit Singhal, Alessandra Mortellaro Nov 2017

Nlrp10 Enhances Cd4+ T-Cell-Mediated Ifnγ Response Via Regulation Of Dendritic Cell-Derived Il-12 Release, Maurizio Vacca, Julia Böhme, Lisa Zambetti, Hanif Javanmard Khameneh, Bhairav S. Paleja, Federica Laudisi, Adrian W. S. Ho, Kurt Neo, Keith Weng Kit Leong, Mardiana Marzuki, Bernett Lee, Michael Poidinger, Laura Santambrogio, Liana Tsenova, Francesca Zolezzi, Gennaro De Libero, Amit Singhal, Alessandra Mortellaro

Publications and Research

NLRP10 is a nucleotide-binding oligomerization domain-like receptor that functions as an intracellular pattern recognition receptor for microbial products. Here, we generated a Nlrp10−/− mouse to delineate the role of NLRP10 in the host immune response and found that Nlrp10−/− dendritic cells (DCs) elicited sub-optimal IFNγ production by antigenspecific CD4+ T cells compared to wild-type (WT) DCs. In response to T-cell encounter, CD40 ligation or Toll-like receptor 9 stimulation, Nlrp10−/− DCs produced low levels of IL-12, due to a substantial decrease in NF-κB activation. Defective IL-12 production was also evident in vivo and affected IFNγ production by CD4+ T cells. Upon …


Chloride Intracellular Channel Proteins Respond To Heat Stress In Caenorhabditis Elegans, Jun Liang, Yakov Shaulov, Cathy Savage-Dunn, Stéphane Boissinot, Tasmia Hoque Sep 2017

Chloride Intracellular Channel Proteins Respond To Heat Stress In Caenorhabditis Elegans, Jun Liang, Yakov Shaulov, Cathy Savage-Dunn, Stéphane Boissinot, Tasmia Hoque

Publications and Research

Chloride intracellular channel proteins (CLICs) are multi-functional proteins that are expressed in various cell types and differ in their subcellular location. Two CLIC homologs, EXL-1 (excretory canal abnormal like-1) and EXC-4 (excretory canal abnormal± 4), are encoded in the Caenorhabditis elegans genome, providing an excellent model to study the functional diversification of CLIC proteins. EXC-4 functions in excretory canal formation during normal animal development. However, to date, the physiological function of EXL-1 remains largely unknown. In this study, we demonstrate that EXL-1 responds specifically to heat stress and translocates from the cytoplasm to the nucleus in intestinal cells and body …


Plasmid Diversity And Phylogenetic Consistency In The Lyme Disease Agent Borrelia Burgdorferi, Sherwood R. Casjens, Eddie B. Gilcrease, Marija Vujadinovic, Emmanuel F. Mongodin, Benjamin J. Luft, Steven E. Schutzer, Claire M. Fraser, Wei-Gang Qiu Feb 2017

Plasmid Diversity And Phylogenetic Consistency In The Lyme Disease Agent Borrelia Burgdorferi, Sherwood R. Casjens, Eddie B. Gilcrease, Marija Vujadinovic, Emmanuel F. Mongodin, Benjamin J. Luft, Steven E. Schutzer, Claire M. Fraser, Wei-Gang Qiu

Publications and Research

Background: Bacteria from the genus Borrelia are known to harbor numerous linear and circular plasmids. We report here a comparative analysis of the nucleotide sequences of 236 plasmids present in fourteen independent isolates of the Lyme disease agent B. burgdorferi.

Results: We have sequenced the genomes of 14 B. burgdorferi sensu stricto isolates that carry a total of 236 plasmids. These individual isolates carry between seven and 23 plasmids. Their chromosomes, the cp26 and cp32 circular plasmids, as well as the lp54 linear plasmid, are quite evolutionarily stable; however, the remaining plasmids have undergone numerous non-homologous and often duplicative recombination …


Identification, Validation, And Targeting Of The Mutant P53- Parp-Mcm Chromatin Axis In Triple Negative Breast Cancer, Wei-Gang Qiu, Alla Polotskaia, Gu Xiao, Lia Di, Yuhan Zhao, Wenwei Hu, John Philip, Ronald C. Hendrickson, Jill Bargonetti Jan 2017

Identification, Validation, And Targeting Of The Mutant P53- Parp-Mcm Chromatin Axis In Triple Negative Breast Cancer, Wei-Gang Qiu, Alla Polotskaia, Gu Xiao, Lia Di, Yuhan Zhao, Wenwei Hu, John Philip, Ronald C. Hendrickson, Jill Bargonetti

Publications and Research

Over 80% of triple negative breast cancers express mutant p53. Mutant p53 often gains oncogenic function suggesting that triple negative breast cancers may be driven by p53 protein type. To determine the chromatin targets of this gain-of-function mutant p53 we used inducible knockdown of endogenous gain-of-function mtp53 in MDA-MB-468 cells in conjunction with stable isotope labeling with amino acids in cell culture and subcellular fractionation. We sequenced over 70,000 total peptides for each corresponding reciprocal data set and were able to identify 3010 unique cytoplasmic fraction proteins and 3403 unique chromatin fraction proteins. The present proteomics experiment corroborated our previous …


Efficient Method For Transfer Of Microinjected Eggs To Mouse Ampulla For Generating Transgenic Mice, Guang Wen, Jin Di, Qian Li, Jianling Chen, Ling Jin, Cheng Wang, Sanqing Xu Dec 2016

Efficient Method For Transfer Of Microinjected Eggs To Mouse Ampulla For Generating Transgenic Mice, Guang Wen, Jin Di, Qian Li, Jianling Chen, Ling Jin, Cheng Wang, Sanqing Xu

Publications and Research

Background: The new method described here is highly efficient in transferring microinjected mouse eggs (MEs) through the bursa membrane of a surrogate mother mouse to the ampulla of the oviduct without damaging the blood vessels on the bursa membrane.

Results: This method causes no loss of blood, and it produces newborn pups/founders from approximately 70% of the transferred MEs, because only a small hole is made on the blood vessel–free area of the bursa membrane and ampulla of the surrogate mother mouse. The infundibulum remains intact. The small hole on the bursa membrane/ ampulla may already heal up before the …


Hiv Glycoprotein Gp120 Impairs Fast Axonal Transport By Activating Tak1 Signaling Pathways, Sarah H. Berth, Nichole Mesnard-Hoaglin, Bin Wang, Hajwa Kim, Yuyu Song, Maria Sapar, Gerardo Morfini, Scott T. Brady Nov 2016

Hiv Glycoprotein Gp120 Impairs Fast Axonal Transport By Activating Tak1 Signaling Pathways, Sarah H. Berth, Nichole Mesnard-Hoaglin, Bin Wang, Hajwa Kim, Yuyu Song, Maria Sapar, Gerardo Morfini, Scott T. Brady

Publications and Research

Sensory neuropathies are the most common neurological complication of HIV. Of these, distal sensory polyneuropathy (DSP) is directly caused by HIV infection and characterized by length-dependent axonal degeneration of dorsal root ganglion (DRG) neurons. Mechanisms for axonal degeneration in DSP remain unclear, but recent experiments revealed that the HIV glycoprotein gp120 is internalized and localized within axons of DRG neurons. Based on these findings, we investigated whether intra-axonal gp120 might impair fast axonal transport (FAT), a cellular process critical for appropriate maintenance of the axonal compartment. Significantly, we found that gp120 severely impaired both anterograde and retrograde FAT. Providing a …


Electro-Chemotactic Fields Induce Cooperative Movement Of Cns Cells, Shawn Mishra, Stephen Redenti, Maribel Vazquez Oct 2016

Electro-Chemotactic Fields Induce Cooperative Movement Of Cns Cells, Shawn Mishra, Stephen Redenti, Maribel Vazquez

Publications and Research

Vision loss in adults with Age Related Macular Degeneration (AMD) is attributed to damage of retinal photoreceptor cells that initiate vision by absorbing light. Mouse models have suggested that transplantation of precursor cells may be a novel approach to restore vision. This project uses a combination of electrotactic and chemotactic stimuli to promote and guide CNS cell migration within a microdevice model.


Insights Into The Molecular Roles Of Heparan Sulfate Proteoglycans (Hspgs-Syndecans) In Autocrine And Paracrine Growth Factor Signaling In The Pathogenesis Of Hodgkin's Lymphoma, Rajendra Ghardbaran Sep 2016

Insights Into The Molecular Roles Of Heparan Sulfate Proteoglycans (Hspgs-Syndecans) In Autocrine And Paracrine Growth Factor Signaling In The Pathogenesis Of Hodgkin's Lymphoma, Rajendra Ghardbaran

Publications and Research

Syndecans (SDC, SYND) comprise a group of four structurally related type 1 transmembrane heparan sulfate proteoglycans (HSPGs) that play important roles in tumorigenic processes. SDCs exert signaling via their protein cores and their conserved transmembrane and cytoplasmic domains or by forming complexes with growth factors (GFs). In classical Hodgkin's lymphoma (cHL), a lymphoid neoplasm of predominantly B cell origin, SDC1 and SDC4 are the active SDCs, and a number of GF (vascular endothelial growth factor, fibroblast growth factor, etc.) signaling pathways have been studied. However, despite extensive pre-clinical and clinical research on SDC-mediated GF signaling in many cancer types, there …


Botanical Therapeutics In The Modern World, Vyacheslav Dushenkov, Brittany L. Graf, Mary Ann Lila Jun 2016

Botanical Therapeutics In The Modern World, Vyacheslav Dushenkov, Brittany L. Graf, Mary Ann Lila

Publications and Research

Plants are the source of a broad spectrum of biologically active phytochemicals. For effective defense against pathogens and abiotic stress, plants have developed complicated chemical strategies with different mechanisms of action. By harnessing these phytochemicals, humans have used plants for medicinal purposes for over 30,000 years, and they remain a valuable source for the development of modern therapeutics. Plant-derived materials are utilized as pharmaceuticals, botanical drugs, dietary supplements (nutraceuticals), functional food ingredients, and cosmeceuticals. The Global Institute for Bioexploration (GIBEX), an international conglomerate of researchers, is involved in multiple botanical therapeutics discovery and development programs.


Mechanism Of Action And Applications Of Interleukin 24 In Immunotherapy, Leah Persaud, Dayenny De Jesus, Oliver Brannigan, Maria Richiez-Paredes, Jeannette Huaman, Giselle Alvarado, Linda Riker, Gissete Mendez, Jordan Dejoie, Moira Sauane Jun 2016

Mechanism Of Action And Applications Of Interleukin 24 In Immunotherapy, Leah Persaud, Dayenny De Jesus, Oliver Brannigan, Maria Richiez-Paredes, Jeannette Huaman, Giselle Alvarado, Linda Riker, Gissete Mendez, Jordan Dejoie, Moira Sauane

Publications and Research

Interleukin 24 (IL-24) is an important pleiotropic immunoregulatory cytokine, whose gene is located in human chromosome 1q32-33. IL-24’s signaling pathways have diverse biological functions related to cell differentiation, proliferation, development, apoptosis, and inflammation, placing it at the center of an active area of research. IL-24 is well known for its apoptotic effect in cancer cells while having no such effect on normal cells. IL-24 can also be secreted by both immune and non-immune cells. Downstream effects of IL-24, after binding to the IL-20 receptor, can occur dependently or independently of the JAK/STAT signal transduction pathway, which is classically involved in …


Epigenetic Profiles Signify Cell Fate Plasticity In Unipotent Spermatogonial Stem And Progenitor Cells, Ying Liu, Eugenia G. Giannopoulou, Duacheng Wen, Ilaria Falciatori, Oliver Elemento, C. David Allis, Shahin Rafii, Marco Seandel Apr 2016

Epigenetic Profiles Signify Cell Fate Plasticity In Unipotent Spermatogonial Stem And Progenitor Cells, Ying Liu, Eugenia G. Giannopoulou, Duacheng Wen, Ilaria Falciatori, Oliver Elemento, C. David Allis, Shahin Rafii, Marco Seandel

Publications and Research

Spermatogonial stem and progenitor cells (SSCs) generate adult male gametes. During in vitro expansion, these unipotent murine cells spontaneously convert to multipotent adult spermatogonial-derived stem cells (MASCs). Here we investigate this conversion process through integrative transcriptomic and epigenomic analyses. We find in SSCs that promoters essential to maintenance and differentiation of embryonic stem cells (ESCs) are enriched with histone H3-lysine4 and -lysine 27 trimethylations. These bivalent modifications are maintained at most somatic promoters after conversion, bestowing MASCs an ESC-like promoter chromatin. At enhancers, the core pluripotency circuitry is activated partially in SSCs and completely in MASCs, concomitant with loss of …


From Mollusks To Medicine: A Venomics Approach For The Discovery And Characterization Of Therapeutics From Terebridae Peptide Toxins, Aida Verdes, Prachi Anand, Juliette Gorson, Stephen Jannetti, Patrick Kelly, Abba Leffler, Danny Simpson, Girish Ramrattan, Mandë Holford Apr 2016

From Mollusks To Medicine: A Venomics Approach For The Discovery And Characterization Of Therapeutics From Terebridae Peptide Toxins, Aida Verdes, Prachi Anand, Juliette Gorson, Stephen Jannetti, Patrick Kelly, Abba Leffler, Danny Simpson, Girish Ramrattan, Mandë Holford

Publications and Research

Animal venoms comprise a diversity of peptide toxins that manipulate molecular targets such as ion channels and receptors, making venom peptides attractive candidates for the development of therapeutics to benefit human health. However, identifying bioactive venom peptides remains a significant challenge. In this review we describe our particular venomics strategy for the discovery, characterization, and optimization of Terebridae venom peptides, teretoxins. Our strategy reflects the scientific path from mollusks to medicine in an integrative sequential approach with the following steps: (1) delimitation of venomous Terebridae lineages through taxonomic and phylogenetic analyses; (2) identification and classification of putative teretoxins through omics …


A Model Of Blood Pressure, Heart Rate, And Vaso-Vagal Responses Produced By Vestibulo-Sympathetic Activation, Theodore Raphan, Bernard Cohen, Yongqing Xiang, Sergei B. Yakushin Mar 2016

A Model Of Blood Pressure, Heart Rate, And Vaso-Vagal Responses Produced By Vestibulo-Sympathetic Activation, Theodore Raphan, Bernard Cohen, Yongqing Xiang, Sergei B. Yakushin

Publications and Research

Blood Pressure (BP), comprised of recurrent systoles and diastoles, is controlled by central mechanisms to maintain blood flow. Periodic behavior of BP was modeled to study how peak amplitudes and frequencies of the systoles are modulated by vestibular activation. The model was implemented as a relaxation oscillator, driven by a central signal related to Desired BP. Relaxation oscillations were maintained by a second order system comprising two integrators and a threshold element in the feedback loop. The output signal related to BP was generated as a nonlinear function of the derivative of the first state variable, which is a summation …


Abnormal Tau Induces Cognitive Impairment Through Two Different Mechanisms: Synaptic Dysfunction And Neuronal Loss, J. Di, L. S. Cohen, C. P. Corbo, Greg R. Phillips, Abdeslem El Idrissi, Alejandra D. Alonso Feb 2016

Abnormal Tau Induces Cognitive Impairment Through Two Different Mechanisms: Synaptic Dysfunction And Neuronal Loss, J. Di, L. S. Cohen, C. P. Corbo, Greg R. Phillips, Abdeslem El Idrissi, Alejandra D. Alonso

Publications and Research

The hyperphosphorylated microtubule-associated protein tau is present in several neurodegenerative diseases, although the causal relationship remains elusive. Few mouse models used to study Alzheimerlike dementia target tau phosphorylation. We created an inducible pseudophosphorylated tau (Pathological Human Tau, PH-Tau) mouse model to study the effect of conformationally modified tau in vivo. Leaky expression resulted in two levels of PH-Tau: low basal level and higher upon induction (4% and 14% of the endogenous tau, respectively). Unexpectedly, low PH-Tau resulted in significant cognitive deficits, decrease in the number of synapses (seen by EM in the CA1 region), reduction of synaptic proteins, and localization …


The Human Disease-Associated Ab Amyloid Core Sequence Forms Functional Amyloids In A Fungal Adhesin, Rachele D. Rameau, Desmond N. Jackson, Audrey Beaussary, Yves F. Dufrêne, Peter N. Lipke Jan 2016

The Human Disease-Associated Ab Amyloid Core Sequence Forms Functional Amyloids In A Fungal Adhesin, Rachele D. Rameau, Desmond N. Jackson, Audrey Beaussary, Yves F. Dufrêne, Peter N. Lipke

Publications and Research

There is increasing evidence that many amyloids in living cells have physiological functions. On the surfaces of fungal cells, amyloid core sequences in adhesins can aggregate into 100- to 1,000-nm-wide patches to form high-avidity adhesion nanodomains on the cell surface. The nanodomains form through interactions that have amyloid-like properties: binding of amyloid dyes, perturbation by antiamyloid agents, and interaction with homologous sequences. To test whether these functional interactions are mediated by typical amyloid interactions, we substituted an amyloid core sequence, LVFFA, from human A protein for the native sequence IVIVA in the 1,419-residue Candida albicans adhesin Als5p. The chimeric protein …


Cellmapper: Rapid And Accurate Inference Of Gene Expression In Difficult-To-Isolate Cell Types, Bradlee D. Nelms, Levi Waldron, Luis A. Barrera, Andrew W. Weflen, Jeremy A. Goettel, Guoji Guo, Robert K. Montgomery, Marian R. Neutra, David T. Breault, Scott B. Snapper, Stuart H. Orkin, Martha L. Bulyk, Curtis Huttenhower, Wayne I. Lencer Jan 2016

Cellmapper: Rapid And Accurate Inference Of Gene Expression In Difficult-To-Isolate Cell Types, Bradlee D. Nelms, Levi Waldron, Luis A. Barrera, Andrew W. Weflen, Jeremy A. Goettel, Guoji Guo, Robert K. Montgomery, Marian R. Neutra, David T. Breault, Scott B. Snapper, Stuart H. Orkin, Martha L. Bulyk, Curtis Huttenhower, Wayne I. Lencer

Publications and Research

We present a sensitive approach to predict genes expressed selectively in specific cell types, by searching publicly available expression data for genes with a similar expression profile to known cell-specific markers. Our method, CellMapper, strongly outperforms previous computational algorithms to predict cell type-specific expression, especially for rare and difficult-to-isolate cell types. Furthermore, CellMapper makes accurate predictions for human brain cell types that have never been isolated, and can be rapidly applied to diverse cell types from many tissues. We demonstrate a clinically relevant application to prioritize candidate genes in disease susceptibility loci identified by GWAS.


Job Stress, Inflammation, And Atherosclerosis: A Reflection, Renzo Bianchi, Irvin Sam Schonfeld Jan 2016

Job Stress, Inflammation, And Atherosclerosis: A Reflection, Renzo Bianchi, Irvin Sam Schonfeld

Publications and Research

Stress in general has been associated with inflammation and atherosclerosis (Sapolsky, 2004; Slavich and Irwin, 2014). The accumulation of inadequately controlled studies has become a concern (Bianchi, 2016; Schonfeld & Bianchi, 2016). Stronger efforts should be made to take into account both empirically identified and theoretically likely confounders in this research field. Assessing the contribution of job-related factors to given outcomes without simultaneously considering the role of relevant non-job factors is unwarranted. Results from inadequately controlled studies can lead to our making ineffective, or even counter-productive, decisions in terms of public health policies.


Lesion-Specific Immune Response In Granulomas Of Patients With Pulmonary Tuberculosis: A Pilot Study, Selvakumar Subbian, Liana Tsenova, Mi-Jeong Kim, Helen C. Wainwright, Annalie Visser, Nirmalya Bandyopadhyay, Joel S. Bader, Petros C. Karakousis, Gabriele B. Murrmann, Linda-Gail Bekker, David G. Russell, Gilla Kaplan Jul 2015

Lesion-Specific Immune Response In Granulomas Of Patients With Pulmonary Tuberculosis: A Pilot Study, Selvakumar Subbian, Liana Tsenova, Mi-Jeong Kim, Helen C. Wainwright, Annalie Visser, Nirmalya Bandyopadhyay, Joel S. Bader, Petros C. Karakousis, Gabriele B. Murrmann, Linda-Gail Bekker, David G. Russell, Gilla Kaplan

Publications and Research

The formation and maintenance of granulomas is central to the host response to Mycobacterium tuberculosis (Mtb) infection. It is widely accepted that the lungs of patients with tuberculosis (TB) usually contain multiple infection foci, and that the granulomas evolve and differentiate independently, resulting in considerable heterogeneity. Although gene expression profiles of human blood cells have been proposed as biomarkers of Mtb infection and/or active disease, the immune profiles of discrete lesion types has not been studied extensively. Using histology, immunopathology and genome-wide transcriptome analysis, we explored the immunological profile of human lung TB granulomas. We show that although the different …


The Regulatory Function Of Sphingosine-1-Phosphate Signaling Axis On Regulatory T Cells In Colorectal Cancer, Andrew V. Nguyen, Yuan-Yuan Wu, Elaine Y. Lin Feb 2015

The Regulatory Function Of Sphingosine-1-Phosphate Signaling Axis On Regulatory T Cells In Colorectal Cancer, Andrew V. Nguyen, Yuan-Yuan Wu, Elaine Y. Lin

Publications and Research

In tumors associated with inflammation such as inflammatory bowel disease (IBD) and colorectal cancer (CRC), high numbers of regulatory T cells (Tregs) are associated with both favorable and poor prognoses. The functions of Tregs in CRC remain elusive and have yet to be clearly defined. With new evidence supporting many subsets of Tregs, the research on the development and functions of these cells has begun to come to fruition. The sphingosine 1 phosphate (S1P) pathway was recently reported to regulate the development and function of regulatory T cells. This pathway may shine new light into the pleiotropic nature of these …


Effects Of Extreme Climate Events On Tea (Camellia Sinensis) Functional Quality Validate Indigenous Farmer Knowledge And Sensory Preferences In Tropical China, Selena Ahmed, John Richard Stepp, Colin M. Orians, Timothy S. Griffin, Corene Matyas, Albert Robbat, Sean Cash, Dayuan Xue, Chunlin Long, Uchenna Unachukwu, Sarabeth Buckley, Edward J. Kennelly Oct 2014

Effects Of Extreme Climate Events On Tea (Camellia Sinensis) Functional Quality Validate Indigenous Farmer Knowledge And Sensory Preferences In Tropical China, Selena Ahmed, John Richard Stepp, Colin M. Orians, Timothy S. Griffin, Corene Matyas, Albert Robbat, Sean Cash, Dayuan Xue, Chunlin Long, Uchenna Unachukwu, Sarabeth Buckley, Edward J. Kennelly

Publications and Research

Climate change is impacting agro-ecosystems, crops, and farmer livelihoods in communities worldwide. While it is well understood that more frequent and intense climate events in many areas are resulting in a decline in crop yields, the impact on crop quality is less acknowledged, yet it is critical for food systems that benefit both farmers and consumers through high-quality products. This study examines tea (Camellia sinensis; Theaceae), the world’s most widely consumed beverage after water, as a study system to measure effects of seasonal precipitation variability on crop functional quality and associated farmer knowledge, preferences, and livelihoods. Sampling was conducted in …


Review: Zinc’S Functional Significance In The Vertebrate Retina, Harris Ripps, Richard L. Chappell Jul 2014

Review: Zinc’S Functional Significance In The Vertebrate Retina, Harris Ripps, Richard L. Chappell

Publications and Research

This review covers a broad range of topics related to the actions of zinc on the cells of the vertebrate retina. Much of this review relies on studies in which zinc was applied exogenously, and therefore the results, albeit highly suggestive, lack physiologic significance. This view stems from the fact that the concentrations of zinc used in these studies may not be encountered under the normal circumstances of life. This caveat is due to the lack of a zinc-specific probe with which to measure the concentrations of Zn2+ that may be released from neurons or act upon them. However, a …


Association Between Symptomatic Vulvovaginal Candidiasis And Hiv Rna Levels In Plasma And Genital Secretions Among Women On Haart, Teke Apalata, William H. Carr, Benjamin Longo-Mbenza, Willem A. Sturm, P. Moodley Jun 2014

Association Between Symptomatic Vulvovaginal Candidiasis And Hiv Rna Levels In Plasma And Genital Secretions Among Women On Haart, Teke Apalata, William H. Carr, Benjamin Longo-Mbenza, Willem A. Sturm, P. Moodley

Publications and Research

Background. Genital tract (GT) inflammation plays a major role in HIV transmission. We aimed to determine the association between symptomatic vulvovaginal candidiasis (VVC) and HIV RNA levels in plasma and GTs of HIV-infected women on highly active antiretroviral therapy (HAART).

Method. Women with VVC on HAART were recruited from a primary healthcare clinic in KwaZulu-Natal Province, South Africa, between June 2011 and December 2011. VVC was diagnosed clinically, supported by Gram staining and culture of genital secretions. HIV RNA load was determined by reverse transcription polymerase chain reaction. CD4+ counts were obtained from patients’ medical records.

Results. Plasma HIV RNA …


Communication And Common Interest, Peter Godfrey-Smith, Manolo Martínez Nov 2013

Communication And Common Interest, Peter Godfrey-Smith, Manolo Martínez

Publications and Research

Explaining the maintenance of communicative behavior in the face of incentives to deceive, conceal information, or exaggerate is an important problem in behavioral biology. When the interests of agents diverge, some form of signal cost is often seen as essential to maintaining honesty. Here, novel computational methods are used to investigate the role of common interest between the sender and receiver of messages in maintaining cost-free informative signaling in a signaling game. Two measures of common interest are defined. These quantify the divergence between sender and receiver in their preference orderings over acts the receiver might perform in each state …


Candidatus Syngnamydia Venezia, A Novel Member Of The Phylum Chlamydiae From The Broad Nosed Pipefish, Syngnathustyphle Typhle, Alexander Fehr, Elisabeth Walther, Heike Schmidt-Posthaus, Lisbeth Nufer, Anthony B. Wilson, Miroslav Svercel, Denis Richter, Helmut Segner, Andreas Pospischil, Lloyd Vaughan Aug 2013

Candidatus Syngnamydia Venezia, A Novel Member Of The Phylum Chlamydiae From The Broad Nosed Pipefish, Syngnathustyphle Typhle, Alexander Fehr, Elisabeth Walther, Heike Schmidt-Posthaus, Lisbeth Nufer, Anthony B. Wilson, Miroslav Svercel, Denis Richter, Helmut Segner, Andreas Pospischil, Lloyd Vaughan

Publications and Research

Chlamydia are obligate intracellular bacteria and important pathogens of humans and animals. Chlamydia-related bacteria are also major fish pathogens, infecting epithelial cells of the gills and skin to cause the disease epitheliocystis. Given the wide distribution, ancient origins and spectacular diversity of bony fishes, this group offers a rich resource for the identification and isolation of novel Chlamydia. The broad-nosed pipefish (Syngnathus typhle) is a widely distributed and genetically diverse temperate fish species, susceptible to epitheliocystis across much of its range. We describe here a new bacterial species, Candidatus Syngnamydia venezia; epitheliocystis agent of S. typhle and close relative to …