المؤلفون: Josep M Comeron, Ramesh Ratnappan, Samuel Bailin

المصدر: PLoS Genetics, Vol 8, Iss 10, p e1002905 (2012)

مصطلحات موضوعية: Genetics, QH426-470

الوصف: Recombination is a fundamental biological process with profound evolutionary implications. Theory predicts that recombination increases the effectiveness of selection in natural populations. Yet, direct tests of this prediction have been restricted to qualitative trends due to the lack of detailed characterization of recombination rate variation across genomes and within species. The use of imprecise recombination rates can also skew population genetic analyses designed to assess the presence and mode of selection across genomes. Here we report the first integrated high-resolution description of genomic and population variation in recombination, which also distinguishes between the two outcomes of meiotic recombination: crossing over (CO) and gene conversion (GC). We characterized the products of 5,860 female meioses in Drosophila melanogaster by genotyping a total of 139 million informative SNPs and mapped 106,964 recombination events at a resolution down to 2 kilobases. This approach allowed us to generate whole-genome CO and GC maps as well as a detailed description of variation in recombination among individuals of this species. We describe many levels of variation in recombination rates. At a large-scale (100 kb), CO rates exhibit extreme and highly punctuated variation along chromosomes, with hot and coldspots. We also show extensive intra-specific variation in CO landscapes that is associated with hotspots at low frequency in our sample. GC rates are more uniformly distributed across the genome than CO rates and detectable in regions with reduced or absent CO. At a local scale, recombination events are associated with numerous sequence motifs and tend to occur within transcript regions, thus suggesting that chromatin accessibility favors double-strand breaks. All these non-independent layers of variation in recombination across genomes and among individuals need to be taken into account in order to obtain relevant estimates of recombination rates, and should be included in a new generation of population genetic models of the interaction between selection and linkage.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC3469467?pdf=renderTest; https://doaj.org/toc/1553-7390Test; https://doaj.org/toc/1553-7404Test

الوصول الحر: https://doaj.org/article/bf4d6e005d43454ca5618a46b58c6306Test

المؤلفون: Ayoda Werede (14321768), James G. Terry (9148351), Sangeeta Nair (14321773), Tecla M. Temu (4452913), Bryan E Shepherd (91892), Samuel Bailin (9312107), Mona Mashayekhi (122116), Curtis L. Gabriel (11953043), Morgan Lima (14321778), Beverly O. Woodward (6477065), LaToya Hannah (11953037), Simon A. Mallal (6477077), Joshua A Beckman (8387334), Jonathan Z. Li (327905), Jesse Fajnzylber (14079285), David G. Harrison (2221333), John Jeffrey Carr (9148369), John R. Koethe (9989742), Celestine N. Wanjalla (11953040)

مصطلحات موضوعية: Infectious agents, Virology, HIV, Atherosclerosis, corCSA, Arterial Remodellig

الوصف: IAS Poster Presentation

العلاقة: https://figshare.com/articles/presentation/Werede_A_AIDS_conference_2022_CW_pdf/21806928Test

الإتاحة: https://doi.org/10.25376/hra.21806928.v1Test

المؤلفون: Ayoda Werede (14321768), James Terry (14321771), Sangeeta Nair (14321773), Tecla M. Temu (4452913), Bryan E Shepherd (91892), Samuel Bailin (9312107), Mona Mashayekhi (122116), Curtis L. Gabriel (11953043), Morgan Lima (14321778), Beverly O. Woodward (6477065), LaToya Hannah (11953037), Simon A. Mallal (6477077), Joshua A Beckman (8387334), Jonathan Z. Li (7035845), Jesse Fajnzylber (14079285), David G. Harrison (2221333), John Jeffrey Carr (9148369), John R. Koethe (9989742), Celestine N. Wanjalla (11953040)

مصطلحات موضوعية: Infectious agents, Virology, HIV, Atherosclerosis, Arterial Remodelling

الوصف: Manuscript

العلاقة: https://figshare.com/articles/journal_contribution/Mean_Coronary_Cross_Sectional_Area_as_a_Measure_of_Arterial_Remodeling_Using_Noncontrast_CT_Imaging_in_Persons_With_HIV/21806886Test

الإتاحة: https://doi.org/10.25376/hra.21806886.v1Test

المؤلفون: Celestine N. Wanjalla, Tecla M. Temu, Mona Mashayekhi, Christian M. Warren, Bryan E. Shepherd, Rama Gangula, Hubaida Fuseini, Samuel Bailin, Curtis L. Gabriel, Pandu Gangula, Meena S. Madhur, Spyros Kalams, Simon A. Mallal, David G. Harrison, Joshua A. Beckman, John R. Koethe

المصدر: AIDS

مصطلحات موضوعية: Immunology, Interleukin-17, HIV Infections, Atherosclerosis, Dilatation, Immunity, Innate, Plaque, Atherosclerotic, Article, Infectious Diseases, Cross-Sectional Studies, Immunology and Allergy, Cytokines, Humans, Th17 Cells, Interleukin-4, Biomarkers

الوصف: OBJECTIVE: Chronic inflammation contributes to the high burden of cardiovascular disease (CVD) in persons with HIV (PWH). HIV has broad effects on innate and adaptive immune cells, including innate lymphoid cells (ILCs) and CD4(+) T-helper cells. At present, the relationship between CVD and plasma cytokines reflecting ILC/T-helper responses in PWH is not well defined. We investigated relationships between plasma cytokines and subclinical atherosclerosis. DESIGN: Cross-sectional study. METHODS: We recruited 70 PWH on a single antiretroviral regimen (efavirenz, tenofovir, and emtricitabine) with at least 12 months of suppressed viremia and 30 HIV-negative controls. We quantified plasma cytokines and chemokines including interferon-γ, interleukin (IL)-4, IL-13, and IL-17A, markers of macrophage activation, and endothelial activation using multiplex assays and ELISA. Cytokines were grouped using Ward’s hierarchical clustering. Brachial artery flow-mediated dilation (FMD) and carotid plaque burden were determined using ultrasound. Multivariable linear regression and negative binomial regression analyses were used to assess the relationships of plasma biomarkers and endpoints adjusted for CVD risk factors. RESULTS: We identified three distinct clusters in PWH, one containing Th1/Th2/ILC1/ILC2 type cytokines, one with Th17/ILC3/macrophage-related cytokines, and a less specific third cluster. Lower FMD was associated with higher plasma IL-17A and macrophage inflammatory protein-1α. In contrast, IL-4, a Th2/ILC2 type cytokine, was associated with carotid plaque. When HIV-negative controls were added to the models clustering was more diffuse, and these associations were attenuated or absent. CONCLUSIONS: Th17/ILC3 and Th2/ILC2-mediated immune mechanisms may have distinct roles in endothelial dysfunction and atherosclerotic plaque formation, respectively, in PWH.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::162c0d7a5a3f71434e352aed9cc254a9Test
https://pubmed.ncbi.nlm.nih.gov/35165215Test

المؤلفون: Samuel Bailin, Jonathan A. Kropski, Rama Gangula, LaToya Hannah, Joshua D. Simmons, Mona Mashayekhi, Fei Ye, Run Fan, Abha Chopra, Ramesh Ram, Simon A. Mallal, Christian M. Warren, Spyros A. Kalams, Curtis L. Gabriel, Celestine N. Wanjalla, John R. Koethe

المصدر: SSRN Electronic Journal.

مصطلحات موضوعية: History, Polymers and Plastics, Business and International Management, Industrial and Manufacturing Engineering

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::e4e9e306ab0943132ec0343eb77ce8a2Test
https://doi.org/10.2139/ssrn.4097122Test

المؤلفون: Celestine N, Wanjalla, Mona, Mashayekhi, Samuel, Bailin, Curtis L, Gabriel, Leslie M, Meenderink, Tecla, Temu, Daniella T, Fuller, Liang, Guo, Kenji, Kawai, Renu, Virmani, Cathy, Jenkins, Chike O, Abana, Christian M, Warren, Rama, Gangula, Rita, Smith, Meena S, Madhur, Aloke V, Finn, Alexander H, Gelbard, Yan Ru, Su, Matthew J, Tyska, Spyros A, Kalams, David G, Harrison, Simon A, Mallal, Tarek S, Absi, Joshua A, Beckman, John R, Koethe

المصدر: Arterioscler Thromb Vasc Biol

مصطلحات موضوعية: Adult, CD4-Positive T-Lymphocytes, Carotid Artery Diseases, Male, Coinfection, Cytomegalovirus, HIV Infections, Coronary Artery Disease, Middle Aged, Risk Assessment, Plaque, Atherosclerotic, Article, CD4 Lymphocyte Count, Vasodilation, Epitopes, Cross-Sectional Studies, Viral Envelope Proteins, Heart Disease Risk Factors, Case-Control Studies, Asymptomatic Diseases, Cytomegalovirus Infections, Humans, Female

الوصف: OBJECTIVE: Persons with human immunodeficiency virus (HIV) have double the risk of developing cardiovascular disease (CVD) compared to the general population. A persistent and heightened immune response to cytomegalovirus (CMV) co-infection may be one contributing factor, but the relationship between CMV replication, virus-specific immune cells and plaque burden is unclear. APPROACH AND RESULTS: We assessed the relationship between CD4(+) T-cell subsets and carotid plaque burden in a cohort of 70 HIV-positive participants with sustained viral suppression on a single antiretroviral regimen and without known CVD. We evaluated relationships between immune parameters, carotid plaque burden, and brachial artery flow-mediated vasodilation (FMD) using multivariable linear and logistic regression models. We found that participants with carotid plaque had increased circulating CX3CR1(+)~GPR56(+)~CD57(+) (i.e., C~G~C)(+) CD4(+) T cells (p=0.03), which is a marker combination associated with anti-viral and cytotoxic responses. In addition, a median of 14.4% [IQR 4.7, 32.7%] of the C~G~C(+) CD4(+) T-cells expressed antigen receptors that recognized a single CMV glycoprotein-B epitope. Notably, using immunofluorescence staining we found that CX3CR1(+) CD4(+) T-cells were present in coronary plaque from deceased HIV-positive persons. C-G-C(+) CD4(+) T cells were also present in cells isolated from the aorta of HIV-negative donors. CONCLUSIONS: HIV-positive persons with carotid atheroma have a higher proportion of circulating CD4(+) T-cells expressing the C~G~C surface marker combination associated with antiviral and cytotoxic responses. These cells can be CMV-specific and are also present in the aorta.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::85756640daadb1a4bdbec6572753510eTest
https://pubmed.ncbi.nlm.nih.gov/33567869Test

المؤلفون: Simon Mallal, Tecla M Temu, Celestine N. Wanjalla, Bryan E. Shepherd, Samuel Bailin, John R. Koethe, Meena S. Madhur, Curtis L. Gabriel, Joshua A. Beckman, Pandu R. Gangula, David G. Harrison, Mona Mashayekhi, Spyros A. Kalams, Hubaida Fuseini

المصدر: SSRN Electronic Journal.

مصطلحات موضوعية: Chemokine, biology, business.industry, medicine.medical_treatment, Interleukin, Inflammation, medicine.disease, Endothelial activation, Immune system, Cytokine, Immunology, biology.protein, Medicine, Endothelial dysfunction, medicine.symptom, business, Macrophage inflammatory protein

الوصف: Objective: Chronic inflammation contributes to the high burden of cardiovascular disease (CVD) in persons with HIV (PWH). HIV has broad effects on immune function, including CD4+T-helper cells which secrete cytokines that regulate innate and adaptive immune pathways implicated in CVD progression. At present, the relationship between T-helper cell responses and CVD in PWH is not well defined. Methods: We recruited 70 PWH on a single antiretroviral regimen (efavirenz, tenofovir, and emtricitabine) with at least 12 months of suppressed viremia. We quantified 19 plasma cytokines and chemokines including interferon (IFN)-γ, interleukin (IL)-2, 4, 13, and 17A, markers of macrophage activation, and markers of endothelial activation using multiplex assays and ELISA. Cytokines were grouped using Ward's hierarchical clustering. Brachial artery flow-mediated dilation (FMD), as a marker of endothelial function, and carotid plaque burden were measured using ultrasound. Multivariable linear regression was used to assess the relationships of biomarkers and endpoints with adjustment for CVD risk factors. Results: We identified three distinct cytokine clusters, one containing Th1/Th2 cytokines, one with Th17-type and macrophage-related cytokines, and a third less specific. Lower brachial artery FMD was associated with higher plasma IL-17A and macrophage inflammatory protein 1α, while higher soluble vascular cell adhesion molecule-1 and intercellular cell adhesion molecule 1 were associated with higher IL-17A, and IL-5. In contrast, IL-10 and the Th2-type cytokine IL-4 were associated with greater plaque burden. Conclusions: Distinct Th2 and Th17-mediated immune mechanisms may have a role at differing stages of atherosclerotic vascular disease in PWH.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::abbdbc45ebe55a94677a861f7a119b71Test
https://doi.org/10.2139/ssrn.3835595Test

المؤلفون: Abha Chopra, Simon Mallal, Christian M. Warren, Morgan C. Lima, Celestine N. Wanjalla, Rama Gangula, Shay Leary, Alyssa M. Hasty, John R. Koethe, Spyros A. Kalams, Briana D. Furch, Curtis L. Gabriel, Joshua D. Simmons, Beverly O. Woodward, Mona Mashayekhi, Ramesh Ram, Wyatt J. McDonnell, Samuel Bailin, LaToya Hannah, Mark A. Pilkinton

المصدر: SSRN Electronic Journal.

مصطلحات موضوعية: Innate immune system, T cell, T-cell receptor, Adipose tissue, Inflammation, Biology, Transcriptome, chemistry.chemical_compound, medicine.anatomical_structure, Single-cell analysis, chemistry, Adipocyte, Immunology, medicine, medicine.symptom

الوصف: Persons with HIV (PWH) are at high risk for diabetes mellitus. Adipose tissue T cells are a central regulator of inflammation and adipocyte function, and the known establishment of a HIV reservoir in adipose could contribute to metabolic dysregulation. Here, we show that CD4+ T cell subsets increased in the adipose of diabetic PWH, specifically CD69+ and CD69lo CD57+ GPR56+ CX3CR1+, are clonally expanded with shared T cell receptors, suggesting a common lineage. We observed that both CD69+ and CX3CR1+ CD4+ T cells have transcriptomes consistent with a TH1 profile in diabetics versus TH2 in non-diabetics. CX3CR1+ CD4+ T cells from diabetic PWH also have increased expression of genes in innate immune pathways, not present in CD69+ cells, suggesting functional differences. This study sets the stage for future investigations to determine whether viral antigens in adipose tissue may promote clonal expansion of pro-inflammatory CX3CR1+ and CD69+ CD4+ T cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::2c5c52037b8484d2f3315435309caaa6Test
https://doi.org/10.2139/ssrn.3489447Test

المؤلفون: Nicolas O. Noiseux, Ambar Haleem, Jean M. Pottinger, Samuel Bailin, Loreen A. Herwaldt, Sarah J Johnson, Birgir Johannsson

المصدر: Infection control and hospital epidemiology. 38(3)

مصطلحات موضوعية: Microbiology (medical), Male, medicine.medical_specialty, Urinalysis, Epidemiology, medicine.medical_treatment, Urinary system, Arthroplasty, Replacement, Hip, 030232 urology & nephrology, Urine, 03 medical and health sciences, Leukocyte Count, 0302 clinical medicine, Anti-Infective Agents, medicine, Humans, Surgical Wound Infection, Prospective Studies, Prospective cohort study, Arthroplasty, Replacement, Knee, Perioperative Period, Aged, Retrospective Studies, 030222 orthopedics, medicine.diagnostic_test, business.industry, Retrospective cohort study, Perioperative, Middle Aged, Arthroplasty, Iowa, Surgery, Leukocyte esterase, Infectious Diseases, Logistic Models, Orthopedic surgery, Urinary Tract Infections, Female, business, Carboxylic Ester Hydrolases

الوصف: OBJECTIVETo identify predictors of treatment for urinary tract infections (UTI) among patients undergoing total hip (THA) or knee (TKA) arthroplasties and to assess an intervention based on these predictors.DESIGNWe conducted a retrospective cohort study of 200 consecutive patients undergoing THA/TKA between February 21, 2011, and June 30, 2011, to identify predictors of treatment for UTI and a prospective cohort study of 50 patients undergoing these procedures between May 21, 2012, and July 17, 2012, to assess the association of signs or symptoms and UTI treatment. We then conducted a before-and-after study to assess whether implementing an intervention affected the frequency of treatment for UTI before or after THA/TKA.SETTINGThe orthopedics department of a university health center.PATIENTSPatients undergoing THA or TKA.INTERVENTIONSurgeons revised their UTI screening and treatment practices.RESULTSPositive leukocyte esterase (PP5 (P=.01;P=.01) were associated with preoperative or postoperative UTI treatment. In the prospective study, 12 patients (24%) had signs and symptoms consistent with UTI. The number of patients treated for presumed UTI decreased 80.2% after the surgeons changed their practices, and surgical site infection (SSI) rates, including prosthetic joint infections (PJIs), did not increase.CONCLUSIONSUrine leukocyte esterase and white blood cell count were the strongest predictors of treatment for UTI before or after THA/TKA. The intervention was associated with a significant decrease in treatment for UTI, and SSI/PJI rates did not increase.Infect Control Hosp Epidemiol2017;38:281–286

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::baf4560afe5ca9ae0c1915e8e8c2a02cTest
https://pubmed.ncbi.nlm.nih.gov/27869063Test

المؤلفون: Ramesh Ratnappan, Samuel Bailin, Josep M. Comeron

المصدر: PLoS Genetics, Vol 8, Iss 10, p e1002905 (2012)
PLoS Genetics

مصطلحات موضوعية: 0106 biological sciences, Male, Cancer Research, lcsh:QH426-470, Population, Gene Conversion, Biology, 010603 evolutionary biology, 01 natural sciences, Chromosomes, Chromosomal crossover, Evolution, Molecular, 03 medical and health sciences, Model Organisms, Meiosis, Genome Analysis Tools, Genetic model, Genetics, Animals, Ectopic recombination, Gene conversion, Crossing Over, Genetic, Nucleotide Motifs, education, Molecular Biology, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Recombination, Genetic, Evolutionary Biology, Evolutionary Theory, 0303 health sciences, education.field_of_study, Genome, Polymorphism, Genetic, Population Biology, Base Sequence, Genetic Maps, Genomics, Animal Models, lcsh:Genetics, Drosophila melanogaster, Female, Homologous recombination, Population Genetics, Recombination, Research Article

الوصف: Recombination is a fundamental biological process with profound evolutionary implications. Theory predicts that recombination increases the effectiveness of selection in natural populations. Yet, direct tests of this prediction have been restricted to qualitative trends due to the lack of detailed characterization of recombination rate variation across genomes and within species. The use of imprecise recombination rates can also skew population genetic analyses designed to assess the presence and mode of selection across genomes. Here we report the first integrated high-resolution description of genomic and population variation in recombination, which also distinguishes between the two outcomes of meiotic recombination: crossing over (CO) and gene conversion (GC). We characterized the products of 5,860 female meioses in Drosophila melanogaster by genotyping a total of 139 million informative SNPs and mapped 106,964 recombination events at a resolution down to 2 kilobases. This approach allowed us to generate whole-genome CO and GC maps as well as a detailed description of variation in recombination among individuals of this species. We describe many levels of variation in recombination rates. At a large-scale (100 kb), CO rates exhibit extreme and highly punctuated variation along chromosomes, with hot and coldspots. We also show extensive intra-specific variation in CO landscapes that is associated with hotspots at low frequency in our sample. GC rates are more uniformly distributed across the genome than CO rates and detectable in regions with reduced or absent CO. At a local scale, recombination events are associated with numerous sequence motifs and tend to occur within transcript regions, thus suggesting that chromatin accessibility favors double-strand breaks. All these non-independent layers of variation in recombination across genomes and among individuals need to be taken into account in order to obtain relevant estimates of recombination rates, and should be included in a new generation of population genetic models of the interaction between selection and linkage.
Author Summary Most sexual eukaryotes require recombination between homologous chromosomes for the proper formation of haploid gametes from diploid germ cells. Evolutionarily, recombination increases the effectiveness of selection in natural populations, thus explaining the pervasiveness of recombination and sex. Recombination is also a central parameter in population genetic studies designed to detect the presence of selection acting across genomes. Current evolutionary analyses are hindered, however, by the use of imprecise recombination rates that can influence the results and skew their interpretation. This limitation is associated with the lack of detailed characterization of natural variation in recombination across genomes and within species. Our study in Drosophila melanogaster represents the first integrated, whole-genome description of recombination that alleviates these deficiencies in any organism. Our results and conclusions will help to characterize the molecular basis of the observed variation in recombination across genomes and have an immediate impact on population genetic analyses of selection, laying the foundation for a new generation of population models that will better capture natural variation in recombination and its consequences.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6a8fa125fb81dd8d631a0f19ca76eb1dTest
https://pubmed.ncbi.nlm.nih.gov/23150039Test