Medicine and Health Sciences Commons^™

Enhanced Interleukin-1 Activity Contributes To Exercise Intolerance In Patients With Systolic Heart Failure, Benjamin W. Van Tassell, Ross A. Arena, Stefano Toldo, Eleonora Mezzaroma, Tania Azam, Ignacio M. Seropian, Keyur Shah, Justin Canada, Norbert F. Voelkel, Charles A. Dinarello, Antonio Abbate

Pharmacotherapy and Outcomes Science Publications

Background

Heart failure (HF) is a complex clinical syndrome characterized by impaired cardiac function and poor exercise tolerance. Enhanced inflammation is associated with worsening outcomes in HF patients and may play a direct role in disease progression. Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that becomes chronically elevated in HF and exerts putative negative inotropic effects.

Methods and Results

We developed a model of IL-1β-induced left ventricular (LV) dysfunction in healthy mice that exhibited a 32% reduction in LV fractional shortening (P

Conclusions

These findings suggest that IL-1β activity contributes to poor exercise tolerance in patients with systolic HF and identifies …

Atorvastatin With Or Without An Antibody To Pcsk9 In Primary Hypercholesterolemia, Eli M. Roth, James M. Mckenny, Corinne Hanotin, Gaelle Asset, Evan A. Stein

Pharmacotherapy and Outcomes Science Publications

Background

Serum proprotein convertase subtilisin/kexin 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, increasing the degradation of LDL receptors and reducing the rate at which LDL cholesterol is removed from the circulation. REGN727/SAR236553 (designated here as SAR236553), a fully human PCSK9 monoclonal antibody, increases the recycling of LDL receptors and reduces LDL cholesterol levels.

Methods

We performed a phase 2, multicenter, double-blind, placebo-controlled trial involving 92 patients who had LDL cholesterol levels of 100 mg per deciliter (2.6 mmol per liter) or higher after treatment with 10 mg of atorvastatin for at least 7 weeks. Patients were randomly assigned to …

Resemblance Of Symptoms For Major Depression Assessed At Interview Versus From Hospital Record Review, Ying Chen, Haimin Li, Yihan Li, Dong Xie, Zhiyang Wang, Fuzhong Wang, Yuan Shen, Sulin Ni, Yan Wei, Yanhua Liu, Lanfen Liu, Chengge Gao, Jun Liu, Lijuan Yan, Gang Wang, Keqing Li, Qiang He, Tiehang Liu, Jinbei Zhang, Yan Ren, Qunli Du, Jing Tian, Honghui Chen, Yanfang Luo, Fengzhi Zhang, Guangwei Sun, Chunjie Shan, Xueyi Wang, Yutang Zhang, Xiaoqin Weng, Yunchun Chen, Zhen Kang, Jing Guan, Yiping Chen, Shenxun Shi, Kenneth S. Kendler, Jonathan Flint, Hong Deng

Psychiatry Publications

Background

Diagnostic information for psychiatric research often depends on both clinical interviews and medical records. Although discrepancies between these two sources are well known, there have been few studies into the degree and origins of inconsistencies.

Principal findings

We compared data from structured interviews and medical records on 1,970 Han Chinese women with recurrent DSM-IV major depression (MD). Correlations were high for age at onset of MD (0.93) and number of episodes (0.70), intermediate for family history (+0.62) and duration of longest episode (+0.43) and variable but generally more modest for individual depressive symptoms (mean kappa = 0.32). Four factors …

Comparison Of Statistical Tests For Association Between Rare Variants And Binary Traits, Silviu-Alin Bacanu, Matthew R. Nelson, John C. Whittaker

Psychiatry Publications

Genome-wide association studies have found thousands of common genetic variants associated with a wide variety of diseases and other complex traits. However, a large portion of the predicted genetic contribution to many traits remains unknown. One plausible explanation is that some of the missing variation is due to the effects of rare variants. Nonetheless, the statistical analysis of rare variants is challenging. A commonly used method is to contrast, within the same region (gene), the frequency of minor alleles at rare variants between cases and controls. However, this strategy is most useful under the assumption that the tested variants have …

Network-Assisted Investigation Of Combined Causal Signals From Genome-Wide Association Studies In Schizophrenia, Peilin Jia, Lily Wang, Ayman H. Fanous, Carlos N. Pato, Todd L. Edwards, Zhongming Zhao

Psychiatry Publications

With the recent success of genome-wide association studies (GWAS), a wealth of association data has been accomplished for more than 200 complex diseases/traits, proposing a strong demand for data integration and interpretation. A combinatory analysis of multiple GWAS datasets, or an integrative analysis of GWAS data and other high-throughput data, has been particularly promising. In this study, we proposed an integrative analysis framework of multiple GWAS datasets by overlaying association signals onto the protein-protein interaction network, and demonstrated it using schizophrenia datasets. Building on a dense module search algorithm, we first searched for significantly enriched subnetworks for schizophrenia in each …

The Interleukin 3 Gene (Il3) Contributes To Human Brain Volume Variation By Regulating Proliferation And Survival Of Neural Progenitors, Xiao-Jian Luo, Ming Li, Liang Huang, Khwangsik Nho, Min Deng, Qiang Chen, Daniel R. Weinberger, Alejandro A. Vasquez, Mark Rijpkema, Venkata S. Mattay, Andrew J. Saykin, Li Shen, Guillen Fernandez, Barbara Franke, Jing-Chun Chen, Xiang-Ning Chen, Jin-Kai Wang, Xiao Xiao, Xue-Bin Qi, Kun Xiang, Ying-Mei Peng, Xiang-Yu Cao, Yi Li, Xiao-Dong Shi, Lin Gan, Bing Su

Psychiatry Publications

One of the most significant evolutionary changes underlying the highly developed cognitive abilities of humans is the greatly enlarged brain volume. In addition to being far greater than in most other species, the volume of the human brain exhibits extensive variation and distinct sexual dimorphism in the general population. However, little is known about the genetic mechanisms underlying normal variation as well as the observed sex difference in human brain volume. Here we show that interleukin-3 (IL3) is strongly associated with brain volume variation in four genetically divergent populations. We identified a sequence polymorphism (rs31480) in the IL3 promoter which …

Low Dose Nicotine And Antagonism Of Β2 Subunit Containing Nicotinic Acetylcholine Receptors Have Similar Effects On Affective Behavior In Mice, Shawn M. Anderson, Darlene H. Brunzell

Pharmacology and Toxicology Publications

Nicotine leads to both activation and desensitization (inactivation) of nicotinic acetylcholine receptors (nAChRs). This study tested the hypothesis that nicotine and a selective antagonist of β2*nAChRs would have similar effects on affective behavior. Adult C57BL/6J male mice were tested in a conditioned emotional response (CER) assay which evaluates the ability of an aversive stimulus to inhibit goal-directed behavior. Mice lever-pressed for a saccharin reinforcer according to a variable schedule of reinforcement during sessions in which two presentations of a compound light/tone conditioned stimulus (CS) co-terminated with a 0.1 or 0.3 mA, 0.5 s footshock unconditioned stimulus (US). During testing in …

Mice Deficient In Gem Gtpase Show Abnormal Glucose Homeostasis Due To Defects In Beta-Cell Calcium Handling, Jenny E. Gunton, Mary Sisavanh, Rebecca A. Stokes, Jon Satin, Leslie S. Satin, Min Zhang, Sue M. Liu, Weikang Cai, Kim Cheng, Gregory J. Cooney, D. Ross Laybutt, Trina So, Juan-Carlos Molero, Shane T. Grey, Douglas A. Andres, Michael S. Rolph, Charles R. Mackay

Pharmacology and Toxicology Publications

Aims and Hypothesis

Glucose-stimulated insulin secretion from beta-cells is a tightly regulated process that requires calcium flux to trigger exocytosis of insulin-containing vesicles. Regulation of calcium handling in beta-cells remains incompletely understood. Gem, a member of the RGK (Rad/Gem/Kir) family regulates calcium channel handling in other cell types, and Gem over-expression inhibits insulin release in insulin-secreting Min6 cells. The aim of this study was to explore the role of Gem in insulin secretion. We hypothesised that Gem may regulate insulin secretion and thus affect glucose tolerance in vivo.

Methods

Gem-deficient mice were generated and their metabolic phenotype characterised by …

Acid Sphingomyelinase Gene Knockout Ameliorates Hyperhomocysteinemic Glomerular Injury In Mice Lacking Cystathionine-Β-Synthase, Krishna M. Boini, Min Xia, Justine M. Abais, Ming Xu, Cai-Xia Li, Pin-Lan Li

Pharmacology and Toxicology Publications

Acid sphingomyelinase (ASM) has been implicated in the development of hyperhomocysteinemia (hHcys)-induced glomerular oxidative stress and injury. However, it remains unknown whether genetically engineering of ASM gene produces beneficial or detrimental action on hHcys-induced glomerular injury. The present study generated and characterized the mice lacking cystathionine β-synthase (Cbs) and Asm mouse gene by cross breeding Cbs+/− and Asm+/− mice. Given that the homozygotes of Cbs−/−/Asm−/− mice could not survive for 3 weeks. Cbs+/−/Asm+/+, Cbs+/−/Asm+/− and Cbs+/−/Asm−/− as well as their Cbs wild type littermates were used to study the role of Asm−/− under a background of Cbs+/− with hHcys. HPLC …

Discovery Of Prostamide F2Α And Its Role In Inflammatory Pain And Dorsal Horn Nociceptive Neuron Hyperexcitability, Luisa Gatta, Fabiana Piscitelli, Catia Giordano, Serana Boccella, Aron H. Lichtman, Sebatino Maione, Vincenzo Di Marzo

Pharmacology and Toxicology Publications

It was suggested that endocannabinoids are metabolized by cyclooxygenase (COX)-2 in the spinal cord of rats with kaolin/λ-carrageenan-induced knee inflammation, and that this mechanism contributes to the analgesic effects of COX-2 inhibitors in this experimental model. We report the development of a specific method for the identification of endocannabinoid COX-2 metabolites, its application to measure the levels of these compounds in tissues, and the finding of prostamide F2α (PMF2α) in mice with knee inflammation. Whereas the levels of spinal endocannabinoids were not significantly altered by kaolin/λ-carrageenan-induced knee inflammation, those of the COX-2 metabolite of AEA, PMF2α, were strongly elevated. The …

A Gga Plus U Approach To Effective Electronic Correlations In Thiolate-Ligated Iron-Oxo (Iv) Porphyrin, Justin Elenewski, John C. Hackett

Medicinal Chemistry Publications

High-valent oxo-metal complexes exhibit correlated electronic behavior on dense, low-lying electronic state manifolds, presenting challenging systems for electronic structure methods. Among these species, the iron-oxo (IV) porphyrin denoted Compound I occupies a privileged position, serving a broad spectrum of catalytic roles. The most reactive members of this family bear a thiolate axial ligand, exhibiting high activity toward molecular oxygen activation and substrate oxidation. The default approach to such systems has entailed the use of hybrid density functionals or multi-configurational/multireference methods to treat electronic correlation. An alternative approach is presented based on the GGA+U approximation to density functional theory, in …

On The Specificity Of Heparin/Heparan Sulfate Binding To Proteins. Anion-Binding Sites On Antithrombin And Thrombin Are Fundamentally Different, Philip D. Mosier, Chandravel Krishnasamy, Glen E. Kellogg, Umesh R. Desai

Medicinal Chemistry Publications

Background

The antithrombin–heparin/heparan sulfate (H/HS) and thrombin–H/HS interactions are recognized as prototypic specific and non-specific glycosaminoglycan (GAG)–protein interactions, respectively. The fundamental structural basis for the origin of specificity, or lack thereof, in these interactions remains unclear. The availability of multiple co-crystal structures facilitates a structural analysis that challenges the long-held belief that the GAG binding sites in antithrombin and thrombin are essentially similar with high solvent exposure and shallow surface characteristics.

Methodology

Analyses of solvent accessibility and exposed surface areas, gyrational mobility, symmetry, cavity shape/size, conserved water molecules and crystallographic parameters were performed for 12 X-ray structures, which include 12 …

Pyridoxal 5′-Phosphate Is A Slow Tight Binding Inhibitor Of E. Coli Pyridoxal Kinase, Mohini S. Ghatge, Roberto Contestabile, Martino L. Di Salvo, Jigar V. Desai, Amit Gandhi, Christina M. Camara, Rita Florio, Isabel N. Gonzalez, Alessia Parroni, Verne Schirch, Martin A. Safo

Medicinal Chemistry Publications

Pyridoxal 5′-phosphate (PLP) is a cofactor for dozens of B6 requiring enzymes. PLP reacts with apo-B6 enzymes by forming an aldimine linkage with the ε-amino group of an active site lysine residue, thus yielding the catalytically active holo-B6 enzyme. During protein turnover, the PLP is salvaged by first converting it to pyridoxal by a phosphatase and then back to PLP by pyridoxal kinase. Nonetheless, PLP poses a potential toxicity problem for the cell since its reactive 4′-aldehyde moiety forms covalent adducts with other compounds and non-B6 proteins containing thiol or amino groups. The regulation of PLP homeostasis in the cell …

Crystal Structures Of Human Pyridoxal Kinase In Complex With The Neurotoxins, Ginkgotoxin And Theophylline: Insights Into Pyridoxal Kinase Inhibition, Amit Gandhi, Jigar V. Desai, Mohini S. Ghatge, Martino L. Di Salvo, Stefano Di Biase, Richmond Danso-Danquah, Faik N. Musayev, Roberto Contestabile, Verne Schirch, Martin A. Safo

Medicinal Chemistry Publications

Several drugs and natural compounds are known to be highly neurotoxic, triggering epileptic convulsions or seizures, and causing headaches, agitations, as well as other neuronal symptoms. The neurotoxic effects of some of these compounds, including theophylline and ginkgotoxin, have been traced to their inhibitory activity against human pyridoxal kinase (hPL kinase), resulting in deficiency of the active cofactor form of vitamin B6, pyridoxal 5′-phosphate (PLP). Pyridoxal (PL), an inactive form of vitamin B6 is converted to PLP by PL kinase. PLP is the B6 vitamer required as a cofactor for over 160 enzymatic activities essential in primary and secondary metabolism. …

Design, Synthesis, And In Vitro And In Vivo Biological Studies Of A 3′-Deoxythymidine Conjugate That Potentially Kills Cancer Cells Selectively, Qiong Wei, Dejun Zhang, Anna Yao, Liyi Mai, Zhiwei Zhang, Qibing Zhou

Medicinal Chemistry Publications

Thymidine kinases (TKs) have been considered one of the potential targets for anticancer therapeutic because of their elevated expressions in cancer cells. However, nucleobase analogs targeting TKs have shown poor selective cytotoxicity in cancer cells despite effective antiviral activity. 3′-Deoxythymidine phenylquinoxaline conjugate (dT-QX) was designed as a novel nucleobase analog to target TKs in cancer cells and block cell replication via conjugated DNA intercalating quinoxaline moiety. In vitro cell screening showed that dT-QX selectively kills a variety of cancer cells including liver carcinoma, breast adenocarcinoma and brain glioma cells; whereas it had a low cytotoxicity in normal cells such as …

Alternatives To Mixture Model Analysis Of Correlated Binomial Data, N. Rao Chaganty, Roy Sabo, Yihao Deng

Biostatistics Publications

While univariate instances of binomial data are readily handled with generalized linear models, cases of multivariate or repeated measure binomial data are complicated by the possibility of correlated responses. Likelihood-based estimation can be applied by using mixture distribution models, though this approach can present computational challenges. The logistic transformation can be used to bypass these concerns and allow for alternative estimating procedures. One popular alternative is the generalized estimating equation (GEE) method, though systematic errors can lead to infeasible correlation estimates or nonconvergence problems. Our approach is the coupling of quasileast squares (QLSs) method with a rarely used matrix factorization, …

Intimate Partner Violence And Alcohol Problems In Interethnic And Intra-Ethnic Couples, Karen G. Chartier, Raul Caetano

Social Work Publications

Despite the growing number of interethnic marriages in the U.S., few studies have examined intimate partner violence (IPV) in interethnic couples. This article examined past-year occurrences of IPV across interethnic and intra-ethnic couples and tested correlates of IPV specifically in interethnic couples. Data were from a national survey of couples 18 years of age and older from the 48 contiguous states. Interethnic couples (n = 116) included partners from different ethnic backgrounds, including black-white, Hispanic-white, and black-Hispanic couples. White (n = 555), black (n = 358), and Hispanic (n = 527) intra-ethnic couples included partners with …

Alcohol Availability And Neighborhood Poverty And Their Relationship To Binge Drinking And Related Problems Among Drinkers In Committed Relationships, Christy M. Mckinney, Karen G. Chartier, Raul Caetano, T. Robert Harris

Social Work Publications

The authors examined the relationship of alcohol outlet density (AOD) and neighborhood poverty with binge drinking and alcohol-related problems among drinkers in married and cohabitating relationships and assessed whether these associations differed across sex. A U.S. national population couples survey was linked to U.S. Census data on AOD and neighborhood poverty. The 1,784 current drinkers in the survey reported on their binge drinking, alcohol-related problems, and other covariates. AOD was defined as the number of alcohol outlets per 10,000 persons and was obtained at the zip code level. Neighborhood poverty was as having a low (<20%) or high (≥20%) proportion of residents living in poverty at the census tract level. We used logistic regression for survey data to estimate odds ratios and 95% confidence intervals and tested for differences of associations by sex. Associations of neighborhood poverty with binge drinking were stronger for male than for female drinkers. The association of neighborhood poverty with alcohol-related problems was also stronger for men than for women. We observed no relationships between AOD and binge drinking or alcohol-related problems in this couples survey. Efforts to reduce binge drinking or alcohol-related problems among partners in committed relationships may have the greatest impact if targeted to male drinkers living in high-poverty neighborhoods. Binge drinking and alcohol-related problems, as well as residence in an impoverished neighborhood are risk factors for intimate partner violence (IPV) and other relationship conflicts.

Patient- And Population-Level Health Consequences Of Discontinuing Antiretroviral Therapy In Settings With Inadequate Hiv Treatment Availability, April D. Kimmel, Stephen C. Resch, Xavier Anglaret, Norman Daniels, Sue J. Goldie, Christine Daniel, Angela Y. Wong, Kenneth A. Freedberg, Milton C. Weinstein

Health Behavior and Policy Publications

Background

In resource-limited settings, HIV budgets are flattening or decreasing. A policy of discontinuing antiretroviral therapy (ART) after HIV treatment failure was modeled to highlight trade-offs among competing policy goals of optimizing individual and population health outcomes.

Methods

In settings with two available ART regimens, we assessed two strategies: (1) continue ART after second-line failure (Status Quo) and (2) discontinue ART after second-line failure (Alternative). A computer model simulated outcomes for a single cohort of newly detected, HIV-infected individuals. Projections were fed into a population-level model allowing multiple cohorts to compete for ART with constraints on treatment capacity. In the …

One Fish, Two Fish, Red Fish, Blue Fish: Effects Of Price Frames, Brand Names, And Choice Set Size In Medicare Part D Insurance Plan Decisions, Andrew J. Barnes, Yaniv Hanoch, Stacey Wood, Pi-Ju Liu, Thomas Rice

Health Behavior and Policy Publications

Because many seniors choose Medicare Part D plans offering poorer coverage at greater cost, the authors examined the effect of price frames, brand names, and choice set size on participants' ability to choose the lowest cost plan. A 2×2×2 within-subjects design was used with 126 participants aged 18 to 91 years old. Mouselab, a web-based program, allowed participants to choose drug plans across eight trials that varied using numeric or symbolic prices, real or fictitious drug plan names, and three or nine drug plan options. Results from the multilevel models suggest numeric versus symbolic prices decreased the likelihood of choosing …

Evaluation Of A Revised Curriculum: A Four-Year Qualitative Study Of Student Perceptions, Sharon K. Lanning, Angela P. Wetzel, Meredith B. Baines, B. Ellen Byrne

Periodontics Publications

Following curricular revisions at the Virginia Commonwealth University School of Dentistry, this longitudinal study was designed to determine students' perceptions of their educational experience in the revised curriculum. A SWOT (Strengths, Weaknesses, Opportunities, and Threats) open-ended response questionnaire was administered to students in the class of 2011 (N=89) in January of each academic year, 2008 through 2011, followed by focus groups three months prior to graduation. The overall response rate for the questionnaire was 69 percent, and a total of fourteen students participated in four focus groups. Cumulatively, 1,382 responses (SWOT=984 and focus groups=398) were qualitatively analyzed, and five themes …

Geriatric Home Makeover, Edward F. Ansello

Director's Editorials from Age in Action

Houses pose substantial risks for falling. Over half of all falls by older adults happen in their homes. Reducing hazards in the home addresses just one set of contributing risk factors involved in older adults falling.

Shared Resistance To Aging And Als In Neuromuscular Junctions Of Specific Muscles, Gregorio Valdez, Juan C. Tapia, Jeff W. Lichtman, Michael A. Fox, Joshua R. Sanes

Anatomy and Neurobiology Publications

Normal aging and neurodegenerative diseases both lead to structural and functional alterations in synapses. Comparison of synapses that are generally similar but respond differently to insults could provide the basis for discovering mechanisms that underlie susceptibility or resistance to damage. Here, we analyzed skeletal neuromuscular junctions (NMJs) in 16 mouse muscles to seek such differences. We find that muscles respond in one of three ways to aging. In some, including most limb and trunk muscles, age-related alterations to NMJs are progressive and extensive during the second postnatal year. NMJs in other muscles, such as extraocular muscles, are strikingly resistant to …

Spxa1 Involved In Hydrogen Peroxide Production, Stress Tolerance And Endocarditis Virulence In Streptococcus Sanguinis, Lei Chen, Xiuchun Ge, Xiaojing Wang, Jenishkumar R. Patel, Ping Xu

Philips Institute for Oral Health Research Publications

Streptococcus sanguinis is one of the most common agents of infective endocarditis. Spx proteins are a group of global regulators that negatively or positively control global transcription initiation. In this study, we characterized the spxA1 gene in S. sanguinis SK36. The spxA1 null mutant displayed opaque colony morphology, reduced hydrogen peroxide (H2O2) production, and reduced antagonistic activity against Streptococcus mutans UA159 relative to the wild type strain. The ΔspxA1 mutant also demonstrated decreased tolerance to high temperature, acidic and oxidative stresses. Further analysis revealed that ΔspxA1 also exhibited a ~5-fold reduction in competitiveness in an animal model of …

Identification And Structural Characterization Of A New Three-Finger Toxin Hemachatoxin From Hemachatus Haemachatus Venom, Vallerinteavide Mavelli Girish, Sundramurthy Kumar, Lissa Joseph, Chacko Jobichen, R. Manjunatha Kini, J. Sivaraman

Biochemistry and Molecular Biology Publications

Snake venoms are rich sources of biologically active proteins and polypeptides. Three-finger toxins are non-enzymatic proteins present in elapid (cobras, kraits, mambas and sea snakes) and colubrid venoms. These proteins contain four conserved disulfide bonds in the core to maintain the three-finger folds. Although all three-finger toxins have similar fold, their biological activities are different. A new three-finger toxin (hemachatoxin) was isolated from Hemachatus haemachatus (Ringhals cobra) venom. Its amino acid sequence was elucidated, and crystal structure was determined at 2.43 Å resolution. The overall fold is similar to other three-finger toxins. The structure and sequence analysis revealed that the …

Metabolic Rate Regulates L1 Longevity In C. Elegans, Inhwan Lee, Amber Hendrix, Jeongho Kim, Jennifer Yoshimoto, Young-Jai You

Biochemistry and Molecular Biology Publications

Animals have to cope with starvation. The molecular mechanisms by which animals survive long-term starvation, however, are not clearly understood. When they hatch without food, C. elegans arrests development at the first larval stage (L1) and survives more than two weeks. Here we show that the survival span of arrested L1s, which we call L1 longevity, is a starvation response regulated by metabolic rate during starvation. A high rate of metabolism shortens the L1 survival span, whereas a low rate of metabolism lengthens it. The longer worms are starved, the slower they grow once they are fed, suggesting that L1 …

Augmenter Of Liver Regeneration (Alr) Promotes Liver Outgrowth During Zebrafish Hepatogenesis, Yan Li, Muhammad Farooq, Donglai Sheng, Chanchal Chandramouli, Tian Lan, Nilesh K. Mahajan, R. Manjunatha Kini, Yunhan Hong, Thomas Lisowsky, Ruowen Ge

Biochemistry and Molecular Biology Publications

Augmenter of Liver Regeneration (ALR) is a sulfhydryl oxidase carrying out fundamental functions facilitating protein disulfide bond formation. In mammals, it also functions as a hepatotrophic growth factor that specifically stimulates hepatocyte proliferation and promotes liver regeneration after liver damage or partial hepatectomy. Whether ALR also plays a role during vertebrate hepatogenesis is unknown. In this work, we investigated the function of alr in liver organogenesis in zebrafish model. We showed that alr is expressed in liver throughout hepatogenesis. Knockdown of alr through morpholino antisense oligonucleotide (MO) leads to suppression of liver outgrowth while overexpression of alr promotes liver growth. …

Species-Level Classification Of The Vaginal Microbiome, Jennifer M. Fettweis, Myrna G. Serrano, Nihar U. Sheth, Abigail L. Glascock, J. Paul Brooks, Kimberly K. Jefferson, Vaginal Microbiome Consortium, Gregory A. Buck

Microbiology and Immunology Publications

Background

The application of next-generation sequencing to the study of the vaginal microbiome is revealing the spectrum of microbial communities that inhabit the human vagina. High-resolution identification of bacterial taxa, minimally to the species level, is necessary to fully understand the association of the vaginal microbiome with bacterial vaginosis, sexually transmitted infections, pregnancy complications, menopause, and other physiological and infectious conditions. However, most current taxonomic assignment strategies based on metagenomic 16S rDNA sequence analysis provide at best a genus-level resolution. While surveys of 16S rRNA gene sequences are common in microbiome studies, few well-curated, body-site-specific reference databases of 16S rRNA …

Preserved Ex Vivo Inflammatory Status In Decidual Cells From Women With Preterm Labor And Subclinical Intrauterine Infection, Violeta Castro-Leyva, Aurora Espejel-Nunez, Gerardo Barroso, Veronica Zaga-Clavellina, Arturo Flores-Pliego, Iyari Morales-Mendez, Silvia Giono-Cerezo, Scott W. Walsh, Guadalupe Estrada-Gutierrez

Obstetrics and Gynecology Publications

Objective

To compare the inflammatory response preserved ex vivo by decidual cells isolated from women who experienced preterm labor with and without subclinical intrauterine infection.

Methods

Fetal membranes were obtained after cesarean section from 35 women who delivered before 37 weeks of gestation following spontaneous preterm labor, with no clinical evidence of intrauterine infection. Decidua was microbiologically tested and cultured. Concentrations of anti-inflammatory cytokines (IL-2, IL-4, IL-10), pro-inflammatory cytokines (IL-6, IL-8, IL-1β and TNF-α), and matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9) were measured in the supernatants using Bio-Plex, and prostaglandin E2 (PGE2) was measured by enzyme immunoassay.

Results …

Cholesterol Side-Chain Cleavage Gene Expression In Theca Cells: Augmented Transcriptional Regulation And Mrna Stability In Polycystic Ovary Syndrome, Jessica K. Wickenheisser, Jessica M. Biegler, Valen L. Nelson-Degrave, Richard S. Legro, Jerome F. Strauss Iii, Jan M. Mcallister

Obstetrics and Gynecology Publications

Hyperandrogenism is characteristic of women with polycystic ovary syndrome (PCOS). Ovarian theca cells isolated from PCOS follicles and maintained in long-term culture produce elevated levels of progestins and androgens compared to normal theca cells. Augmented steroid production in PCOS theca cells is associated with changes in the expression of genes for several steroidogenic enzymes, including CYP11A1, which encodes cytochrome P450 cholesterol side-chain cleavage. Here, we further examined CYP11A1 gene expression, at both the transcriptional and post-transcriptional level in normal and PCOS theca cells propagated in long-term culture utilizing quantitative RT-PCR, functional promoter analyses, and mRNA degradation studies. The minimal …