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Identification and Characteristics of Low-Risk Survivors of an Acute Myocardial Infarction

Thu, 02/16/2017 - 4:04pm

There are limited contemporary data available describing the characteristics of patients who neither died nor were readmitted to the hospital during the first year after hospital discharge for an acute myocardial infarction (AMI) in comparison with those who died and/or were readmitted to the hospital during this high-risk period. Residents of the Worcester, Massachusetts, metropolitan area discharged after an AMI from 3 central Massachusetts hospitals on a biennial basis from 2001 to 2011 comprised the study population. The average age of this population (n = 4,268) was 69 years, 62% were men, and 92% were white. From 2001 to 2011, 43.5% of patients were classified as low-risk survivors of an AMI, 12.3% died, and 44.2% did not die but had at least 1 rehospitalization during the subsequent year. The proportion of low-risk survivors increased from 42.6% to 46.4%, whereas the proportion of those who died within a year after hospital discharge decreased from 14.3% to 10.5%, respectively, during the years under study. After adjusting for several patient characteristics, younger ( < /=65 years) persons, men, those who were married, those who did not present with multimorbidities, and patients who did not develop in-hospital clinical complications were more likely to be classified as a low-risk AMI survivor. Identifying low-risk survivors of an AMI may help health care providers to focus more intensive efforts and interventions on those at higher risk for dying and/or being readmitted to the hospital during the postdischarge transition period after an AMI.

Neighborhood Walkability and Adiposity in the Women's Health Initiative Cohort

Thu, 02/16/2017 - 4:04pm

INTRODUCTION: Neighborhood environments may play a role in the rising prevalence of obesity among older adults. However, research on built environmental correlates of obesity in this age group is limited. The current study aimed to explore associations of Walk Score, a validated measure of neighborhood walkability, with BMI and waist circumference in a large, diverse sample of older women.

METHODS: This study linked cross-sectional data on 6,526 older postmenopausal women from the Women's Health Initiative Long Life Study (2012-2013) to Walk Scores for each participant's address (collected in 2012). Linear and logistic regression models were used to estimate associations of BMI and waist circumference with continuous and categorical Walk Score measures. Secondary analyses examined whether these relationships could be explained by walking expenditure or total physical activity. All analyses were conducted in 2015.

RESULTS: Higher Walk Score was not associated with BMI or overall obesity after adjustment for sociodemographic, medical, and lifestyle factors. However, participants in highly walkable areas had significantly lower odds of abdominal obesity (waist circumference >88 cm) as compared with those in less walkable locations. Observed associations between walkability and adiposity were partly explained by walking expenditure.

CONCLUSIONS: Findings suggest that neighborhood walkability is linked to abdominal adiposity, as measured by waist circumference, among older women and provide support for future longitudinal research on associations between Walk Score and adiposity in this population.

Effects of Obstetric Complications on Adolescent Postpartum Contraception and Rapid Repeat Pregnancy

Thu, 02/16/2017 - 4:04pm

STUDY OBJECTIVE: To determine whether complications during pregnancy or at delivery influence postpartum contraception choices and rapid repeat pregnancy rates in adolescent women.

DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: This retrospective cohort study included 321 adolescents delivering at UMASS Memorial Healthcare. Complications during pregnancy and delivery along with subsequent contraception use were investigated. Postpartum contraception choice (long-acting reversible contraception [LARC] vs non-LARC) at either delivery, hospitalization discharge, or at postpartum outpatient appointment, and rapid repeat pregnancy rate (pregnancy confirmed within 12 months of index delivery), were analyzed according to pregnancy complications. Comparisons were made with chi2 and Fisher exact tests for categorical variables, and with Wilcoxon rank sum test for continuous variables.

RESULTS: Of the study population, 27.7% (n = 89/321) used LARC in the postpartum period. The LARC and non-LARC patient populations differed significantly regarding history of abortion (P = .029), with no differences in obstetric complications between the groups. Of the population, 16.6% (n = 53/320) became pregnant again within 1 year of their index delivery. Those with a rapid repeat pregnancy had significantly increased gravidity (P = .002), parity (P = .003), number of previous spontaneous or therapeutic abortions (P = .026); they were also more like to have nonlive birth as a complication (P = .028), compared with those without repeat pregnancy. No other obstetrical complications were statistically significantly different between the compared groups.

CONCLUSION: Obstetrical complications seem to have little effect on postpartum contraception choice or repeat pregnancy rate with the notable exception of nonlive birth being associated with rapid repeat pregnancy.

Deciphering the Structure and Function of Nuclear Pores Using Single-Molecule Fluorescence Approaches

Thu, 02/16/2017 - 4:04pm

Due to its central role in macromolecular trafficking and nucleocytoplasmic information transfer, the nuclear pore complex (NPC) has been studied in great detail using a wide spectrum of methods. Consequently, many aspects of its architecture, general function, and role in the life cycle of a cell are well understood. Over the last decade, fluorescence microscopy methods have enabled the real-time visualization of single molecules interacting with and transiting through the NPC, allowing novel questions to be examined with nanometer precision. While initial single-molecule studies focused primarily on import pathways using permeabilized cells, it has recently proven feasible to investigate the export of mRNAs in living cells. Single-molecule assays can address questions that are difficult or impossible to answer by other means, yet the complexity of nucleocytoplasmic transport requires that interpretation be based on a firm genetic, biochemical, and structural foundation. Moreover, conceptually simple single-molecule experiments remain technically challenging, particularly with regard to signal intensity, signal-to-noise ratio, and the analysis of noise, stochasticity, and precision. We discuss nuclear transport issues recently addressed by single-molecule microscopy, evaluate the limits of existing assays and data, and identify open questions for future studies. We expect that single-molecule fluorescence approaches will continue to be applied to outstanding nucleocytoplasmic transport questions, and that the approaches developed for NPC studies are extendable to additional complex systems and pathways within cells.

Biochemical and biomechanical drivers of cancer cell metastasis, drug response and nanomedicine

Thu, 02/16/2017 - 4:04pm

Metastasis, drug resistance and recurrence in cancer are regulated by the tumor microenvironment. This review describes recent advances in understanding how cancer cells respond to extracellular environmental cues via integrins, how to build engineered microenvironments to study these interactions in vitro and how nanomaterials can be used to detect and target tumor microenvironments.

Atrial Fibrillation Is Associated With a Worse 90-Day Outcome Than Other Cardioembolic Stroke Subtypes

Thu, 02/16/2017 - 4:04pm

BACKGROUND AND PURPOSE: Patients with a cardioembolic stroke (CES) have worse outcomes than stroke patients with other causes of stroke. Among patients with CES, atrial fibrillation (AF) is a common comorbidity. Mounting data indicate that AF may be related to stroke pathogenesis beyond acute cerebral thromboembolism. We sought to determine whether AF represents an independent risk factor for stroke severity and outcome among patients with CES.

METHODS: We retrospectively analyzed patients with acute hemispheric CES included in an academic medical center's stroke registry. CES was determined using the Causative Classification System of ischemic stroke. Multivariable logistic regression was used to determine whether AF was associated with 90-day outcome functional status.

RESULTS: Our cohort included 140 patients. Of these, 52 had prevalent AF and 28 had incident AF diagnosed during their index hospitalization or within 90 days of hospital discharge. After adjustment for potential confounders or mediators, any AF (odds ratio, 2.51; 95% confidence interval, 1.03-6.33; P=0.049), infarct volume (odds ratio, 1.03; 95% confidence interval, 1.01-1.06; P=0.005), preadmission modified Rankin Scale score (odds ratio, 2.58; 95% confidence interval, 1.66-4.01; P < 0.001), and admission National Institutes of Health Stroke Scale score (odds ratio, 1.17; 95% confidence interval, 1.08-1.28; P < 0.001) remained associated with an unfavorable 90-day outcome (modified Rankin Scale score, 2-6).

CONCLUSIONS: AF is associated with an unfavorable 90-day outcome among patients with a CES independent of established risk factors and initial stroke severity. This suggests that AF-specific mechanisms affect CES severity and functional status after CES. If confirmed in future studies, further investigation into the underlying pathophysiological mechanisms may provide novel avenues to AF detection and treatment.

Multilevel Provider-Based Sampling for Recruitment of Pregnant Women and Mother-Newborn Dyads

Thu, 02/16/2017 - 4:04pm

OBJECTIVE: In 2010, the National Children's Study launched 3 alternative recruitment methods to test possible improvements in efficiency compared with traditional household-based recruitment and participant enrollment. In 2012, a fourth method, provider-based sampling (PBS), tested a probability-based sampling of prenatal provider locations supplemented by a second cohort of neonates born at a convenience sample of maternity hospitals.

METHODS: From a sampling frame of 472 prenatal care provider locations and 59 maternity hospitals, 49 provider and 7 hospital locations within or just outside 3 counties participated in study recruitment. During first prenatal care visits or immediately postdelivery at these locations, face-to-face contact was used to screen and recruit eligible women.

RESULTS: Of 1450 screened women, 1270 were eligible. Consent rates at prenatal provider locations (62%-74% by county) were similar to those at birth locations (64%-77% by county). During 6 field months, 3 study centers enrolled a total prenatal cohort of 530 women (the majority in the first trimester) and during 2 months enrolled a birth cohort of an additional 320 mother-newborn dyads. As personnel became experienced in the field, the time required to enroll a woman in the prenatal cohort declined from up to 200 hours to 50 to 100 hours per woman recruited.

CONCLUSIONS: We demonstrated that PBS was feasible and operationally efficient in recruiting a representative cohort of newborns from 3 diverse US counties. Our findings suggest that PBS is a practical approach to recruit large pregnancy and birth cohorts across the United States.

On Edge: the impact of race-related vigilance on obesity status in African-Americans

Thu, 02/16/2017 - 4:04pm

OBJECTIVE: Nearly half of African-Americans are classified as obese. Perceived racism has been associated with obesity, yet the internal experiences of racism have received little attention. African Americans who face racism may "ready themselves" to cope through survival strategies, including race-related vigilance. This study explores the association between race-related vigilance and obesity in African Americans.

DESIGN AND METHODS: The Reactions to Race module of the Behavioral Risk Factor Surveillance Survey (years 2002-2010) was used. Our sample size consisted of 12,214 African-Americans. Race-related vigilance was assessed as: "How often do you think about your race?" and classified as: never, < daily, daily, and > daily. Obesity was dichotomized as body mass index (BMI) > /=30 kg/m2 vs. < 30 kg/m2 using self-reported weight and height. Multivariable logistic models assessed the association between race-related vigilance and obesity.

RESULTS: Seventeen percent of respondents reported thinking about their race > daily; 14% daily; 31% < daily, and 39% reported never thinking about their race. Compared to those who reported never thinking about their race, the adjusted odds of obesity were 0.91, 95% CI: 0.72-1.15 among those thinking about their race < daily, 1.09, 95%CI: 0.81-1.46 among those thinking about their race daily, and 1.37, 95% CI: 1.07-1.76 among those thinking about their race > daily.

CONCLUSIONS: Frequently thinking about one's race was a risk factor for obesity in African-Americans in this study. Internalized impacts of racism captured through race-related vigilance may be particularly detrimental to African-Americans, driving their risk for obesity.

Book(s) Review: The Medical Library Association Guide to Data Management for Librarians and Data Management: A Practical Guide for Librarians

Wed, 02/15/2017 - 10:52am

Book reviews of:

The Medical Library Association Guide to Data Management for Librarians, edited by Lisa Federer, Rowman & Littlefield, Copyright 2016 by Medical Library Association ISBN 978-1-4422-6428-1

Data Management: A Practical Guide for Librarians, by Margaret E. Henderson, Rowman & Littlefield Publishers, 2017 ISBN 978-1-4422-6439-7.

A microRNA/Runx1/Runx2 network regulates prostate tumor progression from onset to adenocarcinoma in TRAMP mice

Wed, 02/15/2017 - 10:44am

While decades of research have identified molecular pathways inducing and promoting stages of prostate cancer malignancy, studies addressing dynamic changes of cancer-related regulatory factors in a prostate tumor progression model are limited. Using the TRAMP mouse model of human prostate cancer, we address mechanisms of deregulation for the cancer-associated transcription factors, Runx1 and Runx2 by identifying microRNAs with reciprocal expression changes at six time points during 33 weeks of tumorigenesis. We molecularly define transition stages from PIN lesions to hyperplasia/neoplasia and progression to adenocarcinoma by temporal changes in expression of human prostate cancer markers, including the androgen receptor and tumor suppressors, Nkx3.1 and PTEN. Concomitant activation of PTEN, AR, and Runx factors occurs at early stages. At late stages, PTEN and AR are downregulated, while Runx1 and Runx2 remain elevated. Loss of Runx-targeting microRNAs, miR-23b-5p, miR-139-5p, miR-205-5p, miR-221-3p, miR-375-3p, miR-382-5p, and miR-384-5p, contribute to aberrant Runx expression in prostate tumors. Our studies reveal a Runx/miRNA interaction axis centered on PTEN-PI3K-AKT signaling. This regulatory network translates to mechanistic understanding of prostate tumorigenesis that can be developed for diagnosis and directed therapy.

Native and bone marrow-derived cell mosaicism in gastric carcinoma in H. pylori-infected p27-deficient mice

Wed, 02/15/2017 - 10:44am

OBJECTIVE: Chronic Helicobacter pylori (H. pylori) infection promotes non-cardia gastric cancer. Some mouse models suggest that bone marrow derived cells (BMDC) contribute to Helicobacter-associated gastric carcinogenesis. We determined whether this increased susceptibility to Helicobacter-induced gastric carcinogenesis of p27-deficient mice is dependent upon their p27-null BMDC or their p27-null gastric epithelial cells.

DESIGN: Female mice (recipients) were irradiated and transplanted with BMDC from male donors. Wild type (WT) mice in group 1 (control) received BMDC from male GFP-transgenic mice. Female WT and p27 KO mice were engrafted with male p27KO mice BMDC (Group 2) or GFP-transgenic WT BMDC (Group 3). Recipients were infected with H. pylori SS1 for one year.

RESULTS: Mice lacking p27 in either the BM pool or gastric epithelium developed significantly more advanced gastric pathology, including high-grade dysplasia. Co-staining of donor BMDC in dysplastic gastric glands was confirmed by immunofluorescence. Gastric expression of IL-1 beta protein was reduced in groups 2 and 3 (p < 0.05 vs control) whereas expression of IFN-gamma and chemokines MIP-1 beta, MIG, IP-10 and RANTES in group 2 were significantly higher than group 3.

CONCLUSIONS: Both bone marrow-derived and gastric epithelial cells contribute to the increased gastric cancer susceptibility of p27-deficient H. pylori-infected mice.

NK-CD11c+ Cell Crosstalk in Diabetes Enhances IL-6-Mediated Inflammation during Mycobacterium tuberculosis Infection

Wed, 02/15/2017 - 10:44am

In this study, we developed a mouse model of type 2 diabetes mellitus (T2DM) using streptozotocin and nicotinamide and identified factors that increase susceptibility of T2DM mice to infection by Mycobacterium tuberculosis (Mtb). All Mtb-infected T2DM mice and 40% of uninfected T2DM mice died within 10 months, whereas all control mice survived. In Mtb-infected mice, T2DM increased the bacterial burden and pro- and anti-inflammatory cytokine and chemokine production in the lungs relative to those in uninfected T2DM mice and infected control mice. Levels of IL-6 also increased. Anti-IL-6 monoclonal antibody treatment of Mtb-infected acute- and chronic-T2DM mice increased survival (to 100%) and reduced pro- and anti-inflammatory cytokine expression. CD11c+ cells were the major source of IL-6 in Mtb-infected T2DM mice. Pulmonary natural killer (NK) cells in Mtb-infected T2DM mice further increased IL-6 production by autologous CD11c+ cells through their activating receptors. Anti-NK1.1 antibody treatment of Mtb-infected acute-T2DM mice increased survival and reduced pro- and anti-inflammatory cytokine expression. Furthermore, IL-6 increased inflammatory cytokine production by T lymphocytes in pulmonary tuberculosis patients with T2DM. Overall, the results suggest that NK-CD11c+ cell interactions increase IL-6 production, which in turn drives the pathological immune response and mortality associated with Mtb infection in diabetic mice.

In vivo correction of anaemia in beta-thalassemic mice by gammaPNA-mediated gene editing with nanoparticle delivery

Wed, 02/15/2017 - 10:44am

The blood disorder, beta-thalassaemia, is considered an attractive target for gene correction. Site-specific triplex formation has been shown to induce DNA repair and thereby catalyse genome editing. Here we report that triplex-forming peptide nucleic acids (PNAs) substituted at the gamma position plus stimulation of the stem cell factor (SCF)/c-Kit pathway yielded high levels of gene editing in haematopoietic stem cells (HSCs) in a mouse model of human beta-thalassaemia. Injection of thalassemic mice with SCF plus nanoparticles containing gammaPNAs and donor DNAs ameliorated the disease phenotype, with sustained elevation of blood haemoglobin levels into the normal range, reduced reticulocytosis, reversal of splenomegaly and up to 7% beta-globin gene correction in HSCs, with extremely low off-target effects. The combination of nanoparticle delivery, next generation gammaPNAs and SCF treatment may offer a minimally invasive treatment for genetic disorders of the blood that can be achieved safely and simply by intravenous administration.

Can tobacco dependence provide insights into other drug addictions

Wed, 02/15/2017 - 10:44am

Within the field of addiction research, individuals tend to operate within silos of knowledge focused on specific drug classes. The discovery that tobacco dependence develops in a progression of stages and that the latency to the onset of withdrawal symptoms after the last use of tobacco changes over time have provided insights into how tobacco dependence develops that might be applied to the study of other drugs. As physical dependence on tobacco develops, it progresses through previously unrecognized clinical stages of wanting, craving and needing. The latency to withdrawal is a measure of the asymptomatic phase of withdrawal, extending from the last use of tobacco to the emergence of withdrawal symptoms. Symptomatic withdrawal is characterized by a wanting phase, a craving phase, and a needing phase. The intensity of the desire to smoke that is triggered by withdrawal correlates with brain activity in addiction circuits. With repeated tobacco use, the latency to withdrawal shrinks from as long as several weeks to as short as several minutes. The shortening of the asymptomatic phase of withdrawal drives an escalation of smoking, first in terms of the number of smoking days/month until daily smoking commences, then in terms of cigarettes smoked/day.The discoveries of the stages of physical dependence and the latency to withdrawal raises the question, does physical dependence develop in stages with other drugs? Is the latency to withdrawal for other substances measured in weeks at the onset of dependence? Does it shorten over time? The research methods that uncovered how tobacco dependence emerges might be fruitfully applied to the investigation of other addictions.

Seasonal Variations and Trends in Hospitalization for Peptic Ulcer Disease in the United States: A 12-Year Analysis of the Nationwide Inpatient Sample

Wed, 02/15/2017 - 10:44am

BACKGROUND: Peptic ulcer disease (PUD) is a major public health burden significantly impacting the cost of hospitalization in the United States (US). We examined the trends, characteristics, complications, cost, and seasonality of PUD-related hospitalizations from 2000 to 2011.

METHODS: With the use of the Nationwide Inpatient Sample from 2000 through 2011, we identified PUD-related hospitalizations using the International Classification of Diseases (ICD-9), 9th Revision, and the Clinical Modification code 531.00 to 534.91 as the principal discharge diagnosis. The total number of hospitalizations for each calendar month of the year were added over a 12-year period, and this number was divided by the number of days in that particular month to obtain the mean hospitalizations per day for each month.

RESULTS: The study found that 351,921 hospitalizations with the primary discharge diagnosis of peptic ulcer disease (PUD) occurred in the US between 2000 and 2011. This number dropped significantly from 49,524 to 17,499 between 2000 and 2011, and the rate of PUD-related mortality decreased from 4.3% to 3.1%. The mean age of the study population was 66.2 +/- 17.4 years; 52.3% were males, and 56.8% were white. The number of hospitalizations in the US peaked in the spring season (916/day), and reached a nadir in the fall season (861/day). The mean cost of PUD hospitalization increased significantly from $11,755 in 2001 to $13,803 in 2011 (relative increase of 17%; p < 0.001).

CONCLUSION: The incidence of PUD and its mortality has decreased significantly in the last decade, but its economic burden on the healthcare system remains high. A seasonal pattern of PUD hospitalization showed a peak in PUD-related admissions in the spring season and a trough in the fall season.

Endotracheal Tube Cuff Pressures in Patients Intubated Prior to Helicopter EMS Transport

Wed, 02/15/2017 - 10:44am

INTRODUCTION: Endotracheal intubation is a common intervention in critical care patients undergoing helicopter emergency medical services (HEMS) transportation. Measurement of endotracheal tube (ETT) cuff pressures is not common practice in patients referred to our service. Animal studies have demonstrated an association between the pressure of the ETT cuff on the tracheal mucosa and decreased blood flow leading to mucosal ischemia and scarring. Cuff pressures greater than 30 cmH2O impede mucosal capillary blood flow. Multiple prior studies have recommended 30 cmH2O as the maximum safe cuff inflation pressure. This study sought to evaluate the inflation pressures in ETT cuffs of patients presenting to HEMS.

METHODS: We enrolled a convenience sample of patients presenting to UMass Memorial LifeFlight who were intubated by the sending facility or emergency medical services (EMS) agency. Flight crews measured the ETT cuff pressures using a commercially available device. Those patients intubated by the flight crew were excluded from this analysis as the cuff was inflated with the manometer to a standardized pressure. Crews logged the results on a research form, and we analyzed the data using Microsoft Excel and an online statistical analysis tool.

RESULTS: We analyzed data for 55 patients. There was a mean age of 57 years (range 18-90). The mean ETT cuff pressure was 70 (95% CI= [61-80]) cmH2O. The mean lies 40 cmH2O above the maximum accepted value of 30 cmH2O (p < 0.0001). Eighty-four percent (84%) of patients encountered had pressures above the recommended maximum. The most frequently recorded pressure was >120 cmH2O, the maximum pressure on the analog gauge.

CONCLUSION: Patients presenting to HEMS after intubation by the referral agency (EMS or hospital) have ETT cuffs inflated to pressures that are, on average, more than double the recommended maximum. These patients are at risk for tracheal mucosal injury and scarring from decreased mucosal capillary blood flow. Hospital and EMS providers should use ETT cuff manometry to ensure that they inflate ETT cuffs to safe pressures.

Transient RUNX1 Expression during Early Mesendodermal Differentiation of hESCs Promotes Epithelial to Mesenchymal Transition through TGFB2 Signaling

Wed, 02/15/2017 - 10:43am

The transition of human embryonic stem cells (hESCs) from pluripotency to lineage commitment is not fully understood, and a role for phenotypic transcription factors in the initial stages of hESC differentiation remains to be explored. From a screen of candidate factors, we found that RUNX1 is selectively and transiently upregulated early in hESC differentiation to mesendodermal lineages. Transcriptome profiling and functional analyses upon RUNX1 depletion established a role for RUNX1 in promoting cell motility. In parallel, we discovered a loss of repression for several epithelial genes, indicating that loss of RUNX1 impaired an epithelial to mesenchymal transition during differentiation. Cell biological and biochemical approaches revealed that RUNX1 depletion specifically compromised TGFB2 signaling. Both the decrease in motility and deregulated epithelial marker expression upon RUNX1 depletion were rescued by reintroduction of TGFB2, but not TGFB1. These findings identify roles for RUNX1-TGFB2 signaling in early events of mesendodermal lineage commitment.

Sexual Dimorphism in Alcohol Induced Adipose Inflammation Relates to Liver Injury

Wed, 02/15/2017 - 10:43am

Alcoholic liver disease occurs due to chronic, heavy drinking and is driven both by metabolic alterations and immune cell activation. Women are at a higher risk than men for developing alcohol induced liver injury and this dimorphism is reflected in animal models of alcoholic liver disease. The importance of adipose tissue in alcoholic liver disease is emerging. Chronic alcohol consumption causes adipose tissue inflammation, which can influence liver injury. Sex differences in body fat composition are well known. However, it is still unclear if alcohol-induced adipose tissue inflammation occurs in a sex-dependent manner. Here we have employed the clinically relevant NIAAA model of chronic-binge alcohol consumption to investigate this sexual dimorphism. We report that female mice have greater liver injury than male mice despite lower alcohol consumption. Chronic-binge alcohol induces adipose tissue inflammation in vivo in female mice, which is illustrated by increased expression of TNFalpha, IL-6, and CCL2, compared to only IL-6 induction in male adipose tissue. Further, macrophage activation markers such as CD68 as well as the pro-inflammatory activation markers CD11b and CD11c were higher in female adipose tissue. Interestingly, alcohol induced expression of TLR2, 3, 4, and 9 in female but not male adipose tissue, without affecting the TLR adaptor, MyD88. Higher trends of serum endotoxin in female mice may likely contribute to adipose tissue inflammation. In vitro chronic alcohol-mediated sensitization of macrophages to endotoxin is independent of sex. In summary, we demonstrate for the first time that there is a sexual dimorphism in alcohol-induced adipose tissue inflammation and female mice exhibit a higher degree of inflammation than male mice.

A widely employed germ cell marker is an ancient disordered protein with reproductive functions in diverse eukaryotes

Wed, 02/15/2017 - 10:43am

The advent of sexual reproduction and the evolution of a dedicated germline in multicellular organisms are critical landmarks in eukaryotic evolution. We report an ancient family of GCNA (germ cell nuclear antigen) proteins that arose in the earliest eukaryotes, and feature a rapidly evolving intrinsically disordered region (IDR). Phylogenetic analysis reveals that GCNA proteins emerged before the major eukaryotic lineages diverged; GCNA predates the origin of a dedicated germline by a billion years. Gcna gene expression is enriched in reproductive cells across eukarya - either just prior to or during meiosis in single-celled eukaryotes, and in stem cells and germ cells of diverse multicellular animals. Studies of Gcna-mutant C. elegans and mice indicate that GCNA has functioned in reproduction for at least 600 million years. Homology to IDR-containing proteins implicated in DNA damage repair suggests that GCNA proteins may protect the genomic integrity of cells carrying a heritable genome.

The RNA-binding protein ATX-2 regulates cytokinesis through PAR-5 and ZEN-4

Wed, 02/15/2017 - 10:43am

The spindle midzone harbors both microtubules and proteins necessary for furrow formation and the completion of cytokinesis. However, the mechanisms that mediate the temporal and spatial recruitment of cell division factors to the spindle midzone and midbody remain unclear. Here we describe a mechanism governed by the conserved RNA-binding protein ATX-2/Ataxin-2, which targets and maintains ZEN-4 at the spindle midzone. ATX-2 does this by regulating the amount of PAR-5 at mitotic structures, particularly the spindle, centrosomes, and midbody. Preventing ATX-2 function leads to elevated levels of PAR-5, enhanced chromatin and centrosome localization of PAR-5-GFP, and ultimately a reduction of ZEN-4-GFP at the spindle midzone. Codepletion of ATX-2 and PAR-5 rescued the localization of ZEN-4 at the spindle midzone, indicating that ATX-2 mediates the localization of ZEN-4 upstream of PAR-5. We provide the first direct evidence that ATX-2 is necessary for cytokinesis and suggest a model in which ATX-2 facilitates the targeting of ZEN-4 to the spindle midzone by mediating the posttranscriptional regulation of PAR-5.