The coordination of cell growth during fission yeast mating requires Ras1-GTP hydrolysis

The spatial and temporal control of polarity is fundamental to the survival of all organisms. Cells define their polarity using highly conserved mechanisms that frequently rely upon the action of small GTPases, such as Ras and Cdc42. Schizosaccharomyces pombe is an ideal system with which to study the control of cell polarity since it grows from defined tips using Cdc42-mediated actin remodeling. Here we have investigated the importance of Ras1-GTPase activity for the coordination of polarized cell growth during fission yeast mating. Following pheromone stimulation, Ras1 regulates both a MAPK cascade and the activity of Cdc42 to enable uni-directional cell growth towards a potential mating partner. Like all GTPases, when bound to GTP, Ras1 adopts an active conformation returning to an inactive state upon GTP-hydrolysis, a process accelerated through interaction with negative regulators such as GAPs. Here we show that, at low levels of pheromone stimulation, loss of negative regulation of Ras1 increases signal transduction via the MAPK cascade. However, at the higher concentrations observed during mating, hyperactive Ras1 mutations promote cell death. We demonstrate that these cells die due to their failure to coordinate active Cdc42 into a single growth zone resulting in disorganized actin deposition and unsustainable elongation from multiple tips. These results provide a striking demonstration that the deactivation stage of Ras signaling is fundamentally important in modulating cell polarity

Association of kidney function with inflammatory and procoagulant markers in a diverse cohort: A cross-sectional analysis from the Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Prior studies using creatinine-based estimated glomerular filtration rate (eGFR) have found limited associations between kidney function and markers of inflammation. Using eGFR and cystatin C, a novel marker of kidney function, the authors investigated the association of kidney function with multiple biomarkers in a diverse cohort. Methods: The Multi-Ethnic Study of Atherosclerosis consists of 6,814 participants of white, African-American, Hispanic, and Chinese descent, enrolled from 2000-2002 from six U.S. communities. Measurements at the enrollment visit included serum creatinine, cystatin C, and six inflammatory and procoagulant biomarkers. Creatinine-based eGFR was estimated using the fourvariable Modification of Diet in Renal Disease equation, and chronic kidney disease was defined by an eGFR less than 60 mL/min/1.73 m2. Results: Adjusted partial correlations between cystatin C and all biomarkers were statistically significant: C-reactive protein (r = 0.08), interleukin-6 (r = 0.16), tumor necrosis factor-a soluble receptor 1 (TNF-aR1; r = 0.75), intercellular adhesion molecule-1 (r = 0.21), fibrinogen (r = 0.14), and factor VIII (r = 0.11; two-sided p less than 0.01 for all). In participants without chronic kidney disease, higher creatinine-based eGFR was associated only with higher TNF-aR1 levels. Conclusion: In a cohort characterized by ethnic diversity, cystatin C was directly associated with multiple procoagulant and inflammatory markers. Creatinine-based eGFR had similar associations with these biomarkers among subjects with chronic kidney disease.This research was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute (NHLBI)

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Contraceptive Use and Method Preference among Women in Soweto, South Africa: The Influence of Expanding Access to HIV Care and Treatment Services

Objective: Preventing unintended pregnancy among HIV-positive women constitutes a critical and cost-effective approach to primary prevention of mother-to-child transmission of HIV and is a global public health priority for addressing the desperate state of maternal and child health in HIV hyper-endemic settings. We sought to investigate whether the prevalence of contraceptive use and method preferences varied by HIV status and receipt of highly active antiretroviral therapy (HAART) among women in Soweto, South Africa. Methods: We used survey data from 563 sexually active, non-pregnant women (18–44 years) recruited from the Perinatal HIV Research Unit in Soweto (May–December, 2007); 171 women were HIV-positive and receiving HAART (median duration of use = 31 months; IQR = 28, 33), 178 were HIV-positive and HAART-naïve, and 214 were HIV-negative. Medical record review was conducted to confirm HIV status and clinical variables. Logistic regression models estimated adjusted associations between HIV status, receipt of HAART, and contraceptive use. Results: Overall, 78 % of women reported using contraception, with significant variation by HIV status: 86 % of HAART users, 82 % of HAART-naïve women, and 69 % of HIV-negative women (p,0.0001). In adjusted models, compared with HIVnegativ

Emotional problems in preadolescents in Norway: the role of gender, ethnic minority status, and home- and school-related hassles

<p>Abstract</p> <p>Background</p> <p>"The gender gap" refers to a lifelong higher rate of emotional problems in girls, as compared to boys, that appears during adolescence. The gender gap is a well-replicated finding among older adolescents and is assumed to be a cross-cultural phenomenon. However, these cross-cultural studies have not investigated the gender gap in ethnic minorities but sampled ethnic majority adolescents in different countries. Some studies that investigated the gender gap across ethnic groups indirectly (by presenting emotional problem scores stratified by gender and ethnic group) indicate that the gender gap is less prominent or even absent among minorities. The aims of this study were to assess whether the gender gap is found in both majority and minority preadolescents, and to investigate whether a possible (gender and ethnic) group difference can be accounted for by differences in home or school hassles.</p> <p>Methods</p> <p>Participants were 902 preadolescent students (aged 10 to 12) from two cities in Norway. We collected self-report measures of emotional problems and home and school hassles. Using mediated moderation analysis we tested whether the interaction effect between gender and ethnic minority background on emotional problems was mediated by home or school hassles.</p> <p>Results</p> <p>The gender gap in emotional problems was restricted to ethnic majority preadolescents. School hassles but not home hassles accounted in part for this effect.</p> <p>Conclusions</p> <p>The absence of the gender gap among minority as opposed to majority preadolescents may indicate that social circumstances may postpone or hamper the emergence and magnitude of the gender gap in ethnic minority preadolescents. In this study, school hassles partly accounted for the combined gender and ethnic group differences on emotional problems. This indicates that school hassles may play a role in the higher levels of emotional problems in preadolescent minority boys and consequently the absence of a gender gap found in our minority sample.</p

Regulation of Fission Yeast Morphogenesis by PP2A Activator pta2

Cell polarization is key for the function of most eukaryotic cells, and regulates cell shape, migration and tissue architecture. Fission yeast, Schizosaccharomyces pombe cells are cylindrical and polarize cell growth to one or both cell tips dependent on the cell cycle stage. Whereas microtubule cytoskeleton contributes to the positioning of the growth sites by delivering polarity factors to the cell ends, the Cdc42 GTPase polarizes secretion via actin-dependent delivery and tethering of secretory vesicles to plasma membrane. How growth is restricted to cell tips and how re-initiation of tip growth is regulated in the cell cycle remains poorly understood. In this work we investigated the function of protein phosphatase type 2A (PP2A) in S. pombe morphogenesis by deleting the evolutionary conserved PTPA-type regulatory subunit that we named pta2. pta2-deleted cells showed morphological defects and altered growth pattern. Consistent with this, actin patches and active Cdc42 were mislocalized in the pta2 deletion. These defects were additive to the lack of Cdc42-GAP Rga4. pta2Δ cells show upregulated Cdc42 activity and pta2 interacts genetically with polarisome components Tea1, Tea4 and For3 leading to complete loss of cell polarity and rounded morphology. Thus, regulation of polarity by PP2A requires the polarisome and involves Pta2-dependent control of Cdc42 activity

Patterns of Diversity in Soft-Bodied Meiofauna: Dispersal Ability and Body Size Matter

Background: Biogeographical and macroecological principles are derived from patterns of distribution in large organisms, whereas microscopic ones have often been considered uninteresting, because of their supposed wide distribution. Here, after reporting the results of an intensive faunistic survey of marine microscopic animals (meiofauna) in Northern Sardinia, we test for the effect of body size, dispersal ability, and habitat features on the patterns of distribution of several groups.Methodology/Principal Findings: As a dataset we use the results of a workshop held at La Maddalena (Sardinia, Italy) in September 2010, aimed at studying selected taxa of soft-bodied meiofauna (Acoela, Annelida, Gastrotricha, Nemertodermatida, Platyhelminthes and Rotifera), in conjunction with data on the same taxa obtained during a previous workshop hosted at Tjärnö (Western Sweden) in September 2007. Using linear mixed effects models and model averaging while accounting for sampling bias and potential pseudoreplication, we found evidence that: (1) meiofaunal groups with more restricted distribution are the ones with low dispersal potential; (2) meiofaunal groups with higher probability of finding new species for science are the ones with low dispersal potential; (3) the proportion of the global species pool of each meiofaunal group present in each area at the regional scale is negatively related to body size, and positively related to their occurrence in the endobenthic habitat.Conclusion/Significance: Our macroecological analysis of meiofauna, in the framework of the ubiquity hypothesis for microscopic organisms, indicates that not only body size but mostly dispersal ability and also occurrence in the endobenthic habitat are important correlates of diversity for these understudied animals, with different importance at different spatial scales. Furthermore, since the Western Mediterranean is one of the best-studied areas in the world, the large number of undescribed species (37%) highlights that the census of marine meiofauna is still very far from being complete

Patterns of anti-malarial drug treatment among pregnant women in Uganda

BACKGROUND: Prompt use of an effective anti-malarial drug is essential for controlling malaria and its adverse effects in pregnancy. The World Health Organization recommends an artemisinin-based combination therapy as the first-line treatment of uncomplicated malaria in the second and third trimesters of pregnancy. The study objective was to determine the degree to which presumed episodes of uncomplicated symptomatic malaria in pregnancy were treated with a recommended anti-malarial regimen in a region of Uganda. METHODS: Utilizing a population-based random sample, we interviewed women living in Jinja, Uganda who had been pregnant in the past year. RESULTS: Self-reported malaria during the index pregnancy was reported among 67% (n = 334) of the 500 participants. Among the 637 self-reported episodes of malaria, an anti-malarial drug was used for treatment in 85% of the episodes. Use of a currently recommended treatment in the first trimester was uncommon (5.6%). A contraindicated anti-malarial drug (sulphadoxine-pyrimethamine and/or artemether-lumefantrine) was involved in 70% of first trimester episodes. Recommended anti-malarials were used according to the guidelines in only 30.1% of all second and third trimester episodes. CONCLUSIONS: Self-reported malaria was extremely common in this population and adherence to treatment guidelines for the management of malaria in pregnancy was poor. Use of artemether-lumefantrine combined with non-recommended anti-malarials was common practice. Overuse of anti-malarial drugs, especially ones that are no longer recommended, undermines malaria control efforts by fueling the spread of drug resistance and delaying appropriate treatment of non-malarial febrile illnesses. Improved diagnostic capacity is essential to ultimately improving the management of malaria-like symptoms during pregnancy and appropriate use of currently available anti-malarials

Different Effect of Proteasome Inhibition on Vesicular Stomatitis Virus and Poliovirus Replication

Proteasome activity is an important part of viral replication. In this study, we examined the effect of proteasome inhibitors on the replication of vesicular stomatitis virus (VSV) and poliovirus. We found that the proteasome inhibitors significantly suppressed VSV protein synthesis, virus accumulation, and protected infected cells from toxic effect of VSV replication. In contrast, poliovirus replication was delayed, but not diminished in the presence of the proteasome inhibitors MG132 and Bortezomib. We also found that inhibition of proteasomes stimulated stress-related processes, such as accumulation of chaperone hsp70, phosphorylation of eIF2α, and overall inhibition of translation. VSV replication was sensitive to this stress with significant decline in replication process. Poliovirus growth was less sensitive with only delay in replication. Inhibition of proteasome activity suppressed cellular and VSV protein synthesis, but did not reduce poliovirus protein synthesis. Protein kinase GCN2 supported the ability of proteasome inhibitors to attenuate general translation and to suppress VSV replication. We propose that different mechanisms of translational initiation by VSV and poliovirus determine their sensitivity to stress induced by the inhibition of proteasomes. To our knowledge, this is the first study that connects the effect of stress induced by proteasome inhibition with the efficiency of viral infection