LmaPA2G4, a Homolog of Human Ebp1, Is an Essential Gene and Inhibits Cell Proliferation in L. major

We have identified LmaPA2G4, a homolog of the human proliferation-associated 2G4 protein (also termed Ebp1), in aphosphoproteomic screening. Multiple sequence alignment and cluster analysis revealed that LmaPA2G4 is a non-peptidasemember of the M24 family of metallopeptidases. This pseudoenzyme is structurally related to methionine aminopeptidases. Anull mutant system based on negative selection allowed us to demonstrate that LmaPA2G4 is an essential gene inLeishmaniamajor. Over-expression of LmaPA2G4 did not alter cell morphology or the ability to differentiate into metacyclic and amastigotestages. Interestingly, the over-expression affected cell proliferation and virulence in mouse footpad analysis. LmaPA2G4 binds asynthetic double-stranded RNA polyriboinosinic polyribocytidylic acid [poly(I:C)] as shown in an electrophoretic mobility shiftassay (EMSA). Quantitative proteomics revealed that the over-expression of LmaPA2G4 led to accumulation of factors involved intranslation initiation and elongation. Significantly, we found a strong reduction ofde novoprotein biosynthesis in transgenicparasites using a non-radioactive metabolic labeling assay. In conclusion, LmaPA2G4 is an essential gene and is potentiallyimplicated in fundamental biological mechanisms, such as translation, making it an attractive target for therapeutic intervention.Fil: Norris Mullins, Brianna. University Of Notre Dame-Indiana; Estados UnidosFil: VanderKolk, Kaitlin. University Of Notre Dame-Indiana; Estados UnidosFil: Vacchina, Paola. University Of Notre Dame-Indiana; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Joyce, Michelle V.. University Of Notre Dame-Indiana; Estados UnidosFil: Morales, Miguel A.. University Of Notre Dame-Indiana; Estados Unido

The queen of the island : On the density and distribution of the Eurasian Collared-Dove (Streptopelia decaocto) in Cozumel

The Eurasian Collared-Dove (Streptopelia decaocto) is one of the most successful invasive bird species across the world. Worryingly, the invasive dove is a known reservoir of many diseases, some of which can potentially infect mammals (including human beings). Additionally, aggressive behaviors have been recorded toward other bird species resulting in territory and nest usurpation. Thus, the presence of this species poses an important risk for native species with similar habits, particularly in insular systems. Based on this, we carried out this study to assess the density and distribution of the Eurasian Collared-Dove in the island of Cozumel, as well as to evaluate the relationship between their abundance and the environmental characteristics of the places they inhabit. We estimated their distance-corrected densities in the island's largest town and performed an inverse distance weighting (IDW) interpolation to visualize their distribution. We performed a generalized linear model (GLM) to assess relationships between the environmental variables and the abundance of doves using a reduced model procedure. We obtained 137 records of doves present in 94% of all survey sites and an estimated density of 6.8 ind/ha, for a total of 6,670 doves in San Miguel de Cozumel. We did not find a spatial pattern of the dove's distribution on the urban setting, but we found an interaction between their abundances with tree cover and building height. Our findings, together with previous evidence of infection risk and aggressive behavior, make this species a threat to the native species communities of fragile ecosystems such as the island of Cozumel.Peer reviewe

Deconstructing the smoking-preeclampsia paradox through a counterfactual framework.

Although smoking during pregnancy may lead to many adverse outcomes, numerous studies have reported a paradoxical inverse association between maternal cigarette smoking during pregnancy and preeclampsia. Using a counterfactual framework we aimed to explore the structure of this paradox as being a consequence of selection bias. Using a case-control study nested in the Icelandic Birth Registry (1309 women), we show how this selection bias can be explored and corrected for. Cases were defined as any case of pregnancy induced hypertension or preeclampsia occurring after 20 weeks' gestation and controls as normotensive mothers who gave birth in the same year. First, we used directed acyclic graphs to illustrate the common bias structure. Second, we used classical logistic regression and mediation analytic methods for dichotomous outcomes to explore the structure of the bias. Lastly, we performed both deterministic and probabilistic sensitivity analysis to estimate the amount of bias due to an uncontrolled confounder and corrected for it. The biased effect of smoking was estimated to reduce the odds of preeclampsia by 28 % (OR 0.72, 95 %CI 0.52, 0.99) and after stratification by gestational age at delivery ( 1, revealing the structure of the paradox. The bias-adjusted estimation of the smoking effect on preeclampsia showed an OR of 1.22 (95 %CI 0.41, 6.53). The smoking-preeclampsia paradox appears to be an example of (1) selection bias most likely caused by studying cases prevalent at birth rather than all incident cases from conception in a pregnancy cohort, (2) omitting important confounders associated with both smoking and preeclampsia (preventing the outcome to develop) and (3) controlling for a collider (gestation weeks at delivery). Future studies need to consider these aspects when studying and interpreting the association between smoking and pregnancy outcomes

Sleep-Disordered Breathing and Gestational Diabetes Mellitus: A meta-analysis of 9,795 participants enrolled in epidemiological observational studies

OBJECTIVE Recently, sleep-disordered breathing (SDB) has been reported to be associated with the development of gestational diabetes mellitus (GDM). Accordingly, as this is emergent area of research that has significant clinical relevance, the objective of this meta-analysis is to examine the relationship between SDB with GDM. RESEARCH DESIGN AND METHODS We searched several electronic databases for all of the studies published before January 2013 and reviewed references of published articles. Meta-analytic procedures were used to estimate the unadjusted and BMI-adjusted odds ratios (ORs) using a random effects model. Significant values, weighted effect sizes, and 95% CIs were calculated, and tests of homogeneity of variance were performed. RESULTS Results from nine independent studies with a total of 9,795 pregnant women showed that SDB was significantly associated with an increased risk of GDM. Women with SDB had a more than threefold increased risk of GDM, with a pooled BMI-adjusted OR 3.06 (95% CI 1.89–4.96). CONCLUSIONS These findings demonstrate a significant association between SDB and GDM that is evident even after considered confounding by obesity. This meta-analysis indicates a need to evaluate the role of early recognition and treatment of SDB early during pregnancy

A Novel Approach for the Assessment of Cities through Ecosystem Integrity

To tackle urban heterogeneity and complexity, several indices have been proposed, commonly aiming to provide information for decision-makers. In this study, we propose a novel and customizable procedure for quantifying urban ecosystem integrity. Based on a citywide approach, we developed an easy-to-use index that contrasts physical and biological variables of urban ecosystems with a given reference system. The Urban Ecosystem Integrity Index (UEII) is the sum of the averages from the variables that make up its intensity of urbanization and biological components. We applied the UEII in a Mexican tropical city using land surface temperature, built cover, and the richness of native plants and birds. The overall ecosystem integrity of the city, having montane cloud, tropical dry, and temperate forests as reference systems, was low (−0.34 ± SD 0.32), showing that, beyond its biodiverse greenspace network, the built-up structure highly differs from the ecosystems of reference. The UEII showed to be a flexible and easy-to-calculate tool to evaluate ecosystem integrity for cities, allowing for comparisons between or among cities, as well as the sectors/regions within cities. If used properly, the index could become a useful tool for decision making and resource allocation at a city level

A Novel Approach for the Assessment of Cities through Ecosystem Integrity

To tackle urban heterogeneity and complexity, several indices have been proposed, commonly aiming to provide information for decision-makers. In this study, we propose a novel and customizable procedure for quantifying urban ecosystem integrity. Based on a citywide approach, we developed an easy-to-use index that contrasts physical and biological variables of urban ecosystems with a given reference system. The Urban Ecosystem Integrity Index (UEII) is the sum of the averages from the variables that make up its intensity of urbanization and biological components. We applied the UEII in a Mexican tropical city using land surface temperature, built cover, and the richness of native plants and birds. The overall ecosystem integrity of the city, having montane cloud, tropical dry, and temperate forests as reference systems, was low (−0.34 ± SD 0.32), showing that, beyond its biodiverse greenspace network, the built-up structure highly differs from the ecosystems of reference. The UEII showed to be a flexible and easy-to-calculate tool to evaluate ecosystem integrity for cities, allowing for comparisons between or among cities, as well as the sectors/regions within cities. If used properly, the index could become a useful tool for decision making and resource allocation at a city level

Emotional Distress, Alcohol Use, and Bidirectional Partner Violence Among Lesbian Women

This study examined the relationship between emotional distress (defined as depression, brooding, and negative affect), alcohol outcomes, and bidirectional intimate partner violence among lesbian women. Results lend support to the self-medication hypothesis, which predicts that lesbian women who experience more emotional distress are more likely to drink to cope, and in turn report more alcohol use, problem drinking, and alcohol-related problems. These alcohol outcomes were, in turn, associated with bidirectional partner violence (BPV). These results offer preliminary evidence that, similar to findings for heterosexual women, emotional distress, alcohol use, and particularly, alcohol-related problems are risk factors for BPV among lesbian women

A LINE1-Nucleolin partnership regulates early development and ESC identity

Transposable elements represent nearly half of mammalian genomes and are generally described as parasites, or "junk DNA." The LINE1 retrotransposon is the most abundant class and is thought to be deleterious for cells, yet it is paradoxically highly expressed during early development. Here, we report that LINE1 plays essential roles in mouse embryonic stem cells (ESCs) and pre-implantation embryos. In ESCs, LINE1 acts as a nuclear RNA scaffold that recruits Nucleolin and Kap1/Trim28 to repress Dux, the master activator of a transcriptional program specific to the 2-cell embryo. In parallel, LINE1 RNA mediates binding of Nucleolin and Kap1 to rDNA, promoting rRNA synthesis and ESC self-renewal. In embryos, LINE1 RNA is required for Dux silencing, synthesis of rRNA, and exit from the 2-cell stage. The results reveal an essential partnership between LINE1 RNA, Nucleolin, Kap1, and peri-nucleolar chromatin in the regulation of transcription, developmental potency, and ESC self-renewal

Prevalence and risk factors of gestational diabetes mellitus: findings from a universal screening feasibility program in Lima, Peru.

BACKGROUND: Gestational diabetes mellitus (GDM) is a global public health concern with potential implications for the health of a mother and her offspring. However, data on the prevalence and risk factors of GDM in Latin America are scarce. The study was designed to estimate the prevalence of GDM and identify maternal risk factors among Peruvian women. METHODS: A cross-sectional study was conducted among 1300 pregnant women attending a prenatal clinic in Lima, Peru. GDM was diagnosed using an Oral Glucose Tolerance Test (OGTT) performed between 24 and 28 gestational weeks using the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Depression status was assessed using the Patient Health Questionnaire-9. Multivariate logistic regression models were used to identify risk factors of GDM. RESULTS: Approximately 16% of pregnant women were diagnosed with GDM. The prevalence of obesity and depression were 24.4 and 10.6%, respectively. After adjusting for confounders, mid-pregnancy obesity was associated with a 1.64-fold increased odds of GDM (OR: 1.64; 95% CI: 1.03-2.61). Participants with a family history of diabetes had a 1.5-fold increased odds of developing GDM (OR: 1.51, 95% CI: 1.10-2.07) as compared to women without this family history. Depression was associated with a 1.54-fold increased odds of GDM (OR: 1.54; 95% CI:1.09-2.17). CONCLUSIONS: GDM is highly prevalent and was associated with maternal obesity, family history of diabetes and antepartum depression among Peruvian women. Intervention programs aimed at early diagnoses and management of GDM need to take maternal obesity, family history of diabetes and antepartum depression into account