Skin structure and hair morphology of different body parts in the Common Pipistrelle (Pipistrellus pipistrellus)

The bat skin shows an unusual morphology that corresponds to flying adaptations but also performs multiple functions including a protective barrier against microbes and parasites. Here, we compare the microscopic structure of the skin and hairs collected from the membranes with other body parts in the Common Pipistrelle (Pipistrellus pipistrellus) in relation to parasite availability. Statistical analysis of whole‐skin thickness revealed two main groups according to body regions; the first with thin skin (wing and tail membrane) and the second with thick skin (head and dorsum, abdomen, footpad). The density of hair was evaluated by a novel method, and it revealed that the density was significantly higher in the head region than in dorsal and ventral body parts. These differences possibly play a role for bat ectoparasites when choosing the preferred region of their host. Along the axis of each hair, the scale morphology was found to be variable. Hair morphology, however, did not vary among body regions. Mast cells were numerous in the hairy areas around vessels and hair follicles of the dorsum and abdomen, which are easily accessible to ectoparasites. Increased numbers of mast cells in hair‐bearing skin are part of the host adaptation system in parasite‐preferred locations.     

Cyanobacterial dominance in Brazil: distribution and environmental preferences

Based on a literature survey, we evaluated the periods of cyanobacterial dominance in Brazil. We hypothesized that variability of environmental forces along the country will promote or facilitate temporal and spatial mosaic in cyanobacterial dominance. The most striking outcomes are related to the dominance of Cylindrospermopsis, Dolichospermum, and Microcystis. Although they share important adaptive strategies (e.g., aerotopes, large size and toxins production), our findings suggest that they have different environmental preferences. Dolichospermum and Microcystis dominated mainly in warm-rainy periods whereas Cylindrospermopsis was more common during dry periods and in mixed systems, or formed perennial dominance. Maximum phosphorus concentrations were observed in reservoirs dominated by Cylindrospermopsis. Although the main genera reached high biomass levels individually, different abilities to form dominance and co-dominance were observed. The number of co-dominance of Chroococales and Nostocales was almost the same as the individual occurrence of the main genera from these groups. This dataset reveals patterns of dominance of these cyanobacteria and also indicates that physiological features will cause differences in the mechanisms of interactions between species. The understanding of these processes and their relationship to environmental conditions will promote better understanding of cyanobacterial dominance and increase our ability to predict and manage these events.     

Characteristics of Randomized Trials Published in Latin America and the Caribbean According to Funding Source

Introduction

Few studies have assessed the nature and quality of randomized controlled trials (RCTs) in Latin America and the Caribbean (LAC).

Methods and Findings

The aims of this systematic review are to evaluate the characteristics (including the risk of bias assessment) of RCT conducted in LAC according to funding source. A review of RCTs published in 2010 in which the author''s affiliation was from LAC was performed in PubMed and LILACS. Two reviewers independently extracted data and assessed the risk of bias. The primary outcomes were risk of bias assessment and funding source. A total of 1,695 references were found in PubMed and LILACS databases, of which 526 were RCTs (N = 73.513 participants). English was the dominant publication language (93%) and most of the RCTs were published in non-LAC journals (84.2%). Only five of the 19 identified countries accounted for nearly 95% of all RCTs conducted in the region (Brazil 70.9%, Mexico 10.1%, Argentina 5.9%, Colombia 3.8%, and Chile 3.4%). Few RCTs covered priority areas related with Millennium Development Goals like maternal health (6.7%) or high priority infectious diseases (3.8%). Regarding children, 3.6% and 0.4% RCT evaluated nutrition and diarrhea interventions respectively but none pneumonia. As a comparison, aesthetic and sport related interventions account for 4.6% of all trials. A random sample of RCTs (n = 358) was assessed for funding source: exclusively public (33.8%); private (e.g. pharmaceutical company) (15.3%); other (e.g. mixed, NGO) (15.1%); no funding (35.8%). Overall assessments for risk of bias showed no statistically significant differences between RCTs and type of funding source. Statistically significant differences favoring private and others type of funding was found when assessing trial registration and conflict of interest reporting.

Conclusion

Findings of this study could be used to provide more direction for future research to facilitate innovation, improve health outcomes or address priority health problems.     

Interaction of the Human Papillomavirus E6 Oncoprotein with Sorting Nexin 27 Modulates Endocytic Cargo Transport Pathways

A subset of high-risk Human Papillomaviruses (HPVs) are the causative agents of a large number of human cancers, of which cervical is the most common. Two viral oncoproteins, E6 and E7, contribute directly towards the development and maintenance of malignancy. A characteristic feature of the E6 oncoproteins from cancer-causing HPV types is the presence of a PDZ binding motif (PBM) at its C-terminus, which confers interaction with cellular proteins harbouring PDZ domains. Here we show that this motif allows E6 interaction with Sorting Nexin 27 (SNX27), an essential component of endosomal recycling pathways. This interaction is highly conserved across E6 proteins from multiple high-risk HPV types and is mediated by a classical PBM-PDZ interaction but unlike many E6 targets, SNX27 is not targeted for degradation by E6. Rather, in HPV-18 positive cell lines the association of SNX27 with components of the retromer complex and the endocytic transport machinery is altered in an E6 PBM-dependent manner. Analysis of a SNX27 cargo, the glucose transporter GLUT1, reveals an E6-dependent maintenance of GLUT1 expression and alteration in its association with components of the endocytic transport machinery. Furthermore, knockdown of E6 in HPV-18 positive cervical cancer cells phenocopies the loss of SNX27, both in terms of GLUT1 expression levels and its vesicular localization, with a concomitant marked reduction in glucose uptake, whilst loss of SNX27 results in slower cell proliferation in low nutrient conditions. These results demonstrate that E6 interaction with SNX27 can alter the recycling of cargo molecules, one consequence of which is modulation of nutrient availability in HPV transformed tumour cells.     

Blimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF-Mediated Tissue Pathology

Tumor necrosis factor (TNF) is critical for controlling many intracellular infections, but can also contribute to inflammation. It can promote the destruction of important cell populations and trigger dramatic tissue remodeling following establishment of chronic disease. Therefore, a better understanding of TNF regulation is needed to allow pathogen control without causing or exacerbating disease. IL-10 is an important regulatory cytokine with broad activities, including the suppression of inflammation. IL-10 is produced by different immune cells; however, its regulation and function appears to be cell-specific and context-dependent. Recently, IL-10 produced by Th1 (Tr1) cells was shown to protect host tissues from inflammation induced following infection. Here, we identify a novel pathway of TNF regulation by IL-10 from Tr1 cells during parasitic infection. We report elevated Blimp-1 mRNA levels in CD4⁺ T cells from visceral leishmaniasis (VL) patients, and demonstrate IL-12 was essential for Blimp-1 expression and Tr1 cell development in experimental VL. Critically, we show Blimp-1-dependent IL-10 production by Tr1 cells prevents tissue damage caused by IFNγ-dependent TNF production. Therefore, we identify Blimp-1-dependent IL-10 produced by Tr1 cells as a key regulator of TNF-mediated pathology and identify Tr1 cells as potential therapeutic tools to control inflammation.     

Ectonucleoside Triphosphate Diphosphohydrolase-3 Antibody Targets Adult Human Pancreatic β Cells for In Vitro and In Vivo Analysis

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