Following successful anti-leishmanial treatment, neutrophil counts, CD10 expression and phagocytic capacity remain reduced in visceral leishmaniasis patients co-infected with HIV

Visceral leishmaniasis (VL) patients co-infected with HIV (VL/HIV patients) experience frequent treatment failures, VL relapses, opportunistic infections, and higher mortality. Their immune system remains profoundly suppressed after clinical cure and they maintain higher parasite load. This is in contrast with patients with VL alone (VL patients). Since neutrophils play a critical role in the control of Leishmania replication and the regulation of immune responses, we tested the hypothesis that neutrophil activation status and effector functions are fully restored in VL, but not in VL/HIV patients. Our results show the neutrophil counts and all activation markers and effector functions tested in our study were reduced at the time of diagnosis in VL and VL/HIV patients as compared to controls. CD62L, CD63, arginase 1 expression levels and reactive oxygen species production were restored at the end of treatment in both groups. However, neutrophil counts, CD10 expression and phagocytosis remained significantly lower throughout follow-up in VL/HIV patients; suggesting that dysregulated neutrophils contribute to the impaired host defence against pathogens in VL/HIV patients

Endoscopists attitudes on the publication of "quality" data for endoscopic procedures: a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>Whilst the public now have access to mortality & morbidity data for cardiothoracic surgeons, such "quality" data for endoscopy are not generally available. We studied endoscopists' attitudes to and the practicality of this data being published.</p> <p>Methods</p> <p>We sent a questionnaire to all consultant gastrointestinal (GI) surgeons, physicians and medical GI specialist registrars in the Northern region who currently perform GI endoscopic procedures (n = 132). We recorded endoscopist demographics, experience and current data collection practice. We also assessed the acceptability and utility of nine items describing endoscopic "quality" (e.g. mortality, complication & completion rates).</p> <p>Results</p> <p>103 (78%) doctors responded of whom 79 were consultants (77%). 61 (59%) respondents were physicians. 77 (75%) collect any "quality" data. The most frequently collected item was colonoscopic completion rate. Data were most commonly collected for appraisal, audit or clinical governance. The majority of doctors (54%) kept these data only available to themselves, and just one allowed the public to access this. The most acceptable data item was annual number of endoscopies and the least was crude upper GI bleeding mortality. Surgeons rated information less acceptable and less useful than physicians. Acceptability and utility scores were not related to gender, length of experience or current activity levels. Only two respondents thought all items totally unacceptable and useless.</p> <p>Conclusion</p> <p>The majority of endoscopists currently collect "quality" data for their practice although these are not widely available. The endoscopists in this study consider the publication of their outcome data to be "fairly unacceptable/not very useful" to "neutral" (score 2–3). If these data were made available to patients, consideration must be given to both its value and its acceptability.</p

Hidden in plain sight: species richness and habitat characterisation of sublittoral pebble beds

Sublittoral pebble beds are generally considered to be impoverished, but the physical and biological characteristics of these habitats are poorly known. We characterised nineteen pebble bed sites in the Maltese Islands, providing detailed habitat data for Mediterranean sublittoral pebble beds for the first time. Nearly 40,000 individuals belonging to 332 taxa were recorded in all, with total richness estimated to reach 440 taxa; molluscs, crustaceans and polychaetes were the most diverse faunal groups. This high diversity is likely due to the structural complexity of the pebble beds, which had a vertically stratified arrangement of sediment particles that is likely maintained through periodic physical disturbance. Variation in the biotic assemblage from site to site was correlated with changes in the quantity of sand and silt, with the area of the pebble bed, with water depth, and with the thickness of the pebble layer. This indicates that pebble-bed macrofaunal assemblages are sensitive to changes in hydrodynamic conditions and sediment loading, to alterations to the stratification of the pebble beds, and to fragmentation of the habitat patches. These results contradict assertions that sublittoral pebble beds are impoverished, instead showing that they can be highly diverse habitats supporting biotic assemblages that respond to a complex set of environmental variables. The present findings enable better understanding of the ecological importance of pebble beds and of the potential impacts of anthropogenic disturbance, enabling more informed decisions for habitat conservation and management

Observational Properties of Jets in Active Galactic Nuclei

Parsec scale jet properties are shortly presented and discussed. Observational data are used to derive constraints on the jet velocity and orientation, the presence of velocity structures, and the connection between the pc and kpc scale. Two peculiar sources with limb-brightened jets: 1144+35 and Mkn 501 are discussed in detail.Comment: 13 pages with 7 figures. To appear in "Virtual Astrophysical Jets" APSS, Kluwer Academic Publisher - Massaglia, Bodo, Rossi eds - in pres

In vitro selection of miltefosine resistance in promastigotes of Leishmania donovani from Nepal: genomic and metabolomic characterization.

In this study, we followed the genomic, lipidomic and metabolomic changes associated with the selection of miltefosine (MIL) resistance in two clinically derived Leishmania donovani strains with different inherent resistance to antimonial drugs (antimony sensitive strain Sb-S; and antimony resistant Sb-R). MIL-R was easily induced in both strains using the promastigote-stage, but a significant increase in MIL-R in the intracellular amastigote compared to the corresponding wild-type did not occur until promastigotes had adapted to 12.2 μM MIL. A variety of common and strain-specific genetic changes were discovered in MIL-adapted parasites, including deletions at the LdMT transporter gene, single-base mutations and changes in somy. The most obvious lipid changes in MIL-R promastigotes occurred to phosphatidylcholines and lysophosphatidylcholines and results indicate that the Kennedy pathway is involved in MIL resistance. The inherent Sb resistance of the parasite had an impact on the changes that occurred in MIL-R parasites, with more genetic changes occurring in Sb-R compared with Sb-S parasites. Initial interpretation of the changes identified in this study does not support synergies with Sb-R in the mechanisms of MIL resistance, though this requires an enhanced understanding of the parasite's biochemical pathways and how they are genetically regulated to be verified fully.This study was supported by as part of the FP7 EC K aladrug-R project (http://cordis.europa.eu/project/rcn/88823_en.html, grant number: 222895). JAC and MJS are supported by the Wellcome Trust via their core support for the Wellcome Trust Sanger Institute (grant number 098051) . TMF was funded by a BBSRC Research Experience Placement (grant number BB/J014540/1). CJRI was supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 101239/Z/13/Z). This research was supported in part by the National Science Foundation (grant number: NSF PHY11-25915) and by the Belgian Science Policy Office (TRIT, contract P7/41, to J-C.D.).This is the final version of the article. It was first available from Wiley via http://dx.doi.org/10.1111/mmi.1329

Scaling properties of protein family phylogenies

One of the classical questions in evolutionary biology is how evolutionary processes are coupled at the gene and species level. With this motivation, we compare the topological properties (mainly the depth scaling, as a characterization of balance) of a large set of protein phylogenies with a set of species phylogenies. The comparative analysis shows that both sets of phylogenies share remarkably similar scaling behavior, suggesting the universality of branching rules and of the evolutionary processes that drive biological diversification from gene to species level. In order to explain such generality, we propose a simple model which allows us to estimate the proportion of evolvability/robustness needed to approximate the scaling behavior observed in the phylogenies, highlighting the relevance of the robustness of a biological system (species or protein) in the scaling properties of the phylogenetic trees. Thus, the rules that govern the incapability of a biological system to diversify are equally relevant both at the gene and at the species level.Comment: Replaced with final published versio

Target score—a proteomics data selection tool applied to esophageal cancer identifies glut1-sialyl tn glycoforms as biomarkers of cancer aggressiveness

Esophageal cancer (EC) is a life-threatening disease, demanding the discovery of new biomarkers and molecular targets for precision oncology. Aberrantly glycosylated proteins hold tremendous potential towards this objective. In the current study, a series of esophageal squamous cell carcinomas (ESCC) and EC-derived circulating tumor cells (CTCs) were screened by immunoassays for the sialyl-Tn (STn) antigen, a glycan rarely expressed in healthy tissues and widely observed in aggressive gastrointestinal cancers. An ESCC cell model was glycoengineered to express STn and characterized in relation to cell proliferation and invasion in vitro. STn was found to be widely present in ESCC (70% of tumors) and in CTCs in 20% of patients, being associated with general recurrence and reduced survival. Furthermore, STn expression in ESCC cells increased invasion in vitro, while reducing cancer cells proliferation. In parallel, an ESCC mass spectrometry-based proteomics dataset, obtained from the PRIDE database, was comprehensively interrogated for abnormally glycosylated proteins. Data integration with the Target Score, an algorithm developed in-house, pinpointed the glucose transporter type 1 (GLUT1) as a biomarker of poor prognosis. GLUT1-STn glycoproteoforms were latter identified in tumor tissues in patients facing worst prognosis. Furthermore, healthy human tissues analysis suggested that STn glycosylation provided cancer specificity to GLUT1. In conclusion, STn is a biomarker of worst prognosis in EC and GLUT1-STn glycoforms may be used to increase its specificity on the stratification and targeting of aggressive ESCC forms.The authors wish to acknowledge the Portuguese Foundation for Science and Technology (FCT) for the human resources grants: PhD grant SFRH/BD/111242/2015 (AP), SFRH/BD/146500/2019 (MRS), SFRH/BD/142479/2018 (JS), SFRH/BD/105355/2014 (RA) and FCT assistant researcher grant CEECIND/03186/2017 (JAF). FCT is co-financed by European Social Fund (ESF) under Human Potential Operation Programme (POPH) from National Strategic Reference Framework (NSRF). The authors also acknowledge FCT the funding for CI-IPOP research unit (PEst-OE/SAU/UI0776/201) and LAQV-REQUIMTE research unit (UIDB/50006/2020), the Portuguese Oncology Institute of Porto Research Centre (CI-IPOP-29-2016-2020; CI-IPOP-58-2016-2020; CI-IPOP-Proj.70-bolsa2019-GPTE) and PhD Program in Biomedical Sciences of ICBAS-University of Porto. The author also thanks “Early stage cancer treatment, driven by context of molecular imaging (ESTIMA)” framework (NORTE-01-0145-FEDER-000027) and IPO-Score (DSAIPA/DS/0042/2018) for financial support. This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020 and by Portuguese funds through FCT/MCTES—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior. The authors also acknowledge support from the Portuguese League against Cancer grant LPCC-NRN-2020 (DF)

No Detectable Fertility Benefit from a Single Additional Mating in Wild Stalk-Eyed Flies

Background: Multiple mating by female insects is widespread, and the explanation(s) for repeated mating by females has been the subject of much discussion. Females may profit from mating multiply through direct material benefits that increase their own reproductive output, or indirect genetic benefits that increase offspring fitness. One particular direct benefit that has attracted significant attention is that of fertility assurance, as females often need to mate multiply to achieve high fertility. This hypothesis has never been tested in a wild insect population.Methodology/Principal Findings: Female Malaysian stalk-eyed flies (Teleopsis dalmanni) mate repeatedly during their lifetime, and have been shown to be sperm limited under both laboratory and field conditions. Here we ask whether receiving an additional mating alleviates sperm limitation in wild females. In our experiment one group of females received a single additional mating, while a control group received an interrupted, and therefore unsuccessful, mating. Females that received an additional mating did not lay more fertilised eggs in total, nor did they lay proportionately more fertilised eggs. Female fertility declined significantly through time, demonstrating that females were sperm limited. However, receipt of an additional mating did not significantly alter the rate of this decline.Conclusions/Significance: Our data suggest that the fertility consequences of a single additional mating were small. We discuss this effect (or lack thereof), and suggest that it is likely to be attributed to small ejaculate size, a high proportion of failed copulations, and the presence of X-linked meiotic drive in this species

Maximum likelihood models and algorithms for gene tree evolution with duplications and losses

<p>Abstract</p> <p>Background</p> <p>The abundance of new genomic data provides the opportunity to map the location of gene duplication and loss events on a species phylogeny. The first methods for mapping gene duplications and losses were based on a parsimony criterion, finding the mapping that minimizes the number of duplication and loss events. Probabilistic modeling of gene duplication and loss is relatively new and has largely focused on birth-death processes.</p> <p>Results</p> <p>We introduce a new maximum likelihood model that estimates the speciation and gene duplication and loss events in a gene tree within a species tree with branch lengths. We also provide an, in practice, efficient algorithm that computes optimal evolutionary scenarios for this model. We implemented the algorithm in the program DrML and verified its performance with empirical and simulated data.</p> <p>Conclusions</p> <p>In test data sets, DrML finds optimal gene duplication and loss scenarios within minutes, even when the gene trees contain sequences from several hundred species. In many cases, these optimal scenarios differ from the lca-mapping that results from a parsimony gene tree reconciliation. Thus, DrML provides a new, practical statistical framework on which to study gene duplication.</p

Quantifying Variability of Avian Colours: Are Signalling Traits More Variable?

Background Increased variability in sexually selected ornaments, a key assumption of evolutionary theory, is thought to be maintained through condition-dependence. Condition-dependent handicap models of sexual selection predict that (a) sexually selected traits show amplified variability compared to equivalent non-sexually selected traits, and since males are usually the sexually selected sex, that (b) males are more variable than females, and (c) sexually dimorphic traits more variable than monomorphic ones. So far these predictions have only been tested for metric traits. Surprisingly, they have not been examined for bright coloration, one of the most prominent sexual traits. This omission stems from computational difficulties: different types of colours are quantified on different scales precluding the use of coefficients of variation. Methodology/Principal Findings Based on physiological models of avian colour vision we develop an index to quantify the degree of discriminable colour variation as it can be perceived by conspecifics. A comparison of variability in ornamental and non-ornamental colours in six bird species confirmed (a) that those coloured patches that are sexually selected or act as indicators of quality show increased chromatic variability. However, we found no support for (b) that males generally show higher levels of variability than females, or (c) that sexual dichromatism per se is associated with increased variability. Conclusions/Significance We show that it is currently possible to realistically estimate variability of animal colours as perceived by them, something difficult to achieve with other traits. Increased variability of known sexually-selected/quality-indicating colours in the studied species, provides support to the predictions borne from sexual selection theory but the lack of increased overall variability in males or dimorphic colours in general indicates that sexual differences might not always be shaped by similar selective forces