Homozygous mutation in the prokineticin-receptor2 gene (Val274Asp) presenting as reversible Kallmann syndrome and persistent oligozoospermia: case report.

Prokineticin 2 (Prok2) or prokineticin-receptor2 (Prok-R2) gene mutations are associated with Kallmann syndrome (KS). We describe a new homozygous mutation of Prok-R2 gene in a man displaying KS with an apparent reversal of hypogonadism. The proband, offspring of consanguineous parents, presented at age 19 years with absent puberty, no sense of smell, low testosterone and gonadotrophin levels. Magnetic resonance imaging showed olfactory bulb absence. The patient achieved virilization and spermatogenesis with gonadotrophin administration. Two years after discontinuing hormonal therapy, he maintained moderate oligozoospermia and normal testosterone levels. Prok2 and Prok- R2 gene sequence analyses were performed. The proband had a homozygous mutation in Prok-R2 exon 2 that harbours the c.T820>A base substitution, causing the introduction of an aspartic acid in place of valine at position 274 (Val274Asp). His mother had the same mutation in heterozygous state. This report describes a novel homozygous mutation of Prok-R2 gene in a man with variant KS, underlying the role of Prok-R2 gene in the olfactory and reproductive system development in humans. Present findings indicate that markedly delayed activation of gonadotrophin secretion may occur in some KS cases with definite gene defects, and that oligozoospermia might result from a variant form of reversible hypogonadotrophic hypogonadism

Capsule impaction presenting as acute small bowel perforation: a case series

INTRODUCTION: Perforation caused by capsule endoscopy impaction is extremely rare and, at present, only five cases of perforation from capsule endoscopy impaction are reported in the literature. CASE PRESENTATION: We report here two cases of patients with undiagnosed small bowel stenosis presenting with acute perforation after capsule endoscopy. Strictures in the small bowel were likely the inciting mechanism leading to acute small bowel obstruction and subsequent distension and perforation above the capsule in the area of maximal serosal tension. Case 1 was a 55-year-old Italian woman who underwent capsule endoscopy because of recurrent postprandial cramping pain and iron deficiency anemia, in the setting of negative imaging studies including an abdominal ultrasound, upper endoscopy, colonoscopy and small bowel follow-through radiograph. She developed a symptomatic bowel obstruction approximately 36 hours after ingestion of the capsule. Emergent surgery was performed to remove the capsule, which was impacted at a stenosis due to a previously undiagnosed ileal adenocarcinoma, leading to perforation. Case 2 was a 60-year-old Italian man with recurrent episodes of abdominal pain and diarrhea who underwent capsule endoscopy after conventional modalities, including comprehensive blood and stool studies, computed tomography, an abdominal ultrasound, upper endoscopy, colonoscopy, barium enema and small bowel follow-through, were not diagnostic. Our patient developed abdominal distension, acute periumbilical pain, fever and leukocytosis 20 hours after capsule ingestion. Emergent surgery was performed to remove the capsule, which was impacted at a previously undiagnosed ileal Crohn’s stricture, leading to perforation. CONCLUSIONS: The present report shows that, although the risk of acute complication is very low, the patient should be informed of the risks involved in capsule endoscopy, including the need for emergency surgical exploration

A multi-gene signature predicts outcome in patients with pancreatic ductal adenocarcinoma.

© 2014 Haider et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Improved usage of the repertoires of pancreatic ductal adenocarcinoma (PDAC) profiles is crucially needed to guide the development of predictive and prognostic tools that could inform the selection of treatment options

BPGA- an ultra-fast pan-genome analysis pipeline

Recent advances in ultra-high-throughput sequencing technology and metagenomics have led to a paradigm shift in microbial genomics from few genome comparisons to large-scale pan-genome studies at different scales of phylogenetic resolution. Pan-genome studies provide a framework for estimating the genomic diversity of the dataset, determining core (conserved), accessory (dispensable) and unique (strain-specific) gene pool of a species, tracing horizontal gene-flux across strains and providing insight into species evolution. The existing pan genome software tools suffer from various limitations like limited datasets, difficult installation/requirements, inadequate functional features etc. Here we present an ultra-fast computational pipeline BPGA (Bacterial Pan Genome Analysis tool) with seven functional modules. In addition to the routine pan genome analyses, BPGA introduces a number of novel features for downstream analyses like core/pan/MLST (Multi Locus Sequence Typing) phylogeny, exclusive presence/absence of genes in specific strains, subset analysis, atypical G + C content analysis and KEGG & COG mapping of core, accessory and unique genes. Other notable features include minimum running prerequisites, freedom to select the gene clustering method, ultra-fast execution, user friendly command line interface and high-quality graphics outputs. The performance of BPGA has been evaluated using a dataset of complete genome sequences of 28 Streptococcus pyogenes strains

The Human Cytomegalovirus UL116 Glycoprotein Is a Chaperone to Control gH-Based Complexes Levels on Virions

Human cytomegalovirus (HCMV) relies in large part upon the viral membrane fusion glycoprotein B and two alternative gH/gL complexes, gH/gL/gO (Trimer) and gH/gL/UL128/UL130/UL131A (Pentamer) to enter into cells. The relative amounts of Trimer and Pentamer vary among HCMV strains and contribute to differences in cell tropism. Although the viral ER resident protein UL148 has been shown to interact with gH to facilitate gO incorporation, the mechanisms that favor the assembly and maturation of one complex over another remain poorly understood. HCMV virions also contain an alternative non-disulfide bound heterodimer comprised of gH and UL116 whose function remains unknown. Here, we show that disruption of HCMV gene UL116 causes infectivity defects of ∼10-fold relative to wild-type virus and leads to reduced expression of both gH/gL complexes in virions. Furthermore, gH that is not covalently bound to other viral glycoproteins, which are readily detected in wild-type HCMV virions, become undetectable in the absence of UL116 suggesting that the gH/UL116 complex is abundant in virions. We find evidence that UL116 and UL148 interact during infection indicating that the two proteins might cooperate to regulate the abundance of HCMV gH complexes. Altogether, these results are consistent with a role of UL116 as a chaperone for gH during the assembly and maturation of gH complexes in infected cells

History of chemically and radiatively important atmospheric gases from the Advanced Global Atmospheric Gases Experiment (AGAGE)

We present the organization, instrumentation, datasets, data interpretation, modeling, and accomplishments of the multinational global atmospheric measurement program AGAGE (Advanced Global Atmospheric Gases Experiment). AGAGE is distinguished by its capability to measure globally, at high frequency, and at multiple sites all the important species in the Montreal Protocol and all the important non-carbon-dioxide (non-CO₂) gases assessed by the Intergovernmental Panel on Climate Change (CO₂ is also measured at several sites). The scientific objectives of AGAGE are important in furthering our understanding of global chemical and climatic phenomena. They are the following: (1) to accurately measure the temporal and spatial distributions of anthropogenic gases that contribute the majority of reactive halogen to the stratosphere and/or are strong infrared absorbers (chlorocarbons, chlorofluorocarbons – CFCs, bromocarbons, hydrochlorofluorocarbons – HCFCs, hydrofluorocarbons – HFCs and polyfluorinated compounds (perfluorocarbons – PFCs), nitrogen trifluoride – NF₃, sulfuryl fluoride – SO₂F₂, and sulfur hexafluoride – SF₆) and use these measurements to determine the global rates of their emission and/or destruction (i.e., lifetimes); (2) to accurately measure the global distributions and temporal behaviors and determine the sources and sinks of non-CO₂ biogenic–anthropogenic gases important to climate change and/or ozone depletion (methane – CH₄, nitrous oxide – N₂O, carbon monoxide – CO, molecular hydrogen – H₂, methyl chloride – CH₃Cl, and methyl bromide – CH₃Br); (3) to identify new long-lived greenhouse and ozone-depleting gases (e.g., SO₂F₂, NF₃, heavy PFCs (C₄F₁₀, C₅F₁₂, C₆F₁₄, C₇F₁₆, and C₈F₁₈) and hydrofluoroolefins (HFOs; e.g., CH₂  =  CFCF₃) have been identified in AGAGE), initiate the real-time monitoring of these new gases, and reconstruct their past histories from AGAGE, air archive, and firn air measurements; (4) to determine the average concentrations and trends of tropospheric hydroxyl radicals (OH) from the rates of destruction of atmospheric trichloroethane (CH₃CCl₃), HFCs, and HCFCs and estimates of their emissions; (5) to determine from atmospheric observations and estimates of their destruction rates the magnitudes and distributions by region of surface sources and sinks of all measured gases; (6) to provide accurate data on the global accumulation of many of these trace gases that are used to test the synoptic-, regional-, and global-scale circulations predicted by three-dimensional models; and (7) to provide global and regional measurements of methane, carbon monoxide, and molecular hydrogen and estimates of hydroxyl levels to test primary atmospheric oxidation pathways at midlatitudes and the tropics. Network Information and Data Repository: <a href="http://agage.mit.edu/data" target="_blank">http://agage.mit.edu/data</a> or <a href="http://cdiac.ess-dive.lbl.gov/ndps/alegage.html" target="_blank">http://cdiac.ess-dive.lbl.gov/ndps/alegage.html</a> (<a href="https://doi.org/10.3334/CDIAC/atg.db1001" target="_blank">https://doi.org/10.3334/CDIAC/atg.db1001</a>)

Atmospheric Composition Change: Climate-Chemistry Interactions

Chemically active climate compounds are either primary compounds such as methane (CH4), removed by oxidation in the atmosphere, or secondary compounds such as ozone (O3), sulfate and organic aerosols, formed and removed in the atmosphere. Man-induced climate-chemistry interaction is a two-way process: Emissions of pollutants change the atmospheric composition contributing to climate change through the aforementioned climate components, and climate change, through changes in temperature, dynamics, the hydrological cycle, atmospheric stability, and biosphere-atmosphere interactions, affects the atmospheric composition and oxidation processes in the troposphere. Here we present progress in our understanding of processes of importance for climate-chemistry interactions, and their contributions to changes in atmospheric composition and climate forcing. A key factor is the oxidation potential involving compounds such as O3 and the hydroxyl radical (OH). Reported studies represent both current and future changes. Reported results include new estimates of radiative forcing based on extensive model studies of chemically active climate compounds such as O3, and of particles inducing both direct and indirect effects. Through EU projects such as ACCENT, QUANTIFY, and the AEROCOM project, extensive studies on regional and sector-wise differences in the impact on atmospheric distribution are performed. Studies have shown that land-based emissions have a different effect on climate than ship and aircraft emissions, and different measures are needed to reduce the climate impact. Several areas where climate change can affect the tropospheric oxidation process and the chemical composition are identified. This can take place through enhanced stratospheric-tropospheric exchange of ozone, more frequent periods with stable conditions favouring pollution build up over industrial areas, enhanced temperature-induced biogenic emissions, methane releases from permafrost thawing, and enhanced concentration through reduced biospheric uptake. During the last 510 years, new observational data have been made available and used for model validation and the study of atmospheric processes. Although there are significant uncertainties in the modelling of composition changes, access to new observational data has improved modelling capability. Emission scenarios for the coming decades have a large uncertainty range, in particular with respect to regional trends, leading to a significant uncertainty range in estimated regional composition changes and climate impact