Phosphorylation of β-catenin at Serine552 correlates with invasion and recurrence of non-functioning pituitary neuroendocrine tumours.

Non-functioning pituitary tumours (NF-PitNETs) are common intracranial benign neoplasms that can exhibit aggressive behaviour by invading neighbouring structures and, in some cases, have multiple recurrences. Despite resulting in severe co-morbidities, no predictive biomarkers of recurrence have been identified for NF-PitNETs. In this study we have used high-throughput mass spectrometry-based analysis to examine the phosphorylation pattern of different subsets of NF-PitNETs. Based on histopathological, radiological, surgical and clinical features, we have grouped NF-PitNETs into non-invasive, invasive, and recurrent disease groups. Tumour recurrence was determined based on regular clinical and radiological data of patients for a mean follow-up of 10 years (SD ± 5.4 years). Phosphoproteomic analyses identified a unique phosphopeptide enrichment pattern which correlates with disease recurrence. Candidate phosphorylated proteins were validated in a large cohort of NF-PitNET patients by western blot and immunohistochemistry. We identified a cluster of 22 phosphopeptides upregulated in recurrent NF-PitNETs compared to non-invasive and invasive subgroups. We reveal significant phosphorylation of the β-catenin at Ser552 in recurrent and invasive NF-PitNETs, compared to non-invasive/non-recurrent NF-PitNET subgroup. Moreover, β-catenin pSer552 correlates with the recurrence free survival among 200 patients with NF-PitNET. Together, our results suggest that the phosphorylation status of β-catenin at Ser552 could act as potential biomarker of tumour recurrence in NF-PitNETs

Regulatory feedback response mechanisms to phosphate starvation in rice

Phosphorus is a growth-limiting nutrient for plants. The growing scarcity of phosphate stocks threatens global food security. Phosphate-uptake regulation is so complex and incompletely known that attempts to improve phosphorus use efficiency have had extremely limited success. This study improves our understanding of the molecular mechanisms underlying phosphate uptake by investigating the transcriptional dynamics of two regulators: the Ubiquitin ligase PHO2 and the long non-coding RNA IPS1. Temporal measurements of RNA levels have been integrated into mechanistic mathematical models using advanced statistical techniques. Models based solely on current knowledge could not adequately explain the temporal expression profiles. Further modeling and bioinformatics analysis have led to the prediction of three regulatory features: the PHO2 protein mediates the degradation of its own transcriptional activator to maintain constant PHO2 mRNA levels; the binding affinity of the transcriptional activator of PHO2 is impaired by a phosphate-sensitive transcriptional repressor/inhibitor; and the extremely high levels of IPS1 and its rapid disappearance upon Pi re-supply are best explained by Pi-sensitive RNA protection. This work offers both new opportunities for plant phosphate research that will be essential for informing the development of phosphate efficient crop varieties, and a foundation for the development of models integrating phosphate with other stress responses

Identification of Mycobacterium tuberculosis clinical isolates in Bangladesh by a species distinguishable multiplex PCR

<p>Abstract</p> <p>Background</p> <p>Species identification of isolates belonging to the <it>Mycobacterium tuberculosis </it>complex (MTC) seems to be important for the appropriate treatment of patients, since <it>M. bovis </it>is naturally resistant to a first line anti-tuberculosis (TB) drug, pyrazinamide, while most of the other MTC members are susceptible to this antimicrobial agent. A simple and low-cost differentiation method was needed in higher TB burden countries, such as Bangladesh, where the prevalence of <it>M. bovis </it>among people or cattle has not been investigated.</p> <p>Methods</p> <p>Genetic regions <it>cfp32</it>, RD9 and RD12 were chosen as targets for a species distinguishable multiplex PCR and the system was evaluated with twenty reference strains of mycobacterial species including non-tubercular mycobacteria (NTM). A total of 350 clinical MTC isolates obtained in Bangladesh were then analyzed with this multiplex PCR.</p> <p>Results</p> <p>All of the MTC reference strains gave expected banding patterns and no non-specific amplifications were observed in the NTM strains. Out of 350 clinical isolates examined by this method, 347 (99.1%) were positive for all of the <it>cfp32</it>, RD9 and RD12 and determined as <it>M. tuberculosis</it>. Two isolates lacked <it>cfp32 </it>PCR product and one lacked RD12, however, those three samples were further examined and identified as <it>M. tuberculosis </it>by the sequence analyses of <it>hsp65 </it>and <it>gyrB</it>.</p> <p>Conclusions</p> <p>The MTC-discrimination multiplex PCR (MTCD-MPCR) developed in this study showed high specificity and was thought to be very useful as a routine test because of its simplicity. In the current survey, all the 350 MTC isolates obtained from Bangladesh TB patients were determined as <it>M. tuberculosis </it>and no other MTC were detected. This result suggested the general TB treatment regimen including pyrazinamide to be the first choice in Bangladesh.</p

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Rapidity and Centrality Dependence of Proton and Anti-proton Production from Au+Au Collisions at sqrt(sNN) = 130GeV

We report on the rapidity and centrality dependence of proton and anti-proton transverse mass distributions from Au+Au collisions at sqrt(sNN) = 130GeV as measured by the STAR experiment at RHIC. Our results are from the rapidity and transverse momentum range of |y|<0.5 and 0.35 <p_t<1.00GeV/c. For both protons and anti-protons, transverse mass distributions become more convex from peripheral to central collisions demonstrating characteristics of collective expansion. The measured rapidity distributions and the mean transverse momenta versus rapidity are flat within |y|<0.5. Comparisons of our data with results from model calculations indicate that in order to obtain a consistent picture of the proton(anti-proton) yields and transverse mass distributions the possibility of pre-hadronic collective expansion may have to be taken into account.Comment: 4 pages, 3 figures, 1 table, submitted to PR

Drug Susceptibility in Leishmania Isolates Following Miltefosine Treatment in Cases of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis

Resistance to antimonials has emerged as a major hurdle to the treatment and control of VL and led to the introduction of Miltefosine as first line treatment in the Indian subcontinent. MIL is an oral drug with a long half-life, and it is feared that resistance may emerge rapidly, threatening control efforts under the VL elimination program. There is an urgent need for monitoring treatment efficacy and emergence of drug resistance in the field. In a set of VL/PKDL cases recruited for MIL treatment, we observed comparable drug susceptibility in pre- and post-treatment isolates from cured VL patients while MIL susceptibility was significantly reduced in isolates from VL relapse and PKDL cases. The PKDL isolates showed higher tolerance to MIL as compared to VL isolates. Both VL and PKDL isolates were uniformly susceptible to PMM. MIL transporter genes LdMT/LdRos3 were previously reported as potential resistance markers in strains in which MIL resistance was experimentally induced. The point mutations and the down-regulated expression of these transporters observed in vitro could, however, not be verified in natural populations of parasites. LdMT/LdRos3 genes therefore, do not appear to be suitable markers so far for monitoring drug susceptibility in clinical leishmanial isolates

Alcohol-Related Context Modulates Performance of Social Drinkers in a Visual Go/No-Go Task: A Preliminary Assessment of Event-Related Potentials

Background Increased alcohol cue-reactivity and altered inhibitory processing have been reported in heavy social drinkers and alcohol-dependent patients, and are associated with relapse. In social drinkers, these two processes have been usually studied separately by recording event-related potentials (ERPs) during rapid picture presentation. The aim of our study was to confront social drinkers to a task triggering high alcohol cue-reactivity, to verify whether it specifically altered inhibitory performance, by using long-lasting background picture presentation. Methods ERP were recorded during visual Go/No-Go tasks performed by social drinkers, in which a frequent Go signal (letter “M”), and a rare No-Go signal (letter “W”) were superimposed on three different types of background pictures: neutral (black background), alcohol-related and non alcohol-related. Results Our data suggested that heavy social drinkers made more commission errors than light drinkers, but only in the alcohol-related context. Neurophysiologically, this was reflected by a delayed No-Go P3 component. Conclusions Elevated alcohol cue-reactivity may lead to poorer inhibitory performance in heavy social drinkers, and may be considered as an important vulnerability factor in developing alcohol misuse. Prevention programs should be designed to decrease the high arousal of alcohol stimuli and strengthen cognitive control in young, at-risk individuals.This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Sources of variation for indoor nitrogen dioxide in rural residences of Ethiopia

<p>Abstract</p> <p>Background</p> <p>Unprocessed biomass fuel is the primary source of indoor air pollution (IAP) in developing countries. The use of biomass fuel has been linked with acute respiratory infections. This study assesses sources of variations associated with the level of indoor nitrogen dioxide (NO₂).</p> <p>Materials and methods</p> <p>This study examines household factors affecting the level of indoor pollution by measuring NO₂. Repeated measurements of NO₂were made using a passive diffusive sampler. A <it>Saltzman </it>colorimetric method using a spectrometer calibrated at 540 nm was employed to analyze the mass of NO₂on the collection filter that was then subjected to a mass transfer equation to calculate the level of NO₂for the 24 hours of sampling duration. Structured questionnaire was used to collect data on fuel use characteristics. Data entry and cleaning was done in EPI INFO version 6.04, while data was analyzed using SPSS version 15.0. Analysis of variance, multiple linear regression and linear mixed model were used to isolate determining factors contributing to the variation of NO₂concentration.</p> <p>Results</p> <p>A total of 17,215 air samples were fully analyzed during the study period. Wood and crop were principal source of household energy. Biomass fuel characteristics were strongly related to indoor NO₂concentration in one-way analysis of variance. There was variation in repeated measurements of indoor NO₂over time. In a linear mixed model regression analysis, highland setting, wet season, cooking, use of fire events at least twice a day, frequency of cooked food items, and interaction between ecology and season were predictors of indoor NO₂concentration. The volume of the housing unit and the presence of kitchen showed little relevance in the level of NO₂concentration.</p> <p>Conclusion</p> <p>Agro-ecology, season, purpose of fire events, frequency of fire activities, frequency of cooking and physical conditions of housing are predictors of NO₂concentration. Improved kitchen conditions and ventilation are highly recommended.</p