Serum levels of mature microRNAs in DICER1-mutated pleuropulmonary blastoma.

DICER1 is a critical gene in the biogenesis of mature microRNAs, short non-coding RNAs that derive from either -3p or -5p precursor microRNA strands. Germline mutations of DICER1 are associated with a range of human malignancies, including pleuropulmonary blastoma (PPB). Additional somatic 'hotspot' mutations in the microRNA processing ribonuclease IIIb (RNase IIIb) domain of DICER1 are reported in cancer, and which affect microRNA biogenesis, resulting in a -3p mature microRNA strand bias. Here, in a germline (exon11 c.1806_1810insATTGA) DICER1-mutated PPB, we first confirmed the presence of an additional somatic RNase IIIb hotspot mutation (exon25 c.5425G>A [p.G1809R]) by conventional sequencing. Second, we investigated serum levels of mature microRNAs at the time of PPB diagnosis, and compared the findings with serum results from a comprehensive range of pediatric cancer patients and controls (n=52). We identified a panel of 45 microRNAs that were present at elevated levels in the serum at the time of PPB diagnosis, with a significant majority noted be derived from the -3p strand (P=0.013). In addition, we identified a subset of 10 serum microRNAs (namely miR-125a-3p, miR-125b-2-3p, miR-380-5p, miR-125b-1-3p, let-7f-2-3p, let-7a-3p, let-7b-3p, miR-708-3p, miR-138-1-3p and miR-532-3p) that were most abundant in the PPB case. Serum levels of two representative microRNAs, miR-125a-3p and miR-125b-2-3p, were not elevated in DICER1 germline-mutated relatives. In the PPB case, serum levels of miR-125a-3p and miR-125b-2-3p increased before chemotherapy, and then showed an early reduction following treatment. These microRNAs may offer future utility as serum biomarkers for screening patients with known germline DICER1 mutations for early detection of PPB, and for potential disease-monitoring in cases with confirmed PPB.We would like to thank the following for providing financial support: SPARKS (NC, MJM), Medical Research Council Fellowship (MJM), TD Bank/LDI scholarship (LdK), Alex’s Lemonade Stand Foundation (WDF), Cancer Research UK (NC) and European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement No. 310018 (MT).This is the final published version. It first appeared at http://www.nature.com/oncsis/journal/v3/n2/full/oncsis20141a.html

Correlation between Fischer-Tropsch catalytic activity and composition of catalysts

This paper presents the synthesis and characterization of monometallic and bimetallic cobalt and iron nanoparticles supported on alumina. The catalysts were prepared by a wet impregnation method. Samples were characterized using temperature-programmed reduction (TPR), temperature-programmed oxidation (TPO), CO-chemisorption, transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM-EDX) and N2-adsorption analysis. Fischer-Tropsch synthesis (FTS) was carried out in a fixed-bed microreactor at 543 K and 1 atm, with H2/CO = 2 v/v and space velocity, SV = 12L/g.h. The physicochemical properties and the FTS activity of the bimetallic catalysts were analyzed and compared with those of monometallic cobalt and iron catalysts at similar operating conditions

Failure to detect tuberculosis in Black lechwe antelopes (Kobus leche smithemani) in Zambia

<p>Abstract</p> <p>Background</p> <p>Two types of lechwe antelopes exclusively exist in their natural ecosystems in Zambia; the Black lechwe (<it>Kobus leche smithemani</it>) and the Kafue lechwe (<it>Kobus leche kafuensis</it>). Despite inhabiting similar ecosystems, tuberculosis has been reported in Kafue lechwe without its documentation in Black lechwe antelopes. However, the past few decades have seen a drastic decline in both lechwe populations. Whereas studies have postulated that infectious diseases such as tuberculosis are having a negative impact on the Kafue lechwe population, no information is available on Black lechwe antelopes. Thus this study was conducted to investigate tuberculosis in Black lechwe antelopes of the Bangweulu swamps in comparison with the Kafue lechwe antelopes of Lochinvar.</p> <p>Findings</p> <p>A total of 44 lechwe antelopes (Black (<it>n </it>= 30): Kafue (<it>n </it>= 14) were sampled from Bangweulu and Lochinvar respectively. A positive case was defined with findings of gross lesions with Ziehl Nielsen and culture confirmation. Out of the 14 animals examined in Lochinvar, 21.4% [95% CI: 15.4, 44.4%] had necropsy lesions consistent with tuberculosis. The corresponding samples from 30 Black lechwe of Bangweulu yielded negative results on all the three tests.</p> <p>Conclusions</p> <p>Current findings from this study intimate the possible absence of tuberculosis in Black lechwe antelopes whilst confirming the presence of tuberculosis in Kafue lechwe of the Kafue basin. The absence of tuberculosis in the Black lechwe suggests that the observed population decline may not be caused by tuberculosis. However, without detailed molecular epidemiological studies it is not possible to determine the association of <it>M. bovis </it>infection in sympatric animal populations. The possible role of transmission of tuberculosis between wildlife and cattle is discussed herein. <b>Findings</b></p

Healthcare-associated viral and bacterial infections in dentistry

Infection prevention in dentistry is an important topic that has gained more interest in recent years and guidelines for the prevention of cross-transmission are common practice in many countries. However, little is known about the real risks of cross-transmission, specifically in the dental healthcare setting. This paper evaluated the literature to determine the risk of cross-transmission and infection of viruses and bacteria that are of particular relevance in the dental practice environment. Facts from the literature on HSV, VZV, HIV, Hepatitis B, C and D viruses, Mycobacterium spp., Pseudomonas spp., Legionella spp. and multi-resistant bacteria are presented. There is evidence that Hepatitis B virus is a real threat for cross-infection in dentistry. Data for the transmission of, and infection with, other viruses or bacteria in dental practice are scarce. However, a number of cases are probably not acknowledged by patients, healthcare workers and authorities. Furthermore, cross-transmission in dentistry is under-reported in the literature. For the above reasons, the real risks of cross-transmission are likely to be higher. There is therefore a need for prospective longitudinal research in this area, to determine the real risks of cross-infection in dentistry. This will assist the adoption of effective hygiene procedures in dental practice

MRI of the kidney—state of the art

Ultrasound and computed tomography (CT) are modalities of first choice in renal imaging. Until now, magnetic resonance imaging (MRI) has mainly been used as a problem-solving technique. MRI has the advantage of superior soft-tissue contrast, which provides a powerful tool in the detection and characterization of renal lesions. The MRI features of common and less common renal lesions are discussed as well as the evaluation of the spread of malignant lesions and preoperative assessment. MR urography technique and applications are discussed as well as the role of MRI in the evaluation of potential kidney donors. Furthermore the advances in functional MRI of the kidney are highlighted

Angiotensin-(1–7) and the G Protein-Coupled Receptor Mas Are Key Players in Renal Inflammation

Angiotensin (Ang) II mediates pathophysiologial changes in the kidney. Ang-(1–7) by interacting with the G protein-coupled receptor Mas may also have important biological activities

Control of somatosensory cortical processing by thalamic posterior medial nucleus: A new role of thalamus in cortical function

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.Current knowledge of thalamocortical interaction comes mainly from studying lemniscal thalamic systems. Less is known about paralemniscal thalamic nuclei function. In the vibrissae system, the posterior medial nucleus (POm) is the corresponding paralemniscal nucleus. POm neurons project to L1 and L5A of the primary somatosensory cortex (S1) in the rat brain. It is known that L1 modifies sensory-evoked responses through control of intracortical excitability suggesting that L1 exerts an influence on whisker responses. Therefore, thalamocortical pathways targeting L1 could modulate cortical firing. Here, using a combination of electrophysiology and pharmacology in vivo, we have sought to determine how POm influences cortical processing. In our experiments, single unit recordings performed in urethane- anesthetized rats showed that POm imposes precise control on the magnitude and duration of supra- and infragranular barrel cortex whisker responses. Our findings demonstrated that L1 inputs from POm imposed a time and intensity dependent regulation on cortical sensory processing. Moreover, we found that blocking L1 GABAergic inhibition or blocking P/Q-type Ca2+ channels in L1 prevents POm adjustment of whisker responses in the barrel cortex. Additionally, we found that POm was also controlling the sensory processing in S2 and this regulation was modulated by corticofugal activity from L5 in S1. Taken together, our data demonstrate the determinant role exerted by the POm in the adjustment of somatosensory cortical processing and in the regulation of cortical processing between S1 and S2. We propose that this adjustment could be a thalamocortical gain regulation mechanism also present in the processing of information between cortical areas.This work was supported by a grant from Ministerio de Economia y Competitividad (BFU2012- 36107