Study of the role of Mce3R on the transcription of mce genes of Mycobacterium tuberculosis

<p>Abstract</p> <p>Background</p> <p><it>mce3 </it>is one of the four virulence-related <it>mce </it>operons of <it>Mycobacterium tuberculosis</it>. In a previous work we showed that the overexpression of Mce3R in <it>Mycobacterium smegmatis </it>and <it>M. tuberculosis </it>abolishes the expression of <it>lacZ </it>fused to the <it>mce3 </it>promoter, indicating that Mce3R represses <it>mce3 </it>transcription.</p> <p>Results</p> <p>We obtained a knockout mutant strain of <it>M. tuberculosis </it>H37Rv by inserting a hygromycin cassette into the <it>mce3R </it>gene. The mutation results in a significant increase in the expression of <it>mce3 </it>genes either <it>in vitro </it>or in a murine cell macrophages line as it was determined using promoter-<it>lacZ </it>fusions in <it>M. tuberculosis</it>. The abundance of <it>mce1</it>, <it>mce2 </it>and <it>mce4 </it>mRNAs was not affected by this mutation as it was demonstrated by quantitative RT-PCR. The <it>mce3R </it>promoter activity in the presence of Mce3R was significantly reduced compared with that in the absence of the regulator, during the <it>in vitro </it>culture of <it>M. tuberculosis</it>.</p> <p>Conclusion</p> <p>Mce3R repress the transcription of <it>mce3 </it>operon and self regulates its own expression but does not affect the transcription of <it>mce1</it>, <it>mce2 </it>and <it>mce4 </it>operons of <it>M. tuberculosis</it>.</p

Therapy refractory hypertension in adults: aortic coarctation has to be ruled out

In patients with unexplained hypertension, especially in combination with a cardiac murmur, the presence of an aortic coarctation should always be ruled out given the high morbidity and mortality. However, particularly patients with an isolated coarctation often remain asymptomatic for years and the defect may be unnoticed even until the fifth or sixth decade of life. In the present article, we describe two patients with late detected coarctation to illustrate the clinical consequences, diagnostic clues for earlier detection and current therapeutic options to achieve optimal treatment. The key sign of an aortic coarctation, a difference in arterial blood pressure measured between the upper and lower extremities, should always be examined, followed by echocardiography. We conclude that even in case of a late detected severe coarctation, surgical or percutaneous repair has proven to be feasible and substantially effective, improving quality of life and lowering the risk of further hypertension-associated problems

Two stage hybrid approach for complex aortic coarctation repair

<p>Abstract</p> <p>Background</p> <p>Management of an adult patient with aortic coarctation and an associated cardiac pathology poses a great surgical challenge since there are no standard guidelines for the therapy of such complex pathology. Debate exists not only on which lesion should be corrected first, but also upon the type and timing of the procedure. Surgery can be one- or two-staged. Both of these strategies are accomplice with elevate morbidity and mortality.</p> <p>Case report</p> <p>In the face of such an extended surgical approach, balloon dilatation seems preferable for treatment of severe aortic coarctation.</p> <p>We present an adult male patient with aortic coarctation combined with ascending aorta aneurysm and concomitant aortic valve regurgitation. The aortic coarctation was corrected first, using percutaneous balloon dilatation; and in a second stage the aortic regurgitation and ascending aorta aneurysm was treated by Bentall procedure. The patients' postoperative period was uneventful. Three years after the operation he continues to do well.</p

Pulmonary arterial hypertension in children with congenital heart disease: a deeper look into the role of endothelial progenitor cells and circulating endothelial cells to assess disease severity

Endothelial progenitor cells and circulating endothelial cells have been proposed as useful markers of severity and disease progression in certain vascular diseases, including pulmonary arterial hypertension. Our study focused on evaluating the levels of circulating endothelial progenitor cells and circulating endothelial cells in patients with congenital left-to-right shunts and pulmonary hypertension undergoing definitive repair. Endothelial progenitor cells (identified by simultaneous co-expression of CD45dim, CD34 + and KDR2 + surface antibodies) and circulating endothelial cells (identified by simultaneous co-expression of inherent antibodies CD45-, CD31+, CD146 + and CD105+) were prospectively measured in seventy-four children (including children with Down syndrome), median age six years (2.75–10), with clinically significant left-to-right shunts undergoing transcatheter or surgical repair and compared to thirty healthy controls. Endothelial progenitor cells and, particularly, circulating endothelial cells were significantly higher in children with heart disease and pulmonary arterial hypertension when compared to controls. Endothelial progenitor cells showed significant correlation with pulmonary vascular resistance index when measured both systemically (r = 0.259; p = 0.026) and in the superior vena cava (r = 0.302; p = 0.009). Children with Down syndrome showed a stronger correlation between systemic cellularity and pulmonary vascular resistance index (r = 0.829; p = 0.002). Endothelial progenitor cells were reduced along their transit through the lung, whereas circulating endothelial cells did not suffer any modification across the pulmonary circulation. In children with yet to be repaired left-to-right shunts, endothelial progenitor cells and circulating endothelial cell counts are increased compared to healthy subjects

Adult Cognitive and Non-cognitive Skills: An Overview of Existing PIAAC Data

As of summer 2019, more than 60 PIAAC datasets from participating countries worldwide were available for research purposes. These datasets can be differentiated, for example, in terms of their accessibility, the extent of the information provided, the population group in focus, and the design of the underlying study. PIAAC Public Use Files, for instance, are freely available and are therefore highly anonymised, whereas PIAAC Scientific Use Files are available only for scientific research purposes and provide access to more detailed variables. The majority of the PIAAC data are available as public use files, but some participating countries (e.g. Germany and the United States) have also made several scientific use files or other extended file versions available to the research community. Some of the available PIAAC datasets focus on specific population groups - for example, the incarcerated adult population in the United States. Regarding the design of the underlying studies, most available datasets are cross-sectional, but some longitudinal data already exist (e.g. PIAAC-L in Germany). The present chapter provides an overview of the structure, accessibility, and use of the PIAAC datasets available worldwide

Meiotic Recombination Hotspots of Fission Yeast Are Directed to Loci that Express Non-Coding RNA

Polyadenylated, mRNA-like transcripts with no coding potential are abundant in eukaryotes, but the functions of these long non-coding RNAs (ncRNAs) are enigmatic. In meiosis, Rec12 (Spo11) catalyzes the formation of dsDNA breaks (DSBs) that initiate homologous recombination. Most meiotic recombination is positioned at hotspots, but knowledge of the mechanisms is nebulous. In the fission yeast genome DSBs are located within 194 prominent peaks separated on average by 65-kbp intervals of DNA that are largely free of DSBs.). Furthermore, we tested and rejected the hypothesis that the ncRNA loci and DSB peaks localize preferentially, but independently, to a third entity on the chromosomes.Meiotic DSB hotspots are directed to loci that express polyadenylated ncRNAs. This reveals an unexpected, possibly unitary mechanism for what directs meiotic recombination to hotspots. It also reveals a likely biological function for enigmatic ncRNAs. We propose specific mechanisms by which ncRNA molecules, or some aspect of RNA metabolism associated with ncRNA loci, help to position recombination protein complexes at DSB hotspots within chromosomes

Differential immunity as a factor influencing mussel hybrid zone structure

Interspecific hybridisation can alter fitness-related traits, including the response to pathogens, yet immunity is rarely investigated as a potential driver of hybrid zone dynamics, particularly in invertebrates. We investigated the immune response of mussels from a sympatric population at Croyde Bay, within the hybrid zone of Mytilus edulis and Mytilus galloprovincialis in Southwest England. The site is characterised by size-dependent variation in genotype frequencies, with a higher frequency of M. galloprovincialis alleles in large mussels, largely attributed to selective mortality in favour of the M. galloprovincialis genotype. To determine if differences in immune response may contribute to this size-dependent variation in genotype frequencies, we assessed the two pure species and their hybrids in their phagocytic abilities when subject to immune challenge as a measure of immunocompetence and measured the metabolic cost of mounting an antigen-stimulated immune response. Mussels identified as M. galloprovincialis had a greater immunocompetence response at a lower metabolic cost compared to mussels identified as M. edulis. Mussels identified as hybrids had intermediate values for both parameters, providing no evidence for heterosis but suggesting that increased susceptibility compared to M. galloprovincialis may be attributed to the M. edulis genotype. The results indicate phenotypic differences in the face of pathogenic infection, which may be a contributing factor to the differential mortality in favour of M. galloprovincialis, and the size-dependent variation in genotype frequencies associated with this contact zone. We propose that immunity may contribute to European mussel hybrid zone dynamics

Obtención y evaluación de cultivos primarios de origen epitelial para el aislamiento de los virus CAEV y ORFV

Trabajo presentado en la XXI Reunión científico-técnica Dr. Bernardo Jorge Carrillo : Asociación Argentina de Veterinarios de Laboratorio de Diagnóstico, celebrada en San Salvador de Jujuy (Argentina), del 6 al 8 de octubre de 2016En el diagnóstico confirmatorio de enfermedades virales se suelen emplear técnicas serológicas (ELISA e inmunodifusión en agar AGID) o moleculares (PCR, RT-PCR) para la detección de los agentes virales. Si bien, muchas veces los reactivos necesarios suelen ser caros y poco accesibles al evaluar un gran número de muestras. Además, en muestras biológicas donde la carga viral suele ser baja, las técnicas antes mencionadas suelen presentar limitaciones. La forma de confirmar la presencia del agente viral es obtener su aislamiento en cultivo de células, siguiendo la aparición del efecto citopático característico para cada uno de ellos. Sin embargo, es habitual que la cepas de campo no se adapten a su multiplicación in vitro en líneas celulares establecidas, por lo que muchas veces es necesario recurrir a los cultivos primarios. El objetivo de este trabajo consistió en la generación de un cultivo primario de origen epitelial ovino y caprino con el fin de obtener un sistema celular que permita el aislamiento de los virus de artritis y encefalitis caprina (CAEV) y el virus ORF (ORFV),agente causal del Ectima contagioso, a partir de muestras sospechosas.Peer reviewe