MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice

Hepatic steatosis is a global epidemic that is thought to contribute to the pathogenesis of type 2 diabetes. MicroRNAs (miRs) are regulators that can functionally integrate a range of metabolic and inflammatory pathways in liver. We aimed to investigate the functional role of miR-155 in hepatic steatosis. Male C57BL/6 wild-type (WT) and miR-155−/− mice were fed either normal chow or high fat diet (HFD) for 6 months then lipid levels, metabolic and inflammatory parameters were assessed in livers and serum of the mice. Mice lacking endogenous miR-155 that were fed HFD for 6 months developed increased hepatic steatosis compared to WT controls. This was associated with increased liver weight and serum VLDL/LDL cholesterol and alanine transaminase (ALT) levels, as well as increased hepatic expression of genes involved in glucose regulation (Pck1, Cebpa), fatty acid uptake (Cd36) and lipid metabolism (Fasn, Fabp4, Lpl, Abcd2, Pla2g7). Using miRNA target prediction algorithms and the microarray transcriptomic profile of miR-155−/− livers, we identified and validated that Nr1h3 (LXRα) as a direct miR-155 target gene that is potentially responsible for the liver phenotype of miR-155−/− mice. Together these data indicate that miR-155 plays a pivotal role regulating lipid metabolism in liver and that its deregulation may lead to hepatic steatosis in patients with diabetes

Confirmation bias in the utilization of others' opinion strength

Humans tend to discount information that undermines past choices and judgments. This confirmation bias has significant impact on domains ranging from politics to science and education. Little is known about the mechanisms underlying this fundamental characteristic of belief formation. Here we report a mechanism underlying the confirmation bias. Specifically, we provide evidence for a failure to use the strength of others' disconfirming opinions to alter confidence in judgments, but adequate use when opinions are confirmatory. This bias is related to reduced neural sensitivity to the strength of others' opinions in the posterior medial prefrontal cortex when opinions are disconfirming. Our results demonstrate that existing judgments alter the neural representation of information strength, leaving the individual less likely to alter opinions in the face of disagreement

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH

Discrepancies in the diagnosis of intraductal proliferative lesions of the breast and its management implications: results of a multinational survey

To measure discrepancies in diagnoses and recommendations impacting management of proliferative lesions of the breast, a questionnaire of five problem scenarios was distributed among over 300 practicing pathologists. Of the 230 respondents, 56.5% considered a partial cribriform proliferation within a duct adjacent to unequivocal ductal carcinoma in situ (DCIS) as atypical ductal hyperplasia (ADH), 37.7% of whom recommended reexcision if it were at a resection margin. Of the 43.5% who diagnosed the partially involved duct as DCIS, 28.0% would not recommend reexcision if the lesion were at a margin. When only five ducts had a partial cribriform proliferation, 35.7% considered it as DCIS, while if ≥20 ducts were so involved, this figure rose to 60.4%. When one duct with a complete cribriform pattern measured 0.5, 1.5, or 4 mm, a diagnosis of DCIS was made by 22.6, 31.3, and 94.8%, respectively. When multiple ducts with flat epithelial atypia were at a margin, 20.9% recommended reexcision. Much of these discrepancies arise from the artificial separation of ADH and low-grade DCIS and emphasize the need for combining these two under the umbrella designation of ductal intraepithelial neoplasia grade 1 (DIN 1) to diminish the impact of different terminologies applied to biologically similar lesions

Conscious perception of errors and its relation to the anterior insula

To detect erroneous action outcomes is necessary for flexible adjustments and therefore a prerequisite of adaptive, goal-directed behavior. While performance monitoring has been studied intensively over two decades and a vast amount of knowledge on its functional neuroanatomy has been gathered, much less is known about conscious error perception, often referred to as error awareness. Here, we review and discuss the conditions under which error awareness occurs, its neural correlates and underlying functional neuroanatomy. We focus specifically on the anterior insula, which has been shown to be (a) reliably activated during performance monitoring and (b) modulated by error awareness. Anterior insular activity appears to be closely related to autonomic responses associated with consciously perceived errors, although the causality and directions of these relationships still needs to be unraveled. We discuss the role of the anterior insula in generating versus perceiving autonomic responses and as a key player in balancing effortful task-related and resting-state activity. We suggest that errors elicit reactions highly reminiscent of an orienting response and may thus induce the autonomic arousal needed to recruit the required mental and physical resources. We discuss the role of norepinephrine activity in eliciting sufficiently strong central and autonomic nervous responses enabling the necessary adaptation as well as conscious error perception

Quantum Process Tomography of a Universal Entangling Gate Implemented with Josephson Phase Qubits

Quantum logic gates must perform properly when operating on their standard input basis states, as well as when operating on complex superpositions of these states. Experiments using superconducting qubits have validated the truth table for particular implementations of e.g. the controlled-NOT gate [1,2], but have not fully characterized gate operation for arbitrary superpositions of input states. Here we demonstrate the use of quantum process tomography (QPT) [3,4] to fully characterize the performance of a universal entangling gate between two superconducting quantum bits. Process tomography permits complete gate analysis, but requires precise preparation of arbitrary input states, control over the subsequent qubit interaction, and simultaneous single-shot measurement of the output states. We use QPT to measure the fidelity of the entangling gate and to quantify the decoherence mechanisms affecting the gate performance. In addition to demonstrating a promising fidelity, our entangling gate has a on/off ratio of 300, a level of adjustable coupling that will become a requirement for future high-fidelity devices. This is the first solid-state demonstration of QPT in a two-qubit system, as solid-state process tomography has previously only been demonstrated with single qubits [5,6]

Особенности развития малого предпринимательства в Украине

В этой работе рассмотрена эволюция предпринимательства Украины на всех этапах ее общественной жизни, в том числе в период экономического кризиса в годы становления независимости. Отражены основные параметры отнесения предприятий к субъектам малого предпринимательства и их роль в развитии экономики государств.У цій роботі розглянута еволюція підприємництва України на всіх етапах її суспільного життя, зокрема в період економічної кризи в роки становлення незалежності. Відображені основні параметри віднесення підприємств до суб'єктів малого підприємництва і їх роль в розвитку економіки держав