Sparse genetically defined neurons refine the canonical role of periaqueductal gray columnar organization.

During threat exposure, survival depends on defensive reactions. Prior works linked large glutamatergic populations in the midbrain periaqueductal gray (PAG) to defensive freezing and flight, and established that the overarching functional organization axis of the PAG is along anatomically-defined columns. Accordingly, broad activation of the dorsolateral column induces flight, while activation of the lateral or ventrolateral (l and vl) columns induces freezing.

Early maladaptive schemas and depression in adulthood: A systematic review and meta-analysis.

Background: Improved understanding of the specific cognitive risk factors associated with depression is needed to inform prevention and treatment approaches. Recent research has examined the relationship between early maladaptive schemas (EMSs) and depression, but the findings were yet to be integrated using meta-analytic methods. The aim of this review was to synthesize the evidence on the relationship between depression and EMS.

Kappa Opioid Signaling at the Crossroads of Chronic Pain and Opioid Addiction.

Pain is complex and is a unique experience for individuals in that no two people will have exactly the same physiological and emotional response to the same noxious stimulus or injury. Pain is composed of two essential processes: a sensory component that allows for discrimination of the intensity and location of a painful stimulus and an emotional component that underlies the affective, motivational, unpleasant, and aversive response to a painful stimulus. Kappa opioid receptor (KOR) activation in the periphery and throughout the neuroaxis modulates both of these components of the pain experience.

Adverse childhood experiences and early maladaptive schemas in adulthood: A systematic review and meta-analysis.

Background: Schema Therapy is based on the theory that trauma and neglect in childhood lead to early maladaptive schemas and psychopathology in adulthood. The aim of this review was to evaluate support for this theory by synthesizing the literature on childhood adversity and schemas.

Methods: A systematic review and meta-analysis were completed in compliance with PRISMA.

Thoracoscopic lobectomy and segmentectomy for infectious lung disease.

Background: The potential benefits of thoracoscopic lobectomy and segmentectomy for early stage non-small cell lung cancer have been well documented in the literature. However, little is known about the use of these techniques in patients requiring resection for infectious or inflammatory lung disease.

Methods: Using a prospectively collected database, we performed a retrospective review of consecutive operations from July 2004 to June 2010.

Lady Windermere revisited: treatment with thoracoscopic lobectomy/segmentectomy for right middle lobe and lingular bronchiectasis associated with non-tuberculous mycobacterial disease.

Objective: Lady Windermere syndrome is a well-known but poorly understood female predominant phenotype of isolated right middle lobe and lingular bronchiectasis associated with non-tuberculous mycobacterial (NTM) infection. Despite lengthy multidrug antibiotic treatment, the presence of damaged parenchymal tissue leads to symptomatic disease recurrence, often with resistant organisms. The use of surgical resection as an adjunct to medical therapy may alter this cycle, although little is known about the use of thoracoscopic lung resection in this patient population.

Hyphal growth in Candida albicans requires the phosphorylation of Sec2 by the Cdc28-Ccn1/Hgc1 kinase.

Polarized growth is a fundamental property of cell growth and development. It requires the delivery of post-Golgi secretory vesicles to the site of polarized growth. This process is mediated by Rab GTPases activated by their guanine exchange factors (GEFs).

Differential sensitivity of oligodendrocytes and motor neurons to reactive nitrogen species: implications for multiple sclerosis.

Depending on its concentration, nitric oxide (NO) has beneficial or toxic effects. In pathological conditions, NO reacts with superoxide to form peroxynitrite, which nitrates proteins forming nitrotyrosine residues (3NY), leading to loss of protein function, perturbation of signal transduction, and cell death. 3NY immunoreactivity is present in many CNS diseases, particularly multiple sclerosis.

Mitigation of peroxynitrite-mediated nitric oxide (NO) toxicity as a mechanism of induced adaptive NO resistance in the CNS.

During CNS injury and diseases, nitric oxide (NO) is released at a high flux rate leading to formation of peroxynitrite (ONOO(*)) and other reactive nitrogenous species, which nitrate tyrosines of proteins to form 3-nitrotyrosine (3NY), leading to cell death. Previously, we have found that motor neurons exposed to low levels of NO become resistant to subsequent cytotoxic NO challenge; an effect dubbed induced adaptive resistance (IAR). Here, we report IAR mitigates, not only cell death, but 3NY formation in response to cytotoxic NO.

Osmoregulation in Streptomyces coelicolor: modulation of SigB activity by OsaC.

As free-living non-motile saprophytes, Streptomyces need to adapt to a wide range of environmental conditions and this is reflected by an enormous diversity of regulatory proteins encoded by, for example, the genome of the model streptomycete Streptomyces coelicolor. In this organism, we have identified a new osmoregulation gene, osaC, encoding a member of a novel family of regulatory proteins. Members of the family have a predicted domain composition consisting of an N-terminal kinase domain related to anti-sigma factors, sensory Pas and Gaf domains, and a C-terminal phosphatase domain.

Anatomic lung resection for nontuberculous mycobacterial disease.

Background: Chronic lung infections involving nontuberculous mycobacteria are often inadequately treated owing to concomitant lung parenchymal damage, leading to persistence of the offending organisms. Little is known about the results of surgical therapy as part of a multimodality approach to these infections.

Methods: A retrospective review was conducted of 236 consecutive patients who underwent anatomic lung resection for nontuberculous mycobacteria disease at our institution as part of a multimodality treatment program.

Transcript-specific translational regulation in the unfolded protein response of Saccharomyces cerevisiae.

Accumulation of unfolded proteins in the endoplasmic reticulum (ER) causes stress and induces the unfolded protein response (UPR). Genome-wide analysis of translational regulation in response to the UPR-inducing agent dithiothreitol in Saccharomyces cerevisiae is reported. Microarray analysis, confirmed using qRT-PCR, identified transcript-specific translational regulation.

Removal rate model for magnetorheological finishing of glass.

Magnetorheological finishing (MRF) is a deterministic subaperture polishing process. The process uses a magnetorheological (MR) fluid that consists of micrometer-sized, spherical, magnetic carbonyl iron (CI) particles, nonmagnetic polishing abrasives, water, and stabilizers. Material removal occurs when the CI and nonmagnetic polishing abrasives shear material off the surface being polished.

Phenotypic heterogeneity can enhance rare-cell survival in 'stress-sensitive' yeast populations.

Individual cells within isogenic microbial cultures exhibit phenotypic heterogeneity, an issue that is attracting intense interest. Heterogeneity could confer benefits, in generating variant subpopulations that may be better equipped to persist during perturbation. We tested this hypothesis by comparing the survival of wild-type Saccharomyces cerevisiae with that of mutants which are considered stress-sensitive but which, we demonstrate, also have increased heterogeneity.

The therapeutic potential of agents that inactivate myostatin.

Myostatin is a member of the TGF-beta superfamily of secreted growth factors. A lack of functional myostatin or inhibition of the normal myostatin function results in an increased muscling phenotype and, conversely, the systemic administration of myostatin results in muscle wasting. Thus, myostatin is well established as a negative regulator of skeletal muscle mass.

Myostatin auto-regulates its expression by feedback loop through Smad7 dependent mechanism.

Myostatin, a secreted growth factor, is a member of the TGF-beta superfamily and an inhibitor of myogenesis. Previously, we have shown that myostatin gene expression is regulated at the level of transcription and that myostatin is a downstream target gene of MyoD. Here we show that myostatin gene expression is auto-regulated by a negative feedback mechanism.

NO signaling in the CNS: from the physiological to the pathological.

Nitric oxide (NO) is a free radical gas that has a Janus nature. As indicated by the literature and by our studies, in the cell, NO can either function as a beneficial physiological agent utilized for essential functions such as differentiation or neurotransmission, or as a pathological agent that causes or exacerbates central nervous system (CNS) disease and injury. Whether NO is helpful or harmful depends on a variety of factors, such as the cellular environment in which NO is released, the rate of NO flux, as determined by which NOS isozyme is activated, and what array of second messenger cascades are available for utilization by NO for beneficial or toxic cell signalling.

A key role for heme oxygenase-1 in nitric oxide resistance in murine motor neurons and glia.

Nitric oxide is utilized at low levels for intercellular signaling, and at high levels as a cytotoxic weapon during inflammation. Cellular NO resistance can be increased by prior exposure to sublethal NO levels to induce defense gene expression (adaptive NO resistance), which has been correlated with increased expression of heme oxygenase-1 (HO1) and was blocked by a heme oxygenase inhibitor. However, the possibility remained that other activities were affected by the inhibitor.

Systematic insertional mutagenesis of a streptomycete genome: a link between osmoadaptation and antibiotic production.

The model organism Streptomyces coelicolor represents a genus that produces a vast range of bioactive secondary metabolites. We describe a versatile procedure for systematic and comprehensive mutagenesis of the S. coelicolor genome.

Induced adaptive resistance to oxidative stress in the CNS: a discussion on possible mechanisms and their therapeutic potential.

The free radical, nitric oxide (NO), is synthesized by mammalian cells and is utilized for normal cellular functions. High levels of NO are released during disease, injury and inflammation. NO at high concentrations more readily combines with other oxidants to form reactive nitrogenous species (RNS), which can wreak havoc on the cell by damaging a variety of cellular targets, such as DNA and proteins, ultimately leading to apoptosis, mutagenesis or carcinogenesis.

Myostatin inhibits myoblast differentiation by down-regulating MyoD expression.

Myostatin, a negative regulator of myogenesis, is shown to function by controlling the proliferation of myoblasts. In this study we show that myostatin is an inhibitor of myoblast differentiation and that this inhibition is mediated through Smad 3. In vitro, increasing concentrations of recombinant mature myostatin reversibly blocked the myogenic differentiation of myoblasts, cultured in low serum media.