Graversenstallings4367

Taken together, our data suggest that RACK1 is a key factor involved in p38 activation as well as TNF-α-induced cell death.Mice lacking the RIIβ regulatory subunit of cyclic AMP-dependent protein kinase A (PKA) display reduced adiposity and resistance to diet-induced obesity. Here we show that RIIβ knockout (KO) mice have enhanced sensitivity to leptin's effects on both feeding and energy metabolism. After administration of a low dose of leptin, the duration of hypothalamic JAK/STAT3 signalling is increased, resulting in enhanced POMC mRNA induction. Consistent with the extended JAK/STAT3 activation, we find that the negative feedback regulator of leptin receptor signalling, Socs3, is inhibited in the hypothalamus of RIIβ KO mice. During fasting, RIIβ-PKA is activated and this correlates with an increase in CREB phosphorylation. The increase in CREB phosphorylation is absent in the fasted RIIβ KO hypothalamus. Selective inhibition of PKA activity in AgRP neurons partially recapitulates the leanness and resistance to diet-induced obesity of RIIβ KO mice. Our findings suggest that RIIβ-PKA modulates the duration of leptin receptor signalling and therefore the magnitude of the catabolic response to leptin.Microring-based photonic fractional differentiators play an important role in the on-chip all-optical signal processing. Unfortunately, the previous works do not consider the time-reversal and the time delay characteristics of the microring-based fractional differentiator. They also do not include the effect of input pulse width on the output. In particular, it cannot explain why the microring-based differentiator with the differentiation order n > 1 has larger output deviation than that with n 1. In this paper, a comprehensive theoretical model is proposed. The critically-coupled microring resonator is modeled as an ideal first-order differentiator, while the under-coupled and over-coupled resonators are modeled as the time-reversed ideal fractional differentiators. Traditionally, the over-coupled microring resonators are used to form the differentiators with 1 less then n less then 2. However, we demonstrate that smaller fitting error can be obtained if the over-coupled microring resonator is fitted by an ideal differentiator with n less then 1. The time delay of the differentiator is also considered. Finally, the influences of some key factors on the output waveform and deviation are discussed. The proposed theoretical model is beneficial for the design and application of the microring-based fractional differentiators.Acute lung injury is a condition characterized by exacerbate inflammatory reaction in distal airways and lung dysfunction. Here we investigate the treatment of acute lung injury (ALI) by low level laser therapy (LLLT), an effective therapy used for the treatment of patients with inflammatory disorders or traumatic injuries, due to its ability to reduce inflammation and promote tissue regeneration. However, studies in internal viscera remains unclear. C57BL/6 mice were treated with intratracheal lipopolysaccharide (LPS) (5 mg/kg) or phosphate buffer saline (PBS). Six hours after instillation, two groups were irradiated with laser at 660 nm and radiant exposure of 10 J/cm2 . Intratracheal LPS inoculation induced a marked increase in the number of inflammatory cells in perivascular and alveolar spaces. There was also an increase in the expression and secretion of cytokines (TNF-α, IL-1β, IL-6,) and chemokine (MCP-1). The LLLT application induced a significant decrease in both inflammatory cells influx and inflammatory mediators secretion. These effects did not affect lung mechanical properties, since no change was observed in tissue resistance or elastance. In conclusion LLLT is able to reduce inflammatory reaction in lungs exposed to LPS without affecting the pulmonary function and recovery.The aim of this study was to investigate the effect of dietary folic acid on fish growth, the immune and barrier functions of fish gills, and the potential mechanisms of these effects. Young grass carp (Ctenopharyngodon idella) were fed diets containing graded levels of folic acid at 0.10 (basal diet), 0.47, 1.03, 1.48, 1.88 and 3.12 mg kg(-1) diet for 8 weeks. The results showed that acid phosphatase and lysozyme activities and the complement component 3 content in fish gills decreased with folic acid deficiency (P less then 0.05). Folic acid deficiency up-regulated liver-expressed antimicrobial peptide 1, interleukin 1β, interleukin 8, tumor necrosis factor α, nuclear factor κB p65, IκB kinase α (IKK-α), IKK-β and IKK-γ gene expression. Folic acid deficiency down-regulated interleukin 10, transforming growth factor β, IκB and target of rapamycin gene expression in fish gills (P less then 0.05). These results showed that limited folic acid decreased fish gill immune status. Furthermore, folic acid deficied fish gill health status via regulating gene expression of cytokines, tight junction proteins, antioxidant enzymes, NF-κB p65, MLCK and Nrf2. Based on percent weight gain, LZ activity and MDA content in the gills, the dietary folic acid requirements for young grass carp were 1.60, 2.07 and 2.08 mg kg(-1), respectively.The NOD-like receptors (NLRs, nucleotide-binding domain and leucine-rich repeat containing receptors) are a recently identified family of intracellular pathogen recognition receptors in vertebrates. Several subfamilies of NLRs have been characterized in mammals and implicated in immunity and apoptosis, but studies of NLRs in teleost species have been lacking. Here we analyzed three NLR-A subfamily members from miiuy croaker NLRC3, NLRC5, and NLRX1. Structural analysis showed that miiuy croaker NLR-A subfamily members own the feature of 5'UTR intron which may influence their role in enhancing translation level. Comparative analysis revealed NLRX1 duplicated into NLRX1a and NLRX1b, then NLRX1a was lost in actinopterygii and NLRX1b formed NLRX1 that now we called. Simultaneously, molecular evolutionary analysis indicated that the ancestral lineages of NLRX1 in tetrapod and actinopterygii under positive selection pressure. The positively sites in actinopterygii are mainly located in NACHT domain which was the critical region for signal transduction, suggesting that the evolution of NLRX1 gene in the ancestor of actinopterygii is beneficial in immune response. Pathogens challenge demonstrated that the expressions of NLRC3 and NLRC5 in miiuy croaker were induced not only by Vibrio anguillarum but also by poly (IC), whereas NLRX1 exhibited more sensitive response to bacteria than virus.DCIS (Ductal carcinoma in situ) constitutes 15,2% of breast cancers. Conservative surgery coupled with adjuvant radiotherapy is often recommended. The rate of revision surgery is high, from 30 to 60%. The concern is a high quality resection within clear margins with a satisfactory aesthetic result. The objective of this review is to precise the place of oncoplastic surgery in DCIS care. Among risk factors of recurrence, tumoral invasion of surgical margins is capital. In histology, clear margins usually adopted for DCIS are 2mm, even though there is no international consensus. Recent studies show that a 10mm limit would be better. Aesthetic damage caused by surgery, often increased by radiotherapy, has a negative impact on women quality of life oncoplastic surgery may minimize it. Techniques of plastic surgery, arranged into level 1 and 2, allow pushing back conservative treatment limits by removing a larger tumor with clear margins. Often used in invasive cancers, few data exist regarding oncoplastic surgery and DCIS. It allows to increase the dimensions of surgical resection by 20% and to decrease positive margins significantly therefore the rate of revision surgeries. Patients are satisfied with it. Specific indications need to be clarified according to age, size and "comedonecrosis" presence. Oncoplastic surgery should be developed in DCIS specific care.

Screening, Brief Intervention, and Referral to Treatment (SBIRT) is a public health program used to identify, reduce, and prevent problematic use, abuse, and dependence on alcohol and illicit drugs that has been adapted for implementation in emergency departments and ambulatory clinics nationwide.

This study used a combination of observational, timing, and descriptive analyses from a multisite evaluation to understand the workflow processes implemented in 21 treatment settings. Direct observations of 59 SBIRT practitioners and semi-structured interviews with 170 stakeholders, program administrators, practitioners, and program evaluators provided information about workflow in different medical care settings.

The SBIRT workflow processes are presented at three levels service delivery, information storage, and information sharing. Analyses suggest limited variation in the overall workflow processes across settings, although performance sites tailored the program to fit with existing clinical processes, health information technology, and patient characteristics. Strategies for successful integration include co-locating SBIRT providers in the medical care setting and integrating SBIRT data into electronic health records.

Provisions within the Patient Protection and Affordable Care Act of 2010 call for the integration of behavioral health and medical care services. SBIRT is being adapted in different types of medical care settings, and the workflow processes are being adapted to ensure efficient delivery, illustrating the successful integration of behavioral health and medical care.

Provisions within the Patient Protection and Affordable Care Act of 2010 call for the integration of behavioral health and medical care services. SBIRT is being adapted in different types of medical care settings, and the workflow processes are being adapted to ensure efficient delivery, illustrating the successful integration of behavioral health and medical care.

Long-term nucleos(t)ide analogues therapy may reduce hepatocellular carcinoma (HCC) in chronic hepatitis B patients with advanced fibrosis or cirrhosis.

To investigate in a retrospective-prospective study whether this beneficial effect would be reduced in cirrhotic patients who discontinued a successful course of entecavir (ETV) therapy.

The study included 586 hepatitis B e antigen (HBeAg)-negative patients with compensated cirrhosis, mean age of 53.8 ± 10 years and 81% males, treated with ETV for at least 12 months. After ETV therapy for 46.5 ± 22.9 months, 205 patients who achieved hepatitis B virus (HBV) DNA suppression discontinued therapy. The clinical outcomes were assessed and HCC incidence was compared between propensity score (PS)-matched patients who continued and patients who discontinued ETV therapy by Asian Pacific Association for the Study of Liver stopping rule.

During a mean duration of 59.3 ± 19 months after start of ETV therapy, nine and six HCC developed in an estimated annual incidesources setting.Apicomplexa are unicellular parasites causing important human and animal diseases, including malaria and toxoplasmosis. Most of these pathogens possess a relict but essential plastid, the apicoplast. The apicoplast was acquired by secondary endosymbiosis between a red alga and a flagellated eukaryotic protist. As a result the apicoplast is surrounded by four membranes. selleck chemicals llc This complex structure necessitates a system of transport signals and translocons allowing nuclear encoded proteins to find their way to specific apicoplast sub-compartments. Previous studies identified translocons traversing two of the four apicoplast membranes. Here we provide functional support for the role of an apicomplexan Toc75 homolog in apicoplast protein transport. We identify two apicomplexan genes encoding Toc75 and Sam50, both members of the Omp85 protein family. We localize the respective proteins to the apicoplast and the mitochondrion of Toxoplasma and Plasmodium. We show that the Toxoplasma Toc75 is essential for parasite growth and that its depletion results in a rapid defect in the import of apicoplast stromal proteins while the import of proteins of the outer compartments is affected only as the secondary consequence of organelle loss.