Lactobacillus acidophilus Alleviates Platelet-Activating Factor-Induced Inflammatory Responses in Human Intestinal Epithelial Cells

Probiotics have been used as alternative prevention and therapy modalities in intestinal inflammatory disorders including inflammatory bowel diseases (IBD) and necrotizing enterocolitis (NEC). Pathophysiology of IBD and NEC includes the production of diverse lipid mediators, including platelet-activating factor (PAF) that mediate inflammatory responses in the disease. PAF is known to activate NF-κB, however, the mechanisms of PAF-induced inflammation are not fully defined. We have recently described a novel PAF-triggered pathway of NF-κB activation and IL-8 production in intestinal epithelial cells (IECs), requiring the pivotal role of the adaptor protein Bcl10 and its interactions with CARMA3 and MALT1. The current studies examined the potential role of the probiotic Lactobacillus acidophilus in reversing the PAF-induced, Bcl10-dependent NF-κB activation and IL-8 production in IECs. PAF treatment (5 µM×24 h) of NCM460 and Caco-2 cells significantly increased nuclear p65 NF-κB levels and IL-8 secretion (2-3-fold, P<0.05), compared to control, which were blocked by pretreatment of the cells for 6 h with L. acidophilus (LA) or its culture supernatant (CS), followed by continued treatments with PAF for 24 h. LA-CS also attenuated PAF-induced increase in Bcl10 mRNA and protein levels and Bcl10 promoter activity. LA-CS did not alter PAF-induced interaction of Bcl10 with CARMA3, but attenuated Bcl10 interaction with MALT1 and also PAF-induced ubiquitination of IKKγ. Efficacy of bacteria-free CS of LA in counteracting PAF-induced inflammatory cascade suggests that soluble factor(s) in the CS of LA mediate these effects. These results define a novel mechanism by which probiotics counteract PAF-induced inflammation in IECs.     

Sequence trademarks in oncogene associated microRNAs

The last decade was taken by storm when the existence of a class of small (˜22nt long) non ― coding RNA species, known as microRNAs (miRNAs) came into light. MicroRNAs are one of the most abundant groups of regulatory genes in multicellular organisms and play fundamental roles in many cellular processes. Among these, miRNAs have been shown to prevent cell division and drive terminal differentiation, thus playing a causal role in the generation or maintenance of cancerous tumours. The unique expression profiles of different miRNAs in various types and stages of cancer suggest their performance as novel biomarkers. This discussion focuses on miRNAs implicated in cancer-associated events and strives to re-establish their sequential features which may classify them to be oncogenic.     

Recovery of Renal Function among ESRD Patients in the US Medicare Program

Background

Patients started on long term hemodialysis have typically had low rates of reported renal recovery with recent estimates ranging from 0.9–2.4% while higher rates of recovery have been reported in cohorts with higher percentages of patients with acute renal failure requiring dialysis.

Study Design

Our analysis followed approximately 194,000 patients who were initiated on hemodialysis during a 2-year period (2008 & 2009) with CMS-2728 forms submitted to CMS by dialysis facilities, cross-referenced with patient record updates through the end of 2010, and tracked through December 2010 in the CMS SIMS registry.

Results

We report a sustained renal recovery (i.e no return to ESRD during the available follow up period) rate among Medicare ESRD patients of > 5% - much higher than previously reported. Recovery occurred primarily in the first 2 months post incident dialysis, and was more likely in cases with renal failure secondary to etiologies associated with acute kidney injury. Patients experiencing sustained recovery were markedly less likely than true long-term ESRD patients to have permanent vascular accesses in place at incident hemodialysis, while non-White patients, and patients with any prior nephrology care appeared to have significantly lower rates of renal recovery. We also found widespread geographic variation in the rates of renal recovery across the United States.

Conclusions

Renal recovery rates in the US Medicare ESRD program are higher than previously reported and appear to have significant geographic variation. Patients with diagnoses associated with acute kidney injury who are initiated on long-term hemodialysis have significantly higher rates of renal recovery than the general ESRD population and lower rates of permanent access placement.     

Thermal and Structural Stability of Adsorbed Proteins

Experimental evidence suggests that proteins adsorbed to hydrophobic surfaces at low coverages are stabilized relative to the bulk. For larger coverages, proteins unfold and form β-sheets. We performed computer simulations on model proteins and found that: 1), For weakly adsorbing surfaces, unfolded conformations lose more entropy upon adsorption than folded ones. 2), The melting temperature, both in the bulk and at surfaces, decreases with increasing protein concentration because of favorable interprotein interactions. 3), Proteins in the bulk show large unfolding free energy barriers; this barrier decreases at stronger adsorbing surfaces. We conjecture that typical experimental temperatures appear to be below the bulk melting temperature for a single protein, but above the melting temperature for concentrated protein solutions. Purely thermodynamic factors then explain protein stabilization on adsorption at low concentrations. However, both thermodynamic and kinetic factors are important at higher concentrations. Thus, proteins in the bulk do not denature with increasing concentration due to large kinetic barriers, even though the aggregated state is thermodynamically preferred. However, they readily unfold upon adsorption, with the surface acting as a heterogeneous catalyst. The thermal behavior of proteins adsorbed to hydrophobic surfaces thus appears to follow behavior independent of their chemical specificity.     

μ-chain-deficient mice possess B-1 cells and produce IgG and IgE, but Not IgA, following systemic sensitization and inhalational challenge in a fungal asthma model

Allergic bronchopulmonary aspergillosis is often difficult to treat and results in morbidity associated with chronic airway changes. This study assessed the requirement for B cells and their products in the allergic pulmonary phenotype in a murine model of fungal allergic asthma that mimics allergic bronchopulmonary aspergillosis. C57BL/6 and μMT mice (assumed to lack peripheral B cells) were sensitized with Aspergillus fumigatus extract and challenged with two inhalation exposures of live conidia to induce airway disease. Airway hyperresponsiveness after methacholine challenge, peribronchovascular inflammation, goblet cell metaplasia, and fibrotic remodeling of the airways was similar between μMT mice and their wild-type counterparts (C57BL/6). Surprisingly, even in the absence of the μ-chain, these μMT mice produced IgE and IgG Abs, although the Abs induced did not have specificity for A. fumigatus Ags. In contrast, IgA was not detected in either the lavage fluid or serum of μMT mice that had been exposed to A. fumigatus. Our findings also reveal the existence of CD19(+)CD9(+)IgD(+) B-1 cells in the lungs of the μMT animals. These data show the μMT mice to have a developmental pathway independent of the canonical μ-chain route that allows for their survival upon antigenic challenge with A. fumigatus conidia, although this pathway does not seem to allow for the normal development of Ag-specific repertoires. Additionally, this study shows that IgA is not required for either clearance or containment of A. fumigatus in the murine lung, as fungal outgrowth was not observed in the μMT animals after multiple inhalation exposures to live conidia.     

Spatial pattern of freshwater habitats and their prioritization using additive partitions of beta diversity of inhabitant piscine assemblages in the Terai–Dooars ecoregion of Eastern Himalayas

Limnology - Underlying spatial and habitat attributes of a river network are crucial to comprehend the bio-spatial arrangements within it, the study of which suffers from a paucity of information....     

Therapeutic Effect of Agmatine on Neurological Disease: Focus on Ion Channels and Receptors

The central nervous system (CNS) is the most injury-prone part of the mammalian body. Any acute or chronic, central or peripheral neurological disorder is related to abnormal biochemical and electrical signals in the brain cells. As a result, ion channels and receptors that are abundant in the nervous system and control the electrical and biochemical environment of the CNS play a vital role in neurological disease. The N-methyl-d-aspartate receptor, 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid receptor, kainate receptor, acetylcholine receptor, serotonin receptor, α2-adrenoreceptor, and acid-sensing ion channels are among the major channels and receptors known to be key components of pathophysiological events in the CNS. The primary amine agmatine, a neuromodulator synthesized in the brain by decarboxylation of l-arginine, can regulate ion channel cascades and receptors that are related to the major CNS disorders. In our previous studies, we established that agmatine was related to the regulation of cell differentiation, nitric oxide synthesis, and murine brain endothelial cell migration, relief of chronic pain, cerebral edema, and apoptotic cell death in experimental CNS disorders. In this review, we will focus on the pathophysiological aspects of the neurological disorders regulated by these ion channels and receptors, and their interaction with agmatine in CNS injury.

     

Polyacrylamide grafted Agar: Synthesis and applications of conventional and microwave assisted technique

Polyacrylamide grafted Agar (Ag-g-PAM) has been successfully synthesized by conventional method and microwave assisted method. The former method employs ceric ammonium nitrate (CAN) as the free radical initiator while the latter uses the combination of ceric ammonium nitrate (CAN) and microwave irradiation. The synthesized graft copolymers have been characterized by elemental analysis (C, H, N, O and S), FTIR spectroscopy, intrinsic viscosity measurement and scanning electron micrograph (SEM); taking agar as a reference. Flocculation efficacy of synthesized graft copolymers was studied in kaolin suspension and in waste water through 'Jar test' procedure. In the present investigation, we have observed that polyacrylamide grafted agar synthesized by microwave assisted technique shows superior properties than conventional technique. These properties are reported in terms of intrinsic viscosity, flocculation efficacy and pollutant load reduction of waste water.     

Human Cep192 is required for mitotic centrosome and spindle assembly

As cells enter mitosis, centrosomes dramatically increase in size and ability to nucleate microtubules. This process, termed centrosome maturation, is driven by the accumulation and activation of gamma-tubulin and other proteins that form the pericentriolar material on centrosomes during G2/prophase. Here, we show that the human centrosomal protein, Cep192 (centrosomal protein of 192 kDa), is an essential component of the maturation machinery. Specifically, we have found that siRNA depletion of Cep192 results in a complete loss of functional centrosomes in mitotic but not interphase cells. In mitotic cells lacking Cep192, microtubules become organized around chromosomes but rarely acquire stable bipolar configurations. These cells contain normal numbers of centrioles but cannot assemble gamma-tubulin, pericentrin, or other pericentriolar proteins into an organized PCM. Alternatively, overexpression of Cep192 results in the formation of multiple, extracentriolar foci of gamma-tubulin and pericentrin. Together, our findings support the hypothesis that Cep192 stimulates the formation of the scaffolding upon which gamma-tubulin ring complexes and other proteins involved in microtubule nucleation and spindle assembly become functional during mitosis.