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Alkylphenol polyethoxylates (APEs) are widely used as nonionic surfactants. Nonylphenol (NP), one of the derivatives of APEs, has been found in the aquatic environment in ranges from nanograms per liter to milligrams per liter. In this study, juvenile rainbow trout were exposed to 0 (control), 66, 220, or 660 micro g NP/L for up to 28 days. Fish remained healthy under NP exposures of 0, 66, and 220 micro g/L for the length of the experiment. All fish died after 4 days of exposure to 660 micro g NP/L. Time-dependent NP bioaccumulation was detected in the tissues of fish exposed to 220 micro g NP/L (P<0.05) and histopathological changes were observed in the livers of fish exposed to 220 micro g NP/L. Furthermore, an increase in the activity of glutathione-S-transferase (GST) was found in the liver of fish exposed to 220 micro g NP/L for 1 week (P<0.05). There was an increase in GST activity in the liver of fish exposed to 66 micro g NP/L but it did not occur before 2 weeks of exposure to NP. The GST activity then decreased in a time-dependent manner in treatment groups, and this decrease was lower in the livers of fish treated with 66 and 220 micro g NP/L than in control fish after 3 weeks of exposure (P<0.05). These results indicated that sublethal doses of NP were accumulating in the bodies of the fish and causing histopathological and biochemical changes in the livers of rainbow trout.

OBJECTIVES : For the choice of treatment in children with inflammatory bowel disease (IBD), it is important to make a distinction between Crohn disease (CD) and ulcerative colitis (UC). To look for pathognomonic features of CD, upper gastrointestinal tract (UGT) endoscopy has become part of the routine evaluation of children with suspected IBD; however, pathological changes can also be found in the UGT in patients with UC. The aims of the present study were to establish the role of UGT involvement in the diagnostic assessment of suspected IBD in children and to detect histopathological changes in the UGT mucosa, which can distinguish CD from non-CD (UC and non-IBD). METHODS : Biopsies (colon, ileum, duodenum, stomach, esophagus) from children suspected of having IBD who underwent endoscopy between 2003 and 2008 were reassessed by a blinded, expert pathologist. The histological findings of the UGT were compared with the diagnosis based on ileocolonic biopsies and the final diagnosis. RESULTS : In 11% of the children with CD, the diagnosis was based solely on the finding of granulomatous inflammation in the UGT. Focal cryptitis of the duodenum and focally enhanced gastritis were found significantly more frequently in children with CD compared with children with UC and non-IBD, with a specificity and positive predictive value of 99% and 93% and 87.1% and 78.6%, respectively. CONCLUSIONS : Histology on ileocolonic biopsies alone is insufficient for a correct diagnosis of CD or UC in children. UGT endoscopy should, therefore, be performed in the diagnostic assessment of all children suspected of having IBD.

The dynamics of different cytoskeletal networks are coordinated to bring about many fundamental cellular processes, from neuronal pathfinding to cell division. Increasing evidence points to the importance of spectraplakins in integrating cytoskeletal networks. Spectraplakins are evolutionarily conserved giant cytoskeletal cross-linkers, which belong to the spectrin superfamily. Their genes consist of multiple promoters and many exons, yielding a vast array of differential splice forms with distinct functions. Spectraplakins are also unique in their ability to associate with all three elements of the cytoskeleton: F-actin, microtubules, and intermediate filaments. Recent studies have begun to unveil their role in a wide range of processes, from cell migration to tissue integrity.

While exome sequencing is readily amenable to single-nucleotide variant discovery, the sparse and non-uniform nature of the exome capture reaction has hindered exome-based detection and characterization of genic copy number variation. We developed a novel method using singular value decomposition (SVD) normalization to discover rare genic copy number variants (CNVs) as well as genotype copy number polymorphic (CNP) loci with high sensitivity and specificity from exome sequencing data. We estimate the precision of our algorithm using 122 trios (366 exomes) and show that this method can be used to reliably predict (94% overall precision) both de novo and inherited rare CNVs involving three or more consecutive exons. We demonstrate that exome-based genotyping of CNPs strongly correlates with whole-genome data (median r2 = 0.91), especially for loci with fewer than eight copies, and can estimate the absolute copy number of multi-allelic genes with high accuracy (78% call level). The resulting user-friendly computational pipeline, CoNIFER (copy number inference from exome reads), can reliably be used to discover disruptive genic CNVs missed by standard approaches and should have broad application in human genetic studies of disease.

Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) reduces symptoms of intractable obsessive-compulsive disorder (OCD), but the mechanism of action is unknown. OCD is characterized by avoidance behaviors that fail to extinguish, and DBS could act, in part, by facilitating extinction of fear. We investigated this possibility by using auditory fear conditioning in rats, for which the circuits of fear extinction are well characterized. We found that DBS of the VS (the VC/VS homolog in rats) during extinction training reduced fear expression and strengthened extinction memory. Facilitation of extinction was observed for a specific zone of dorsomedial VS, just above the anterior commissure; stimulation of more ventrolateral sites in VS impaired extinction. DBS effects could not be obtained with pharmacological inactivation of either dorsomedial VS or ventrolateral VS, suggesting an extrastriatal mechanism. Accordingly, DBS of dorsomedial VS (but not ventrolateral VS) increased expression of a plasticity marker in the prelimbic and infralimbic prefrontal cortices, the orbitofrontal cortex, the amygdala central nucleus (lateral division), and intercalated cells, areas known to learn and express extinction. Facilitation of fear extinction suggests that, in accord with clinical observations, DBS could augment the effectiveness of cognitive behavioral therapies for OCD.

Store-operated Ca2+(SOC) entry is one of the major mechanisms to raise intracellular Ca2+ concentration in non-excitable cells. Ca2+-release-activated-Ca2+(CRAC) channels are a subtype of SOC channels that are extensively characterized in immune cells. Identification of STIM1 as an ER Ca2+ sensor and Orai1 as the pore subunit has dramatically advanced the molecular understanding of CRAC channels. Recent efforts have focused on understanding the physiological aspects of CRAC channels at an organism level using transgenic animal models and at a molecular level using electrophysiological and biochemical tools. In this review, we summarize our current understanding of the interacting partners of Orai and STIM proteins in regulation of CRAC channel activity and other non-CRAC channel-related functions.