Warped alternatives to Froggatt-Nielsen models

We consider the Randall-Sundrum (RS) setup to be a theory of flavor, as an alternative to Froggatt-Nielsen models instead of as a solution to the hierarchy problem. The RS framework is modified by taking the low-energy brane to be at the grand unified theory (GUT) scale. This also alleviates constraints from flavor physics. Fermion masses and mixing angles are fit at the GUT scale. The ranges of the bulk mass parameters are determined using a chi(2) fit taking into consideration the variation in O(1) parameters. In the hadronic sector, the heavy top quark requires large bulk mass parameters localizing the right-handed top quark close to the IR brane. Two cases of neutrino masses are considered: (a) Planck scale lepton number violation and (b) Dirac neutrino masses. Contrary to the case of weak scale RS models, both these cases give reasonable fits to the data, with the Planck scale lepton number violation fitting slightly better compared to the Dirac case. In the supersymmetric version, the fits are not significantly different except for the variation in tan beta. If the Higgs superfields and the supersymmetry breaking spurion are localized on the same brane, then the structure of the sfermion masses are determined by the profiles of the zero modes of the hypermultiplets in the bulk. Trilinear terms have the same structure as the Yukawa matrices. The resultant squark spectrum is around similar to 2-3 TeV required by the light Higgs mass to be around 125 GeV and to satisfy the flavor violating constraints.

NOD2-Nitric Oxide-responsive MicroRNA-146a Activates Sonic Hedgehog Signaling to Orchestrate Inflammatory Responses in Murine Model of Inflammatory Bowel Disease

Background: Genetic variants of NOD2 are linked to inflammatory bowel disease (IBD) etiology. Results: DSS model of colitis in wild-type and inducible nitric-oxide synthase (iNOS) null mice revealed that NOD2-iNOS/NO-responsive microRNA-146a targets NUMB gene facilitating Sonic hedgehog (SHH) signaling. Conclusion: miR-146a-mediated NOD2-SHH signaling regulates gut inflammation. Significance: Identification of novel regulators of IBD provides new insights into pathophysiology and development of new therapy concepts. Inflammatory bowel disease (IBD) is a debilitating chronic inflammatory disorder of the intestine. The interactions between enteric bacteria and genetic susceptibilities are major contributors of IBD etiology. Although genetic variants with loss or gain of NOD2 functions have been linked to IBD susceptibility, the mechanisms coordinating NOD2 downstream signaling, especially in macrophages, during IBD pathogenesis are not precisely identified. Here, studies utilizing the murine dextran sodium sulfate model of colitis revealed the crucial roles for inducible nitric-oxide synthase (iNOS) in regulating pathophysiology of IBDs. Importantly, stimulation of NOD2 failed to activate Sonic hedgehog (SHH) signaling in iNOS null macrophages, implicating NO mediated cross-talk between NOD2 and SHH signaling. NOD2 signaling up-regulated the expression of a NO-responsive microRNA, miR-146a, that targeted NUMB gene and alleviated the suppression of SHH signaling. In vivo and ex vivo studies confirmed the important roles for miR-146a in amplifying inflammatory responses. Collectively, we have identified new roles for miR-146a that established novel cross-talk between NOD2-SHH signaling during gut inflammation. Potential implications of these observations in therapeutics could increase the possibility of defining and developing better regimes to treat IBD pathophysiology.

A Kunitz-type serine protease inhibitor from Butea monosperma seed and its influence on developmental physiology of Helicoverpa armigera

A protease inhibitor from the seeds of Butea monosperma (BmPI) was purified, characterized and studied for its influence on developmental physiology of Helicover-pa armigera. BmPI on two-dimensional separations indicated the presence of a 14 kDa protein with an isoelectric point in the acidic region (pl 5.6). Multiple Sequence Analysis data suggested that the BmPI contains a sequence motif which is conserved in various trypsin and chymotrypsin inhibitors of Kunitz-type. The inhibitor exhibited trypsin inhibitory activity in a broad range of pH (4-10) and temperature (10-80 degrees C). The enzyme kinetic studies revealed BmPI as a competitive inhibitor with a K-i value of 1.2 x 10(-9) M. In vitro studies with BmPI indicated measurable inhibitory activity on total gut proteolytic enzymes of H. armigera (IC(50)2.0 mu g/ml) and bovine trypsin. BmPI supplemented artificial diet caused dose dependent mortality and reduction in growth and weight. The fertility and fecundity of H. armigera, declined whereas the larval-pupal duration of the insect life cycle extended. These detrimental effects on H. armigera suggest the usefulness of BmPl in insect pest management of food crops. (C) 2014 Elsevier Ltd. All rights reserved.

Highly Efficient Glutathione Peroxidase and Peroxiredoxin Mimetics Protect Mammalian Cells against Oxidative Damage

Novel isoselenazoles with high glutathione peroxidase (GPx) and peroxiredoxin (Prx) activities provide remarkable cytoprotection to human cells, mainly by exhibiting antioxidant activities in the presence of cellular thiols. The cytotoxicity of the isoselenazoles is found to be significantly lower than that of ebselen, which is being clinically evaluated by several groups for the treatment of reperfusion injuries and stroke, hearing loss, and bipolar disorder. The compounds reported in this paper have the potential to be used as therapeutic agents for disorders mediated by reactive oxygen species.

Ischaemic concentrations of lactate increase TREK1 channel activity by interacting with a single histidine residue in the carboxy terminal domain

Key points The physiological metabolite, lactate and the two-pore domain leak potassium channel, TREK1 are known neuroprotectants against cerebral ischaemia. However, it is not known whether lactate interacts with TREK1 channel to provide neuroprotection. In this study we show that lactate increases TREK1 channel activity and hyperpolarizes CA1 stratum radiatum astrocytes in hippocampal slices. Lactate increases open probability and decreases longer close time of the human (h)TREK1 channel in a concentration dependent manner. Lactate interacts with histidine 328 (H328) in the carboxy terminal domain of hTREK1 channel to decrease its dwell time in the longer closed state. This interaction was dependent on the charge on H328. Lactate-insensitive mutant H328A hTREK1 showed pH sensitivity similar to wild-type hTREK1, indicating that the effect of lactate on hTREK1 is independent of pH change. AbstractA rise in lactate concentration and the leak potassium channel TREK1 have been independently associated with cerebral ischaemia. Recent literature suggests lactate to be neuroprotective and TREK1 knockout mice show an increased sensitivity to brain and spinal cord ischaemia; however, the connecting link between the two is missing. Therefore we hypothesized that lactate might interact with TREK1 channels. In the present study, we show that lactate at ischaemic concentrations (15-30mm) at pH7.4 increases TREK1 current in CA1 stratum radiatum astrocytes and causes membrane hyperpolarization. We confirm the intracellular action of lactate on TREK1 in hippocampal slices using monocarboxylate transporter blockers and at single channel level in cell-free inside-out membrane patches. The intracellular effect of lactate on TREK1 is specific since other monocarboxylates such as pyruvate and acetate at pH7.4 failed to increase TREK1 current. Deletion and point mutation experiments suggest that lactate decreases the longer close dwell time incrementally with increase in lactate concentration by interacting with the histidine residue at position 328 (H328) in the carboxy terminal domain of the TREK1 channel. The interaction of lactate with H328 is dependent on the charge on the histidine residue since isosteric mutation of H328 to glutamine did not show an increase in TREK1 channel activity with lactate. This is the first demonstration of a direct effect of lactate on ion channel activity. The action of lactate on the TREK1 channel signifies a separate neuroprotective mechanism in ischaemia since it was found to be independent of the effect of acidic pH on channel activity. Key points The physiological metabolite, lactate and the two-pore domain leak potassium channel, TREK1 are known neuroprotectants against cerebral ischaemia. However, it is not known whether lactate interacts with TREK1 channel to provide neuroprotection. In this study we show that lactate increases TREK1 channel activity and hyperpolarizes CA1 stratum radiatum astrocytes in hippocampal slices. Lactate increases open probability and decreases longer close time of the human (h)TREK1 channel in a concentration dependent manner. Lactate interacts with histidine 328 (H328) in the carboxy terminal domain of hTREK1 channel to decrease its dwell time in the longer closed state. This interaction was dependent on the charge on H328. Lactate-insensitive mutant H328A hTREK1 showed pH sensitivity similar to wild-type hTREK1, indicating that the effect of lactate on hTREK1 is independent of pH change.

Peptide-utilizing carbon starvation gene yjiY is required for flagella-mediated infection caused by Salmonella

Peptide metabolism forms an important part of the metabolic network of Salmonella and to acquire these peptides the pathogen possesses a number of peptide transporters. Whilst various peptide transporters known in Salmonella are well studied, very little is known about the carbon starvation (cst) genes cstA and yjiY, which are also predicted to be involved in peptide metabolism. We investigated the role of these genes in the metabolism and pathogenesis of Salmonella, and demonstrated for the first time, to the best of our knowledge, that cst genes actually participate in transport of specific peptides in Salmonella. Furthermore, we established that the carbon starvation gene yjiY affects the expression of flagella, leading to poor adhesion of the bacterium to host cells. In contrast to the previously reported role of cstA in virulence of Salmonella in Caenorhabditis elegans, we showed that yjiY is required for successful colonization of Salmonella in the mouse gut. Thus, cst genes not only contribute to the metabolism of Salmonella, but also influence its virulence.

Peptide-utilizing carbon starvation gene yjiY is required for flagella-mediated infection caused by Salmonella

Peptide metabolism forms an important part of the metabolic network of Salmonella and to acquire these peptides the pathogen possesses a number of peptide transporters. Whilst various peptide transporters known in Salmonella are well studied, very little is known about the carbon starvation (cst) genes cstA and yjiY, which are also predicted to be involved in peptide metabolism. We investigated the role of these genes in the metabolism and pathogenesis of Salmonella, and demonstrated for the first time, to the best of our knowledge, that cst genes actually participate in transport of specific peptides in Salmonella. Furthermore, we established that the carbon starvation gene yjiY affects the expression of flagella, leading to poor adhesion of the bacterium to host cells. In contrast to the previously reported role of cstA in virulence of Salmonella in Caenorhabditis elegans, we showed that yjiY is required for successful colonization of Salmonella in the mouse gut. Thus, cst genes not only contribute to the metabolism of Salmonella, but also influence its virulence.

Dynamical generation of flavour

We propose the generation of Standard Model fermion hierarchy by the extension of renormalizable SO(10) GUT with O(N (g) ) family gauge symmetry. In this scenario, Higgs representations of SO(10) also carry family indices and are called Yukawons. Vacuum expectation values of these Yukawon fields break GUT and family symmetry and generate MSSM Yukawa couplings dynamically. We have demonstrated this idea using Higgs irrep, ignoring the contribution of 1 2 0-plet which is, however, required for complete fitting of fermion mass-mixing data. The effective MSSM matter fermion couplings to the light Higgs pair are determined by the null eigenvectors of the MSSM-type Higgs doublet superfield mass matrix . A consistency condition on the doublet (1,2,+/- 1]) mass matrix ( 0) is required to keep one pair of Higgs doublets light in the effective MSSM. We show that the Yukawa structure generated by null eigenvectors of are of generic kind required by the MSSM. A hidden sector with a pair of (S (a b) ; I center dot (a b) ) fields breaks supersymmetry and facilitates 0. SUSY breaking is communicated via supergravity. In this scenario, matter fermion Yukawa couplings are reduced from 15 to just 3 parameters in MSGUT with three generations.

Gravitational rescue of minimal gauge mediation

Gravity mediated supersymmetry breaking becomes comparable to gauge mediated supersymmetry breaking contributions when messenger masses are close to the GUT scale. By suitably arranging the gravity contributions, one can modify the soft supersymmetry breaking sector to generate a large stop mixing parameter and a light Higgs mass of 125 GeV. In this kind of hybrid models, however, the nice features of gauge mediation like flavor conservation, etc. are lost. To preserve the nice features, gravitational contributions should become important for lighter messenger masses and should be important only for certain fields. This is possible when the hidden sector contains multiple (at least two) spurions with hierarchical vacuum expectation values. In this case, the gravitational contributions can be organized to be ``just right.'' We present a complete model with two spurion hidden sector where the gravitational contribution is from a warped flavor model in a Randall-Sundrum setting. Along the way, we present simple expressions to handle renormalization group equations when supersymmetry is broken by two different sectors at two different scales.

Signature-tagged transposon mutagenesis studies demonstrate the dynamic nature of cecal colonization of 2-week-old chickens by Campylobacter jejuni.

We have constructed plasmids to be used for in vitro signature-tagged mutagenesis (STM) of Campylobacter jejuni and used these to generate STM libraries in three different strains. Statistical analysis of the transposon insertion sites in the C. jejuni NCTC 11168 chromosome and the plasmids of strain 81-176 indicated that their distribution was not uniform. Visual inspection of the distribution suggested that deviation from uniformity was not due to preferential integration of the transposon into a limited number of hot spots but rather that there was a bias towards insertions around the origin. We screened pools of mutants from the STM libraries for their ability to colonize the ceca of 2-week-old chickens harboring a standardized gut flora. We observed high-frequency random loss of colonization proficient mutants. When cohoused birds were individually inoculated with different tagged mutants, random loss of colonization-proficient mutants was similarly observed, as was extensive bird-to-bird transmission of mutants. This indicates that the nature of campylobacter colonization in chickens is complex and dynamic, and we hypothesize that bottlenecks in the colonization process and between-bird transmission account for these observations.

Electrical and optical spectroscopy for quantitative screening of hepatic steatosis in donor livers.

Macro-steatosis in deceased donor livers is increasingly prevalent and is associated with poor or non-function of the liver upon reperfusion. Current assessment of the extent of steatosis depends upon the macroscopic assessment of the liver by the surgeon and histological examination, if available. In this paper we demonstrate electrical and optical spectroscopy techniques which quantitatively characterize fatty infiltration in liver tissue. Optical spectroscopy showed a correlation coefficient of 0.85 in humans when referenced to clinical hematoxylin and eosin (H&E) sections in 20 human samples. With further development, an optical probe may provide a comprehensive measure of steatosis across the liver at the time of procurement.

Development of kelp rockfish, Sebastes atrovirens (Jordan and Gilbert 1880), and brown rockfish, S. auriculatus (Girard 1854), from birth to pelagic juvenile stage, with notes on early larval development of black-and-yellow rockfish, S. chrysomelas (Jordan and Gilbert 1880), reared in the laboratory (Pisces: Sebastidae).

Larval kelp (Sebastes atrovirens), brown (S. auriculatus), and blackand-yellow (S. chrysomelas) rockfish were reared from known adults, to preflexion stage, nine days after birth for S. chrysomelas, to late postflexion stage for S. atrovirens, and to pelagic juvenile stage for S. auriculatus. Larval S. atrovirens and S. chrysomelas were about 4.6 mm body length (BL) and S. auriculatus about 5.2 mm BL at birth. Both S. atrovirens and S. auriculatus underwent notochord flexion at about 6–9 mm BL. Sebastes atrovirens transform to the pelagic juvenile stage at about 14–16 mm BL and S. auriculatus transformed at ca. 25 mm BL. Early larvae of all three species were characterized by melanistic pigment dorsally on the head, on the gut, on most of the ventral margin of the tail, and in a long series on the dorsal margin of the tail. Larval S. atrovirens and S. auriculatus developed a posterior bar on the tail during the flexion or postflexion stage. In S. atrovirens xanthic pigment resembled the melanistic pattern throughout larval development. Larval S. auriculatus lacked xanthophores except on the head until late preflexion stage, when a pattern much like the melanophore pattern gradually developed. Larval S. chrysomelas had extensive xanthic pigmentation dorsally, but none ventrally, in preflexion stage. All members of the Sebastes subgenus Pteropodus (S. atrovirens, S. auriculatus, S. carnatus, S. caurinus, S. chrysomelas, S. dalli, S. maliger, S. nebulosus, S. rastrelliger) are morphologically similar and all share the basic melanistic pigment pattern described here. Although the three species reared in this study can be distinguished on the basis of xanthic pigmentation, it seems unlikely that it will be possible to reliably identify field-collected larvae to species using traditional morphological and melanistic pigmentation characters. (PDF file contains 36 pages.)

Guide to the Identification of Larval and Early Juvenile Poachers (Scorpaeniformes: Agonidae) from the Northeastern Pacific Ocean and Bering Sea

Developmental stages of 22 species representing 16 genera of agonid fishes occurring in the northeastern Pacific Ocean from San Francisco Bay to the Arctic Ocean are presented. Three of these species also occur in the North Atlantic Ocean. Larval stages of nine species are described for the first time. Additional information or illustrations intended to augment original descriptions are provided for eight species. Information on five other species is provided from the literature for comparative purposes. The primary objective of this guide is to present taxonomic characters to help identify the early life history stages of agonid fishes in field collections. Meristic, morphometric, osteological, and pigmentation characters are used to identify agonid larvae. Meristic features include numbers of median-fin elements, pectoral-fin rays, dermal plates, and vertebrae. Eye diameter, body depth at the pectoral-fin origin, snout to first dorsal-fin length, and pectoral-fin length are the most useful morphological characters. Presence, absence, numbers, and/or patterns of dermal plates in lateral rows or on the ventral surface of the gut are also useful. Other important characters are the presence, absence, numbers, and ornamentation of larval head spines. Lastly, distinct pigmentation patterns are often diagnostic. The potential utility of larval characters in phylogenetic analysis of the family Agonidae is discussed. (PDF file contains 92 pages.)

Intestinal absorption by Sarotherodon galilaeus (syn Tilapia galilaea ) of Lake Kainji, Nigeria

Carbohydrates, protein, lipid and crude fibre were found to reduce in amount from the anterior to posterior regions along the gut of Sarotherodon galilaeus collected from Lake Kainji. Different regions of the gut exhibited different absorptive powers and all the compounds were differently absorbed in amount. Different sizes of fish showed different absorptive capacity

Mehr Nachwuchs bei Nutzfischarten der Nordsee, ausser beim Kabeljau

Ninety-one half-hour tows with the Grande Ouverture Verticale bottom trawl (GOV), 111 hydrographic stations and 100 catches with the Methot-Isaac-Kidd Net (MIK) were this years’ contribution of “Walther Herwig III” to the IBTS in various areas of the North Sea. Preliminary results indicate that especially haddock and, to some extent, whiting and Norway pout generated an ample 1999 yearclass. Indices for herring are also well above last years’ index whereas the cod indices indicate no substantial improvement of the stock. Largest concentrations of herring larvae were found in Moray Firth and west of the Dogger Bank/The Gut area. Temperatures of the North Sea were found to be above the long term means: 1 Centigrade on the open sea and up to 3 Centigrades in coastal areas. This years’ “WH III” IBTS activities at sea were considerably hampered by rough weather