Association analysis of polymorphism in KIAA1717, HUMMLC2B, DECR1 and FTO genes with meat quality traits of the Berkshire breed

Single nucleotide polymorphisms (SNPs) in KIAA1717, HUMMLC2B, DECR1, and FTO genes have been found to be associated with some pork meat quality traits. In this study, we discovered that, in addition to meat quality traits reported previously, SNPs in these genes also are significantly associated with other meat quality traits in the Berkshire breed. A total of 323 Berkshire pigs bred under the same conditions were used for meat quality evaluation and polymerase chain reaction-amplified genes with restriction endonucleases (PCR-RFLP) genotyping analyses. The association analysis of RFLP genotyping with meat quality traits revealed that the SNPs in these 4 genes have novel associations with multiple meat quality traits (p < 0.01 or p < 0.05); a SNP in KIAA1717 was associated with meat color (CIE L), backfat thickness, drip loss, water-holding capacity, and pH24hr; a SNP in HUMMLC2B was associated with chemical composition (collagen), drip loss, shear force, and pH24hr; a SNP in DECR1 was associated with meat color (CIE a and b) and backfat thickness; and a SNP in FTO was associated with meat color (CIE L, a and b), protein content, drip loss, and water-holding capacity. Taken collectively, our results suggest that these 4 SNPs may be used for marker-assisted selection as a genetic marker for meat quality traits in Berkshire pigs.Key words: Berkshire, genetic markers, meat quality, SN

Collider and Dark Matter Phenomenology of Models with Mirage Unification

We examine supersymmetric models with mixed modulus-anomaly mediated SUSY breaking (MM-AMSB) soft terms which get comparable contributions to SUSY breaking from moduli-mediation and anomaly-mediation. The apparent (mirage) unification of soft SUSY breaking terms at Q=mu_mir not associated with any physical threshold is the hallmark of this scenario. The MM-AMSB structure of soft terms arises in models of string compactification with fluxes, where the addition of an anti-brane leads to an uplifting potential and a de Sitter universe, as first constructed by Kachru {\it et al.}. The phenomenology mainly depends on the relative strength of moduli- and anomaly-mediated SUSY breaking contributions, and on the Higgs and matter field modular weights, which are determined by the location of these fields in the extra dimensions. We delineate the allowed parameter space for a low and high value of tan(beta), for a wide range of modular weight choices. We calculate the neutralino relic density and display the WMAP-allowed regions. We show the reach of the CERN LHC and of the International Linear Collider. We discuss aspects of MM-AMSB models for Tevatron, LHC and ILC searches, muon g-2 and b->s \gamma branching fraction. We also calculate direct and indirect dark matter detection rates, and show that almost all WMAP-allowed models should be accessible to a ton-scale noble gas detector. Finally, we comment on the potential of colliders to measure the mirage unification scale and modular weights in the difficult case where mu_mir>>M_GUT.Comment: 34 pages plus 42 EPS figures; version with high resolution figures is at http://www.hep.fsu.edu/~bae

A stitch in time: Efficient computation of genomic DNA melting bubbles

Background: It is of biological interest to make genome-wide predictions of the locations of DNA melting bubbles using statistical mechanics models. Computationally, this poses the challenge that a generic search through all combinations of bubble starts and ends is quadratic. Results: An efficient algorithm is described, which shows that the time complexity of the task is O(NlogN) rather than quadratic. The algorithm exploits that bubble lengths may be limited, but without a prior assumption of a maximal bubble length. No approximations, such as windowing, have been introduced to reduce the time complexity. More than just finding the bubbles, the algorithm produces a stitch profile, which is a probabilistic graphical model of bubbles and helical regions. The algorithm applies a probability peak finding method based on a hierarchical analysis of the energy barriers in the Poland-Scheraga model. Conclusions: Exact and fast computation of genomic stitch profiles is thus feasible. Sequences of several megabases have been computed, only limited by computer memory. Possible applications are the genome-wide comparisons of bubbles with promotors, TSS, viral integration sites, and other melting-related regions.Comment: 16 pages, 10 figure

SUMO-Specific Protease 2 (SENP2) Is an Important Regulator of Fatty Acid Metabolism in Skeletal Muscle

Small ubiquitin-like modifier (SUMO)-specific proteases (SENPs) that reverse protein modification by SUMO are involved in the control of numerous cellular processes, including transcription, cell division, and cancer development. However, the physiological function of SENPs in energy metabolism remains unclear. Here, we investigated the role of SENP2 in fatty acid metabolism in C2C12 myotubes and in vivo. In C2C12 myotubes, treatment with saturated fatty acids, like palmitate, led to nuclear factor-B-mediated increase in the expression of SENP2. This increase promoted the recruitment of peroxisome proliferator-activated receptor (PPAR) and PPAR, through desumoylation of PPARs, to the promoters of the genes involved in fatty acid oxidation (FAO), such as carnitine-palmitoyl transferase-1 (CPT1b) and long-chain acyl-CoA synthetase 1 (ACSL1). In addition, SENP2 overexpression substantially increased FAO in C2C12 myotubes. Consistent with the cell culture system, muscle-specific SENP2 overexpression led to a marked increase in the mRNA levels of CPT1b and ACSL1 and thereby in FAO in the skeletal muscle, which ultimately alleviated high-fat diet-induced obesity and insulin resistance. Collectively, these data identify SENP2 as an important regulator of fatty acid metabolism in skeletal muscle and further implicate that muscle SENP2 could be a novel therapeutic target for the treatment of obesity-linked metabolic disorders.11116Ysciescopu

Visual Field Compromised In Patients Suffering From Severe Menorrhagia

Purpose: To evaluate menorrhagia as a risk factor for compromised visual field Design: A cross-sectional cohort study Participants: 25 Menorrhagic patients and 23 non-menorrhagic female subjects Methods: Patients were recruited from the Obstetrics and Gynaecology clinic and divided into two groups. Those suffering from active menorrhagia were allocated into the disease group while those had never suffered from menorrhagia constituted the control group. All subjects completed a pictorial blood assessment chart (PBAC) to quantify the severity of their menorrhagia. All subjects then underwent an eye examination and investigations including visual field and optical coherent tomography. Main Outcome Measures: The mean PBAC was compared between the disease group and the control group. Correlation analysis was tested between PBAC and visual field global indices. Results: Subjects suffering from menorrhagia have a compromised performance in visual field when compared with subjects with no menorrhagia. A positive association was observed between the severity of menorrhagia and a poorer visual field performance. Conclusions: Menorrhagia may be a risk factor for visual field defects. Further research is encouraged to evaluate whether it may be a risk factor for glaucoma development or progression.published_or_final_versio

A pseudo-randomised clinical trial of in situ gels of fluconazole for the treatment of oropharngeal candidiasis

<p>Abstract</p> <p>Background</p> <p>Oropharyngeal candidasis is a common opportunistic infection seen in immunocompromised patients. Fluconazole has a broad spectrum antifungal activity including a wide variety of <it>candida </it>species. Aim of the present investigation was to formulate and find out the relative efficacy of <it>in situ </it>gels of fluconazole.</p> <p>Method</p> <p>The <it>in situ </it>gels were prepared using polymers which exhibited sol-to-gel phase transition due to change in specific physico-chemical parameters, such as ion triggered system using gellan gum (0.5% w/v) along with sodium carboxylmethylcellulose (0.35%w/v). The study design was bicenter, 'pseudo-randomised, single blind trial conducted in Mangalore., India, which includes 15 HIV positive patients, 15 patients with partial or completes dentures, and 15 patients who were treated with (active control) fluconazole tablets 100 mg/day for 14 days. Severity of disease was scored clinically before treatment and at clinical evaluations on day 3, 7, 14, 18, 21, 35, and 42. Semiquantitative microbiological cultures of oral swabs were also obtained on same days.</p> <p>Results</p> <p>All patients had mycological documented oropharyngeal candidiasis and were treated with fluconazole (0.5%w/v) <it>in situ </it>gels for 14 days Severity of disease was scored clinically before treatment and at different predetermined time intervals along with semi quantitative culture of oral swabs. The clinical response rate showed 97% cure after 14 days in the treated with <it>in situ </it>gel. In comparison, the control group treated with fluconazole tablets showed 85% improvement in symptoms of oral candidiasis. The patients suffering from HIV infection showed relapse in oral candidiasis at the end of 21 days. The patients having oral candidiasis due to partial or complete dentures showed complete recovery and were free from signs and symptoms of oral candidiasis.</p> <p>Conclusions</p> <p>The <it>in situ </it>gel formulation of fluconazole was well tolerated with no severe adverse reaction and offers a better alternative to tablet formulation in the treatment of oropharyngeal candidasis.</p> <p>Trial registration</p> <p>Current Controlled Trails <a href="http://www.controlled-trials.com/ISRCTN90634047">ISRCTN90634047</a></p

Low-Energy Brane-World Effective Actions and Partial Supersymmetry Breaking

As part of a programme for the general study of the low-energy implications of supersymmetry breaking in brane-world scenarios, we study the nonlinear realization of supersymmetry which occurs when breaking N=2 to N=1 supergravity. We consider three explicit realizations of this supersymmetry breaking pattern, which correspond to breaking by one brane, by one antibrane or by two (or more) parallel branes. We derive the minimal field content, the effective action and supersymmetry transformation rules for the resulting N=1 theory perturbatively in powers of kappa = 1/M_{Planck}. We show that the way the massive gravitino and spin-1 fields assemble into N=1 multiplets implies the existence of direct brane-brane contact interactions at order O(kappa). This result is contrary to the O(kappa^2) predicted by the sequestering scenario but in agreement with recent work of Anisimov et al. Our low-energy approach is model independent and is a first step towards determining the low-energy implications of more realistic brane models which completely break all supersymmetries.Comment: Latex, 29 Page

Sphingosine 1-phosphate receptor 4 promotes nonalcoholic steatohepatitis by activating NLRP3 inflammasome

BACKGROUND & AIMS: Sphingosine 1-phosphate receptors (S1PRs) are a group of G-protein-coupled receptors that confer a broad range of functional effects in chronic inflammatory and metabolic diseases. S1PRs also may mediate the development of nonalcoholic steatohepatitis (NASH), but the specific subtypes involved and the mechanism of action are unclear. METHODS: We investigated which type of S1PR isoforms is activated in various murine models of NASH. The mechanism of action of S1PR4 was examined in hepatic macrophages isolated from high-fat, high-cholesterol diet (HFHCD)-fed mice. We developed a selective S1PR4 functional antagonist by screening the fingolimod (2-amino-2-[2-(4- n-octylphenyl)ethyl]-1,3-propanediol hydrochloride)-like sphingolipid-focused library. RESULTS: The livers of various mouse models of NASH as well as hepatic macrophages showed high expression of S1pr4. Moreover, in a cohort of NASH patients, expression of S1PR4 was 6-fold higher than those of healthy controls. S1pr4(++/-) mice were protected from HFHCD-induced NASH and hepatic fibrosis without changes in steatosis. S1pr4 depletion in hepatic macrophages inhibited lipopolysaccharide-mediated Ca++ release and deactivated the Nod-like receptor pyrin domaincontainning protein 3 (NLRP3) inflammasome. S1P increased the expression of S1pr4 in hepatic macrophages and activated NLRP3 inflammasome through inositol trisphosphate/inositol trisphosphate-receptor-dependent [Ca++] signaling. To further clarify the biological function of S1PR4, we developed SLB736, a novel selective functional antagonist of SIPR4. Similar to S1pr4(+/-) mice, administration of SLB736 to HFHCD-fed mice prevented the development of NASH and hepatic fibrosis, but not steatosis, by deactivating the NLRP3 inflammasome. CONCLUSIONS: S1PR4 may be a new therapeutic target for NASH that mediates the activation of NLRP3 inflammasome in hepatic macrophages

Bezielle Selectively Targets Mitochondria of Cancer Cells to Inhibit Glycolysis and OXPHOS

Bezielle (BZL101) is a candidate oral drug that has shown promising efficacy and excellent safety in the early phase clinical trials for advanced breast cancer. Bezielle is an aqueous extract from the herb Scutellaria barbata. We have reported previously that Bezielle was selectively cytotoxic to cancer cells while sparing non-transformed cells. In tumor, but not in non-transformed cells, Bezielle induced generation of ROS and severe DNA damage followed by hyperactivation of PARP, depletion of the cellular ATP and NAD, and inhibition of glycolysis. We show here that tumor cells' mitochondria are the primary source of reactive oxygen species induced by Bezielle. Treatment with Bezielle induces progressively higher levels of mitochondrial superoxide as well as peroxide-type ROS. Inhibition of mitochondrial respiration prevents generation of both types of ROS and protects cells from Bezielle-induced death. In addition to glycolysis, Bezielle inhibits oxidative phosphorylation in tumor cells and depletes mitochondrial reserve capacity depriving cells of the ability to produce ATP. Tumor cells lacking functional mitochondria maintain glycolytic activity in presence of Bezielle thus supporting the hypothesis that mitochondria are the primary target of Bezielle. The metabolic effects of Bezielle towards normal cells are not significant, in agreement with the low levels of oxidative damage that Bezielle inflicts on them. Bezielle is therefore a drug that selectively targets cancer cell mitochondria, and is distinguished from other such drugs by its ability to induce not only inhibition of OXPHOS but also of glycolysis. This study provides a better understanding of the mechanism of Bezielle's cytotoxicity, and the basis of its selectivity towards cancer cells