Higher-order scalar interactions and SM vacuum stability

Investigation of the structure of the Standard Model effective potential at very large field strengths opens a window towards new phenomena and can reveal properties of the UV completion of the SM. The map of the lifetimes of the vacua of the SM enhanced by nonrenormalizable scalar couplings has been compiled to show how new interactions modify stability of the electroweak vacuum. Whereas it is possible to stabilize the SM by adding Planck scale suppressed interactions and taking into account running of the new couplings, the generic effect is shortening the lifetime and hence further destabilisation of the SM electroweak vacuum. These findings have been illustrated with phase diagrams of modified SM-like models. It has been demonstrated that stabilisation can be achieved by lowering the suppression scale of higher order operators while picking up such combinations of new couplings, which do not deepen the new minima of the potential. Our results show the dependence of the lifetime of the electroweak minimum on the magnitude of the new couplings, including cases with very small couplings (which means very large effective suppression scale) and couplings vastly different in magnitude (which corresponds to two different suppression scales).Comment: plain Latex, 9 figure

Central oxytocin and food intake: focus on macronutrient-driven reward

Centrally acting oxytocin (OT) is known to terminate food consumption in response to excessive stomach distension, increase in salt loading, and presence of toxins. Hypothalamic-hindbrain OT pathways facilitate these aspects of OT-induced hypophagia. However, recent discoveries have implicated OT in modifications of feeding via reward circuits: OT has been found to differentially affect consumption of individual macronutrients in choice and no-choice paradigms. In this mini-review, we focus on presenting and interpreting evidence that defines OT as a key component of mechanisms that reduce eating for pleasure and shape macronutrient preferences. We also provide remarks on challenges in integrating the knowledge on physiological and pathophysiological states in which both OT activity and macronutrient preferences are affected

Adhesion GPCRs are widely expressed throughout the subsections of the gastrointestinal tract

Background: G protein-coupled receptors (GPCRs) represent one of the largest families of transmembrane receptors and the most common drug target. The Adhesion subfamily is the second largest one of GPCRs and its several members are known to mediate neural development and immune system functioning through cell-cell and cell-matrix interactions. The distribution of these receptors has not been characterized in detail in the gastrointestinal (GI) tract. Here we present the first comprehensive anatomical profiling of mRNA expression of all 30 Adhesion GPCRs in the rat GI tract divided into twelve subsegments. Methods: Using RT-qPCR, we studied the expression of Adhesion GPCRs in the esophagus, the corpus and antrum of the stomach, the proximal and distal parts of the duodenum, ileum, jejunum and colon, and the cecum. Results: We found that twenty-one Adhesion GPCRs (70%) had a widespread (expressed in five or more segments) or ubiquitous (expressed in eleven or more segments) distribution, seven (23%) were restricted to a few segments of the GI tract and two were not expressed in any segment. Most notably, almost all Group III members were ubiquitously expressed, while the restricted expression was characteristic for the majority of group VII members, hinting at more specific/localized roles for some of these receptors. Conclusions: Overall, the distribution of Adhesion GPCRs points to their important role in GI tract functioning and defines them as a potentially crucial target for pharmacological interventions. © 2012 Badiali et al.; licensee BioMed Central Ltd

Glutamate, aspartate and nucleotide transporters in the SLC17 family form four main phylogenetic clusters: evolution and tissue expression

<p>Abstract</p> <p>Background</p> <p>The SLC17 family of transporters transports the amino acids: glutamate and aspartate, and, as shown recently, also nucleotides. Vesicular glutamate transporters are found in distinct species, such as <it>C. elegans</it>, but the evolutionary origin of most of the genes in this family has been obscure.</p> <p>Results</p> <p>Our phylogenetic analysis shows that the SLC17 family consists of four main phylogenetic clades which were all present before the divergence of the insect lineage. One of these clades has not been previously described and it is not found in vertebrates. The clade containing Slc17a9 had the most restricted evolutionary history with only one member in most species. We detected expression of Slc17a1-17a4 only in the peripheral tissues but not in the CNS, while Slc17a5- Slc17a9 are highly expressed in both the CNS and periphery.</p> <p>Conclusions</p> <p>The <it>in situ </it>hybridization studies on vesicular nucleotide transporter revealed high expression throughout the cerebral cortex, certain areas in the hippocampus and in specific nuclei of the hypothalamus and thalamus. Some of the regions with high expression, such as the medial habenula and the dentate gyrus of the hippocampus, are important sites for purinergic neurotransmission. Noteworthy, other areas relying on purine-mediated signaling, such as the molecular layer of the dentate gyrus and the periaqueductal gray, lack or have a very low expression of Slc17a9, suggesting that there could be another nucleotide transporter in these regions.</p

Higher-order scalar interactions and SM vacuum stability

Investigation of the structure of the Standard Model effective potential at very large field strengths opens a window towards new phenomena and can reveal properties of the UV completion of the SM. The map of the lifetimes of the vacua of the SM enhanced by nonrenormalizable scalar couplings has been compiled to show how new interactions modify stability of the electroweak vacuum. Whereas it is possible to stabilize the SM by adding Planck scale suppressed interactions and taking into account running of the new couplings, the generic effect is shortening the lifetime and hence further destabilisation of the SM electroweak vacuum. These findings have been illustrated with phase diagrams of modified SM-like models. It has been demonstrated that stabilisation can be achieved by lowering the suppression scale of higher order operators while picking up such combinations of new couplings, which do not deepen the new minima of the potential. Our results show the dependence of the lifetime of the electroweak minimum on the magnitude of the new couplings, including cases with very small couplings (which means very large effective suppression scale) and couplings vastly different in magnitude (which corresponds to two different suppression scales).Comment: plain Latex, 9 figure

Genetic polymorphisms in DNA base excision repair gene XRCC1 and the risk of squamous cell carcinoma of the head and neck

<p>Abstract</p> <p>Background</p> <p>The genes of base excision repair (BER) pathway have been extensively studied in the association with various human cancers. We performed a case-control study to test the association between two common single nucleotide polymorphisms (SNPs) of <it>XRCC1 </it>gene with human head and neck squamous cell carcinoma (HNSCC).</p> <p>Methods</p> <p>The genotype analysis of Arg194Trp and Arg399Gln gene polymorphisms for 92 HNSCC patients and 124 controls of cancer free subjects, in Polish population were performed using the PCR-based restriction fragment length polymorphism (PCR-RFLP) with endonuclease <it>Msp</it>I.</p> <p>Results</p> <p>No altered risk has been found individually for these SNPs, however haplotypes analysis showed high association with head and neck cancer. The highest frequency, according to wild-type of Arg194Arg and Arg399Arg genotypes, was identified for Arg194Trp-Arg399Arg haplotype (OR, 2.96; 95% CI, 1.01–8.80).</p> <p>Conclusion</p> <p>Finally, we identified the combined Arg194Trp-Arg399Arg genotype of base excision repair gene <it>XRCC1 </it>that was associated with HNSCC and may have an impact on identification of a high-risk cancer population.</p

Functional coupling analysis suggests link between the obesity gene FTO and the BDNF-NTRK2 signaling pathway

<p>Abstract</p> <p>Background</p> <p>The Fat mass and obesity gene (FTO) has been identified through genome wide association studies as an important genetic factor contributing to a higher body mass index (BMI). However, the molecular context in which this effect is mediated has yet to be determined. We investigated the potential molecular network for FTO by analyzing co-expression and protein-protein interaction databases, Coxpresdb and IntAct, as well as the functional coupling predicting multi-source database, FunCoup. Hypothalamic expression of FTO-linked genes defined with this bioinformatics approach was subsequently studied using quantitative real time-PCR in mouse feeding models known to affect FTO expression.</p> <p>Results</p> <p>We identified several candidate genes for functional coupling to FTO through database studies and selected nine for further study in animal models. We observed hypothalamic expression of Profilin 2 (Pfn2), cAMP-dependent protein kinase catalytic subunit beta (Prkacb), Brain derived neurotrophic factor (Bdnf), neurotrophic tyrosine kinase, receptor, type 2 (Ntrk2), Signal transducer and activator of transcription 3 (Stat3), and Btbd12 to be co-regulated in concert with Fto. Pfn2 and Prkacb have previously not been linked to feeding regulation.</p> <p>Conclusions</p> <p>Gene expression studies validate several candidates generated through database studies of possible FTO-interactors. We speculate about a wider functional role for FTO in the context of current and recent findings, such as in extracellular ligand-induced neuronal plasticity via NTRK2/BDNF, possibly via interaction with the transcription factor CCAAT/enhancer binding protein β (C/EBPβ).</p