Chiral perturbation theory in a magnetic background - finite-temperature effects

We consider chiral perturbation theory for SU(2) at finite temperature $T$ in a constant magnetic background $B$. We compute the thermal mass of the pions and the pion decay constant to leading order in chiral perturbation theory in the presence of the magnetic field. The magnetic field gives rise to a splitting between $M_{\pi^0}$ and $M_{\pi^{\pm}}$ as well as between $F_{\pi^0}$ and $F_{\pi^{\pm}}$. We also calculate the free energy and the quark condensate to next-to-leading order in chiral perturbation theory. Both the pion decay constants and the quark condensate are decreasing slower as a function of temperature as compared to the case with vanishing magnetic field. The latter result suggests that the critical temperature $T_c$ for the chiral transition is larger in the presence of a constant magnetic field. The increase of $T_c$ as a function of $B$ is in agreement with most model calculations but in disagreement with recent lattice calculations.Comment: 24 pages and 9 fig

Expression of PROKR1 and PROKR2 in Human Enteric Neural Precursor Cells and Identification of Sequence Variants Suggest a Role in HSCR

Background The enteric nervous system (ENS) is entirely derived from neural crest and its normal development is regulated by specific molecular pathways. Failure in complete ENS formation results in aganglionic gut conditions such as Hirschsprung's disease (HSCR). Recently, PROKR1 expression has been demonstrated in mouse enteric neural crest derived cells and Prok-1 was shown to work coordinately with GDNF in the development of the ENS. Principal Findings In the present report, ENS progenitors were isolated and characterized from the ganglionic gut from children diagnosed with and without HSCR, and the expression of prokineticin receptors was examined. Immunocytochemical analysis of neurosphere-forming cells demonstrated that both PROKR1 and PROKR2 were present in human enteric neural crest cells. In addition, we also performed a mutational analysis of PROKR1, PROKR2, PROK1 and PROK2 genes in a cohort of HSCR patients, evaluating them for the first time as susceptibility genes for the disease. Several missense variants were detected, most of them affecting highly conserved amino acid residues of the protein and located in functional domains of both receptors, which suggests a possible deleterious effect in their biological function. Conclusions Our results suggest that not only PROKR1, but also PROKR2 might mediate a complementary signalling to the RET/GFRα1/GDNF pathway supporting proliferation/survival and differentiation of precursor cells during ENS development. These findings, together with the detection of sequence variants in PROKR1, PROK1 and PROKR2 genes associated to HSCR and, in some cases in combination with RET or GDNF mutations, provide the first evidence to consider them as susceptibility genes for HSCR.This work was supported by Fondo de Investigación Sanitaria, Spain (PI070080, PI1001290 and PI071315 for the E-Rare project), Consejería de Innovación Ciencia y Empresa de la Junta de Andalucía (CTS 2590) and Consejería de Salud de la Junta de Andalucía (PI0249-2008). The CIBER de Enfermedades Raras is an initiative of the ISCIII. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Positive words carry less information than negative words

We show that the frequency of word use is not only determined by the word length \cite{Zipf1935} and the average information content \cite{Piantadosi2011}, but also by its emotional content. We have analyzed three established lexica of affective word usage in English, German, and Spanish, to verify that these lexica have a neutral, unbiased, emotional content. Taking into account the frequency of word usage, we find that words with a positive emotional content are more frequently used. This lends support to Pollyanna hypothesis \cite{Boucher1969} that there should be a positive bias in human expression. We also find that negative words contain more information than positive words, as the informativeness of a word increases uniformly with its valence decrease. Our findings support earlier conjectures about (i) the relation between word frequency and information content, and (ii) the impact of positive emotions on communication and social links.Comment: 16 pages, 3 figures, 3 table

A cholinergic neuroskeletal interface promotes bone formation during postnatal growth and exercise.

The autonomic nervous system is a master regulator of homeostatic processes and stress responses. Sympathetic noradrenergic nerve fibers decrease bone mass, but the role of cholinergic signaling in bone has remained largely unknown. Here, we describe that early postnatally, a subset of sympathetic nerve fibers undergoes an interleukin-6 (IL-6)-induced cholinergic switch upon contacting the bone. A neurotrophic dependency mediated through GDNF-family receptor-α2 (GFRα2) and its ligand, neurturin (NRTN), is established between sympathetic cholinergic fibers and bone-embedded osteocytes, which require cholinergic innervation for their survival and connectivity. Bone-lining osteoprogenitors amplify and propagate cholinergic signals in the bone marrow (BM). Moderate exercise augments trabecular bone partly through an IL-6-dependent expansion of sympathetic cholinergic nerve fibers. Consequently, loss of cholinergic skeletal innervation reduces osteocyte survival and function, causing osteopenia and impaired skeletal adaptation to moderate exercise. These results uncover a cholinergic neuro-osteocyte interface that regulates skeletogenesis and skeletal turnover through bone-anabolic effects

Comprehensive Analysis of NRG1 Common and Rare Variants in Hirschsprung Patients

Hirschsprung disease (HSCR, OMIM 142623) is a developmental disorder characterized by the absence of ganglion cells along variable lengths of the distal gastrointestinal tract, which results in tonic contraction of the aganglionic gut segment and functional intestinal obstruction. The RET proto-oncogene is the major gene for HSCR with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology. Many other genes have been described to be associated with the pathology, as NRG1 gene (8p12), encoding neuregulin 1, which is implicated in the development of the enteric nervous system (ENS), and seems to contribute by both common and rare variants. Here we present the results of a comprehensive analysis of the NRG1 gene in the context of the disease in a series of 207 Spanish HSCR patients, by both mutational screening of its coding sequence and evaluation of 3 common tag SNPs as low penetrance susceptibility factors, finding some potentially damaging variants which we have functionally characterized. All of them were found to be associated with a significant reduction of the normal NRG1 protein levels. The fact that those mutations analyzed alter NRG1 protein would suggest that they would be related with HSCR disease not only in Chinese but also in a Caucasian population, which reinforces the implication of NRG1 gene in this pathology

Oxidation mechanisms occurring in wines

The present review aims to show the state of the art on the oxidation mechanisms occurring in wines, as well as the methods to monitor, classify and diagnose wine oxidation. Wine oxidation can be divided in enzymatic oxidation and non-enzymatic oxidation. Enzymatic oxidation almost entirely occurs in grape must and is largely correlated with the content of hydroxycinnamates, such as caffeoyltartaric acid and para-coumaroyltartaric acid, and flavan-3-ols. Non-enzymatic oxidation, also called chemical oxidation of wine, prevails in fermented wine and begin by the oxidation of polyphenols containing a catechol or a galloyl group. These phenolic. reactions, both enzymatic and non-enzymatic, result in by-products named quinones. However, in non-enzymatic oxidation, oxygen does not react directly with phenolic compounds. The limitation on the reactivity of triplet oxygen is overcome by the stepwise addition of a single electron, which can be provided by reduced transition metal ions, essentially iron(II) and copper(I). The sequential electron transfer leads to the formation of hydroperoxide radical (HOO center dot), hydrogen peroxide (H2O2), and hydroxyl radical (HO center dot). The later radical will oxidize almost any organic molecule found in wine and will react with the first species it encounters, depending on their concentration. Sulfur dioxide (SO2) and ascorbic acid, when added to wine, are able to reduce the quinones. Alternative options have been assessed for the prevention of oxidation during wine storage; nevertheless, these are not fully understood or commonly accepted. During aging, aldehydes are important intermediates in the chemical transformations occurring in wines, leading to color and flavor changes. In the same way, a range of off-flavors can be formed from wine oxidation. At low concentrations these flavors may add to the complexity of a wine, but as these increase they begin to detract from wine quality. In addition to the major chemical browning involving wine phenols, the main oxidation reactions occurring during grape juice heating or storage are caramelization and Maillard reaction, which are temperature dependent. Different methods have been proposed in the literature, addressing the complexity and multi-scale related with the oxidation process, to attempt the quantification of antioxidant activity in wines. These methods can be broadly divided in: i) methods based on chemical reactions and ii) methods based on the chemical-physical properties of antioxidants

Novel association of severe neonatal encephalopathy and Hirschsprung disease in a male with a duplication at the Xq28 region

<p>Abstract</p> <p>Background</p> <p>Hirschsprung disease (HSCR) is a neurocristopathy characterized by the absence of parasympathetic intrinsic ganglion cells in the submucosal and myenteric plexuses along a variable portion of the intestinal tract. In approximately 18% of the cases HSCR also presents with multiple congenital anomalies including recognized syndromes.</p> <p>Methods</p> <p>A combination of MLPA and microarray data analysis have been undertaken to refine a duplication at the Xq28 region.</p> <p>Results</p> <p>In this study we present a new clinical association of severe neonatal encephalopathy (Lubs syndrome) and HSCR, in a male patient carrying a duplication at the Xq28 region which encompasses the <it>MECP2 </it>and <it>L1CAM </it>genes.</p> <p>Conclusions</p> <p>While the encephalopathy has been traditionally attributed to the <it>MECP2 </it>gene duplication in patients with Lubs syndrome, here we propose that the enteric phenotype in our patient might be due to the dosage variation of the L1CAM protein, together with additional molecular events not identified yet. This would be in agreement with the hypothesis previously forwarded that mutations in <it>L1CAM </it>may be involved in HSCR development in association with a predisposing genetic background.</p

The endogenous anti-angiogenic VEGF isoform, VEGF165b inhibits human tumour growth in mice

Vascular endothelial growth factor-A is widely regarded as the principal stimulator of angiogenesis required for tumour growth. VEGF is generated as multiple isoforms of two families, the pro-angiogenic family generated by proximal splice site selection in the terminal exon, termed VEGFxxx, and the anti-angiogenic family formed by distal splice site selection in the terminal exon, termed VEGFxxxb, where xxx is the amino acid number. The most studied isoforms, VEGF165 and VEGF165b have been shown to be present in tumour and normal tissues respectively. VEGF165b has been shown to inhibit VEGF- and hypoxia-induced angiogenesis, and VEGF-induced cell migration and proliferation in vitro. Here we show that overexpression of VEGF165b by tumour cells inhibits the growth of prostate carcinoma, Ewing's sarcoma and renal cell carcinoma in xenografted mouse tumour models. Moreover, VEGF165b overexpression inhibited tumour cell-mediated migration and proliferation of endothelial cells. These data show that overexpression of VEGF165b can inhibit growth of multiple tumour types in vivo indicating that VEGF165b has potential as an anti-angiogenic, anti-tumour strategy in a number of different tumour types, either by control of VEGF165b expression by regulation of splicing, overexpression of VEGF165b, or therapeutic delivery of VEGF165b to tumours

Prescriptions of Traditional Chinese Medicine Are Specific to Cancer Types and Adjustable to Temperature Changes

Targeted cancer therapies, with specific molecular targets, ameliorate the side effect issue of radiation and chemotherapy and also point to the development of personalized medicine. Combination of drugs targeting multiple pathways of carcinogenesis is potentially more fruitful. Traditional Chinese medicine (TCM) has been tailoring herbal mixtures for individualized healthcare for two thousand years. A systematic study of the patterns of TCM formulas and herbs prescribed to cancers is valuable. We analysed a total of 187,230 TCM prescriptions to 30 types of cancer in Taiwan in 2007, a year's worth of collection from the National Health Insurance reimbursement database (Taiwan). We found that a TCM cancer prescription consists on average of two formulas and four herbs. We show that the percentage weights of TCM formulas and herbs in a TCM prescription follow Zipf's law with an exponent around 0.6. TCM prescriptions to benign neoplasms have a larger Zipf's exponent than those to malignant cancers. Furthermore, we show that TCM prescriptions, via weighted combination of formulas and herbs, are specific to not only the malignancy of neoplasms but also the sites of origins of malignant cancers. From the effects of formulas and natures of herbs that were heavily prescribed to cancers, that cancers are a ‘warm and stagnant’ syndrome in TCM can be proposed, suggesting anti-inflammatory regimens for better prevention and treatment of cancers. We show that TCM incorporated relevant formulas to the prescriptions to cancer patients with a secondary morbidity. We compared TCM prescriptions made in different seasons and identified temperatures as the environmental factor that correlates with changes in TCM prescriptions in Taiwan. Lung cancer patients were among the patients whose prescriptions were adjusted when temperatures drop. The findings of our study provide insight to TCM cancer treatment, helping dialogue between modern western medicine and TCM for better cancer care