The influence of defined ante-mortem stressors on the early post-mortem biochemical processes in the abdominal muscle of the Norway lobster, Nephrops norvegicus (Linnaeus, 1758)

The effects of four different ante-mortem stressors (exercise, emersion, starvation and a patent infection with the parasite Hematodinium sp.) on post-mortem processes have been investigated in the abdominal muscle of Norway lobster Nephrops norvegicus by measuring changes in the pH, the levels of glycogen, l-lactate, arginine phosphate, ATP, ADP, AMP, IMP, HxR, Hx and the adenylate energy charge (AEC) over a time course of 24 h with samples being taken at 0, 3, 6, 12 and 24 h. The acute stresses of intense exercise and 2 h emersion resulted in a premature onset of anaerobic glycolysis, leading both to an enhanced glycogen depletion rate and an early accumulation of l-lactate. The chronic stressors, starvation and parasite infection, resulted in a complete ante-mortem depletion of muscle glycogen and consequently the failure of post-mortem glycolytic fermentation. Post-mortem pH and ATP inter-conversion were significantly altered in chronically stressed animals. Ante-mortem, a rapid, almost complete depletion of arginine phosphate was observed in all stress groups. The AEC was altered significantly by all stresses, indicating a strong energy demand. The findings suggest that ante-mortem stressors strongly influence the post-mortem biochemical processes. The laboratory-based results are compared to 'field' data and effects on post-harvest product quality are discussed

Dynamic regulation of serum aryl hydrocarbon receptor agonists in MS

Objective: Several factors influence the clinical course of autoimmune inflammatory diseases such as MS and inflammatory bowel disease. Only recently, the complex interaction between the gut microbiome, dietary factors, and metabolism has started to be appreciated with regard to its potential to modulate acute and chronic inflammation. One of the molecular sensors that mediates the effects of these environmental signals on the immune response is the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor with key functions in immune cells. Methods: In this study, we analyzed the levels of AHR agonists in serum samples from patients with MS and healthy controls in a case-control study. Results: We detected a global decrease of circulating AHR agonists in relapsing-remitting MS patients as compared to controls. However, during acute CNS inflammation in clinically isolated syndrome or active MS, we measured increased AHR agonistic activity. Moreover, AHR ligand levels in patients with benign MS with relatively mild clinical impairment despite longstanding disease were unaltered as compared to healthy controls. Conclusions: Collectively, these data suggest that AHR agonists in serum are dynamically modulated during the course of MS. These findings may guide the development of biomarkers to monitor disease activity as well as the design of novel therapeutic interventions for MSInstituto de Salud Carlos III, Unión Europea PT13/0010/004

Bone growth during rapamycin therapy in young rats

<p>Abstract</p> <p>Background</p> <p>Rapamycin is an effective immunosuppressant widely used to maintain the renal allograft in pediatric patients. Linear growth may be adversely affected in young children since rapamycin has potent anti-proliferative and anti-angiogenic properties.</p> <p>Methods</p> <p>Weanling three week old rats were given rapamycin at 2.5 mg/kg daily by gavage for 2 or 4 weeks and compared to a Control group given equivalent amount of saline. Morphometric measurements and biochemical determinations for serum calcium, phosphate, iPTH, urea nitrogen, creatinine and insulin-growth factor I (IGF-I) were obtained. Histomorphometric analysis of the growth plate cartilage, in-situ hybridization experiments and immunohistochemical studies for various proteins were performed to evaluate for chondrocyte proliferation, chondrocyte differentiation and chondro/osteoclastic resorption.</p> <p>Results</p> <p>At the end of the 2 weeks, body and tibia length measurements were shorter after rapamycin therapy associated with an enlargement of the hypertrophic zone in the growth plate cartilage. There was a decrease in chondrocyte proliferation assessed by <it>histone-4 </it>and <it>mammalian target of rapamycin </it>(<it>mTOR</it>) expression. A reduction in <it>parathyroid hormone/parathyroid hormone related peptide (PTH/PTHrP) </it>and an increase in <it>Indian hedgehog </it>(<it>Ihh</it>) expression may explain in part, the increase number of hypertrophic chondrocytes. The number of TRAP positive multinucleated chondro/osteoclasts declined in the chondro-osseous junction with a decrease in the <it>receptor activator of nuclear factor kappa β ligand </it>(<it>RANKL</it>) and <it>vascular endothelial growth factor </it>(<it>VEGF</it>) expression. Although body and tibial length remained short after 4 weeks of rapamycin, changes in the expression of chondrocyte proliferation, chondrocyte differentiation and chondro/osteoclastic resorption which were significant after 2 weeks of rapamycin improved at the end of 4 weeks.</p> <p>Conclusion</p> <p>When given to young rats, 2 weeks of rapamycin significantly decreased endochondral bone growth. No catch-up growth was demonstrated at the end of 4 weeks, although markers of chondrocyte proliferation and differentiation improved. Clinical studies need to be done to evaluate these changes in growing children.</p

Proteomics as a quality control tool of pharmaceutical probiotic bacterial lysate products

Probiotic bacteria have a wide range of applications in veterinary and human therapeutics. Inactivated probiotics are complex samples and quality control (QC) should measure as many molecular features as possible. Capillary electrophoresis coupled to mass spectrometry (CE/MS) has been used as a multidimensional and high throughput method for the identification and validation of biomarkers of disease in complex biological samples such as biofluids. In this study we evaluate the suitability of CE/MS to measure the consistency of different lots of the probiotic formulation Pro-Symbioflor which is a bacterial lysate of heat-inactivated Escherichia coli and Enterococcus faecalis. Over 5000 peptides were detected by CE/MS in 5 different lots of the bacterial lysate and in a sample of culture medium. 71 to 75% of the total peptide content was identical in all lots. This percentage increased to 87–89% when allowing the absence of a peptide in one of the 5 samples. These results, based on over 2000 peptides, suggest high similarity of the 5 different lots. Sequence analysis identified peptides of both E. coli and E. faecalis and peptides originating from the culture medium, thus confirming the presence of the strains in the formulation. Ontology analysis suggested that the majority of the peptides identified for E. coli originated from the cell membrane or the fimbrium, while peptides identified for E. faecalis were enriched for peptides originating from the cytoplasm. The bacterial lysate peptides as a whole are recognised as highly conserved molecular patterns by the innate immune system as microbe associated molecular pattern (MAMP). Sequence analysis also identified the presence of soybean, yeast and casein protein fragments that are part of the formulation of the culture medium. In conclusion CE/MS seems an appropriate QC tool to analyze complex biological products such as inactivated probiotic formulations and allows determining the similarity between lots

The novel mu-opioid antagonist, GSK1521498, reduces ethanol consumption in C57BL/6J mice.

RATIONALE Using the drinking-in-the-dark (DID) model, we compared the effects of a novel mu-opioid receptor antagonist, GSK1521498, with naltrexone, a licensed treatment of alcohol dependence, on ethanol consumption in mice. OBJECTIVE We test the ability of GSK1521498 to reduce alcohol consumption and compare its intrinsic efficacy to that of naltrexone by comparing the two drugs at doses matched for equivalent receptor occupancy. METHODS Thirty-six C57BL/6J mice were tested in a DID procedure. In 2-day cycles, animals experienced one baseline, injection-free session, and one test session when they received two injections, one of test drug and one placebo. All animals received GSK1521498 (0, 0.1, 1 and 3 mg/kg, i.p., 30 min pre-treatment) and naltrexone (0, 0.1, 1 and 3 mg/kg, s.c. 10 min pre-treatment) in a cross-over design. Receptor occupancies following the same doses were determined ex vivo in separate groups by autoradiography, using [3H]DAMGO. Binding in the region of interest was measured integrally by computer-assisted microdensitometry and corrected for non-specific binding. RESULTS Both GSK1521498 and naltrexone dose-dependently decreased ethanol consumption. When drug doses were matched for 70-75 % receptor occupancy, GSK1521498 3 mg/kg, i.p., caused a 2.5-fold greater reduction in alcohol consumption than naltrexone 0.1 mg/kg, s.c. Both GSK1521498 and naltrexone significantly reduced sucrose consumption at a dose of 1 mg/kg but not 0.1 mg/kg. In a test of conditioned taste aversion, GSK1521498 (3 mg/kg) reduced sucrose consumption 24 h following exposure to a conditioning injection. CONCLUSIONS Both opioid receptor antagonists reduced alcohol consumption but GK1521498 has higher intrinsic efficacy than naltrexone

Interferon regulatory factor 8-deficiency determines massive neutrophil recruitment but T cell defect in fast growing granulomas during tuberculosis

Following Mycobacterium tuberculosis (Mtb) infection, immune cell recruitment in lungs is pivotal in establishing protective immunity through granuloma formation and neogenesis of lymphoid structures (LS). Interferon regulatory factor-8 (IRF-8) plays an important role in host defense against Mtb, although the mechanisms driving anti-mycobacterial immunity remain unclear. In this study, IRF-8 deficient mice (IRF-8−/−) were aerogenously infected with a low-dose Mtb Erdman virulent strain and the course of infection was compared with that induced in wild-type (WT-B6) counterparts. Tuberculosis (TB) progression was examined in both groups using pathological, microbiological and immunological parameters. Following Mtb exposure, the bacterial load in lungs and spleens progressed comparably in the two groups for two weeks, after which IRF-8−/− mice developed a fatal acute TB whereas in WT-B6 the disease reached a chronic stage. In lungs of IRF-8−/−, uncontrolled growth of pulmonary granulomas and impaired development of LS were observed, associated with unbalanced homeostatic chemokines, progressive loss of infiltrating T lymphocytes and massive prevalence of neutrophils at late infection stages. Our data define IRF-8 as an essential factor for the maintenance of proper immune cell recruitment in granulomas and LS required to restrain Mtb infection. Moreover, IRF-8−/− mice, relying on a common human and mouse genetic mutation linked to susceptibility/severity of mycobacterial diseases, represent a valuable model of acute TB for comparative studies with chronically-infected congenic WT-B6 for dissecting protective and pathological immune reactions

Group formation under limited resources: narrow basin of equality

The formation of groups in competition and the aggressive interactions between them are ubiquitous phenomena in society. These include student activities in the classroom, election races between political parties, and intensifying trade wars between countries. Why do individuals form themselves into groups? What is the optimal size of groups? And how does the group size distribution affect resource allocations? These questions have been the subjects of intense research in economics, political science, sociology, and ethology. In this study, we explore the group-size effects on the formation of groups and resource allocations from an economic standpoint. While being in a large group is generally advantageous in competition, an increase in the management costs would set an upper bound to the individual benefit of members. Under such counteracting size effects, we consider the dynamics of group formation in which people seek a conservative measure to reduce their possible maximum loss. We are especially interested in the effects of group size on social inequalities at both group and individual level in resource allocation. Our findings show that the low positive size-effect and the high negative size-effect result in different types of social inequalities. We conclude, from the relation between the inequality measures and group distributions predicted within the model, that overall social equality only can be achieved within a narrow region where two counteracting size-effects are balanced

Characterizing, modelling and understanding the climate variability of the deep water formation in the North-Western Mediterranean Sea

Observing, modelling and understanding the climate-scale variability of the deep water formation (DWF) in the North-Western Mediterranean Sea remains today very challenging. In this study, we first characterize the interannual variability of this phenomenon by a thorough reanalysis of observations in order to establish reference time series. These quantitative indicators include 31 observed years for the yearly maximum mixed layer depth over the period 1980–2013 and a detailed multi-indicator description of the period 2007–2013. Then a 1980–2013 hindcast simulation is performed with a fully-coupled regional climate system model including the high-resolution representation of the regional atmosphere, ocean, land-surface and rivers. The simulation reproduces quantitatively well the mean behaviour and the large interannual variability of the DWF phenomenon. The model shows convection deeper than 1000 m in 2/3 of the modelled winters, a mean DWF rate equal to 0.35 Sv with maximum values of 1.7 (resp. 1.6) Sv in 2013 (resp. 2005). Using the model results, the winter-integrated buoyancy loss over the Gulf of Lions is identified as the primary driving factor of the DWF interannual variability and explains, alone, around 50 % of its variance. It is itself explained by the occurrence of few stormy days during winter. At daily scale, the Atlantic ridge weather regime is identified as favourable to strong buoyancy losses and therefore DWF, whereas the positive phase of the North Atlantic oscillation is unfavourable. The driving role of the vertical stratification in autumn, a measure of the water column inhibition to mixing, has also been analyzed. Combining both driving factors allows to explain more than 70 % of the interannual variance of the phenomenon and in particular the occurrence of the five strongest convective years of the model (1981, 1999, 2005, 2009, 2013). The model simulates qualitatively well the trends in the deep waters (warming, saltening, increase in the dense water volume, increase in the bottom water density) despite an underestimation of the salinity and density trends. These deep trends come from a heat and salt accumulation during the 1980s and the 1990s in the surface and intermediate layers of the Gulf of Lions before being transferred stepwise towards the deep layers when very convective years occur in 1999 and later. The salinity increase in the near Atlantic Ocean surface layers seems to be the external forcing that finally leads to these deep trends. In the future, our results may allow to better understand the behaviour of the DWF phenomenon in Mediterranean Sea simulations in hindcast, forecast, reanalysis or future climate change scenario modes. The robustness of the obtained results must be however confirmed in multi-model studies

Light hadron, Charmonium(-like) and Bottomonium(-like) states

Hadron physics represents the study of strongly interacting matter in all its manifestations and the understanding of its properties and interactions. The interest on this field has been revitalized by the discovery of new light hadrons, charmonium- and bottomonium-like states. I review the most recent experimental results from different experiments.Comment: Presented at Lepton-Photon 2011, Mumbai, India; 21 pages, 18 figures; add more references; some correctio