Characterisation of an epitope recognised by a monoclonal antibody against horse alcohol dehydrogenase using peptides synthesised on solid support

AbstractImmunological analysis, using the Pepscan technique, of the tetradecapeptide, Pro344-Glu357 (PLITHVLPFEKINE), from horse liver alcohol dehydrogenase has identified a five amino acid sequence, HVLPF, which binds a monoclonal antibody. The epitope seems to be rather flexible with only two of the amino adds. Pro and Phe, having the characteristics of contact residues. However, the presence of the adjacent glutamic acid residue as part of the Pepscan peptide has a dramatic negative neighbourhood effect and inhibits binding. This highlights the potential risk of missing an epitope altogether when using the Pepscan procedure for epitope mapping

Evidence that stimulation of gluconeogenesis by fatty acid is mediated through thermodynamic mechanisms

AbstractWe have studied the stimulatory effects of palmitate on the rate of glucose synthesis from lactate in isolated hepatocytes. Control of the metabolic flow was achieved by modulating the activity of enolase using graded concentrations of fluoride. Unexpectedly, palmitate stimulated gluconeogenesis even when enolase was rate-limiting. This stimulation was also observed when the activities of phosphoenolpyruvate carboxykinase and aspartate aminotransferase were modulated using graded concentrations of quinolinate and aminooxyacetate, respectively. Linear force-flow relationships were found between the rate of gluconeogenesis and indicators of cellular energy status (i.e. mitochondrial membrane and redox potentials and cellular phosphorylation potential). These findings suggest that the fatty acid stimulation of glucose synthesis is in part mediated through thermodynamic mechanisms

Characterising wood properties for deployment of elite subtropical and tropical hardwoods.

Queensland has over 42,000 hectares of hardwood plantations, with 13,700 hectares currently managed for sawn timber and high-value products. Previously, a major impediment to expansion of the hardwood sawn timber and high-value products industry in Queensland was that improved varieties of the key subtropical and tropical species were not available for plantation establishment. Trees from earlier projects, such as Hardwoods Queensland and the Private Plantations Initiative, have now reached an age where selection for growth, form and wood properties is possible. The current project used non-destructive and destructive wood evaluation techniques to characterise the timber quality of 443 subtropical and tropical Corymbia and Eucalyptus trees in these plantings, allowing selection of trees with the best growth, form and wood properties under Queensland conditions. Ecological assessments were also undertaken in the Corymbia plantings to identify germplasm that posed minimal risk of gene flow into native forests. Elite varieties are being fast tracked for deployment in Queensland using economical systems for germplasm capture and nursery production. The project identified and captured 108 new Corymbia and Eucalyptus varieties that can be grown with confidence in Queensland over a shorter rotation length and which produce well-characterised high-quality hardwood timber

The Glauber model and the heavy ion reaction cross section

We reexamine the Glauber model and calculate the total reaction cross section as a function of energy in the low and intermediate energy range, where many of the corrections in the model, are effective. The most significant effect in this energy range is by the modification of the trajectory due to the Coulomb field. The modification in the trajectory due to nuclear field is also taken into account in a self consistent way. The energy ranges in which particular corrections are effective, are quantified and it is found that when the center of mass energy of the system becomes 30 times the Coulomb barrier, none of the trajectory modification to the Glauber model is really required. The reaction cross sections for light and heavy systems, right from near coulomb barrier to intermediate energies have been calculated. The exact nuclear densities and free nucleon-nucleon (NN) cross sections have been used in the calculations. The center of mass correction which is important for light systems, has also been taken into account. There is an excellent agreement between the calculations with the modified Glauber model and the experimental data. This suggests that the heavy ion reactions in this energy range can be explained by the Glauber model in terms of free NN cross sections without incorporating any medium modification.Comment: RevTeX, 21 pages including 9 Postscript figures, submitted to Phys. Rev.

Extragalactic neutrino background from very young pulsars surrounded by supernova envelopes

We estimate the extragalactic muon neutrino background which is produced by hadrons injected by very young pulsars at an early phase after supernova explosion. It is assumed that hadrons are accelerated in the pulsar wind zone which is filled with thermal photons captured below the expanding supernova envelope. In collisions with those thermal photons hadrons produce pions which decay into muon neutrinos. At a later time, muon neutrinos are also produced by the hadrons in collisions with matter of the expanding envelope. We show that extragalactic neutrino background predicted by such a model should be detectable by the planned 1 km$^2$ neutrino detector if a significant part of pulsars is born with periods shorter than $\sim 10$ ms. Since such population of pulsars is postulated by the recent models of production of extremely high energy cosmic rays, detection of neutrinos with predicted fluxes can be used as their observational test.Comment: 4 pages, 2 figures, A&A style, accepted to A&A Let

Genome-wide association study in an admixed case series reveals IL12A as a new candidate in Behçet Disease

Introduction: The etiology of Behçet's disease (BD) is unknown, but widely considered an excessive T-cell mediated inflammatory response in a genetically susceptible host. Recent genomewide association studies (GWAS) have shown limited number of novel loci-associations. The rarity and unequal distribution of the disease prevalence amongst different ethnic backgrounds have hampered the use of GWAS in cohorts of mixed ethnicity and sufficient sample size. However, novel statistical approaches have now enabled GWAS in admixed cohorts. Methods: We ran a GWAS on 336 BD cases and 5,843 controls. The cases consisted of Western Europeans, Middle Eastern and Turkish individuals. Participants from the Generation R study, a multiethnic birth cohort in Rotterdam, The Netherlands were used as controls. All samples were genotyped and data was combined. Linear regression models were corrected for population stratification using Genomic Principal Components and Linear Mixed Modelling. Meta-analysis was performed on selected results previously published. Results: We identified SNPs associated at genome-wide significant level mapping to the 6p21.33 (HLA) region. In addition to this known signal two potential novel associations on chromosomes 6 and 18 were identified, yet with low minor allele frequencies. Extended metaanalysis reveal a GWS association with the IL12A variant rs17810546 on chromosome 3. Discussion: We demonstrate that new statistical techniques enable GWAS analyses in a limited sized cohort of mixed ethnicity. After implementation, we confirmed the central role of the HLA region in the disease and identified new regions of interest. Moreover, we validated the association of a variant in the IL2A gene by meta-analysis with previous work. These findings enhance our

Effect of maternal oxytocin on umbilical venous and arterial blood flows during physiological-based cord clamping in preterm lambs

Background Delayed umbilical cord clamping (UCC) after birth is thought to cause placental to infant blood transfusion, but the mechanisms are unknown. It has been suggested that uterine contractions force blood out of the placenta and into the infant during delayed cord clamping. We have investigated the effect of uterine contractions, induced by maternal oxytocin administration, on umbilical artery (UA) and venous (UV) blood flows before and after ventilation onset to determine whether uterine contractions cause placental transfusion in preterm lambs.Methods and findingsAt similar to 128 days of gestation, UA and UV blood flows, pulmonary arterial blood flow (PBF) and carotid arterial (CA) pressures and blood flows were measured in three groups of fetal sheep during delayed UCC; maternal oxytocin following mifepristone, mifepristone alone, and saline controls. Each successive uterine contraction significantly (pDevelopmen

Subclinical Thyroid Dysfunction and Fracture Risk: A Meta-analysis

IMPORTANCE Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. OBJECTIVE To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. DATA SOURCES AND STUDY SELECTION The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. DATA EXTRACTION Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH <0.45 mIU/L), and subclinical hypothyroidism (TSH ≥4.50-19.99 mIU/L) with normal thyroxine concentrations. MAIN OUTCOME AND MEASURES The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes. RESULTS Among 70,298 participants, 4092 (5.8%) had subclinical hypothyroidism and 2219 (3.2%) had subclinical hyperthyroidism. During 762,401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56,471); for any fracture, HR was 1.28 (95% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25,901); for nonspine fracture, HR was 1.16 (95% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21,722); and for spine fracture, HR was 1.51 (95% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20,328). Lower TSH was associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HR was 1.61 for hip fracture (95% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous subclinical hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95% CI, 1.19-1.93) for hip fracture, 1.42 (95% CI, 1.16-1.74) for any fracture, and 1.74 (95% CI, 1.01-2.99) for spine fracture. No association was found between subclinical hypothyroidism and fracture risk. CONCLUSIONS AND RELEVANCE Subclinical hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous subclinical hyperthyroidism. Further study is needed to determine whether treating subclinical hyperthyroidism can prevent fractures

Hypogene Calcitization: Evaporite Diagenesis in the Western Delaware Basin

Evaporite calcitization within the Castile Formation of the Delaware Basin is more widespread and diverse than originally recognized. Coupled field and GIS studies have identified more than 1000 individual occurrences of calcitization within the Castile Formation outcrop area, which includes both calcitized masses (limestone buttes) and laterally extensive calcitized horizons (limestone sheets). Both limestone buttes and sheets commonly contain a central brecciated zone that we attribute to hypogene dissolution. Lithologic fabric of calcitized zones ranges from little alteration of original varved laminae to fabrics showing extensive laminae distortion as well as extensive vuggy and open cavernous porosity. Calcitization is most abundant in the western portion of the Castile outcrop region where surface denudation has been greatest. Calcitization often forms linear trends, indicating fluid migration along fractures, but also occurs as dense clusters indicating focused, ascending, hydrocarbon-rich fluids. Native sulfur, secondary tabular gypsum (i.e. selenite) and hypogene caves are commonly associated with clusters of calcitization. This assemblage suggests that calcium sulfate diagenesis within the Castile Formation is dominated by hypogene speleogemesis