The Pharmacological Effect Of Bothrops Neuwiedii Pauloensis (jararaca-pintada) Snake Venom On Avian Neuromuscular Transmission.

The neuromuscular effects of Bothrops neuwiedii pauloensis (jararaca-pintada) venom were studied on isolated chick biventer cervicis nerve-muscle preparations. Venom concentrations of 5-50 micro g/ml produced an initial inhibition and a secondary increase of indirectly evoked twitches followed by a progressive concentration-dependent and irreversible neuromuscular blockade. At venom concentrations of 1-20 micro g/ml, the responses to 13.4 mM KCl were inhibited whereas those to 110 micro M acetylcholine alone and cumulative concentrations of 1 micro M to 10 mM were unaffected. At venom concentrations higher than 50 micro g/ml, there was pronounced muscle contracture with inhibition of the responses to acetylcholine, KCl and direct stimulation. At 20-24 degrees C, the venom (50 g/ml) produced only partial neuromuscular blockade (30.7 +/- 8.0%, N = 3) after 120 min and the initial inhibition and the secondary increase of the twitch responses caused by the venom were prolonged and pronounced and the response to KCl was unchanged. These results indicate that B.n. pauloensis venom is neurotoxic, acting primarily at presynaptic sites, and that enzyme activity may be involved in this pharmacological action.36617-2

Relationships between physiological characteristics and trace metal body burdens of banded garden spiders Argiope trifasciata (Araneae, Araneidae)

Banded garden spiders (Argiope trifasciata) were collected at the Ballona Wetlands, a metal contaminated salt marsh. The relationship between spider body size and individual metal loads was investigated. Biochemical markers were identified in spider fecal material and found to correlate to body metal levels. Body metal dry weight concentrations of Cd, Cr, Cu, Zn and total metals in female A. trifasciata exhibited distinct patterns of spatial and annual variation during 2006 and 2007. Spider body size was homogeneous across sites in both years, while increased Cd and Cr concentrations were sometimes associated with a reduction in spider size, though the influence of Cr was quite minor. Spiders with higher body Cu levels showed a reduction in peak area for hypoxanthine and an un-identified component in fecal material chromatograms. Spatial and annual differences in metal bioaccumulation are likely mediated by variation in site-specific environmental parameters and rainfall, while the negative relationships between body size and metal levels are presumably a consequence of a spider\u27s expenditure of energy for metal tolerance mechanisms vs. foraging and growth. Finally, correlating body metal levels with excreta products constitutes a novel method to non-invasively predict metal levels in spiders

Designing and implementing an assay for the detection of rare and divergent NRPS and PKS clones in European, Antarctic and Cuban soils

The ever increasing microbial resistome means there is an urgent need for new antibiotics. Metagenomics is an underexploited tool in the field of drug discovery. In this study we aimed to produce a new updated assay for the discovery of biosynthetic gene clusters encoding bioactive secondary metabolites. PCR assays targeting the polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS) were developed. A range of European soils were tested for their biosynthetic potential using clone libraries developed from metagenomic DNA. Results revealed a surprising number of NRPS and PKS clones with similarity to rare Actinomycetes. Many of the clones tested were phylogenetically divergent suggesting they were fragments from novel NRPS and PKS gene clusters. Soils did not appear to cluster by location but did represent NRPS and PKS clones of diverse taxonomic origin. Fosmid libraries were constructed from Cuban and Antarctic soil samples; 17 fosmids were positive for NRPS domains suggesting a hit rate of less than 1 in 10 genomes. NRPS hits had low similarities to both rare Actinobacteria and Proteobacteria; they also clustered with known antibiotic producers suggesting they may encode for pathways producing novel bioactive compounds. In conclusion we designed an assay capable of detecting divergent NRPS and PKS gene clusters from the rare biosphere; when tested on soil samples results suggest the majority of NRPS and PKS pathways and hence bioactive metabolites are yet to be discovere

Design and development of machinery to plant daffodil bulbs in upland pasture and harvest the above ground biomass

The number of people suffering from dementia is considerable and growing at a significant rate. Alzheimer’s disease accounts for between 50 and 75% of these cases. Galantamine is a pharmaceutical compound that has been an approved treatment for Alzheimer’s disease since 1998. Galantamine can be synthesised chemically but it is a difficult and expensive process. Producing galantamine from the alkeloid galanthamine extracted from daffodils is more cost effective, but supplies are limited. Research has suggested that the environmental challenges associated with upland areas trigger a higher concentration of galanthamine in daffodils compared to daffodils grown under lowland conditions. A 4.5 year UK Agri-Tech Catalyst Industrial Research project is investigating daffodil-derived galanthamine production by integrating daffodil growing into permanent upland sheep pasture. The aim is to increase the economic sustainability of hill farming by providing farmers with a high value supplementary daffodil crop while maintaining a traditional farming system. Machinery is readily available for lowland daffodil production for the cut flower market and for the production of bulbs. Soils are typically deep, fertile and free draining. However, the UK uplands are characterised by low temperatures; exposure to wind; high rainfall; winter snow and frosts; thin impoverished stony soils; a shortage of major nutrients and steep slopes. As part of the research project Harper Adams University agricultural engineers have developed machines for planting daffodil bulbs and harvesting the above ground daffodil biomass in these arduous upland grassland pastures. The planter uses belts to meter and deliver bulbs from the storage hopper to two drop chutes positioned above the purpose built ground opening winged tines. The harvester removes and collects the above ground biomass which is then transferred to sealed containers before being processed

Characterisation of the microbiome along the gastrointestinal tract of growing turkeys

The turkey microbiome is largely understudied, despite its relationship with bird health and growth, and the prevalence of human pathogens such as Campylobacter spp. In this study we investigated the microbiome within the small intestine (SI), caeca (C), large intestine (LI) and cloaca (CL) of turkeys at 6, 10 and 16 weeks of age. Eight turkeys were dissected within each age category and the contents of the SI, C, LI and CL were harvested. 16S rDNA based QPCR was performed on all samples and samples for the 4 locations within 3 birds/age group were sequenced using ion torrent-based sequencing of the 16S rDNA. Sequencing data showed on a genus level, an abundance of Lactobacillus, Streptococcus and Clostridium XI (38.2, 28.1 and 13.0% respectively) irrespective of location and age. The caeca exhibited the greatest microbiome diversity throughout the development of the turkey. PICRUSt data predicted an array of bacterial function, with most differences being apparent in the caeca of the turkeys as they matured. QPCR revealed that the caeca within 10 week old birds, contained the most Campylobacter spp. Understanding the microbial ecology of the turkey gastrointestinal tract is essential in terms of understanding production efficiency and in order to develop novel strategies for targeting Campylobacter spppublishersversionPeer reviewe

Sex differential in mortality trends of old-aged Danes: a nation wide study of age, period and cohort effects

Objective Over the last half century the mortality rates in Denmark for females above age 80 have declined dramatically whereas the decline for males have been modest, resulting in a change in sex-ratio for centenarians from 2 to 5. Here we investigate whether this mortality pattern is mainly explained by period effects, cohort effects or both. This can provide clues for where to search for causes behind the changes in sex differential in mortality seen in many Western countries during the last decades. Methods Age-period-cohort study of mortality for all Danish women and men aged 79–98 during the period 1949–2006. Outcome measures Relative risks for deaths and second order differences for exploration of the nonlinear variation. Results Both the overall trends in mortality differences and the fluctuations in mortality for both men and women were better explained by period effects than by cohort effects. The observed rates were better described by the age, period and cohort model than by other models. Conclusions Our results suggest that causes for both the overall increased difference in mortality and the short term fluctuations in mortality rates are primarily to be found in the period dimension. Cohort effects on the mortality of the oldest Danish women and men played a significant but minor role compared to period effects

Post-Transcriptional Regulation of Cadherin-11 Expression by GSK-3 and β-Catenin in Prostate and Breast Cancer Cells

The cell-cell adhesion molecule cadherin-11 is important in embryogenesis and bone morphogenesis, invasion of cancer cells, lymphangiogenesis, homing of cancer cells to bone, and rheumatoid arthritis. However, very little is known about the regulation of cadherin-11 expression.Here we show that cell density and GSK-3beta regulate cadherin-11 levels in cancer cells. Inactivation of GSK3beta with lithium chloride or the GSK3 inhibitor BIO and GSK3beta knockdown with siRNA repressed cadherin-11 mRNA and protein levels. RNA Polymerase II chromatin immunoprecipitation experiments showed that inhibition of GSK3 does not affect cadherin-11 gene transcription. Although the cadherin-11 3'UTR contains putative microRNA target sites and is regulated by Dicer, its stability is not regulated by GSK3 inhibition or density. Our data show that GSK3beta regulates cadherin-11 expression in two ways: first a beta-catenin-independent regulation of cadherin-11 steady state mRNA levels, and second a beta-catenin-dependent effect on cadherin-11 3'UTR stability and protein translation.Cadherin-11 mRNA and protein levels are regulated by the activity of GSK3beta and a significant degree of this regulation is exerted by the GSK3 target, beta-catenin, at the level of the cadherin-11 3'UTR

Twist1 Directly Regulates Genes That Promote Cell Proliferation and Migration in Developing Heart Valves

Twist1, a basic helix-loop-helix transcription factor, is expressed in mesenchymal precursor populations during embryogenesis and in metastatic cancer cells. In the developing heart, Twist1 is highly expressed in endocardial cushion (ECC) valve mesenchymal cells and is down regulated during valve differentiation and remodeling. Previous studies demonstrated that Twist1 promotes cell proliferation, migration, and expression of primitive extracellular matrix (ECM) molecules in ECC mesenchymal cells. Furthermore, Twist1 expression is induced in human pediatric and adult diseased heart valves. However, the Twist1 downstream target genes that mediate increased cell proliferation and migration during early heart valve development remain largely unknown. Candidate gene and global gene profiling approaches were used to identify transcriptional targets of Twist1 during heart valve development. Candidate target genes were analyzed for evolutionarily conserved regions (ECRs) containing E-box consensus sequences that are potential Twist1 binding sites. ECRs containing conserved E-box sequences were identified for Twist1 responsive genes Tbx20, Cdh11, Sema3C, Rab39b, and Gadd45a. Twist1 binding to these sequences in vivo was determined by chromatin immunoprecipitation (ChIP) assays, and binding was detected in ECCs but not late stage remodeling valves. In addition identified Twist1 target genes are highly expressed in ECCs and have reduced expression during heart valve remodeling in vivo, which is consistent with the expression pattern of Twist1. Together these analyses identify multiple new genes involved in cell proliferation and migration that are differentially expressed in the developing heart valves, are responsive to Twist1 transcriptional function, and contain Twist1-responsive regulatory sequences

Interface engineering of quantum Hall effects in digital transition metal oxide heterostructures

Topological insulators are characterized by a nontrivial band topology driven by the spin-orbit coupling. To fully explore the fundamental science and application of topological insulators, material realization is indispensable. Here we predict, based on tight-binding modeling and first-principles calculations, that bilayers of perovskite-type transition-metal oxides grown along the [111] crystallographic axis are potential candidates for two-dimensional topological insulators. The topological band structure of these materials can be fine-tuned by changing dopant ions, substrates, and external gate voltages. We predict that LaAuO$_3$ bilayers have a topologically-nontrivial energy gap of about 0.15 eV, which is sufficiently large to realize the quantum spin-Hall effect at room temperature. Intriguing phenomena, such as fractional quantum Hall effect, associated with the nearly-flat topologically-nontrivial bands found in $e_g$ systems are also discussed.Comment: Main text 11 pages with 4 figures and 1 table. Supplementary materials 4 pages with 2 figure