Draft Genome Sequence of the Caffeine-Degrading Methylotroph Methylorubrum populi Pinkel.

A pink-pigmented facultative methylotroph, Methylorubrum populi Pinkel, was isolated from compost by selective enrichment with caffeine (3,5,7-trimethylxanthine) as the sole carbon, nitrogen, and energy source. We report here its high-quality draft genome sequence, assembled in 35 contigs totaling 5,630,907 bp. We identified 5,681 protein-coding sequences, including those putatively involved in caffeine degradation

An Investigation of the Ability of Antipsoriatic Drugs to Inhibit Calmodulin Activity: A Possible Mode of Action of Dithranol (Anthralin)

Epidermal calmodulin (CaM) has been reported to be elevated in psoriasis and to decrease following clearance of psoriasis with treatment. We set out to investigate whether any of the principle drugs used in the treatment of psoriasis had inherent CaM antagonist activity. Utilizing a CaM-activated phosphodiesterase we have demonstrated that even at very high concentrations, the systemic drugs etretinate, methotrexate, and 8-methoxypsoralen, and the topical agents hydrocortisone and crude coal tar showed minimal CaM inhibitory activity. Dithranol (anthralin), however, whether freshly prepared or oxidized, produced substantial inhibition of CaM activity and was demonstrated to be a potent competitive antagonist of CaM, suggesting another possible therapeutic mode of action of dithranol in psoriasis

Serological detection of infection with canine distemper virus, canine parvovirus and canine adenovirus in communal dogs from Zimbabwe

Domestic dogs are common amongst communities in sub-Saharan Africa and may serve as important reservoirs for infectious agents that may cause diseases in wildlife. Two agents of concern are canine parvovirus (CPV) and canine distemper virus (CDV), which may infect and cause disease in large carnivore species such as African wild dogs and African lions, respectively. The impact of domestic dogs and their diseases on wildlife conservation is increasing in Zimbabwe, necessitating thorough assessment and implementation of control measures. In this study, domestic dogs in north-western Zimbabwe were evaluated for antibodies to CDV, CPV, and canine adenovirus (CAV). These dogs were communal and had no vaccination history. Two hundred and twenty-five blood samples were collected and tested using a commercial enzyme-linked immunosorbent assay (ELISA) for antibodies to CPV, CDV, and CAV. Of these dogs, 75 (34%) had detectable antibodies to CDV, whilst 191 (84%) had antibodies to CPV. Antibodies to canine adenovirus were present in 28 (13%) dogs. Canine parvovirus had high prevalence in all six geographic areas tested. These results indicate that CPV is circulating widely amongst domestic dogs in the region. In addition, CDV is present at high levels. Both pathogens can infect wildlife species. Efforts for conservation of large carnivores in Zimbabwe must address the role of domestic dogs in disease transmission

Drug-responsive autism phenotypes in the 16p11.2 deletion mouse model: a central role for gene-environment interactions

There are no current treatments for autism, despite its high prevalence. Deletions of chromosome 16p11.2 dramatically increase risk for autism, suggesting that mice with an equivalent genetic rearrangement may offer a valuable model for the testing of novel classes of therapeutic drug. 16p11.2 deletion (16p11.2 DEL) mice and wild-type controls were assessed using an ethological approach, with 24 h monitoring of activity and social interaction of groups of mice in a home-cage environment. The ability of the excitation/inhibition modulator N-acetyl cysteine (NAC) and the 5-HT1B/1D/1F receptor agonist eletriptan to normalise the behavioural deficits observed was tested. 16p11.2 DEL mice exhibited largely normal behaviours, but, following the stress of an injection, showed hyperlocomotion, reduced sociability, and a strong anxiolytic phenotype. The hyperactivity and reduced sociability, but not the suppressed anxiety, were effectively attenuated by both NAC and eletriptan. The data suggest that 16p11.2 DEL mice show an autism-relevant phenotype that becomes overt after an acute stressor, emphasising the importance of gene-environmental interactions in phenotypic analysis. Further, they add to an emerging view that NAC, or 5-HT1B/1D/1F receptor agonist treatment, may be a promising strategy for further investigation as a future treatment

The effect of exenatide on cardiovascular risk markers in women with polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is associated with an adverse cardiovascular risk profile including a prothrombotic state. Exenatide has been shown to be effective at improving insulin sensitivity and weight loss in PCOS; therefore this study was undertaken to assess its effects on weight, endothelial function, inflammatory markers, and fibrin structure/function in overweight/obese women with PCOS.Methods: Thirty overweight/obese anovulatory women with all 3 Rotterdam criteria received exenatide 5 mcg bd for 4 weeks then 10 mcg bd for 12 weeks. The primary outcome was change in weight; secondary outcomes were changes in endothelial function [Reactive Hyperemia-Peripheral Arterial Tonometry (RH-PAT)], serum endothelial markers (ICAM-1, VCAM-1, E-selectin, and P-selectin), change in inflammation (hsCRP), and alteration in clot structure and function [maximum absorbance (MA), and time from full clot formation to 50% lysis (LT)].Results: Twenty patients completed the study. Exenatide reduced weight 111.8 ± 4.8 to 108.6 ± 4.6 kg p = 0.003. Serum endothelial markers changed with a reduction in ICAM-1 (247.2 ± 12.9 to 231.3 ± 11.5 ng/ml p = 0.02), p-selectin (101.1 ± 8.2 to 87.4 ± 6.6 ng/ml p = 0.01), and e-selectin (38.5 ± 3.3 to 33.6 ± 2.6 ng/ml p = 0.03), without an overt change in endothelial function. Inflammation improved (CRP; 8.5 ± 1.4 to 5.6 ± 0.8 mmol/L p = 0.001), there was a reduction in clot function (LT; 2,987 ± 494 to 1,926 ± 321 s p = 0.02) but not clot structure.Conclusion: Exenatide caused a 3% reduction in weight, improved serum markers of endothelial function, inflammation, and clot function reflecting an improvement in cardiovascular risk indices in these women with PCOS. This suggests exenatide could be an effective treatment for obese women with PCOS

Indirect crustal contamination: evidence from isotopic and chemical disequilibria in minerals from alkali basalts and nephelinites from northern Tanzania

 Alkali basalts and nephelinites from the volcanic province of northern Tanzania contain pyroxene and nepheline that show evidence for chemical and/or isotopic disequilibria with their host magmas. Olivine, pyroxene, nepheline and plagioclase all appear to be partially xenocrystic in origin. Five whole rock/mineral separate pairs have been analyzed for Sr, Nd, and Pb isotopic compositions. The 206 Pb/ 204 Pb ratios are distinct by as much as 20.94 (whole rock) vs. 19.10 (clinopyroxene separate). The Sr and Nd isotopic disequilibria vary from insignificant in the case of nepheline, to Δ 87 Sr/ 86 Sr of 0.0002 and Δɛ Nd of 0.7 in the case of clinopyroxene. The mineral chemistry of 25 samples indicates the ubiquitous presence of minerals that did not crystallize from a liquid represented by the host rock. The northern Tanzanian magmas are peralkaline and exhibit none of the xenocrystic phases expected from crustal assimilation. The disequilibria cannot be the result of mantle source variations. Rather the xenocrystic phases present appear to have been derived from earlier alkali basaltic rocks or magmas that were contaminated by the crust. Material from this earlier magma was then mixed with batches of magma that subsequently erupted on the surface. Disequilibrium in volcanic rocks has potentially serious consequences for the use of whole rock data to identify source reservoirs. However, mass balance calculations reveal that the 206 Pb/ 204 Pb isotopic compositions of the erupted lavas were changed by less than 0.25% as a result of this indirect crustal contamination.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42220/1/410-125-4-277_61250277.pd

Resource competition drives an invasion-replacement event among shrew species on an island

Invasive mammals are responsible for the majority of native species extinctions on islands. While most of these extinction events will be due to novel interactions between species (e.g. exotic predators and naive prey), it is more unusual to find incidences where a newly invasive species causes the decline/extinction of a native species on an island when they normally coexist elsewhere in their overlapping mainland ranges. We investigated if resource competition between two insectivorous small mammals was playing a significant role in the rapid replacement of the native pygmy shrew Sorex minutus in the presence of the recently invading greater white-toothed shrew Crocidura russula on the island of Ireland. We used DNA metabarcoding of gut contents from >300 individuals of both species to determine each species' diet and measured the body size (weight and length) during different stages of the invasion in Ireland (before, during and after the species come into contact with one another) and on a French island where both species have long coexisted (acting as a natural ‘control’ site). Dietary composition, niche width and overlap and body size were compared in these different stages. The body size of the invasive C. russula and composition of its diet changes between when it first invades an area and after it becomes established. During the initial stages of the invasion, individual shrews are larger and consume larger sized invertebrate prey species. During later stages of the invasion, C. russula switches to consuming smaller prey taxa that are more essential for the native species. As a result, the level of interspecific dietary overlap increases from between 11% and 14% when they first come into contact with each other to between 39% and 46% after the invasion. Here we show that an invasive species can quickly alter its dietary niche in a new environment, ultimately causing the replacement of a native species. In addition, the invasive shrew could also be potentially exhausting local resources of larger invertebrate species. These subsequent changes in terrestrial invertebrate communities could have severe impacts further downstream on ecosystem functioning and services

Thermally activated resonant tunnelling in GaAs/AlGaAs triple barrier tunnelling structures

A thermally activated resonant tunnelling feature has been observed in the current-voltage characteristics (I(V)) of triple barrier resonant tunnelling structures (TBRTS) due to alignment of the n=1 confined states in the two quantum wells (QWs) within the active region. With rising sample temperature, the tunnelling current of the resonant feature increases in magnitude, showing a small negative differential resistance region which is discernable even at 293K. This behaviour is unique to multiple barrier devices and cannot be observed in conventional double barrier resonant tunnelling structures. Symmetric TBRTS, of nominal well widths 67Å and asymmetric QW, with decreasing second well widths, nominally 64Å to 46Å, have been studied with temperature dependent resonant tunnelling behaviour observed in both symmetric and asymmetric designs. Activation energies have been extracted from Arrhenius plots of the magnitude of the thermally activated peak current for each device design. This activation energy decreases as the second well width is decreased due to alignment occurring at increasingly greater bias and as such at energies closer to the Fermi level in the emitter region of the devices. Experimentally determined activation energies are in good agreement with theoretical values obtained by modelling the device I(V) characteristic