Ab initio electronic structure calculations of solid, solution-processed metallotetrabenzoporphyrins

An ab initio study of the electronic structures of solid metallotetrabenzoporphyrins (MTBPs) utilized in organic transistors and photovoltaics is presented. Bandstructures, densities of states, and orbitals are calculated for H2, Cu, Ni, and Zn core substitutions of the unit cell of solid TBP, as deposited via soluble precursors that are thermally annealed to produce polycrystalline, semiconducting thin-films. While the unit cells of the studied MTBPs are nearly isomorphous, substitution of the core atoms alters the structure of the bands around the energy bandgap and the composition of the densities of states. Cu and Ni core substitutions introduce nearly-dispersionless energy bands near the valence and conduction band edges, respectively, that form acceptor or deep generation/recombination states.Comment: 7 pages, 3 figures, 4 table

Interval gangrene complicating superficial femoral artery stent placement

Interval gangrene—necrosis of tissue proximal to a successful distal revascularization procedure—is an exceeding rare complication. To date, only nine cases have been reported in the literature, and all were secondary to traditional open bypass procedures. We report the first case, to our knowledge, of interval gangrene after endovascular stent placement in the superficial femoral artery. We believe that with the increasing utilization of endovascular techniques to treat limb ischemia, the serious complication of interval gangrene must be revisited. Assessment of collateral circulation, precise stent placement, and the appropriate choice of stents and stent grafts will become increasing important as more and more of these lesions are treated with endovascular techniques

Higher body weight is associated with lower concentrations of progesterone and estrogen in early pregnancy following in vitro fertilization

To evaluate if body weight impacts progesterone and estradiol concentration levels in early pregnancy in women conceiving following single embryo transfer

Hemodynamic and Metabolic Observations Associated with Intracoronary Stenting for Acute Closure Following Percutaneous Transluminal Coronary Angioplasty

Emergency stent implantation appears to be an effective method for restoring antegrade flow in case of an abrupt coronary occlusion during percutaneous transluminal coronary angioplasty (PTCA). In this case report, hemodynamic and metabolic changes throughout abrupt coronary closure and stent implantation were followed in order to study the efficacy of this bail out technique in restoring metabolic and hemodynamic disturbances due to acute coronary occlusion. Copyrigh

Human Frataxin: Iron and Ferrochelatase Binding Surface

The coordinated iron structure and ferrochelatase binding surface of human frataxin have been characterized to provide insight into the protein’s ability to serve as the iron chaperone during heme biosynthesis

Bitopic binding mode of an M1 muscarinic acetylcholine receptor agonist associated with adverse clinical trial outcomes

The realisation of the therapeutic potential of targeting the M1 muscarinic acetylcholine receptor (M1 mAChR) for the treatment of cognitive decline in Alzheimer's disease has prompted the discovery of M1 mAChR ligands showing efficacy in alleviating cognitive dysfunction in both rodents and humans. Among these is GSK1034702, described previously as a potent M1 receptor allosteric agonist, which showed pro-cognitive effects in rodents and improved immediate memory in a clinical nicotine withdrawal test but induced significant side-effects. Here we provide evidence using ligand binding, chemical biology and functional assays to establish that rather than the allosteric mechanism claimed, GSK1034702 interacts in a bitopic manner at the M1 mAChR such that it can concomitantly span both the orthosteric and an allosteric binding site. The bitopic nature of GSK1034702 together with the intrinsic agonist activity and a lack of muscarinic receptor subtype selectivity reported here, all likely contribute to the adverse effects of this molecule in clinical trials. We conclude that these properties, whilst imparting beneficial effects on learning and memory, are undesirable in a clinical candidate due to the likelihood of adverse side effects. Rather, our data supports the notion that "pure" positive allosteric modulators showing selectivity for the M1 mAChR with low levels of intrinsic activity would be preferable to provide clinical efficacy with low adverse responses

Seroconversion of Raccoons Following Two Oral Rabies Vaccination Baiting Strategies

Seroprevalence of rabies virus neutralizing antibodies (rVNA) in raccoons (Procyon lotor) following oral rabies vaccination (ORV) with RABORAL V-RG® in the United States has annually averaged 30% since 1997, a level that is unlikely to successfully interrupt rabies transmission in raccoon populations. A longitudinal ORV zone is maintained in the eastern United States with raccoon variant rabies established east of the zone but absent to the west. However, questions remain regarding the effect of the bait application strategy towards achieving optimal population immunity. We estimated the number of ORV baits/km2 of raccoon home range and calculated rVNA seroprevalence following 2 ORV baiting strategies: cluster baiting (≤10 baits dropped at a time) via helicopter and hand distribution of individual baits at regular intervals along roads and trails in suburban Chattanooga, Tennessee, USA, during fall 2013 and 2014. We applied baits at 75 baits/km2 under both strategies. We established 6 1-km2 cells in each treatment area, and fitted ≤2 raccoons with global positioning system collars in each cell. We trapped and sampled ≤25 raccoons in each study cell pre- and post-ORV application for rVNA analysis. Overall raccoon home range and core area estimates were 80.7 ha and 17.5 ha, respectively (n=36). Average bait application for home ranges (n=32 home ranges that received bait) was 80.9 baits/km2 for helicopter baiting and 63.6 baits/km2 for hand baiting sites. Average bait application for core areas was 104.7 baits/km2 for helicopter baiting and 69.2 baits/ km2 for hand baiting sites. All home ranges were baited in both treatment areas, whereas 10/18 and 13/14 core areas were baited in the helicopter and hand distribution sites, respectively. Overall, helicopter cluster ORV delivered more baits/km2 of raccoon home range than hand distribution but was less effective in reaching core areas. Seroprevalence did not change as a function of baiting strategy (helicopter vs. hand baiting). The average overall increase in seroprevalence following ORV application was 8.9%. Evaluation of additional strategies are needed because both methods failed to achieve herd immunity necessary to disrupt rabies transmission in raccoons

Fox Squirrels (Sciurus niger) Develop West Nile Virus Viremias Sufficient for Infecting Select Mosquito Species

The West Nile virus (WNV) viremia and shedding profiles of 11 adult fox squirrels (Sciurus niger) infected by needle inoculation or mosquito bite were characterized. Daily mean titers (95% confidence intervals) for all squirrels on days 1 through 6 postexposure (p.e.) were: 10(1.7 (1.32.1)), 10(4.4 (4.04.8)), 10(5.3 (5.05.6)), 10(4.4 (3.94.9)), 10(2.7 (2.03.4)), and 10(1.1 (0.52.1)) plaque-forming units (PFU)/mL. The highest WNV serum titers of individual squirrels infected by needle inoculation or mosquito bite ranged from 10(4.5) to 10(6.1) and from 10(5.1) to 10(5.3) PFU/mL, respectively. Nine (82%) squirrels, including all 4 squirrels infected by mosquito bite, had WNV serum titers \u3e or =10(5.1) PFU/mL that persisted on average for 1.6 +/- 0.3 days. Infection and dissemination rates of Culex pipiens (L.) that fed on squirrels with serum titers of 10(4.4 +/- 0.1) PFU/mL were 56% and 13%, respectively. Both of these rates increased to over 80% when fed on squirrels with a mean WNV titer of 10(5.5 +/- 0.1) PFU/mL. Infection and dissemination also occurred in Aedes triseriatus (Say) but at a much lower rate. WNV was isolated from the oral and rectal cavities of all squirrels and from urine that was opportunistically collected from 5 squirrels. The largest quantity of WNV recovered from swabs of the oral cavity and urine was 10(3.1) PFU. The longest periods after exposure that WNV was isolated from the oral cavity and urine from a squirrel were 22 and 17 days p.e., respectively. WNV RNA was also detected in kidney tissue in 1 squirrel 29 days p.e., suggesting that fox squirrels can be persistently infected. Collectively these observations provide further evidence that squirrels can contribute to the natural history and epidemiology of WNV, especially in peridomestic environments

Species richness, but not phylogenetic diversity, influences community biomass production and temporal stability in a re‐examination of 16 grassland biodiversity studies

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111813/1/fec12432.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/111813/2/fec12432-sup-0002-Suppinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/111813/3/fec12432-sup-0001-LaySummary.pd

Genomic Distribution and Inter-Sample Variation of Non-CpG Methylation across Human Cell Types

DNA methylation plays an important role in development and disease. The primary sites of DNA methylation in vertebrates are cytosines in the CpG dinucleotide context, which account for roughly three quarters of the total DNA methylation content in human and mouse cells. While the genomic distribution, inter-individual stability, and functional role of CpG methylation are reasonably well understood, little is known about DNA methylation targeting CpA, CpT, and CpC (non-CpG) dinucleotides. Here we report a comprehensive analysis of non-CpG methylation in 76 genome-scale DNA methylation maps across pluripotent and differentiated human cell types. We confirm non-CpG methylation to be predominantly present in pluripotent cell types and observe a decrease upon differentiation and near complete absence in various somatic cell types. Although no function has been assigned to it in pluripotency, our data highlight that non-CpG methylation patterns reappear upon iPS cell reprogramming. Intriguingly, the patterns are highly variable and show little conservation between different pluripotent cell lines. We find a strong correlation of non-CpG methylation and DNMT3 expression levels while showing statistical independence of non-CpG methylation from pluripotency associated gene expression. In line with these findings, we show that knockdown of DNMTA and DNMT3B in hESCs results in a global reduction of non-CpG methylation. Finally, non-CpG methylation appears to be spatially correlated with CpG methylation. In summary these results contribute further to our understanding of cytosine methylation patterns in human cells using a large representative sample set