Influence of supercoiling on the disruption of dsDNA

We propose that supercoiling energizes double-stranded DNA (dsDNA) so as to facilitate thermal fluctuations to an unzipped state. We support this with a model of two elastic rods coupled via forces that represent base pair interactions. Supercoiling is shown to lead to a spatially localized higher energy state in a small region of dsDNA consisting of a few base pairs. This causes the distance between specific base pairs to be extended, enhancing the thermal probability for their disruption. Our theory permits the development of an analogy between this unzipping transition and a second order phase transition, for which the possibility of a new set of critical exponents is identified

Anorexia Nervosa, Major Depression, and Suicide Attempts: Shared Genetic Factors

We evaluated the extent to which genetic and environmental factors influenced anorexia nervosa (AN), major depressive disorder (MDD), and suicide attempts (SA). Participants were 6,899 women from the Swedish Twin study of Adults Genes and Environment. A Cholesky decomposition assessed independent and overlapping genetic and environmental contributions to AN, MDD, and SA. Genetic factors accounted for a substantial amount of liability to all three traits; unique environmental factors accounted for most of the remaining liability. Shared genetic factors may underlie the co-expression of these traits. Results underscore the importance of assessing for signs of suicide among individuals with AN

Evaluation of intravenous voriconazole in patients with compromised renal function

BACKGROUND: Incorporation of the solubilizing excipient, sulfobutylether-β-cyclodextrin (SBECD), in the intravenous (IV) formulation of voriconazole has resulted in the recommendation that this formulation be used with caution in patients with creatinine clearances (Clcr) \u3c 50 mL/min. This study evaluated the safety of IV voriconazole compared with two other IV antifungals not containing SBECD in patients with compromised renal function. METHODS: A total of 128 patients aged 11-93 years who had a baseline Clcr \u3c 50 mL/min between January 1, 2007 and December 31, 2010 were identified from a database of a university-affiliated inpatient healthcare system; of these, 55 patients received caspofungin, 54 patients received fluconazole, and 19 patients received voriconazole. Changes in serum creatinine (Scr) and Clcr levels while on therapy were compared with baseline values and between groups. RESULTS: The groups had similar characteristics apart from the larger proportion of females that received fluconazole. Baseline Scr was higher in those receiving caspofungin, but maximal increases of Scr and decreases in Clcr were greatest for the fluconazole group. Acute kidney injury (AKI), assessed by RIFLE criteria, was more frequent in the fluconazole vs. the caspofungin group (p \u3c 0.01); incidence of AKI in the voriconazole group was not significantly different than found in the other two groups. The infecting organism was a predictor of AKI and formulation with SBECD was not. CONCLUSIONS: Treatment of fungal infections in patients with compromised renal function with an SBECD-containing antifungal agent was not associated with AKI in clinical practice. Since the infecting organism was associated with AKI, decision on which antifungal to use should be determined by susceptibilities to the organism and not the incorporation of SBECD in the IV formulation

A retinoblastoma allele that is mutated at its common E2F interaction site inhibits cell proliferation in gene-targeted mice

The retinoblastoma protein (pRB) is best known for regulating cell proliferation through E2F transcription factors. In this report, we investigate the properties of a targeted mutation that disrupts pRB interactions with the transactivation domain of E2Fs. Mice that carry this mutation endogenously (Rb1δG) are defective for pRB-dependent repression of E2F target genes. Except for an accelerated entry into S phase in response to serum stimulation, cell cycle regulation in Rb1δG/δG mouse embryonic fibroblasts (MEFs) strongly resembles that of the wild type. In a serum deprivation-induced cell cycle exit, Rb1δG/δG MEFs display a magnitude of E2F target gene derepression similar to that of Rb1-/- cells, even though Rb1δG/δG cells exit the cell cycle normally. Interestingly, cell cycle arrest in Rb1δG/δG MEFs is responsive to p16 expression and gamma irradiation, indicating that alternate mechanisms can be activated in G1 to arrest proliferation. Some Rb1δG/δG mice die neonatally with a muscle degeneration phenotype, while the others live a normal life span with no evidence of spontaneous tumor formation. Most tissues appear histologically normal while being accompanied by derepression of pRB-regulated E2F targets. This suggests that non- E2F-, pRB-dependent pathways may have a more relevant role in proliferative control than previously identified. © 2014, American Society for Microbiology

Modelling spatiotemporal patterns of dubas bug infestations on date palms in northern Oman: A geographical information system case study

The aim of this paper is to demonstrate how Geographical Information System (GIS) can be used effectively to study infestations of Dubas bug (DB), 'Ommatissus lybicus' Bergevin, in date palm ('Phoenix dactylifera L.') that occurred in northern Oman during 2006-2015. The ability to produce geographical and spatiotemporal layers using GIS is expected to serve an important role in both monitoring and surveillance of DB infestation and its impact in the study area. By using of spatial analytic and geostatistical functions in ArcGIS 10.3™, data that quantified the infestation levels of DB over a 10-year period from 2006 to 2015 were used to map and model the risk of infestation spatiotemporally. We modelled the spatiotemporal risk of DB infestation by performing hotspot analysis using the Getis-Ord statistic, Gi*. Our results show that annual hotspots over the study period were mainly concentrated in the mountain plains, particularly where farms are located between gradient elevations. Furthermore, the distribution pattern varied considerably with time and space. These results demonstrated the usefulness in following annual DB infestation patterns by studying the average seasonal infestation levels and distribution of hotspots as they can facilitate the allocation of resources for the treatment of infestations and allow for more effective monitoring of its influence on date palm trees