Getting DNA twist rigidity from single molecule experiments

We use an elastic rod model with contact to study the extension versus rotation diagrams of single supercoiled DNA molecules. We reproduce quantitatively the supercoiling response of overtwisted DNA and, using experimental data, we get an estimation of the effective supercoiling radius and of the twist rigidity of B-DNA. We find that unlike the bending rigidity, the twist rigidity of DNA seems to vary widely with the nature and concentration of the salt buffer in which it is immerged

Genetic Variation and Population Substructure in Outbred CD-1 Mice: Implications for Genome-Wide Association Studies

Outbred laboratory mouse populations are widely used in biomedical research. Since little is known about the degree of genetic variation present in these populations, they are not widely used for genetic studies. Commercially available outbred CD-1 mice are drawn from an extremely large breeding population that has accumulated many recombination events, which is desirable for genome-wide association studies. We therefore examined the degree of genome-wide variation within CD-1 mice to investigate their suitability for genetic studies. The CD-1 mouse genome displays patterns of linkage disequilibrium and heterogeneity similar to wild-caught mice. Population substructure and phenotypic differences were observed among CD-1 mice obtained from different breeding facilities. Differences in genetic variation among CD-1 mice from distinct facilities were similar to genetic differences detected between closely related human populations, consistent with a founder effect. This first large-scale genetic analysis of the outbred CD-1 mouse strain provides important considerations for the design and analysis of genetic studies in CD-1 mice.</p

Gauge vortex dynamics at finite mass of bosonic fields

The simple derivation of the string equation of motion adopted in the nonrelativistic case is presented, paying the special attention to the effects of finite masses of bosonic fields of an Abelian Higgs model. The role of the finite mass effects in the evaluation of various topological characteristics of the closed strings is discussed. The rate of the dissipationless helicity change is calculated. It is demonstrated how the conservation of the sum of the twisting and writhing numbers of the string is recovered despite the changing helicity.Comment: considerably revised to include errata to journal versio

A human cell atlas of fetal gene expression

The gene expression program underlying the specification of human cell types is of fundamental interest. We generated human cell atlases of gene expression and chromatin accessibility in fetal tissues. For gene expression, we applied three-level combinatorial indexing to >110 samples representing 15 organs, ultimately profiling ~4 million single cells. We leveraged the literature and other atlases to identify and annotate hundreds of cell types and subtypes, both within and across tissues. Our analyses focused on organ-specific specializations of broadly distributed cell types (such as blood, endothelial, and epithelial), sites of fetal erythropoiesis (which notably included the adrenal gland), and integration with mouse developmental atlases (such as conserved specification of blood cells). These data represent a rich resource for the exploration of in vivo human gene expression in diverse tissues and cell types

An evaluation and comparison of conservation guidelines for an at-risk migratory songbird

For at-risk wildlife species, it is important to consider conservation within the process of adaptive management. Golden-winged Warblers (Vermivora chrysoptera) are Neotropical migratory songbirds that are experiencing long-term population declines due in part to the loss of early-successional nesting habitat. Recently-developed Golden-winged Warbler habitat management guidelines are being implemented by USDA: Natural Resource Conservation Service (2014) and its partners through the Working Lands For Wildlife (WLFW) program. During 2012–2014, we studied the nesting ecology of Golden-winged Warblers in managed habitats of the eastern US that conformed to WLFW conservation practices. We evaluated five NRCS “management scenarios” with respect to nesting success and attainment of recommended nest site vegetation conditions outlined in the Golden-winged Warbler breeding habitat guidelines. Using estimates of territory density, pairing rate, nest survival, and clutch size, we also estimated fledglingproductivity (number of fledglings/ha) for each management scenario. In general, Golden-winged Warbler nest survival declined as each breeding season advanced, but nest survival was similar across management scenarios. Within each management scenario, vegetation variables had little influence on nest survival. Still, percent Rubus cover and density of \u3e2 m tall shrubs were relevant in some management scenarios. All five management scenarios rarely attained recommended levels of nest site vegetation conditions for Golden-winged, yet nest survival was high. Fledgling productivity estimates for each management scenario ranged from 2.1 to 8.6 fledglings/10 hectares. Our results indicate that targeted habitat management for Golden-winged Warblers using a variety of management techniques on private lands has the capability to yield high nest survival and fledgling productivity, and thus have the potential to contribute to the species recovery

Uncemented and cemented primary total hip arthroplasty in the Swedish Hip Arthroplasty Register: Evaluation of 170,413 operations

BACKGROUND AND PURPOSE: Since the introduction of total hip arthroplasty (THA) in Sweden, both components have most commonly been cemented. A decade ago the frequency of uncemented fixation started to increase, and this change in practice has continued. We therefore analyzed implant survival of cemented and uncemented THA, and whether the modes of failure differ between the two methods of fixation. PATIENTS AND METHODS: All patients registered in the Swedish Hip Arthroplasty Register between 1992 and 2007 who received either totally cemented or totally uncemented THA were identified (n = 170,413). Kaplan-Meier survival analysis with revision of any component, and for any reason, as the endpoints was performed. Cox regression models were used to calculate risk ratios (RRs) for revision for various reasons, adjusted for sex, age, and primary diagnosis. RESULTS: Revision-free 10-year survival of uncemented THA was lower than that of cemented THA (85% vs. 94%, p &lt; 0.001). No age or diagnosis groups benefited from the use of uncemented fixation. Cox regression analysis confirmed that uncemented THA had a higher risk of revision for any reason (RR = 1.5, 95% CI: 1.4-1.6) and for aseptic loosening (RR = 1.5, CI: 1.3-1.6). Uncemented cup components had a higher risk of cup revision due to aseptic loosening (RR = 1.8, CI: 1.6-2.0), whereas uncemented stem components had a lower risk of stem revision due to aseptic loosening (RR = 0.4, CI: 0.3-0.5) when compared to cemented components. Uncemented stems were more frequently revised due to periprosthetic fracture during the first 2 postoperative years than cemented stems (RR = 8, CI: 5-14). The 5 most common uncemented cups had no increased risk of revision for any reason when compared with the 5 most commonly used cemented cups (RR = 0.9, CI: 0.6-1.1). There was no significant difference in the risk of revision due to infection between cemented and uncemented THA. INTERPRETATION: Survival of uncemented THA is inferior to that of cemented THA, and this appears to be mainly related to poorer performance of uncemented cups. Uncemented stems perform better than cemented stems; however, unrecognized intraoperative femoral fractures may be an important reason for early failure of uncemented stems. The risk of revision of the most common uncemented cup designs is similar to that of cemented cups, indicating that some of the problems with uncemented cup fixation may have been solved.Open Access - This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the source is credited

Variables associated with nest survival of Golden-winged Warblers (Vermivora chrysoptera) among vegetation communities commonly used for nesting

Among shrubland- and young forest-nesting bird species in North America, Golden-winged Warblers (Vermivora chrysoptera) are one of the most rapidly declining partly because of limited nesting habitat. Creation and management of high quality vegetation communities used for nesting are needed to reduce declines. Thus, we examined whether common characteristics could be managed across much of the Golden-winged Warbler’s breeding range to increase daily survival rate (DSR) of nests. We monitored 388 nests on 62 sites throughout Minnesota, Wisconsin, New York, North Carolina, Pennsylvania, Tennessee, and West Virginia. We evaluated competing DSR models in spatial-temporal (dominant vegetation type, population segment, state, and year), intraseasonal (nest stage and time-within-season), and vegetation model suites. The best-supported DSR models among the three model suites suggested potential associations between daily survival rate of nests and state, time-within-season, percent grass and Rubus cover within 1 m of the nest, and distance to later successional forest edge. Overall, grass cover (negative association with DSR above 50%) and Rubus cover (DSR lowest at about 30%) within 1 m of the nest and distance to later successional forest edge (negative association with DSR) may represent common management targets across our states for increasing Golden-winged Warbler DSR, particularly in the Appalachian Mountains population segment. Context-specific adjustments to management strategies, such as in wetlands or areas of overlap with Blue-winged Warblers (Vermivora cyanoptera), may be necessary to increase DSR for Golden-winged Warblers

Spatiotemporal expansion of primary progenitor zones in the developing human cerebellum

We present histological and molecular analyses of the developing human cerebellum from 30 days after conception to 9 months after birth. Differences in developmental patterns between humans and mice include spatiotemporal expansion of both ventricular and rhombic lip primary progenitor zones to include subventricular zones containing basal progenitors. The human rhombic lip persists longer through cerebellar development than in the mouse and undergoes morphological changes to form a progenitor pool in the posterior lobule, which is not seen in other organisms, not even in the nonhuman primate the macaque. Disruptions in human rhombic lip development are associated with posterior cerebellar vermis hypoplasia and Dandy-Walker malformation. The presence of these species-specific neural progenitor populations refines our insight into human cerebellar developmental disorders