Molecular evolution of cytochrome \u3ci\u3eb\u3c/i\u3e in high- and low-altitude deer mice (genus \u3ci\u3ePeromyscus\u3c/i\u3e)

Patterns of amino-acid polymorphism in human mitochondrial genes have been interpreted as evidence for divergent selection among populations that inhabit climatically distinct environments. If similar patterns are mirrored in other broadly distributed mammalian species, then adaptive modifications of mitochondrial protein function may be detected in comparisons among locally adapted populations of a single wide-ranging species, or among closely related species that have adapted to different environments. Here, we test for evidence of positive selection on cytochrome b variation within and among species of the ecologically diverse rodent genus Peromyscus. We used likelihood-based comparisons of synonymous and nonsynonymous substitution rates to test for evidence of divergent selection between high- and low-altitude haplogroups of the deer mouse, Peromyscus maniculatus. We also tested for evidence of divergent selection among different species of Peromyscus that inhabit different thermal environments. In contrast to the purported evidence for positive selection on mitochondrial proteins in humans and other nonhuman mammals, results of our tests suggest that the evolution of cytochrome b in Peromyscus is chiefly governed by purifying selection

Molecular evolution of cytochrome \u3ci\u3eb\u3c/i\u3e in high- and low-altitude deer mice (genus \u3ci\u3ePeromyscus\u3c/i\u3e)

Patterns of amino-acid polymorphism in human mitochondrial genes have been interpreted as evidence for divergent selection among populations that inhabit climatically distinct environments. If similar patterns are mirrored in other broadly distributed mammalian species, then adaptive modifications of mitochondrial protein function may be detected in comparisons among locally adapted populations of a single wide-ranging species, or among closely related species that have adapted to different environments. Here, we test for evidence of positive selection on cytochrome b variation within and among species of the ecologically diverse rodent genus Peromyscus. We used likelihood-based comparisons of synonymous and nonsynonymous substitution rates to test for evidence of divergent selection between high- and low-altitude haplogroups of the deer mouse, Peromyscus maniculatus. We also tested for evidence of divergent selection among different species of Peromyscus that inhabit different thermal environments. In contrast to the purported evidence for positive selection on mitochondrial proteins in humans and other nonhuman mammals, results of our tests suggest that the evolution of cytochrome b in Peromyscus is chiefly governed by purifying selection

Variation in Flight Morphology in a Damselfly with Female-Limited Polymorphism

Background: Female-limited colour polymorphisms occur in many species of dragonflies and damselflies. Often one female morph appears male-like in coloration (androchromes) whereas one or more others are distinct from males (gynochromes). These androchromes are hypothesized to be male-mimics, thereby avoiding the harassment of excessive male mating attempts. Organism: The damselfly Ischnura ramburii, Rambur’s forktail, is a widespread New World species with androchrome and gynochrome females. It was introduced to the Hawaiian Islands in the mid-1970s and females were thought to be exclusively gynochromatic there. Questions: How do males and females differ in their flight apparatus? Do females with different colour morphologies also differ in flight morphology? Hypothesis: Because male-like coloration is sometimes associated with male-like flight behaviours, androchrome females should have more male-like wings than gynochrome females. Methods: We caught individuals of I. ramburii in the field from seven populations on three of the Hawaiian Islands and three populations in Texas (part of its native range). Using digitized wing and body images, we compared body size, wing size, and wing shape between sexes, between female morphs, and among geographic regions. Results: Male I. ramburii are smaller than females and have smaller, more slender wings. Although androchromes are absent from the Big Island of Hawaii, both androchrome and gynochrome females are common on Oahu and Kauai. Androchrome females are indistinguishable from gynochrome females in all aspects of their flight apparatus except for forewing size, which is smaller than that of gynochromes and thus more-male like. Wing shape and size vary geographically. Body- and wing-size differences between males and females are consistent across regions, although the degree and direction of sexual dimorphism in wing shape are not

Localized High-Concentration Electrolytes Get More Localized Through Micelle-Like Structures

Liquid electrolytes in batteries are typically treated as macroscopically homogeneous ionic transport media despite having complex chemical composition and atomistic solvation structures, leaving a knowledge gap of microstructural characteristics. Here, we reveal a unique micelle-like structure in a localized high-concentration electrolyte (LHCE), in which the solvent acts as a surfactant between an insoluble salt in diluent. The miscibility of the solvent with the diluent and simultaneous solubility of the salt results in a micelle-like structure with a smeared interface and an increased salt concentration at the centre of the salt-solvent clusters that extends the salt solubility. These intermingling miscibility effects have temperature dependencies, wherein an exemplified LHCE peaks in localized cluster salt concentration near room temperature and is utilized to form a stable solid-electrolyte interphase (SEI) on Li-metal anode. These findings serve as a guide to predicting a stable ternary phase diagram and connecting the electrolyte microstructure with electrolyte formulation and formation protocols to form stable SEI for enhanced battery cyclability

Gfi1aa and Gfi1b set the pace for primitive erythroblast differentiation from hemangioblasts in the zebrafish embryo

The transcriptional repressors G fi 1(a) and G fi 1b are epigenetic regulators with unique and overlapping roles in hematopoiesis. In different contexts, G fi 1 and G fi 1b restrict or promote cell proliferation, prevent apoptosis, in fl uence cell fate decisions, and are essential for terminal differentiation. Here, we show in primitive red blood cells (prRBCs) that they can also set the pace for cellular differentiation. In zebra fi sh, prRBCs express 2 of 3 zebra fi sh G fi 1/ 1bparalogs,G fi 1aaandG fi 1b.Therecentlyidenti fi edzebra fi sh gfi1aa gene trap allele qmc551 drives erythroid green fl uorescent protein (GFP) instead of G fi 1aa expression, yet homozygous carriers have normal prRBCs. prRBCs display a maturation defect only after splice morpholino-mediated knockdown of G fi 1b in gfi1aa qmc551 homozygous embryos. To study the transcriptome of the G fi 1aa/1b double-depleted cells, we performed an RNA-Seq experi- ment on GFP-positive prRBCs sorted from 20-h our-old embryos that were heterozygous or homozygous for gfi1aa qmc551 ,aswellas wt or morphant for gfi1b .Wesubsequentlycon fi rmed and extended these data in whole-mount in situ hybridization experiments on newly generated single- and double-mutant embryos. Combi ned, the data showed that in the absence of G fi 1aa, the synchronously developing prRBCs were delayed in activating late erythr oid differentiation, as they struggled to suppress early erythroid and endothelial transcripti on programs. The latter highlighted the bipotent natu re of the progenitors from which prRBCs arise. In the absence of G fi 1aa, G fi 1b promoted erythroid differentiation as stepwise loss of wt gfi1b copies progressively delayed G fi 1aa-depleted prRBCs even further, showing that G fi 1aa and G fi 1b together set the pace for prRBC diffe rentiation from hemangioblasts

CONFIDENCE dissemination meeting: summary on the scenario-based workshop

The CONFIDENCE dissemination workshop “Coping with uncertainties for improved modelling and decision making in nuclear emergencies” was held in December 2–5, 2019 (Bratislava, Slovak Republic). About 90 scientists and decision makers attended the workshop. The dissemination workshop allowed the presentation of the CONFIDENCE project results, demonstration of the applicability of the developed methods and tools in interactive discussion sessions and the collection of feedback from the participants. The results were disseminated not only in the form of presentations and posters but also through interactive workshops where all participants were involved in round table working groups. A fictive accidental release scenario taking place at a nuclear power plant was developed and used by each work package in the workshop to provide the basis for interactive sessions and discussions

Finite-element-method (FEM) model generation of time-resolved 3D echocardiographic geometry data for mitral-valve volumetry

INTRODUCTION: Mitral Valve (MV) 3D structural data can be easily obtained using standard transesophageal echocardiography (TEE) devices but quantitative pre- and intraoperative volume analysis of the MV is presently not feasible in the cardiac operation room (OR). Finite element method (FEM) modelling is necessary to carry out precise and individual volume analysis and in the future will form the basis for simulation of cardiac interventions. METHOD: With the present retrospective pilot study we describe a method to transfer MV geometric data to 3D Slicer 2 software, an open-source medical visualization and analysis software package. A newly developed software program (ROIExtract) allowed selection of a region-of-interest (ROI) from the TEE data and data transformation for use in 3D Slicer. FEM models for quantitative volumetric studies were generated. RESULTS: ROI selection permitted the visualization and calculations required to create a sequence of volume rendered models of the MV allowing time-based visualization of regional deformation. Quantitation of tissue volume, especially important in myxomatous degeneration can be carried out. Rendered volumes are shown in 3D as well as in time-resolved 4D animations. CONCLUSION: The visualization of the segmented MV may significantly enhance clinical interpretation. This method provides an infrastructure for the study of image guided assessment of clinical findings and surgical planning. For complete pre- and intraoperative 3D MV FEM analysis, three input elements are necessary: 1. time-gated, reality-based structural information, 2. continuous MV pressure and 3. instantaneous tissue elastance. The present process makes the first of these elements available. Volume defect analysis is essential to fully understand functional and geometrical dysfunction of but not limited to the valve. 3D Slicer was used for semi-automatic valve border detection and volume-rendering of clinical 3D echocardiographic data. FEM based models were also calculated. METHOD: A Philips/HP Sonos 5500 ultrasound device stores volume data as time-resolved 4D volume data sets. Data sets for three subjects were used. Since 3D Slicer does not process time-resolved data sets, we employed a standard movie maker to animate the individual time-based models and visualizations. Calculation time and model size were minimized. Pressures were also easily available. We speculate that calculation of instantaneous elastance may be possible using instantaneous pressure values and tissue deformation data derived from the animated FEM

NMN Deamidase Delays Wallerian Degeneration and Rescues Axonal Defects Caused by NMNAT2 Deficiency In Vivo

Axons require the axonal NAD-synthesizing enzyme NMNAT2 to survive. Injury or genetically induced depletion of NMNAT2 triggers axonal degeneration or defective axon growth. We have previously proposed that axonal NMNAT2 primarily promotes axon survival by maintaining low levels of its substrate NMN rather than generating NAD; however, this is still debated. NMN deamidase, a bacterial enzyme, shares NMN-consuming activity with NMNAT2, but not NAD-synthesizing activity, and it delays axon degeneration in primary neuronal cultures. Here we show that NMN deamidase can also delay axon degeneration in zebrafish larvae and in transgenic mice. Like overexpressed NMNATs, NMN deamidase reduces NMN accumulation in injured mouse sciatic nerves and preserves some axons for up to three weeks, even when expressed at a low level. Remarkably, NMN deamidase also rescues axonal outgrowth and perinatal lethality in a dose-dependent manner in mice lacking NMNAT2. These data further support a pro-degenerative effect of accumulating NMN in axons in vivo. The NMN deamidase mouse will be an important tool to further probe the mechanisms underlying Wallerian degeneration and its prevention.We thank Tim Self, Denise McLean, Ian Ward, and CSI/SLIM for use of imaging facilities and help with tissue processing. This work was funded by a Faculty of Medicine and Health Sciences, University of Nottingham nonclinical senior fellowship (to L.C.); a Marie Curie Intra European Fellowship (project number 301897) within the European Community 7th Framework Programme (to M.D.S. and L.C.); and an Institute Strategic Programme Grant from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) grant MR/N004582/1 (to J.G. and M.P.C.)

Creating Physical 3D Stereolithograph Models of Brain and Skull

The human brain and skull are three dimensional (3D) anatomical structures with complex surfaces. However, medical images are often two dimensional (2D) and provide incomplete visualization of structural morphology. To overcome this loss in dimension, we developed and validated a freely available, semi-automated pathway to build 3D virtual reality (VR) and hand-held, stereolithograph models. To evaluate whether surface visualization in 3D was more informative than in 2D, undergraduate students (n = 50) used the Gillespie scale to rate 3D VR and physical models of both a living patient-volunteer's brain and the skull of Phineas Gage, a historically famous railroad worker whose misfortune with a projectile tamping iron provided the first evidence of a structure-function relationship in brain. Using our processing pathway, we successfully fabricated human brain and skull replicas and validated that the stereolithograph model preserved the scale of the VR model. Based on the Gillespie ratings, students indicated that the biological utility and quality of visual information at the surface of VR and stereolithograph models were greater than the 2D images from which they were derived. The method we developed is useful to create VR and stereolithograph 3D models from medical images and can be used to model hard or soft tissue in living or preserved specimens. Compared to 2D images, VR and stereolithograph models provide an extra dimension that enhances both the quality of visual information and utility of surface visualization in neuroscience and medicine