Delayed conduction and its implications in murine Scn5a+/− hearts: independent and interacting effects of genotype, age, and sex

We explored for relationships between SCN5A haploinsufficiency, implicated in clinical arrhythmogenicity, and right ventricular (RV) conduction disorders in Langendorff-perfused, male and female, and young (3 months) and old (>12 month old) Scn5a+/− and wild type (WT) hearts. The investigated conditions of genotype, age, and sex affected latencies but not repolarization time courses of RV monophasic action potentials. This prompted examination of the patterns of RV epicardial activation, its dispersion, and their interrelationships as possible arrhythmic mechanisms using a 64-channel, multi-electrode array. Mean ventricular activation times (T*MEAN), spatial dispersions (D*S) between recording channels/cardiac cycle, and maximum activation times (T*MAX) representing the slowest possible conduction in any given heart were all higher in old male Scn5a+/− compared with young male and old female Scn5a+/− and old male WT. Temporal dispersions (D*T) of recording channels were similarly higher in old male Scn5a+/− compared with old male WT. All groupings of D*T, D*S, and T*MAX nevertheless linearly correlated with T*MEAN, with indistinguishable slopes. The variates explored thus influence D*T, D*S, and T*MAX through actions on T*MEAN. These findings in turn correlated with increased levels of fibrosis in young male, young female, and old male Scn5a+/− compared with the corresponding WTs. We thus demonstrate for the first time independent and interacting effects of genotype, age, and sex on epicardial conduction and its dispersions at least partially attributable to fibrotic change, resulting in the greatest effects in old male Scn5a+/− in an absence of alterations in repolarization time courses. This directly implicates altered depolarization in the clinical arrhythmogenicity associated with Scn5a+/−

The Magnetic Field Structure of Mercury’s Magnetotail

In this study, we use the magnetic field data measured by MErcury Surface, Space ENvironment, GEochemistry, and Ranging from 2011 to 2015 to investigate the average magnetic field morphology of Mercury’s magnetotail in the down tail 0–3 RM (RM = 2,440 km, Mercury’s radius). It is found that Mercury has a terrestrial‐like magnetotail; the magnetic field structure beyond 1.5 RM down tail is stretched significantly with typical lobe field 50 nT. A cross‐tail current sheet separating the antiparallel field lines of lobes is present in the equatorial plane. The magnetotail width in north‐south direction is about 5 RM, while the transverse width is about 4 RM. Thus, the magnetotail shows elongation along the north‐south direction. At the cross‐tail current sheet center, the normal component of magnetic field (10–20 nT) is much larger than the cross‐tail component. The lobe‐field‐aligned component of magnetic field over current sheet can be well fitted by Harris sheet model. The curvature radius of field lines at sheet center usually reaches a minimum around midnight (100–200 km) with stronger current density (40–50 nA/m2), while the curvature radius increases toward both flanks (400–600 km) with the decreased current density (about 20 nA/m2). The half‐thickness of current sheet around midnight is about 0.25 RM or 600 km, and the inner edge of current sheet is located at the down tail about 1.5 RM. Our results about the field structure in the near Mercury’s tail show an evident dawn‐dusk asymmetry as that found in the Earth’s magnetotail, but reasons should be different. Possible reasons are discussed.Key PointsThe magnetic field distribution, configuration, and current density in Mercury’s magnetotail are quantitatively addressedMercury’s magnetotail is elongated along the south‐north direction, which is probably due to the effect of the dipole offset or the induction effect of coreThe magnetic structure of tail current sheet shows a clear dawn‐dusk asymmetry with smaller Bz and less flaring field on the dusksidePeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142544/1/jgra54041.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142544/2/jgra54041_am.pd

Numbat nirvana: the conservation ecology of the endangered numbat Myrmecobius fasciatus (Marsupialia: Myrmecobiidae) reintroduced to Scotia and Yookamurra Sanctuaries, Australia

Despite a vigorous reintroduction program between 1985 and 2010, numbat populations in Western Australia are either static or declining. This study aimed to document the population ecology of numbats at two sites that are going against this trend: Scotia Sanctuary in far western New South Wales and Yookamurra Sanctuary in the riverland of South Australia. Scotia (64 659 ha) and Yookamurra (5026 ha) are conservation reserves owned and managed by the Australian Wildlife Conservancy and where numbats were reintroduced in 1999 and 1993 respectively. Both sites have large conservation-fence-protected introduced-species-free areas where there are no cats (Felis catus) or red foxes (Vulpes vulpes). Numbats were sourced from both wild and captive populations. From small founder populations, the Scotia numbats are now estimated to number 169 (113–225) with 44 at Yookamurra. Radio-collared individuals at Scotia were active between 13 and 31°C. Females had home ranges of 28.3 ± 6.8 ha and males 96.6 ± 18.2 ha, which leads to an estimated sustainable population or carrying capacity of 413–502 at Scotia. Captive-bred animals from Perth Zoo had a high mortality rate upon reintroduction at Scotia due to predation by raptors and starvation. The habitat preferences for mallee with a shrub understorey appear to be driven by availability of termites, and other reintroduced ecosystem engineers appear to have been facilitators by creating new refuge burrows for numbats. This study shows that numbats can be successfully reintroduced into areas of their former range if protected from introduced predators, and illustrates the difficulties in monitoring such cryptic species.</jats:p

Stressful first impressions in job interviews

Stress can impact many aspects of our lives, such as the way we interact and work with others, or the first impressions that we make. In the past, stress has been most commonly assessed through self-reported questionnaires; however, advancements in wearable technology have enabled the measurement of physiological symptoms of stress in an unobtrusive manner. Using a dataset of job interviews, we investigate whether first impressions of stress (from annotations) are equivalent to physiological measurements of the electrodermal activity (EDA). We examine the use of automatically extracted nonverbal cues stemming from both the visual and audio modalities, as well EDA stress measurements for the inference of stress impressions obtained from manual annotations. Stress impressions were found to be significantly negatively correlated with hireability ratings i.e individuals who were perceived to be more stressed were more likely to obtained lower hireability scores. The analysis revealed a significant relationship between audio and visual features but low predictability and no significant effects were found for the EDA features. While some nonverbal cues were more clearly related to stress, the physiological cues were less reliable and warrant further investigation into the use of wearable sensors for stress detection

Potential use of plasma focus radiation sources in superficial cancer therapy

The new multidisciplinary field of plasma medicine combines plasma physics, electrical engineering, life sciences and clinical medicine. Here we explore potential uses in medicine, most particularly cancer therapy, the plasma source being brought out of the field of industrial applications into the life sciences, the focus being on superficial cancer radiotherapy strategies. Existing radiotherapy practices for such cancers rely on the use of rather large facilities, most popularly the electron linear accelerator and X-ray tube-based devices. Conversely, a compact plasma radiation source can be housed in a relatively small space, there being considerable promise for such devices to produce the fluence requirements of radiotherapy for treatment of skin cancers. The present study of feasibility investigates the plasma focus device, with the emission produced by a single discharge shown to generate an X-ray dose of few tens of mGy. The X-ray dose is the integration of emission in the discharge durations of less than a μs, it is therefore possible using these devices to build up fractional irradiation dose through repetitive operation of the discharge system

Planar Graph Coloring with Forbidden Subgraphs: Why Trees and Paths Are Dangerous

We consider the problem of coloring a planar graph with the minimum number of colors such that each color class avoids one or more forbidden graphs as subgraphs. We perform a detailed study of the computational complexity of this problem. We present a complete picture for the case with a single forbidden connected (induced or non-induced) subgraph. The 2-coloring problem is NP-hard if the forbidden subgraph is a tree with at least two edges, and it is polynomially solvable in all other cases. The 3-coloring problem is NP-hard if the forbidden subgraph is a path, and it is polynomially solvable in all other cases. We also derive results for several forbidden sets of cycles

Erythropoietic protoporphyria

Erythropoietic protoporphyria (EPP) is an inherited disorder of the haem metabolic pathway characterised by accumulation of protoporphyrin in blood, erythrocytes and tissues, and cutaneous manifestations of photosensitivity. EPP has been reported worldwide, with prevalence between 1:75,000 and 1:200,000. It usually manifests in early infancy upon the first sun exposures. EPP is characterised by cutaneous manifestations of acute painful photosensitivity with erythema and oedema, sometimes with petechiae, together with stinging and burning sensations upon exposure to sunlight, without blisters. These episodes have a variable severity depending on the exposure duration and may result in chronic permanent lesions on exposed skin. As protoporphyrin is a lipophilic molecule that is excreted by the liver, EPP patients are at risk of cholelithiasis with obstructive episodes, and chronic liver disease that might evolve to rapid acute liver failure. In most patients, EPP results from a partial deficiency of the last enzyme of the haem biosynthetic pathway, ferrochelatase, EC 4.99.1.1/FECH (encoded by the FECH gene). EPP appears to be inherited as an autosomal dominant disease, the clinical expression of which is modulated by the presence of the hypomorphic FECH IVS3-48C allele trans, but recessive inheritance with two mutated FECH alleles has also been described. In about 2% of patients, overt disease was recently shown to be caused by gain-of-function mutations in the erythroid-specific aminolevulinic acid synthase 2 (ALAS2/ALAS, EC 2.3.1.27) gene and named X-linked dominant protoporphyria. Diagnosis is established by finding increased levels of protoporphyrin in plasma and red blood cells, and detection of a plasma fluorescence peak at 634 nm. Investigations for hepatic involvement, ferrochelatase activity level, genetic analysis (FECH mutations, presence of the hypomorphic FECH IVS3-48C allele trans and ALAS2 mutations) and family studies are advisable. Differential diagnosis includes phototoxic drug reactions, hydroa vacciniforme, solar urticaria, contact dermatitis, angio-oedema and, in some cases, other types of porphyria. Management includes avoidance of exposure to light, reduction of protoporphyrin levels and prevention of progression of possible liver disease to liver failure. As the major risk in EPP patients is liver disease, a regular follow-up of hepatic involvement is essential. Sequential hepatic and bone marrow transplantation should be considered as a suitable treatment for most severe cases of EPP with hepatic involvement. EPP is a lifelong disorder whose prognosis depends on the evolution of the hepatic disease. However, photosensitivity may have a significant impact on quality of life of EPP patients

Multiple Traits for People Identification

Present biometric systems mostly rely on a single physical or behavioral feature for either identification or verification. However, day to day use of single biometries in massive or uncontrolled scenarios still has several shortcomings. These can be due to complex or unstable hardware settings, to changing environmental conditions or even to immature software procedures: some classification problems are intrinsically hard to solve. Possible spoofing of single biometric features is an additional issue. Last but not least, some features may occasionally lack the requisite of universality. As a consequence, biometric systems based on a single feature often have poor reliability, especially in applications where high security is needed. Multimodal systems, i.e., systems that concurrently exploit multiple features, are a possible way to achieve improved effectiveness and reliability. There are several issues that must be addressed when designing such a system, including the choice of the set of biometric features, the normalization method, the integration schema and the fusion process, and the use of a measure of reliability for each subsystem on a single response basis. This chapter describes the state of the art regarding such issues and sketches some suggestions for future work

Evolutionary Analysis of Mitogenomes from Parasitic and Free-Living Flatworms

Copyright: © 2015 Solà et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

Dominant protection from HLA-linked autoimmunity by antigen-specific regulatory T cells

Susceptibility and protection against human autoimmune diseases, including type I diabetes, multiple sclerosis, and Goodpasture disease, is associated with particular human leukocyte antigen (HLA) alleles. However, the mechanisms underpinning such HLA-mediated effects on self-tolerance remain unclear. Here we investigate the molecular mechanism of Goodpasture disease, an HLA-linked autoimmune renal disorder characterized by an immunodominant CD4+ T-cell self-epitope derived from the α3 chain of type IV collagen (α3135–145)1,2,3,4. While HLA-DR15 confers a markedly increased disease risk, the protective HLA-DR1 allele is dominantly protective in trans with HLA-DR15 (ref. 2). We show that autoreactive α3135–145-specific T cells expand in patients with Goodpasture disease and, in α3135–145-immunized HLA-DR15 transgenic mice, α3135–145-specific T cells infiltrate the kidney and mice develop Goodpasture disease. HLA-DR15 and HLA-DR1 exhibit distinct peptide repertoires and binding preferences and present the α3135–145 epitope in different binding registers. HLA-DR15-α3135–145 tetramer+ T cells in HLA-DR15 transgenic mice exhibit a conventional T-cell phenotype (Tconv) that secretes pro-inflammatory cytokines. In contrast, HLA-DR1-α3135–145 tetramer+ T cells in HLA-DR1 and HLA-DR15/DR1 transgenic mice are predominantly CD4+Foxp3+ regulatory T cells (Treg cells) expressing tolerogenic cytokines. HLA-DR1-induced Treg cells confer resistance to disease in HLA-DR15/DR1 transgenic mice. HLA-DR15+ and HLA-DR1+ healthy human donors display altered α3135–145-specific T-cell antigen receptor usage, HLA-DR15-α3135–145 tetramer+ Foxp3− Tconv and HLA-DR1-α3135–145 tetramer+ Foxp3+CD25hiCD127lo Treg dominant phenotypes. Moreover, patients with Goodpasture disease display a clonally expanded α3135–145-specific CD4+ T-cell repertoire. Accordingly, we provide a mechanistic basis for the dominantly protective effect of HLA in autoimmune disease, whereby HLA polymorphism shapes the relative abundance of self-epitope specific Treg cells that leads to protection or causation of autoimmunity