Equation of state of cosmic strings with fermionic current-carriers

The relevant characteristic features, including energy per unit length and tension, of a cosmic string carrying massless fermionic currents in the framework of the Witten model in the neutral limit are derived through quantization of the spinor fields along the string. The construction of a Fock space is performed by means of a separation between longitudinal modes and the so-called transverse zero energy solutions of the Dirac equation in the vortex. As a result, quantization leads to a set of naturally defined state parameters which are the number densities of particles and anti-particles trapped in the cosmic string. It is seen that the usual one-parameter formalism for describing the macroscopic dynamics of current-carrying vortices is not sufficient in the case of fermionic carriers.Comment: 30 pages, 15 figures, uses ReVTeX, equation of state corrected, comments and references added. Accepted for publication in Phys. Rev.

Recent advances in alcohol-related liver disease (ALD): summary of a Gut roundtable meeting

Alcohol-related liver disease (ALD), which includes a range of disorders of different severity and is one of the most prevalent types of liver disease worldwide, has recently regained increased attention. Among other reasons, the realisation that any alcohol intake, regardless of type of beverage represents a health risk, and the new therapeutic strategies tested in recently published or undergoing clinical trials spur scientific interest in this area. In April 2019, Gut convened a round table panel of experts during the European Association for the Study of the Liver (EASL) International Liver Congress (ILC) in Vienna to discuss critical and up-to-date issues and clinical trial data regarding ALD, its epidemiology, diagnosis, management, pathomechanisms, possible future treatments and prevention. This paper summarises the discussion and its conclusions

Биофизика зрительной сенсорной системы человека

Зрительная сенсорная система – это система, которая воспринимает излучение видимого спектра, после чего формируется изображение предметов окружающей среды в виде определенных ощущений (сенсорных чувств)

Population structure of the malaria vector Anopheles moucheti in the equatorial forest region of Africa

<p>Abstract</p> <p>Background</p> <p><it>Anopheles moucheti </it>is a major malaria vector in forested areas of Africa. However, despite its important epidemiological role, it remains poorly known and insufficiently studied. Here, levels of genetic differentiation were estimated between different <it>A. moucheti </it>populations sampled throughout its distribution range in Central Africa.</p> <p>Methods</p> <p>Polymorphism at ten microsatellite markers was compared in mosquitoes sampled in Cameroon, the Democratic Republic of Congo and an island on Lake Victoria in Uganda. Microsatellite data were used to estimate genetic diversity within populations, their relative long-term effective population size, and the level of genetic differentiation between them.</p> <p>Results</p> <p>All specimens collected in Tsakalakuku (Democratic Republic of Congo) were identified as <it>A. m. bervoetsi </it>while other samples consisted of <it>A. m. moucheti</it>. Successful amplification was obtained at all microsatellite loci within all <it>A. m. moucheti </it>samples while only six loci amplified in <it>A. m. bervoetsi</it>. Allelic richness and heterozygosity were high for all populations except the island population of Uganda and <it>A. m. bervoetsi</it>. High levels of genetic differentiation were recorded between <it>A. m. bervoetsi </it>and each <it>A. m. moucheti </it>sample as well as between the island population of <it>A. m. moucheti </it>and mainland populations. Significant isolation by distance was evidenced between mainland populations.</p> <p>Conclusion</p> <p>High levels of genetic differentiation supports complete speciation of <it>A. m. bervoetsi </it>which should henceforth be recognized as a full species and named <it>A. bervoetsi</it>. Isolation by distance is the main force driving differentiation between mainland populations of <it>A. m. moucheti</it>. Genetically and geographically isolated populations exist on Lake Victoria islands, which might serve as relevant field sites for evaluation of innovative vector control strategies.</p

Increased IKKα Expression in the Basal Layer of the Epidermis of Transgenic Mice Enhances the Malignant Potential of Skin Tumors

Non-melanoma skin cancer is the most frequent type of cancer in humans. In this study we demonstrate that elevated IKKα expression in murine epidermis increases the malignancy potential of skin tumors. We describe the generation of transgenic mice overexpressing IKKα in the basal, proliferative layer of the epidermis and in the outer root sheath of hair follicles. The epidermis of K5-IKKα transgenic animals shows several alterations such as hyperproliferation, mislocalized expression of integrin-α6 and downregulation of the tumor suppressor maspin. Treatment of the back skin of mice with the mitogenic agent 12-O-tetradecanoylphorbol-13-acetate causes in transgenic mice the appearance of different preneoplastic changes such as epidermal atypia with loss of cell polarity and altered epidermal tissue architecture, while in wild type littermates this treatment only leads to the development of benign epidermal hyperplasia. Moreover, in skin carcinogenesis assays, transgenic mice carrying active Ha-ras (K5-IKKα-Tg.AC mice) develop invasive tumors, instead of the benign papillomas arising in wild type-Tg-AC mice also bearing an active Ha-ras. Therefore we provide evidence for a tumor promoter role of IKKα in skin cancer, similarly to what occurs in other neoplasias, including hepatocarcinomas and breast, prostate and colorectal cancer. The altered expression of cyclin D1, maspin and integrin-α6 in skin of transgenic mice provides, at least in part, the molecular bases for the increased malignant potential found in the K5-IKKα skin tumors

Caucasian Ethnicity, but Not Treatment Cessation is Associated with HBsAg Loss Following Nucleos(t)ide Analogue-Induced HBeAg Seroconversion

It is well appreciated that ethnicity influences the natural history and immune responses during a chronic hepatitis B infection. In this study, we explore the effect of ethnicity and treatment cessation on Hepatitis B surface Antigen (HBsAg) seroclearance in patients with Nucleos(t)ide Analogue (NA)-induced Hepatitis B e Antigen (HBeAg) seroconversion. We performed a multi-ethnic, multicentric observational cohort study. The analyzed cohort consisted of 178 mono-infected, predominantly male (75.3%) chronic hepatitis B patients of mixed ethnicity (44.4% Asians, 48.9% Caucasians) with nucleos(t)ide analogue-induced HBeAg seroconversion. Treatment was withdrawn in 105 patients and continued in 73, leading to HBsAg loss in 14 patients off- and 16 patients on-treatment, respectively. Overall, HBsAg loss rates were not affected by treatment cessation (hazard ratio 1.45, p = 0.372), regardless of consolidation treatment duration. Caucasian ethnicity was associated with an increased chance of HBsAg loss (hazard ratio 6.70, p = 0.001), but hepatitis B virus genotype was not (p = 0.812). In conclusion, ethnicity is the most important determinant for HBsAg loss after NA-induced HBeAg seroconversion, with up to six-fold higher HBsAg loss rates in Caucasians compared to Asians, irrespective of treatment cessation and consolidation treatment duration

Inhibition of the Soluble Epoxide Hydrolase Promotes Albuminuria in Mice with Progressive Renal Disease

Epoxyeicotrienoic acids (EETs) are cytochrome P450-dependent anti-hypertensive and anti-inflammatory derivatives of arachidonic acid, which are highly abundant in the kidney and considered reno-protective. EETs are degraded by the enzyme soluble epoxide hydrolase (sEH) and sEH inhibitors are considered treatment for chronic renal failure (CRF). We determined whether sEH inhibition attenuates the progression of CRF in the 5/6-nephrectomy model (5/6-Nx) in mice. 5/6-Nx mice were treated with a placebo, an ACE-inhibitor (Ramipril, 40 mg/kg), the sEH-inhibitor cAUCB or the CYP-inhibitor fenbendazole for 8 weeks. 5/6-Nx induced hypertension, albuminuria, glomerulosclerosis and tubulo-interstitial damage and these effects were attenuated by Ramipril. In contrast, cAUCB failed to lower the blood pressure and albuminuria was more severe as compared to placebo. Plasma EET-levels were doubled in 5/6 Nx-mice as compared to sham mice receiving placebo. Renal sEH expression was attenuated in 5/6-Nx mice but cAUCB in these animals still further increased the EET-level. cAUCB also increased 5-HETE and 15-HETE, which derive from peroxidation or lipoxygenases. Similar to cAUCB, CYP450 inhibition increased HETEs and promoted albuminuria. Thus, sEH-inhibition failed to elicit protective effects in the 5/6-Nx model and showed a tendency to aggravate the disease. These effects might be consequence of a shift of arachidonic acid metabolism into the lipoxygenase pathway

Structural Insights into Viral Determinants of Nematode Mediated Grapevine fanleaf virus Transmission

Many animal and plant viruses rely on vectors for their transmission from host to host. Grapevine fanleaf virus (GFLV), a picorna-like virus from plants, is transmitted specifically by the ectoparasitic nematode Xiphinema index. The icosahedral capsid of GFLV, which consists of 60 identical coat protein subunits (CP), carries the determinants of this specificity. Here, we provide novel insight into GFLV transmission by nematodes through a comparative structural and functional analysis of two GFLV variants. We isolated a mutant GFLV strain (GFLV-TD) poorly transmissible by nematodes, and showed that the transmission defect is due to a glycine to aspartate mutation at position 297 (Gly297Asp) in the CP. We next determined the crystal structures of the wild-type GFLV strain F13 at 3.0 Å and of GFLV-TD at 2.7 Å resolution. The Gly297Asp mutation mapped to an exposed loop at the outer surface of the capsid and did not affect the conformation of the assembled capsid, nor of individual CP molecules. The loop is part of a positively charged pocket that includes a previously identified determinant of transmission. We propose that this pocket is a ligand-binding site with essential function in GFLV transmission by X. index. Our data suggest that perturbation of the electrostatic landscape of this pocket affects the interaction of the virion with specific receptors of the nematode's feeding apparatus, and thereby severely diminishes its transmission efficiency. These data provide a first structural insight into the interactions between a plant virus and a nematode vector

The Schizosaccharomyces pombe Hsp104 Disaggregase Is Unable to Propagate the [PSI+] Prion

The molecular chaperone Hsp104 is a crucial factor in the acquisition of thermotolerance in yeast. Under stress conditions, the disaggregase activity of Hsp104 facilitates the reactivation of misfolded proteins. Hsp104 is also involved in the propagation of fungal prions. For instance, the well-characterized [PSI+] prion of Saccharomyces cerevisiae does not propagate in Δhsp104 cells or in cells overexpressing Hsp104. In this study, we characterized the functional homolog of Hsp104 from Schizosaccharomyces pombe (Sp_Hsp104). As its S. cerevisiae counterpart, Sp_hsp104+ is heat-inducible and required for thermotolerance in S. pombe. Sp_Hsp104 displays low disaggregase activity and cannot propagate the [PSI+] prion in S. cerevisiae. When overexpressed in S. cerevisiae, Sp_Hsp104 confers thermotolerance to Δhsp104 cells and reactivates heat-aggregated proteins. However, overexpression of Sp_Hsp104 does not propagate nor eliminate [PSI+]. Strikingly, [PSI+] was cured by overexpression of a chimeric chaperone bearing the C-terminal domain (CTD) of the S. cerevisiae Hsp104 protein. Our study demonstrates that the ability to untangle aggregated proteins is conserved between the S. pombe and S. cerevisiae Hsp104 homologs, and points to a role of the CTD in the propagation of the S. cerevisiae [PSI+] prion