Highlights • NRG1 protects against OGD-induced cortical neuronal apoptosis. • NRG1-mediated neuroprotection is blocked by neutralizing NRG1 and ErbB4 inhibition. • GABA receptor agonists have no ...synergistic effect with NRG1. • NRG1-mediated neuroprotection is partly blocked by GABA receptor antagonists. • The NRG1 neuroprotection against brain ischemia is abolished in PV-ErbB4−/− mice.
Summary
Background
Inherited epidermodysplasia verruciformis (EV) is a rare skin disorder characterized by susceptibility to specific types of human papilloma virus (HPV) and is strongly associated ...with skin carcinomas. Inactivating mutations in EVER1/EVER2 account for most cases of EV. However, more phenotypes related to but distinct from EV have been reported with an immunodeficiency state but without EVER1/EVER2 mutation, and the genetic basis for these atypical EV cases is poorly understood.
Objectives
To identify the causative gene responsible for three siblings affected by atypical EV but without EVER1/EVER2 mutation.
Methods
Whole‐exome sequencing followed by Sanger sequencing was performed to identify the gene responsible for the patients with atypical EV enrolled in our study.
Results
A homozygous splicing mutation was detected in LCK (c.188‐2A>G). This mutation resulted in an exon 3 deletion T lymphocyte‐specific protein tyrosine kinase isoform, which further led to frameshift mutation and subsequent mRNA decay.
Conclusions
We demonstrate a novel mutation in LCK in a family affected by atypical EV with T‐cell defects, HPV infection and virus‐induced malignancy, providing new clues in the understanding of host defences against HPV and better genetic counselling of patients with the EV phenotype.
What's already known about this topic?
Epidermodysplasia verruciformis (EV) is an unusual genodermatosis characterized by an increased susceptibility to β‐human papillomavirus and is associated with a high risk of skin carcinoma.
Inactivating mutations in EVER1/EVER2 account for most cases of EV.
What does this study add?
Our study suggests an association between a novel splicing mutation in LCK and EV susceptibility.
What is the translational message?
Patients with EV should be tested for T lymphocyte‐specific protein tyrosine kinase deficiency and T‐cell function, which will help guide treatment.
Linked Comment: Uitto and Vahidnezhad. Br J Dermatol 2016; 175:1138–1139.
•We model thermal performance of U-pipe evacuated solar tube.•Temperature distribution along fine circumferential direction is in consideration.•Tube size parameters affects on thermal efficiency is ...studied.•Mass flow rate optimal design is analyzed.•Tube thermal parameters adaptation to metrological condition is proposed.
This paper proposes a mathematical model for predicting the thermal performance of U-pipe evacuated solar tube (UpEST) collector, which takes into account the temperature distribution along the tube axis and radius. Furthermore, the modeling predictions were validated using experimental data. Theoretical results agreed well with the measured results that validated the feasibility of the mathematical model. The dependence of the thermal efficiency on meteorological conditions and important tube design parameters, including tube size, thermal characteristics (flow rate, heat loss coefficient, absorption coefficient of the selective absorbing coating), was investigated. In particular, the adaptation of collector thermal parameters to meteorological conditions was analyzed. The analysis results will be helpful for UpEST collector optimization design and application.
This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer.
In this phase III, ...double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 103/μl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review.
Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 95% confidence interval (CI), 10.9-not evaluable versus 5.4 (95% CI, 3.7-5.7) months hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001, and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%).
Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.
•Chinese patients with platinum-sensitive recurrent ovarian cancer received maintenance niraparib (n = 177) or placebo (n = 88).•Median PFS was longer for niraparib versus placebo: 18.3 versus 5.4 months (HR = 0.32; 95% CI, 0.23-0.45; P < 0.0001).•Niraparib had a similar PFS benefit for 249 patients receiving individualized dosing based on bodyweight and platelet count.•Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively.•In the niraparib group, Grade ≥3 platelet count decreased/thrombocytopenia occurred in 11.3% of patients.
The aqueous reactivity of five prominent endocrine disrupting chemicals (EDCs) with potassium ferrate has been studied. The degradation kinetics and reaction pathways for bisphenol A (BPA) have been ...considered in detail, and the reaction rate constants for 17
α-ethynylestradiol (EE2), estrone (E1),
β-estradiol (E2), and estriol (E3) have been determined, from tests carried out in the pH range of 8–12 and at different reactant molar ratios. The rate constants were determined by a kinetic model incorporating the various species equilibria for the EDC compounds and ferrate, using observations of the temporal reduction in EDC and ferrate concentrations. In agreement with other studies, the oxidation of the EDCs was found to be greater for mono-protonated ferrate,
HFeO
4
-
, than for non-protonated ferrate,
FeO
4
2
-
. Among the five EDCs, all of which have phenol moieties, the ferrate oxidation of the four steroid estrogens (each incorporating the cyclopentanoperhydrophenanthrene ring) had higher reaction rates than BPA. The by-products of BPA degradation by ferrate were analyzed by liquid chromatography/mass spectrometry–mass spectrometry (LC/MS–MS) and gas chromatography/mass spectrometry–mass spectrometry (GC/MS–MS) and nine specific compounds were identified, including
p-isopropylphenol, 4-isopropanolphenol,
p-isopropenylphenol, and some dicarboxylic acids, etc. It is concluded that ferrate oxidation could be an effective treatment method for the purification of waters containing these particular EDCs.
Background Ultraviolet (UV) exposure results in the production reactive oxygen species. Resveratrol has attracted considerable attentions owing to its natural abundance and multiple biological ...effects.
Objective To investigate the protective effects of resveratrate against damage to human skin induced by repetitive solar simulator ultraviolet radiation (ssUVR).
Materials and methods Fifteen healthy volunteers were enrolled, and six sites on the non‐exposed dorsal skin of each volunteer were marked for study. Sites 1–4 were exposed to ssUVR at a dosage of 1.5 minimal erythema dose for consecutive 4 days. Immediately after each exposure, one test material (resveratrate + antioxidant, antioxidant, resveratrate, vehicle) was applied to one of the four sites. Site 5 and site 6 were marked as positive control site (UVR only) and baseline control site (no treatment, no UVR). L*a*b values were assessed preprocedure and postprocedure. Skin biopsies were taken 24 h after the last irradiation. The specimens were stained to determine the number of sunburn cells and melanin content melanin.
Results On resveratrate treated sites, erythema was barely seen with only slight decrease of L value and insignificant increase of *a value. Furthermore, resveratrate significantly inhibited sunburn cell formation, and decreased Fontana‐Masson staining in skin samples.
Conclusions Resveratrate exerts protective effects against repetitive ssUVR‐induced sunburn and suntan.
Abstract
WormBase (https://wormbase.org/) is a mature Model Organism Information Resource supporting researchers using the nematode Caenorhabditis elegans as a model system for studies across a broad ...range of basic biological processes. Toward this mission, WormBase efforts are arranged in three primary facets: curation, user interface and architecture. In this update, we describe progress in each of these three areas. In particular, we discuss the status of literature curation and recently added data, detail new features of the web interface and options for users wishing to conduct data mining workflows, and discuss our efforts to build a robust and scalable architecture by leveraging commercial cloud offerings. We conclude with a description of WormBase's role as a founding member of the nascent Alliance of Genome Resources.
Aims
Sustainable agriculture requires effective and safe biofertilizers and biofungicides with low environmental impact. Natural ecosystems that closely resemble the conditions of biosaline ...agriculture may present a reservoir for fungal strains that can be used as novel bioeffectors.
Methods and Results
We isolated a library of fungi from the rhizosphere of three natural halotolerant plants grown in the emerging tidal salt marshes on the south‐east coast of China. DNA barcoding of 116 isolates based on the rRNA ITS1 and 2 and other markers (tef1 or rpb2) revealed 38 fungal species, including plant pathogenic (41%), saprotrophic (24%) and mycoparasitic (28%) taxa. The mycoparasitic fungi were mainly species from the hypocrealean genus Trichoderma, including at least four novel phylotypes. Two of them, representing the taxa Trichoderma arenarium sp. nov. (described here) and T. asperelloides, showed antagonistic activity against five phytopathogenic fungi, and significant growth promotion on tomato seedlings under the conditions of saline agriculture.
Conclusions
Trichoderma spp. of salt marshes play the role of natural biological control in young soil ecosystems with a putatively premature microbiome.
Significance and Impact of the Study
The saline soil microbiome is a rich source of halotolerant bioeffectors that can be used in biosaline agriculture.
The effects of silicon carbide (SiC) dimensions on the microstructure and mechanical properties have been investigated by comparing SiC nanowires (SiCnw) reinforced Mg–2Zn-0.1Y(ZW20) matrix composite ...with the other two composites reinforced by nano-SiC (SiCnp) and submicron-SiC (SiCsp) particles. Three kinds of 0.3 wt% SiC reinforced ZW20 matrix composites (SiCnw/ZW20, SiCsp/ZW20, SiCnp/ZW20) were successfully fabricated by ultrasonic assisted with semi-solid stirring cast followed extrusion. The microstructures of the three composites were analyzed by Scanning Electron Microscope (SEM) equipped with Energy Dispersive Spectroscopy (EDS), Transmission Electron Microscope (TEM), X-Ray diffraction (XRD) and optical microscope (OM). Then, the tensile test was performed to unravel the mechanical properties of composites. The results showed that relatively complete dynamic recrystallization (DRX) occurred in the three composites generating plentiful fine grains, the second phases proven be MgZn2 phases by EDS and XRD precipitated near grain boundaries and SiC. Among the three composites, the average grain size of SiCnw/ZW20 was the finest (only 0.37 μm), which was mainly ascribed to the fact that one-dimensional SiCnw could hinder the growth of grains more effectively by twisting along grain boundaries. And the most complete recrystallization occurred in SiCnp/ZW20 due to the maximum number of SiCnp. Moreover, the volume fraction of precipitates in SiCnw/ZW20 was ∼50% more than that of SiCsp/ZW20 and SiCnp/ZW20, relevant with more nucleation sites contributed by SiCnw. Accordingly, the microstructure given by different dimensions of SiC led to the improvements of yield strength (YS) and ultimate tensile strength (UTS). The synergy of fine-grain strengthening from DRXed grains, dislocation strengthening caused by hot deformation and Orowan strengthening originating from precipitations and SiC may primarily account for the high YS, over 440 MPa.
•The effect of SiC dimensions on the microstructure was discovered in three SiC/ZW20 composites.•Low temperature extrusion was achieved in three SiC/ZW20 composites.•The strengthening mechanism in three SiC/ZW20 composites was clarified.•The three SiC/ZW20 composites exhibited YS of 430–500 MPa and UTS of 440–510 MPa.
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