The Putative Antilipogenic Role of NRG4 and ERBB4: First Expression Study on Human Liver Samples.

Background: Epidermal growth factor receptor 4 (ERBB4) and neuregulin 4 (NRG4) have been shown to reduce steatosis and prevent the development of non-alcoholic steatohepatitis in mouse models, but little to nothing is known about their role in non-alcoholic fatty liver disease (NAFLD) in humans. This study is the first to investigate the expression of and mRNAs and their role in lipid metabolism in the livers of individuals with obesity, type 2 diabetes and biopsy-proven NAFLD.

Methods: Liver biospecimens were obtained intraoperatively from 80 individuals.

Mathematical Modeling of the Evaporation of a Water Drop from a Heated Surface.

This paper presents the results of mathematical modeling of the evaporation of a single water drop from the surface of a copper substrate using a new model, which does not require special experiments to close the system of equations and the corresponding boundary conditions with empirical constants. On the basis of the results of mathematical modeling, it was found that convective currents that occur in a small water drop (≤1 mm in diameter) do not significantly affect the characteristics or conditions of heat and mass transfer processes occurring in a liquid drop heated on a copper substrate. The results of numerical simulation showed that during the initial period of droplet heating, the latter undergoes a rapid transformation of the flow field.

The Association of Integrins β3, β4, and αVβ5 on Exosomes, CTCs and Tumor Cells with Localization of Distant Metastasis in Breast Cancer Patients.

Integrins are cell adhesion receptors, which play a role in breast cancer invasion, angiogenesis, and metastasis. Moreover, it has been shown that exosomal integrins provide organotropic metastasis in a mouse model. In our study, we aimed to investigate the expression of integrins β3, β4, and αVβ5 on exosomes and tumor cells (circulating tumor cells and primary tumor) and their association with the localization of distant metastasis.

Emissions from the combustion of high-potential slurry fuels.

Slurry fuels based on wood and coal processing and petroleum refinery waste are an environmentally friendly and economically feasible alternative to the conventional solid fuel-coal. As part of this experimental research, we compared a set of fuels (coal and coal-water slurries with and without petrochemicals) by normalizing and calculating the specific concentrations of pollutants from their combustion. The pollutant concentrations were normalized with respect to the mass of burnt fuel, the thermal energy released by combustion, specific mass emissions per unit time, specific maximum mass emissions, and specific mass emissions per 1 kg of fuel equivalent or 1 MJ of thermal energy.

Composition of a gas and ash mixture formed during the pyrolysis and combustion of coal-water slurries containing petrochemicals.

This paper presents the results of experimental research into the component composition of gases and ash residue from the combustion of a set of high-potential coal-water slurries containing petrochemicals. We have established that the use of slurry fuels provides a decrease in the CO, CH, SO, and NO concentrations as compared to those from coal combustion. The content of carbon monoxide and hydrogen in the gas environment from the combustion of slurries is higher due to the intense water evaporation.

Effects of plant additives on the concentration of sulfur and nitrogen oxides in the combustion products of coal-water slurries containing petrochemicals.

The active use of solid fossil fuels (coal) in the production of heat and electricity has led to significant pollution, climate change, environmental degradation, and an increase in morbidity and mortality. Many countries (in particular, European ones, China, Japan, the USA, Canada, etc.) have launched programs for using plant and agricultural raw materials to produce heat and electricity by burning them instead of or together with traditional fuels.

[The treatment efficacy of disturbed swallowing function in patients with ischemic stroke and neurogenous dysfagia in the intensive care unit].

Aim: To evaluate the efficacy of the training method of rehabilitation of patients with neurogenic dysphagia in ischemic stroke carried out with the use of special nutrient mixtures as part of combination therapy.

Material And Methods: The study included 65 patients (35 men and 30 women, aged 45 to 80 years) with dysphagia in the acute period of ischemic stroke. Thirty patients were treated with special binding compounds as part of a combination therapy.

Droplet state and mechanism of contact line movement on laser-textured aluminum alloy surfaces.

Hypothesis: Contact line movement over laser-textured metal alloy surfaces depends on the texture, droplet state, inversion of wettability, and liquid flow rate.

Experiments: Ordered and anisotropic textures were created by a nanosecond pulse laser on aluminum-magnesium alloy surfaces. Microrelief was studied on a profilometer and scanning electron microscope.

Author Correction: Evasion of immunosurveillance by genomic alterations of PPARγ/RXRα in bladder cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Discovery of Selective Estrogen Receptor Covalent Antagonists for the Treatment of ERα and ERα Breast Cancer.

Mutations in estrogen receptor alpha (ERα) that confer resistance to existing classes of endocrine therapies are detected in up to 30% of patients who have relapsed during endocrine treatments. Because a significant proportion of therapy-resistant breast cancer metastases continue to be dependent on ERα signaling, there remains a critical need to develop the next generation of ERα antagonists that can overcome aberrant ERα activity. Through our drug-discovery efforts, we identified H3B-5942, which covalently inactivates both wild-type and mutant ERα by targeting Cys530 and enforcing a unique antagonist conformation.

[The radicular cyst in the maxillary sinus encountered in the clinical otorhinolaryngological practice].

This article was designed to report the clinical case of the radicular cyst localized in the maxillary sinus of the 23 year-old man that had been detected before the surgical intervention was undertaken for its treatment. In the preceding visits of the patient to other medical settings, this condition was misinterpreted as a genuine (rhinogenic) cyst. It accounted for the choice of the inadequate surgical strategy for the management of this pathology.

EP4 Antagonism by E7046 diminishes Myeloid immunosuppression and synergizes with Treg-reducing IL-2-Diphtheria toxin fusion protein in restoring anti-tumor immunity.

Reprogramming of immunosuppressive tumor microenvironment (TME) by targeting alternatively activated tumor associated macrophages (M2TAM), myeloid-derived suppressor cells (MDSC), and regulatory T cells (Tregs), represents a promising strategy for developing novel cancer immunotherapy. Prostaglandin E2 (PGE), an arachidonic acid pathway metabolite and mediator of chronic inflammation, has emerged as a powerful immunosuppressor in the TME through engagement with one or more of its 4 receptors (EP1-EP4). We have developed E7046, an orally bioavailable EP4-specific antagonist and show here that E7046 has specific and potent inhibitory activity on PGE-mediated pro-tumor myeloid cell differentiation and activation.

Evasion of immunosurveillance by genomic alterations of PPARγ/RXRα in bladder cancer.

Muscle-invasive bladder cancer (MIBC) is an aggressive disease with limited therapeutic options. Although immunotherapies are approved for MIBC, the majority of patients fail to respond, suggesting existence of complementary immune evasion mechanisms. Here, we report that the PPARγ/RXRα pathway constitutes a tumor-intrinsic mechanism underlying immune evasion in MIBC.

Millstone: software for multiplex microbial genome analysis and engineering.

Inexpensive DNA sequencing and advances in genome editing have made computational analysis a major rate-limiting step in adaptive laboratory evolution and microbial genome engineering. We describe Millstone, a web-based platform that automates genotype comparison and visualization for projects with up to hundreds of genomic samples. To enable iterative genome engineering, Millstone allows users to design oligonucleotide libraries and create successive versions of reference genomes.

Optimizing complex phenotypes through model-guided multiplex genome engineering.

We present a method for identifying genomic modifications that optimize a complex phenotype through multiplex genome engineering and predictive modeling. We apply our method to identify six single nucleotide mutations that recover 59% of the fitness defect exhibited by the 63-codon E. coli strain C321.

Correction: Preclinical Evidence of Anti-Tumor Activity Induced by EZH2 Inhibition in Human Models of Synovial Sarcoma.

[This corrects the article DOI: 10.1371/journal.pone.

Identification of Novel CD4+ T Cell Subsets in the Target Tissue of Sjögren's Syndrome and Their Differential Regulation by the Lymphotoxin/LIGHT Signaling Axis.

Despite being one of the most common rheumatologic diseases, there is still no disease-modifying drug for primary Sjögren's syndrome (pSS). Advancing our knowledge of the target tissue has been limited by the low dimensionality of histology techniques and the small size of human salivary gland biopsies. In this study, we took advantage of a molecularly validated mouse model of pSS to characterize tissue-infiltrating CD4 T cells and their regulation by the lymphotoxin/LIGHT signaling axis.

Emergent rules for codon choice elucidated by editing rare arginine codons in Escherichia coli.

The degeneracy of the genetic code allows nucleic acids to encode amino acid identity as well as noncoding information for gene regulation and genome maintenance. The rare arginine codons AGA and AGG (AGR) present a case study in codon choice, with AGRs encoding important transcriptional and translational properties distinct from the other synonymous alternatives (CGN). We created a strain of Escherichia coli with all 123 instances of AGR codons removed from all essential genes.

Design, synthesis, and testing toward a 57-codon genome.

Recoding--the repurposing of genetic codons--is a powerful strategy for enhancing genomes with functions not commonly found in nature. Here, we report computational design, synthesis, and progress toward assembly of a 3.97-megabase, 57-codon Escherichia coli genome in which all 62,214 instances of seven codons were replaced with synonymous alternatives across all protein-coding genes.

Preclinical Evidence of Anti-Tumor Activity Induced by EZH2 Inhibition in Human Models of Synovial Sarcoma.

The catalytic activities of covalent and ATP-dependent chromatin remodeling are central to regulating the conformational state of chromatin and the resultant transcriptional output. The enzymes that catalyze these activities are often contained within multiprotein complexes in nature. Two such multiprotein complexes, the polycomb repressive complex 2 (PRC2) methyltransferase and the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeler have been reported to act in opposition to each other during development and homeostasis.

[Morphophysiological and Behavioral Adaptations of Elk to Wintering].

This paper studies morphometric parameters (body weight, weight of internal organs, body size, etc.) in 170 elk of various sex and age obtained in the Vyatka taiga area in winter. A number of physiological parameters (specific metabolism and thermal conductivity, heat loss rate, etc.

Biocontainment of genetically modified organisms by synthetic protein design.

Genetically modified organisms (GMOs) are increasingly deployed at large scales and in open environments. Genetic biocontainment strategies are needed to prevent unintended proliferation of GMOs in natural ecosystems. Existing biocontainment methods are insufficient because they impose evolutionary pressure on the organism to eject the safeguard by spontaneous mutagenesis or horizontal gene transfer, or because they can be circumvented by environmentally available compounds.