Optimized Spheroid Model of Pancreatic Cancer Demonstrates Influence of Macrophage-T Cell Interaction for Intratumoral T Cell Motility.

Background: Most spheroid models use size measurements as a primary readout parameter; some models extend analysis to T cell infiltration or perform caspase activation assays. However, to our knowledge, T cell motility analysis is not regularly included as an endpoint in imaging studies on cancer spheroids.

Methods: Here, we intend to demonstrate that motility analysis of macrophages and T cells is a valuable functional endpoint for studies on molecular interventions in the tumor microenvironment.

Sodium chloride in the tumor microenvironment enhances T cell metabolic fitness and cytotoxicity.

The efficacy of antitumor immunity is associated with the metabolic state of cytotoxic T cells, which is sensitive to the tumor microenvironment. Whether ionic signals affect adaptive antitumor immune responses is unclear. In the present study, we show that there is an enrichment of sodium in solid tumors from patients with breast cancer.

Diversity and phage sensitivity to phages of porcine enterotoxigenic .

Enterotoxigenic (ETEC) is a diverse and poorly characterized pathotype that causes diarrhea in humans and animals. Phages have been proposed for the veterinary biocontrol of ETEC, but effective solutions require understanding of porcine ETEC diversity that affects phage infection. Here, we sequenced and analyzed the genomes of the PHAGEBio ETEC collection, gathering 79 diverse ETEC strains isolated from European pigs with post-weaning diarrhea (PWD).

Characterization and Abundance of Plasmid-Dependent Alphatectivirus Bacteriophages.

Antimicrobial resistance (AMR) is a major public health threat, exacerbated by the ability of bacteria to rapidly disseminate antimicrobial resistance genes (ARG). Since conjugative plasmids of the incompatibility group P (IncP) are ubiquitous mobile genetic elements that often carry ARG and are broad-host-range, they are important targets to prevent the dissemination of AMR. Plasmid-dependent phages infect plasmid-carrying bacteria by recognizing components of the conjugative secretion system as receptors.

Harmonic Imaging of Stem Cells in Whole Blood at GHz Pixel Rate.

The pre-clinical validation of cell therapies requires monitoring the biodistribution of transplanted cells in tissues of host organisms. Real-time detection of these cells in the circulatory system and identification of their aggregation state is a crucial piece of information, but necessitates deep penetration and fast imaging with high selectivity, subcellular resolution, and high throughput. In this study, multiphoton-based in-flow detection of human stem cells in whole, unfiltered blood is demonstrated in a microfluidic channel.

DYRK1B blockade promotes tumoricidal macrophage activity in pancreatic cancer.

Objective: Highly malignant pancreatic ductal adenocarcinoma (PDAC) is characterised by an abundant immunosuppressive and fibrotic tumour microenvironment (TME). Future therapeutic attempts will therefore demand the targeting of tumours and stromal compartments in order to be effective. Here we investigate whether dual specificity and tyrosine phosphorylation-regulated kinase 1B (DYRK1B) fulfil these criteria and represent a promising anticancer target in PDAC.

Agtrevirus phage AV101 recognizes four different O-antigens infecting diverse .

Bacteriophages in the genus are known for expressing multiple tail spike proteins (TSPs), but little is known about their genetic diversity and host recognition apart from their ability to infect diverse species. Here, we aim to determine the genetic differences that may account for the diverse host ranges of phages. We performed comparative genomics of 14 and identified only a few genetic differences including genes involved in nucleotide metabolism.

Isolation and characterization of novel plasmid-dependent phages infecting bacteria carrying diverse conjugative plasmids.

This work was undertaken because plasmid-dependent phages can reduce the prevalence of conjugative plasmids and can be leveraged to prevent the acquisition and dissemination of ARGs by bacteria. The two novel phages described in this study, Lu221 and Hi226, can infect , , sp. and sp.

Regulation of CO by the sea in areas around Latin America in a context of climate change.

Anthropogenic activities are increasing the atmospheric carbon dioxide (CO); around a third of the CO emitted by these activities has been taken up by the ocean. Nevertheless, this marine ecosystem service of regulation remains largely invisible to society, and not enough is known about regional differences and trends in sea-air CO fluxes (FCO2), especially in the Southern Hemisphere. The objectives of this work were as follows: first to put values of FCO2 integrated over the exclusive economic zones (EEZ) of five Latin-American countries (Argentina, Brazil, Mexico, Peru, and Venezuela) into perspective regarding total country-level greenhouse gases (GHG) emissions.

IL-17A-producing CD8 T cells promote PDAC via induction of inflammatory cancer-associated fibroblasts.

Objective: Pancreatic ductal adenocarcinoma (PDAC) is characterised by an abundant desmoplastic stroma composed of cancer-associated fibroblasts (CAF) and interspersed immune cells. A non-canonical CD8 T-cell subpopulation producing IL-17A (Tc17) promotes autoimmunity and has been identified in tumours. Here, we evaluated the Tc17 role in PDAC.

IL18 Receptor Signaling Regulates Tumor-Reactive CD8+ T-cell Exhaustion via Activation of the IL2/STAT5/mTOR Pathway in a Pancreatic Cancer Model.

Intratumoral cytotoxic CD8+ T cells (CTL) enter a dysfunctional state characterized by expression of coinhibitory receptors, loss of effector function, and changes in the transcriptional landscape. Even though several regulators of T-cell exhaustion have been identified, the molecular mechanisms inducing T-cell exhaustion remain unclear. Here, we show that IL18 receptor (IL18R) signaling induces CD8+ T-cell exhaustion in a murine pancreatic cancer model.

CRISPR-Cas9 Shaped Viral Metagenomes Associated with Bacillus subtilis.

Phages are viruses of bacteria and have been known for over a century. They do not have a metabolism or protein synthesis machinery and rely on host cells for replication. The model organism Bacillus subtilis has served as a host strain for decades and enabled the isolation of many unique viral strains.

A semaphorin-plexin-Rasal1 signaling pathway inhibits gastrin expression and protects against peptic ulcers.

Peptic ulcer disease is a frequent clinical problem with potentially serious complications such as bleeding or perforation. A decisive factor in the pathogenesis of peptic ulcers is gastric acid, the secretion of which is controlled by the hormone gastrin released from gastric G cells. However, the molecular mechanisms regulating gastrin plasma concentrations are poorly understood.

The Bacillus phage SPβ and its relatives: a temperate phage model system reveals new strains, species, prophage integration loci, conserved proteins and lysogeny management components.

The Bacillus phage SPβ has been known for about 50 years, but only a few strains are available. We isolated four new wild-type strains of the SPbeta species. Phage vB_BsuS-Goe14 introduces its prophage into the spoVK locus, previously not observed to be used by SPβ-like phages.

The POLD1 variant increases the sensitivity of colorectal cancer cells to ATR and CHK1 inhibitors.

Inhibition of the kinase ATR, a central regulator of the DNA damage response, eliminates subsets of cancer cells in certain tumors. As previously shown, this is at least partly attributable to synthetic lethal interactions between ATR and POLD1, the catalytic subunit of the polymerase δ. Various POLD1 variants have been found in colorectal cancer, but their significance as therapeutic targets for ATR pathway inhibition remains unknown.

A CRISPR-Cas9 tool to explore the genetics of Bacillus subtilis phages.

Here, we present pRH030, a new CRISPR-Cas9 tool for the genetic engineering of Bacillus phages and beyond. It is based on the Streptococcus pyogenes cas9 with its native constitutive promoter, tracrRNA, and a gRNA precursor. The constitutive expression of Cas9 was conducive to the inactivation of viral attackers and enhanced phage mutagenesis efficiency up to 100%.

Investigation of the influence of thrombophilic genes polymorphism, including serpin 1 (pai-i), fii, prothrombin and itgb3-˩ integrin, on the frequency of stroke in association with controllable risk factors for its occurrence.

Objective: The aim is the analysis of the relationship between the polymorphism of thrombophilic genes, in particular Serpin 1 (PAI-1), F2-prothrombin and ITGB3-α integrin, and the incidence of stroke, as well as the study of factor effects of this polymorphism in association with controlled risk factors (hypertonic disease, smoking, alcohol consumption, diabetes mellitus, obesity, atrial fibrillation).

Patients And Methods: Materials and methods: A total of 134 patients were examined (men accounted for 44.8%, women 55.

The differential statin effect on cytokine production of monocytes or macrophages is mediated by differential geranylgeranylation-dependent Rac1 activation.

Monocytes and macrophages contribute to pathogenesis of various inflammatory diseases, including auto-inflammatory diseases, cancer, sepsis, or atherosclerosis. They do so by production of cytokines, the central regulators of inflammation. Isoprenylation of small G-proteins is involved in regulation of production of some cytokines.

Draft Genome Sequence of the Butanoic Acid-Producing Bacterium Clostridium luticellarii DSM 29923, Used for Strong Aromatic Chinese Liquor Production.

The strictly anaerobic, Gram-positive bacterium , which has straight or slightly curved rod-shaped cells, polar endospores, and peritrichous flagella, is used for the production of strong aromatic Chinese liquors. is able to produce butanoic acid. The draft genome sequence consists of 3.

A genome-wide association study in a large F2-cross of laying hens reveals novel genomic regions associated with feather pecking and aggressive pecking behavior.

Background: Feather pecking and aggressive pecking in laying hens are serious economic and welfare issues. In spite of extensive research on feather pecking during the last decades, the motivation for this behavior is still not clear. A small to moderate heritability has frequently been reported for these traits.

The presence of extreme feather peckers in groups of laying hens.

Feather pecking is a serious economic and welfare problem in laying hens. Feather damage occurs mainly through severe feather pecking (SFP). Selection experiments have proved that this behavior is heritable and lines have been divergently selected for high (HFP) and low feather pecking (LFP).

Synthesis and Characterization of Tin(IV) Oxide Obtained by Chemical Vapor Deposition Method.

The effect of precursors on the characteristics of tin oxide obtained by chemical vapor deposition (CVD) method was investigated. The synthesis of nanosized tin(IV) oxide was carried out with the use of two different precursors: tin(II) oxalate obtained using tin chloride(II) and oxalic acid; tin(II) oxalate obtained using tin chloride(II); and ammonium oxalate. The synthesized tin(IV) oxide samples were studied by electron microscopy, X-ray diffraction and optical spectra.

Quantitative genetic analysis of causal relationships among feather pecking, feather eating, and general locomotor activity in laying hens using structural equation models.

The objective of this research was to analyze the relationship between feather pecking (FP) and feather eating (FE) as well as general locomotor activity (GLA) using structural equation models, which allow that one trait can be treated as an explanatory variable of another trait. This provides an opportunity to infer putative causal links among the traits. For the analysis, 897 F2-hens set up from 2 lines divergently selected for high and low FP were available.

Prospective evaluation of frequency of signs of systemic sclerosis in 76 patients with morphea.

Objectives: Some authors consider that morphoea and systemic sclerosis (SSc) could be part of the same disease spectrum. The aim of this study was to analyse the prevalence of signs indicative of SSc in a cohort of patients with morphoea.

Methods: This is a prospective multi-centre study performed in four French academic dermatology departments: 76 patients with morphoea and 101 age- and sex-matched controls, who underwent complete clinical examination, were enrolled.

SAR studies on hydropentalene derivatives--Important core units of biologically active tetramic acid macrolactams and ptychanolides.

Structurally diverse bicyclo[3.3.0]octanes were prepared and tested for their biological activity.