Multi-omic investigation identifies key antifungal biochemistry during fermentation of a Streptomyces biological control agent.

The use of multi-omic approaches has significantly advanced the exploration of microbial traits, leading to the discovery of new bioactive compounds and their mechanisms of action. Streptomyces sp. MH71 is known for its antifungal properties with potential for use in crop protection.

Numerical and Experimental Research of the Plastic Forming Process of Hastelloy X Alloy Sheets Using Elastomeric and Steel Tools.

The results of experimental and numerical studies of plastic forming of sheets made of the difficult-to-deform Hastelloy X, a nickel-based alloy with a thickness of 1 mm, using layered elastomeric punches and steel dies, are presented in this publication. The elastomeric punches were characterized by hardness in the range of 50-90 Shore A, while the dies were made of 90MnCrV8 steel with a hardness of over 60 HRC. The principle of operating the stamping die was based on the Guerin method.

Microbial communities associated with marine sponges from diverse geographic locations harbor biosynthetic novelty.

Marine sponges are a prolific source of biologically active small molecules, many of which originate from sponge-associated bacteria. Identifying the producing bacteria is a key step in developing sustainable routes for the production of these metabolites. To facilitate the required computational analyses, we developed MetaSing, a reproducible singularity-based pipeline for assembly, identification of high-quality metagenome-assembled genomes (MAGs), and analysis of biosynthetic gene clusters (BGCs) from metagenomic short-read data.

Genome Mining Analysis Uncovers the Previously Unknown Biosynthetic Capacity for Secondary Metabolites in Verrucomicrobia.

Bacteria of the phylum Verrucomicrobia is widely distributed in diverse ecological environments. Their limited cultivability has greatly caused the significant knowledge gap surrounding their secondary metabolites and their mediating ecological functions. This study delved into the diversity and novelty of secondary metabolite biosynthetic gene clusters (BGCs) of Verrucomicrobia by employing a gene-first approach to investigate 2323 genomes.

Confidence of Emergency Department doctors in managing ophthalmic emergencies: a systematic review.

Background: Eye emergencies constitute a significant portion of attendances to general Emergency Departments (EDs) in the UK, therefore it is important to assess the confidence of doctors who work in this setting in managing these potentially sight- and life-threatening presentations. This systematic review aims to assess the confidence of UK doctors working in general EDs in managing ophthalmic emergencies.

Methods: MEDLINE (Ovid), EMBASE (Ovid), ProQuest Central and Web of Science databases and grey literature were searched from inception to 1 October 2022 for publications that (1) featured doctors working in UK general EDs, (2) assessed doctors' confidence in managing ophthalmic emergencies, (3) contained original data, (4) were full-text, and (5) written in English.

Treatment with the apoptosis inhibitor Asunercept reduces clone sizes in patients with lower risk Myelodysplastic Neoplasms.

In low-risk Myelodysplastic Neoplasms (MDS), increased activity of apoptosis-promoting factors such as tumor necrosis factor (TNFα) and pro-apoptotic Fas ligand (CD95L) have been described as possible pathomechanisms leading to impaired erythropoiesis. Asunercept (APG101) is a novel therapeutic fusion protein blocking CD95, which has previously shown partial efficacy in reducing transfusion requirement in a clinical phase I trial for low-risk MDS patients (NCT01736436; 2012-11-26). In the current study we aimed to evaluate the effect of Asunercept therapy on the clonal bone marrow composition to identify potential biomarkers to predict response.

mutations are associated with a response to alvocidib and 5-azacytidine combination in myelodysplastic neoplasms.

Inhibitors of anti-apoptotic BCL-2 family proteins in combination with chemotherapy and hypomethylating agents (HMA) are promising therapeutic approaches in acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS). Alvocidib, a cyclin-dependent kinase 9 (CDK9) inhibitor and indirect transcriptional repressor of the anti-apoptotic factor MCL-1, has previously shown clinical activity in AML. Availability of biomarkers for response to the alvocidib + 5-azacytidine (5-AZA) could also extend the rationale of this treatment concept to high-risk MDS.

Significant improvement of bone marrow-derived MSC expansion from MDS patients by defined xeno-free medium.

Background: Robust and reliable in vitro and in vivo models of primary cells are necessary to study the pathomechanisms of Myelodysplastic Neoplasms (MDS) and identify novel therapeutic strategies. MDS-derived hematopoietic stem and progenitor cells (HSPCs) are reliant on the support of bone marrow (BM) derived mesenchymal stroma cells (MSCs). Therefore, isolation and expansion of MCSs are essential for successfully modeling this disease.

Inhibition of lysyl oxidases synergizes with 5-azacytidine to restore erythropoiesis in myelodysplastic and myeloid malignancies.

Limited response rates and frequent relapses during standard of care with hypomethylating agents in myelodysplastic neoplasms (MN) require urgent improvement of this treatment indication. Here, by combining 5-azacytidine (5-AZA) with the pan-lysyl oxidase inhibitor PXS-5505, we demonstrate superior restoration of erythroid differentiation in hematopoietic stem and progenitor cells (HSPCs) of MN patients in 20/31 cases (65%) versus 9/31 cases (29%) treated with 5-AZA alone. This effect requires direct contact of HSPCs with bone marrow stroma components and is dependent on integrin signaling.

A Genomic Survey of the Natural Product Biosynthetic Potential of Actinomycetes Isolated from New Zealand Lichens.

Actinomycetes are prolific producers of industrially valuable and medically important compounds. Historically, the most efficient method of obtaining compounds has been bioactivity-guided isolation and characterization of drug-like molecules from culturable soil actinomycetes. Unfortunately, this pipeline has been met with an increasing number of rediscoveries, to the point where it is no longer considered an attractive approach for drug discovery.

A patient-reported outcome measure for patients with pituitary adenoma undergoing transsphenoidal surgery.

Purpose: Pituitary adenomas affect patients' quality-of-life (QoL) across several domains, with long-term implications even following gross-total resection or disease remission. While clinical outcomes can assess treatment efficacy, they do not capture variations in QoL. We present the development and validation of a patient reported outcome measure (PROM) for patients with pituitary adenomas undergoing transsphenoidal surgery.

Correction: Mapping and predictive variations of soil bacterial richness across France.

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

Comparison of Lesser Toe Proximal Interphalangeal Joint Arthrodesis Versus Resection Arthroplasty: A Randomized Controlled Study.

The goal of this study was to compare operative outcomes after lesser toe deformity correction with either proximal interphalangeal (PIP) joint arthrodesis or PIP joint resection arthroplasty. A prospective randomized controlled trial was performed with 37 patients (48 toes) operated on with one of these two procedures. Evaluation of the numeric rating scale score, the American Orthopedic Foot and Ankle Society score, osseous consolidation, and clinical outcome was performed preoperatively and at 6 weeks and 6 months postoperatively.

Humanized three-dimensional scaffold xenotransplantation models for myelodysplastic syndromes.

Patient-derived xenograft (PDX) models have emerged as versatile preclinical platforms for investigation of functional pathomechanisms in myelodysplastic syndromes (MDS) and other myeloid neoplasms. However, despite increasingly improved methodology, engraftment efficiencies frequently remain low. Humanized three-dimensional scaffold models (ossicle xenotransplantation models) in immunocompromised mice have recently been found to enable improved engraftment rates of healthy and malignant human hematopoiesis.

Confidence of UK Ophthalmology Registrars in Managing Posterior Capsular Rupture: Results from a National Trainee Survey.

Introduction: To establish the level of confidence amongst UK ophthalmology specialist registrars (residents) in managing posterior capsule rupture (PCR) during cataract surgery.

Methods: An online nine-item questionnaire was distributed to all registrars, recruited nationwide via regional representatives. Data collected included stage of training, number of completed cataract operations, cumulative PCR rate, number of PCRs independently managed, understanding of vitrectomy settings and fluidic parameters and access to simulation.

Bone marrow derived stromal cells from myelodysplastic syndromes are altered but not clonally mutated in vivo.

The bone marrow (BM) stroma in myeloid neoplasms is altered and it is hypothesized that this cell compartment may also harbor clonal somatically acquired mutations. By exome sequencing of in vitro expanded mesenchymal stromal cells (MSCs) from n = 98 patients with myelodysplastic syndrome (MDS) and n = 28 healthy controls we show that these cells accumulate recurrent mutations in genes such as ZFX (n = 8/98), RANK (n = 5/98), and others. MDS derived MSCs display higher mutational burdens, increased replicative stress, senescence, inflammatory gene expression, and distinct mutational signatures as compared to healthy MSCs.

Microbial transfers from permanent grassland ecosystems to milk in dairy farms in the Comté cheese area.

The specificity of dairy Protected Designation of Origin (PDO) products is related to their "terroir" of production. This relationship needs better understanding for efficient and sustainable productions preserving the agroecological equilibrium of agroecosystems, especially grasslands. Specificity of PDO Comté cheese was related to the diversity of natural raw milk bacterial communities, but their sources need to be determined.

Skyllamycins D and E, Non-Ribosomal Cyclic Depsipeptides from Lichen-Sourced .

The skyllamycins are a class of heavily modified, non-ribosomal peptides, first isolated from sp. KY11784. A strain with potent antibiotic activity against was isolated from a sample of the New Zealand lichen .

Complete Genome Sequence of a Novel Pseudomonas fluorescens Strain Isolated from the Flower of Kūmarahou (Pomaderris kumeraho).

Kūmarahou (Pomaderris kumeraho) is a shrub endemic to New Zealand used in rongoā (traditional medicine). While studying the antimicrobial properties of kūmarahou, we isolated a new strain of Pseudomonas fluorescens, which we designated KF1 (for "kūmarahou flower 1"). Here, we report the complete genome sequence of P.

Preclinical evaluation of eltrombopag in a PDX model of myelodysplastic syndromes.

Preclinical research of myelodysplastic syndromes (MDSs) is hampered by a lack of feasible disease models. Previously, we have established a robust patient-derived xenograft (PDX) model for MDS. Here we demonstrate for the first time that this model is applicable as a preclinical platform to address pending clinical questions by interrogating the efficacy and safety of the thrombopoietin receptor agonist eltrombopag.