Optimizing Amphipathic Antimicrobial Peptides via Helical Wheel Rotation.

Antimicrobial peptides (AMPs) have emerged as promising candidates for combating drug-resistant pathogens and certain cancer types. However, their therapeutic applications are often limited by undesired hemolytic activity, while many AMPs exhibit only moderate potency. Herein, the "helical wheel rotation" strategy as a simple, cost-effective, and modular approach to optimize the pharmacological properties of amphipathic α-helical AMPs without altering their amino acid composition is explored.

Genetic suppression features ABHD18 as a Barth syndrome therapeutic target.

Cardiolipin (CL) is the signature phospholipid of the inner mitochondrial membrane, where it stabilizes electron transport chain protein complexes. The final step in CL biosynthesis relates to its remodelling: the exchange of nascent acyl chains with longer, unsaturated chains. However, the enzyme responsible for cleaving nascent CL (nCL) has remained elusive.

Large-Scale Expansion of the MALDI-TOF MS Library for Comprehensive Identification of Yeasts and Filamentous Fungi in Clinical and Sanitary Contexts.

The rapid identification of microbes using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is gaining attention, particularly in clinical laboratories and hygiene management in food manufacturing. However, unlike bacteria, technical issues related to preprocessing and a lack of comprehensive reference libraries pose challenges in fungi. In this study, we constructed a new MALDI-TOF MS database, named EMALiMB, that expands the existing reference library to accurately identify a wider range of microbial species.

Enrichment of Horizontally Transferred Gene Clusters in Bacterial Extracellular Vesicles via Non-Lytic Mechanisms.

Bacterial extracellular vesicles are emerging as key mediators of horizontal gene transfer, enhancing microbial adaptability. A critical factor determining the effectiveness of horizontal gene transfer is the fraction of vesicles containing specific functional genes. However, the proportion of containing specific DNA fragments has not been adequately determined, which hinders the understanding of the conditions and mechanisms that facilitate the incorporation of specific genes into the vesicles and possible evolutionary roles of vesicle-derived DNA.

Structural analysis of a symbiotic system involving a Nanobdellati archaeon by cryo-electron tomography.

Nanobdellati (formerly DPANN) archaea are considered as primitive archaeal organisms that often live in symbiosis with archaeal hosts. In this study, we investigated the symbiotic mechanism between a Nanobdellati archaeon, Nanobdella aerobiophila strain MJ1, and its host archaeon Metallosphaera sedula strain MJ1HA, using cryo-electron tomography. In our tomographic observations, we identified a conical attachment organelle at the interface between MJ1 and MJ1HA during symbiosis.

Functional division of labor in motility, lignocellulose digestion, and nitrogen metabolism revealed for the Mixotricha paradoxa holobiont.

Mixotricha paradoxa is a large, cellulolytic flagellate present in the hindgut of the termite Mastotermes darwiniensis. This parabasalid flagellate is unique in its reliance on ectosymbiotic spirochetes for motility. We analyzed the transcriptome of M.

Insights from public database sequences related to the replication initiation protein TrfA of the IncP-1 plasmid RK2.

Replicon typing identifies sequences similar to known DNA replication initiators and is widely used to detect specific plasmid groups (e.g., IncP-1) in genome and metagenome sequencing data.

Pseudonocardia phyllosphaerae sp. nov., a Novel Actinomycete Isolated from Phylloplane of Rhizophora apiculata Blume.

A Gram-stain-positive actinomycete, designated strain 1LY6.1, was isolated from the phylloplane of a mangrove plant (Rhizophora apiculata Blume). Phylogenetic analysis based on 16S rRNA gene sequences revealed that the strain was most closely related to Pseudonocardia nantongensis KLBMP 1282 (98.

Allogeneic germline stem cell transplantation restores fertility in nonablated recipient mice†.

Spermatogonial stem cells (SSCs) colonize nonablated recipient testes. Autotransplantation of SSCs is expected to restore fertility in boys who become infertile due to cancer therapy. However, since the number of SSCs recovered from testis biopsies is small, increasing SSC number is a prerequisite.

Discovery of Streptomyces marinisediminis sp. nov., a new thiolutin producing actinomycete isolated from Thai marine sediment.

Thiolutin and 2,2-dioxidothiolutin are sulfur-containing antibiotics discovered through a targeted high-throughput screening strategy designed to identify compounds with antimicrobial activity. The producing strain, JHD1, is an actinomycete isolated from marine sediment collected in Chonburi Province, Thailand. Chemotaxonomic characteristics and 16S rRNA gene sequence analysis indicated that strain JHD1 belongs to the genus Streptomyces.

PPARγ-induced upregulation of fatty acid metabolism confers resistance to venetoclax and decitabine therapy in AML.

The combination of the B-cell lymphoma 2 (BCL2) inhibitor venetoclax (VEN) and the hypomethylating agent decitabine (DEC; VEN/DEC) constitutes a primary therapeutic strategy for treating older adults with acute myeloid leukemia (AML). However, a notable subset of patients exhibits resistance to VEN/DEC, demonstrating either no disease response or relapse after initial remission. This study aimed to elucidate the molecular mechanisms underlying this resistance through analyses of gene expression and DNA methylation profiles.

A simplified protocol for vitrification of hamster embryos.

Golden hamsters (Mesocricetus auratus) have been extensively used in biomedical research. With the advent of genome-editing technology, it is now possible to generate gene-knockout hamsters, providing unique research models that cannot be achieved with mice or rats. Therefore, the development of cryopreservation techniques for hamster embryos is in high demand.

A partial deletion of the Tardbp 3´UTR affects TDP-43 regulation and leads to motor dysfunction in mice.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that causes the selective loss of motor neurons. A histopathological hallmark of ALS is the cytoplasmic aggregation of TDP-43, a ubiquitously expressed RNA-binding protein involved in transcription and splicing regulation. To prevent abnormal accumulation, TDP-43 controls its expression levels through an autoregulatory feedback loop.

A taxonomic re-evaluation of , a hyperparasitic synnematous hyphomycete on , with gen. et comb. nov. ().

About 70 y after the first report by Yosio Kobayasi, we collected a little-known synnematous hyphomycete, , on decaying basidiocarps of growing on dead culms of two bamboo species in Tateyama (on ), Chichibu (type locality of ; on ), and Shigakogen (on ) in Japan, and obtained isolates of both the parasite and its host. Kobayasi provided only brief Latin and Japanese descriptions and quite elementary illustrations for , without depositing any herbarium specimens including the holotype. In this paper, a lectotype and an epitype of this species are designated respectively from the original protolog (illustration) of Kobayasi and our new material collected in Chichibu.

EML4-ALK Rearrangement Creates a Distinctive Myeloid Cell-Dominant Immunosuppressive Microenvironment in Lung Cancer.

Tyrosine kinase inhibitors are initially efficacious against anaplastic lymphoma kinase (ALK) fusion gene-positive lung adenocarcinoma, but acquired resistance inevitably occurs. Therefore, alternative treatment strategies are needed for tyrosine kinase inhibitor-resistant cases. Although the use of immune checkpoint inhibitors (ICI) has improved the prognosis of patients with lung cancer, patients with ALK+ lung adenocarcinoma exhibit little or no response to immunotherapy and the underlying resistance mechanisms remain unknown.

Difficult-to-culture micro-organisms specifically isolated using the liquid-liquid co-culture method - towards the identification of bacterial species and metabolites supporting their growth.

In this study, the liquid-liquid co-culture method was applied using faecal samples and specific bacterial species as growth-supporting bacteria. We aimed to isolate new, difficult-to-culture bacterial species using metabolites produced by supportive bacteria to promote the growth of small bacteria selected using filter treatment. This study aimed to identify the supporting bacteria and their metabolites that promote the growth of these isolates.

sp. nov., a novel bacterium, isolated from sea foam at Noto Peninsula, Ishikawa, Japan.

A Gram-stain-negative, aerobic, rod-shaped bacterium, designated as NT6N, was isolated from sea foam collected at the Maura Coast of the Noto Peninsula, Ishikawa, Japan. Strain NT6N was able to grow optimally at pH 7.8, 25-30 °C with 3.

Integration of single nucleus RNA-seq and bulk RNA-seq reveals gene regulatory networks for vascular connection between parasitic plants and host plants.

The facultative parasitic plant Phtheirospermum japonicum forms a specialized organ, the haustorium, to invade its host, Arabidopsis thaliana, establishing a vascular connection via the formation of a xylem bridge. This connection depends on coordinated interactions between the vascular systems of both plants, yet the molecular dynamics of these interactions within the haustorium and the host roots remain elusive. This study aimed to unravel the transcriptomic heterogeneity of haustoria and gene regulatory networks involved in this process by integrating single nucleus RNA sequencing (snRNA-seq) and bulk RNA sequencing (bulk RNA-seq).

Control of bioenergetic balance in mouse spermatogonial stem cells by alanine metabolism.

Although spermatogonial stem cells (SSCs) are considered to rely on glycolysis, they also require specific amino acids for self-renewal. Here we demonstrate a unique role of alanine in sustaining SSCs in vitro through pyruvate generation. Analysis of amino acid requirements in cultured SSCs revealed that alanine is indispensable for SSCs, even in the presence of glucose.

Ocular Phenotyping of Knockout Mice Identifies Genes Associated With Late Adult Retinal Phenotypes.

Purpose: Analyze phenotypic data from knockout mice with late-adult retinal pathologic phenotypes to identify genes associated with development of adult-onset retinal diseases.

Methods: The International Mouse Phenotyping Consortium (IMPC) database was queried for genes associated with abnormal retinal phenotypes in the late-adult knockout mouse pipeline (49-80 weeks postnatal age). We identified human orthologs and performed protein-protein analysis and biological pathways analysis with known inherited retinal disease (IRD) and age-related macular degeneration (AMD) genes using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), PLatform for Analysis of single cell Eye in a Disk (PLAE), Protein Analysis Through Evolutionary Relationships (PANTHER), and Kyoto Encyclopedia of Genes and Genomes (KEGG).

sp. nov., isolated from the Mekong River in Thailand.

Two Gram-stain-negative, aerobic, non-motile, non-gliding, rod-shaped bacterial strains, designated as TBRC 19031 and TBRC 19032, were isolated from water samples collected from the Mekong River, Thailand. Strain TBRC 19031 was obtained from Chiang Saen in the upstream section near the borders with China and Myanmar, while TBRC 19032 originated from Khong Chiam, in the downstream section where the river exits Thailand. Colonies of both strains were circular, smooth and deep yellow on Reasoner's 2A agar and did not produce flexirubin-type pigments.