Biocon (Switzerland)

Understanding the ecology of fungi in Aspergillus section Flavi is necessary to identify factors that contribute to aflatoxin accumulation risk and to improve interventions to reduce contamination. For example, interactions between non‑aflatoxigenic and aflatoxigenic Aspergillus species play a key role in determining the aflatoxin-producing potential of crop-associated fungi. The non-aflatoxigenic species A. tamarii is often associated with agricultural soils and occasionally with crops, prompting the question as to whether A. tamarii and aflatoxigenic A. flavus compete on these crops. In this study, interactions between A. tamarii and A. flavus during co-colonization and sporulation on maize kernels were assessed. In co-culture experiments, mycelial and conidial growth was measured for each species using a custom quantitative PCR assay, and aflatoxin was measured via lateral flow. Both A. tamarii and A. flavus exhibited reduced growth under co-culture, confirming these species compete for shared resources in maize kernels. However, their responses diverged in ways that suggest distinct life history strategies. In competition, there was a significant relationship between mycelial growth and production of conidia for A. tamarii. In contrast, for A. flavus isolates mycelial biomass in kernels and conidia production during co-colonization of maize kernels with A. tamarii were not correlated. This suggests differences in resource allocation between growth and reproduction between the two species. Additionally, isolate identity influenced competitive outcomes and aflatoxin production, underscoring the importance of genotype-level variation in fungal interactions. Understanding these species-specific interactions provides insight into fungal dynamics on crops and may inform strategies for managing aflatoxin contamination events.

Mitsuokella multacida AGMB01124 isolated from the feces of healthy swine was evaluated for its safety and potential as a next-generation probiotic (NGP). These bacteria have been increasingly reported to be positively correlated with short-chain fatty acids (SCFA), which are a beneficial energy source in the gut environment. We investigated the potential application of M. multacida AGMB01124 as an NGP by examining its genomic features, probiotic properties, cytotoxicity, oral toxicity, and its effect on SCFA levels in feces. Genome analysis did not identify any virulence-associated factors, and the strain harbored two antibiotic resistance genes (tetW/N/W and ermB). Furthermore, endoglucanase D (CelD) exhibited differences in four surface-exposed amino acid residues, three of which were located near the active site and one within the signal peptide region, suggesting a role in modulating catalytic function. Phenotypically, the strain exhibited susceptibility to most antibiotics recommended by Clinical & Laboratory Standards Institute and was non-hemolytic, non-cytotoxic. The strain demonstrated some tolerance to acidic and bile conditions, strong self-aggregation, co-aggregation with pathogens, and low cell surface hydrophilicity. Oral toxicity studies indicated no adverse effects on clinical signs, body weight, diet intake, relative organ weights, hematology, serum biochemistry, histopathology, or harmful enzyme activities. Short-chain fatty acid concentrations were significantly higher in the M. multacida AGMB01124-administered group than in the control group, suggesting potential contributions to host gut health and metabolic regulation. Therefore, this study provides preliminary evidence supporting the safety of the M. multacida AGMB01124 strain and its potential application as a candidate NGP.

Protein-Inspired Reconfigurable Nanovector-Based Coacervates Intrinsically disordered protein–inspired nanovectors undergo reversible conformational transitions that enable coacervate formation with diverse biomacromolecules. The resulting nanocoacervates remain stable under physiological conditions and can directly penetrate cellular membranes through the dynamic motion of the nanovectors. This platform supports efficient cytosolic delivery of a wide range of cargos, providing a versatile approach for intracellular transport technologies. More details can be found in the Research Article by Kwan Hyi Lee, Ja-Hyoung Ryu, Youngdo Jeong, and co-workers (DOI: 10.1002/adma.202507877).

Targeting intracellular tumor antigens presented by peptide human leukocyte antigen (pHLA) complexes offers a promising immunotherapeutic strategy for patients with limited treatment options. However, development of pHLA-targeted drugs such as T-cell receptor (TCR) mimic antibodies (TCRm) and TCR-based therapeutics remains challenging due to severe offtumor and off-target toxicities arising from incomplete pHLA off-target profiling. The fatal neurological toxicities observed in the MAGEA3 TCR-T cell trial, potentially linked to unanticipated cross-reactivity with EPS8L2- and MAGEA12-derived peptides, underscore the urgent need for more comprehensive safety assessment. While current preclinical de-risking methods utilize sequence similarity searches, they lack the layered integration of genetic context, HLA binding profiles, and structured risk assessment needed to comprehensively evaluate peptide cross-reactivity. To address these limitations, we developed EpiTox, a computational multi-modular platform that systematically identifies and evaluates pHLA off-targets. EpiTox integrates proteome-wide sequence similarity, genetic context, HLA binding profiles, and layered risk assessment to provide a holistic evaluation of potential cross-reactive peptides. Using MAGEA3 as a model, EpiTox identified known toxic off-targets and predicted novel epitopes. Notably, an anti-MAGEA3 therapeutic TCRm antibody bound several newly predicted off-targets, including three SNP-derived peptides. By enabling comprehensive and predictive preclinical safety screening, Epi-Tox supports safer TCRm drug development and may help prevent future clinical failures.

ABSTRACTAdipose tissue is a key determinant of the sensory, nutritional, and functional qualities of meat, yet its faithful replication in vitro remains one of the central challenges for cultured meat production. This review first examines the roles of fat in conventional meat, encompassing its contributions to flavor, texture, and nutritional value through diverse lipid classes such as triacylglycerols, phospholipids, and cholesterol. The biological basis of adipogenesis is then outlined across the phases of proliferation, differentiation, and maturation, emphasizing transcriptional regulators, metabolic transitions, and lipid remodeling that collectively shape adipocyte development. Building on these foundations, insights from in vivo regulation—including species, sex, cuts, and dietary influences—are integrated with in vitro culture strategies. These integrations illustrate how physiological cues can inform the design of media formulations, signaling environments, and scaffolding platforms to enhance lipid composition and improve nutritional quality as well as co‐culture strategies with myocytes to reproduce marbling‐like structures. By bridging adipose biology with tissue engineering, this review establishes a framework for cultured fat design that meets the sensory and nutritional benchmarks of conventional adipose tissue while offering opportunities for functional tailoring. Finally, remaining challenges are briefly discussed as critical steps for translating laboratory progress into viable and socially accepted food applications.

In eukaryotic cells, membraneless organelles (MLOs) are formed via liquid‒liquid phase separation (LLPS) involving intrinsically disordered proteins (IDPs) and biomacromolecules, enabling biomacromolecule transport without vesicles, transporters, or channels. Although MLO-mimetic coacervates generated from synthetic biomaterials can deliver biomacromolecules into cells, they lack the conformational adaptability of IDPs and a defined internalization mechanism, limiting their stability under physiological conditions and hindering biomedical translation. Here, IDP-inspired nanovectors (IDP-NVs) are developed with conformational adaptability capable of forming nanocoacervates (NCs) with biomacromolecules for cytosolic delivery. Mixing with IDP-NVs and cargos results in stable NCs under physiological conditions, and the NCs can directly penetrate cellular membranes through the molecular motion of IDP-NVs. After the internalization, cytoplasmic glutathione triggers NC disassembly, releasing biomacromolecules in the cytosol. The NCs effectively deliver biomacromolecules of diverse sizes, charges, shapes (globular proteins and antibodies), and functions (mRNAs and CRISPR units), demonstrating their versatility and potential for biomedical applications.

Abstract Essential genes are crucial for bacterial growth and the pathogenicity. However, how gene essentiality varies under distinct growth conditions and its role in virulence remains poorly understood. In this study, we constructed high-saturation Tn5 transposon mutant libraries for Xanthomonas citri subsp. citri (Xac), the causative agent of citrus canker disease, which results in substantial economic losses to the citrus industry. These libraries were generated under two growth conditions: nutrient-rich medium (NB) and plant-mimicking medium (XVM2). The libraries achieved an average insertion density of 6.85 base pairs, ensuring high-quality coverage. Using these libraries, we identified 568 genes in both bacterial populations as essential genes of Xac, while the 61 (NB) and 54 (XVM2) as conditional essential genes. To validate the findings, two allele-replacement mutants, ∆ublA and ∆pgl, were generated based on variations in insertion density and gap ratios between two growth conditions. These mutants exhibited significant growth defects in XVM2 and compromised virulence in citrus plants, as evidenced by weaker canker symptoms and reduced bacterial populations in planta. Additionally, we performed a comparative analysis of essential gene conservation across the Xanthomonas genus and other species within the class Gammaproteobacteria. A pan-essentialome dataset was assembled from four Xanthomonas strains, revealing a broad pan-essentialome and a precise core-essentialome. To facilitate further research, we developed XanthoBrowser ( http://xacdb.lumoxuan.cn/), an online resource that provides user-friendly interface for searching and comparison of essential genes across four Xanthomonas strains. In conclusion, this study provides comprehensive insights into bacterial adaptation mechanisms and highlight potential targets for bactericide development.

Abstract Study question What role do genetic factors play in infertile men acting fertilization and cleavage failures? Summary answer We identified novel variants in DNAH10, DNAH12, CFAP47, and PLCZ1 associated with sperm structural defects, contributing to male infertility through fertilization and cleavage failures. What is known already Male infertility is a significant global issue affecting a substantial number of individuals. Although numerous pathogenic candidate genes have been identified, the genetic causes underlying fertilization and cleavage failures in infertile men remain largely unexplored. Study design, size, duration This study involved whole-exome sequencing of 20 unrelated patients experiencing multiple IVF failures due to fertilization and cleavage issues at our IVF center. Sperm analyses were conducted using transmission electron microscopy and light microscopy. Abnormal embryos were assessed through morphological evaluation, whole-genome amplification, and next-generation sequencing. Candidate gene variants were validated via Sanger sequencing, followed by bioinformatics analysis, protein structural modeling, and functional assays. Participants/materials, setting, methods Twenty unrelated male patients with a history of recurrent IVF failures attributed to fertilization and cleavage defects. Main results and the role of chance We identified novel compound heterozygous variants in DNAH10 (c.2569C>T: p.Arg857*; c.4102A>G: p.Met1368Val) and DNAH12 (c.2439delG: p.Thr814Leufs*8; c.10254G>T: p.Trp3418Cys) in patients with fertilization failures during conventional IVF. Additionally, a hemizygous missense variant in CFAP47 (c.8006C>T: p.Thr2669Met) was linked to cleavage failures, and a homozygous missense variant in PLCZ1 (c.589C>T: p.Arg197Cys) was associated with polyspermy and fertilization failures. A quantitative parental contamination test using next-generation sequencing confirmed the involvement of PLCZ1 in polyspermy-related fertilization failures. Intracytoplasmic sperm injection (ICSI) emerged as a potential effective treatment for patients with DNAH10 and DNAH12 variants, while combining ICSI with assisted oocyte activation (AOA) may improve reproductive outcomes for those with CFAP47 and PLCZ1 deficiencies. Limitations, reasons for caution In this study, we uncovered the relationship between the genotype and phenotype of novel causative variants associated with sperm head deformities in humans. However, the precise molecular mechanisms by which these genes contribute to sperm head development remain unclear and warrant further investigation in future research. Wider implications of the findings This genetic evidence enhances our understanding of the mechanisms behind fertilization and cleavage failures in male infertility. It provides valuable insights that can inform personalized treatment strategies and improve reproductive outcomes for affected individuals. Trial registration number No

In 2023 and 2024, record global temperatures and numerous extreme weather events underscored the urgency of addressing climate change and its far-reaching environmental, social, and economic impacts. As these changes intensify, it is more important than ever for the scientific community to effectively communicate their findings to society and decision-makers. Bridging the gap between scientific knowledge and public understanding is essential for favoring informed decision-making and meaningful action on climate issues. Although scientists are among the most trusted professionals, inter- and transdisciplinary collaboration with communication experts is essential to improve scientific outreach on this critical issue. At the 2024 Annual Meeting of the European Meteorological Society (EMS) in Barcelona, we organized a workshop targeted to climate scientists to address challenges in climate science communication. Featuring experts from neuroscience, communication studies, activism, and journalism, the workshop fostered cross-disciplinary dialogue to identify strategies to raise public awareness of the climate crisis. This paper summarizes the key insights of the workshop, emphasizing the importance of training climate scientists in effective communication, enlarging networks for collaborative communication efforts, and integrating neuroscientific knowledge about cognitive biases and attitude change into messaging. Key takeaways from the workshop include: 1. recognizing and valuing the expertise and perspectives of the other party in the dialogue (dialogue-model), 2. understanding the influence of cognitive dissonance and biases in climate science communication, and 3. developing compelling research-based narratives that address both problem and solution through collaboration with communication professionals, such as journalists. These recommendations aim to empower the next generation of climate scientists to engage with society as trusted and impactful communicators.