Biology Open最新文献

Antibiotic treatment is often necessary to eliminate life-threatening bacterial infections. However, these treatments can alter production of bacterial extracellular vesicles (BEVs), which often contain pro-inflammatory biomolecules. In this study, we examined how the clinically relevant antibiotics meropenem, tobramycin, and ciprofloxacin impacted BEV production from a urinary tract infection-associated Escherichia coli strain (CFT073 [WAM2267]) and a meningitis-associated strain (K1 RS218). BEVs from both strains caused a dose-dependent increase in expression of intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells, priming the endothelium for interactions with immune cells. Blockade of toll-like receptor 4 revealed that this receptor was responsible for BEV-endothelial interactions. Treatment with meropenem, a β-lactam antibiotic, increased production of BEVs from strain K1 RS218. Furthermore, meropenem treatment caused strain CFT073 [WAM2267] to produce BEVs with heightened stimulatory capacity, possibly by amplifying the content of lipoprotein Lpp in these BEVs as measured by mass spectrometry. To our knowledge, this is the first study examining the interplay between antibiotic treatment and the effects of the resulting BEVs on endothelial ICAM-1 expression. Our results indicate treatment risks of certain antibiotics against specific strains of E. coli and could help identify therapeutic targets to reduce BEV-mediated endothelial stimulation during infection.

During embryogenesis, the establishment of left-right (LR) asymmetry depends on directional fluid flow generated by motile cilia within the left-right organizer (LRO). Disruption of this process can lead to laterality disorders such as situs inversus, heterotaxy, and congenital heart defects. Here, we identify CCDC57 as a regulator of ciliary function and LR patterning. Depletion of ccdc57 via morpholino oligonucleotides (MOs) led to abnormal cilia in the multiciliated cells of the embryonic epidermis of Xenopus. Additionally, LR markers, dand5 and pitx2c were misexpressed resulting in defects in normal rightward cardiac looping. Finally, we identified a patient with situs inversus carrying compound heterozygous CCDC57 missense variants. We tested these variants in Xenopus depleted of ccdc57. Wild-type human CCDC57 mRNA, but not the patient variants, rescued ciliary structure and function. These findings establish ccdc57 as a regulator of LR patterning and suggest its potential involvement in human laterality disorders.

The International Dutch Embryo Model Meeting took place at Radboud University in Nijmegen, the Netherlands, on March 27 and 28, 2025. This year's meeting, which was previously held twice as a Dutch event, served as a platform to discuss the progress made in studying embryonic development using in vitro embryo-like structures. Organised into sessions on pluripotency, blastoids, gastruloids, and gametes, the meeting featured presentations by invited (inter)national speakers. These talks were complemented by shorter presentations from academics and industry professionals, as well as poster presentations interspersed between sessions. The meeting included an interactive ethics session that explored the opportunities and risks of researching embryos and embryo-like structures. This Meeting Review aims to provide an overview of the first International Dutch Embryo Model Meeting by highlighting the topics discussed by leading experts in embryo modelling.

Environmental context profoundly influences organismal biology, yet laboratory studies often rely on simplified conditions that may not fully capture natural phenotypic repertoire. This exploratory study investigated how rearing environment affects various aspects of Caenorhabditis elegans biology by comparing worms cultured in three-dimensional decellularized fruit tissue scaffolds with those raised on standard two-dimensional agar plates. While fat content and feeding rate remained stable across conditions, other life history traits demonstrated varying degrees of plasticity in response to environmental context. We observed that scaffold-grown worms exhibited reduced body size, altered reproductive strategies, and mild enhancements in stress resistance, burrowing ability, swimming kinematics and exploratory behavior. RNA sequencing revealed distinct transcriptional profiles between scaffold-grown and agar-grown worms, with most changes arising within one generation. Some traits showed evidence of intergenerational inheritance. Our findings highlight the sensitivity of C. elegans biology to rearing conditions and underscore the importance of considering environmental context in interpreting laboratory results. This work sets the foundation for future research into the mechanisms underlying environmental adaptation and phenotypic plasticity in model organisms.

Precise genome editing remains a major challenge in functional genomics, particularly for generating knock-in (KI) alleles in model organisms. Here, we introduce the mini-golden system, a versatile Golden Gate-based subcloning platform that enables rapid assembly of donor constructs containing homology arms and a gene of interest. This system offers a library of middle entry vectors including diverse genes, enhancing the preparation of donor minicircles for KI applications. Using the mini-golden system, we efficiently generated a foxd3CreER KI zebrafish line, allowing conditional recombination in neural crest cells. To further improve genome editing precision, we developed a synthetic exon-based donor template strategy combined with fluorescence screening. Using this approach, we successfully engineered a targeted isoleucine-to-valine substitution (Ile-to-Val) in hbaa1.2, one of the two adult hemoglobin alpha genes in zebrafish. Importantly, despite the high sequence similarity between hbaa1.2 and its paralog hbaa1.1, our strategy specifically edited hbaa1.2, demonstrating the effectiveness of the synthetic exon approach. This method minimized undesired recombination and significantly improved the identification of lines carrying the edited genome. Together, we provide a robust toolkit for efficient and precise genome engineering in zebrafish, with broad applicability to other model systems.

The unpredictability of the environment can shape not only the mean behavioral expression but also the structure of behavioral variance within wild populations. Yet, empirical tests integrating individual variation, trait covariances, and correlated plasticities across ecologically relevant gradients remain rare, particularly those aimed at phenotype integration. Using wild zebrafish, we examined how long-term exposure to turbidity and immediate changes in water clarity influence behavioral means, individual (co)variances, and plasticity integration across three coping behaviors - activity, aggression, and boldness. Adult fish were conditioned in clear and turbid water for a month, followed by repeated behavioral tests in clear as well as in turbid water. Individuals that were maintained in clear or turbid water for a month showed substantial variation in their behavioral adjustments when exposed to perturbations in the water-clarity. Mean behaviors changed primarily in response to immediate change in water turbidity and trial repetition, not long-term conditioning. However, conditioning strongly altered individual variance structure; turbid-conditioned individuals showed reduced consistency across testing waters, indicating greater behavioral flexibility under sensory uncertainty. The only evidence to behavioral syndromes was between activity and boldness [r=-0.379] among clear-conditioned treatment, whereas within-individual correlations between aggression and boldness were prominent in turbid-conditioned fish. Despite substantial variation in behavioral plasticity, we detected no among-individual correlations in plasticity across traits. Together, these results demonstrate that turbidity modulates multi-scale behavioral variation, influencing how traits covary and integrate within individuals, and highlight how environmental unpredictability shapes flexibility in coping strategies.

Coordinated cell polarity and force-responsive protein localization are essential for tissue morphogenesis, yet how embryonic cells sense forces and respond to mechanical cues remains a challenging question. Afadin- and α-actinin-binding protein (ADIP) has been implicated in microtubule minus-end anchoring, centrosome maturation and ciliogenesis. ADIP is also proposed to associate with the actomyosin cortex and regulate collective cell migration. ADIP behaves as a mechanosensitive planar cell polarity (PCP) protein when overexpressed in Xenopus embryos, but the distribution and regulation of endogenous ADIP has been unknown. Here we show that ADIP is present in early ectoderm as randomly distributed puncta that rapidly reorganize and polarize during epithelial wound repair. Endogenous ADIP also becomes enriched and planar polarized in the anterior neural plate towards the midline, consistent with its regulation by mechanical forces that operate during neural tube closure. ADIP polarization is attenuated by depletion of the core PCP component Diversin/Ankrd6, in agreement with the proposed interaction between the two proteins during PCP establishment. Finally, pharmacological disruption of microtubules, F-actin, and nonmuscle myosin II eliminates ADIP polarization in the neuroectoderm, indicating roles for microtubules and actomyosin networks in PCP. Together, these findings suggest that endogenous ADIP senses mechanical cues via the cytoskeletal machinery and functions in a context-dependent manner to control collective cell behaviors during vertebrate morphogenesis.

The Notch signaling pathway is crucial for germline stem cell (GSC) regulation in Caenorhabditis elegans, yet the molecular and biological consequences of GLP-1/Notch mutations remain poorly understood. This study systematically analyzes commonly used and pathological glp-1 loss- (lf) and gain-of-function (gf) mutations to investigate their effects on Notch activity at nascent transcript (ATS), mRNA, and germline levels. Using complementary direct readouts of Notch activation, including sygl-1 activation sites, mRNA levels, and germline functional assays of the Notch-responsive GSC pool and progenitor zone (PZ), we demonstrate that the severity of glp-1 mutations is dependent on their position within the GLP-1 protein. Among the commonly used glp-1 alleles we examined, NICD mutations reduced Notch transcriptional activation at cellular and germline levels while having little impact at the chromosomal (ATS) level, whereas partial lf NECD mutations have minimal effects across all biological levels. Furthermore, a series of regression analyses of sygl-1 activation, mRNA production, and PZ size reveal strong correlations, qualifying these readouts as predictive markers for germline function. These findings provide a comprehensive framework for understanding glp-1 mutation effects and offer new insights into the regulation of Notch signaling in stem cell biology.

Camellia rubriflora (C. rubriflora), a member of the genus Camellia, is an endemic species in the northern mountainous region of Vietnam. However, overexploitation of this species has placed it at risk of extinction, and conservation strategies need to be implemented to ensure its continued survival. This study evaluated the ex-vitro propagation potential of C. rubriflora using cuttings obtained from a nursery. The effects of seasonality, rooting media, and NAA concentration on survival rate, bud break rate, rooting ability of cuttings were investigated. Spring propagation of cuttings performed significantly better than those in other seasons. Using a rooting medium composed of soil and carbonized rice husk, combined with 150 ppm NAA, significantly enhanced growth parameters, achieving a 77.8% survival rate, 94.4% bud break rate, and 72.2% rooting rate, significantly higher than the control using soil without NAA. Root number and root length were also significantly increased under optimal conditions, reaching 5.2±1.0 roots per cutting and 9.4±0.9 mm, respectively. The high correlation between survival rate, bud break rate, and rooting rate was observed, especially when using Soil+CRH, ranging from 0.709 to 0.843, showing the simultaneous impact of experimental factors on the evaluation criteria. Evaluating optimal conditions for the propagation of C. rubriflora played an important role in enhancing the conservation potential of this endemic species at risk of extinction.

The Loke Centre for Trophoblast Research Annual Meeting, 'The Placenta at Term', was held on 7-8 July, 2025, at the University of Cambridge, UK. The meeting brought together leading clinical and basic scientists from around the world to explore how robust research methods can improve understanding of placental complications such as preeclampsia, fetal growth restriction, and gestational diabetes. This Meeting Review highlights emerging research directions and emphasises the remarkable potential of the placenta, not only as a window into obstetrical complications, but also as a diagnostic tool for predicting the short- and long-term health of both mother and child.