Biology Open最新文献

Honey bees (Apis mellifera) provide important ecosystem services to both natural and human-managed environments, but are increasingly threatened by a variety of pathogens, the most common of which is deformed wing virus (DWV). DWV is known to replicate in the honey bee brain and has been documented as both improving and impairing olfactory learning and memory. We examined the transcriptomic response of the honey bee mushroom bodies - an area of the insect brain associated with higher cognitive functions - in bees with naturally occurring DWV infections, which varied in their ability to perform an associative learning task. RNA-sequencing analysis detected increased expression of genes involved in the immune response, including important antimicrobial peptides such as hymenoptaecin, apidaecin, and abaecin, and the downregulation of lysozyme, prophenoloxidase, and other genes associated with responses to a range of stressors. Additionally, gene ontology enrichment analysis revealed overrepresentation of key biological processes that form part of the immune response. We also noted significant differential expression of long non-coding RNAs (lncRNAs) presumed to be acting in a regulatory manner, and used these lncRNAs to construct gene regulatory networks. Strikingly, in contrast to previous studies on bees with artificially induced infections that have examined viral loads in the abdomen and non-specific areas of the brain, no correlation between DWV load in the mushroom bodies and cognitive function was noted. This highlights the complexity of host-pathogen interactions in honey bee neural tissues and the benefits of a spatially refined approach to brain transcriptomics in naturally occurring infections.

Enteroendocrine cells (EECs) are rare intestinal epithelial cells producing multiple hormones that regulate essential aspects of digestion and energy. EEC subtypes, their hormone repertoire and differentiation mechanisms from intestinal stem cells have been characterized in the adult intestine. Although EECs must be functional from birth because their absence leads to severe intestinal malabsorption in newborns, the processes that determine their subtype specification during development remain largely unknown. We used mouse embryos, human pluripotent stem cell-derived intestinal organoid models and single-cell transcriptomics to characterize EEC lineages and dynamics during development. Our findings demonstrate that in both mice and humans, the majority of EECs are specified during development through similar differentiation trajectories to those observed in the adult intestine. This suggests that EEC subtype specification occurs independently of fully organized crypt-villus structures and stimulation by diet or microbiota. However, the emergence of certain EEC subtypes depends on tissue maturation. Finally, our integrative approach infers lineage-specific regulators dynamically, identifying new candidates controlling EEC differentiation in the developing human gut.

Plant phytochemicals found in nectar impact bee learning and memory and plant pollination success. Especially for generalist pollinators, dietary changes that alter phytochemical consumption could be common sources of behavioral variation. For honey bee (Apis mellifera L.) foragers, a major potential change in phytochemical consumption occurs when individuals switch from collecting nectar from flowers to collecting honey from neighboring colonies, a phenomenon known as honey robbing. In this study we investigated whether phytochemicals dominant in honey compared to nectar act as a short-term trigger of robbing behaviors in honey bee, which include increased aggression. We fed forager honey bees sucrose diets containing different phytochemicals found in nectar and honey and tested aggression using a lab-based assay. We found no evidence that phytochemicals altered forager behavior. We also compared the microbiome composition for foragers fed different phytochemicals and again found no effects. Our results suggest that neither direct effects of neuroactive phytochemicals, nor indirect effects through the structure or function of the gut microbiome, trigger honey robbing behaviors.

First Person is a series of interviews with the first authors of a selection of papers published in Biology Open, helping researchers promote themselves alongside their papers. Julio Fierro Morales is first author on ' Differential PaxillinB dynamics at Dictyostelium cell-substrate adhesions', published in BiO. Julio conducted the research described in this article while a PhD student in Dr Minna Roh-Johnson's lab at the University of Utah, Salt Lake City, USA. He is now a postdoc in the lab of Dr Florentine Rutaganira at the Beckman Center, Stanford, USA, elucidating the evolution of molecular machinery such as cell-substrate adhesions using non-Metazoan model organisms.

The primary cilium, a microtubule-based membrane protrusion, is essential for eukaryotic development and health. Import and export of proteins in and out of the primary cilium relies on intraflagellar transport protein complexes (IFT) IFT-B and IFT-A, in conjunction with their respective motor proteins. Here, using mouse fibroblast cells, we investigated the function of IFT139 (Thm1, TTC21B) in Hedgehog signaling, cilia structure, and ciliary protein localization, as well as the effect of the P209L ciliopathy mutation on cell proliferation and Hedgehog signaling. In cells without IFT139, Ptch1 retains normal localization, Smo and Gli accumulate in the distal tips of cilia with or without pathway activation, while SuFu fails to accumulate in cilia upon pathway activation. We also found that Arl13b abnormally accumulates at the distal tips of cilia, but acetylated tubulin does not. Lastly, the ciliopathy mutation P209L impairs cell proliferation and Hedgehog transcriptional response, mimicking a loss of function in IFT139. Our work highlights the multifaceted roles IFT139 have on distinct ciliary proteins, and its importance in ciliopathies.

ADAMTS13 is a metalloprotease that cleaves the von Willebrand factor and prevents pathological thrombosis. Severe genetic deficiency of ADAMTS13 causes congenital thrombotic thrombocytopenic purpura, a life-threatening thrombotic microangiopathy. Increasing evidence suggests that ADAMTS13 contributes to physiological processes beyond hemostasis, including vascular development and tissue homeostasis, but these functions remain poorly understood. To address this gap, we generated a transparent, multitransgenic adamts13i5 zebrafish model and began investigating the developmental and disease-related roles of ADAMTS13 in vivo. The adamts13i5 mutants recapitulated hallmark features of congenital thrombotic thrombocytopenic purpura, including erythrocyte fragmentation and schistocyte formation in adults. In larvae, ADAMTS13 loss unveiled a prothrombotic response to vascular injury, a phenotype masked in patients by thrombocytopenia. Mechanistically, ADAMTS13 deficiency impaired developmental vascular patterning, suppressed vegfa expression, and reduced macrophage number, accompanied by diminished inflammatory and pro-angiogenic signaling. ADAMTS13 loss disrupted hematopoietic homeostasis in adulthood, with myeloid expansion and lymphoid depletion in the kidney marrow. These findings establish ADAMTS13 as a multifaceted regulator of thrombosis, vascular development, inflammation, and hematopoietic lineage specification. The adamts13i5 zebrafish provides a powerful vertebrate model for dissecting the mechanisms of thrombotic thrombocytopenic purpura pathogenesis and identifying therapeutic strategies extending beyond hemostasis.

Temperature is a critical factor that modulates cellular metabolism and stem cell regulation. Despite extensive studies, the influence of temperature on stem cell regulation via Notch signaling has been limited to studies relying on studies that involve indirect readouts to Notch activation. This study systematically analyzes the effects of temperature on the Notch signaling transcriptional response at the chromosomal, cellular, and tissue levels. Using complementary direct Notch readouts, we demonstrate that Notch activation remains largely unchanged across temperatures, suggesting the presence of temperature-compensatory mechanisms that maintain robust Notch activation. Notch transcriptional activity readouts, however, increased with temperature, indicating that elevated temperatures may enhance Notch transcriptional activity at the chromosomal level. These findings provide a comprehensive framework for understanding effects of temperature and offer new insights into the regulation of Notch signaling in stem cell biology.

Physiological stress responses are energy intensive. Animals can meet their stress-induced energetic demands by altering foraging or selectively retaining ingested nutrients, although the latter is poorly studied. We tested the effects of elevated stress on elemental retention in Psammophilus dorsalis. Adult lizards of both sexes were allotted to either a stressed group (daily constraint) or control group for 10 days. We measured baseline corticosterone, glucose, and triglyceride levels of lizards at the beginning and end of the experiment, as well as the total amounts of carbon and nitrogen retained based on the ingested and egested content during the treatment phase. Both control and stressed groups had higher corticosterone levels at the end of the experiment, with stressed group males showing the greatest increase. Glucose and triglyceride levels were variable. Contrary to expectation, lizards from both treatments retained similar amounts of carbon and nitrogen during the experiment phase. Our results do not show support for changes in elemental retention under stressful conditions, although the stress of captivity itself could have masked the potential effect on elemental retention. Our study highlights the need to test elemental retention as a potential strategy to meet stress-induced energetic demands when foraging opportunities are limited.

Prolonged fasting impacts skeletal muscle by inducing atrophy, thereby limiting contractile capacity and altering tissue mechanical behavior. This study investigated the effects of 48 h of fasting (FAS) versus ad libitum food consumption (CON) on the mechanical properties of fast-twitch (extensor digitorum longus, EDL) and slow-twitch (soleus, SOL) muscles in three mouse strains with distinct muscle phenotypes: C57BL/6J (normal-sized), BEH+/+ (larger muscles), and BEH (myostatin-deficient with markedly larger muscles). Isolated SOL and EDL were subjected to 100 isometric-eccentric contraction cycles, and peak and specific force, rate of force development, fatigue, stiffness, and tangent modulus were assessed. Fasting significantly reduced muscle size and force production capacity (isometric and eccentric) across all strains (P<0.05). SOL muscles showed a greater decline in tetanic force (fatigue index: SOL 67% versus EDL 33%, P<0.05), while BEH mice exhibited the steepest contractile impairment (P<0.05). Fasting also reduced stiffness and tangent modulus across all strains and muscle types (P<0.05). These findings demonstrate that fasting consistently impairs contractile and mechanical properties of skeletal muscle, with slow-twitch muscles and larger muscles phenotypes being particularly vulnerable. Muscle type and genetic background thus play key roles in determining the extent of functional decline under metabolic stress.

Transgene expression in eHAP cells, a haploid cell line commonly used to generate gene knockouts, is difficult due to its low transfection efficiency and poor expression of integrated transgenes. To enable simple and reliable transgene expression, we engineered insulated integrating plasmids that sustain high levels of transgene expression in eHAP cells, and that can be used in other cell lines. These vectors are compatible with FLP-FRT and piggyBac integration, they flank a gene-of-interest bilaterally with tandem cHS4 core insulators, and co-express nuclear-localized blue fluorescent protein for identification of high expressing cells. We further demonstrate that transgenic haploid eHAP cells can be fused to form transgenic heterozygous diploid cells. This method creates diploid cells carrying the transgenic material of the haploid progenitors and allows for engineering of cells with defined heterozygous genotypes. These tools expand the range of experiments that can be performed in eHAP cells and other cultured cells.