Journal of Biosciences最新文献

The epithelial sheath covering the stingray spine results in wounds to humans that are characterized by edema, necrosis, effusive bleeding and extreme pain. Kinins are potent autocoids that produce each of these symptoms. In this study, the dorsal and ventral portions of the epithelial sheath covering the spine of the Atlantic stingray (Hypanus sabinus) spine were analysed for components of the kallikrein-kinin system. Colorimetric assays showed kallikrein activity in both dorsal and ventral epithelial sheath preparations. Trypsin, which cleaves the inactive proenzyme to its active (kallikrein) form, resulted in an increase in the median kallikrein of 2.02 and 0.94 in dorsal and ventral spine preparations, respectively. Radioimmunoassay of kinin itself showed detectable immunoreactivity in the entire integumentary sheath. Trypsin treatment resulted in an increase in median immunoreactivity by 12.88. In vivo analyses for effects of epithelial extract on mammalian capillary leakage showed an increase in median capillary leakage of 5.25 in spine epithelia-treated animals compared to controls. Components of the kallikrein-kinin system are present in the Atlantic stingray spine epithelium and may account for some of the pathologies of stings in humans.

Exosomes (Exos) derived from mesenchymal stem cells (MSCs) are known to influence cancer cell behavior; however, the clinical use of MSCs is limited due to the gradual loss of their differentiation potential with continuous passaging. Induced mesenchymal stem cells (iMSCs) have emerged as a promising alternative source, but the effects of Exos derived from iMSCs (iMSC-Exos) on cancer cells remain incompletely understood. This study aims to compare the effects of iMSC-Exos with ADMSC-Exos derived from adipose tissue-derived mesenchymal stem cells (ADMSCs) on the viability, invasion, and migration of breast (MCF7) and lung (A549) cancer cells. Conditioned media from iMSCs and ADMSCs were collected for isolation and characterization of Exos. MCF7 and A549 cell lines were treated with iMSC- and ADMSC-Exos, and Exos uptake, cell viability, migration, senescence, and expression of BAX and BCL-2 genes were evaluated. iMSCand ADMSC-Exos were successfully internalized into cancer cells, with a higher efficiency of ADMSC-Exos uptake in MCF7 cells. Cell viability decreased and migration increased in both cancer cell lines upon treatment. BAX expression was significantly reduced in MCF7 cells following ADMSC-Exos treatment and in A549 cells after iMSC-Exos treatment. In contrast, BCL-2 expression was significantly reduced in MCF7 cells treated with both iMSC- and ADMSC-Exos, while it significantly increased in A549 cells after ADMSC-Exos treatment. A549 lung cancer cells showed a higher level of senescence than MCF7 breast cancer cells, particularly when treated with iMSC-Exos. Minimal overall differences were observed in viability, apoptosis, and migration assays between iMSC- and ADMSC-Exos in MCF7 and A549 cells. However, significant differences were observed in the senescence and expression of BAX and BCL-2 genes across cancer cell lines. These findings highlight the importance of further investigation into the distinct effects of iMSC- and ADMSC-Exos on cancer cell biology.

Neuromodulators such as neuropeptides activate specific G-protein-coupled receptors to reconfigure activity patterns of neural circuits and alter animal behavior. However, we have an incomplete understanding of the context-dependent mechanisms through which neuromodulators alter in vivo behavioral states. Here, we report a novel off-food behavioral requirement of the Caenorhabditis elegans RFamide receptor npr-1. Removal from food initiates a unique motor program where wild-type worms increase their turning frequency during local search for food. Upon longer exposure to starvation, the turns are suppressed and replaced by forward locomotion that favors efficient dispersal during global food search to locate new resources. Animals with loss of mutation in the npr-1 locus or the NPR-1(215F) variant exhibit strikingly reduced turning ability during global search. Moreover, in contrast to their high-speed on-food locomotion, mutations in NPR-1 or its ligands FLP-18 and FLP-21 produce dramatic reduction in locomotion rate and dispersal efficiency during global search. Interestingly, npr-1 mutants are still capable of resuming high-speed locomotion when re-introduced into food after starvation. Thus, our results probably suggest alternate circuit mechanisms underlying the contradictory NPR-1-mediated modulation of locomotion in the presence and absence of food.

Rhythmic behaviors controlled by internal biological clocks are universal among living organisms, ranging from single cells to humans. The inner workings and modulations of the intrinsic oscillatory activities that underlie these rhythmic behaviors are diverse and not well understood across different systems. The Caenorhabditis elegans defecation behavior, also known as the defecation motor program, is a particularly intriguing rhythmic behavior that has been studied for over 30 years since James Thomas' pioneering work in 1990. Numerous conserved genes and signaling molecules have been identified through meticulous studies of every detail of its genetics, physiology, and behavior. Since earlier works have been reviewed until 2006 in the literature, this review is not intended to be comprehensive and will instead focus on progress since then, with emphases on intestinal calcium and proton oscillations as well as the modulation of the defecation rhythm by the enteric nervous system.

Polymerization of branched actin networks by the ARP2/3 complex plays a critical role in diverse cellular processes. ARP2/3 activity is tightly controlled by the upstream CDC-42 GTPase and effectors such as the Wiscott-Aldrich syndrome protein (N-WASP/Wiscott-Aldrich Syndrome Protein (WSP-1)) and members of the F-BAR containing transducer of CDC-42-dependent actin assembly (TOCA) protein family. While the mechanisms governing WASP/N-WASP (neural-WASP) functioning are well understood, the regulatory dynamics of TOCA proteins at the cell cortex remain poorly characterized. Here, using the Caenorhabditis elegans zygote as a model system, we investigated the role of cortical F-actin structures - both branched and linear - in modulating surface dynamics of CeTOCA-1, the nematode ortholog of mammalian TOCA-1. In our in silico analysis, iPTM values associated with the interaction between different domains of CeTOCA-1 and CDC-42 suggested that while the HR-1 domain is essential for this interaction, the SH3 domain is dispensable for complex formation between the two proteins. Further, we experimentally disrupted ARP2/3 and CYK-1/ formin-polymerized F-actin structures in C. elegans zygotes to examine the role of cortical F-actin on CeTOCA-1 assembly dynamics and biophysical properties. Co-localization studies revealed a preferential association between CeTOCA-1 and the pool of F-actin structures polymerized by ARP2/3. Disruption of ARP2/3 led to the formation of larger CeTOCA-1 clusters, prolonged cluster lifetime on the cell surface, and reduced cluster mobility. These findings suggest that distinct F-actin structures play specialized roles in mediating plasma membrane interactions and regulating surface dynamics of CeTOCA-1 clusters.

YAP and TAZ are downstream effectors of the Hippo signaling pathway, known to shuttle between the cytoplasm and nucleus, where they primarily function as transcriptional coactivators. Although their nuclear role has been well characterized, the non-transcriptional functions of YAP/TAZ remain poorly understood. In this study, we report that YAP/TAZ localize to the metaphase spindle in a microtubule-dependent manner. Specifically, we demonstrate that YAP interacts with α-tubulin via its WW domain. Notably, while the spindle localization of YAP/TAZ does not affect the mechanics of mitotic cell division, it does influence the distribution of YAP/TAZ protein levels between the resulting daughter cells. These findings reveal a novel, nontranscriptional role for YAP/TAZ during mitosis.

Psoriasis (PS) is one of the comorbidities of type 2 diabetes mellitus (T2DM). The molecular processes leading to the T2DM-PS comorbidity are not fully understood. Recently, six genes (IL23R, IL12B, IL23A, GSK3B, PTPN1, and STX4) were identified as associated with the T2DM-PS comorbidity. Both diseases are multi-genic disorders with the involvement of thousands of genes. We used an integrative approach by sourcing the genes associated with T2DM and PS from the DISGENET database, the genes associated with the T2DM-PS comorbidity from the literature, the differentially expressed genes in a PS blood sample dataset (GSE55201), and the differentially expressed genes in each of three T2DM gene expression datasets of blood samples (GSE69528, GSE15932, and GSE21321). We constructed pathway networks by importing the enriched pathways of these genes into a biological network simulator software. Simulations of these pathway networks were carried out using the average expression values of cases and controls separately in each T2DM dataset until a steady state was reached. Finally, pathway enrichment analysis of the perturbed genes revealed the perturbed pathways in the T2DM condition in the three datasets of T2DM patients. Five perturbed pathways were common among the three T2DM datasets: the NF-κB signaling pathway, necroptosis pathway, NOD-like receptor signaling pathway, TNF signaling pathway, and Toll-like receptor signaling pathway. The involvement of these pathways in PS is reported in the literature, thereby suggesting potential susceptibility to PS arising in the T2DM condition. This approach offers a holistic view of T2DM conditions and the pathways reported in individual studies with potential susceptibility to PS.

Animals exhibit behavioural responses to environmental stimuli. To date, various experimental assays have been conducted to investigate the molecular and neural mechanisms underlying behavioural responses in Caenorhabditis elegans. However, behavioural outcomes can vary even under the same stimulus due to factors such as past experience, individual circumstances, and modifications in behavioural assay procedures, which complicate the interpretation of results. In this study, we focussed on the composition of the behavioural assay media and compared the behaviours of C. elegans in response to temperature and odour stimuli using three commonly used media: nematode growth medium (NGM), thermotaxis (TTX), and chemotaxis (Chemo) assay media. Our results demonstrated that in thermotaxis, C. elegans exhibited stable behavioural decisions across all examined media. However, the population of worms reaching the preferable areas was smaller in Chemo and TTX media compared with NGM due to prolonged exploration period and reduced migration speed. By contrast, in chemotaxis, we did not observe significant differences across the tested media. This study provides insights into the significant effects on C. elegans behaviour caused by the modifications of the behavioural assay media and emphasises the importance of further studies to explore the detailed neural mechanisms that regulate animal behaviour under diverse environmental factors.

In an earlier editorial (Borges 2022), I had talked about the keystone concept formulated by Robert Paine. This important concept (Paine 1966) emphasised the idea that biodiversity is maintained by a top-down process in which the removal of a keystone predator would allow the unchecked proliferation of herbivores; during this process a dominant herbivore might outcompete another herbivore species, resulting in the removal of the lesser competitor from the community and a reduction in overall species richness (i.e., the number of species present). The keystone predator concept is well-established in community ecology. Are there keystone molecules whose presence can influence the diversity of communities? At an extreme, of course, one may say that oxygen is a most important molecule whose presence has fuelled the diversification of autotrophs such as diatoms and plants, and hence the flowering of life. A key feature of Paine's keystone concept is that the species must exert an impact that is disproportionate to its abundance (Power et al. 1996). By this definition, oxygen, although vital to all life, would fail to be recognised as a keystone chemical or molecule in species communities. Are there chemical compounds that can govern species diversity within trophic levels of an ecological community, as defined by Paine's keystone concept?

Abiotic stresses such as heat, drought, and salinity significantly impact rice cultivation by affecting its yield and quality. Identifying molecular candidates that confer resistance or tolerance to these stresses is crucial. This study identifies unique and overlapping molecular signatures mediated by coding and non-coding RNAs during heat, drought, and salt stresses in rice. It uses RNA-Seq data from 66 rice samples, including those treated with heat, drought, and salt stresses, to identify both unique and shared differentially expressed mRNAs and long non-coding RNAs (lncRNAs). Analyses reveal key regulatory hubs in transcriptional networks, particularly the ERF, DOF, and MYB family transcription factors, which are central to abiotic stress responses. Stress-specific competing endogenous RNA networks reveal conserved regulatory elements that coordinate these responses. Overlap analysis identifies 637 shared mRNAs and 76 lncRNAs among the three stresses. These findings enhance our understanding of the molecular mechanisms underlying stress resilience in rice and provide a foundation for developing stress-resistant cultivars.