Journal of Biosciences最新文献

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.

The molecular chaperone Hsp70 is a pivotal player in cellular protein quality control due to its wide range of substrates ranging from unfolded, native, to misfolded proteins. Increasing evidence suggests that Hsp70 decides the fate of proteins; however, the inherent rules that govern the decision-making capacity of Hsp70 are not clear. In this review, we have articulated the functions of Hsp70 with respect to proteostasis and established a link between its co-chaperones in deciding the fate of the substrate. The substrate binding of Hsp70 is mediated by its catalytic cycle where Hsp70 achieves high- and low-substrate-affinity ADP- and ATP-bound forms, respectively. This catalytic cycle of Hsp70 is maintained by co-chaperones J-domain proteins (JDPs), and nucleotide exchange factors (NEFs). JDPs bind to the ATP-bound form of Hsp70 and hydrolyze ATP that enhances substrate binding, whereas NEFs exchange ADP with ATP and facilitate substrate release. During evolution, several isoforms of Hsp70 and its co-chaperones have emerged which may have functional significance. Apart from facilitating the catalytic cycle of Hsp70, co-chaperones often mediate collaboration between Hsp70 and downstream protein quality-control pathways such as the ubiquitin proteasome system, autophagy, or disaggregase machinery. Therefore, co-chaperones have a significant role in Hsp70's triage decision of whether to fold, hold, or degrade.

Prey-predator interactions favor the aggregation of generalist predators adept at avoiding competition in foraging on temporary food resources. There is scant information on the predator guild on clumpy patches of woolly aphids on bamboo host plants in forested landscapes. Results of a field-cum-laboratory study explain the aggregation of generalist and specialist predators in patchy resources of the bamboo-feeding woolly aphid, Ceratovacuna silvestrii, with particular reference to the specialist giant ladybird predator, Anisolemnia dilatata. This predator's larvae share food resources for 26 weeks including 11 weeks of coexistence with 2 small-sized generalist predators and 11 weeks with the larvae of specialist moth predator. Results show a preference for low prey density patches by small-sized predators in contrast to high prey density by the giant ladybird predator. Between the two woolly aphid prey-specialist predators, the moth caterpillars (Dipha aphidivora) avoided competition with the giant ladybirds by foraging in silken nests in less aggregated aphid patches. Eggs and larvae of the giant ladybird predator are defended from heterospecific and conspecific predators. This trait deters other predators of the guild that avoid prey patches visited by the giant ladybirds. Bigger size, preference for high-density prey patches, and anti-predation trait of eggs and larvae confer selection advantages to giant ladybirds as the top predator of the guild of woolly aphids. This has evolutionary significance for the ecological stability of prey-predator dynamics in a forested landscape.

One of the most remarkable events in cellular evolution is the endosymbiosis of α-proteobacteria with a single archaean host cell, a rare evolutionary process, which eventually led to the transformation of symbionts into fully functional mitochondrial organelles in eukaryotes. Evolutionary events related to plants occurred almost 1.6 billion years ago, when eukaryotic heterotrophs acquired a β-cyanobacterium (containing 1B RUBISCO) in what is termed as primary endosymbiosis. Further, this composite cell lineage evolved into three photosynthetic lineages: green algae (plants), red algae and the glaucophytes. Thereafter, a secondary, and tertiary endosymbiosis event occurred giving rise to distinct kinds of green and red-derived photosynthetic plastids, which can be observed in a few haptophytes and dinoflagellates respectively. Eventually, these endosymbionts acquired characteristic cellular properties such as two/multiple envelope membranes and reduction of their genomes through either loss or concerted endosymbiotic gene transfer (EGT) into the nucleus, which ultimately led to the decline of more than three quarters of coding capacity and complete loss of several metabolic pathways. This loss, however, is partly compensated by import of nuclearencoded proteins as well as proteins acquired by horizontal gene transfer (HGT). For most proteins, specific transport mechanisms from nucleus/cytoplasm to organelle exist. The proteins are typically translated as a preprotein with specific signal sequences targeted to the organelle membrane. These membranes harbour receptors, in some cases soluble receptors, for recognition of these signal sequences. Proteins are then internalised using a set of translocation machineries (Gould et al. 2006).

In Saccharomyces cerevisiae, the iron-sulfur cluster biogenesis late-acting subsystem (Fe-S-IBG) comprises the mitochondrial glutaredoxin (Grx5), Isa1, Isa2, and iron-sulfur cluster assembly factor IBA57 (Iba57) proteins. The Fe-S-IBG subsystem assists in inserting [4Fe-4S] clusters into apoproteins, some of which belong to the electron transport chain (ETC). However, whether the Fe-S-IBG subsystem indirectly stabilizes respiratory supercomplexes and proper ETC function via insertion of [Fe-S] proteins into ETC complexes remains to be elucidated. We compared the effects of ISA2- and GRX5-independent mutations on the insertion of Rip1p, a [2Fe-2S]-containing protein involved in both electron transfer in the bc₁ complex and the formation of respiratory supercomplexes. The levels of Rip1p, supercomplex assembly, ETC function, oxidative stress, and resistance of yeast to ethanol stress were evaluated on haploid S. cerevisiae cells with independent mutations of the ISA2 and GRX5 genes. Susceptibility to ethanol was increased in the isa2Δ and grx5Δ mutants, which was associated with enhanced glutathione oxidation due to higher levels of free iron and increased oxidants. Furthermore, the isa2Δ mutant showed decreased Rip1p expression, respiratory dysfunction, and defective respiratory supercomplex formation, which was restored by ISA2 complementation. These results suggest that Isa2p is essential for proper respiratory chain function and resistance to oxidative stress by stabilizing supercomplexes in a manner dependent on Rip1p insertion in the cytochrome bc₁ complex.

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.