Journal of Biosciences最新文献

Pulmonary fibrosis is a chronic, life-threatening respiratory disease characterized by high incidence and lack of effective treatments. This disease is associated with damage to the alveolar epithelium and heightened proapoptotic activity of p53, attributed to increased acetylation of its Lys381 residue. On the other hand, SIRT1 has been proposed as a therapeutic target for its ability to deacetylate key proteins such as histone 3 (H3), NF-ĸB, and p53, thus modulating cellular processes such as inflammation, apoptosis, differentiation, and oxidative stress, which could improve epithelial damage and fibrogenesis. Because SIRT1 can modulate key molecules related to lung fibrosis, this study examined the effect and localization of SIRT1 overexpression in A549 alveolar epithelial cells after bleomycin-induced injury. Two plasmids were used, one with SIRT1 cDNA and the other with a mutant H363Y catalytic site. SIRT1 expression and localization were analyzed by double immunofluorescence. SIRT1 phosphorylation at serine 47 as well as acetylation of p53 and H3 at lysine 381 and lysine 9, respectively, were also analyzed. Our results indicate that SIRT1 overexpression promotes H3 deacetylation, impacting epithelial-mesenchymal transition (EMT) and preventing pulmonary fibrosis. Additionally, our findings reveal that SIRT1 overexpression boosts its nuclear translocation and phosphorylation, deacetylates p53 and H3 after bleomycin damage, and preserves cell survival. The effect of SIRT1 on p53 and H3 deacetylation supports epigenetic control which may prevent cell death and EMT in pulmonary fibrosis.

The devouring of crops by wild herbivores is a major issue in human-wildlife conflict. Although many studies identify the conflict, attempt to estimate the extent of economic loss and its consequences, and suggest some mitigation measures, many fundamental issues remain unaddressed. A number of speculations about the root causes behind the problem have been made, but they have not been treated and tested as alternative hypotheses. In this article, (a) we make a list of alternative hypotheses collected from a wide variety of sources; (b) we evaluate their plausibility, logical integrity and compatibility with existing data; (c) we suggest differential testable predictions; and (d) we discuss their differential implications for mitigation measures. It is important to identify the specific causes of the conflict because the efficacy of mitigation measures crucially depends on the predominant underlying cause. Measures applied without a good understanding of the causal factors might turn out to be ineffective and even counterproductive. Substantial research needs to be focused on differentially testing the predictions of the alternative hypotheses to be able to handle the problem and promote healthy coexistence of wildlife with indigenous people. Although our perceptions of the problem and illustrative examples are in the Indian wildlife context, some of the emerging outcomes will have global importance.

Microphysiological systems (MPS) have enabled a paradigm shift from reliance on animals to human-relevant tools for drug development. Following progressive regulations by USA, Europe, Canada, and other nations, India authorized the use of MPS in its New Drugs and Clinical Trials Rules (Amendment) 2023. However, while the use of these models by the pharmaceutical industry has been documented globally, this information is sorely lacking among developing nations such as India. We uncovered that embracing MPS in the Indian community is challenged by multiple factors. To actively participate in the global shift toward human-centric biomedical research, India must enhance its MPS awareness, skill development, regulatory guidelines, local resource availability, and return on investments. We found that there is a significant diversity in the costs of different MPS in India and provide recommendations to manage their expenses in the context of low-income nations. In conclusion, our findings will hasten MPS adoption, limit archaic animal use, help in formulation of institute policies, and shape the country's investment in contemporary science.

Correction to:J Biosci (2025) 50:86 https://doi.org/10.1007/s12038-025-00569-5 In Volume 50 of the Journal of Biosciences, in the article titled 'Brain dystrophinopathies and cognitive impairment: Pathogenesis, diagnosis, and therapies' by Aadi Saluja, Kyriloss Gad, Phillipa Iyede, Praveen Parkali and Narendra Chirmule, published on 17 November 2025 (https://doi.org/10.1007/s12038-025-00569-5), the legends of figures 1 and 2 are interchanged. Please read the description of figure 1 in the legend to figure 2, and vice versa.

The insulin/IGF-I-like signaling (IIS) pathway is a highly conserved signaling cascade that plays a crucial role in regulating longevity across species. Given its significance in aging, identifying novel kinases interacting with the IIS pathway can provide deeper insights into the mechanisms governing longevity. In this study, we performed a targeted RNAi screening of the Caenorhabditis elegans kinome, using dauer formation as a phenotypic readout. We identified several known and novel kinase modulators of the IIS pathway. These hits were enriched with both previously documented and undocumented lifespan regulators. Thermotolerance assays revealed mixed trends, with some kinase inhibitions increasing while others decreasing protection against thermal stress. We observed a positive correlation between thermotolerance and lifespan extension, as well as between dauer formation and lifespan extension, with thermotolerance proving to be a better predictor of longevity. Our findings offer a valuable resource for researchers exploring the IIS pathway and highlight novel, unannotated kinases as potential new therapeutic targets for aging interventions.

The bulk of malaria rapid diagnostic tests (RDTs) target Plasmodium falciparum histidine-rich protein 2 (PfHRP2), but several reports have shown that sequence variations in this protein are associated with falsenegative RDT results. The polymorphism of PfHRP2/3 was analyzed from Cameroonian and Indian P. falciparum isolates. Cameroon and India are two of eleven countries with the highest malaria burden. Exon 2 of pfhrp 2/3 genes were PCR-amplified, and the amplicons were purified and sequenced. A total of 25 PfHRP2 and 12 PfHRP3 novel repeat type variants were found. The nature and organization of PfHRP3 sequences were quite similar between Cameroon and India. Some structurally unique PfHRP2/3 sequences, characterized by a high proportion of proline (5.8-10.3%) for PfHRP2, and two non-repeat regions for PfHRP3, were found in both countries. Most of the Cameroonian isolates belonged to group B (66.7%), while the Indian isolates belonged to group C (69.2%) (p=0.03). Three epitope motifs (AHHAHHA, HATDAHH, and YAHHAHHA) were found in all Cameroonian and Indian PfHRP2 sequences. Mutations observed in unique sequences were mainly associated with alterations of helical structures in the PfHRP2 C-terminal region. The high genetic diversity, epitope availability, and structural basis patterns found here could help develop the next generation of RDTs with improved quality.

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.