Journal of Biosciences最新文献

Globally, opioid use disorder (OUD) presents a significant public health challenge linked to high mortality and disability rates. Heroin and other morphine derivatives are prevalent among abused opioids. Prolonged exposure to these substances in individuals with OUD can trigger an immune response, leading to the production of antibodies to morphine that may bind to morphine and potentially mitigate its rewarding effects. In our study, we analyzed serum samples from patients diagnosed with OUD to explore the nature and properties of antibodies to morphine, aiming to characterize the generation of antibodies to morphine due to long-term exposure to morphine. We observed varying titers of antibodies to morphine in OUD patients, absent in healthy controls, with both free morphine and morphine complexes detected bound to these antibodies, indicating less potency. Furthermore, our analysis revealed elevated levels of FoxP3, a critical transcription factor in regulatory T-cells (Tregs) responsible for maintaining immunosuppression. Concurrently, reduced levels of inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) indicated immunosuppressive activity. Notably, decreased antibody titers against the Acr1 protein of Mycobacterium tuberculosis suggested that morphine-induced immune suppression might compromise responses to other pathogens. These findings indicate that chronic morphine exposure not only suppresses host immunity but also induces the production of antibodies to morphine. Investigating whether these antibodies contribute to immune suppression or can be harnessed to combat morphine dependence presents an intriguing avenue for future research.

Hepatitis B virus (HBV), a lethal virus that results in the loss of two lives every minute, induces chronic and acute infections. Chronic infections may result in liver cirrhosis, which in turn may lead to hepatocellular carcinoma (HCC). Our study analysed 1,06,970 protein sequences of HBV genotypes (Gen A to H) from the HBV database (HBVdb) to construct position-specific scoring matrices. A total of 5,058 mutations were detected across all proteins, reflecting the notorious mutability of HBV. Among these, 2,658 significant mutations (sigmuts) with frequencies ranging between 10 and 80 were screened. Gen A presented the greatest number of sigmuts, whereas Gen H presented the least. Gen C, the most common HBV gene, featured 417 sigmuts, which we used for structural studies using DynaMut2 and molecular docking. We found that most core protein signatures significantly impact functions, including B-cell receptor binding and dimerisation. Interestingly, most sigmuts of the RNase H domain (694-843) of polymerase proteins promoted structural disorder, with possible impact on interactions with LINE-1 elements and progression to hepatocellular carcinoma. Intriguingly, despite the use of prominent nucleoside reverse transcriptase inhibitors (NRTIs) for over two decades, the drug-binding pockets of polymerase proteins have been found to be highly conserved. Nevertheless, since the long-term use of a few drugs as monotherapies has resulted in the development of drug resistance in recent years, we propose novel HBV targets for alternative therapeutic interventions.

The history of the study of nematodes to understand aspects of genetics, cell biology, and development began as early as the late 1800s, when Marcella and Theodor Boveri worked on early development of horse ascarids. Their work was instrumental in advancing the understanding of the chromosome theory of heredity. This work was followed by that of many scientists who studied multiple nematodes over the years. Caenorhabditis elegans was identified through a series of serendipitous discoveries. In 1944 Margaret Briggs Gochnauer found a nematode that at that time was identified as a Rhabditis species on the Stanford University campus, where she worked on studying the effect of antibiotics on these worms. Ellsworth Dougherty, who at that time, was studying another nematode of the Rhabditis species became interested in Gochnauer's work, as the nematode she was studying was self-fertilizing. A few years after beginning their work on these worms Ellsworth Dougherty and Victor Nigon named the nematodes first found by Briggs Gochnauer as Rhabditis briggsae. This was also based on a related species that was found circa 1900 in Algeria by E´ mile Moupas and called Rhabditis elegans. In 1952, these two species were placed in the subgenus Caenorhabditis. This subgenus was elevated to the rank of genus by Dougherty in 1955. Nigon established the culture conditions for growing and successfully set up crossing strategies in a largely hermaphroditic lifestyle. We now use nematodes that were found in 1900 extensively as the model organism Caenorhabditis elegans. This strain was later popularized by Sydney Brenner's MRC lab, which received it from Dougherty and went on to perform seminal work on the development of C. elegans. A large number of talented individuals came to the MRC to work with Brenner, thus allowing for the spread of C. elegans as a model of choice by thousands of researchers worldwide.

In most individuals with type 2 diabetes mellitus (T2DM), aggregation of amylin or islet amyloid polypeptide (IAPP) leads to β-cell apoptosis, impairs glucose-stimulated insulin secretion, and causes islet disorganisation (Cooper et al. 1987; Westermark and Westermark 2000). Amylin is sorted within the immature secretory granules (ISGs) of pancreatic β-cells and co-secreted with insulin upon nutrient stimulation to regulate metabolism. Under normal conditions, it remains soluble in ISGs due to its low concentration and is stabilised by insulin and zinc, in an acidic environment (Westermark et al. 1987; Janson et al. 1996; Abedini and Raleigh 2006). However, under stress or with overproduction of amylin, it aggregates into insoluble amyloid fibrils both intracellularly and extracellularly after secretion (Gurlo et al. 2010).

A biphasic pattern of reorganization in the somatosensory cortical area, representing the hindlimb or forelimb, has been shown after complete spinal cord injury (cSCI) in rats. The present study hypothesized that extremely low-frequency magnetic fields (ELF-MF) would favourably modulate this biphasic pattern of cortical plasticity by altering brain-derived neurotrophic factor (BDNF) and neurite outgrowth inhibitor A (isoform of reticulon- 4) (Nogo-A) levels, leading to functional and electrophysiological recovery in cSCI rats. Adult male Wistar rats underwent cSCI at the T-13 spinal level, followed by ELF-MF exposure for either 5, 12, or 32 days, for analysis of the biphasic pattern. A set of motor and sensorimotor behavioural tests, spinal cord lesion volume, cortical electroencephalography (EEG), expression of neurotrophic factor (BDNF), and inhibitory molecule (Nogo-A) were recorded at each time period. Significant (p≤0.01) recovery was evident in the Basso-Beattie- Bresnahan (BBB) locomotor score, allodynia, grip strength, power spectrum of EEG waves, and lesion volume after 32 days of ELF-MF. Although both SCI and SCI+MF rats exhibited characteristic biphasic patterns in the expression of Nogo-A and BDNF, the SCI+MF group showed a significant increase in BDNF levels along with a decrease in Nogo-A. These findings suggest that ELF-MF enhances functional recovery after cSCI by moderating molecular and electrophysiological markers of cortical plasticity, without disrupting the inherent biphasic expression dynamics.

Can extant and ancestral enzymes provide insights into structural evolution shaped by environmental factors and biological phenotypes? And how might one gain access to the structures of ancestral enzymes? The analysis of nitrogenases reported by Cuevas-Zuviría et al. (2025) describes how conformational features, active-site composition, and sequence modifications can be correlated with evolutionary pressures and environmental conditions over geological timescales. Nitrogenases are key to life on Earth. These enzymes enable access to bio-essential nitrogen by catalysing the reduction of highly inert atmospheric nitrogen (N≡N) with its hard-to-cleave triple bond to ammonia (NH₃). Nitrogenases thus have an outsized role in the adaptation of species as they survive diverse environmental conditions, whether terrestrial or aquatic. Despite this, not much is known about the variation in the enzymatic activity of nitrogenases as a function of ecological niche or evolution. What is well known, however, is that nitrogenases are extremely sensitive to oxygen, which degrades the bound metalloclusters that are essential for enzymatic activity and oligomerisation. Consequently, nitrogenases that evolved under anaerobic conditions must have been subjected to unprecedented selection pressures as oxygen levels increased especially during the Great Oxidation Event in Earth's geological history (Moody et al. 2025). In this context, molecular features acquired as an adaptation mechanism to environments, such as increased oxygen levels, have not been well understood in this family of enzymes. Nitrogenases employ redox-sensitive trace metals such as molybdenum, vanadium, and iron. The environmental bioavailability of these metal ions is also altered by oxygenation. It thus appears likely that novel features within the nitrogenase enzymes evolved as an adaptive mechanism to maintain biological nitrogen fixation amid global marine geochemical shifts while life was developing in these environments (Cuevas-Zuviría et al. 2024). Understanding the linkages between these molecular innovations and environmental transitions is essential to rationalise how evolution shaped an enzyme capable of catalysing a challenging reaction. Understanding the evolution of nitrogenases, especially structure-function correlations, reveals important cues about how these enzymes adapted to changes in the environment, including oxygen levels and changes in metal availability.

Correction: J Biosci (2025) 50:65 https://doi.org/10.1007/s12038-025-00516-4.

In today's world, food safety is of paramount importance. Even a slight lapse can lead to significant economic losses and place a heavy burden on the healthcare system. Over the years, multiple mathematical models have been developed to predict microbial growth in commercial foods. However, each of these models had to give up at least one of the factors, i.e., generality, realism, or precision. The Baranyi and Roberts model was proposed in the 1990s and was an extension of the logistic model. It took 'realism' into account and bridged the gap between the conditions affecting populations in nature and how they are represented on paper. The realistic attributes of the model allowed it to model, for the first time, the lag time. In this review, we have discussed the model in detail, along with its extrapolations that made it flexible. We have further discussed how the Baranyi model is still important in food safety regimes. We have also discussed how one can explain the setting up of the adjustment factor used in this model. Our literature review has revealed how the Baranyi and Roberts model continues to be relevant even after 30 years of its proposition, and further insights on the biochemical aspects of the model's assumptions might help in strengthening its predictions.

In the wild, the nematode Caenorhabditis elegans primarily feeds on microbes, which are abundant in rotting vegetation. Studies show that several gram-positive and gram-negative bacterial populations predominantly constitute the C. elegans gut microbiome, but surprisingly lack any yeast species. To understand the lack of yeast in the intestine of C. elegans, we studied the behaviour of worms on pathogenic and non-pathogenic yeast diets. We show that C. elegans displays low satiety on a yeast diet of Cryptococcus neoformans, Cryptococcus laurentii or Saccharomyces cerevisiae. We find that the average size of cells of budding yeast is much larger than that of Escherichia coli, which constitute the laboratory diet of C. elegans. We have shown that yeast cells cause pharyngeal obstruction, diminished feeding, and lower level of neutral lipids in adult C. elegans. Using scanning electron microscopy, we show that the mouth size of C. elegans larvae is smaller than the average yeast cell. The larvae have no detectable yeast in their alimentary canal, and they undergo delayed development on a yeast diet. We propose that microbial cell size or bite size could be crucial factors in the regulation of feeding in C. elegans, and the composition of the microbiome in its intestine.

Non-syndromic hearing loss (NSHL) is a genetically heterogeneous disorder affecting millions worldwide. Recent advances in genetic technologies have expanded our understanding of its molecular basis, but challenges remain in identifying and interpreting causative variants. This study aimed to investigate the genetic etiology of NSHL using comprehensive genetic screening, with a focus on identifying rare and potentially pathogenic variants. We performed genetic analysis on 43 participants diagnosed with NSHL using whole exome sequencing (WES) technology. Variant filtering, in silico prediction tools, and segregation analysis were employed to evaluate the pathogenicity of identified variants. Our analysis revealed 20 rare and deleterious variants (4 novel and 16 previously reported) in 16 NSHL-related genes among 43 participants. These variants included 3 known pathogenic, 4 likely pathogenic, and 13 variants of uncertain significance (VUS). Notably, we identified compound heterozygous variants in the GPSM2 gene (NM_013296:c.185G>A;p.Ser62Asn and NM_013296:c.1264delG;p.Val422Tyrfs*28) in one participant, with segregation analysis confirming their trans configuration. This study expands our understanding of the genetic landscape of NSHL by identifying several rare variants in known NSHL-related genes. Notably, we report the first case of compound heterozygous variants in the GPSM2 gene in the Indian population, a finding not previously documented. This discovery underscores the importance of comprehensive genetic screening in diverse populations and contributes to the growing body of evidence for the role of GPSM2 in NSHL.