Journal of Biosciences最新文献

Amyloids interact with plasma membranes. Extracellular amyloids cross the plasma membrane barrier. Internalized extracellular amyloids are reported to trigger amyloidogenesis of endogenous proteins in recipient cells. To what extent these extracellular and intracellular amyloids perturb the plasma membrane proteome is not investigated. Using α-synuclein as a model amyloid protein, we performed membrane shaving followed by mass spectrometry experiments to identify the conformational changes in cell surface proteins after extracellular amyloid challenge. We also performed membrane proteomics after the biogenesis of intracellular α-synuclein amyloids. Our results suggest that promiscuous interactions with extracellular amyloids stochastically alter the conformation of plasma membrane proteins. This affects the biological processes through the plasma membrane and results in loss of cell viability. Cells that survive the extracellular amyloid shock can grow normally and gradually develop intracellular amyloids which do not directly impact the plasma membrane proteome and associated biological processes. Thus, our results suggest that α-synuclein amyloids can damage the plasma membrane and related processes during cell-to-cell transfer and not during their intracellular biogenesis.

Itch is a unique sensory experience that is responded to by scratching. How pruritogens, which are mechanical and chemical stimuli with the potential to cause itch, engage specific pathways in the peripheral and central nervous system has been a topic of intense investigation over the last few years. Studies employing recently developed molecular, physiological, and behavioral techniques have delineated the dedicated mechanisms that transmit itch information to the brain. This review outlines the genetically defined and evolutionary conserved circuits for itch ranging from the skin-innervating peripheral neurons to the cortical neurons that drive scratching. Moreover, scratch suppression of itch is attributed to the concurrent activation of pain and itch pathways. Hence, we discuss the similarities between circuits driving pain and itch.

Owing to the lack of effective vaccines, current control measures and eradication strategies for the African swine fever virus (ASFV) rely on early detection and stringent stamping-out procedures. In the present study, we developed two independent isothermal amplification assays, namely, loop-mediated isothermal amplification (LAMP) and polymerase spiral reaction (PSR), for quick visualization of the ASFV genome in clinical samples. Additionally, a quantitative real-time PCR (qRT-PCR)-based hydrolysis probe assay was developed for comparative assessment of sensitivity with the developed isothermal assays. The analytical sensitivity of the LAMP, PSR, and qRT-PCR was found to be 2.64 ×10⁵ copies/µL, 2.64 ×10² copies/µL, and 2.64 ×10¹ copies/µL, respectively. A total of 165 clinical samples was tested using the developed visual assays. The relative accuracy, relative specificity, and relative diagnostic sensitivity for LAMP vs PSR were found to be 95.37% vs 102.48%, 97.46% vs 101.36%, and 73.33% vs 113.33%, respectively.

Koragas, recognized as a particularly vulnerable tribal group (PVTG) by the Government of India, are from coastal Karnataka and Kerala. They are experiencing severe socioeconomic and health-related issues and rapid depopulation. The unique genetic makeup of Koragas has been maintained by the practice of endogamy. We aimed to identify genetic factors potentially associated with the predisposition of Koragas towards genetic and multifactorial disorders. We employed genome-wise data of 29 Koraga individuals genotyped on the Infinium Global Screening Array-24 v3.0 BeadChip platform and performed various population genetic analyses including kinship, identity by descent (IBD), and runs of homozygosity (RoH). A high degree of haplotype sharing among the Koraga participants may be indicative of a recent founder event. We identified genetic variants and genes associated with several genetic disorders, higher infant mortality rate, neurological disorders, deafness, and lower fertility rate of this agrarian tribe. Ours is the first genome-wide study on the Koraga tribe that identified genetic factors associated with various genetic disorders. Our findings can provide public healthcare providers with essential genetic information that can be useful in augmenting medical and healthcare services and improving the quality of life of Koragas.

Noradrenaline (NA) and serotonin (5-HT) induce nociception and antinociception. This antagonistic effect can be explained by the dose and type of activated receptors. We investigated the existence of synergism between the noradrenergic and serotonergic systems during peripheral antinociception. The paw pressure test was performed in mice that had increased sensitivity by intraplantar injection of prostaglandin E₂ (PGE₂). Noradrenaline (80 ng) administered intraplantarly induced an antinociceptive effect, that was reversed by the administration of selective antagonists of serotoninergic receptors 5-HT_1B isamoltan, 5-HT_1D BRL15572, 5-HT_2A ketanserin, 5-HT₃ ondansetron, but not by selective receptor antagonist 5-HT₇ SB-269970. The administration of escitalopram, a serotonin reuptake inhibitor, potentiated the antinociceptive effect at a submaximal dose of NA. These results, indicate the existence of synergism between the noradrenergic and serotonergic systems in peripheral antinociception in mice.

Fibroblasts embedded in a 3D matrix microenvironment can remodel the matrix to regulate cell adhesion and function. Collagen hydrogels are a useful in vitro system to study cell–matrix interactions in a 3D microenvironment. While major matrix reorganizations are easily recognizable, subtle changes in response to environmental or biochemical cues are challenging to discern in 3D hydrogels. Three-dimensional collagen gels at 1.0 mg/ml vs 1.5 mg/ml were labelled with DQ-collagen and imaged by confocal reflectance microscopy to evaluate these small changes. An image analysis pipeline was developed, hydrogel area and number of cross-sections analysed were optimized, and fibrillar collagen properties (number of branches, number of junctions, and average branch length) were quantified. While no significant changes were seen in fibrillar collagen organization between 1.0 mg/ml and 1.5 mg/ml collagen hydrogels, embedded mouse fibroblasts caused a significant increase in collagen branching and organization. Using the phalloidin-labelled cells, this change was quantitated in immediate proximity of the cell. A distinct increase in branch and junction numbers was observed, significantly altered by small changes in collagen concentration (1.0 mg/ml vs 1.5 mg/ml). Together, this analysis gives a quantitative evaluation of how cells respond to and modify their immediate microenvironment in a 3D collagen hydrogel.

Immunotherapy is a promising and safer alternative to conventional cancer therapies. It involves adaptive T-cell therapy, cancer vaccines, monoclonal antibodies, immune checkpoint blockade (ICB), and chimeric antigen receptor (CAR) based therapies. However, most of these modalities encounter restrictions in solid tumours owing to a dense, highly hypoxic and immune-suppressive microenvironment as well as the heterogeneity of tumour antigens. The elevated intra-tumoural pressure and mutational rates within fast-growing solid tumours present challenges in efficient drug targeting and delivery. The tumour microenvironment is a dynamic niche infiltrated by a variety of immune cells, most of which are macrophages. Since they form a part of the innate immune system, targeting macrophages has become a plausible immunotherapeutic approach. In this review, we discuss several versatile approaches (both at pre-clinical and clinical stages) such as the direct killing of tumour-associated macrophages, reprogramming pro-tumour macrophages to anti-tumour phenotypes, inhibition of macrophage recruitment into the tumour microenvironment, novel CAR macrophages, and genetically engineered macrophages that have been devised thus far. These strategies comprise a strong and adaptable macrophage-toolkit in the ongoing fight against cancer and by understanding their significance, we may unlock the full potential of these immune cells in cancer therapy.

We have extensively described that the neoplastic process (NP) has deep evolutionary roots and we have made specific predictions about the connection between cancer and the formation of the first embryo, which allowed for the evolutionary radiation of metazoans. My main hypothesis is that the NP is at the heart of cellular mechanisms responsible for animal morphogenesis, and given its embryological basis, also at the center of cell differentiation—one of the most interesting and relevant aspects of embryogenesis. In this article, I take forward the idea of the role of physics in the modeling of the neoplastic functional module (NFM) and its contribution to morphogenesis to reveal the totipotency of the zygote. In my consideration of these arguments, I examine mechanical and biophysical clues and their intimate connection with cellular differentiation. I expound on how cancer biology is perfectly intertwined with embryonic differentiation and why it is considered a disease of cell differentiation. The neoplasia is controlled by textural gradients that lead to cell differentiation within the embryo. Thus, the embryo would be a benign tumor. Finally, inspired by evolutionary history and by what the nervous system represents for current biology and based on the impressive nervous system of ctenophores as seen in fossil records, I propose a hypothesis with physical foundations (mechanical morphogenesis) for the formation of a preneural pattern of the nervous system of the first animal embryo.

Milk is a source of essential nutrients, but food safety across the milk supply chain has emerged as an integral part of food trade. Of the several food safety hazards, antimicrobial-resistant Staphylococcus species have emerged as one of the major microbial hazards with significant public health concerns. The present cross-sectional study was undertaken with the objective to isolate Staphylococcus species from the milk supply chain, characterize isolates for antimicrobial resistance, and trace the origin of isolates using molecular techniques. Samples collected from the formal and informal milk supply chains showed prevalence of Staphylococcus species of 4.3% (n=720); isolates were identified as coagulase-positive (S. aureus 67.7% and S. intermedius 6.4%) and coagulase-negative (S. lentus 9.6%, S. sciuri 3.2%, S. xylosus 3.2%, S. schleiferi 3.2%, S. felis 3.2%, and S. gallinarum 3.2%) species. Staphylococcus isolates showed antimicrobial resistance to methicillin (32.2%), β-lactam (41.9%), and macrolide-lincosamide-streptogramin B (3.2%). Staphylococcus isolates phenotypically resistant to methicillin also carried the mecA gene and displayed diverse pulsed field gel electrophoresis (PFGE) profiles, indicating their diverse origins in the milk supply chain. Based on the similarity of PFGE profile, the origin of one of the Staphylococcus isolates was traced to the soil in contact with milch cows. The findings of this study highlight the need for more comprehensive microbial risk analysis studies across the milk supply chain, capacity building, creation of awareness among stakeholders about the judicious use of antimicrobials, and protection of public health using a One-Health approach.

ATP-uncoupling alternative oxidase (AOX) in the plant respiratory chain is often induced under stress conditions such as low temperature (LT). The importance of AOX in photosynthesis has been examined, and leaves having larger amounts of AOX tended to show larger decrease in photosynthetic electron transport rate (ETR) by AOX inhibition. However, the details were not clarified. Here, we used three ecotypes of Arabidopsis thaliana which differed in AOX amounts and their responses to LT, and examined whether AOX amount was related to the degree of decrease in ETR by AOX inhibition. In Tiv-0, which originates from a warmer site, grown at high temperature (HT), AOX inhibition decreased ETR, but not in the other ecotypes. LT treatment significantly increased ETR and AOX, especially in Bur-0, but AOX inhibition did not decrease ETR in LT plants of any ecotype. AOX inhibition significantly increased the non-regulated energy dissipation in photosystem II (PSII), Y(NO), and decreased the maximal quantum yield of PSII, F_v/F_m, especially in LT plants. Since AOX inhibition did not affect the parameters of PSI, AOX inhibition may directly affect the reaction center of PSII in LT plants.