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Jose, M.

Publications and source records attributed to Jose, M..

4 recordsLinked to original sources

Nanoscale Lattice Organization of Molecular Condensates Drives Compositional Degeneracy in Synaptic Plasticity

Synaptic plasticity is essential for neuronal communication, involving coordinated structural, molecular and functional changes that are shaped by the nanoscale alterations of the active zone and postsynaptic density. Emerging evidence suggests that synapses function as complex information processing machines, where unique molecular assemblies shape transmission properties. Central to this is the organization of voltage-gated calcium channels (VGCCs) and Bassoon within active zones. Utilizing advanced techniques like liquid-liquid phase separation, super-resolution microscopy, and data-driven models of synaptic transmission, we reveal how nanoscale "compositional degeneracy" in Bassoon and VGCCs enables synapses to achieve functional adaptability through multiple molecular configurations. By modulation of local uncertainty and implementing probabilistic inference, synapses fine-tune transmission efficiency by regulating dynamic entropy and free energy. These principles are especially evident during homeostatic scaling, where synaptic scaling mechanisms differ with neuronal maturity. This study highlights how distinct thermodynamic states in VGCC and Bassoon organization optimize information transfer at different plasticity stages. Our findings propose a refined framework for understanding synaptic transmission as an adaptable, entropy-modulated process, balancing resilience and efficiency.

neuroscience↗

Diversity and functions of soil microbial communities in the Trans-Himalayan grazing ecosystem: influence of herbivores and abiotic factors

O_LIDiversity-function relationships are well known for producers, and these are also known to be influenced by consumers at higher trophic levels. However, these are not well known for microbial decomposers and decomposition processes in soil. Further, it also remains unknown whether and how consumers such as large mammalian herbivores, who are a major feature across more than one-third of the worlds terrestrial realm, influence soil microbial decomposer diversity-function relationships. C_LIO_LIWe used a14-year old long-term herbivore-exclusion experiment to answer two questions: (a) whether microbial functions vary with microbial diversity (both species richness and composition), and (b) whether herbivores alter the diversity-function relationships among microbial decomposers. We measured functional richness, and functional dispersion from the utilization profiles of 30 metabolic substrates. Alongside, we also measured species richness and species composition of soil microbes. C_LIO_LIWe analysed soils from n=10 paired grazed-and-fenced plots, and sampled them three times during the growth season of 2019. Data were from 60 16S rDNA gene amplicon sequences with 7.6 million reads covering 1937 operational taxonomic units (OTU) across 47 phyla (of which 924 OTUs were identifiable to genus level), and 1800 catabolic profiles. C_LIO_LIFunctional diversity in soil was positively related to microbial community composition, but not to species richness. This parallels the diversity-function relationships between producers and production; it also challenges the prevailing notion of functional redundancy in hyper-diverse soil microbial communities. Since certain combinations of species can outperform others, global change factors which can alter microbial communities may also impact decomposition processes and services. But this coupling between diversity and functions was unaffected by experimental herbivore-exclusion, indicating resilience and resistance among decomposers. C_LIO_LIStructural equation models suggested that the strength of this relationship is favoured by availability of soil moisture. These also showed microbial functions varied more strongly with temporal variables (e.g., seasonality) than with spatial variables (e.g., edaphic factors such as soil texture and pH). Although interpretations can be constrained by which and how many functions are investigated, the relationship between diversity and functions was generalizable and robust once 16 or more functions were quantified. C_LIO_LIWhile ecosystem functions and services derived from microbial decomposers have intrinsic resilience and resistance, they respond strongly to variability in water availability. Decomposition in grazing ecosystems may be particularly susceptible to how microbial community composition responds to rising precipitation variability under ongoing and projected climate change. C_LI HighlightsO_LIDiversity-function relationships for microbial decomposers remain uncertain. C_LIO_LIMicrobial diversity is positively related to functions C_LIO_LIThis relationship is robust to herbivore-exclusion. C_LIO_LIMicrobial diversity-function relationship can be susceptible to altered precipitation C_LI

ecology↗

Production of anti-SARS-CoV-2 hyperimmune globulin from convalescent plasma

BACKGROUNDIn late 2019, the SARS-CoV-2 virus emerged in China and quickly spread into a world-wide pandemic. Prior to the development of specific drug therapies or a vaccine, more immediately available treatments were sought including convalescent plasma. A potential improvement from convalescent plasma could be the preparation of anti-SARS-CoV-2 hyperimmune globulin (hIVIG). STUDY DESIGN AND METHODSConvalescent plasma was collected from an existing network of plasma donation centers. A caprylate/chromatography purification process was used to manufacture hIVIG. Initial batches of hIVIG were manufactured in a versatile, small-scale facility designed and built to rapidly address emerging infectious diseases. RESULTSProcessing convalescent plasma into hIVIG resulted in a highly purified IgG product with more concentrated neutralizing antibody activity. hIVIG will allow for the administration of greater antibody activity per unit of volume with decreased potential for several adverse events associated with plasma administration. IgG concentration and IgG antibody specific to SARS-CoV-2 were increased over 10-fold from convalescent plasma to the final product. Normalized ELISA activity (per mg/mL IgG) was maintained throughout the process. Protein content in these final product batches was 100% IgG, consisting of 98% monomer and dimer forms. Potentially hazardous proteins (IgM, IgA, and anti-A, anti-B and anti-D antibodies) were reduced to minimal levels. CONCLUSIONSMultiple batches of anti-SARS-CoV-2 hyperimmune globulin (hIVIG) that met regulatory requirements were manufactured from human convalescent plasma. The first clinical study in which the hIVIG will be evaluated will be Inpatient Treatment with Anti-Coronavirus Immunoglobulin (ITAC) [NCT04546581].

immunology↗

The structural proteome for the primordial glycolysis/gluconeogenesis

Comprehending the constitution of early biological metabolism is indispensable for the understanding of the origin and evolution of life on Earth. Here, we analyzed the structural proteome before the Last Universal Common Ancestor (LUCA) based in the reconstruction of the ancestral sequences and structure for proteins involved in glycolysis/gluconeogenesis. The results are compatible with the notion that the first portions of the proteins were the areas homologous to the present-day catalytic sites. Those \"proto-proteins\" had a simple function: binding to cofactors. Upon the accretion of new elements to the structure, the catalytic function could have emerged. Also, the first structural motifs might have been related to the emergence of the different proteins that work in modern organisms.

evolutionary biology↗