Biology subjects

Garrido, J. L.

Publications and source records attributed to Garrido, J. L..

4 recordsLinked to original sources

bioRxiv2025

Maximum entropy networks show that plant-arbuscular mycorrhizal fungal associations are anti-nested and modular

Many applications of network theory to plant-mycorrhizal associations have used a bipartite description, in which one set of nodes is the plants, and the other set is the fungi. Most applications have relied on null models from algorithms that randomly rewire the observed connections to test for non-random patterns in the network. We used existing plant-arbuscular mycorrhizal (AM) fungal datasets to apply a new, well validated generation of network models relaxing the very limiting assumptions of traditional null models. We focused on nestedness and modularity, which have been related to the functioning and stability of communities. Given the existent literature, we expected nestedness and modularity to be prevalent. We modelled plant-AM fungal associations using maximum entropy networks with a degree sequence, soft constraint to generate null distributions for nestedness and modularity. Most plant-AM fungal associations were anti-nested and modular. This pattern was consistent across habitat types and multiple spatial scales. Anti-nestedness can easily emerge from modularity when network patterns are determined by the identity of the plant and AM fungal nodes. Future studies will have to test how the observed patterns determine the ability of the associations to adapt to environmental changes.

ecology↗

bioRxiv2024

Developmentally-regulated proteolysis by MdfA and ClpCP mediates metabolic differentiation during Bacillus subtilis sporulation

Bacillus subtilis sporulation entails a dramatic transformation of the two cells required to assemble a dormant spore, with the larger mother cell engulfing the smaller forespore to produce the cell-within-a-cell structure that is a hallmark of endospore formation. Sporulation also entails metabolic differentiation, whereby key metabolic enzymes are depleted from the forespore but maintained in the mother cell. This reduces the metabolic potential of the forespore, which becomes dependent on mother-cell metabolism and the SpoIIQ-SpoIIIA channel to obtain metabolic building blocks necessary for development. We demonstrate that metabolic differentiation depends on the ClpCP protease and a forespore-produced protein encoded by the yjbA gene, which we have renamed MdfA (metabolic differentiation factor A). MdfA is conserved in aerobic endospore-formers and required for spore resistance to hypochlorite. Using mass spectrometry and quantitative fluorescence microscopy, we show that MdfA mediates the depletion of dozens of metabolic enzymes and key transcription factors from the forespore. An accompanying study by Massoni, Evans and collaborators demonstrates that MdfA is a ClpC adaptor protein that directly interacts with and stimulates ClpCP activity. Together, these results document a developmentally-regulated proteolytic pathway that reshapes forespore metabolism, reinforces differentiation, and is required to produce spores resistant to the oxidant hypochlorite.

microbiology↗

bioRxiv2024

Longitudinal transcriptional changes reveal genes from the natural killer cell-mediated cytotoxicity pathway as critical players underlying COVID-19 progression

Patients present a wide range of clinical severities in response SARS-CoV-2 infection, but the underlying molecular and cellular reasons why clinical outcomes vary so greatly within the population remains unknown. Here, we report that negative clinical outcomes in severely ill patients were associated with divergent RNA transcriptome profiles in peripheral immune cells compared with mild cases during the first weeks after disease onset. Protein-protein interaction analysis indicated that early-responding cytotoxic NK cells were associated with an effective clearance of the virus and a less severe outcome. This innate immune response was associated with the activation of select cytokine-cytokine receptor pathways and robust Th1/Th2 cell differentiation profiles. In contrast, severely ill patients exhibited a dysregulation between innate and adaptive responses affiliated with divergent Th1/Th2 profiles and negative outcomes. This knowledge forms the basis of clinical triage that may be used to preemptively detect high-risk patients before life-threatening outcomes ensue. Highlights- Mild COVID-19 patients displayed an early transcriptional commitment with NK cell function, whereas severe patients do so with neutrophil function. - The identified co-expressed genes give insights into a coordinated transcriptional program of NK cell cytotoxic activity being associated with mild patients. - Key checkpoints of NK cell cytotoxicity that were enriched in mild patients include: KLRD1, CD247, and IFNG. - The early innate immune response related to NK cells connects with the Th1/Th2 adaptive immune responses, supporting their relevance in COVID-19 progression.

immunology↗

bioRxiv2020

Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions

Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive repository. Up until March 27, 2020, we downloaded 53 illumina datasets, mostly from China, USA (Washington DC) and Australia (Victoria). Of 30 high quality datasets, 27 datasets (90%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA sequencing samples. Sequencing samples from USA in GenBank present this signature with 50% allele frequencies among samples. Australian mutation signatures were more diverse than USA samples, but still, clonal events were found in those samples. Mutations in the helicase and orf1a coding regions from SARS-CoV-2 were predominant, among others, suggesting that these proteins are prone to evolve by natural selection. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing.

genomics↗