Biology subjects

Garcia, B. J.

Publications and source records attributed to Garcia, B. J..

4 recordsLinked to original sources

bioRxiv2023

Ontogeny of the organized nasopharynx-associated lymphoid tissue in rainbow trout

Understanding the ontogeny of teleost mucosa-associated lymphoid tissues (MALT) is critical for determining the earliest timepoint for effective mucosal vaccination of young fish. Here, we describe the developmental sequence that leads to the formation of an organized MALT structure in rainbow trout, the organized nasopharynx-associated lymphoid tissue (O-NALT). Control rainbow trout were sampled between 340 and 1860 degree days (DD) and routine histology and immunofluorescence staining were used to determine cellular changes in immune cells in the nasal cavity as well as O-NALT formation. We identified that O-NALT is first seeded by CD8+ T cells at 700DD followed by IgM+ B cells and CD4-2b+ T cells at 1000DD. Histomorphologically, trout O-NALT is fully formed at 1400DD when it is composed of 67% CD4-2b+ cells, 20% IgM+ cells, 13% CD8+ T cells, and no IgT+ B cells. Whole body gene expression analyses uncovered waves of igmh, cd4-2b, and cd8a expression that recapitulate the cellular seeding sequence of O-NALT by specific lymphocyte subsets. Our results indicate that 1) O-NALT formation results from a specific sequence of lymphocyte subset colonization pioneered by CD8+ T cells and 2) the presence of the full O-NALT structure at 1400DD may mark this timepoint as the earliest developmental stage at which mucosal vaccines can induce long lasting, specific immune responses.

immunology↗

bioRxiv2023

Clustering the Planet: An Exascale Approach to Determining Global Climatype Zones

We present an exascale approach for producing global scale, high resolution, longitudinally based geoclimate classifications. Using a GPU implementation of the DUO Similarity Metric on the Summit supercomputer, we calculated the pairwise environmental similarity of 156,384,190 vectors of 414,640 encoded elements derived from 71 environmental variables over a 50-year time span at 1km2 resolution. GPU matrix-matrix (GEMM) kernels were optimized for the GPU architecture and their outputs were managed through aggressive concurrent MPI rank CPU communication, calculations, and transfers. Using vector transformation and highly optimized operations of generalized distributed dense linear algebra, calculation of all-vector-pairs similarity resulted in 5.07 x 1021 element comparisons and reached a peak performance of 2.31 exaflops. We demonstrated this method using existing and synthesized climate layers to show how geography can be parsed using high-performance computing. Geoclimate zones are important tools for understanding how environmental variables impact natural systems, particularly for agriculture and conservation with relevance to climate change. Historically, classification systems have been low resolution, based on limited variables, or subjective. To identify climate classes, we clustered DUO outputs at varying stringency, producing 69, 133, 340, and 717 global geoclimate zones. Our approach produced global scale, high resolution, longitudinally informed climate classifications that can be used in precision agriculture, cultivar breeding efforts, and conservation programs.

bioinformatics↗

bioRxiv2023

Rational Prediction of PROTAC-compatible Protein-Protein Interfaces by Molecular Docking

Proteolysis targeting chimeras (PROTACS) are heterobifunctional ligands that mediate the interaction between a protein target and an E3 ligase, resulting in a ternary complex whose interaction with the ubiquitination machinery leads to target degradation. This technology is emerging as an exciting new avenue for therapeutic development, with several PROTACS currently undergoing clinical trials targeting cancer. Here, we describe a general and computationally efficient methodology combining restraint-based docking, energy-based rescoring, and a filter based on minimal solvent-accessible surface distance to produce PROTAC-compatible PPIs suitable for when there is no a priori known PROTAC ligand. In a benchmark employing a manually curated dataset of 13 ternary complex crystals, we achieved accuracy of 92% when starting from bound structures, and 77% when starting from unbound structures, respectively. Our method only requires that the ligand-bound structures of the monomeric forms of the E3 ligase and target proteins be given to run, making it general, accurate and highly efficient, with the ability to impact early stage PROTAC-based drug design campaigns where no structural information about the ternary complex structure is available.

bioinformatics↗

bioRxiv2019

Differences in resources use lead to coexistence of seed-transmitted microbial populations

Seeds are involved in the vertical transmission of microorganisms in plants and act as reservoirs for the plant microbiome. They could serve as carriers of pathogens, making the study of microbial interactions on seeds important in the emergence of plant diseases. We studied the influence of biological disturbances caused by seed transmission of two phytopathogenic agents, Alternaria brassicicola Abra43 (Abra43) and Xanthomonas campestris pv. campestris 8004 (Xcc8004), on the structure and function of radish seed microbial assemblages, as well as the nutritional overlap between Xcc8004 and the seed microbiome, to find seed microbial residents capable of outcompeting this pathogen. According to taxonomic and functional inference performed on metagenomics reads, no shift in structure and function of the seed microbiome was observed following Abra43 and Xcc8004 transmission. This lack of impact derives from a limited overlap in nutritional resources between Xcc8004 and the major bacterial populations of radish seeds. However, two native seed-associated bacterial strains belonging to Stenotrophomonas rhizophila displayed a high overlap with Xcc8004 regarding the use of resources; they might therefore limit its transmission. The strategy we used may serve as a foundation for the selection of seed indigenous bacterial strains that could limit seed transmission of pathogens.

plant biology↗