Biology subjects

Garcia, E. L.

Publications and source records attributed to Garcia, E. L..

6 recordsLinked to original sources

bioRxiv2026

Comparative genomics of the unusual arachnid order Solifugae spotlight the molecular and genetic basis for adaptations to arid habitats

The evolutionary transition to terrestrial life required overcoming several physiological hurdles; however, such challenges were amplified in desert environments. While several xeric-adapted arachnids utilize permanent burrows or "sit-and-wait" foraging strategies as possible energy conservation adaptations in harsh habitats, camel spiders exhibit a counterintuitive, high-energy lifestyle. To investigate the molecular underpinnings distinguishing Solifugae within Chelicerata, we utilized a comparative genomics framework that incorporates a newly sequenced, previously unpublished solifuge genome. We identified lineage-specific expanded orthogroups and evaluated selective pressures acting upon paralogous sequences within our ingroup solifuge species. Additionally, we also focused on fatty acid-associated proteins and heat shock proteins to elucidate how Solifugae may have evolved such anomalous behaviors compared to their arachnid relatives. Our analyses revealed significant signatures of positive selection within key gene families across the solifuge lineage. Notably, paralogs within the cytochrome P450 and biotinidase families showed consistent evidence of selection across all three taxa, suggesting specialized metabolic or detoxification requirements. Furthermore, we identified candidate loci implicated in axonal guidance and lipid metabolism, and a specialized fatty acid enzyme repertoire. While subsequent research is required to determine whether some of the genomic signatures unveiled here are shared across a broader phylogenetic distribution within Solifugae, we establish a critical baseline for future functional validation.

evolutionary biology↗

bioRxiv2026

Genetic and Glycosylation Variability of the GP5 Glycoprotein in Betaarterivirus americense NADC34 Variant Isolates from Peru

Lima is a major swine production hub in Peru; therefore, these data provide an initial overview of GP5 variability in a high-risk epidemiological setting. This study aimed to characterize the genetic variability, N-glycosylation sites, and recombination events in the ORF5 (GP5) gene of lineage 1A (NADC34) Betaarterivirus americense strains circulating in Lima, Peru. Bioinformatics servers and software were employed, including Nextclade v3, NetNGlyc 1.0, RDP v4.1, DnaSP v6, and MEGA6. Nextclade v3 supported the classification of 24 strains within lineage 1, sublineage 1A (NADC34), which exhibited high divergence based on GP5 phylogenetic analysis. Significant amino acid substitutions were identified in the hypervariable regions HVR1 and HVR2, which are associated with the induction of neutralizing and non-neutralizing antibodies: 16/24 at N32 (S/G/R/E), 3/24 at S34 (N/T), 6/24 at S35 (N/I), 7/24 at L39 (F), 6/24 at Q40 (L/R), 3/24 at L41 (Y/V), 15/24 at K58 (E/V/R), and 8/24 at S59 (H/R/N), located within GP5 epitopes A, B, and C. Nine N-glycosylation patterns (A-I) were identified across the 24 strains, comprising nine putative sites at N30, N32, N33, N34, N35, N44, N50, N51, and N57. Patterns A, B, E, and G exhibited five to six glycosylation sites in 12/24 strains. A statistically robust recombination event was detected in strain 42_Montana2019 (lineage 1A), with a putative major parent MH719138_1 (lineage 1A, Peru-2016/5 variant; 95.3% sequence similarity) and an unknown minor parent, although strain 36_Montana2019 showed the closest phylogenetic affinity. Genetic diversity analysis revealed 530 polymorphic sites, and Tajimas D test yielded a value of -0.78746, indicating high genetic variability within the Lima cohort. Overall, this study provides the first comprehensive molecular characterization of ORF5 (GP5) genetic variability in sublineage 1A (NADC34) Betaarterivirus americense strains circulating in swine farms in Lima. Broader and temporally structured sampling is warranted to assess nationwide evolutionary patterns.

microbiology↗

bioRxiv2024

Chaperoning the chaperones: Proteomic analysis of the SMN complex reveals conserved and etiologic connections to the proteostasis network

Molecular chaperones and co-chaperones are highly conserved cellular components that perform variety of duties related to the proper three-dimensional folding of the proteome. The web of factors that carries out this essential task is called the proteostasis network (PN). Ribonucleoproteins (RNPs) represent an underexplored area in terms of the connections they make with the PN. The Survival Motor Neuron (SMN) complex is an RNP assembly chaperone and serves as a paradigm for studying how specific small nuclear (sn)RNAs are identified and paired with their client substrate proteins. SMN protein is the eponymous component of a large complex required for the biogenesis of uridine-rich small nuclear ribonucleoproteins (U-snRNPs) and localizes to distinct membraneless organelles in both the nucleus and cytoplasm of animal cells. SMN forms the oligomeric core of this complex, and missense mutations in its YG box self-interaction domain are known to cause Spinal Muscular Atrophy (SMA). The basic framework for understanding how snRNAs are assembled into U-snRNPs is known, the pathways and mechanisms used by cells to regulate their biogenesis are poorly understood. Given the importance of these processes to normal development as well as neurodegenerative disease, we set out to identify and characterize novel SMN binding partners. Here, we carried out affinity purification mass spectrometry (AP-MS) of SMN using stable fly lines exclusively expressing either wildtype or SMA-causing missense alleles. Bioinformatic analyses of the pulldown data, along with comparisons to proximity labeling studies carried out in human cells, revealed conserved connections to at least two other major chaperone systems including heat shock folding chaperones (HSPs) and histone/nucleosome assembly chaperones. Notably, we found that heat shock cognate protein Hsc70-4 and other HspA family members preferentially interacted with SMA-causing alleles of SMN. Hsc70-4 is particularly interesting because its mRNA is aberrantly sequestered by a mutant form of TDP-43 in mouse and Drosophila ALS (Amyotrophic Lateral Sclerosis) disease models. Most important, a missense allele of Hsc70-4 (HspA8 in mammals) was recently identified as a bypass suppressor of the SMA phenotype in mice. Collectively, these findings suggest that chaperone-related dysfunction lies at the etiological root of both ALS and SMA.

genomics↗

bioRxiv2023

Dysregulation of innate immune signaling in animal models of Spinal Muscular Atrophy

BackgroundSpinal Muscular Atrophy (SMA) is a devastating neuromuscular disease caused by hypomorphic loss of function in the Survival Motor Neuron (SMN) protein. SMA presents across broad spectrum of disease severity. Unfortunately, vertebrate models of intermediate SMA have been difficult to generate and are thus unable to address key aspects of disease etiology. To address these issues, we developed a Drosophila model system that recapitulates the full range of SMA severity, allowing studies of pre-onset biology as well as late-stage disease processes. ResultsHere, we carried out transcriptomic and proteomic profiling of mild and intermediate Drosophila models of SMA to elucidate molecules and pathways that contribute to the disease. Using this approach, we elaborated a role for the SMN complex in the regulation of innate immune signaling. We find that mutation or tissue-specific depletion of SMN induces hyperactivation of the Immune Deficiency (IMD) and Toll pathways, leading to overexpression of antimicrobial peptides (AMPs) and ectopic formation of melanotic masses in the absence of an external challenge. Furthermore, knockdown of downstream targets of these signaling pathways reduced melanotic mass formation caused by SMN loss. Importantly, we identify SMN as a negative regulator of an ubiquitylation complex that includes Traf6, Bendless and Diap2, and plays a pivotal role in several signaling networks. ConclusionsIn alignment with recent research on other neurodegenerative diseases, these findings suggest that hyperactivation of innate immunity contributes to SMA pathology. This work not only provides compelling evidence that hyperactive innate immune signaling is a primary effect of SMN depletion, but it also suggests that the SMN complex plays a regulatory role in this process in vivo. In summary, immune dysfunction in SMA is a consequence of reduced SMN levels and is driven by cellular and molecular mechanisms that are conserved between insects and mammals.

genetics↗

bioRxiv2022

Paired Associates Learning is Disrupted After Unilateral Parietal Lobe Controlled Cortical Impact in Rats: A Trial-by-Trial Behavioral Analysis

Approximately 60-70 million people suffer from a traumatic brain injury (TBI) each year. As animal models continue to be paramount in understanding and treating cognitive impairment following TBI, the necessity of testing intervention strategies in clinically relevant settings cannot be ignored. This study used a unilateral parietal lobe controlled cortical impact (CCI) model of TBI and tested rats on a touchscreen-based associative learning task, Paired Associates Learning (PAL). In humans, PAL has been used to assess cognitive deficits in stimulus-location association in a multitude of disease states, including TBI. To date, the extent to which a rat model of TBI produces deficits in PAL has not yet been reported, although the usage of PAL will be important for understanding the clinical consequences of cognitive impairment post-injury and throughout intervention treatment. This study details the behavioral and histological consequences of the CCI injury model and closes a translational research gap between basic and clinical TBI research. HIGHLIGHTSO_LIPAL performance declines in a rat model of TBI. C_LIO_LIResponse-driven bias in PAL becomes elevated after TBI. C_LIO_LIInflammatory microglial response in the thalamus correlates with PAL deficit. C_LI

animal behavior and cognition↗

bioRxiv2021

Tales of schizomid tails: patterns in schizomid flagellum shape from elliptical Fourier analysis

The arachnid order Schizomida is a relatively understudied group of soil-dwelling predators found on all continents except Antarctica. While efforts to understand their biology are growing, there is still much to know about them. A curious aspect of their morphology is the male flagellum, a sexually dimorphic, tail-like structure which differs in shape across the order and functions in their courtship rituals. The flagellar shape is important for taxonomic classification, yet few efforts have been made to examine shape diversity across the group. Using elliptical Fourier analysis, a type of geometric morphometrics based on outline shape, we quantified shape differences across a combined nearly 550 outlines in the dorsal and lateral views, categorizing them based on genus, family, biogeographic realm, and habitat, with special emphasis on Caribbean and Cuban fauna. We tested for allometric relationships, differences in disparity based on locations and sizes in morphospace among these categories, and for clusters of shapes in morphospace. We found multiple differences in all categories despite apparent overlaps in morphospace, evolutionary allometry, and evidence for discrete clusters in some flagellum shapes. This study can serve as a foundation for further study on the evolution, diversification, and taxonomic utility of the male flagellum.

zoology↗