Biology subjects

Juarez, A.

Publications and source records attributed to Juarez, A..

6 recordsLinked to original sources

bioRxiv2026

Highly prevalent cargo genes of F plasmids harbored in pathogenic Escherichia coli

Analysis of prevalent orthogroups (OGs) in a collection of F plasmids from extraintestinal Escherichia coli ST131 isolates has led to the identification of two groups of previously uncharacterized cargo genes that may be widely distributed among F plasmids of pathogenic E. coli. Group 1 comprises four OGs whose encoded proteins are predicted to be involved in transport-related functions. The corresponding genes cluster with other genes associated with metabolism and are highly prevalent in extraintestinal ST131 isolates. Group 2 comprises several OGs whose encoded proteins currently have unknown functions. These OGs are present in a large proportion of F plasmids from both intestinal and extraintestinal E. coli isolates. The corresponding genes cluster within an F-plasmid region that also contains genes involved in DNA metabolism, suggesting that the proteins encoded by these newly identified OGs may likewise contribute to F-plasmid DNA biology. Characterizing the functions of these newly identified proteins may improve our understanding of the contribution of F plasmid to E. coli virulence and reveal novel targets for antimicrobial intervention, either by limiting F-plasmid dissemination among multidrug-resistant (MDR) E. coli strains or by directly targeting plasmid-carrying bacteria.

genomics↗

bioRxiv2026

A conserved pituitary response to tissue loss controls regeneration across vertebrates

Regenerating complex tissues requires coordination between local cellular responses and body-wide systemic signals. As a central endocrine regulator, the pituitary is well positioned to coordinate this process. Here, we identify the pituitary as an injury-responsive regulator of axolotl limb and tilapia fin regeneration. Limb loss triggered sustained transcriptional responses in the axolotl pituitary. Single-cell transcriptomics linked pituitary loss to altered gene expression in prolactin- and growth hormone-responsive limb cells. Local disruption of the prolactin receptor impaired digit formation, whereas combined hormone treatment partially restored regeneration in hypophysectomized axolotls. In tilapia, pituitary removal impaired fin regeneration and prolactin-related signaling. Mouse digits differed from axolotls and tilapia in how and when they received pituitary signals during regeneration, suggesting pituitary-dependent regrowth is evolutionarily divergent among highly regenerative vertebrates.

systems biology↗

bioRxiv2024

Associations between regional blood-brain barrier disruption, aging, and Alzheimers disease biomarkers in cognitively normal older adults

BackgroundBlood-brain barrier disruption (BBBd) has been hypothesized as a feature of aging that may lead to the development of Alzheimers disease (AD). We sought to identify the brain regions most vulnerable to BBBd during aging and examine their regional relationship with neuroimaging biomarkers of AD. MethodsWe studied 31 cognitively normal older adults (OA) and 10 young adults (YA) from the Berkeley Aging Cohort Study (BACS). Both OA and YA received dynamic contrast-enhanced MRI (DCE-MRI) to quantify Ktrans values, as a measure of BBBd, in 37 brain regions across the cortex. The OA also received Pittsburgh compound B (PiB)-PET to create distribution volume ratios (DVR) images and flortaucipir (FTP)-PET to create partial volume corrected standardized uptake volume ratios (SUVR) images. Repeated measures ANOVA assessed the brain regions where OA showed greater BBBd than YA. In OA, Ktrans values were compared based on sex, A{beta} positivity status, and APOE4 carrier status within a composite region across the areas susceptible to aging. We used linear models and sparse canonical correlation analysis (SCCA) to examine the relationship between Ktrans and AD biomarkers. ResultsOA showed greater BBBd than YA predominately in the temporal lobe, with some involvement of parietal, occipital and frontal lobes. Within an averaged ROI of affected regions, there was no difference in Ktrans values based on sex or A{beta} positivity, but OA who were APOE4 carriers had significantly higher Ktrans values. There was no direct relationship between averaged Ktrans and global A{beta} pathology, but there was a trend for an A{beta} status by tau interaction on Ktrans in this region. SCCA showed increased Ktrans was associated with increased PiB DVR, mainly in temporal and parietal brain regions. There was not a significant relationship between Ktrans and FTP SUVR. DiscussionOur findings indicate that the BBB shows regional vulnerability during normal aging that overlaps considerably with the pattern of AD pathology. Greater BBBd in brain regions affected in aging is related to APOE genotype and may also be related to the pathological accumulation of A{beta}.

neuroscience↗

bioRxiv2023

Targeting plasmid-encoded proteins that contain immunoglobulin-like domains to combat antimicrobial resistance.

Antimicrobial resistance (AMR) poses a significant threat to human health. Although vaccines have been developed to combat AMR, it has proven challenging to associate specific vaccine antigens with AMR. Bacterial plasmids play a crucial role in the transmission of AMR. Our recent research has identified a group of bacterial plasmids (specifically, IncHI plasmids) that encode large molecular mass proteins containing bacterial immunoglobulin-like domains. These proteins are found on the external surface of the bacterial cells, such as in the flagella or conjugative pili. In this study, we show that these proteins are antigenic and can protect mice from infection caused by an AMR Salmonella strain harboring one of these plasmids. Furthermore, we successfully generated nanobodies targeting these proteins, that were shown to interfere with the conjugative transfer of IncHI plasmids. Considering that these proteins are also encoded in other groups of plasmids, such as IncA/C and IncP2, targeting them could be a valuable strategy in combating AMR infections caused by bacteria harboring different groups of AMR plasmids. Since the selected antigens are directly linked to AMR itself, the protective effect extends beyond specific microorganisms to include all those carrying the corresponding resistance plasmids.

microbiology↗

bioRxiv2021

Roles of proteins containing immunoglobulin-like domains in the conjugation of bacterial plasmids.

Horizontal transfer of bacterial plasmids generates genetic variability and contributes to the dissemination of the genes that enable bacterial cells to develop antimicrobial resistance (AMR). Several aspects of the conjugative process have long been known, namely, those related to the proteins that participate in the establishment of cell-to-cell contact and to the enzymatic processes associated with the processing of plasmid DNA and its transfer to the recipient cell. In this work, we describe the role of newly identified proteins that influence the conjugation of several plasmids. Genes encoding high-molecular-weight proteins that contain one or several immunoglobulin-like domains (Big) are located in the transfer regions of several plasmids that usually harbor AMR determinants. These Big proteins are exported to the external medium and target two extracellular organelles: the flagella and the conjugative pili. The plasmid-encoded Big proteins facilitate conjugation by reducing cell motility and facilitating cell-to-cell contact by binding both to the flagella and to the conjugative pilus. They use the same export machinery as that used by the conjugative pilus components. In the examples characterized in this paper, these proteins influence conjugation at environmental temperatures (i.e., 25{degrees}C). This suggests that they may play relevant roles in the dissemination of plasmids in natural environments. Taking into account that they interact with outer surface organelles, they could be targeted to control the dissemination of different bacterial plasmids carrying AMR determinants.

microbiology↗

bioRxiv2020

High-density amplicon sequencing identifies community spread and ongoing evolution of SARS-CoV-2 in the Southern United States

SARS-CoV-2 is constantly evolving. Prior studies have focused on high case-density locations, such as the Northern and Western metropolitan areas in the U.S. This study demonstrates continued SARS-CoV-2 evolution in a suburban Southern U.S. region by high-density amplicon sequencing of symptomatic cases. 57% of strains carried the spike D614G variant. The presence of D614G was associated with a higher genome copy number and its prevalence expanded with time. Four strains carried a deletion in a predicted stem loop of the 3 untranslated region. The data are consistent with community spread within the local population and the larger continental U.S. No strain had mutations in the target sites used in common diagnostic assays. The data instill confidence in the sensitivity of current tests and validate "testing by sequencing" as a new option to uncover cases, particularly those not conforming to the standard clinical presentation of COVID-19. This study contributes to the understanding of COVID-19 by providing an extensive set of genomes from a non-urban setting and further informs vaccine design by defining D614G as a dominant and emergent SARS-CoV-2 isolate in the U.S.

microbiology↗