Biology subjects

Rodriguez, M.

Publications and source records attributed to Rodriguez, M..

42 records · Page 3Linked to original sources

bioRxiv2019

Non-Canonical Regulation of Phosphatidylserine Metabolism by a Phosphatidylinositol Transfer Protein and a Phosphatidylinositol 4-OH Kinase

The phosphatidylserine (PtdSer) decarboxylase Psd2 is proposed to engage in an endoplasmic reticulum (ER)-Golgi/endosome membrane contact site (MCS) that facilitates phosphatidylserine decarboxylation to phosphatidylethanomaine (PtdEtn) in Saccharomyces cerevisiae. While this MCS is envisioned to consist of Psd2, the Sec14-like phosphatidylinositol transfer protein (PITP) Sfh4, the Stt4 phosphatidylinositol (PtdIns) 4-OH kinase, the Scs2 tether, and at least one other uncharacterized protein, functional data that address key foundations of this model are sparse. We now report that Psd2, Sfh4 and Stt4 are the only components individually required for biologically sufficient Psd2-dependent PtdEtn production. Surprisingly, neither the PtdIns-transfer activity of Sfh4 nor its capacity to activate Stt4 is required to stimulate the Psd2 pathway. Instead, Sfh4 activates the Psd2 pathway via a specific Sfh4-Psd2 physical interaction. Whereas the data indicate an Sfh4-independent association of Stt4 with Psd2 as well, we find Stt4 also regulates Psd2 activity indirectly by influencing the PtdSer pool accessible to Psd2 for decarboxylation. These collective results demonstrate that the proposed ER-Golgi/endosomal MCS model fails to provide an accurate description of the Psd2 system in yeast, and provide an example where the biological function of a Sec14-like PITP is uncoupled from its canonical activity as a PtdIns transfer protein.

cell biology↗

bioRxiv2019

Prevalence of parasitic infections among recent immigrants to Chicago

BackgroundParasitic infections are likely under-recognized among immigrant populations in the United States (US). We conducted a cross-sectional study to evaluate the frequency of such infections among recent immigrants in Chicago and to identify predictive factors for parasitic infections.\n\nMethodology and principal findings133 recent immigrants were enrolled, filling out a standardized questionnaire regarding medical history and exposures and providing blood and stool samples for evaluation. Fifteen of 125 subjects (12%) who provided a blood or stool sample for testing were found to have evidence of current or prior infection with a pathogenic parasite, of which Toxocara spp. (8 subjects, 6.4%) and Strongyloides stercoralis (5 subjects, 4%) were most commonly identified. Parasitic infection was more likely among subjects who had immigrated within the previous 2 years and those with a self-reported history of ever having seen worms in the stool. Infected individuals were likely to have multiple nonspecific physical complaints; however, classic symptoms of parasitic infections (skin rashes, diarrhea, etc.) were not increased among infected individuals. The most useful surrogate markers identified for parasitic infections were an elevated Immunoglobulin E level (seen in 7/15 subjects with parasitic infections, 46.7% and 22/110 uninfected individuals, 20%, p=0.04) and the presence of Blastocystis hominis cysts on Ova & Parasite exam (detected in 5/13 subjects with parasitic infections who provided a stool sample, 38.5% and 5/98 uninfected subjects, 5.1%, p=0.002). In contrast, the Absolute Eosinophil Count (typically thought of as an indicator of parasites) was not found to be a good screening test for parasitic infections in this study.\n\nConclusionsOur study found that parasitic infections are common in recent US immigrants, which highlights an important health disparity among a vulnerable population. Further, we found that classically used symptoms and laboratory tests had a low predictive value for parasitic infections in this population.\n\nAUTHOR SUMMARYParasitic infections, though rare in the United States (US), are common in many areas of the world including the regions of origin of many US immigrants. However, the prevalence rates and health impacts of these infections in immigrant populations are undefined. We conducted a study to identify the frequency of parasitic infections among healthy immigrants in one community, recruiting 133 immigrants from 28 countries. Subjects completed a standardized questionnaire regarding symptoms and infection risk-factors and provided blood and stool samples for testing. Twelve percent of subjects in our study had evidence of current or previous pathogenic parasitic infections. Symptoms and risk factors classically thought to be associated with parasitic infection (allergic symptoms, elevated blood eosinophil counts, etc.) were common among enrolled subjects, but did not differ significantly between those with and without evidence for infection. Overall, our results suggest that many immigrants, even those who are asymptomatic, may have undiagnosed parasitic infections. These results highlight an important health disparity among a vulnerable underserved population in the US. As most of these infections are easily treatable, more research should be done to further characterize the optimal testing strategies for recent immigrants.

epidemiology↗

bioRxiv2018

Inhalation of marijuana affects Drosophila heart function

Medical uses of marijuana have been recently approved in many countries, and after a long ban on research, there is despicable scientific evidence regarding its action and side effects. We investigated the effect of inhalation of vaporized marijuana on cardiac function in Drosophila melanogaster, a suitable genetic model for assessing cardiovascular function. Chronic exposure of adult flies to vaporized marijuana reduces heart rate, increments contractility and prolongs relaxation. These changes are manifested in the cardiomyocytes with no effect in calcium handling, and in the absence of the canonical cannabinoids receptors identified in mammals. Our results are the first evidence of the in vivo impact of phytocannabinoids in D. melanogaster and open new paths for genetic screenings using vaporized compounds, providing a simple and affordable platform prior to mammalian models.

physiology↗

bioRxiv2018

Expanding an expanded genome: long-read sequencing of Trypanosoma cruzi

Although the genome of Trypanosoma cruzi, the causative agent of Chagas disease, was first made available in 2005, with additional strains reported later, the intrinsic genome complexity of this parasite (abundance of repetitive sequences and genes organized in tandem) has traditionally hindered high-quality genome assembly and annotation. This also limits diverse types of analyses that require high degree of precision. Long reads generated by third-generation sequencing technologies are particularly suitable to address the challenges associated with T. cruzi{acute}s genome since they permit directly determining the full sequence of large clusters of repetitive sequences without collapsing them. This, in turn, allows not only accurate estimation of gene copy numbers but also circumvents assembly fragmentation. Here, we present the analysis of the genome sequences of two T. cruzi clones: the hybrid TCC (DTU TcVI) and the non-hybrid Dm28c (DTU TcI), determined by PacBio SMRT technology. The improved assemblies herein obtained permitted us to accurately estimate gene copy numbers, abundance and distribution of repetitive sequences (including satellites and retroelements). We found that the genome of T. cruzi is composed of a \"core compartment\" and a \"disruptive compartment\" which exhibit opposite gene and GC content composition. New tandem and disperse repetitive sequences were identified, including some located inside coding sequences. Additionally, homologous chromosomes were separately assembled, allowing us to retrieve haplotypes as separate contigs instead of a unique mosaic sequence. Finally, manual annotation of surface multigene families MUC and trans-sialidases allows now a better overview of these complex groups of genes.

genomics↗

bioRxiv2017

A Point Of No Return Leading To Death During Heat-Shock In C. elegans

There is considerable insight into pathways and genes associated with heat-stress conditions. Most genes involved in stress response have been identified using mutant screens or gene knockdowns. Yet, there is limited understanding of the temporal dynamics of global gene expression in stressful environments. Here, we studied global gene expression profiles during 12 hours of heat stress in the nematode C. elegans. Using a high-resolution time series of increasing stress exposures, we found a distinct shift in gene expression patterns between 3-4 hours into the stress response, separating an initially highly dynamic phase from a later relatively stagnant phase. This turning point in expression dynamics coincided with a phenotypic turning point, as shown by a strong decrease in movement, survival and, progeny count in the days following the stress. Both detectable at transcriptional and phenotypic level, this study pin-points a relatively small time frame during heat stress at which enough damage is accumulated, making it impossible to recover the next few days.

genomics↗

bioRxiv2017

Genetical genomics reveals Ras/MAPK modifier loci

The oncogenic Ras/MAPK pathway is evolutionary conserved across metazoans and is essential for many cellular functions. Mutant screens in the model nematode Caenorhabditis elegans have been invaluable for elucidating Ras/MAPK pathway characteristics and identification of the genes involved. Almost all of these screens have been conducted in a single genetic background. However, phenotypic traits of induced mutations can vary widely depending on the genetic background. At the moment, we lack insight into how different genetic backgrounds modulate Ras/MAPK-signaling and which genetic modifiers are involved.\n\nWe previously introduced a gain-of-function mutation in the Ras/MAPK pathway gene let-60 in over 200 recombinant inbred lines (mutant introgressed RILs: miRILs) and detected genetic modifiers affecting this pathway by studying variation in vulval development. In the present study, we investigate how gene expression regulation is affected by the let-60 gain-of-function mutation and the genetic background by mapping eQTL using 33 miRILs. We found that the majority ([~]73%) of the 1516 detected cis-eQTL are not specific for the let-60 mutation, whereas most ([~]76%) of the 898 detected trans-eQTL are associated with the let-60 mutation. We detected 6 eQTL trans-bands that were specific for the interaction between the genetic background and the mutation. One of these eQTL hotspots co-localizes with the previously identified polymorphic Ras/MAPK modifier amx-2. Comparing gene expression profiles between transgenic lines expressing either the N2 or the CB4856 alleles of amx-2 showed the involvement of amx-2 in 79% of the trans-eQTLs for genes mapping to this trans-band.\n\nTogether, our results have revealed hidden loci affecting Ras/MAPK signaling using sensitized backgrounds in C. elegans. These loci harbor putative polymorphic modifier genes that would not have been detected using mutant screens in single genetic backgrounds.

genetics↗