Biology subjects

Torres, A.

Publications and source records attributed to Torres, A..

35 records · Page 2Linked to original sources

bioRxiv2022

Unearthing the global impact of mining construction minerals on biodiversity

Construction minerals - sand, gravel, limestone - are the most extracted solid raw materials1 and account for most of the worlds anthropogenic mass, which as of 2020 outweighed all of Earths living biomass2. However, knowledge about the magnitude, geography, and profile of this widespread threat to biodiversity remains scarce and scattered3-6. Combining long-term data from the IUCN Red List and new species descriptions we provide the first systematic evaluation of species threatened by mining of construction minerals globally. We found 1,047 species in the Red List impacted by this type of mining, of which 58.5% are threatened with extinction and four species already went extinct. We also identified 234 new species descriptions in 20 biodiversity hotspots reporting impacts from mining. Temporal trends in the assessments highlight the increased saliency of this threat to biodiversity, whose full extent may well reach over 24,000 animal and plant species. While rock quarrying mostly threatens karst biodiversity and narrow-ranged species, sand and gravel extraction is a more prominent threat to freshwater and coastal systems. This study provides the first evidence base to support a global strategy to limit the biodiversity impacts of construction mineral extraction.

ecology↗

bioRxiv2021

NFIC regulates ribosomal biology and ER stress in pancreatic acinar cells and suppresses PDAC initiation

Tissue-specific differentiation is driven by specialized transcriptional networks. Pancreatic acinar cells crucially rely on the PTF1 complex, and on additional transcription factors, to deploy their transcriptional program. Here, we identify NFIC as a novel regulator of acinar differentiation using a variety of methodological strategies. NFIC binding sites are found at very short distances from NR5A2-bound genomic regions and both proteins co-occur in the same complex. Nfic knockout mice show reduced expression of acinar genes and, in ChIP-seq experiments, NFIC binds the promoters of acinar genes. In addition, NFIC binds to the promoter of, and regulates, genes involved in RNA and protein metabolism; in Nfic knockout mice, p-RS6K1 and p-IEF4E are down-regulated indicating reduced activity of the mTOR pathway. In 266-6 acinar cells, NFIC dampens the ER stress program through its binding to ER stress gene promoters and is required for complete resolution of Tunicamycin-mediated ER stress. Normal human pancreata from subjects with low NFIC mRNA levels display reduced epxression of genes down-regulated in Nfic knockout mice. Consistently, NFIC displays reduced expression upon induced acute pancreatitis and is required for proper recovery after damage. Finally, expression of NFIC is lower in samples of mouse and human pancreatic ductal adenocarcinoma and Nfic knockout mice develop an increased number of mutant Kras-driven pre-neoplastic lesions.

cell biology↗

bioRxiv2021

Monosodium Urate Crystals regulate a unique JNK-dependent macrophage metabolic and inflammatory response

How macrophages are programmed to respond to monosodium urate crystals (MSUc) is incompletely understood partly due to the use of a toll-like receptor-induced priming step. Here, using genome wide transcriptomic analysis and biochemical assays we demonstrate that MSUc alone induces an in vitro metabolic-inflammatory transcriptional program in both human and murine macrophages markedly distinct from that induced by LPS. Genes uniquely up-regulated in response to MSUc belonged to lipids, glycolysis, and transport of small molecules via SLC transporters pathways. Sera from individuals and mice with acute gouty arthritis provided further evidence for this metabolic rewiring. This distinct macrophage activation may explain the initiating mechanisms in acute gout flares and is regulated through JUN binding to the promoter of target genes through activation of JNK -but not by P38-in a process that is independent of inflammasome activation. Finally, pharmacological JNK inhibition limited MSUc-induced inflammation in animal models of acute gouty inflammation.

cell biology↗

bioRxiv2021

Effect of diet modification in intestinal Escherichia coli population and antimicrobial resistance

The fluctuations in the number of some intestinal bacterial lineages may be associated with increased antimicrobial resistance and disease. Adaptation to a given environment may select bacterial mutants that have reduced ability to adapt to new environments and changes in diet have been associated with alterations in microbiome taxon composition. We wanted to see the effect of diet change in linage composition and antimicrobial resistance profiles of numerically dominant E. coli. We subjected 50 chickens from an industrial operation (under corn-based diet supplemented with antimicrobials) to 2 antimicrobial-free diets; one based on corn and the other based on alfalfa. Fecal samples were obtained from all animals at arrival and after five weeks under different diets. Five E. coli colonies (from each sample) were subjected to genetic typing and antimicrobial susceptibility testing. We observed high diversity and high turnover rate of numerically dominant E. coli strains from animals from both diet groups. We did not find differences in antimicrobial resistance profiles in isolates from different diet groups. Our results suggest that there is high diversity and high turnover rate of E. coli strains in the intestines regardless of the diet. Chicken intestines seemed to contain many E. coli lineages able to thrive in different substrates. The absence of differences in antimicrobial resistance among bacteria, from animals in different diets, may indicate that the carriage of antimicrobial resistance genes does not affect the bacterial ability to adapt to different substrates.

microbiology↗

bioRxiv2020

Comprehensive quantitative proteome analysis of Aedes aegypti identifies proteins and pathways involved in Wolbachia pipientis and Zika virus interference phenomenon

Zika virus is a global public health emergency due to its association with microcephaly, Guillain-Barre syndrome, neuropathy, and myelitis in children and adults. A total of 87 countries have had evidence of autochthonous mosquito-borne transmission of Zika virus, distributed across four continents, and no antivirus therapy or vaccines are available. Therefore, several strategies have been developed to target the main mosquito vector, Aedes aegypti, to reduce the burden of different arboviruses. Among such strategies, the use of the maternally-inherited endosymbiont Wolbachia pipientis has been applied successfully to reduce virus susceptibility and decrease transmission. However, the mechanisms by which Wolbachia orchestrate resistance to ZIKV infection remain to be elucidated. In this study, we apply isobaric labeling quantitative mass spectrometry-based proteomics to quantify proteins and identify pathways altered during ZIKV infection; Wolbachia infection; co-infection with Wolbachia/ZIKV in the Ae. aegypti heads and salivary glands. We show that Wolbachia regulates proteins involved in ROS production, regulates humoral immune response, and antioxidant production. The reduction of ZIKV polyprotein in the presence of Wolbachia in mosquitoes was determined by mass spectrometry and corroborates the idea that Wolbachia helps to block ZIKV infections in Ae. aegypti. The present study offers a rich resource of data that may help to elucidate mechanisms by which Wolbachia orchestrate resistance to ZIKV infection in Ae. aegypti, and represents a step further on the development of new targeted methods to detect and quantify ZIKV and Wolbachia directly in complex tissues. HighlightsO_LIThe abundance of ZIKV polyprotein is reduced in the presence of Wolbachia C_LIO_LIShotgun proteomics quantifies ZIKV and Wolbachia proteins directly in tissues C_LIO_LIWolbachia regulates proteins involved in ROS production C_LIO_LIWolbachia regulates humoral immune response and antioxidant production C_LIO_LIMetabolism and detoxification processes were associated with mono infections C_LI

biochemistry↗

bioRxiv2020

A selective projection from the subthalamic nucleus to parvalbumin-expressing interneurons of the striatum

The striatum and subthalamic nucleus (STN) are considered to be the primary input nuclei of the basal ganglia. Projection neurons of both striatum and STN can extensively interact with other basal ganglia nuclei, and there is growing anatomical evidence of direct axonal connections from the STN to striatum. There remains, however, a pressing need to elucidate the organization and impact of these subthalamostriatal projections in the context of the diverse cell types constituting the striatum. To address this, we carried out monosynaptic retrograde tracing from genetically-defined populations of dorsal striatal neurons in adult male and female mice, quantifying the connectivity from STN neurons to spiny projection neurons, GABAergic interneurons, and cholinergic interneurons. In parallel, we used a combination of ex vivo electrophysiology and optogenetics to characterize the responses of a complementary range of dorsal striatal neuron types to activation of STN axons. Our tracing studies showed that the connectivity from STN neurons to striatal parvalbumin-expressing interneurons is significantly higher (~ four-to eight-fold) than that from STN to any of the four other striatal cell types examined. In agreement, our recording experiments showed that parvalbumin-expressing interneurons, but not the other cell types tested, commonly exhibited robust monosynaptic excitatory responses to subthalamostriatal inputs. Taken together, our data collectively demonstrate that the subthalamostriatal projection is highly selective for target cell type. We conclude that glutamatergic STN neurons are positioned to directly and powerfully influence striatal activity dynamics by virtue of their enriched innervation of GABAergic parvalbumin-expressing interneurons.

neuroscience↗

bioRxiv2020

Neutralizing antibodies from early cases of SARS-CoV-2 infection offer cross-protection against the SARS-CoV-2 D614G variant.

The emergence of a SARS-CoV-2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross-neutralize against the G614 variant. In this report, profiling of the anti-SARS-CoV-2 humoral immunity reveals similar neutralization profiles against both S protein variants, albeit waning neutralizing antibody capacity at the later phase of infection. These findings provide further insights towards the validity of current immune-based interventions. IMPORTANCERandom mutations in the viral genome is a naturally occurring event that may lead to enhanced viral fitness and immunological resistance, while heavily impacting the validity of licensed therapeutics. A single point mutation from aspartic acid (D) to glycine (G) at position 614 of the SARS-CoV-2 spike (S) protein, termed D614G, has garnered global attention due to the observed increase in transmissibility and infection rate. Given that a majority of the developing antibody-mediated therapies and serological assays are based on the S antigen of the original Wuhan reference sequence, it is crucial to determine if humoral immunity acquired from the original SARS-CoV-2 isolate is able to induce cross-detection and cross-protection against the novel prevailing D614G variant.

immunology↗

bioRxiv2019

Human follicular helper T cell promoter connectomes reveal novel genes and regulatory elements at SLE GWAS loci

Systemic lupus erythematosus (SLE) is a complex inflammatory disease mediated by autoreactive antibodies that damages multiple tissues in children and adults. Genome-wide association studies (GWAS) have statistically implicated hundreds of loci in the susceptibility to human disease, including SLE, but the majority have failed to identify the causal variants or the effector genes. As a physicochemical approach to detecting functional variants and connecting them to target genes, we generated comprehensive, high-resolution maps of SLE variant accessibility and gene connectivity in the context of the three-dimensional chromosomal architecture of human tonsillar follicular helper T cells (TFH), a cell type required for the production of anti-nuclear antibodies characteristic of SLE. These spatial epigenomic maps identified a shortlist of over 400 potentially functional variants across 48 GWAS-implicated SLE loci. Twenty percent of these variants were located in open promoters of highly-expressed TFH genes, while 80% reside in non-promoter genomic regions that are connected in 3D to genes that likewise tend to be highly expressed in TFH. Importantly, we find that 90% of SLE-associated variants exhibit spatial proximity to genes that are not nearby in the 1D sequence of the genome, and over 60% of variants skip the nearest gene to physically interact only with the promoters of distant genes. Gene ontology confirmed that genes in spatial proximity to SLE variants reside in highly SLE-relevant networks, including accessible variants that loop 200-1000 kb to interact with the promoters of the canonical TFH genes BCL6 and CXCR5. CRISPR-Cas9 genome editing confirmed that these variants reside in novel, distal regulatory elements required for normal BCL6 and CXCR5 expression by T cells. Furthermore, SLE-associated SNP-promoter interactomes implicated a set of novel genes with no known role in TFH or SLE disease biology, including the homeobox-interacting protein kinase HIPK1 and the Ste kinase homolog MINK1. Targeting these kinases in primary human TFH cells inhibited production of IL-21, a requisite cytokine for production of class-switched antibodies by B cells. This 3D-variant-to-gene mapping approach gives mechanistic insight into the SLE-associated regulatory architecture of the human genome.

genomics↗

bioRxiv2019

Evaluating the efficacy of enzalutamide and the development of resistance in a preclinical mouse model of type-I endometrial carcinoma

Androgen Receptor (AR) signaling is a critical driver of hormone-dependent prostate cancer and has also been proposed to have biological activity in female hormone-dependent cancers, including type I endometrial carcinoma (EMC). In this study, we evaluated the preclinical efficacy of a third-generation AR antagonist, enzalutamide, in a genetic mouse model of EMC, Sprr2f-Cre;Ptenfl/fl. In this model, ablation of Pten in the uterine epithelium leads to localized and distant malignant disease as observed in human EMC. We hypothesized that administering enzalutamide through the diet would temporarily decrease the incidence of invasive and metastatic carcinoma, while prolonged administration would result in development of resistance and loss of efficacy. Short-term treatment with enzalutamide reduced overall tumor burden through increased apoptosis but failed to prevent progression of invasive and metastatic disease. These results suggest that AR signaling may have biphasic, oncogenic and tumor suppressive roles in EMC that are dependent on disease stage. Enzalutamide treatment increased Progesterone Receptor (PR) expression within both stromal and tumor cell compartments. Prolonged administration of enzalutamide decreased apoptosis, increased tumor burden and resulted in the clonal expansion of tumor cells expressing high levels of p53 protein, suggestive of acquired Trp53 mutations. In conclusion, we show that enzalutamide induces apoptosis in EMC but has limited efficacy overall as a single agent. Induction of PR, a negative regulator of endometrial proliferation, suggests that adding progestin therapy to enzalutamide administration may further decrease tumor burden and result in a prolonged response.

cancer biology↗

bioRxiv2019

Gene copy number is associated with phytochemistry in Cannabis sativa

Gene copy number variation is known to be important in nearly every species where it has been examined. Alterations in gene copy number may provide a fast way of acquiring diversity, allowing rapid adaptation under strong selective pressures, and may also be a key component of standing genetic variation within species. Cannabis sativa plants produce a distinguishing set of secondary metabolites, the cannabinoids, many having medicinal utility. Two major cannabinoids -- THCA and CBDA -- are products of a three-step biochemical pathway. Using genomic data for 69 Cannabis cultivars from diverse lineages within the species, we found that genes encoding the synthases in this pathway vary in copy number, and that the cannabinoid paralogs may be differentially expressed. We also found that copy number partially explains variation in cannabinoid content levels among Cannabis plants.

genomics↗

bioRxiv2019

Assessment of a loop-mediated isothermal amplification (LAMP) assay for the rapid detection of pathogenic bacteria from respiratory samples in patients with hospital-acquired pneumonia

IntroductionHospital-acquired pneumonia (HAP) is the one that presents clinically two or more days after admission into the hospital. Rapid identification of the causative agent of HAP will allow an earlier administration of a more appropriate antibiotic therapy and could lead to an improved outcome of patients with HAP.\n\nMethodsFirst of all, a rapid procedure (< 30 min) to extract the DNA from bronchoalveolar lavage (BAL), endotracheal aspirate (EA) or bronchoaspirate (BAS) was set up. A loop-mediated isothermal amplification reaction (LAMP) specific for Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter baumannii was carried out with the extracted solution. The reaction was performed at 65{o}C for 30-40 min. LAMP was compared with bacterial culture method.\n\nResultsOverall, 58 positive BAL and 83 EA/BAS samples were tested. The limits of detection varied according to the microorganism detected and to the respiratory sample analyzed. Validation of the LAMP assay with BAL samples showed that the assay was 100% specific and 86.3% sensitive (positive predictive value of 100% and a negative predictive value of 50%). Meanwhile for BAS/EA samples, the assay rendered the following statistical parameters: 100% specificity, 94.6% sensitivity, 100% positive predictive value and 69.2% negative predictive value. These scores were obtained including minor errors as correct. The turnaround time including preparation of the sample and LAMP was circa 1 hour.\n\nConclusionsLAMP method may be used to detect the most frequent bacteria causing HAP. It is a simple, cheap, sensitive, specific and rapid assay.

microbiology↗

bioRxiv2019

Withdraw of prophylactic antimicrobials does not change the pigs’ resistome

The use of antimicrobials in the animal industry has increased the prevalence of antimicrobial resistant commensal bacteria in food products derived from animals, which could be associated with antimicrobial resistance in human pathogens. To reduce the influx of antibiotic resistant bacteria (and genes) to the human microbiota, restrictions on antimicrobials (in food animals) have been implemented in different countries. We investigated the impact of antimicrobial restriction in the frequency of antimicrobial resistant bacteria in pigs. No differences in antimicrobial resistance or antimicrobial resistance genes (richness or abundance) was found when we compared animals fed with and without antibiotics. Fitness costs of antimicrobial resistance in bacteria (in the field) seems to be overestimated.

microbiology↗

bioRxiv2018

Assessing mitochondrial function in angiosperms with highly divergent mitochondrial genomes

Angiosperm mitochondrial (mt) genes are generally slow-evolving, but multiple lineages have undergone dramatic accelerations in rates of nucleotide substitution and extreme changes in mt genome structure. While molecular evolution in these lineages has been investigated, very little is known about their mt function. Here, we develop a new protocol to characterize respiration in isolated plant mitochondria and apply it to species of Silene with mt genomes that are rapidly evolving, highly fragmented, and exceptionally large ([~]11 Mbp). This protocol, complemented with traditional measures of plant fitness, cytochrome c oxidase activity assays, and fluorescence microscopy, was used to characterize inter-and intraspecific variation in mt function. Contributions of the individual \"classic\" OXPHOS complexes, the alternative oxidase, and external NADH dehydrogenases to overall mt respiratory flux were found to be similar to previously studied angiosperms with more typical mt genomes. Some differences in mt function could be explained by inter-and intraspecific variation, possibly due to local adaptation or environmental effects. Although this study suggests that these Silene species with peculiar mt genomes still show relatively normal mt function, future experiments utilizing the protocol developed here can explore such questions in a more detailed and comparative framework.

plant biology↗

bioRxiv2017

Lymphopenic community acquired pneumonia, an unnoticed phenotype associated to mortality in non immuno-suppressed patients: a retrospective cohort study

BackgroundThe role of neutrophil and lymphocyte counts as predictors of prognosis in Community Acquired Pneumonia (CAP) has not been appropriately studied.\n\nMethodsThis was a retrospective study to evaluate by multivariate regression analysis, the association between neutrophil and lymphocyte counts with mortality at 30-days post discharge in two large cohorts of hospitalized patients with CAP and no prior immunosupression: a multicentric with 1550 patients recruited at 14 hospitals in Spain and a unicentric with 2840 patients recruited at the Hospital Clinic-Barcelona.\n\nFindingsThe unicentric cohort accounted with a higher proportion of critically ill patients: 586 (20{middle dot}6%) vs 131 (8{middle dot}5%) and non survivors 245 (8{middle dot}6%) vs 74 (4{middle dot}8%). Lymphopenia (< 1000 lymphocytes/mm3) was present in the 52{middle dot}8% of the patients in both cohorts. A sub-group of lymphopenic patients, those with lymphocyte counts below decil 3 (677 lymphocytes/mm3 in the multicentric cohort and 651 lymphocytes/mm3 in the unicentric one), showed > 2-fold increase in the risk of mortality, independently of the CURB-65 score, critical illness and receiving an appropriated antibiotic treatment: (OR [CI95%], p) (2{middle dot}18 [1{middle dot}21- 3{middle dot}92], 0{middle dot}009) and (2{middle dot}33 [1{middle dot}61-3{middle dot}33], <0{middle dot}001) respectively. Neutrophil counts were not associated with mortality risk.\n\nInterpretationLymphopenia is present in a half of the patients with CAP needing of hospitalization, in absence of antecendents of immunosupression. Lymphopenic CAP with lymphocyte counts < 664 lymphocytes/mm3 constitutes a particular immunological phenotype of the disease which is associated to an increased risk of mortality.\n\nFundingCibeRes, 2009 Support to Research Groups of Catalonia 911, IDIBAPS, SEPAR, SVN

immunology↗

bioRxiv2017

Characterization Of Beta Tubulin Isotypes During Foam Cell Formation

Foam cells contribute to the development of a cardiovascular condition called atherosclerosis. They arise when monocytes become engorged and lipid-laden after exposure to native low-density lipoproteins (Falk, 2006). It is assumed that the cytoskeleton is responsible for the morphological changes observed during foam cell formation. Beta tubulin and alpha tubulin are proteins that dimerize and polymerize to form microtubules, which are an important component of the cytoskeleton (Joshi, 1998). Little is known regarding the changes in cytoskeletal composition, particularly that of beta tubulins, throughout foam cell induction. The purpose of this study was to elucidate the expression patterns of beta tubulin isotypes 1-4 in human THP-1 monocytes throughout foam cell formation and to determine what relationship exists between beta tubulin expression and foam cell lipid aggregation. Levels of beta tubulin 1-4 were measured by western blot and immunofluorescence throughout the stages of foam cell differentiation, and beta tubulin isotypes were manipulated by siRNA to determine the effects of diminished beta tubulin expression on foam cell formation. Regardless of isotype, beta tubulin was always present in the highest amounts in monocytes. Levels of beta tubulin-1 and -4 were significantly decreased in macrophage and foam cells relative to monocytes (p < 0.0079, p < 0.0208, respectively). Beta 3 levels also exhibited a decrease. Beta 2 levels remained low regardless of differentiation stage. The distribution of beta tubulin 1 was shown to be more spindle-like (stretching across cells), compared to beta tubulins 2, 3, and 4, which exhibited a more \"clumped,\" less interconnected arrangement. When expression of beta tubulin isotypes 1, 3, and 4 were reduced in monocytes, resulting foam cells appeared to have more lipid aggregates and were significantly larger (p<0.0001) when compared to the size of foam cells without siRNA following treatment with PMA + LDL. In conclusion, the distribution of beta tubulins 1, 3, and 4 changes throughout the stages of foam cell induction, and manipulation of beta tubulins altered foam cell formation. Unexpectedly, the silencing or decreasing of beta tubulin enhanced lipid aggregation. Information concerning how beta tubulin expression can effect foam cell formation may offer insight into how to reduce plaque formation in patients with atherosclerosis.

cell biology↗

bioRxiv2017

An efficient FLP-based toolkit for spatiotemporal control of gene expression in Caenorhabditis elegans

Site-specific recombinases are potent tools to regulate gene expression. In particular, the Cre and FLP enzymes are widely used to either activate or inactivate genes in a precise spatiotemporal manner. Both recombinases work efficiently in the popular model organism Caenorhabditis elegans but their use in this nematode is still only sporadic. To increase the utility of the FLP system in C. elegans we have generated a series of single-copy transgenic strains that stably express an optimized version of FLP in specific tissues or by heat induction. We show that recombination efficiencies reach 100 percent in several cell types, such as muscles, intestine and serotonin producing neurons. Moreover, we demonstrate that most promoters drive recombination exclusively in the expected tissues. As examples of the potentials of the FLP lines we describe novel tools for induced cell ablation by expression of the PEEL-1 toxin and a versatile FLP-out cassette for generation of GFP-tagged conditional knockout alleles. Together with other recombinase-based reagents created by the C. elegans community this toolkit increases the possibilities for detailed analyses of specific biological processes at developmental stages inside intact animals.

genetics↗

bioRxiv2016

Compromised External Validity: Federally Produced Cannabis Does Not Reflect Legal Markets

As the most widely used illicit drug, the basis of the fastest growing major industry in the US, and as a source of numerous under-studied psychoactive compounds, understanding the psychological and physiological effects of Cannabis is essential. The National Institute on Drug Abuse (NIDA) is designated as the sole legal producer of Cannabis for use in US research studies. We sought to compare the chemical profiles of Cannabis varieties that are available to consumers in states that have state-legalized use versus what is available to researchers interested in studying the plant and its effects. Our results demonstrate that the federally produced Cannabis has significantly less variety and lower concentrations of cannabinoids. Current research, which has focused on material that is far less diverse and less potent than that used by the public, limits our understanding of the plants chemical, biological, psychological, medical, and pharmacological properties. Investigation is urgently needed on the diverse forms of Cannabis used by the public in state-legal markets.

plant biology↗