Biology subjects

Diaz, A.

Publications and source records attributed to Diaz, A..

42 records · Page 3Linked to original sources

bioRxiv2019

High-resolution synchrotron imaging studies of intact fresh roots reveal soil bacteria promoted bioremediation and bio-fortification

Plant-microbe interactions can be utilized in bio-based processes such as bioremediation and biofortification, either to remove hazardous radionuclides and heavy metals from the soil, or to increase the accumulation of desired elements into crops to improve their quality. Optimizing such elegant plant-microbe interactions requires detailed understanding of the chemical element compositions of fresh plant tissues at cellular organelle resolution. However, such analyses remain challenging because conventional methods lack the required spatial resolution, contrast or sensitivity. Using a novel combination of nanoscaleresolution 3D cryogenic synchrotron-light ptychography, holotomography and fluorescence tomography, we show how soil bacteria interact with Arabidopsis thaliana and promote the uptake of various metals. Co-cultivation with Pseudomonas sp. strain T5-6-I alters root anatomy and increases levels of selenium (Se), iron (Fe) and other micronutrients in roots. Our approach highlights the interaction of plants and microbes in bioremediation and biofortification on the subcellular level.

plant biology↗

bioRxiv2019

Culex saltanensis and Culex interfor (Diptera: Culicidae) are susceptible and competent to transmit St. Louis encephalitis virus (Flavivirus: Flaviviridae) in central Argentina.

AO_SCPLOWBSTRACTC_SCPLOWInfectious diseases caused by mosquito-borne viruses constitute health and economic problems worldwide. St. Louis encephalitis virus (SLEV) is endemic and autochthonous in the American continent. Culex pipiens quinquefasciatus is the primary urban vector of SLEV; however, Culex interfor and Culex saltanensis have also been found naturally infected with the virus, suggesting their potential role as vectors. OBJECTIVEThe aim of this study was to determine the vector competence of Cx. interfor and Cx. saltanensis for SLEV from central Argentina in comparison to Cx. p. quinquefasciatus. METHODSAdult female mosquitoes of the three Culex species were orally infected by feeding on viremic chicks that had been inoculated with SLEV. Then, abdomens, legs and saliva blood-fed mosquitoes were analyzed by viral plaque assay and the presence of cytopathic effect on the cell culture monolayer. RESULTSMosquitoes were permissive to orally acquired infections, to virus dissemination, and transmission of SLEV in the saliva. Cx. saltanensis and Cx. interfor are potential vectors of SLEV. CONCLUSIONSOur results demonstrate that in Argentina both Cx. saltanensis and Cx. interfor are susceptible to SLEV and competent for its transmission. Moreover they are abundant during SLEV epidemic period in urban area, positive for this virus in nature, and found to feed on natural hosts. This article has been peer-reviewed and recommended by Peer Community in Entomology

microbiology↗

bioRxiv2018

Farnesyl Transferase Inhibition for the Treatment of Tauopathies

Tau inclusions are a shared feature of many neurodegenerative conditions and tau mutations lead to frontotemporal dementia. Approaches to treatment of these conditions have focused directly on the tau protein by targeting its post-translational modifications, its levels and its tendency to aggregate. We discovered a novel regulatory pathway for tau degradation that operates through the Rhes protein, a GTPase. Rhes is farnesylated and treatment with the farnesyl transferase inhibitor, lonafarnib, reduced Rhes, attenuated behavioral abnormalities, significantly reduced atrophy, tau inclusions, sumoylation and ubiquitination, as well as microgliosis in the rTg4510 tauopathy mouse. Direct reduction of Rhes levels reproduced the results observed with lonafarnib. The mechanism of lonafarnib action, as mediated by Rhes to reduce tau pathology, operates through the lysosome without involvement of the proteasome. Finally we show that the developmental increase in Rhes levels can be homeostatically regulated in the presence of tau mutations as a protective mechanism through which cells sense abnormal tau before any pathology is present. The extensive human trials of lonafarnib for other conditions, makes this drug ideal for repurposing to treat tauopathies.\n\nOne-sentence summaryVia a mechanism that involves targeting Rhes, lonafarnib can induce lysosomal-mediated tau degradation and prevent pathology in a tau mouse model

neuroscience↗

bioRxiv2018

Does women’s interpersonal anxiety track changes in steroid hormone levels?

Findings for progesterone and anxiety in non-human animals led to the hypothesis that womens interpersonal anxiety will track changes in progesterone during the menstrual cycle. There have been few direct tests of this hypothesis, however. Consequently, we used a longitudinal design to investigate whether interpersonal anxiety (assessed using the anxious jealousy subscale of the relationship jealousy questionnaire) tracked changes in salivary steroid hormones during the menstrual cycle in a large sample of young adult women (N=383). We found no evidence for within-subject effects of progesterone, estradiol, their interaction or ratio, testosterone, or cortisol on anxious jealousy. There was some evidence that other components of jealousy (e.g., reactive jealousy) tracked changes in womens cortisol, however. Collectively, these results provide no evidence for the hypothesis that interpersonal anxiety tracks changes in progesterone during the menstrual cycle.

animal behavior and cognition↗

bioRxiv2018

A draft single-cell atlas of human glioblastoma reveals a single axis of phenotype in tumor-propagating cells.

Tumor-propagating glioblastoma (GBM) stem-like cells (GSCs) of the proneural and mesenchymal molecular subtypes have been described. However, it is unknown if these two GSC populations are sufficient to generate the spectrum of cellular heterogeneity observed in GBM. The lineage relationships and niche interactions of GSCs have not been fully elucidated. We perform single-cell RNA-sequencing (scRNA-seq) and matched exome sequencing of human GBMs (12 patients; >37,000 cells) to identify recurrent hierarchies of GSCs and their progeny. We map sequenced cells to tumor-anatomical structures and identify microenvironment interactions using reference atlases and quantitative immunohistochemistry. We find that all GSCs can be described by a single axis of variation, ranging from proneural to mesenchymal. Increasing mesenchymal GSC (mGSC) content, but not proneural GSC (pGSC) content, correlates with significantly inferior survival. All clonal expressed mutations are found in the GSC populations, with a greater representation of mutations found in mGSCs. While pGSCs upregulate markers of cell-cycle progression, mGSCs are largely quiescent and overexpress cytokines mediating the chemotaxis of myeloid-derived suppressor cells. We find mGSCs enriched in hypoxic regions while pGSCs are enriched in the tumors invasive edge. We show that varying proportions of mGSCs, pGSCs, their progeny and stromal/immune cells are sufficient to explain the genetic and phenotypic heterogeneity observed in GBM. This study sheds light on a long-standing debate regarding the lineage relationships between GSCs and other glioma cell types.

cancer biology↗

bioRxiv2017

The transcriptionally permissive chromatin state of ES cells is acutely tuned totranslational output

A permissive chromatin environment coupled to hypertranscription is critical to drive the rapid proliferation of Embryonic Stem (ES) cells and peri-implantation embryos. We carried out a genome-wide screen to systematically dissect the regulation of the euchromatic state of ES cells. The results reveal that activity of cellular growth pathways, prominently protein synthesis, perpetuates the euchromatic state and hypertranscription of ES cells. Acute, mild inhibition of translation results in rapid depletion of euchromatic marks in ES cells and blastocysts, concurrent with delocalization of RNA polymerase II and reduction in nascent transcription. Remarkably, reduced translational output leads to rewiring of open chromatin within 3 hours, including decreased accessibility at a subset of active developmental enhancers and increased accessibility at histone genes and transposable elements. Using a proteome-scale analysis, we show that several euchromatin regulators are unstable proteins and thus continuously depend on a high translational output. We propose that this mechanistic interdependence of euchromatin, transcription and translation sets the pace of proliferation at peri-implantation and may be employed generally by stem/progenitor cells.

molecular biology↗