Biology subjects

Peralta, J. M.

Publications and source records attributed to Peralta, J. M..

7 recordsLinked to original sources

bioRxiv2025

Independent signaling pathways provide a fail-safe mechanism to prevent tumorigenesis

Controlled signaling activity is vital for normal tissue homeostasis and oncogenic signaling activation facilitates tumorigenesis. Here we use single-cell transcriptomics to investigate the effects of pro-proliferative signaling on epithelial homeostasis using the Drosophila follicle cell lineage. Notably, EGFR-Ras overactivation induces cell cycle defects by activating the transcription factors Pointed and E2f1 and impedes differentiation. Hh signaling simultaneously promotes an undifferentiated state and induces differentiation via activation of EMT-associated transcription factors zfh1 and Mef2. As a result, overactivation of Hh signaling generates a transcriptional hybrid state comparable to epithelial-mesenchymal-transition. Co-overactivation of Hh signaling with EGFR-Ras signaling blocks differentiation and induces key characteristics of tumor cells including a loss of tissue architecture caused by reduced expression of cell adhesion molecules, sustained proliferation and an evasion of cell cycle checkpoints. These findings provide new insight into how non-interacting signaling pathways converge at the transcriptional level to prevent malignant cell behavior. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=194 HEIGHT=200 SRC="FIGDIR/small/640798v2_ufig1.gif" ALT="Figure 1"> View larger version (59K): org.highwire.dtl.DTLVardef@762724org.highwire.dtl.DTLVardef@103d1a6org.highwire.dtl.DTLVardef@1b90caforg.highwire.dtl.DTLVardef@1eff5a4_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2022

Cell surface receptor kinase FERONIA linked to nutrient sensor TORC1 signaling controls root hair growth at low temperature in Arabidopsis thaliana

Root hairs (RH) are excellent model systems for studying cell size and polarity since they elongate several hundred-fold their original size. Their tip growth is determined both by intrinsic and environmental signals. Although nutrient availability and temperature are key factors for a sustained plant growth, the molecular mechanisms underlying their sensing and downstream signaling pathways remain unclear. Here, we identified that low temperature (10{degrees}C) triggers a strong RH elongation response involving the cell surface receptor kinase FERONIA (FER) and the nutrient sensing TOR Complex 1 (TORC). In this study, we found that FER is required to perceive limited nutrient availability caused by low temperature. FER interacts with and activates TORC downstream components to trigger RH growth. In addition, the small GTPase Rho-related protein from plants 2 (ROP2) is also involved in this RH growth response linking FER and TOR. We also found that limited nitrogen nutrient availability can mimic the RH growth response at 10{degrees}C in a NRT1.1-dependent manner. These results uncover a molecular mechanism by which a central hub composed by FER-ROP2-TORC is involved in the control of RH elongation under low temperature and nitrogen deficiency.

plant biology↗

bioRxiv2021

Paving the way towards understanding the inflammatory pathways triggered by giant viruses in mammalian cells: effect of mimivirus-cell interactions on IκBα degradation

Even after two decades since the identification of the first giant virus, the Acanthamoeba polyphaga mimivirus (APMV), it still elude scientists. Their gigantic size and genome are unique in the whole virosphere, and many aspects of their biology are still unknown, including their possible hosts. They are cultivated in laboratories using Acanthamoeba cells as hosts, but little is known about the infectivity of these giant viruses in vertebrate cells. However, there is evidence of the possible involvement of APMV in pneumonia and activation of inflammatory pathways. Among the hundreds of prospected giant viruses members is Tupanvirus, isolated in Brazil. Its particles have a characteristically large size varying between 1.2 to 2 m and are covered by fibrils. In the present work, we aim to study the consequences of the incubation of APMV and Tupanvirus with mammalian cells. These cells express Toll-like receptors (TLR) that are capable of recognizing lipopolysaccharides, favoring the internalization of the antigen and activation of the inflammatory system. We used a lineage of human lung adenocarcinoma cells (A549) to evaluate possible effects of TLR activation by the giant viruses and if we could detect the probable cause of the said giant-virus dependent pneumonia. Our results show that APMV and Tupanvirus (TPV) activate cellular receptors related to the Toll-like 4 type-induced inflammatory response and that the A549 cells are capable of internalizing the latter virus. Therefore, this study brings new insights into the possible interactions established between mimiviruses (here represented by APMV and Tupanvirus) and members of the innate cellular immune response.

microbiology↗

bioRxiv2021

Apoplastic class III peroxidases PRX62 and PRX69 regulate ROS-homeostasis and cell wall associated extensins linked to root hair growth at low-temperature in Arabidopsis thaliana

Root Hairs (RHs) growth is highly influenced by endogenous as well as by external environmental signals that coordinately regulate its final cell size. RHs actively expand the root surface responsible for nutrient uptake and water absorption. We have recently determined that RH growth was unexpectedly boosted when Arabidopsis thaliana seedlings are cultivated at low temperatures. It was proposed that RH growth plasticity in response to low temperature was linked to a reduced nutrient availability in the media. Here, we explored the molecular basis of this strong RH growth response by using the Genome Wide Association Studies (GWAS) approach on Arabidopsis thaliana natural accessions. We identified the poorly characterized PEROXIDASE 62 (PRX62) as a key protein triggering this conditional growth under a moderate low-temperature stress. In addition, we identified the related protein PRX69 as an important factor in this developmental process. The prx62 prx69 double mutant and the PRX62 and PRX69 over-expressing lines showed contrasting RH phenotypes, peroxidase activities and cyt/apoReactive Oxygen Species (ROS) levels. Strikingly, a cell wall protein extensin (EXT) reporter revealed the effect of peroxidase activity on the EXT cell wall association at 10{degrees}C in the RH apical zone. EXT cell wall insolubilization was enhanced at 10{degrees}C, which was completely abolished under the PRX inhibitor salicylhydroxamic acid (SHAM) treatment. Finally, we demonstrated that the Root Hair defective 6-like 4 (RSL4) bHLH family transcription factor directly controls the expression of PRX69. Collectively, our results indicate that both PRX62 and PRX69 are key apoplastic PRXs that modulate ROS-homeostasis and cell wall EXT-insolubilization linked to RH elongation at low-temperature.

plant biology↗

bioRxiv2020

Transcriptomic profiling of fibropapillomatosis in green sea turtles (Chelonia mydas) from South Texas

Sea turtle fibropapillomatosis (FP) is a tumor promoting disease that is one of several threats globally to endangered sea turtle populations. The prevalence of FP is highest in green sea turtle (Chelonia mydas) populations, and historically has shown considerable temporal growth. FP tumors can significantly affect the ability of turtles to forage for food and avoid predation and can grow to debilitating sizes. In the current study, based in South Texas, we have applied transcriptome sequencing to FP tumors and healthy control tissue to study the gene expression profiles of FP. By identifying differentially expressed turtle genes in FP, and matching these genes to their closest human ortholog we draw on the wealth of human based knowledge, specifically human cancer, to identify new insights into the biology of sea turtle FP. We show that several genes aberrantly expressed in FP tumors have known tumor promoting biology in humans, including CTHRC1 and NLRC5, and provide support that disruption of the Wnt signaling pathway is a feature of FP. Further, we profiled the expression of current targets of immune checkpoint inhibitors from human oncology in FP tumors and identified potential candidates for future studies.

cancer biology↗

bioRxiv2019

Impact of rare and common genetic variants on diabetes diagnosis by hemoglobin A1c in multi-ancestry cohorts: The Trans-Omics for Precision Medicine Program.

Hemoglobin A1c (HbA1c) is widely used to diagnose diabetes and assess glycemic control in patients with diabetes. However, nonglycemic determinants, including genetic variation, may influence how accurately HbA1c reflects underlying glycemia. Analyzing the NHLBI Trans-Omics for Precision Medicine (TOPMed) sequence data in 10,338 individuals from five studies and four ancestries (6,158 Europeans, 3,123 African-Americans, 650 Hispanics and 407 East Asians), we confirmed five regions associated with HbA1c (GCK in Europeans and African-Americans, HK1 in Europeans and Hispanics, FN3K/FN3KRP in Europeans and G6PD in African-Americans and Hispanics) and discovered a new African-ancestry specific low-frequency variant (rs1039215 in HBG2/HBE1, minor allele frequency (MAF)=0.03). The most associated G6PD variant (p.Val98Met, rs1050828-T, MAF=12% in African-Americans, MAF=2% in Hispanics) lowered HbA1c (-0.88% in hemizygous males, -0.34% in heterozygous females) and explained 23% of HbA1c variance in African-Americans and 4% in Hispanics. Additionally, we identified a rare distinct G6PD coding variant (rs76723693 - p.Leu353Pro, MAF=0.5%; -0.98% in hemizygous males, -0.46% in heterozygous females) and detected significant association with HbA1c when aggregating rare missense variants in G6PD. We observed similar magnitude and direction of effects for rs1039215 (HBG2) and rs76723693 (G6PD) in the two largest TOPMed African-American cohorts and replicated the rs76723693 association in the UK Biobank African-ancestry participants. These variants in G6PD and HBG2 were monomorphic in the European and Asian samples. African or Hispanic ancestry individuals carrying G6PD variants may be underdiagnosed for diabetes when screened with HbA1c. Thus, assessment of these variants should be considered for incorporation into precision medicine approaches for diabetes diagnosis.

genetics↗

bioRxiv2017

Accurate Phasing of Pedigree Genotypes Using Whole Genome Sequence Data

Phasing, the process of predicting haplotypes from genotype data, is an important undertaking in genetics and an ongoing area of research. Phasing methods, and associated software, designed specifically for pedigrees are urgently needed. Here we present a new method for phasing genotypes from whole genome sequencing data in pedigrees: PULSAR (Phasing Using Lineage Specific Alleles / Rare variants). The method is built upon the idea that alleles that are specific to a single founding chromosome within a pedigree, which we refer to as lineage-specific alleles, are highly informative for identifying haplotypes that are identical-by-decent between individuals within a pedigree. Through extensive simulation we assess the performance of PULSAR in a variety of pedigree sizes and structures, and we explore the effects of genotyping errors and presence of non-sequenced individuals on its performance. If the genotyping error rate is sufficiently low PULSAR can phase > 99.9% of heterozygous genotypes with a switch error rate below 1 x 10-4 in pedigrees where all individuals are sequenced. We demonstrate that the method is highly accurate and consistently outperforms the long-range phasing approach used for comparison in our benchmarking. The method also holds promise for fixing genotype errors or imputing missing genotypes. The software implementation of this method is freely available.

genetics↗