Biology subjects

Ortiz, A.

Publications and source records attributed to Ortiz, A..

12 recordsLinked to original sources

bioRxiv2026

Two redundant paralogs of MAR1-BINDING FILAMENT PROTEIN affect B-type granule initiation in wheat

Starch synthesis in wheat endosperm involves the initiation of large A-type starch granules during early grain development, followed by small B-type granules in later grain development. It is established that MAR-BINDING FILAMENT-LIKE PROTEIN 1 (MFP1) plays an important role in granule initiation in Arabidopsis chloroplasts, but how it influences A- and B-type initiations in wheat amyloplasts is not known. We discovered that due to a gene duplication in cereals, wheat contains two MFP1 paralogs, MFP1.1 and MFP1.2, which are both expressed in the developing endosperm. We generated a series of durum wheat mutants defective in all homoeologs of either MFP1.1 or MFP1.2, or both. While starch granule size distributions and granule morphology of mfp1.1 and mfp1.2 mutants were identical to those of the wild-type, the mfp1.1 mfp1.2 mutants had fewer, but larger B-type granules - suggesting that the two paralogs play redundant roles in B-type granule initiation. Consistent with this, both paralogs interacted with B-GRANULE CONTENT 1 (BGC1), a key protein required for proper B-type granule initiation in wheat, and both paralogs could partially complement defects in starch initiation in the Arabidopsis mfp1 mutant. Our work demonstrates that MFP1 is required for establishing correct starch granule number in non-photosynthetic amyloplasts, but its role in wheat is limited to B-type granule initiation. One-sentence summaryWheat has two MFP1 paralogs that interact with the granule initiation protein, BGC1 and influence B-type granule initiation in non-photosynthetic amyloplasts of endosperm.

plant biology↗

bioRxiv2026

Early Lipid Remodeling During Ischemia Reperfusion Injury Is Associated with Damage- and Protection-Related Lipid Signatures in Acute Kidney Injury.

Acute kidney injury (AKI) secondary to kidney ischemia-reperfusion (IRI) is driven by profound metabolic perturbations that shape oxidative stress, inflammation, and cell death responses. Despite growing evidence of lipid dysregulation in AKI, its biological and mechanistic relevance remains unclear. To address this gap, we performed comprehensive untargeted kidney lipidomics using LC-QTOF-MS to delineate dynamic lipid changes during the acute phase of murine kidney IRI. Integration of lipidomic signatures with kidney gene-expression profiling and curated datamining revealed early activation of lipid pathways associated with injury responses. IRI induced marked lipidomic reprogramming, characterized by a marked accumulation of glycerolipids, including triacylglycerols (TGs) species detected exclusively after injury, together with increased levels of sphingolipids (ceramides, sphingomyelins, and hexosylceramides). Cardiolipins and most glycerophospholipids declined sharply following IRI, whereas specific phosphatidylcholines (PCs) exhibited opposite regulation, consistent with dynamic membrane remodeling. Datamining linked TG accumulation and altered transcriptional regulation of PC metabolism to repair-prone type 1 injured proximal tubular cells, highlighting its role in early tubular injury. Correlation analyses revealed strong associations between glycerolipids/sphingolipids and markers of renal dysfunction and inflammation, identifying TG 54:9 as a candidate for injury biomarker. Conversely, PE 40:6, PI 38:6, together with several lysophosphatidylcholines and ether-linked phospholipids, correlated positively with nephroprotective and antioxidant markers. Together, these patterns delineate two major lipid modules: a damage-associated module and a nephroprotection-associated module. These findings establish lipid remodeling as a central yet underexplored determinant of AKI pathogenesis and underscore lipidomics as a powerful discovery tool for identifying novel biomarkers and mechanistic targets in kidney disease.

pathology↗

bioRxiv2025

Diploid potato lines for the study and improvement of starch metabolism and structure

Diploid potato breeding enables faster genetic improvement via selection against deleterious alleles in inbred lines, unlike breeding by intercrossing tetraploid varieties. Starch is the major source of calories in potato tubers, but the starch properties of diploid lines have rarely been reported. In this study, we provide a comprehensive characterisation of tuber and starch properties in two diploid lines that are early isolates from the Solynta breeding program, B26 and B100, and their F1 hybrids. B100 produced fewer, but larger tubers compared to B26, and both diploid lines produced tubers that are smaller than the tetraploid variety, Clearwater Russet. The low tuber yield of B100 correlates with its high self-compatibility and fruit production. Pruning of fruits in B100 significantly increased total tuber yield per plant by stimulating more tuber initiations, but had no effect on average tuber weight, starch content or starch structure. Among the diploid, hybrid and tetraploid lines examined, there were no differences in the total starch content of tubers. Although amylopectin structure and amylose content were similar between the two diploid lines and the tetraploid comparison, B26 had elevated levels of resistant starch and a striking elongated granule morphology. Our results showcase the variation in source-sink relations and starch structure in diploid potato breeding material, demonstrating their potential for research into the genetics underpinning metabolic and quality traits.

plant biology↗

bioRxiv2024

Targeting STING in experimental peritoneal damage: a novel approach in peritoneal dialysis therapy

Peritoneal dialysis (PD) is a widely used kidney replacement therapy for end-stage kidney disease (ESKD) patients. However, long-term exposure to PD fluids (PDF) can lead to peritoneal membrane (PM) damage, causing ultrafiltration failure and thus PD discontinuation. Investigating the molecular mechanisms underlying this damage is crucial for identifying new therapeutic targets to mitigate peritoneal deterioration in PD patients. Therefore, in this work we study the role of STING in peritoneal inflammation and fibrosis. To this aim, we performed different preclinical mouse models of peritoneal inflammation, fibrosis, and adhesions. In a chlorhexidine gluconate (CHX)-induced inflammation model, we found changes in the peritoneal transcriptomic profile, and cytosolic DNA-sensing signaling was one of the most enriched KEGG pathways. STING, as a conspicuous member of this pathway, was upregulated in CHX-and PDF-exposed mice, and in peritoneal biopsies from PD patients. STING genetic deficiency diminished peritoneal inflammation, by downregulating inflammatory gene expression, preventing NF-{kappa}B pathway activation, and decreasing cell infiltration, in early (10 days) and advanced (30 days) stages of the CHX model. STING absence also decreased PM thickness and fibrosis in the advanced CHX model, reduced adhesion scores in a post-surgical intra-abdominal adhesion model, and decreased inflammation in an S. epidermidis-induced peritonitis model. Furthermore, pharmacological inhibition of STING with C-176 decreased inflammation and macrophage-mediated mesothelial-to-mesenchymal transition in cultured mesothelial cells, and reduced CHX-induced PM thickness and inflammation in mice. Altogether, these findings highlight STING as a key mediator of peritoneal damage and suggest it may be a novel therapeutic target for preventing PD-associated peritoneal deterioration.

pathology↗

bioRxiv2024

Cell type specific roles of FOXP1 during early neocortical murine development

FOXP1, a transcription factor enriched in the neocortex, is associated with autism spectrum disorders (ASD) and FOXP1 syndrome. Emx1Cre/+;Foxp1fl/flconditional deletion (Foxp1 cKO) in the mouse cortex leads to overall reduced cortex thickness, alterations in cortical lamination, and changes in the relative thickness of cortical layers. However, the developmental and cell type-specific mechanisms underlying these changes remained unclear. We find that Foxp1 deletion results in accelerated pseudo-age during early neurogenesis, increased cell cycle exit during late neurogenesis, altered gene expression and chromatin accessibility, and selective migration deficits in a subset of upper-layer neurons. These data explain the postnatal differences observed in cortical layers and relative cortical thickness. We also highlight genes regulated by FOXP1 and their enrichment with high-confidence ASD or synaptic genes. Together, these results underscore a network of neurodevelopmental disorder-related genes that may serve as potential modulatory targets for postnatal modification relevant to ASD and FOXP1 syndrome.

neuroscience↗

bioRxiv2024

Xylazine enhances the tranq, but not the fentanyl dope

The adulteration of illicit fentanyl with the alpha-2 agonist xylazine has been designated an emerging public health threat. The clinical rationale for combining fentanyl with xylazine is currently unclear, and the inability to study fentanyl/xylazine interactions in humans warrants the need for preclinical research. We studied fentanyl and xylazine pharmacodynamic and pharmacokinetic interactions in male and female rats using drug self-administration behavioral economic methods. Fentanyl, but not xylazine, functioned as a reinforcer under both fixed-ratio and progressive-ratio drug self-administration procedures. Xylazine combined with fentanyl at three fixed dose-proportion mixtures did not significantly alter fentanyl reinforcement as measured using behavioral economic analyses. Xylazine produced a proportion-dependent decrease in the behavioral economic Q0 endpoint compared to fentanyl alone. However, xylazine did not significantly alter fentanyl self-administration at FR1. Fentanyl and xylazine co-administration did not result in changes to pharmacokinetic endpoints. The present results demonstrate that xylazine does not enhance the addictive effects of fentanyl or alter fentanyl plasma concentrations. The premise for why illicitly manufacture fentanyl has been adulterated with xylazine remains to be determined.

pharmacology and toxicology↗

bioRxiv2022

Photosynthetically active radiation is required for seedling growth promotion by volcanic dacitic tuff breccia (Azomite)

A plants growth and development are shaped by its genome and the capacity to negotiate its environment for access to light, water, and nutrients. There is a vital need to understand the interactions between the plant, its physical environment, and the fertilizers used in agriculture. In this study, a commercially available volcanic ash fertilizer, Azomite(R), characterized as dacitic (rhyolitic) tuff breccia (DTB), was tested for its effect on promoting early seedling vigor. Early growth and photomorphogenesis processes are well studied in Arabidopsis. Seedling assays under different light conditions were used to dissect the underlying mechanisms involved. These assays are well established and can be translated to agriculturally important crop plants. The volcanic ash fertilizer was tested at different concentrations on seedlings grown on basic media lacking sucrose either in continuous darkness (Dc), continuous Red (Rc), Far-Red (FRc), or White Light (WLc). Micronutrients in the volcanic ash significantly increased seedling growth under Rc and WLc, but not under Dc and FRc, indicating that photosynthetically active radiation (PAR) was required for the observed growth increase. Furthermore, red-light photoreceptor mutant, phyB-9 lacked the growth response, and higher amount of fertilizer reduced growth in all conditions tested. These data suggest that light triggers the ability of the seedling to utilize micronutrients in volcanic ash in a dose-dependent manner. The methods described here can be used to establish mechanisms of activity of various nutrient inputs, and coupled with whole-genome expression profiling, can lead to better insights into optimizing nutrient field applications to improve crop production.

developmental biology↗

bioRxiv2021

Tomato CRABS CLAW paralogues interact with chromatin remodelling factors to mediate carpel development and floral determinacy

CRABS CLAW (CRC) orthologues play a crucial role in floral meristem (FM) determinacy and gynoecium formation across angiosperms, key developmental processes for ensuring successful plant reproduction and crop production. Here, we revealed that the incomplete penetrance and variable expressivity of the carpel-inside-carpel phenotype observed in flowers of the tomato fruit iterative growth (fig) mutant is due to a lack of function of a homologue of the CRC gene, Solanum lycopersicum CRCa (SlCRCa). Likewise, a comprehensive functional analysis of SlCRCa and SlCRCb paralogues, including Arabidopsis complementation experiments, allowed us to propose that they operate as positive regulators of FM determinacy by acting in a compensatory and partially redundant manner to safeguard the proper formation of flowers and fruits. Furthermore, we provide the first evidence for the role of putative CRC orthologues as members of the chromatin remodelling complex that terminates floral stem cell activity by repressing WUSCHEL expression.

developmental biology↗

bioRxiv2021

Differential effects of the second SARS-CoV-2 mRNA vaccine dose on T cell immunity in naive and COVID-19 recovered individuals

The rapid development and deployment of mRNA-based vaccines against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the design of accelerated vaccination schedules that have been extremely effective in naive individuals. While a two-dose immunization regimen with the BNT162b2 vaccine has been demonstrated to provide a 95% efficacy in naive individuals, the effects of the second vaccine dose in individuals who have previously recovered from natural SARS-CoV-2 infection has been questioned. Here we characterized SARS-CoV-2 spike-specific humoral and cellular immunity in naive and previously infected individuals during full BNT162b2 vaccination. Our results demonstrate that the second dose increases both the humoral and cellular immunity in naive individuals. On the contrary, the second BNT162b2 vaccine dose results in a reduction of cellular immunity in COVID-19 recovered individuals, which suggests that a second dose, according to the current standard regimen of vaccination, may be not necessary in individuals previously infected with SARS-CoV-2.

immunology↗

bioRxiv2020

Establishing a Living Biobank of Patient-Derived Organoids of Intraductal Papillary Mucinous Neoplasms of the Pancreas

Pancreatic cancer (PaCa) is the third leading cause of cancer-related deaths in the United States. There is an unmet need to develop strategies to detect PaCa at an early, operable stage and prevent its progression. Intraductal papillary mucinous neoplasms (IPMNs) are cystic PaCa precursors that comprise nearly 50% of pancreatic cysts detected incidentally via cross-sectional imaging. Since IPMNs can progress from low- and moderate-grade dysplasia to high-grade dysplasia and invasion, the study of these lesions offers a prime opportunity to develop early detection and prevention strategies. Organoids are an ideal preclinical platform to study IPMNs, and the objective of the current investigation was to establish a living biobank of patient-derived organoids (PDO) from IPMNs. IPMN tumors and adjacent normal pancreatic tissues were successfully harvested from 15 patients with IPMNs undergoing pancreatic surgical resection at Moffitt Cancer Center & Research Institute (Tampa, FL) between May of 2017 and March of 2019. Organoid cultures were also generated from cryopreserved tissues. Organoid count and size were determined over time by both Image-Pro Premier 3D Version 9.1 digital platform and Matlab application of a Circular Hough Transform algorithm, and histologic and genomic characterization of a subset of the organoids was performed using immunohistochemistry and targeted sequencing, respectively. The success rates for organoid generation from IPMN tumor and adjacent normal pancreatic tissues were 81% and 87%, respectively. IPMN organoids derived from different epithelial subtypes showed different morphologies in vitro, and organoids recapitulated histologic and genomic characteristics of the parental IPMN tumor. In summary, this pre-clinical model has the potential to provide new opportunities to unveil mechanisms of IPMN progression to invasion and to shed insight into novel biomarkers for early detection and targets for chemoprevention.

cancer biology↗

bioRxiv2020

Positive interactions are common among culturable bacteria

Interspecies interactions shape the structure and function of microbial communities. In particular, positive, growth-promoting interactions can significantly affect the diversity and productivity of natural and engineered communities. However, the prevalence of positive interactions and the conditions in which they occur are not well understood. To address this knowledge gap, we used kChip, an ultra-high throughput coculture platform, to measure 180,408 interactions among 20 soil bacteria across 40 carbon environments. We find that positive interactions, often described to be rare, occur commonly, primarily as parasitisms between strains that differ in their carbon consumption profiles. Notably, non-growing strains are almost always promoted by strongly growing strains (85%), suggesting a simple positive interaction-mediated approach for cultivation, microbiome engineering, and microbial consortium design. One Sentence SummaryExperimental measurement of >150,000 bacterial cocultures reveals that growth-promoting interactions occur commonly and depend on differences in nutrient consumption preferences.

ecology↗

bioRxiv2020

T2 heterogeneity provides a sensitive measure of early tumor response to radiotherapy

PurposeExternal beam radiotherapy (XRT) is a widely used cancer treatment, yet responses vary dramatically between patients. These differences are not accounted for in clinical practice, in part due to a lack of sensitive biomarkers of early response. In this work, we test the hypothesis that quantification of intratumor heterogeneity is a sensitive and robust biomarker of early response to XRT. A novel Magnetic Resonance Imaging (MRI) approach is proposed, utilizing histogram analysis of clinically-used T2 relaxation measurements to assess early changes in the tumor heterogeneity following irradiation in murine models of pancreatic cancer, indicative of radiotherapy response. Methods and MaterialsDynamic Magnetic Resonance T2 relaxation imaging was performed every 72h following 10 Gy dose XRT in two murine models of pancreatic cancer. Proposed biomarker of radiotherapy response was compared with tumor growth kinetics, and biological validation was performed through quantitative histology analysis. ResultsQuantification of tumor T2 interquartile range (IQR) as a measure of histogram width showed excellent sensitivity for detection of XRT-induced tumor changes as early as 72h after treatment, outperforming whole tumor T2 and Diffusion weighted MRI metrics. This response was observed both in quantitative T2 maps and in T2-weighted images that are routine in clinical practice. Histological comparison revealed the T2 IQR provides a measure of spatial heterogeneity in tumor cell density, related to radiation-induced necrosis. The early IQR changes were found to presage subsequent tumor volume changes in two distinct pancreatic models, suggesting promise for treatment response prediction. The metric showed excellent test-retest robustness. ConclusionsOur preclinical findings indicate that spatial heterogeneity analysis of T2 MRI can provide a sensitive and readily translatable method for early radiotherapy response assessment in pancreatic cancer. We propose that this will be useful in adaptive radiotherapy, specifically in MRI-guided treatment paradigms.

biophysics↗