Biology subjects

Perez, C. A.

Publications and source records attributed to Perez, C. A..

6 recordsLinked to original sources

bioRxiv2025

Modelling the tumor metallome in vitro reveals manganese as a unique tumor-promoting element

The microenvironment (TME) undergoes significant modification in tumor progression. TME comprises locally secreted molecules, cells, and metal ions. Metals interact with the cell surface or are internalized, modulating downstream pathways related to adhesion, migration, and proliferation. Our group showed that tumor-bearing mice present altered Mn distribution. Mn-exposed tumor cells showed in vitro higher proliferation and migration, associated with changes in glycocalyx organization. In this work, we modulated, in vitro, tumor cells metallome, and evaluated metals internalization, cellular distribution and its early effect on migration. Cell viability and survival were evaluated using the MTT and clonogenic assays. Metal retention and distribution were assessed with inductively coupled plasma optical emission spectroscopy (ICP-OES) and high-resolution X-ray fluorescence (XRF). Cell migration was evaluated with wound healing assay. Our results indicate that an early interaction between Mn and the cell surface, probably the negatively-charged glycocalyx, induces morphological changes that lead to increased invasiveness. Future investigations will help to better understand the mechanisms of Mn retention and internalization during tumor progression.

cancer biology↗

bioRxiv2025

Double knockout of rice OsVIT1 and OsVIT2 genes reveals a trade-off between iron biofortification and iron excess tolerance

Rice (Oryza sativa L.) is a staple food for half of the worlds population, but lacks essential nutrients such as iron (Fe). Fe deficiency is one of the most common nutritional problems in humans, and biofortification of rice grains is a cost-effective approach to deliver more Fe to peoples diet. Two Vacuolar Iron Transporters, OsVIT1 and OsVIT2, were shown to negatively regulate Fe translocation to rice developing panicles, as single mutants osvit1 and osvit2 have increased Fe concentration in seeds. Importantly, rice plants are frequently cultivated in waterlogged soils that are highly reductive and prone to Fe3+ reduction to the more soluble Fe2+, which can accumulate and cause Fe toxicity. Little is known about which genes control Fe excess detoxification. OsVIT1 and OsVIT2 transport Fe into the vacuole, and OsVIT2 is induced under Fe excess, but whether they play a role in Fe detoxification was not demonstrated. We generated double mutants osvit1osvit2 using CRISPR-Cas9 to test whether loss of function of both genes could increase Fe concentration in seeds, and to test whether their loss of function has impact in rice Fe excess tolerance. We showed that osvit1osvit2 double mutants accumulated more Fe in brown rice. Fe accumulation was clear in embryo scutellum and plumule, suggesting VIT transporters have a role in determining Fe spatial distribution. We also showed that root uptake contributed significantly for increased Fe accumulation in osvit1osvit2 seeds, suggesting OsVIT1 and OsVIT2 are involved in sequestering Fe in vegetative tissues and decreasing translocation. Strikingly, we found that osvit1osvit2 plants were more sensitive to Fe excess, revealing a trade-off between Fe biofortification and Fe excess tolerance. Our data indicates OsVIT1 and OsVIT2 are key for Fe excess detoxification, which should be considered in their use as targets for biofortification.

plant biology↗

bioRxiv2025

Storage protein biosynthesis is affected by ionome composition in soybean (Glycine max (L.) Merrill) seeds

Soybean seeds are a significant source of protein for human and animal nutrition, primarily due to seed storage proteins (SSPs) from the albumin and globulin families, which are predominantly located in protein storage vacuoles within cotyledon cells. This study characterised the dynamics of protein and mineral nutrient accumulation in four soybean genotypes with contrasting protein content--two transgenic (tg1 and tg2) and two conventional (ct1 and ct2)--from the beginning of seed filling (R5.5) through to maturity (R8) under field conditions. Profiles of globulin SSPs (glycinin and {beta}-conglycinin), as well as the protein and elemental distribution in mature seed cotyledons were examined. Results revealed that genotypes with higher protein content showed increased S and Zn concentrations and a higher glycinin:{beta}-conglycinin ratio. Subcellular analyses further indicated co-localisation of proteins and Zn within cotyledon cells. Our findings reveal a complex association between S and Zn accumulation and SSPs biosynthesis, indicating that their availability can limit the SSP content. HIGHLIGHTSoybean seed genotypes containing higher sulphur (S) and zinc (Zn) content in the cotyledonary cells exhibit a distinct storage proteins profile by increasing the abundance of sulphur-amino acids rich globulins.

plant biology↗

bioRxiv2023

Tipifarnib potentiates the antitumor effects of PI3Kα inhibition in PIK3CA- and HRAS-dysregulated HNSCC via convergent inhibition of mTOR activity

Outcomes for patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) are poor, with median overall survival ranging from 6 to 18 months. For those who progress on standard of care (chemo)immunotherapy, treatment options are limited, necessitating the development of rational therapeutic strategies. Toward this end, we targeted the key HNSCC drivers PI3K-mTOR and HRAS via the combination of tipifarnib, a farnesyltransferase inhibitor, and alpelisib, a PI3K inhibitor, in multiple molecularly defined subsets of HNSCC. We find that tipifarnib synergizes with alpelisib at the level of mTOR in PI3K-or HRAS-dependent HNSCCs, leading to marked cytotoxicity in vitro and tumor regression in vivo. Based on these findings, we have launched the KURRENT-HN trial to evaluate the effectiveness of this combination in PIK3CA-mutant/amplified and/or HRAS-overexpressing R/M HNSCC. Preliminary evidence supports the clinical activity of this molecular biomarker-driven combination therapy. SignificanceBacked by strong mechanistic rationale, the combination of alpelisib and tipifarnib has the potential to benefit >45% of R/M HNSCC patients. By blocking feedback reactivation of mTORC1, tipifarnib may prevent adaptive resistance to additional targeted therapies, thereby enhancing their clinical utility.

cancer biology↗

bioRxiv2019

Glucose metabolism promotes neonatal heart regeneration

The mammalian heart switches its main metabolic substrate from glucose to fatty acids shortly after birth. This metabolic switch coincides with the loss of regenerative capacity in the heart. However, it is unknown whether glucose metabolism itself regulates heart regeneration. Here, we report that glucose metabolism is a determinant of regenerative capacity in the neonatal mammalian heart. Cardiac-specific overexpression of Glut1, the embryonic form of constitutively active glucose transporter, resulted in an increase in glucose uptake and concomitant glycogen storage in postnatal heart. Upon cryoinjury, Glut1 transgenic hearts showed higher regenerative capacity with less fibrosis than non-transgenic control hearts. Interestingly, flow cytometry analysis revealed two distinct populations of ventricular cardiomyocytes: Tnnt2-high and Tnnt2-low cardiomyocytes, the latter of which showed significantly higher mitotic activity in response to high intracellular glucose in Glut1 transgenic hearts. Metabolic profiling shows that Glut1-transgenic hearts have a significant increase in the glucose metabolites upon injury, and inhibition of the nucleotide biosynthesis abrogated the regenerative advantage of high intra-cardiomyocyte glucose level. Our data suggest that the increased in glucose metabolism promotes cardiac regeneration in neonatal mouse heart.

developmental biology↗

bioRxiv2019

Physiological response to slalom water skiing: A case study of a sit-skier with paraplegia

Recreational and competitive slalom waterskiing is popular among those with spinal cord injuries. People with paraplegia can practice on the slalom course using a sit-ski. A slalom run consists of a boat towing the sit-skier through a set of buoys and normally begins with a deep-water start. Despite its popularity, very little is known about the physiological aspects of the sit-skier's preparation. We examined the internal training load (TL) experienced by a sit-skier with paraplegia while learning and improving the slalom deep-water starts, executed with both the traditional technique and an alternative method. The TL was determined by means of heart rate (HR) and session rating of perceived exertion (sRPE) methods. The percentage of maximal heart rate values ranged from from 63.2% to 81.3% during deep-water starts. Training sessions were performed most of the time below the ventilatory threshold and tended to be qualitatively described as hard. A moderate but non-significant correlation existed between HR and sRPE-based methods. We also found a significant decrement in handgrip strength after practice. These findings indicate that the intensity of training experienced by our sit-skier was moderate in terms of physiological internal load during an adaptive slalom waterskiing training program.

physiology↗