Biology subjects

Cruz, M. C.

Publications and source records attributed to Cruz, M. C..

5 recordsLinked to original sources

bioRxiv2026

DRP1-mediated mitochondrial fission integrates growth hormone signaling with metabolic and stress adaptation in triple-negative breast cancer

Triple-negative breast cancer (TNBC) relies on metabolic plasticity to sustain growth under diverse microenvironmental conditions. Although growth hormone (GH) signaling has been linked to breast cancer progression, its mechanistic integration with mitochondrial dynamics and metabolic reprogramming remains unclear. Here, we show that GH promotes TNBC progression accompanied by DRP1-associated mitochondrial remodeling, as indicated by sensitivity to Mdivi-1. The MDA-MB-231 line enabled integrated assessment across 2D, 3D, hypoxia, and in vivo xenografts using consistent workflows and readouts. GH increased proliferation and mitochondrial mass without increasing OCR under protein normalization. Instead, GH selectively enhanced glycolytic flux and metabolic flexibility. Inhibition of DRP1 uncoupled GH-induced glycolysis from proliferation, demonstrating that mitochondrial fission is required to link metabolic reprogramming to cell-cycle progression. DRP1 inhibition with Mdivi-1 was associated with altered TP53 and HIF1A expression and extended GH activity to the regulation of a pro-inflammatory tumor microenvironment marked by cxcr4b, il8, and il12. Consistent with these findings, analysis of human TNBC transcriptomes revealed conserved enrichment of mitochondrial, metabolic, and inflammatory pathways. Together, these results support the GH-DRP1 axis as a candidate regulator of mitochondrial dynamics, metabolic plasticity, tumor progression and tumor microenvironment interactions in TNBC.

cancer biology↗

bioRxiv2025

Acinetobacter spp. with lower susceptibility to quaternary ammonium compounds enriched in microbial communities of frequently used sinks

Sanitary environments that undergo frequent cleaning and disinfection may harbor microbial communities with potential health risks. While biofilms in healthcare settings are well studied, comparatively less is known about sink microbiomes in public and educational buildings, where hundreds of people may interact with shared sink fixtures. This study characterized the spatial and temporal heterogeneity of sink drain biofilm microbiomes in academic buildings. We sampled 16 sinks from two buildings (four floors each, with sinks closest and furthest to the bathroom entrance), which are cleaned daily with quaternary ammonium compound (QAC) disinfectants, during periods of low and high student traffic (during and after academic breaks, respectively) across winter, spring, and summer. We observed significant spatial and temporal variations in microbial assemblages. Individual sinks accounted for 43% (PERMANOVA, p < 0.0001) of the variation in microbial communities. Microbiomes in each building were dominated by two genera, which together accounted for 30% of the community composition: Acinetobacter and Enhydrobacter (also classified as Moraxella) in the newer building, and Sphingomonas and Mycobacterium in the older building. Acinetobacter abundance varied seasonally and showed higher relative abundance during periods of high traffic. Metagenomic analysis of selected sinks revealed a high prevalence of qac genes and metagenome-assembled genomes (MAGs) harboring antimicrobial resistance genes (ARGs) including A. parvus. Notably, 34-53% of qac genes were co-localized on contigs associated with mobile genetic elements. These findings suggest that disinfected sink drains serve as persistent reservoirs of diverse microorganisms and potentially mobile resistance elements. IMPORTANCESink drains are recognized environmental reservoirs for multidrug-resistant bacteria and have been linked to healthcare-associated outbreaks. In public and educational buildings, these microbiomes are shaped by frequent human activity, making them potential sources of exposure and contributors to the environmental dissemination of antibiotic resistance genes. Quaternary ammonium compound (QAC) disinfectants are widely used on surfaces; however, they can select for resistant taxa and co-select for antibiotic resistance. In this study, despite routine cleaning with QACs, public restroom drains remain colonized by resilient biofilms, posing a potential risk to multiple users. Additionally, factors such as human traffic and seasonal variation may influence drain usage and microbial community composition. Elucidating how seasonal dynamics and human activity shape sink biofilms is essential for understanding their role in the environmental transmission of antimicrobial resistance and informing mitigation strategies in nonclinical settings.

microbiology↗

bioRxiv2023

Multiplexed Digital Characterisation of Misfolded Protein Oligomers via Solid-State Nanopores

Misfolded protein oligomers are of central importance in both the detection and treatment of Alzheimers and Parkinsons diseases. However, accurate high-throughput methods to identify and quantify oligomer populations are currently lacking. We present here a single-molecule approach for the detection of oligomeric species. The approach is based on the use of solid state nanopores and multiplexed DNA barcoding to identify and characterise oligomers from multiple samples. We study -synuclein oligomers in the presence of several small molecule inhibitors of -synuclein aggregation, as an illustration of the applicability of this method to assist the development of diagnostic and therapeutic methods for Parkinsons disease.

biophysics↗

bioRxiv2023

α-Synuclein oligomers form by secondary nucleation

Oligomeric species arising during aggregation of -synuclein are proposed to be a major source of toxicity in Parkinsons disease, and thus a major potential drug target. However, their mechanism of formation and role in aggregation are largely unresolved. Here we first show that, at physiological pH, -synuclein aggregates by secondary nucleation, rather than fragmentation, and that this process is enhanced by agitation. Moreover, using a combination of single molecule and bulk level techniques, we identify secondary nucleation on the surfaces of existing fibrils, rather than formation directly from monomers, as the dominant source of oligomers. Our results highlight secondary nucleation as not only the key source of oligomers, but also the main mechanism of aggregate formation, and show that these processes take place under physiologically relevant conditions.

biophysics↗

bioRxiv2020

Sensing soluble uric acid by Naip1-Nlrp3 platform

The immune system can recognize microbes and sterile tissue damage. Among the damage-associated molecular patterns (DAMPs), uric acid is considered a major component which can trigger inflammation. It represents a breakpoint in the evolutionary history of humans as our ancestors lost the uricase gene, the enzyme responsible for its cleavage. High soluble uric acid (sUA) concentration is able to increase IL-1{beta} in murine, but not human macrophages. We observed that sUA increased the mRNA expression of Naip1 in murine macrophages, and, therefore, we hypothesized that the recognition of sUA can be made by a Naip1-Nlrp3 inflammasome platform. Additionally, we used genome-wide transcriptome analysis, functional analyses and structural modeling predictions and observed that virus-transduction of murine Naip1 into human macrophages induced IL-1{beta} after sUA stimulus, besides leading to fatty acid production and an inflammation-related response. Moreover, pharmacologic inhibition and genetic loss of Nlrp3 led to decreased IL-1{beta} production upon sUA stimulus. Surface plasmon resonance and quartz crystal microbalance showed that sUA is able to interact with Naip1. Naip could be a lost receptor for sUA in the evolutionary process and a better understanding of the immune modulatory function of sUA could lead to design rational novel anti-hyperuricemic therapies.

immunology↗