Biology subjects

Machado, S.

Publications and source records attributed to Machado, S..

5 recordsLinked to original sources

bioRxiv2025

The role of autoproteolysis and mitoribosomal proteins in regulation of mitochondrial LACTB tumor suppressor

Tumor suppressors represent one of the first lines of defense against malignant transformation and their inactivation in cells leads to onset of tumorigenesis. Cancer cells employ a variety of ways to inactivate cellular tumor suppressors, such as their epigenetic silencing or mutagenesis. Less understood are mechanisms by which cancer cells inactivate tumor suppressors post-translationally. Here, we uncovered a previously undescribed post-translational strategy that cancer cells use to inactivate the potent mitochondrial tumor suppressor LACTB in breast cancers. We discovered that substrate of LACTB can be LACTB itself; that LACTB possesses autoproteolytic ability, which is important for the modulation of its tumor suppressor activity. We show that cancer cells misuse this feature of LACTB to force LACTB into self-degradation. This is mechanistically realized through upregulation of mitochondrial MRPS34 protein, which, through interaction with LACTB, is a positive regulator of the autoproteolytic activity of LACTB and a negative regulator of LACTB. This study, through in vitro, in vivo, human clinical tumor samples and mutagenesis, provides important new insights into how cancer cells fine-tune the expression and activity of tumor suppressors to promote tumorigenesis. Statement of SignificanceWe uncovered a unique post-translational strategy and mechanism cancer cells employ to inactivate the potent mitochondrial tumor suppressor LACTB in breast cancers thus expanding our knowledge on regulatory and adaptive mechanisms cancer cells use to silence tumor suppressors.

cancer biology↗

bioRxiv2025

Myeloid FtH Regulates Macrophage Response to Kidney Injury by Modulating Snca and Ferroptosis

This study explored the role of myeloid ferritin heavy chain (FtH) in coordinating kidney iron trafficking in health and disease. Synuclein- (Snca) was the sole iron-binding protein upregulated in response to myeloid FtH deletion (FtH{Delta}/{Delta}). Following kidney injury, FtH{Delta}/{Delta} mice showed worsened kidney function. Transcriptome analysis revealed coupling of FtH deficiency with ferroptosis activation, a regulated cell death associated with iron accumulation. Adverse effects of ferroptosis were evidenced by upregulation of ferroptosis-related genes, increased oxidative stress markers, and significant iron deposition in kidney tissues. This iron buildup in FtH{Delta}/{Delta} kidneys stemmed from macrophage reprogramming into an iron-recycling phenotype, driven by Spic induction. Mechanistically, we establish that monomeric Snca functions as a ferrireductase catalyst, intensifying oxidative stress and triggering ferroptosis. Additionally, Snca accumulates in kidney diseases distinguished by leukocyte expansion across species. These findings position myeloid FtH as a pivotal orchestrator of the FtH-Snca-Spic axis driving macrophage reprogramming and kidney injury. HighlightsO_LIMyeloid FtH deficiency drives kidney injury via activation of ferroptosis C_LIO_LIM{Phi} FtH deficiency induces Snca, linking iron dysregulation to M{Phi} function and response to kidney injury C_LIO_LIFerrireductase activity of monomeric Snca augments oxidative stress, promoting lipid peroxidation and ferroptosis C_LI In briefM{Phi} FtH modulates Snca and Spic to coordinate the injury response, linking iron trafficking to ferroptosis-induced kidney injury

pathology↗

bioRxiv2024

The Effects of Acute Coordinative vs. Acute Endurance Exercise on the Cortisol Concentration

BackgroundPhysical exercise interventions can cause neuroendocrine activation, which in turn increases salivary cortisol concentrations. Until now there have been no studies comparing endurance and coordinative exercise. ObjectiveThe purpose of this study was to examine the effects of these different interventions with an intraindividual comparison. Methods61 students between 18 and 30 years of age were included and first completed a coordinative exercise and one week later an endurance exercise of the same intensity and length which was self-set on the first day, with a maximum heart rate of 64 - 76% (HRmax) over a period of 15 min. To measure changes in the hypothalamic-pituitary-adrenal axis (HPA-axis) activity, saliva samples were collected before (t1) and after exercise (t2 and t3). ResultsBaseline values of cortisol (t0) did not differ significantly between coordinative and endurance exercise, t(55) = .233, p = .816. Post hoc tests revealed that the cortisol values of the second coordinative vs. endurance time point, t(55) = 2.097, p = .040, d = .741, and third coordinative vs. endurance time point, t(55) = 3.004, p = .004, d = .735, differed significantly with large effect sizes. ConclusionThe results show for the first time that coordinative exercise produced a higher cortisol release than endurance exercise of the same intensity and duration. Interventions such as coordinative exercise require higher cognitive components resulting in stronger cortisol release than endurance exercise. Thus, the type of acute exercise is a psychophysiological factor in determining the neuroendocrine stress response. Key pointsCortisol is an important catabolic hormone when it comes to overtraining or burnout in an athlete. Our results show for the first time that acute coordinative exercise produces a higher cortisol release than endurance exercise of the same intensity and duration.

physiology↗

bioRxiv2019

Natural infection and vertical transmission of two flaviviruses (Yellow fever and Zika) in mosquitoes in primary forests in the Brazilian state of Rio de Janeiro (Diptera: Culicidae)

BackgroundZika virus (ZIKV) was recently introduced in the American continent, probably transmitted by Aedes aegypti and possibly by Ae. albopictus and Culex quinquefasciatus in urban environments. ZIKV represents a known public health problem as it has been involved in newborn cases of congenital microcephaly in South America since 2005. The transmission of this virus in forested areas of other countries and its relative ubiquity in relation to its vectors and reservoirs raises suspicions of its adaptation to non-human modified environments (i.e., natural forests reserve) or on this continent, similar to those seen for Yellow fever virus (YFV). The objective of this work was to have an epidemiological monitoring tool mapping insects as well as circulating arboviruses in wild areas with low human interference. This study was based on the history of the insect flavivirus spreading cycle.\n\nMethods/Principal FindingsUsing a previously described sensitive PCR-based assay to assess the conserved NS5 region of the Flavivirus genus, both YFV partial genome and ZIKV were found in pools of Aedes albopictus, a sylvatic mosquito adapted to human-modified environments, and in Haemagogus leucocelaenus, a sylvatic mosquito.\n\nConclusionsThis is the first report of natural infection by ZIKV in mosquitoes in a sylvatic environment on the American continent. The wide distribution of these mosquitoes is probably important in the transmission of ZIKV. Vertical transmission indicates a higher efficiency for the maintenance and transmission of the virus in nature as well as the presence of the ZIKV in permanent character in the forest areas as it occurs with the YFV thus making more difficult the prevention of new cases of Zika in humans.\n\nAuthor SummaryArboviruses are diseases transmitted by arthropod vectors, hence the origin of the term ARthropod BOrne VIRUS, which is adopted since 1942. This work had as objective to survey the circulating insects as well as to detect the presence of viruses in them. Arboviruses circulate between insects and vertebrate hosts, having importance for promoting diseases in humans and animals. The diseases most known at the time, due to the recent cases reported by South America, are Dengue, Zika, Yellow Fever and Chikungunya. For this study, we used appropriate traps to collect the insects and their eggs in wild areas where there is little human interference. After collection, mosquitoes and / or eggs were identified and separated as to the source and species. The eggs were kept in laboratory conditions for the hatching of new insects. All the insects obtained were separated into pools to be macerated and thus extract the RNA from the viruses to be studied. Using molecular biology techniques, in our case the RT-PCR (Reverse Transcriptase Polymerase Chain Reaction), we amplified the RNA and in sequentially, we performed the sequencing reaction. With sequencing, it is possible to identify which virus material is present since each virus has a characteristic arrangement. For the identification of the sequences, we need to use some computational programs that guarantee us the correct result.

molecular biology↗

bioRxiv2018

LimeSeg: A coarsed-grained lipid membrane simulation for 3D image segmentation

Bioimage analysis is an important preliminary step required for data representation and quantitative studies. To carry out these tasks, we developed LimeSeg, an easy-to-use, efficient and modular 3D image segmentation method. Based on the idea of SURFace ELements, LimeSeg resembles a highly coarse-grained simulation of a lipid membrane in which a set of particles, analogous to lipid molecules, are attracted to local image maxima. The particles are self-generating and self-destructing thus providing the ability for the membrane to evolve towards the contour of the object of interest. We characterize the emergent mechanical properties of this system and show how it can be used to segment many 3D objects from numerous types of image of biological samples (brain MRI, cell epithelium, cellular organelles). LimeSeg is available as a Fiji plugin that includes simple commands, a 3D visualizer, and customization options via ImageJ scripting.

bioinformatics↗