Biology subjects

Martins, L.

Publications and source records attributed to Martins, L..

5 recordsLinked to original sources

bioRxiv2026

Quantitative muscle color as a proxy for structural and functional characteristics during muscle remodeling in Gryllus lineaticeps

Understanding the cellular and physiological mechanisms underlying muscle remodeling requires model systems that allow rapid, reliable, and quantitative assessment of muscle state. The cricket Gryllus lineaticeps naturally undergoes non-pathological striated muscle breakdown (histolysis), making it a promising system for studying this process. However, current assessments of muscle state are largely qualitative, subjective, and poorly standardized across experiments. Here, we developed and validated a continuous, quantitative muscle color metric to objectively capture histolysis progression and functional changes in muscle. We show that this metric robustly tracks variation in muscle color across remodeling stages, including the challenging fully transparent stage, and strongly predicts protein content, mitochondrial abundance, and iron content in a muscle- and trait-specific manner. The reproducibility of these relationships across independent datasets demonstrates the generality and robustness of this approach. By providing a rapid, objective, and biologically informative proxy of muscle state, this framework not only advances the utility of G. lineaticeps as a model for muscle remodeling but also offers a strategy for exploring the cellular dynamics underlying age-related muscle diseases and disorders, addressing an increasing public health concern in aging populations.

physiology↗

bioRxiv2025

Early endothelial activation at the blood-nerve barrier defines a hallmark of ALS

Vascular defects are common in Amyotrophic Lateral Sclerosis (ALS). The prevailing view is that breakdown of the blood-brain and blood-spinal cord barriers contributes to neurodegeneration. Here, we reveal that selective and early vulnerability of peripheral nerve endothelium --manifested as endothelial cell activation and interlinked blood-nerve barrier dysfunction-- constitutes a core feature of ALS pathogenesis, arising before vascular alterations in the central nervous system (CNS) and motor neuron pathology. Vascular changes in ALS patients have been largely studied in postmortem samples, limiting insight into their onset, causes, and pathogenic role. Surveying diagnostic motor nerve samples from ALS patients across clinical stages, we observed endothelial damage that preceded axonal loss and demyelination, marking vascular dysfunction as an early disease event. Similar ultrastructural abnormalities were detected in pre-symptomatic ALS mouse models (SOD1 and TARDBP mutants). Notably, endothelial cells became dysfunctional even when not carrying mutant TDP-43, indicating they respond to non-cell autonomous disease signals. Transcriptional, histological, and functional analyses revealed that these alterations were largely confined to peripheral nerves, while spinal cord vessels exhibited delayed and more focal changes. Single-cell sequencing identified ALS-susceptible endothelial cell subsets prone to a pro-inflammatory phenotype and impaired blood-nerve barrier function, increasing permeability via the transcellular route. These changes coincided with reactivity of nerve-resident macrophages and neutrophil infiltration. Neutrophil depletion attenuated endothelial activation and barrier leakiness, mitigating axonopathy in ALS mice. Our work unmasks the greater susceptibility of the peripheral nerve vasculature in ALS relative to the CNS. The early activation of peripheral nerve endothelium, combined with its potential reversibility, identifies a therapeutic window and suggests strategies for targeting the vascular-immune axis to protect the motor system.

neuroscience↗

bioRxiv2024

Diseased skin dermal proteomic profiles reflect shared extracellular matrix dysregulation patterns

Extracellular matrix (ECM) plays a major role in the maintenance of skin homeostasis and modifications in its structure are commonly linked with skin diseases of different origins. Recent evidence shows that epidermal fibroblasts can be important regulators of epidermal pathology. However, despite recent advances, the intricate mechanisms responsible for the ECM defects in a wide range of skin pathologies are still evasive. In this work we used Dystrophic Epidermolysis Bullosa, Pemphigus vulgaris and Squamous Cell Carcinoma, as the models for epidermal diseases of distinct etiology, in order to explore potential shared alterations in diseased dermal fibroblasts. Our proteome analysis revealed that differentially expressed proteins in all diseases are commonly enriched in processes related to supramolecular fiber organization, complex of collagen trimers and actomyosin, however with opposite patterns. Nevertheless, Collagen XII is significantly downregulated in all diseases. Additionally, an algorithmic pipeline predicts that MAPKs and CDKs are major regulators of dermal proteome alterations across all diseases. Altogether, our results highlight a possible shared mechanism where downregulation of Collagen XII mediates ECM organization disruption leading to diverse disease phenotypes.

cell biology↗

bioRxiv2021

Comparative cytogenomics reveals genome reshuffling and centromere repositioning in the legume tribe Phaseoleae

The tribe Phaseoleae (Leguminosae; Papilionoideae) includes several legume crops with assembled genomes. Comparative genomic studies indicate the preservation of large genomic blocks among legumes, however, the chromosome dynamics during Phaseoleae evolution has not been investigated yet. We conducted a comparative genomic analysis to define an informative genomic block (GB) system and to reconstruct the ancestral Phaseoleae karyotype (APK). We defined the GBs based on the orthologous genes between Phaseolus vulgaris and Vigna unguiculata genomes. We searched for these GBs in different genome species belonging to the Phaseolinae (P. lunatus) and Glycininae subtribes (Amphicarpaea edgeworthii and Spatholobus suberectus), and in the Medicago truncaluta outgroup. To support our in silico analysis, we used oligo-FISH probes of P. vulgaris chromosomes 2 and 3 to paint the orthologous chromosomes of two non-sequenced Phaseolinae species (Macroptilium atropurpureum and Lablab purpureus). We inferred the APK with n = 11 and 19 GBs (A to S). We hypothesized five chromosome fusions that reduced the ancestral legume karyotype with n = 16 to n = 11 in APK. Furthermore, we identified the main rearrangements within Phaseolinae and observed an extensive centromere repositioning resulting from evolutionary new centromeres (ENC) in the Phaseolus lineage. Additionally, we demonstrated that the A. edgeworthii genome is more reshuffled than the dysploid S. suberectus genome, in which we could reconstruct the main events that lead the chromosome number reduction. The development of the GB system and the proposed APK provide useful approaches for future comparative genomic analyses of legume species.

genomics↗

bioRxiv2020

Redox response of iron-sulfur glutaredoxin GRXS17 activates its holdase activity to protect plants from heat stress

Living organisms use a large panel of mechanisms to protect themselves from environmental stress. Particularly, heat stress induces misfolding and aggregation of proteins which are guarded by chaperone systems. Here, we examine the function the glutaredoxin GRXS17, a member of thiol reductases families in the model plant Arabidopsis thaliana. GRXS17 is a nucleocytosolic monothiol glutaredoxin consisting of an N-terminal thioredoxin (TRX)-domain and three CGFS-active site motif-containing GRX-domains that coordinate three iron-sulfur (Fe-S) clusters in a glutathione (GSH)-dependent manner. As a Fe-S cluster-charged holoenzyme, GRXS17 is likely involved in the maturation of cytosolic and nuclear Fe-S proteins. In addition to its role in cluster biogenesis, we showed that GRXS17 presents both foldase and redox-dependent holdase activities. Oxidative stress in combination with heat stress induces loss of its Fe-S clusters followed by subsequent formation of disulfide bonds between conserved active site cysteines in the corresponding TRX domains. This oxidation leads to a shift of GRXS17 to a high-MW complex and thus, activates its holdase activity. Moreover, we demonstrate that GRXS17 is specifically involved in plant tolerance to moderate high temperature and protects root meristematic cells from heat-induced cell death. Finally, we showed that upon heat stress, GRXS17 changes its client proteins, possibly to protect them from heat injuries. Therefore, we propose that the iron-sulfur cluster enzyme glutaredoxin GRXS17 is an essential guard to protect proteins against moderate heat stress, likely through a redox-dependent chaperone activity. All in all, we reveal the mechanism of an Fe-S cluster-dependent activity shift, turning the holoenzyme GRXS17 into a holdase that prevents damage caused by heat stress.

plant biology↗