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"Martinez, Pablo A."
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Water constraints drive allometric patterns in the body shape of tree frogs
by
Amado, Talita F.
,
Martinez, Pablo A.
,
Olalla-Tárraga, Miguel Á.
in
631/158
,
631/181
,
Allometry
2021
The origin of morphological diversity is a critical question in evolutionary biology. Interactions between the environment and developmental processes have determining roles in morphological diversity, creating patterns through space and over time. Also, the shape of organisms tends to vary with increasing size as a result of those developmental processes, known as allometry. Several studies have demonstrated that the body sizes of anurans are associated with hydric conditions in their environments and that localities with high water stress tend to select for larger individuals. However, how environmental conditions alter those patterns of covariance between size and shape is still elusive. We used 3D geometric morphometric analyses, associated with phylogenetic comparative methods, to determine if the morphological variations and allometric patterns found in Arboranae (Anura) is linked to water conservation mechanisms. We found effects of the hydric stress on the shape of Arboranae species, favouring globular shapes. Also, the allometric patterns varied in intensity according to the water stress gradient, being particularly relevant for smaller frogs, and more intense in environments with higher water deficits. Our study provides empirical evidence that more spherical body shapes, especially among smaller species, reflect an important adaptation of anurans to water conservation in water-constrained environments.
Journal Article
In Silico Identification of Potential Inhibitors of SARS-CoV-2 Main Protease (Mpro)
by
Medina-Franco, José L.
,
Cardenas-Granados, Luis Alfonso
,
Martínez-Soriano, Pablo A.
in
3CLpro
,
Antiviral agents
,
Antiviral Agents - chemistry
2024
The ongoing Coronavirus Disease 19 (COVID-19) pandemic has had a profound impact on the global healthcare system. As the SARS-CoV-2 virus, responsible for this pandemic, continues to spread and develop mutations in its genetic material, new variants of interest (VOIs) and variants of concern (VOCs) are emerging. These outbreaks lead to a decrease in the efficacy of existing treatments such as vaccines or drugs, highlighting the urgency of new therapies for COVID-19. Therefore, in this study, we aimed to identify potential SARS-CoV-2 antivirals using a virtual screening protocol and molecular dynamics simulations. These techniques allowed us to predict the binding affinity of a database of compounds with the virus Mpro protein. This in silico approach enabled us to identify twenty-two chemical structures from a public database (QSAR Toolbox Ver 4.5 ) and ten promising molecules from our in-house database. The latter molecules possess advantageous qualities, such as two-step synthesis, cost-effectiveness, and long-lasting physical and chemical stability. Consequently, these molecules can be considered as promising alternatives to combat emerging SARS-CoV-2 variants.
Journal Article
Treatment with synthetic lipophilic tyrosyl ester controls Leishmania major infection by reducing parasite load in BALB/c mice
by
LAOUINI, DHAFER
,
SGHAIER, RABIAA M.
,
LEON MARTINEZ, PABLO A.
in
Animals
,
antileishmanial properties
,
Antiprotozoal Agents - administration & dosage
2016
Synthesized lipophilic tyrosyl ester derivatives with increasing lipophilicity were effective against Leishmania (L.) major and Leishmania infantum species in vitro. These findings prompted us to test in vivo leishmanicidal properties of these molecules and their potential effect on the modulation of immune responses. The experimental BALB/c model of cutaneous leishmaniasis was used in this study. Mice were infected with L. major parasites and treated with three in vitro active tyrosyl esters derivatives. Among these tested tyrosylcaprate (TyC) compounds, only TyC10 exhibited an in vivo anti-leishmanial activity, when injected sub-cutaneously (s.c.). TyC10 treatment of L. major-infected BALB/c mice resulted in a decrease of lesion development and parasite load. TyC10 s.c. treatment of non-infected mice induced an imbalance in interferon γ/interleukin 4 (IFN-γ/IL-4) ratio cytokines towards a Th1 response. Our results indicate that TyC10 s.c. treatment improves lesions’ healing and parasite clearance and may act on the cytokine balance towards a Th1 protective response by decreasing IL-4 and increasing IFN-γ transcripts. TyC10 is worthy of further investigation to uncover its mechanism of action that could lead to consider this molecule as a potential drug candidate.
Journal Article
Biome stability in South America over the last 30 kyr: Inferences from long-term vegetation dynamics and habitat modelling
2018
Aim: The aim was to examine the links between past biome stability, vegetation dynamics and biodiversity patterns. Location: South America. Time period: Last 30,000 years. Major taxa studied: Plants. Methods: We classified South America into major biomes according to their dominant plant functional groups (grasses, trees and shrubs) and ran a random forest (RF) classification with data on current climate. We then fitted the algorithm to predict biome distributions for every 1,000 years back to 21,000 yr BP and estimated biome stability by counting how many times a change in climate was predicted to shift a grid cell from one biome to another. We compared our model-based stability map with empirical estimates from selected pollen records covering the past 30 kyr in terms of vegetation shifts, changes in species composition and time-lag of vegetation responses. Results: We found a strong correlation between our habitat stability map and regional vegetation dynamics. Four scenarios emerged according to the way forest distribution shifted during a climate change. Each scenario related to specific regional features of biome stability and diversity, allowing us to formulate specific predictions on how taxonomic, genetic and functional components of biodiversity might be impacted by modern climate change. Main conclusions: Our validated map of biome stability provides important baseline information for studying the impacts of past climate on biodiversity in South America. By focusing exclusively on climatic changes of manifested relevance (i.e., those resulting in significant habitat changes), it provides a novel perspective that complements previous datasets and allows scientists to explore new questions and hypotheses at the local, regional and continental scales.
Journal Article
Preservation effects in geometric morphometric approaches: freezing and alcohol in a freshwater fish
by
Berbel-Filho, Waldir M.
,
Jacobina, Uedson P.
,
Martinez, Pablo A.
in
alcohols
,
Animal Systematics/Taxonomy/Biogeography
,
Biomedical and Life Sciences
2013
The present study analyzes the effects of freezing and alcohol preservation in geometric morphometric data, using 15 individuals of the peacock fish
Cichla kelberi
(12.9–26.4 cm SL) divided into freezing and alcohol groups, conserved in each preservation method for 90 days. Discriminant analysis revealed significant difference between before and after treatments, and principal component analysis also showed separation between treatments, for both conservation methods. These results introduce a significant preservation influence that should be considered in biological, ecological and evolutionary interpretations of fish data in geometric morphometric approaches.
Journal Article
Hypoxic Cardioprotection by New Antihypertensive Compounds in High Salt-Diet Hypertensive Rats: Glucose Transport Participation and Its Possible Pathway
by
Martínez-Soriano, Pablo A.
,
Lerma, Claudia
,
Alarcón-López, Aldo Y.
in
Animals
,
Antibodies
,
Antihypertensive Agents - pharmacology
2024
Hypertension (HP) is a health condition that overloads the heart and increases the risk of heart attack and stroke. In an infarction, the lack of oxygen causes an exclusive use of glycolysis, which becomes a crucial source of ATP for the heart with a higher glucose uptake mediated by glucose transporters (GLUTs). Due to the unpleasant effects of antihypertensives, new drugs need to be researched to treat this disease. This study aimed to evaluate the cardioprotective effect of three novel antihypertensive compounds (LQMs, “Laboratorio de Química Medicinal”) synthesized from Changrolin under hypoxic conditions with the participation of two primary cardiac GLUT1 and GLUT4 using a high-salt diet HP model. The model used a diet with 10% salt to increase arterial blood pressure in Wistar rats. In isolated cardiomyocytes from these rats, glucose uptake was measured during hypoxia, evaluating the participation of GLUTs with or without the animals’ previous treatment with LQM312, 319, and 345 compounds. In silico calculations were performed to understand the affinity of the compounds for the trafficking of GLUTs. Results: Control cells do shift to glucose uptake exclusively in hypoxia (from 1.84 ± 0.09 µg/g/h to 2.67 ± 0.1 µg/g/h). Meanwhile, HP does not change its glucose uptake (from 2.38 ± 0.24 µg/g/h to 2.33 ± 0.26 µg/g/h), which is associated with cardiomyocyte damage. The new compounds lowered the systolic blood pressure (from 149 to 120 mmHg), but only LQM312 and LQM319 improved the metabolic state of hypoxic cardiomyocytes mediated by GLUT1 and GLUT4. In silico studies suggested that Captopril and LQM312 may mimic the interaction with the AMPK γ-subunit. Therefore, these compounds could activate AMPK, promoting the GLUT4 trafficking signaling pathway. These compounds are proposed to be cardioprotective during hypoxia under HP.
Journal Article
Colonizing polar environments : thermal niche evolution in Collembola
by
Martinez, Pablo A.
,
Janion‐Scheepers, Charlene
,
Escribano‐Álvarez, Pablo
in
Antarctica
,
Biogeography
,
Climate change
2024
Temperature is a primary driver to define the ecophysiological activity and performance of ectotherms. Thus, thermal tolerance limits have a profound effect in determining geographic ranges. In regions with extreme cold temperatures, lower thermal limits of species are a key physiological trait for survival. Moreover, thermal niche breadth also plays an important role in allowing organisms to withstand climatic variability and confers species with broader potential to establish in new regions. Here we study the evolution of thermal tolerance limits among Collembola (Arthropoda) and explore how they are affected by the colonization of polar environments. In addition, we test the hypothesis that globally invasive species are more eurythermal than non‐invasive ones. Critical thermal limits (CTmin and CTmax), classic measurements of thermal tolerance, were compiled from the literature and complemented with experimental assays for springtail species. Genetic data of the mitochondrial gene cytochrome oxidase subunit 1 (COI) was used to assemble a phylogeny. Our results show that polar springtails have lower CTmin and lower CTmax compared to species from temperate and tropical regions, consistent with the Polar pressure hypothesis. We found no phylogenetic signal for CTmax, but low values of phylogenetic signal for CTmin. Globally invasive species do not have significantly broader thermal tolerance breadth (CTrange) than non‐invasive ones, thus not supporting the predictions of the Eurythermality hypothesis. We conclude that polar springtails have evolved their thermal niches in order to adapt to extremely cold environments, which has led to decreasing both upper and lower thermal tolerance limits.
Journal Article
Physical constraints on thermoregulation and flight drive morphological evolution in bats
by
Cruz-Neto, Ariovaldo P.
,
Martinez, Pablo A.
,
Dobrovolski, Ricardo
in
Adaptation
,
Animals
,
Bats
2022
Body size and shape fundamentally determine organismal energy requirements by modulating heat and mass exchange with the environment and the costs of locomotion, thermoregulation, and maintenance. Ecologists have long used the physical linkage between morphology and energy balance to explain why the body size and shape of many organisms vary across climatic gradients, e.g., why larger endotherms are more common in colder regions. However, few modeling exercises have aimed at investigating this link from first principles. Body size evolution in bats contrasts with the patterns observed in other endotherms, probably because physical constraints on flight limit morphological adaptations. Here, we develop a biophysical model based on heat transfer and aerodynamic principles to investigate energy constraints on morphological evolution in bats. Our biophysical model predicts that the energy costs of thermoregulation and flight, respectively, impose upper and lower limits on the relationship of wing surface area to body mass (S-MR), giving rise to an optimal S-MR at which both energy costs are minimized. A comparative analysis of 278 species of bats supports the model’s prediction that S-MR evolves toward an optimal shape and that the strength of selection is higher among species experiencing greater energy demands for thermoregulation in cold climates. Our study suggests that energy costs modulate the mode of morphological evolution in bats—hence shedding light on a long-standing debate over bats’ conformity to ecogeographical patterns observed in other mammals—and offers a procedure for investigating complex macroecological patterns from first principles.
Journal Article
Molecular Docking and Dynamic Studies of Amide Derivatives from Cinnamic Acid with Potential Anti‐Dengue Virus Activity
by
Castro‐Jiménez, Tannya Karen
,
Angeles, Enrique
,
Bustos‐Arriaga, José
in
Amides - chemistry
,
Amides - pharmacology
,
Amino acids
2025
Dengue, classified as a neglected tropical disease and transmitted by Aedes mosquitoes, remains a significant global health challenge, often evolving into severe clinical manifestations such as hemorrhagic fever. Despite its widespread impact, no antiviral therapy has been approved to date, highlighting the urgent need for effective and accessible treatment options. In the present work, computational analysis is performed on an in‐house library of easily synthesized caffeic acid phenethyl ester analogs, which exhibit potential activity against the viral envelope (E) protein, a critical mediator of dengue virus entry and membrane fusion. Among them, LQM778 demonstrated consistent stability within the protein–ligand complex during molecular dynamics simulations. This finding provides a foundation for in vitro studies and future structural optimizations that could transform the landscape of antiviral development against dengue. A library of easily synthesizable CAPE analogs was screened in silico against the dengue virus envelope protein. Compound LQM778 showed stable binding and promising inhibitory potential. This study highlights LQM778 as a candidate for future in vitro validation and structural optimization toward accessible antiviral agents against dengue.
Journal Article
Climate effects on fish body size–trophic position relationship depend on ecosystem type
by
Martinez, Pablo A.
,
Carneiro, Luciana S.
,
Attayde, José L.
in
Actinopterygii
,
Animal behavior
,
Aquatic ecosystems
2019
The energetic demand of consumers increases with body size and temperature. This implies that energetic constraints may limit the trophic position of larger consumers, which is expected to be lower in tropical than in temperate regions to compensate for energy limitation. Using a global dataset of 3635 marine and freshwater ray‐finned fish species, we addressed if and how climate affects the fish body size–trophic position relationship in both freshwater and marine ecosystems, while controlling for the effects of taxonomic affiliation. We observed significant fish body size–trophic position relationships for different ecosystems. However, only in freshwater systems larger tropical fish presented a significantly lower trophic position than their temperate counterparts. Climate did not affect the fish body size–trophic position relationship in marine systems. Our results suggest that larger tropical freshwater fish may compensate for higher energetic constraints feeding at lower trophic positions, compared to their temperate counterparts of similar body size. The lower latitudinal temperature range in marine ecosystems and/or their larger ecosystem size may attenuate and/or compensate for the energy limitation of larger marine fish. Based on our results, temperature may determine macroecological patterns of aquatic food webs, but its effect is contingent on ecosystem type. We suggest that freshwater ecosystems may be more sensitive to warming‐induced alterations in food web topology and food chain length than marine ecosystems.
Journal Article