Manel Esteller

Manel Esteller estudia les alteracions genètiques de les malalties. Ha participat en el desenvolupament de fàrmacs per tractar el càncer i de noves tecnologies per a la investigació en aquest àmbit.Manel Esteller estudia las alteraciones genéticas de las enfermedades. Ha participado en el desarrollo de fármacos para tratar el cáncer y de nuevas tecnologías para la investigación en este ámbito

Telomeres in a spatial context: a tool for understanding ageing pattern variation in wild populations

Ageing refers to the loss of organismal functionality with age, a process that is characterised by decreased reproduction and survival probability. In natural populations, it is expected that environmental conditions influence an individual's ageing trajectory. Understanding the role of environmental heterogeneity on ageing variation could provide critical insights into population resilience and species distribution but remains overlooked. Telomeres, the end cap of chromosomes, are a promising integrative physiological marker of an individual's health and a possible proxy to aid the understanding of variation in ageing trajectories. Here, we review the existing information on telomere length and its dynamics in wild populations distributed across spatial scales. Despite a relative scarcity of information, there is evidence for divergence in telomere length between populations facing contrasting environments. Nonetheless, a higher spatial resolution and temporal replication are needed to fully understand the role that environmental conditions play on telomere length variation. Since most of the existing studies are correlational, future field and laboratory experiments are required. For the first time, we demonstrate the use of population telomere data to predict species habitat suitability through species distribution models (SDMs). This represents a promising new research area in the study of ageing pattern variation in wild populations. Furthermore, the inclusion of telomere data in future physiological SDMs may improve our understanding of species distribution and population resilience. However, the use of telomeres within this context could be limited if no previous knowledge on the relevance of telomeres as markers of health and survival at the species level is available. Finally, we suggest some key practical and theoretical considerations that, ideally, future studies combining biogeographic and telomere data should pay attention

Human activity is altering the world’s zoogeographical regions

Zoogeographical regions, or zooregions, are areas of the Earth defined by species pools that reflect ecological, historical, and evolutionary processes acting over millions of years. Consequently, researchers have assumed that zooregions are robust and unlikely to change on a human timescale. However, the increasing number of human-mediated introductions and extinctions can challenge this assumption. By delineating zooregions with a network-based algorithm, here we show that introductions and extinctions are altering the zooregions we know today. Introductions are homogenising the Eurasian and African mammal zooregions and also triggering less intuitive effects in birds and amphibians, such as dividing and redefining zooregions representing the Old and New World. Furthermore, these Old and New World amphibian zooregions are no longer detected when considering introductions plus extinctions of the most threatened species. Our findings highlight the profound and far-reaching impact of human activity and call for identifying and protecting the uniqueness of biotic assemblages

The Area of Pressure-Induced Referred Pain Is Dependent on the Intensity of the Suprathreshold Stimulus: An Explorative Study

Objective: To investigate the pain referral area (number of pixels) and extent (vector length) as elicited from increasing intensities of pressure-induced pain at the shoulder. Design: Cross-sectional design. Setting: Clinical laboratory setting. Participants: Twenty-two healthy men and women participated in two experimental sessions. Methods: Delayed onset of muscle soreness (DOMS) was induced in the dominant shoulder and assessed 24 hours later. Participants rated the level of DOMS on a 6-point Likert scale. Four different intensities (pressure pain threshold [PPT]+20%, PPT+30%, PPT+40%, and PPT+50%) were applied to the infraspinatus in a randomized, balanced fashion for 60 seconds from low to high intensity or vice versa. The resulting location, area, and extent of referred pain as drawn by the participants on a digital body chart were extracted and expressed in pixels. The extent of pain was defined as the vector length extending from the ipsilateral earlobe to the most distal location of the pain. Results: The referred pain area from PPT+20% was smaller than PPT+30%, PPT+40%, and PPT+50%. The extent of referred pain did not differ between the pressure pain intensities. Conclusions: Pressure intensity at PPT+30%, but no more, produces the greatest referred pain area as compared with the traditional pressure intensity of PPT+20%. Thus, the intensity of PPT+30% may be ideal for exploring the mechanisms of referred pain. The extent of the pain represents an independent expression of the intensity of the provoking stimulus and may be more closely related to the location of the stimulus

Machine learning aplicado a remote sensing: aplicaciones en gobernanza digital para el desarrollo sustentable

El presente trabajo muestra las problemáticas abordadas mediante tecnologías de Machine Learning aplicadas a Remote Sensing, las que pueden servir de soporte a la gobernanza digital para el desarrollo sustentable. Para ello se realiza una revisión bibliográfica de la utilización de estas dos tecnologías con el fin de mostrar cuáles son los avances alcanzados en el área, en qué se está trabajando y cuáles son las aplicaciones relacionadas con la gobernanza electrónica para el desarrollo sustentable.Trabajo presentado por el Instituto de Investigación y Transferencia en Tecnología (ITT

PEPCK-M recoups tumor cell anabolic potential in a PKC-ζ-dependent manner

Background: Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M; PCK2) is expressed in all cancer types examined and in neuroprogenitor cells. The gene is upregulated by amino acid limitation and ER-stress in an ATF4- dependent manner, and its activity modulates the PEP/Ca2+ signaling axis, providing clear arguments for a functional relationship with metabolic adaptations for cell survival. Despite its potential relevance to cancer metabolism, the mechanisms responsible for its pro-survival activity have not been completely elucidated. Methods: [U-13C]glutamine and [U-13C]glucose labeling of glycolytic and TCA cycle intermediates and their anabolic end-products was evaluated quantitatively using LC/MS and GC/MS in conditions of abundant glucose and glucose limitation in loss-of-function (shRNA) and gain-of-function (lentiviral constitutive overexpression) HeLa cervix carcinoma cell models. Cell viability was assessed in conjunction with various glucose concentrations and in xenografts in vivo. Results: PEPCK-M levels linearly correlated with [U-13C]glutamine label abundance in most glycolytic and TCA cycle intermediate pools under nutritional stress. In particular, serine, glycine, and proline metabolism, and the anabolic potential of the cell, were sensitive to PEPCK-M activity. Therefore, cell viability defects could be rescued by supplementing with an excess of those amino acids. PEPCK-M silenced or inhibited cells in the presence of abundant glucose showed limited growth secondary to TCA cycle blockade and increased ROS. In limiting glucose conditions, downregulation of PKC-ζ tumor suppressor has been shown to enhance survival. Consistently, HeLa cells also sustained a survival advantage when PKC-ζ tumor suppressor was downregulated using shRNA, but this advantage was abolished in the absence of PEPCK-M, as its inhibition restores cell growth to control levels. The relationship between these two pathways is also highlighted by the anti-correlation observed between PEPCK-M and PKC-ζ protein levels in all clones tested, suggesting co-regulation in the absence of glucose. Finally, PEPCK-M loss negatively impacted on anchorage-independent colony formation and xenograft growth in vivo. Conclusions: All in all, our data suggest that PEPCK-M might participate in the mechanisms to regulate proteostasis in the anabolic and stalling phases of tumor growth. We provide molecular clues into the clinical relevance of PEPCK-M as a mechanism of evasion of cancer cells in conditions of nutrient stress

Alternative usage of miRNA-biogenesis co-factors in plants at low temperatures

Plants use molecular mechanisms to sense temperatures, trigger quick adaptive responses and thereby cope with environmental changes. MicroRNAs (miRNAs) are key regulators of plant development under such conditions. The catalytic action of DICER LIKE 1 (DCL1), in conjunction with HYPONASTIC LEAVES 1 (HYL1) and SERRATE (SE), produces miRNAs from double-stranded RNAs. As plants lack a stable internal temperature to which enzymatic reactions could be optimized during evolution, reactions such as miRNA processing have to be adjusted to fluctuating environmental temperatures. Here, we report that with decreasing ambient temperature, the plant miRNA biogenesis machinery becomes more robust, producing miRNAs even in the absence of the key DCL1 co-factors HYL1 and SE. This reduces the morphological and reproductive defects of se and hyl1 mutants, restoring seed production. Using small RNA-sequencing and bioinformatics analyses, we have identified specific miRNAs that become HYL1/SE independent for their production in response to temperature decrease. We found that the secondary structure of primary miRNAs is key for this temperature recovery. This finding may have evolutionary implications as a potential adaptation-driving mechanism to a changing climate.Fil: Ré, Delfina Adela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; ArgentinaFil: Lang, Patricia L. M.. Institut Max Planck Fuer Gesellschaft. Institut Fur Entwicklungsbiolobie. Developmental Biology; AlemaniaFil: Yones, Cristian Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional; ArgentinaFil: Arce, Agustín Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; ArgentinaFil: Stegmayer, Georgina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional; ArgentinaFil: Milone, Diego Humberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional; ArgentinaFil: Manavella, Pablo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; Argentin

Folding and Dynamics Are Strongly pH-Dependent in a Psychrophile Frataxin

Protein dynamics, folding, and thermodynamics represent a central aspect of biophysical chemistry. pH, temperature, and denaturant perturbations inform our understanding of diverse contributors to stability and rates. In this work, we performed a thermodynamic analysis using a combined experimental and computational approach to gain insights into the role of electrostatics in the folding reaction of a psychrophile frataxin variant from Psychromonas ingrahamii. This folding reaction is strongly modulated by pH with a single, narrow, and well-defined transition state with ∼80% compactness, ∼70% electrostatic interactions, and ∼60% hydration shell compared to the native state (αD = 0.82, αH = 0.67, and αδCp = 0.59). Our results are best explained by a two-proton/two-state model with very different pKa values of the native and denatured states (∼5.5 and ∼8.0, respectively). As a consequence, the stability strongly increases from pH 8.0 to 6.0 (|δδG°| = 5.2 kcal mol-1), mainly because of a decrease in the TδS°. Variation of δH° and δS° at pH below 7.0 is dominated by a change in δHf= and δSf=, while at pH above 7.0, it is governed by δHu= and δSu=. Molecular dynamics simulations showed that these pH modulations could be explained by the fluctuations of two regions, rich in electrostatic contacts, whose dynamics are pH-dependent and motions are strongly correlated. Results presented herein contribute to the understanding of the stability and dynamics of this frataxin variant, pointing to an intrinsic feature of the family topology to support different folding mechanisms.Fil: González Lebrero, Rodolfo M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Defelipe, Lucas Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Modenutti, Carlos Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Roitberg, Adrián. University of Florida; Estados UnidosFil: Batastini, Nicolás Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Noguera, Martín Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Santos, Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; ArgentinaFil: Roman, Ernesto Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentin