CUERPO, ENVEJECIMIENTO Y ESPACIO. UNA GEOGRAFÍA DEL ENVEJECIMIENTO EN EL ESPACIO RURAL LATINO-AMERICANO

The objective of this paper is to present a theoretical proposal called the geography of aging in rural areas. The body is taken as a paradigm for the understanding of space, retaking the arguments that Lefebvre offered in his monumental The Production of Space, in relation to the body as synthesis of the perceived-conceived-lived triad. At the same time, the aging process is considered as a spatial process. In Latin American countries, the issue of the body as a producer of space and produced by space, takes relevance in the middle of an unprecedented demographic conjuncture and the advance of agribusiness and agroindustry versus traditional, agrarian or peasant populations.El objetivo del artículo es presentar una propuesta teórica llamada geografía del envejecimiento en el espacio rural. El cuerpo es tomado como un paradigma para la comprensión del espacio, retomando los argumentos que Lefebvre ofreció en su monumental La Producción del Espacio, en relación al cuerpo como síntesis de la tríada de lo percibido-concebido-vivido. Paralelamente, el proceso de envejecimiento se considera un proceso espacial. En los países latinoamericanos, la cuestión del cuerpo como productor de espacio y producido por el espacio, lleva relevancia en medio de una coyuntura demográfica sin precedentes y el avance del agronegocio y agroindustrias frente a poblaciones tradicionales, agrarias o campesinas

A naturally occurring calcineurin variant inhibits FoxO activity and enhances skeletal muscle regeneration

The calcium-activated phosphatase calcineurin (Cn) transduces physiological signals through intracellular pathways to influence the expression of specific genes. Here, we characterize a naturally occurring splicing variant of the CnAβ catalytic subunit (CnAβ1) in which the autoinhibitory domain that controls enzyme activation is replaced with a unique C-terminal region. The CnAβ1 enzyme is constitutively active and dephosphorylates its NFAT target in a cyclosporine-resistant manner. CnAβ1 is highly expressed in proliferating myoblasts and regenerating skeletal muscle fibers. In myoblasts, CnAβ1 knockdown activates FoxO-regulated genes, reduces proliferation, and induces myoblast differentiation. Conversely, CnAβ1 overexpression inhibits FoxO and prevents myotube atrophy. Supplemental CnAβ1 transgene expression in skeletal muscle leads to enhanced regeneration, reduced scar formation, and accelerated resolution of inflammation. This unique mode of action distinguishes the CnAβ1 isoform as a candidate for interventional strategies in muscle wasting treatment

A meso-scale model for fluid-microstructure interactions

Particle-fluid and fluid-structure interactions are important areas in particle technology. Typical processes where such interactions are prevalent include fluidized beds, filtration and sedimentation. In addition, fluid-structure interactions are significant in applications such as nuclear waste management, for example in the cementation process used to store radioactive materials, as well as in carbon capture and storage applications where the leakage of gas injected in underground geological reservoirs must be considered in hazard and risk assessments. Given the difficulties in directly measuring the propagation of cracks in solid structures, their permeability or the internal build-up of any gases, for example, numerical techniques in conjunction with non-destructive measurements are important tools of value in assessing and predicting the behavior of fluid-structure interactions. In this work, coupling between the lattice Boltzmann method and a digital packing algorithm based on the discrete element method is used to provide a basis for predicting such coupled interactions. The development of the coupled algorithm is described, with the calculations performed on a regular lattice grid and based on the momentum exchange method to evaluate the force exerted by the fluid on a solid boundary. A number of test cases are reported to allow assessment of the coupled model’s capabilities. Overall, these test cases demonstrate reasonable quantitative agreement with available analytical and experimental results for the case of a sphere settling in a liquid, and the expected qualitative behavior for the case of different orientation cylinders settling in a fluid, and for three dynamic packing processes

Calcineurin splicing variant calcineurin Aβ1 improves cardiac function after myocardial infarction without inducing hypertrophy

BACKGROUND: Calcineurin is a calcium-regulated phosphatase that plays a major role in cardiac hypertrophy. We previously described that alternative splicing of the calcineurin Aβ (CnAβ) gene generates the CnAβ1 isoform, with a unique C-terminal region that is different from the autoinhibitory domain present in all other CnA isoforms. In skeletal muscle, CnAβ1 is necessary for myoblast proliferation and stimulates regeneration, reducing fibrosis and accelerating the resolution of inflammation. Its role in the heart is currently unknown. METHODS AND RESULTS: We generated transgenic mice overexpressing CnAβ1 in postnatal cardiomyocytes under the control of the α-myosin heavy chain promoter. In contrast to previous studies using an artificially truncated calcineurin, CnAβ1 overexpression did not induce cardiac hypertrophy. Moreover, transgenic mice showed improved cardiac function and reduced scar formation after myocardial infarction, with reduced neutrophil and macrophage infiltration and decreased expression of proinflammatory cytokines. Immunoprecipitation and Western blot analysis showed interaction of CnAβ1 with the mTOR complex 2 and activation of the Akt/SGK cardioprotective pathway in a PI3K-independent manner. In addition, gene expression profiling revealed that CnAβ1 activated the transcription factor ATF4 downstream of the Akt/mTOR pathway to promote the amino acid biosynthesis program, to reduce protein catabolism, and to induce the antifibrotic and antiinflammatory factor growth differentiation factor 15, which protects the heart through Akt activation. CONCLUSIONS: Calcineurin Aβ1 shows a unique mode of action that improves cardiac function after myocardial infarction, activating different cardioprotective pathways without inducing maladaptive hypertrophy. These features make CnAβ1 an attractive candidate for the development of future therapeutic approaches.British Heart Foundation [PG/07/020/22503]; Spanish Ministry of Science and Innovation [BFU2009-10016]; National Institutes of Health Research, Cardiovascular Biomedical Research Unit at the Royal Brompton; Hare-field NHS Foundation Trust; Imperial College; Spanish Fondo Nacional de Investigaciones Sanitarias [EIF-040545, ERG-239158, CP08/00144

A Decade of SN1993J: Discovery of Wavelength Effects in the Expansion Rate

We have studied the growth of the shell-like radio structure of supernova SN1993J in M81 from September 1993 through October 2003 with very-long-baseline interferometry (VLBI) observations at the wavelengths of 3.6, 6, and 18cm. For this purpose, we have developed a method to accurately determine the outer radius (R) of any circularly symmetric compact radio structure like SN1993J. The source structure of SN1993J remains circularly symmetric (with deviations from circularity under 2%) over almost 4000 days. We characterize the decelerated expansion of SN 1993J through approximately day 1500 after explosion with an expansion parameter $m= 0.845\pm0.005$ ($R \propto t^{m}$). However, from that day onwards the expansion is different when observed at 6 and 18cm. Indeed, at 18cm, the expansion can be well characterized by the same $m$ as before day 1500, while at 6cm the expansion appears more decelerated, and is characterized by another expansion parameter, $m_{6}= 0.788\pm0.015$. Therefore, since about day 1500 on, the radio source size has been progressively smaller at 6cm than at 18cm. These findings are in stark contrast to previous reports by other authors on the details of the expansion. In our interpretation the supernova expands with a single expansion parameter, $m= 0.845\pm0.005$, and the 6cm results beyond day 1500 are due to physical effects, perhaps also coupled to instrumental limitations. Two physical effects may be involved: (a) a changing opacity of the ejecta to the 6cm radiation, and (b) a radial decrease of the magnetic field in the emitting region. (Long abstract cut. Please, read full abstract in manuscript).Comment: 21 pages, 19 figures, accepted in A&

Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution

Hidrodinámica y evolución del fondo en ecosistemas vegetados intermareales

Este trabajo ha sido financiado por el proyecto HyWEdges (hydrodynamics at coastal wetland edges) dentro de Hydralab+, financiado por el programa EUHorizon2020 Research and Innovation Programme, Grant Agreement 654110

Widening Access to Applied Machine Learning with TinyML

Broadening access to both computational and educational resources is critical to diffusing machine-learning (ML) innovation. However, today, most ML resources and experts are siloed in a few countries and organizations. In this paper, we describe our pedagogical approach to increasing access to applied ML through a massive open online course (MOOC) on Tiny Machine Learning (TinyML). We suggest that TinyML, ML on resource-constrained embedded devices, is an attractive means to widen access because TinyML both leverages low-cost and globally accessible hardware, and encourages the development of complete, self-contained applications, from data collection to deployment. To this end, a collaboration between academia (Harvard University) and industry (Google) produced a four-part MOOC that provides application-oriented instruction on how to develop solutions using TinyML. The series is openly available on the edX MOOC platform, has no prerequisites beyond basic programming, and is designed for learners from a global variety of backgrounds. It introduces pupils to real-world applications, ML algorithms, data-set engineering, and the ethical considerations of these technologies via hands-on programming and deployment of TinyML applications in both the cloud and their own microcontrollers. To facilitate continued learning, community building, and collaboration beyond the courses, we launched a standalone website, a forum, a chat, and an optional course-project competition. We also released the course materials publicly, hoping they will inspire the next generation of ML practitioners and educators and further broaden access to cutting-edge ML technologies.Comment: Understanding the underpinnings of the TinyML edX course series: https://www.edx.org/professional-certificate/harvardx-tiny-machine-learnin

Oxytocin: Crossing the Bridge between Basic Science and Pharmacotherapy

Is oxytocin the hormone of happiness? Probably not. However, this small nine amino acid peptide is involved in a wide variety of physiological and pathological functions such as sexual activity, penile erection, ejaculation, pregnancy, uterus contraction, milk ejection, maternal behavior, osteoporosis, diabetes, cancer, social bonding, and stress, which makes oxytocin and its receptor potential candidates as targets for drug therapy. In this review, we address the issues of drug design and specificity and focus our discussion on recent findings on oxytocin and its heterotrimeric G protein-coupled receptor OTR. In this regard, we will highlight the following topics: (i) the role of oxytocin in behavior and affectivity, (ii) the relationship between oxytocin and stress with emphasis on the hypothalamo–pituitary–adrenal axis, (iii) the involvement of oxytocin in pain regulation and nociception, (iv) the specific action mechanisms of oxytocin on intracellular Ca2+ in the hypothalamo neurohypophysial system (HNS) cell bodies, (v) newly generated transgenic rats tagged by a visible fluorescent protein to study the physiology of vasopressin and oxytocin, and (vi) the action of the neurohypophysial hormone outside the central nervous system, including the myometrium, heart and peripheral nervous system. As a short nine amino acid peptide, closely related to its partner peptide vasopressin, oxytocin appears to be ideal for the design of agonists and antagonists of its receptor. In addition, not only the hormone itself and its binding to OTR, but also its synthesis, storage and release can be endogenously and exogenously regulated to counteract pathophysiological states. Understanding the fundamental physiopharmacology of the effects of oxytocin is an important and necessary approach for developing a potential pharmacotherapy