Identifying the Factors behind Climate Diversification and Refugial Capacity in Mountain Landscapes: The Key Role of Forests

Recent studies have shown the importance of small-scale climate diversification and climate microrefugia for organisms to escape or suffer less from the impact of current climate change. These situations are common in topographically complex terrains like mountains, where many climate-forcing factors vary at a fine spatial resolution. We investigated this effect in a high roughness area of a southern European range (the Pyrenees), with the aid of a network of miniaturized temperature and relative humidity sensors distributed across 2100 m of elevation difference. We modeled the minimum (Tn) and maximum (Tx) temperatures above- and below-ground, and maximum vapor pressure deficit (VPDmax), as a function of several topographic and vegetation variables derived from ALS-LiDAR data and Landsat series. Microclimatic models had a good fit, working better in soil than in air, and for Tn than for Tx. Topographic variables (including elevation) had a larger effect on above-ground Tn, and vegetation variables on Tx. Forest canopy had a significant effect not only on the spatial diversity of microclimatic metrics but also on their refugial capacity, either stabilizing thermal ranges or offsetting free-air extreme temperatures and VPDmax. Our integrative approach provided an overview of microclimatic differences between air and soil, forests and open areas, and highlighted the importance of preserving and managing forests to mitigate the impacts of climate change on biodiversity. Remote-sensing can provide essential tools to detect areas that accumulate different factors extensively promoting refugial capacity, which should be prioritized based on their high resilience

Trypanosoma evansi: ultrastructural cardiac muscle and cardiac microvasculature changes in experimental murine infections

Background:  :  :  : Trypanosoma evansi is the etiologic agent of the equine trypanosomosis, a disease related to the detriment of the extensive bovine farming in the Venezuelan grasslands. Even though macroscopic pathologies such as anemia, pale mucosa, icteric tissues, generalized edema, splenomegaly, liver and renal hypertrophy, abortion, anoestrus, emaciation, lymphadenopathies, striated muscle atrophy as well as epicardiac and endocardiac hemorrhages have been describedfor infections with the agent, no reports of any heart ultrastructural change in experimental or natural infections induced by Venezuelan T.evansi isolates are available. This, a transmission electron microscopic approach to the problem was needed. This work describes cell features of the cardiac myocyte and the cardiac microvasculature ultrastructure in mice experimentally infected with an equine local isolate of T. evansi, also providing an account of the infection with the mice’s survival. Material, Methods & Results: NMRI Mus musculus were inoculated with a Venezuelan T. evansi isolate derived from a naturally infected Equus caballus. From day three post-infection, and every other day until the mice’s death, one rodent was randomly sacrificed, the heart apex was isosmotically removed and cut in symmetrical blocks, which were fixed, post-fixed, dehydrated, infiltrated, included, sectioned, contrasted and studied by means of transmission electron microscopy (TEM), with the subsequent characterization of the cardiac myocyte and the cardiac microvasculature transformations. The evaluation of the micrographs demonstrated ultrastructural time-increasing harmful mitochondrial alterations that included reduction in the number of mitochondria per cell, decrease in mitochondrial dimensions and lessening of the number of cristae per mitochondrion. Myofibrillar destruction, myofilament loss and atrophy were also evident. In addition, damaging augmentation of the vascular endothelium thickness, appearance of abnormal endothelial projections and caveolae loss were incontestable changes. The presence of trypanosomes in the lumen of the heart capillary system was indubitable; however, neither intraendothelial nor intra-cardiac myocyte parasites were observed; no inter-tissular parasites were found either. Discussion: The ultrastructural modifications in the muscular heart tissue and in the heart capillaries of experimentally infected mice with a Venezuelan isolate of T. evansi, derived from a feral domesticated E. caballus, were incontrovertible being characterized by the deleterious gradual mitochondrial decline. In such a context, the close relationship between the mitochondrion and the ribosome disposition is related to protein synthesis being associated to diverse functions and stress reactions to non-proper substances like T. evansi, such circumstance could lead to cardiac myocyte mitochondrial deterioration. Additionally, changes in the mitochondrial dimensions and/or the number of cristae/mitochondrion are related to the mitochondrial enzyme activity. The myofilament loss and the myofibrillar destruction reported in this work could derive from the capillary damage per se. The overexpression of serum deprivation protein response induces caveolae deformation and endothelial cell membrane tubulation. The heart’s myodamage could be additionally caused by autoimmunity and/or electrolytic unbalance induced by the trypanosome. The endothelial cell detriment could be the result of a distant effect of parasitic toxic catabolites, intense edema, hypoxia and/or ischemia. The atrophy was put in evidence by a growing volume reduction as a result of myofibril loss probably due to collateral ischemic and hypoxic mechanisms caused by the parasite. Furthermore, the effect due to toxins could cause intramuscular microvasculature damage, hypoxia and fibrillar atrophy.The trypanosomes were present in the cardiac capillary circulation, being able, as an inducible result of the liberation of active materials, to provoke mononuclear and polymorphonuclear infiltration, contributing to the inflammatory response.The subcellular damage in the cardiac myocites and in the cardiac microvascularure, along with the presence of trypanosomes in the coronary circulation, and the lack of association between parasites and cardiac myocites or parasites and cardiac endothelial cells, are attributes with a remarkable pathological meaning since it represents a non described phenomenon of gradual ultrastructural change that take part of the events, resulting in the murine host death through a degenerative mechanism

EVALUACIÓN ACÚSTICA DE LA EFECTIVIDAD DE LA TOXINA BOTULÍNICA EN EL TRATAMIENTO DE LA DISFONÍA ESPASMÓDICA

La disfonía espasmódica es un trastorno neurológico de la voz en la que se produce una serie de espasmos a nivel de determinados músculos intrínsecos de la laringe, irregulares, de carácter involuntario, que interrumpen el flujo normal del habla. La infiltración de toxina botulínica es el tratamiento de elección, la cual permite reducir dichas contracciones de forma temporal. El análisis acústico mide de forma objetiva y no invasiva parámetros de la voz, y permite monitorizar los cambios a lo largo del tiempo. Mediante este estudio analizaremos las modificaciones de los distintos parámetros acústicos de la voz antes y después del tratamiento en pacientes del Servicio de Otorrinolaringología del Hospital Clínico Universitario Lozano Blesa.<br /

Cambios en los parámetros objetivos y subjetivos de la voz de pacientes con edema de Reinke tras tratamiento quirúrgico.

Introducción: El edema de Reinke (ER) es una enfermedad benigna de las cuerdas vocales (CV) que consiste en la acumulación de líquido en el espacio de Reinke, como consecuencia del hábito tabáquico. Para su diagnóstico basta con observar las CV mediante una laringoscopia indirecta, sin embargo, para obtener datos objetivos y subjetivos de la voz de estos pacientes debemos ampliar el estudio mediante el análisis acústico y escalas perceptuales. A pesar de que el ER puede mejorar con el cese del hábito tabáquico, aquellos pacientes que presentan una disfonía incapacitante pueden ser susceptibles de tratamiento quirúrgico.Objetivos: Analizar los cambios que se producen en los parámetros objetivos (análisis acústico y estudio aerodinámico) y subjetivos (escala GRABS e índice VHI) de la voz de pacientes con ER tras el tratamiento quirúrgico, así como conocer si existe correlación entre los cambios de ambos tipos de parámetros.Material y Métodos: Se trata de un estudio analítico, observacional, longitudinal y prospectivo en el que se realizó un estudio de voz completo (análisis acústico, estudio aerodinámico, escala GRABS y VHI) a 11 pacientes con ER antes de su intervención quirúrgica. La misma evaluación se repitió a los 45 días de la operación, completándose únicamente en cuatro pacientes.Resultados: Los parámetros en los que se observó una mejoría estadísticamente significativa tras la intervención fueron el jitter (p=0,041), el shimmer (p=0,03), el HNR (p=0,034), el SPI (p=0,002) y el VHI (p=0,002). Los cambios en la F0 se correlacionaron significativamente con los ocurridos en las variables G (Grado) y R (aspereza) de la escala GRABS (r= -0,913 y r= -0,822, respectivamente), así como los cambios del VHI con los del TMF (r= -0,766), entre otras correlaciones significativas.Conclusiones: Los hallazgos orientan a que el tratamiento quirúrgico mejora la disfonía producida por el ER, siendo el VHI uno de los parámetros más útiles para cuantificar dicha mejoría.<br /

The Advantage of Arriving First: Characteristic Times in Finite Size Populations of Error-Prone Replicators

We study the evolution of a finite size population formed by mutationally isolated lineages of error-prone replicators in a two-peak fitness landscape. Computer simulations are performed to gain a stochastic description of the system dynamics. More specifically, for different population sizes, we compute the probability of each lineage being selected in terms of their mutation rates and the amplification factors of the fittest phenotypes. We interpret the results as the compromise between the characteristic time a lineage takes to reach its fittest phenotype by crossing the neutral valley and the selective value of the sequences that form the lineages. A main conclusion is drawn: for finite population sizes, the survival probability of the lineage that arrives first to the fittest phenotype rises significantly

Genomics reveals introgression and purging of deleterious mutations in the Arabian leopard (Panthera pardus nimr)

In endangered species, low-genetic variation and inbreeding result from recent population declines. Genetic screenings in endangered populations help to assess their vulnerability to extinction and to create informed management actions toward their conservation efforts. The leopard, Panthera pardus, is a highly generalist predator with currently eight different subspecies. Yet, genomic data are still lacking for the Critically Endangered Arabian leopard (P. p. nimr). Here, we sequenced the whole genome of two Arabian leopards and assembled the most complete genomic dataset for leopards to date. Our phylogenomic analyses show that leopards are divided into two deeply divergent clades: the African and the Asian. Conservation genomic analyses indicate a prolonged population decline, which has led to an increase in inbreeding and runs of homozygosity, with consequent purging of deleterious mutations in both Arabian individuals. Our study represents the first attempt to genetically inform captive breeding programmes for this Critically Endangered subspecies

Core Circadian Clock Genes Regulate Leukemia Stem Cells in AML

Leukemia stem cells (LSCs) have the capacity to self-renew and propagate disease upon serial transplantation in animal models, and elimination of this cell population is required for curative therapies. Here, we describe a series of pooled, in vivo RNAi screens to identify essential transcription factors (TFs) in a murine model of acute myeloid leukemia (AML) with genetically and phenotypically defined LSCs. These screens reveal the heterodimeric, circadian rhythm TFs Clock and Bmal1 as genes required for the growth of AML cells in vitro and in vivo. Disruption of canonical circadian pathway components produces anti-leukemic effects, including impaired proliferation, enhanced myeloid differentiation, and depletion of LSCs. We find that both normal and malignant hematopoietic cells harbor an intact clock with robust circadian oscillations, and genetic knockout models reveal a leukemia-specific dependence on the pathway. Our findings establish a role for the core circadian clock genes in AML.National Institutes of Health (U.S.) (Grant P01 CA066996)National Institutes of Health (U.S.) (Grant R01 HL082945)National Cancer Institute (U.S.) (Grant P30-CA14051

The relationship between the error catastrophe, survival of the flattest, and natural selection

<p>Abstract</p> <p>Background</p> <p>The quasispecies model is a general model of evolution that is generally applicable to replication up to high mutation rates. It predicts that at a sufficiently high mutation rate, quasispecies with higher mutational robustness can displace quasispecies with higher replicative capacity, a phenomenon called "survival of the flattest". In some fitness landscapes it also predicts the existence of a maximum mutation rate, called the error threshold, beyond which the quasispecies enters into error catastrophe, losing its genetic information. The aim of this paper is to study the relationship between survival of the flattest and the transition to error catastrophe, as well as the connection between these concepts and natural selection.</p> <p>Results</p> <p>By means of a very simplified model, we show that the transition to an error catastrophe corresponds to a value of zero for the selective coefficient of the mutant phenotype with respect to the master phenotype, indicating that transition to the error catastrophe is in this case similar to the selection of a more robust species. This correspondence has been confirmed by considering a single-peak landscape in which sequences are grouped with respect to their Hamming distant from the master sequence. When the robustness of a classe is changed by modification of its quality factor, the distribution of the population changes in accordance with the new value of the robustness, although an error catastrophe can be detected at the same values as in the general case. When two quasispecies of different robustness competes with one another, the entry of one of them into error catastrophe causes displacement of the other, because of the greater robustness of the former. Previous works are explicitly reinterpreted in the light of the results obtained in this paper.</p> <p>Conclusions</p> <p>The main conclusion of this paper is that the entry into error catastrophe is a specific case of survival of the flattest acting on phenotypes that differ in the trade-off between replicative ability and mutational robustness. In fact, entry into error catastrophe occurs when the mutant phenotype acquires a selective advantage over the master phenotype. As both entry into error catastrophe and survival of the flattest are caused by natural selection when mutation rate is increased, we propose differentiating between them by the level of selection at which natural selection acts. So we propose to consider the transition to error catastrophe as a phenomenon of intra-quasispecies selection, and survival of the flattest as a phenomenon of inter-quasispecies selection.</p

Mutagenesis-Mediated Virus Extinction: Virus-Dependent Effect of Viral Load on Sensitivity to Lethal Defection

Background: Lethal mutagenesis is a transition towards virus extinction mediated by enhanced mutation rates during viral genome replication, and it is currently under investigation as a potential new antiviral strategy. Viral load and virus fitness are known to influence virus extinction. Here we examine the effect or the multiplicity of infection (MOI) on progeny production of several RNA viruses under enhanced mutagenesis. Results: The effect of the mutagenic base analogue 5-fluorouracil (FU) on the replication of the arenavirus lymphocytic choriomeningitis virus (LCMV) can result either in inhibition of progeny production and virus extinction in infections carried out at low multiplicity of infection (MOI), or in a moderate titer decrease without extinction at high MOI. The effect of the MOI is similar for LCMV and vesicular stomatitis virus (VSV), but minimal or absent for the picornaviruses foot-and-mouth disease virus (FMDV) and encephalomyocarditis virus (EMCV). The increase in mutation frequency and Shannon entropy (mutant spectrum complexity) as a result of virus passage in the presence of FU was more accentuated at low MOI for LCMV and VSV, and at high MOI for FMDV and EMCV. We present an extension of the lethal defection model that agrees with the experimental results. Conclusions: (i) Low infecting load favoured the extinction of negative strand viruses, LCMV or VSV, with an increase of mutant spectrum complexity. (ii) This behaviour is not observed in RNA positive strand viruses, FMDV or EMCV. (iii) The accumulation of defector genomes may underlie the MOI-dependent behaviour. (iv) LCMV coinfections are allowed but superinfection is strongly restricted in BHK-21 cells. (v) The dissimilar effects of the MOI on the efficiency of mutagenic-based extinction of different RNA viruses can have implications for the design of antiviral protocols based on lethal mutagenesis, presently under development. © 2012 Moreno et al.Centro de Biología Molecular Severo Ochoa; Ministerio de Ciencia e Innovación (MICINN); Fundación Ramón ArecesPeer Reviewe

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries