Clarifying the relationship between metformin, acute kidney injury and lactic acidosis

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The role of asymmetric interactions on the effect of habitat destruction in mutualistic networks

Plant-pollinator mutualistic networks are asymmetric in their interactions: specialist plants are pollinated by generalist animals, while generalist plants are pollinated by a broad involving specialists and generalists. It has been suggested that this asymmetric ---or disassortative--- assemblage could play an important role in determining the equal susceptibility of specialist and generalist plants under habitat destruction. At the core of the argument lies the observation that specialist plants, otherwise candidates to extinction, could cope with the disruption thanks to their interaction with generalist pollinators. We present a theoretical framework that supports this thesis. We analyze a dynamical model of a system of mutualistic plants and pollinators, subject to the destruction of their habitat. We analyze and compare two families of interaction topologies, ranging from highly assortative to highly disassortative ones, as well as real pollination networks. We found that several features observed in natural systems are predicted by the mathematical model. First, there is a tendency to increase the asymmetry of the network as a result of the extinctions. Second, an entropy measure of the differential susceptibility to extinction of specialist and generalist species show that they tend to balance when the network is disassortative. Finally, the disappearance of links in the network, as a result of extinctions, shows that specialist plants preserve more connections than the corresponding plants in an assortative system, enabling them to resist the disruption.Comment: 14 pages, 7 figure

Síntomas de pacientes antes de la primera hospitalización por Síndrome Coronario Agudo

Este estudo objetivou caracterizar os pacientes quanto ao relato da presença de sintomas de dor torácica, dispneia e limitação das atividades diárias uma semana antes da primeira hospitalização por Síndrome Coronariana Aguda, segundo a forma de apresentação clínica, e compará-las. Estudo transversal, descritivo e correlacional. Utilizou-se um instrumento de avaliação clínica que investigou a presença e a gravidade dos sintomas de dispneia, precordialgia e restrição física decorrentes da isquemia do miocárdio. Com relação à limitação para realização de atividades físicas, pacientes com diagnóstico de angina instável mostraram maior comprometimento na semana que antecedeu a internação, assim como relataram a presença de dispneia e precordialgia com maior frequência do que os pacientes infartados em situações que vão desde realizarem grandes esforços como, por exemplo, caminhar na subida ou muito rápido no plano, até situações de repouso ou de pequenos esforços.The objective of this study was to characterize and compare patients regarding their report of experiencing chest pain, dyspnea and limitation of the daily life activities one week before their first hospitalization due to Acute Coronary Syndrome, according to the clinical presentation form, and compare them. This is a cross-sectional, descriptive and correlational study. A clinical evaluation instrument was used to investigate the presence and severity of dyspnea, chest pain and physical restriction due to myocardial ischemia. Regarding the limitation to carry out physical activities, patients diagnosed with unstable angina showed lower capacity the week before hospitalization, and reported experiencing dyspnea and chest pain more frequently than patients who had an infarction in situations ranging from making strong efforts, such as walking uphill or on a flat surface but very quickly, to resting and in situations of little effort.Estudio que objetivó caracterizar a pacientes en cuanto al relato de presencia de síntomas de dolor torácico, disnea y limitación de actividades diarias una semana antes de la primera hospitalización por Síndrome Coronario Agudo, según la forma de presentación clínica, y compararlas. Estudio transversal, descriptivo y correlacional. Se utilizó un instrumento de evaluación clínica que investigó la presencia y gravedad de síntomas de disnea, precordialgia y restricción física derivadas de isquemia de miocardio. En relación a limitaciones para realización de actividades físicas, pacientes con diagnóstico de angina inestable mostraron mayor compromiso en la semana que antecedió a la internación, así como relataron la presencia de disnea y precordialgia con mayor frecuencia que en los pacientes infartados en situaciones tales como realizar grandes esfuerzos como, por ejemplo, caminar en pendiente ascendiente o muy rápido en el llano, hasta situaciones de reposo o pequeños esfuerzos

Enhanced insulin sensitivity associated with provision of mono and polyunsaturated fatty acids in skeletal muscle cells involves counter modulation of PP2A

International audienceAims/Hypothesis: Reduced skeletal muscle insulin sensitivity is a feature associated with sustained exposure to excess saturated fatty acids (SFA), whereas mono and polyunsaturated fatty acids (MUFA and PUFA) not only improve insulin sensitivity but blunt SFA-induced insulin resistance. The mechanisms by which MUFAs and PUFAs institute these favourable changes remain unclear, but may involve stimulating insulin signalling by counter-modulation/repression of protein phosphatase 2A (PP2A). This study investigated the effects of oleic acid (OA; a MUFA), linoleic acid (LOA; a PUFA) and palmitate (PA; a SFA) in cultured myotubes and determined whether changes in insulin signalling can be attributed to PP2A regulation. Principal Findings: We treated cultured skeletal myotubes with unsaturated and saturated fatty acids and evaluated insulin signalling, phosphorylation and methylation status of the catalytic subunit of PP2A. Unlike PA, sustained incubation of rat or human myotubes with OA or LOA significantly enhanced Akt-and ERK1/2-directed insulin signalling. This was not due to heightened upstream IRS1 or PI3K signalling nor to changes in expression of proteins involved in proximal insulin signalling, but was associated with reduced dephosphorylation/inactivation of Akt and ERK1/2. Consistent with this, PA reduced PP2Ac demethylation and tyrosine 307 phosphorylation-events associated with PP2A activation. In contrast, OA and LOA strongly opposed these PA-induced changes in PP2Ac thus exerting a repressive effect on PP2A.Conclusions/Interpretation: Beneficial gains in insulin sensitivity and the ability of unsaturated fatty acids to oppose palmitate-induced insulin resistance in muscle cells may partly be accounted for by counter-modulation of PP2A

Environmental Conditions Influence Allometric Patterns in the Blow Fly, Chrysomya albiceps

The objective of this research was to study variations in allometry of body characters in females and males of two populations of blow flies, Chrysomya albiceps (Wiedemann) (Diptera: Calliphoridae), under different environmental conditions to establish patterns of morphological variation. Body size of both males and females in the experimental population was significantly higher than in the individuals of the natural population, indicating an important influence of food on body size. All genitalic and non-genitalic characters in males and females of the two populations showed a trend towards negative allometry rather than isometry. Allometric patterns were modified in both sexes and between populations. The data show generally larger allometric slopes in females than in males. We confirmed that the environmental conditions have an important effect on allometric patterns and body size

CagI Is an Essential Component of the Helicobacter pylori Cag Type IV Secretion System and Forms a Complex with CagL

Helicobacter pylori, the causative agent of type B gastritis, peptic ulcers, gastric adenocarcinoma and MALT lymphoma, uses the Cag type IV secretion system to induce a strong proinflammatory response in the gastric mucosa and to inject its effector protein CagA into gastric cells. CagA translocation results in altered host cell gene expression profiles and cytoskeletal rearrangements, and it is considered as a major bacterial virulence trait. Recently, it has been shown that binding of the type IV secretion apparatus to integrin receptors on target cells is a crucial step in the translocation process. Several bacterial proteins, including the Cag-specific components CagL and CagI, have been involved in this interaction. Here, we have examined the localization and interactions of CagI in the bacterial cell. Since the cagI gene overlaps and is co-transcribed with the cagL gene, the role of CagI for type IV secretion system function has been difficult to assess, and conflicting results have been reported regarding its involvement in the proinflammatory response. Using a marker-free gene deletion approach and genetic complementation, we show now that CagI is an essential component of the Cag type IV secretion apparatus for both CagA translocation and interleukin-8 induction. CagI is distributed over soluble and membrane-associated pools and seems to be partly surface-exposed. Deletion of several genes encoding essential Cag components has an impact on protein levels of CagI and CagL, suggesting that both proteins require partial assembly of the secretion apparatus. Finally, we show by co-immunoprecipitation that CagI and CagL interact with each other. Taken together, our results indicate that CagI and CagL form a functional complex which is formed at a late stage of secretion apparatus assembly

Finite Size Effects in Simulations of Protein Aggregation

It is becoming increasingly clear that the soluble protofibrillar species that proceed amyloid fibril formation are associated with a range of neurodegenerative disorders such as Alzheimer's and Parkinson diseases. Computer simulations of the processes that lead to the formation of these oligomeric species are starting to make significant contributions to our understanding of the determinants of protein aggregation. We simulate different systems at constant concentration but with a different number of peptides and we study the how the finite number of proteins affects the underlying free energy of the system and therefore the relative stability of the species involved in the process. If not taken into account, this finite size effect can undermine the validity of theoretical predictions regarding the relative stability of the species involved and the rates of conversion from one to the other. We discuss the reasons that give rise to this finite size effect form both a probabilistic and energy fluctuations point of view and also how this problem can be dealt by a finite size scaling analysis

Shape - but Not Size - Codivergence between Male and Female Copulatory Structures in Onthophagus Beetles

Genitalia are among the fastest evolving morphological traits in arthropods. Among the many hypotheses aimed at explaining this observation, some explicitly or implicitly predict concomitant male and female changes of genital traits that interact during copulation (i.e., lock and key, sexual conflict, cryptic female choice and pleiotropy). Testing these hypotheses requires insights into whether male and female copulatory structures that physically interact during mating also affect each other's evolution and patterns of diversification. Here we compare and contrast size and shape evolution of male and female structures that are known to interact tightly during copulation using two model systems: (a) the sister species O. taurus (1 native, 3 recently established populations) and O. illyricus, and (b) the species-complex O. fracticornis-similis-opacicollis. Partial Least Squares analyses indicated very little to no correlation between size and shape of copulatory structures, both in males and females. Accordingly, comparing shape and size diversification patterns of genitalia within each sex showed that the two components diversify readily - though largely independently of each other - within and between species. Similarly, comparing patterns of divergence across sexes showed that relative sizes of male and female copulatory organs diversify largely independent of each other. However, performing this analysis for genital shape revealed a signature of parallel divergence. Our results therefore suggest that male and female copulatory structures that are linked mechanically during copulation may diverge in concert with respect to their shapes. Furthermore, our results suggest that genital divergence in general, and co-divergence of male and female genital shape in particular, can evolve over an extraordinarily short time frame. Results are discussed in the framework of the hypotheses that assume or predict concomitant evolutionary changes in male and female copulatory organs

Regulated Expression of CCL21 in the Prostate Tumor Microenvironment Inhibits Tumor Growth and Metastasis in an Orthotopic Model of Prostate Cancer

Currently there are no curative therapies available for patients with metastatic prostate cancer. Thus, novel therapies are needed to treat this patient population. Immunotherapy represents one promising approach for the elimination of occult metastatic tumors. However, the prostate tumor microenvironment (TME) represents a hostile environment capable of suppressing anti-tumor immunity and effector cell function. In view of this immunosuppressive activity, we engineered murine prostate cancer cells with regulated expression (tet-on) of CCL21. Prostate tumor cells implanted orthotopically produced primary prostate tumors with predictable metastatic disease in draining lymph nodes and distant organs. Expression of CCL21 in the prostate TME enhanced survival, inhibited tumor growth and decreased the frequency of local (draining lymph node) and distant metastasis. Therefore, these studies provide a strong rationale for further evaluation of CCL21 in tumor immunity and its use in cancer immunotherapy