36 research outputs found
Anomalous Diffusion Induced by Cristae Geometry in the Inner Mitochondrial Membrane
Diffusion of inner membrane proteins is a prerequisite for correct functionality of mitochondria. The complicated structure of tubular, vesicular or flat cristae and their small connections to the inner boundary membrane impose constraints on the mobility of proteins making their diffusion a very complicated process. Therefore we investigate the molecular transport along the main mitochondrial axis using highly accurate computational methods. Diffusion is modeled on a curvilinear surface reproducing the shape of mitochondrial inner membrane (IM). Monte Carlo simulations are carried out for topologies resembling both tubular and lamellar cristae, for a range of physiologically viable crista sizes and densities. Geometrical confinement induces up to several-fold reduction in apparent mobility. IM surface curvature per se generates transient anomalous diffusion (TAD), while finite and stable values of projected diffusion coefficients are recovered in a quasi-normal regime for short- and long-time limits. In both these cases, a simple area-scaling law is found sufficient to explain limiting diffusion coefficients for permeable cristae junctions, while asymmetric reduction of the junction permeability leads to strong but predictable variations in molecular motion rate. A geometry-based model is given as an illustration for the time-dependence of diffusivity when IM has tubular topology. Implications for experimental observations of diffusion along mitochondria using methods of optical microscopy are drawn out: a non-homogenous power law is proposed as a suitable approach to TAD. The data demonstrate that if not taken into account appropriately, geometrical effects lead to significant misinterpretation of molecular mobility measurements in cellular curvilinear membranes
Decline of Birds in a Human Modified Coastal Dune Forest Landscape in South Africa
Previous studies demonstrate that old-growth forest remnants and vegetation regenerating after anthropogenic disturbance provide habitat for birds in a human modified coastal dune forest landscape in northern KwaZulu-Natal, South Africa. However, occurrence does not ensure persistence. Based on a 13-year monitoring database we calculated population trends for 37 bird species and general trends in overall bird density in different vegetation types. We evaluated species' characteristics as covariates of population trend and assessed changes in rainfall and proportional area and survey coverage per vegetation type. 76% of species assessed have declined, 57% significantly so at an average rate of 13.9% per year. Overall, bird density has fallen at 12.2% per year across old-growth forest and woody regenerating vegetation types. Changes in proportional area and coverage per vegetation type may partly explain trends for a few species but are unlikely to account for most. Below average rainfall may have contributed to bird declines. However, other possibilities warrant further investigation. Species with larger range extents tended to decline more sharply than did others, and these species may be responding to environmental changes on a broader geographical scale. Our results cast doubt on the future persistence of birds in this human modified landscape. More research is needed to elucidate the mechanisms driving population decline in the study area and to investigate whether the declines identified here are more widespread across the region and perhaps the continent
Plasmodium falciparum Parasites Are Killed by a Transition State Analogue of Purine Nucleoside Phosphorylase in a Primate Animal Model
Plasmodium falciparum causes most of the one million annual deaths from malaria. Drug resistance is widespread and novel agents against new targets are needed to support combination-therapy approaches promoted by the World Health Organization. Plasmodium species are purine auxotrophs. Blocking purine nucleoside phosphorylase (PNP) kills cultured parasites by purine starvation. DADMe-Immucillin-G (BCX4945) is a transition state analogue of human and Plasmodium PNPs, binding with picomolar affinity. Here, we test BCX4945 in Aotus primates, an animal model for Plasmodium falciparum infections. Oral administration of BCX4945 for seven days results in parasite clearance and recrudescence in otherwise lethal infections of P. falciparum in Aotus monkeys. The molecular action of BCX4945 is demonstrated in crystal structures of human and P. falciparum PNPs. Metabolite analysis demonstrates that PNP blockade inhibits purine salvage and polyamine synthesis in the parasites. The efficacy, oral availability, chemical stability, unique mechanism of action and low toxicity of BCX4945 demonstrate potential for combination therapies with this novel antimalarial agent
Evidence-based Kernels: Fundamental Units of Behavioral Influence
This paper describes evidence-based kernels, fundamental units of behavioral influence that appear to underlie effective prevention and treatment for children, adults, and families. A kernel is a behavior–influence procedure shown through experimental analysis to affect a specific behavior and that is indivisible in the sense that removing any of its components would render it inert. Existing evidence shows that a variety of kernels can influence behavior in context, and some evidence suggests that frequent use or sufficient use of some kernels may produce longer lasting behavioral shifts. The analysis of kernels could contribute to an empirically based theory of behavioral influence, augment existing prevention or treatment efforts, facilitate the dissemination of effective prevention and treatment practices, clarify the active ingredients in existing interventions, and contribute to efficiently developing interventions that are more effective. Kernels involve one or more of the following mechanisms of behavior influence: reinforcement, altering antecedents, changing verbal relational responding, or changing physiological states directly. The paper describes 52 of these kernels, and details practical, theoretical, and research implications, including calling for a national database of kernels that influence human behavior
Post-surgery and recovery experiences following one- and two-stage revision for prosthetic joint infection—A qualitative study of patients’ experiences
Qualidade do melão cantaloupe cv. Hy-Mark minimamente processado e armazenado sob refrigeração Quality of cantaloupe melon cv. Hy-Mark minimally processed and refrigerated
A maioria das pesquisas em melão minimamente processado é concentrada no tipo 'cantaloupe', devido à sua importância no mercado internacional. O objetivo deste trabalho foi avaliar a qualidade do melão cantaloupe cv. Hy-Mark minimamente processado. Os frutos foram lavados e sanitizados, sendo em seguida cortados na forma de cubos, imersos em solução de CaCl2, acondicionados em embalagens flexíveis PET (tereftalato de polietileno) e armazenados a 4ºC por 9 dias. O delineamento foi conduzido inteiramente casualizado, com três repetições. A intervalos de três dias, amostras foram coletadas e analisadas quanto a coliformes totais e fecais, e contagem de bactérias aeróbias mesófilas e bolores e leveduras, pH, sólidos solúveis totais, acidez, vitamina C, açúcares redutores totais, atividade de água, firmeza e análise sensorial através do atributo de aceitação global. O melão minimamente processado apresentou boa estabilidade física, físico-química, microbiológica e sensorial, estimando-se em 9 dias a vida útil deste produto a 4ºC.<br>Most of the research into minimally processed melon is focused on cantaloupe melon, due to its importance in the international market. The objective of this work was to evaluate the quality of cantaloupe melon cv. Hy-Mark, minimally processed and refrigerated. Fruits were washed, sanitized, cut and imbedded in a calcium chloride solution and packed in PET and stored at 4ºC during 9 days. At three-day intervals samples were collected and analyzed for total and fecal coliforms, counting of aerobic mesophilic bacterias, molds and yeast, SS (soluble solids), TTA (total titrable acidity), firmness, pH, TRS (total reducing sugar), Aw, vitamin C, color and acceptability. The minimally processed melon showed good overall physical, pyisico-chemical, microbiological and sensorial stability during the storage period