Host-guest system of 4-nerolidylcatechol in 2-hydroxypropyl-beta-cyclodextrin: preparation, characterization and molecular modeling

The interaction of 4-nerolidylcatechol (4-NRC), a potent antioxidant agent, and 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was investigated by the solubility method using Fourier transform infrared (FTIR) methods in addition to UV-Vis, (1)H-nuclear magnetic resonance (NMR) spectroscopy and molecular modeling. The inclusion complexes were prepared using grinding, kneading and freeze-drying methods. According to phase solubility studies in water a B(S)-type diagram was found, displaying a stoichiometry complexation of 2:1 (drug:host) and stability constant of 6494 +/- A 837 M(-1). Stoichiometry was established by the UV spectrophotometer using Job's plot method and, also confirmed by molecular modeling. Data from (1)H-NMR, and FTIR, experiments also provided formation evidence of an inclusion complex between 4-NRC and HP-beta-CD. 4-NRC complexation indeed led to higher drug solubility and stability which could probably be useful to improve its biological properties and make it available to oral administration and topical formulations.

PHYSICAL FACTORS IN B CELL ACTIN DYNAMICS AND ACTIVATION

Cells adapt to their changing world by sensing environmental cues and responding appropriately. This is made possible by complex cascades of biochemical signals that originate at the cell membrane. In the last decade it has become apparent that the origin of these signals can also arise from physical cues in the environment. Our motivation is to investigate the role of physical factors in the cellular response of the B lymphocyte. B cells patrol the body for signs of invading pathogens in the form of antigen on the surface of antigen presenting cells. Binding of antigen with surface proteins initiates biochemical signaling essential to the immune response. Once contact is made, the B cell spreads on the surface of the antigen presenting cell in order to gather as much antigen as possible. The physical mechanisms that govern this process are unexplored. In this research, we examine the role of the physical parameters of antigen mobility and cell surface topography on B cell spreading and activation. Both physical parameters are biologically relevant as immunogens for vaccine design, which can provide laterally mobile and immobile antigens and topographical surfaces. Another physical parameter that influences B cell response and the formation of the cell-cell junction is surface topography. This is biologically relevant as antigen presenting cells have highly convoluted membranes, resulting in variable topography. We found that B cell activation required the formation of antigen-receptor clusters and their translocation within the attachment plane. We showed that cells which failed to achieve these mobile clusters due to prohibited ligand mobility were much less activation competent. To investigate the effect of topography, we use nano- and micro-patterned substrates, on which B cells were allowed to spread and become activated. We found that B cell spreading, actin dynamics, B cell receptor distribution and calcium signaling are dependent on the topographical patterning of the substrate. A quantitative understanding of cellular response to physical parameters is essential to uncover the fundamental mechanisms that drive B cell activation. The results of this research are highly applicable to the field of vaccine development and therapies for autoimmune diseases. Our studies of the physical aspects of lymphocyte activation will reveal the role these factors play in immunity, thus enabling their optimization for biological function and potentially enabling the production of more effective vaccines.

The scientific rationale, design and implementation plan for a Biogeochemical-Argo float array

Biogeochemical-Argo is the extension of the Argo array of profiling floats to include floats that are equipped with biogeochemical sensors for pH, oxygen, nitrate, chlorophyll, suspended particles, and downwelling irradiance. Argo is a highly regarded, international program that measures the changing ocean temperature (heat content) and salinity with profiling floats distributed throughout the ocean. Newly developed sensors now allow profiling floats to also observe biogeochemical properties with sufficient accuracy for climate studies. This extension of Argo will enable an observing system that can determine the seasonal to decadal-scale variability in biological productivity, the supply of essential plant nutrients from deep-waters to the sunlit surface layer, ocean acidification, hypoxia, and ocean uptake of CO2. Biogeochemical-Argo will drive a transformative shift in our ability to observe and predict the effects of climate change on ocean metabolism, carbon uptake, and living marine resource management. Presently, vast areas of the open ocean are sampled only once per decade or less, with sampling occurring mainly in summer. Our ability to detect changes in biogeochemical processes that may occur due to the warming and acidification driven by increasing atmospheric CO2, as well as by natural climate variability, is greatly hindered by this undersampling. In close synergy with satellite systems (which are effective at detecting global patterns for a few biogeochemical parameters, but only very close to the sea surface and in the absence of clouds), a global array of biogeochemical sensors would revolutionize our understanding of ocean carbon uptake, productivity, and deoxygenation. The array would reveal the biological, chemical, and physical events that control these processes. Such a system would enable a new generation of global ocean prediction systems in support of carbon cycling, acidification, hypoxia and harmful algal blooms studies, as well as the management of living marine resources. In order to prepare for a global Biogeochemical-Argo array, several prototype profiling float arrays have been developed at the regional scale by various countries and are now operating. Examples include regional arrays in the Southern Ocean (SOCCOM ), the North Atlantic Sub-polar Gyre (remOcean ), the Mediterranean Sea (NAOS ), the Kuroshio region of the North Pacific (INBOX ), and the Indian Ocean (IOBioArgo ). For example, the SOCCOM program is deploying 200 profiling floats with biogeochemical sensors throughout the Southern Ocean, including areas covered seasonally with ice. The resulting data, which are publically available in real time, are being linked with computer models to better understand the role of the Southern Ocean in influencing CO2 uptake, biological productivity, and nutrient supply to distant regions of the world ocean. The success of these regional projects has motivated a planning meeting to discuss the requirements for and applications of a global-scale Biogeochemical-Argo program. The meeting was held 11-13 January 2016 in Villefranche-sur-Mer, France with attendees from eight nations now deploying Argo floats with biogeochemical sensors present to discuss this topic. In preparation, computer simulations and a variety of analyses were conducted to assess the resources required for the transition to a global-scale array. Based on these analyses and simulations, it was concluded that an array of about 1000 biogeochemical profiling floats would provide the needed resolution to greatly improve our understanding of biogeochemical processes and to enable significant improvement in ecosystem models. With an endurance of four years for a Biogeochemical-Argo float, this system would require the procurement and deployment of 250 new floats per year to maintain a 1000 float array. The lifetime cost for a Biogeochemical-Argo float, including capital expense, calibration, data management, and data transmission, is about $100,000. A global Biogeochemical-Argo system would thus cost about $25,000,000 annually. In the present Argo paradigm, the US provides half of the profiling floats in the array, while the EU, Austral/Asia, and Canada share most the remaining half. If this approach is adopted, the US cost for the Biogeochemical-Argo system would be ~$12,500,000 annually and ~$6,250,000 each for the EU, and Austral/Asia and Canada. This includes no direct costs for ship time and presumes that float deployments can be carried out from future research cruises of opportunity, including, for example, the international GO-SHIP program (http://www.go-ship.org). The full-scale implementation of a global Biogeochemical-Argo system with 1000 floats is feasible within a decade. The successful, ongoing pilot projects have provided the foundation and start for such a system.

Environmental and grazing influence on spatial variability of intertidal biofilm on subtropical rocky shores

Epilithic biofilm on rocky shores is regulated by physico-chemical and biological factors and is important as a source of food for benthic organisms. The influences of environmental and grazing pressure on spatial variability of biomass of biofilm were evaluated on shores on the north coast of São Paulo State (SE Brazil). A general trend of greater abundance of microalgae was observed lower on the shore, but neither of the environmental factors evaluated (wave exposure and shore level) showed consistent effects, and differences were found among specific shores or times (September 2007 and March 2008). The abundance of slow-moving grazers (limpets and littorinids) showed a negative correlation with chlorophyll a concentration on shores. However, experimental exclusion of these grazers failed to show consistent results at small spatial scales. Observations of divergent abundances of the isopod Ligia exotica and biomass of biofilm on isolated boulders on shores led to a short exclusion experiment, where the grazing pressure by L. exotica significantly decreased microalgal biomass. The result suggests that grazing activities of this fast-moving consumer probably mask the influence of slow-moving grazers at small spatial scales, while both have an additive effect at larger scales that masks environmental influences. This is the first evaluation of the impact of the fast-moving herbivore L. exotica on microalgal biomass on rocky shores and opens an interesting discussion about the role of these organisms in subtropical coastal environments.

Metastability and dynamics of stem cells: from direct observations to inference at the single cell level

Organismal development, homeostasis, and pathology are rooted in inherently probabilistic events. From gene expression to cellular differentiation, rates and likelihoods shape the form and function of biology. Processes ranging from growth to cancer homeostasis to reprogramming of stem cells all require transitions between distinct phenotypic states, and these occur at defined rates. Therefore, measuring the fidelity and dynamics with which such transitions occur is central to understanding natural biological phenomena and is critical for therapeutic interventions.

While these processes may produce robust population-level behaviors, decisions are made by individual cells. In certain circumstances, these minuscule computing units effectively roll dice to determine their fate. And while the 'omics' era has provided vast amounts of data on what these populations are doing en masse, the behaviors of the underlying units of these processes get washed out in averages.

Therefore, in order to understand the behavior of a sample of cells, it is critical to reveal how its underlying components, or mixture of cells in distinct states, each contribute to the overall phenotype. As such, we must first define what states exist in the population, determine what controls the stability of these states, and measure in high dimensionality the dynamics with which these cells transition between states.

To address a specific example of this general problem, we investigate the heterogeneity and dynamics of mouse embryonic stem cells (mESCs). While a number of reports have identified particular genes in ES cells that switch between 'high' and 'low' metastable expression states in culture, it remains unclear how levels of many of these regulators combine to form states in transcriptional space. Using a method called single molecule mRNA fluorescent in situ hybridization (smFISH), we quantitatively measure and fit distributions of core pluripotency regulators in single cells, identifying a wide range of variabilities between genes, but each explained by a simple model of bursty transcription. From this data, we also observed that strongly bimodal genes appear to be co-expressed, effectively limiting the occupancy of transcriptional space to two primary states across genes studied here. However, these states also appear punctuated by the conditional expression of the most highly variable genes, potentially defining smaller substates of pluripotency.

Having defined the transcriptional states, we next asked what might control their stability or persistence. Surprisingly, we found that DNA methylation, a mark normally associated with irreversible developmental progression, was itself differentially regulated between these two primary states. Furthermore, both acute or chronic inhibition of DNA methyltransferase activity led to reduced heterogeneity among the population, suggesting that metastability can be modulated by this strong epigenetic mark.

Finally, because understanding the dynamics of state transitions is fundamental to a variety of biological problems, we sought to develop a high-throughput method for the identification of cellular trajectories without the need for cell-line engineering. We achieved this by combining cell-lineage information gathered from time-lapse microscopy with endpoint smFISH for measurements of final expression states. Applying a simple mathematical framework to these lineage-tree associated expression states enables the inference of dynamic transitions. We apply our novel approach in order to infer temporal sequences of events, quantitative switching rates, and network topology among a set of ESC states.

Taken together, we identify distinct expression states in ES cells, gain fundamental insight into how a strong epigenetic modifier enforces the stability of these states, and develop and apply a new method for the identification of cellular trajectories using scalable in situ readouts of cellular state.

Harmonised framework for ecological risk assessment of sediments from ports and estuarine zones of North and South Atlantic

This paper presents a harmonised framework of sediment quality assessment and dredging material characterisation for estuaries and port zones of North and South Atlantic. This framework, based on the weight-of-evidence approach, provides a structure and a process for conducting sediment/dredging material assessment that leads to a decision. The main structure consists of step 1 (examination of available data); step 2 (chemical characterisation and toxicity assessment); decision 1 (any chemical level higher than reference values? are sediments toxic?); step 3 (assessment of benthic community structure); step 4 (integration of the results); decision 2 (are sediments toxic or benthic community impaired?); step 5 (construction of the decision matrix) and decision 3 (is there environmental risk?). The sequence of assessments may be interrupted when the information obtained is judged to be sufficient for a correct characterisation of the risk posed by the sediments/dredging material. This framework brought novel features compared to other sediment/dredging material risk assessment frameworks: data integration through multivariate analysis allows the identification of which samples are toxic and/or related to impaired benthic communities; it also discriminates the chemicals responsible for negative biological effects; and the framework dispenses the use of a reference area. We demonstrated the successful application of this framework in different port and estuarine zones of the North (Gulf of Cadiz) and South Atlantic (Santos and Paranagua Estuarine Systems).

Cortisol Reactivity and Observed Parenting among Mothers of Children with and without ADHD

Parenting is a robust predictor of developmental outcomes among children with ADHD. Early parenting predicts the persistence and course of ADHD and comorbid problems above and beyond risk associated with shared genetic effects. Yet, on average, mothers of children with ADHD are less positive and more negative in their parent-child interactions compared to mothers of non-disordered children. Little is known about psychobiological markers which may be associated with individual variations in maternal parenting in families of children with ADHD. Neurobiological models of parenting suggest that maternal cortisol levels following a stressor may be positively associated with hostile and intrusive parenting; however, to date no studies have examined maternal cortisol reactivity and parenting in school-age, or clinical samples of, children. Mothers’ regulation of physiological stress responses may be particularly important for families of children with ADHD, as parenting a child with chronically challenging behaviors represents a persistent environmental stressor. The current study sought to extend the existing literature by providing an empirical examination of the relationship between maternal cortisol reactivity following two laboratory stressors and parenting among mothers of children with and without ADHD. It was hypothesized that child ADHD group would moderate the relationship between cortisol reactivity and self-reported and observed parenting. Greater total cortisol output and greater increase in cortisol during the TSST were associated with decreased positive parenting and increased negative and directive parenting, with the exception of parental involvement, which was associated with increased cortisol output during the TSST. Conversely, cortisol output during the PCI was associated with increased positive parenting, increased parental involvement, and decreased negative parenting. In contrast to the TSST, a greater decrease in cortisol during the PCI indicated more positive parenting and parental involvement. These associations were specific to mothers of children with ADHD, with the exception of maternal directiveness, which was specific to comparison mothers. Findings add to our understanding of physiological processes associated with maternal parenting and contribute to an integrative biological, psychological, and cognitive process model of parenting in families of children with ADHD.

Generation and screening of natural product-like compounds for antibiotic discovery

Avec l’apparition de plus en plus de souches de bactérie résistante aux antibiotiques, le développement de nouveaux antibiotiques est devenu une important problématique pour les agences de santé. C’est pour cela que la création de nouvelles plateformes pour accélérer la découverte de médicaments est devenu un besoin urgent. Dans les dernières décennies, la recherche était principalement orientée sur la modification de molécules préexistantes, la méta-analyse d’organismes produisant des molécules activent et l’analyse de librairies moléculaires pour trouver des molécules synthétiques activent, ce qui s’est avéré relativement inefficace. Notre but était donc de développer de nouvelles molécules avec des effets thérapeutiques de façon plus efficace à une fraction du prix et du temps comparé à ce qui se fait actuellement. Comme structure de base, nous avons utilisé des métabolites secondaires qui pouvaient altérer le fonctionnement des protéines ou l’interaction entre deux protéines. Pour générer ces molécules, j’ai concentré mes efforts sur les terpènes, une classe de métabolites secondaires qui possède un large éventail d’activités biologiques incluant des activités antibactériennes. Nous avons développé un système de chromosome artificiel de levure (YAC) qui permet à la fois l’assemblage directionnel et combinatoire de gènes qui permet la création de voies de biosynthèse artificielles. Comme preuve de concept, j’ai développé des YACs qui contiennent les gènes pour l’expression des enzymes impliquées dans la biosynthèse de la -carotène et de l’albaflavenone et produit ces molécules avec un haut rendement. Finalement, Des YACs produits à partir de librairies de gènes ont permis de créer une grande diversité de molécules.

Generation and screening of natural product-like compounds for antibiotic discovery

Avec l’apparition de plus en plus de souches de bactérie résistante aux antibiotiques, le développement de nouveaux antibiotiques est devenu une important problématique pour les agences de santé. C’est pour cela que la création de nouvelles plateformes pour accélérer la découverte de médicaments est devenu un besoin urgent. Dans les dernières décennies, la recherche était principalement orientée sur la modification de molécules préexistantes, la méta-analyse d’organismes produisant des molécules activent et l’analyse de librairies moléculaires pour trouver des molécules synthétiques activent, ce qui s’est avéré relativement inefficace. Notre but était donc de développer de nouvelles molécules avec des effets thérapeutiques de façon plus efficace à une fraction du prix et du temps comparé à ce qui se fait actuellement. Comme structure de base, nous avons utilisé des métabolites secondaires qui pouvaient altérer le fonctionnement des protéines ou l’interaction entre deux protéines. Pour générer ces molécules, j’ai concentré mes efforts sur les terpènes, une classe de métabolites secondaires qui possède un large éventail d’activités biologiques incluant des activités antibactériennes. Nous avons développé un système de chromosome artificiel de levure (YAC) qui permet à la fois l’assemblage directionnel et combinatoire de gènes qui permet la création de voies de biosynthèse artificielles. Comme preuve de concept, j’ai développé des YACs qui contiennent les gènes pour l’expression des enzymes impliquées dans la biosynthèse de la -carotène et de l’albaflavenone et produit ces molécules avec un haut rendement. Finalement, Des YACs produits à partir de librairies de gènes ont permis de créer une grande diversité de molécules.

Developmental and physical-fitness associations with gross motor coordination problems in peruvian children

he aims of this cross-sectional study were to examine the developmental characteristics (biological maturation and body size) associated with gross motor coordination problems in 5193 Peruvian children (2787 girls) aged 6–14 years from different geographical locations, and to investigate how the probability that children suffer with gross motor coordination problems varies with physical fitness. Children with gross motor coordination problems were more likely to have lower flexibility and explosive strength levels, having adjusted for age, sex, maturation and study site. Older children were more likely to suffer from gross motor coordination problems, as were those with greater body mass index. However, more mature children were less likely to have gross motor coordination problems, although children who live at sea level or at high altitude were more likely to suffer from gross motor coordination problems than children living in the jungle. Our results provide evidence that children and adolescents with lower physical fitness are more likely to have gross motor coordination difficulties. The identification of youths with gross motor coordination problems and providing them with effective intervention programs is an important priority in order to overcome such developmental problems, and help to improve their general health status.

Cavotricuspid isthmus: anatomy and electrophysiology features: its evaluation before radiofrequency ablation

The cavotricuspid isthmus (CTI) in the lower pan of the right atrium, between the inferior caval vein and the tricuspid valve, is considered crucial in producing a conduction delay and. hence, favoring the perpetuation of a reentrant circuit. Non-uniform wall thickness, muscle fiber orientation and the marked variability in muscular architecture in the CTI should be taken into consideration from the perspective of anisotropic conduction, thus producing an electrophysiologic isthmus. The purpose of this article is to review the anatomy and electrophysiology of the CTI in human hearts to provide useful information to plan CTI radio frequency ablation for the patients with atrial flutter.

Characteristics of microRNAs and their potential relevance for the diagnosis and therapy of the acute respiratory distress syndrome: from bench to bedside

Acute respiratory distress syndrome (ARDS) is a complex disease associated with high morbidity and mortality. Biomarkers and specific pharmacologic treatment of the syndrome are lacking. MicroRNAs (miRNAs) are small (∼19–22 nucleotides) noncoding RNA molecules whose function is the regulation of gene expression. Their uncommon biochemical characteristics (eg, their resistance to degradation because of extreme temperature and pH fluctuations, freeze-thaw cycles, long storage times in frozen conditions, and RNAse digestion) and their presence in a wide range of different biological fluids and the relatively low number of individual miRNAs make these molecules good biomarkers in different clinical conditions. In addition, miRNAs are suitable therapeutic targets as their expression can be modulated by different available strategies. The aim of the present review is to offer clinicians a global perspective of miRNA, covering their structure and nomenclature, biogenesis, effects on gene expression, regulation of expression, and features as disease biomarkers and therapeutic targets, with special attention to ARDS. Because of the early stage of research on miRNAs applied to ARDS, attention has been focused on how knowledge sourced from basic and translational research could inspire future clinical studies.

Detectability of migrating raptors and its effect on bias and precision of trend estimates

Annual counts of migrating raptors at fixed observation points are a widespread practice, and changes in numbers counted over time, adjusted for survey effort, are commonly used as indices of trends in population size. Unmodeled year-to-year variation in detectability may introduce bias, reduce precision of trend estimates, and reduce power to detect trends. We conducted dependent double-observer surveys at the annual fall raptor migration count at Lucky Peak, Idaho, in 2009 and 2010 and applied Huggins closed-capture removal models and information-theoretic model selection to determine the relative importance of factors affecting detectability. The most parsimonious model included effects of observer team identity, distance, species, and day of the season. We then simulated 30 years of counts with heterogeneous individual detectability, a population decline (λ = 0.964), and unexplained random variation in the number of available birds. Imperfect detectability did not bias trend estimation, and increased the time required to achieve 80% power by less than 11%. Results suggested that availability is a greater source of variance in annual counts than detectability; thus, efforts to account for availability would improve the monitoring value of migration counts. According to our models, long-term trends in observer efficiency or migratory flight distance may introduce substantial bias to trend estimates. Estimating detectability with a novel count protocol like our double-observer method is just one potential means of controlling such effects. The traditional approach of modeling the effects of covariates and adjusting the index may also be effective if ancillary data is collected consistently.

Developmental and physical-fitness associations with gross motor coordination problems in peruvian children

he aims of this cross-sectional study were to examine the developmental characteristics (biological maturation and body size) associated with gross motor coordination problems in 5193 Peruvian children (2787 girls) aged 6–14 years from different geographical locations, and to investigate how the probability that children suffer with gross motor coordination problems varies with physical fitness. Children with gross motor coordination problems were more likely to have lower flexibility and explosive strength levels, having adjusted for age, sex, maturation and study site. Older children were more likely to suffer from gross motor coordination problems, as were those with greater body mass index. However, more mature children were less likely to have gross motor coordination problems, although children who live at sea level or at high altitude were more likely to suffer from gross motor coordination problems than children living in the jungle. Our results provide evidence that children and adolescents with lower physical fitness are more likely to have gross motor coordination difficulties. The identification of youths with gross motor coordination problems and providing them with effective intervention programs is an important priority in order to overcome such developmental problems, and help to improve their general health status.

Biological Approaches for Remediation of Metal-Contaminated Sites

Environmental pollution by several heavy metals and metalloids is a severe problem worldwide, as soils became increasingly contaminated, posing a threat to ecosystems and ultimately to human health. Contamination derives from large scale urbanization and industrialization, threatening land ecosystems, surface and groundwater, as well as food safety and human health. Remediation strategies for heavy metal-contaminated sites are necessary to protect from their toxic effects and conserve the environment for future generations. Numerous physicochemical techniques have been adopted including excavation and deposition in landfills, thermal treatment, leaching and electro-reclamation. These techniques are fast but inadequate, costly, cause adverse effects on soil physical, chemical and biological properties, and may lead to secondary pollution. In fact, many of these approaches only change the problem from one form or place to another, and do not completely destroy the pollutants. There was an urgent need to develop new technologies which are cost-effective and eco-friendly. In this context, biological remediation has tremendous potential. It uses plants and microorganisms to remove or contain toxic contaminants and is considered as the most effective method because it is a natural process, environmentally-friendly, has a low cost, and wide public acceptance. The present chapter aims to provide a comprehensive review of some of the promising processes mediated by plant and microbes to remediate metal-contaminated environments. Some biological processes used for the decontamination of organic compounds will also be included because of their relevance and potential common use for both purposes.