Autocrine activity of soluble Flt-1 controls endothelial cell function and angiogenesis

Background - The negative feedback system is an important physiological regulatory mechanism controlling angiogenesis. Soluble vascular endothelial growth factor (VEGF) receptor-1 (sFlt-1), acts as a potent endogenous soluble inhibitor of VEGF- and placenta growth factor (PlGF)-mediated biological function and can also form dominant-negative complexes with competent full-length VEGF receptors. Methods and results - Systemic overexpression of VEGF-A in mice resulted in significantly elevated circulating sFlt-1. In addition, stimulation of human umbilical vein endothelial cells (HUVEC) with VEGF-A, induced a five-fold increase in sFlt-1 mRNA, a time-dependent significant increase in the release of sFlt-1 into the culture medium and activation of the flt-1 gene promoter. This response was dependent on VEGF receptor-2 (VEGFR-2) and phosphoinositide-3'-kinase signalling. siRNA-mediated knockdown of sFlt-1 in HUVEC stimulated the activation of endothelial nitric oxide synthase, increased basal and VEGF-induced cell migration and enhanced endothelial tube formation on growth factor reduced Matrigel. In contrast, adenoviral overexpression of sFlt-1 suppressed phosphorylation of VEGFR-2 at tyrosine 951 and ERK-1/-2 MAPK and reduced HUVEC proliferation. Preeclampsia is associated with elevated placental and systemic sFlt-1. Phosphorylation of VEGFR-2 tyrosine 951 was greatly reduced in placenta from preeclamptic patients compared to gestationally-matched normal placenta. Conclusion - These results show that endothelial sFlt-1 expression is regulated by VEGF and acts as an autocrine regulator of endothelial cell function.

Analysis of protein carbonylation - pitfalls and promise in commonly used methods

Abstract Oxidation of proteins has received a lot of attention in the last decades due to the fact that they have been shown to accumulate and to be implicated in the progression and the patho-physiology of several diseases such as Alzheimer, coronary heart diseases, etc. This has also resulted in the fact that research scientist became more eager to be able to measure accurately the level of oxidized protein in biological materials, and to determine the precise site of the oxidative attack on the protein, in order to get insights into the molecular mechanisms involved in the progression of diseases. Several methods for measuring protein carbonylation have been implemented in different laboratories around the world. However, to date no methods prevail as the most accurate, reliable and robust. The present paper aims at giving an overview of the common methods used to determine protein carbonylation in biological material as well as to highlight the limitations and the potential. The ultimate goal is to give quick tips for a rapid decision making when a method has to be selected and taking into consideration the advantage and drawback of the methods.

New biomarkers and risk stratification in atrial fibrillation:simplicity and practicality matter

Advances in our understanding of pathological mechanisms can inform the identification of various biomarkers for risk stratification, monitoring drug efficacy and toxicity; and enabling careful monitoring of polypharmacy. Biomarkers in the broadest sense refer to 'biological markers' and this can be blood-based (eg. fibrin D-dimer, von Willebrand factor, etc) urine-based (eg. thromboxane), or even related to cardiac or cerebral imaging(1). Most biomarkers offer improvements over clinical risk scores in predicting high risk patients - at least statistically - but usually at the loss of simplicity and practicality for easy application in everyday clinical practice. Given the various biomarkers can be informed by different aspects of pathophysiology (e.g. inflammation, clotting, collagen turnover) they can nevertheless contribute to a better understanding of underlying disease processes(2). Indeed, many age-related diseases share common modifiable underpinning mechanisms e.g. inflammation, oxidative stress and visceral adiposity.

Fiber-type transitions and satellite cell activation in low-frequency-stimulated muscles of young and aging rats

We examined satellite cell content and the activity of satellite cell progeny in tibialis anterior muscles of young (15 weeks) and aging (101 weeks) Brown Norway (BN) rats, after they were exposed for 50 days to a standardized and highly reproducible regime of chronic low-frequency electrical stimulation. Chronic low-frequency electrical stimulation was successful in inducing fast-to-slow fiber-type transformation, characterized by a 2.3-fold increase in the proportion of IIA fibers and fourfold and sevenfold decreases in the proportion of IID/X and IIB fibers in both young and aging BN rats. These changes were accompanied by a twofold increase in the satellite cell content in both the young and aging groups; satellite cell content reached a level that was significantly higher in the young group (p < .04). The total muscle precursor cell content (i.e., satellite cells plus progeny), however, did not differ between groups, because there was a greater number of satellite cell progeny passing through the proliferative and differentiative compartments of the aging group. The resulting 1.5-fold increase in myonuclear content was similar in the young and aging groups. We conclude that satellite cells and satellite cell progeny of aging BN rats possess an unaltered capacity to contribute to the adaptive response.

Advancing the psychology of entrepreneurship:a review of the psychological literature and an introduction

This article provides a narrative review of psychology of entrepreneurship research published in leading psychology journals, based on which we develop an organising framework for future psychological contributions to this field. Furthermore, we introduce the manuscripts collected in this special issue. Our review identified five research areas, broadly corresponding with basic psychological domains, namely personal differences; careers; health and well-being; cognition and behaviour; and leadership; as well as three cross-cutting themes: gender issues; genetic and biological foundations; and context. With the aim to stimulate integration across different approaches and disciplines, we propose a framework to understand how psychologists can offer innovative contributions to the multi-disciplinary entrepreneurship literature. This includes a focus on the entrepreneur embedded in and in interaction with his or her immediate and wider context; attention to different types of entrepreneurs; and a focus on dynamic within-person processes evolving over time.

The non-linear acousto-mechanical and thermodynamic response of spherical absorbers to laser pulses of various temporal profiles

This study is to theoretically investigate shockwave and microbubble formation due to laser absorption by microparticles and nanoparticles. The initial motivation for this research was to understand the underlying physical mechanisms responsible for laser damage to the retina, as well as the predict threshold levels for damage for laser pulses with of progressively shorter durations. The strongest absorbers in the retina are micron size melanosomes, and their absorption of laser light causes them to accrue very high energy density. I theoretically investigate how this absorbed energy is transferred to the surrounding medium. For a wide range of conditions I calculate shockwave generation and bubble growth as a function of the three parameters; fluence, pulse duration and pulse shape. In order to develop a rigorous physical treatment, the governing equations for the behavior of an absorber and for the surrounding medium are derived. Shockwave theory is investigated and the conclusion is that a shock pressure explanation is likely to be the underlying physical cause of retinal damage at threshold fluences for sub-nanosecond pulses. The same effects are also expected for non-biological micro and nano absorbers. ^

The effects of parental nurturance and involvement on peer relationships and psychosocial functioning of young adults

This study examined peer relationships and psychosocial functioning as a function of maternal and paternal involvement and nurturance along with the moderating effects of gender, family form, and ethnicity. Prior research has shown the influence of mother’s involvement on peer relationship quality but not of fathers. Further, previous studies did not examine moderation by family form, gender, or ethnicity. The sample consisted of 1359 students who identified their biological mother and father as the most influential parental figures in their lives. Their ages ranged from 18 to 26; Sixty-one percent of the sample was Hispanic, 13% non-Hispanic Black, 25% non-Hispanic White; 76% female and 70% from intact families. The analytical strategy included using bivariate correlations and structural equation modeling to examine these relationships. ^ All dimensions of maternal and paternal nurturing and involvement were positively related to positive characteristics of peer relationships, self-esteem and life satisfaction consistent with the multicultural findings of PARTheory (Rohner, Khalique, & Cournoyer, 2005). A structural model was developed that was able to adequately account for the relationship between parental influence, peer relationships, and psychosocial functioning. These effects of both maternal and paternal influence were strongly moderated by culture, family form, and gender. Finally, a differential effect was found among parental influence with fathers having a greater influence on friendship quality and importance than mothers, despite greater maternal involvement. ^ These findings have theoretical, clinical, and social implications as they call for a socially based theoretical perspective within which to study these relationships. Such a perspective would better inform clinicians when using impaired social functioning as indicative of axial diagnosis, and for the implementation of social policy to encourage paternal involvement. ^

Alligators and crocodiles as indicators for restoration of Everglades ecosystems

Alligators and crocodiles integrate biological impacts of hydrological operations, affecting them at all life stages through three key aspects of Everglades ecology: (1) food webs, (2) diversity and productivity, and (3) freshwater flow. Responses of crocodilians are directly related to suitability of environmental conditions and hydrologic change. Correlations between biological responses and environmental conditions contribute to an understanding of species’ status and trends over time. Positive or negative trends of crocodilian populations relative to hydrologic changes permit assessment of positive or negative trends in restoration. The crocodilian indicator uses monitoring parameters (performance measures) that have been shown to be both effective and efficient in tracking trends. The alligator component uses relative density (reported as an encounter rate), body condition, and occupancy rates of alligator holes; the crocodile component uses juvenile growth and hatchling survival. We hypothesize that these parameters are correlated with hydrologic conditions including depth, duration, timing, spatial extent and water quality. Salinity is a critical parameter in estuarine habitats. Assessments of parameters defined for crocodilian performance measures support these hypotheses. Alligators and crocodiles are the charismatic megafauna of the Everglades. They are both keystone and flagship species to which the public can relate. In addition, the parameters used to track trends are easy to understand. They provide answers to the following questions: How has the number of alligators or crocodiles changed? Are the animals fatter or thinner than they should be? Are the animals in the places (in terms of habitat and geography) where they should be? As surely as there is no other Everglades, no other single species defines the Everglades as does the American alligator. The Everglades is the only place in the world where both alligators and crocodiles exist. Crocodilians clearly respond to changes in hydrologic parameters of management interest. These relationships are easy to communicate and mean something to managers, decision makers, and the public. Having crocodilians on the list of system-wide, general indicators provides us with one of the most powerful tools we have to communicate progress of ecosystem restoration in Greater Everglades ecosystems to diverse audiences.

Interval and Point Estimators for the Location Parameter of the Three-Parameter Lognormal Distribution

The three-parameter lognormal distribution is the extension of the two-parameter lognormal distribution to meet the need of the biological, sociological, and other fields. Numerous research papers have been published for the parameter estimation problems for the lognormal distributions. The inclusion of the location parameter brings in some technical difficulties for the parameter estimation problems, especially for the interval estimation. This paper proposes a method for constructing exact confidence intervals and exact upper confidence limits for the location parameter of the three-parameter lognormal distribution. The point estimation problem is discussed as well. The performance of the point estimator is compared with the maximum likelihood estimator, which is widely used in practice. Simulation result shows that the proposed method is less biased in estimating the location parameter. The large sample size case is discussed in the paper.

Biomarker Assessment of Spatial and Temporal Changes in the Composition of Flocculent Material (Floc) in the Subtropical Wetland of the Florida Coastal Everglades

Flocculent material (floc) is an important energy source in wetlands. In the Florida Everglades, floc is present in both freshwater marshes and coastal environments and plays a key role in food webs and nutrient cycling. However, not much is known about its environmental dynamics, in particular its biological sources and bio-reactivity. We analysed floc samples collected from different environments in the Florida Everglades and applied biomarkers and pigment chemotaxonomy to identify spatial and seasonal differences in organic matter sources. An attempt was made to link floc composition with algal and plant productivity. Spatial differences were observed between freshwater marsh and estuarine floc. Freshwater floc receives organic matter inputs from local periphyton mats, as indicated by microbial biomarkers and chlorophyll-a estimates. At the estuarine sites, the floc is dominated by mangrove as well as diatom inputs from the marine end-member. The hydroperiod (duration and depth of inundation) at the freshwater sites influences floc organic matter preservation, where the floc at the short-hydroperiod site is more oxidised likely due to periodic dry-down conditions. Seasonal differences in floc composition were not consistent and the few that were observed are likely linked to the primary productivity of the dominant biomass (periphyton in the freshwater marshes and mangroves in the estuarine zone). Molecular evidence for hydrological transport of floc material from the freshwater marshes to the coastal fringe was also observed. With the on-going restoration of the Florida Everglades, it is important to gain a better understanding of the biogeochemical dynamics of floc, including its sources, transformations and reactivity.

Location and ages of terrestrial peatlands located on continental shelves and in coastal sediments

This synthesis dataset contains records of freshwater peat and lake sediments from continental shelves and coastal areas. Information included is site location (when available), thickness and description of terrestrial sediments as well as underlying and overlying sediments, dates (when available), and references.

Fast pyrolysis of biomass for energy and fuels

Bioenergy is now accepted as having the potential to provide the major part of the projected renewable energy provisions of the future as biofuels in the form of gas, liquid or solid fuels or electricity and heat. There are three main routes to providing these biofuels — thermal conversion, biological conversion and physical conversion — all of which employ a range of chemical reactor configurations and process designs. This paper focuses on fast pyrolysis from which the liquid, often referred to as bio-oil, can be used on-site or stored or transported to centralised and/or remote user facilities for utilisation for example as a fuel, or further processing to biofuels and/or chemicals. This offers the potential for system optimisation, much greater economies of scale and exploitation of the concepts of biorefineries. The technology of fast pyrolysis is described, particularly the reactors that have been developed to provide the necessary conditions to optimise performance. The primary liquid product is characterised, as well as the secondary products of electricity and/or heat, liquid fuels and a considerable number of chemicals. The main technical and non-technical barriers to the market deployment of the various technologies are identified and briefly discussed.

Highly stable PEGylated gold nanoparticles in water: applications in biology and catalysis

Gold nanoparticles (Au NPs) with diameters ranging between 5-60 nm have been synthesised in water, and further stabilized with polyethylene glycol-based thiol polymers (mPEG-SH). Successful PEGylation of the Au NPs was confirmed by Dynamic Light scattering (DLS) and Zeta potential measurements. PEG coating of the Au NPs is the key of their colloidal stabilty, and its successful applications. Catalytic efficiency testing of the PEG-AuNPs were carried out on homocoupling of boronic acid. PEG-Au NPs with AuNps diameter < 30 nm were useful as catalyst in water. Finally, the PEG-Au NPs were also shown to be stable in biological fluid and not cytotoxic on B16.F10 cell line, making them attractive for further studies.

Contributions of Dorsal/Ventral Hippocampus and Dorsolateral/Dorsomedial Striatum to Interval Timing

Humans and animals have remarkable capabilities in keeping time and using time as a guide to orient their learning and decision making. Psychophysical models of timing and time perception have been proposed for decades and have received behavioral, anatomical and pharmacological data support. However, despite numerous studies that aimed at delineating the neural underpinnings of interval timing, a complete picture of the neurobiological network of timing in the seconds-to-minutes range remains elusive. Based on classical interval timing protocols and proposing a Timing, Immersive Memory and Emotional Regulation (TIMER) test battery, the author investigates the contributions of the dorsal and ventral hippocampus as well as the dorsolateral and the dorsomedial striatum to interval timing by comparing timing performances in mice after they received cytotoxic lesions in the corresponding brain regions. On the other hand, a timing-based theoretical framework for the emergence of conscious experience that is closely related to the function of the claustrum is proposed so as to serve both biological guidance and the research and evolution of “strong” artificial intelligence. Finally, a new “Double Saturation Model of Interval Timing” that integrates the direct- and indirect- pathways of striatum is proposed to explain the set of empirical findings.

Genetics and the Life Course

A life-course perspective is committed to the proposition that from conception to death, all human outcomes are the result of a continual interaction between the indi- vidual and all of the environments that he or she inhabits at any given point in time. Early development is a critical period, a window of time during the life course when a given exposure can have a critical or permanent in uence on later outcomes. But the impact of exposures upon outcomes does not end at any speci c point in time, inasmuch as life is a continuing interactive and adaptive process. We now know that what applies to human beings also applies to their genomes. The “outcome” of any gene at any given point in time (whether or not it is used to transcribe a particular protein, what form of that protein, and how much) is a product of the interaction between the gene and the multiple environments of which it is a part, which include the epigenome, the cell, the biological human, and the assorted environments he or she occupies (e.g., geographical, socioeconomic, ethnic, etc.). Early life experiences can permanently “reprogram” the epigenome and gene transcription with life-long behavioral consequences. At the same time, the epigenome as well as the genome continue to be environmentally responsive throughout the life course.