Planar solar concentrator featuring alignment-free total-internal-reflection collectors and an innovative compound tracker.
This study proposed a planar solar concentrator featuring alignment-free total-internal-reflection (TIR) collectors and an innovative compound tracker. The compound tracker, combining a mechanical single-axis tracker and scrollable prism sheets, can achieve a performance on a par with dual-axis tracking while reducing the cost of the tracking system and increasing its robustness. The alignment-free TIR collectors are assembled on the waveguide without requiring alignment, so the planar concentrator is relatively easily manufactured and markedly increases the feasibility for use in large concentrators. Further, the identical TIR collector is applicable to various-sized waveguide slab without requiring modification, which facilitates flexibility regarding the size of the waveguide slab. In the simulation model, the thickness of the slab was 2 mm, and its maximal length reached 6 m. With an average angular tolerance of ±0.6°, and after considering both the Fresnel loss and the angular spread of the sun, the simulation indicates that the waveguide concentrator of a 1000-mm length provides the optical efficiencies of 62-77% at the irradiance concentrations of 387-688, and the one of a 2000-mm length provides the optical efficiencies of 52-64.5% at the irradiance concentrations of 645-1148. Alternatively, if a 100-mm horizontally staggered waveguide slab is collocated with the alignment-free TIR collectors, the optical efficiency would be greatly improved up to 91.5% at an irradiance concentration of 1098 (C(geo) = 1200X).


Nutrition guidelines for strength sports: sprinting, weightlifting, throwing events, and bodybuilding.
Strength and power athletes are primarily interested in enhancing power relative to body weight and thus almost all undertake some form of resistance training. While athletes may periodically attempt to promote skeletal muscle hypertrophy, key nutritional issues are broader than those pertinent to hypertrophy and include an appreciation of the sports supplement industry, the strategic timing of nutrient intake to maximize fuelling and recovery objectives, plus achievement of pre-competition body mass requirements. Total energy and macronutrient intakes of strength-power athletes are generally high but intakes tend to be unremarkable when expressed relative to body mass. Greater insight into optimization of dietary intake to achieve nutrition-related goals would be achieved from assessment of nutrient distribution over the day, especially intake before, during, and after exercise. This information is not readily available on strength-power athletes and research is warranted. There is a general void of scientific investigation relating specifically to this unique group of athletes. Until this is resolved, sports nutrition recommendations for strength-power athletes should be directed at the individual athlete, focusing on their specific nutrition-related goals, with an emphasis on the nutritional support of training.


The staging model in schizophrenia, and its clinical implications.
Illnesses which develop in a complex way are best described in stages, and those stages will describe not only a particular point in the course of the disease but also the appropriate treatment for that stage. This approach has, over the years, proved to be very appropriate for planning the treatment of various cancers. It is suggested that in the same way, it can be very important in planning the treatment of a complex illness such as schizophrenia. We aim to describe the staging model of schizophrenia, show the neuroimaging and clinical evidence for it, and discuss its implications for treatment. We propose that the development of schizophrenia can be described in at least three stages; the prodrome, the first episode, and the chronic phase. In order to describe these stages, we will use data derived wherever possible from literature published in Europe, and we will compare this with data produced from other continents of the world, notably Australia. This is done by reference to and examination of the original published literature, in order that this evidence may be tested against criteria for evidence of a staging model which we propose. There is much data, from clinical studies which show that schizophrenia develops over time and that its presentation can be described in at least three stages in the development of a schizophrenic illness; the prodrome, the first episode, and the long term chronic phase. It is also true that there is a pre-morbid phase before the prodrome, where it is possible to identify delays in such signs of early neurodevelopment as early paediatric milestones which may suggest an increased risk of schizophrenia in the future. This is mirrored in descriptions of the MRI findings, with loss of gray matter beginning in the prodrome, as well as in changes in cognition which develop as the illness develops over time. It follows from this model that treatment is different in all these three stages, and that the expected outcome of treatment will be different in each of the various stages of the illness. In all the phases of the illness, evidence based psychological interventions, including psycho-education, cognitive therapy, family interventions, and other interventions to prevent relapse work together with medication in order to optimise treatment. Consequently, any attempt to optimise treatment in schizophrenia must take into account the different stages of the illness, and target outcomes must be appropriate for these stages. The treatments, both pharmacological and psychological must be appropriate to the stage of the disease. The application of treatment protocols which are inappropriate to the stage of the disease may lead to sub-optimal outcomes, and even to iatrogenic harm.


Experimental, theoretical and computational investigation of the inelastic neutron scattering spectrum of a homonuclear diatomic molecule in a nearly spherical trap: H2@C60.
In this paper we report a methodology for calculating the inelastic neutron scattering spectrum of homonuclear diatomic molecules confined within nano-cavities of spherical symmetry. The method is based on the expansion of the confining potential into multipoles of the coupled rotational and translational angular variables. The Hamiltonian and the INS transition probabilities are evaluated analytically. The method affords a fast and computationally inexpensive way to simulate the inelastic neutron scattering spectrum of molecular hydrogen confined in fullerene cages. The potential energy surface is effectively parametrized in terms of few physical parameters comprising an harmonic term, anharmonic corrections and translation-rotation couplings. The parameters are refined by matching the simulations against the experiments and the excitation modes are identified for transfer energies up to 215 meV.


A unique phenotype of skin-associated lymphocytes in humans. Preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneous sites.
It has been proposed that the skin is a functionally unique compartment of the immune system, although little direct evidence supporting this hypothesis has been presented. Here we show that lymphocyte populations at cutaneous sites can be differentiated from otherwise similar populations at noncutaneous sites by their preferential expression of an epitope defined by the MAb HECA-452. This MAb recognizes a predominantly 200-kd cell-surface glycoprotein present on about 16% of peripheral blood T cells, including both CD4+ and CD8+ T cells (17% and 11% HECA-452+, respectively), as well as TCR-delta-bearing T cells (32%+). Most thymocytes (99%) lacked HECA-452 antigen expression, and essentially all the HECA-452+ peripheral blood T cells were found in the adhesion molecule high, CD45R low putative memory cell subset, findings suggesting that HECA-452 expression develops peripherally as a consequence of antigenic stimulation. However, the HECA-452 antigen is not a conventional activation antigen because it was not upregulated with mitogen stimulation of peripheral blood T cells. Most significantly, among 54 diverse specimens of normal/reactive lymphoid tissues and sites of chronic inflammation, there was a clear association of lymphocyte HECA-452 expression and cutaneous location. In extracutaneous sites (n = 38) only about 5% of lymphocytes within the T-cell areas of these tissues expressed this antigen, whereas in inflammatory skin lesions (n = 16), 85% were HECA-452+. The association of HECA-452 expression and cutaneous location was also seen in a series of T-cell lymphomas. The malignant cells of 16 of 18 cases of epidermotropic (patch/plaque) stage mycosis fungoides were HECA-452+, as well as 2 of 7 nonmycosis fungoides peripheral T-cell lymphomas in skin. In contrast, this antigen was not expressed in thymic (lymphoblastic) lymphomas (n = 14), nonepidermotropic (tumor) stage mycosis fungoides (n = 5), and noncutaneous peripheral T-cell lymphomas (n = 15). Among lymphocytes, the preferential expression of the HECA-452 determinant by cutaneous T cells supports the hypothesis that the skin constitutes a immunologically unique lymphoid tissue and suggests that this molecule may play a role in either lymphocyte homing to skin or in lymphocyte interactions with the epidermis.


Climate mitigation and the future of tropical landscapes.
Land-use change to meet 21st-century demands for food, fuel, and fiber will depend on many interactive factors, including global policies limiting anthropogenic climate change and realized improvements in agricultural productivity. Climate-change mitigation policies will alter the decision-making environment for land management, and changes in agricultural productivity will influence cultivated land expansion. We explore to what extent future increases in agricultural productivity might offset conversion of tropical forest lands to crop lands under a climate mitigation policy and a contrasting no-policy scenario in a global integrated assessment model. The Global Change Assessment Model is applied here to simulate a mitigation policy that stabilizes radiative forcing at 4.5 W m(-2) (approximately 526 ppm CO(2)) in the year 2100 by introducing a price for all greenhouse gas emissions, including those from land use. These scenarios are simulated with several cases of future agricultural productivity growth rates and the results downscaled to produce gridded maps of potential land-use change. We find that tropical forests are preserved near their present-day extent, and bioenergy crops emerge as an effective mitigation option, only in cases in which a climate mitigation policy that includes an economic price for land-use emissions is in place, and in which agricultural productivity growth continues throughout the century. We find that idealized land-use emissions price assumptions are most effective at limiting deforestation, even when cropland area must increase to meet future food demand. These findings emphasize the importance of accounting for feedbacks from land-use change emissions in global climate change mitigation strategies.


Geographic barriers isolate endemic populations of hyperthermophilic archaea.
Barriers to dispersal between populations allow them to diverge through local adaptation or random genetic drift. High-resolution multilocus sequence analysis revealed that, on a global scale, populations of hyperthermophilic microorganisms are isolated from one another by geographic barriers and have diverged over the course of their recent evolutionary history. The identification of a biogeographic pattern in the archaeon Sulfolobus challenges the current model of microbial biodiversity in which unrestricted dispersal constrains the development of global species richness.


Rewiring and regulation of cross-compartmentalized metabolism in protists.
Plastid acquisition, endosymbiotic associations, lateral gene transfer, organelle degeneracy or even organelle loss influence metabolic capabilities in many different protists. Thus, metabolic diversity is sculpted through the gain of new metabolic functions and moderation or loss of pathways that are often essential in the majority of eukaryotes. What is perhaps less apparent to the casual observer is that the sub-compartmentalization of ubiquitous pathways has been repeatedly remodelled during eukaryotic evolution, and the textbook pictures of intermediary metabolism established for animals, yeast and plants are not conserved in many protists. Moreover, metabolic remodelling can strongly influence the regulatory mechanisms that control carbon flux through the major metabolic pathways. Here, we provide an overview of how core metabolism has been reorganized in various unicellular eukaryotes, focusing in particular on one near universal catabolic pathway (glycolysis) and one ancient anabolic pathway (isoprenoid biosynthesis). For the example of isoprenoid biosynthesis, the compartmentalization of this process in protists often appears to have been influenced by plastid acquisition and loss, whereas for glycolysis several unexpected modes of compartmentalization have emerged. Significantly, the example of trypanosomatid glycolysis illustrates nicely how mathematical modelling and systems biology can be used to uncover or understand novel modes of pathway regulation.


Prediction of survival to discharge following cardiopulmonary resuscitation using classification and regression trees.
To predict the likelihood that an inpatient who experiences cardiopulmonary arrest and undergoes cardiopulmonary resuscitation survives to discharge with good neurologic function or with mild deficits (Cerebral Performance Category score = 1). Classification and Regression Trees were used to develop branching algorithms that optimize the ability of a series of tests to correctly classify patients into two or more groups. Data from 2007 to 2008 (n = 38,092) were used to develop candidate Classification and Regression Trees models to predict the outcome of inpatient cardiopulmonary resuscitation episodes and data from 2009 (n = 14,435) to evaluate the accuracy of the models and judge the degree of over fitting. Both supervised and unsupervised approaches to model development were used. 366 hospitals participating in the Get With the Guidelines-Resuscitation registry. Adult inpatients experiencing an index episode of cardiopulmonary arrest and undergoing cardiopulmonary resuscitation in the hospital. The five candidate models had between 8 and 21 nodes and an area under the receiver operating characteristic curve from 0.718 to 0.766 in the derivation group and from 0.683 to 0.746 in the validation group. One of the supervised models had 14 nodes and classified 27.9% of patients as very unlikely to survive neurologically intact or with mild deficits (< 3%); the best unsupervised model had 11 nodes and classified 21.7% as very unlikely to survive. We have developed and validated Classification and Regression Tree models that predict survival to discharge with good neurologic function or with mild deficits following in-hospital cardiopulmonary arrest. Models like this can assist physicians and patients who are considering do-not-resuscitate orders.


Limonene suppresses lipopolysaccharide-induced production of nitric oxide, prostaglandin E2, and pro-inflammatory cytokines in RAW 264.7 macrophages.
The monoterpene D-limonene and its metabolites have been shown to exert chemopreventive and chemotherapeutic effects against different tumours in animal models and clinical trials. However, it is unknown whether these compounds modulate the inflammatory response in RAW 264.7 macrophage cells. The present study was therefore designed to elucidate the pharmacological and biological effects of D-limonene on the production of pro-inflammatory cytokines and inflammatory mediators in macrophages. The results indicate that D-limonene is an effective inhibitor of lipopolysaccharide (LPS)-induced NO and prostaglandin E(2) production in RAW 264.7 cells. These inhibitory effects of D-limonene included dose-dependent decreases in the expression of iNOS and COX-2 proteins. To evaluate the inhibitory effects of D-limonene on other cytokines, we also measured TNF-alpha, IL-1beta, and IL-6 levels in the cell supernatants of LPS-stimulated RAW 264.7 macrophages by enzyme-linked immunosorbent assay. In these assays, D-limonene decreased the expression of TNF-alpha, IL-1beta, and IL-6 in a dose-dependent manner. To assess the suitability of D-limonene for cosmetic applications, we also performed 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assays on HaCaT keratinocytes. D-limonene did not display any cytotoxicity in these assays. From these results, we suggest that D-limonene may be considered a potential anti-inflammatory candidate.


Performing under pressure: Exploring the psychological state underlying clutch performance in sport.
Clutch performance is improved performance under pressure. However, little research has examined the psychological state experienced by athletes in these situations. Therefore, this study qualitatively examined the subjective experience underlying clutch performance across a range of sports (e.g., team, individual) and standards (Olympic to recreational athletes). Sixteen athletes (Mage = 27.08 years; SD = 6.48) took part in in-depth, semi-structured interviews primarily after an exceptional performance (M = 4.38 days later; SD = 3.14). Data were analysed inductively and thematically. Clutch states involved 12 characteristics, including heightened and deliberate concentration, intense effort, and heightened awareness, which distinguished the experience of clutch from other optimal psychological states such as flow. Other characteristics, such as perceptions of control, were also reported and supported previous experimental research on clutch. These findings present in-depth qualitative insights into the psychological state underlying clutch performance, and are discussed in relation to the existing literature on optimal psychological states in sport.


Perspectives of Vietnamese, Sudanese and South Sudanese immigrants on targeting migrant communities for latent tuberculosis screening and treatment in low-incidence settings: A report on two Victorian community panels.
Tuberculosis (TB) elimination strategies in Australia require a focus on groups who are at highest risk of TB infection, such as immigrants from high-burden settings. Understanding attitudes to different strategies for latent TB infection (LTBI) screening and treatment is an important element of justifiable elimination strategies. Two community panels were conducted in Melbourne with members of the Vietnamese (n = 11), Sudanese and South Sudanese communities (n = 9). Panellists were provided with expert information about LTBI and different screening and health communication strategies, then deliberated on how best to pursue TB elimination in Australia. Both panels unanimously preferred LTBI screening to occur pre-migration rather than in Australia. Participants were concerned that post-migration screening would reach fewer migrants, noted that conducting LTBI screening in Australia could stigmatize participants and that poor awareness of LTBI would hamper participation. If targeted screening was to occur in Australia, the Vietnamese panel preferred 'place-based' communication strategies, whereas the Sudanese and South Sudanese panel emphasized that community leaders should lead communication strategies to minimize stigma. Both groups emphasized the importance of maintaining community trust in Australian health service providers, and the need to ensure targeting did not undermine this trust. Pre-migration screening was preferred. If post-migration screening is necessary, the potential for stigma should be reduced, benefit and risk profile clearly explained and culturally appropriate communication strategies employed. Cultural attitudes to health providers, personal health management and broader social vulnerabilities of targeted groups need to be considered in the design of screening programs.


Prenatal cocaine exposures and dose-related cocaine effects on infant tone and behavior.
In experimental models, prenatal cocaine exposure has been found to perturb monoaminergic development. In humans, numerous studies have sought clinical correlates, but few have focused on dose-related effects, especially as regards neurologic function beyond the neonatal period. To assess whether prenatal cocaine exposure has adverse effects on infant neurologic, developmental and behavioral outcomes and whether any effects are dose-dependent. Infants (398) were enrolled at birth from an urban hospital. Drug exposure was ascertained with biomarkers in hair (n=395), urine (n=170) and meconium (n=109). Children were followed prospectively and 286 (72%) were evaluated blind to drug exposure at 6 months of age with the Bayley scales, Fagan Scale of Infant Intelligence and a standardized neurological examination. Certain neurological findings increased significantly by the amount of cocaine detected in maternal hair, e.g. abnormality of tone, as indicated by extensor posture was detected among 28% of cocaine-unexposed infants, 43% of infants exposed to lower and 48% exposed to higher cocaine levels in maternal hair (p<0.009). Persistent fisting increased in a similar dose-dependent manner. These associations persisted in adjusted analyses. Prenatal cocaine exposure was not associated with developmental scores (mental, motor or novelty preference) but was associated with lower orientation scores in adjusted analyses. At 6 months of age, prenatal cocaine exposure was associated with abnormalities of tone and posture and with lower orientation scores. Perturbations in monoaminergic systems by cocaine exposure during fetal development may explain the observed neurological and behavioral symptoms. Whether such findings in infancy increase the risk of later neurobehavioral problems requires further study.


A Bayesian dose-finding procedure for phase I clinical trials based only on the assumption of monotonicity.
Despite an enormous and growing statistical literature, formal procedures for dose-finding are only slowly being implemented in phase I clinical trials. Even in oncology and other life-threatening conditions in which a balance between efficacy and toxicity has to be struck, model-based approaches, such as the Continual Reassessment Method, have not been universally adopted. Two related concerns have limited the adoption of the new methods. One relates to doubts about the appropriateness of models assumed to link the risk of toxicity to dose, and the other is the difficulty of communicating the nature of the process to clinical investigators responsible for early phase studies. In this paper, we adopt a new Bayesian approach involving a simple model assuming only monotonicity in the dose-toxicity relationship. The parameters that define the model have immediate and simple interpretation. The approach can be applied automatically, and we present a simulation investigation of its properties when it is. More importantly, it can be used in a transparent fashion as one element in the expert consideration of what dose to administer to the next patient or group of patients. The procedure serves to summarize the opinions and the data concerning risks of a binary characterization of toxicity which can then be considered, together with additional and less tidy trial information, by the clinicians responsible for making decisions on the allocation of doses. Graphical displays of these opinions can be used to ease communication with investigators.


N-linked glycosylation restricts the function of Short gastrulation to bind and shuttle BMPs.
Disorders of N-linked glycosylation are increasingly reported in the literature. However, the targets that are responsible for the associated developmental and physiological defects are largely unknown. Bone morphogenetic proteins (BMPs) act as highly dynamic complexes to regulate several functions during development. The range and strength of BMP activity depend on interactions with glycosylated protein complexes in the extracellular milieu. Here, we investigate the role of glycosylation for the function of the conserved extracellular BMP antagonist Short gastrulation (Sog). We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue. Mechanistically, we provide evidence that N-terminal and stem glycosylation controls extracellular Sog levels and distribution. The identification of similar residues in vertebrate Chordin proteins suggests that N-glycosylation may be an evolutionarily conserved process that adds complexity to the regulation of BMP activity.


Transcriptome and proteome dynamics in larvae of the barnacle Balanus Amphitrite from the Red Sea.
The barnacle Balanus amphitrite is widely distributed in marine shallow and tidal waters, and has significant economic and ecological importance. Nauplii, the first larval stage of most crustaceans, are extremely abundant in the marine zooplankton. However, a lack of genome information has hindered elucidation of the molecular mechanisms of development, settlement and survival strategies in extreme marine environments. We sequenced and constructed the genome dataset for nauplii to obtain comprehensive larval genetic information. We also investigated iTRAQ-based protein expression patterns to reveal the molecular basis of nauplii development, and to gain information on larval survival strategies in the Red Sea marine environment. A nauplii larval transcript dataset, containing 92,117 predicted open reading frames (ORFs), was constructed and used as a reference for the proteome analysis. Genes related to translation, oxidative phosphorylation and cytoskeletal development were highly abundant. We observed remarkable plasticity in the proteome of Red Sea larvae. The proteins associated with development, stress responses and osmoregulation showed the most significant differences between the two larval populations studied. The synergistic overexpression of heat shock and osmoregulatory proteins may facilitate larval survival in intertidal habitats or in extreme environments. We presented, for the first time, comprehensive transcriptome and proteome datasets for Red Sea nauplii. The datasets provide a foundation for future investigations focused on the survival mechanisms of other crustaceans in extreme marine environments.


Calbindin-D28k-immunoreactivity in the trigeminal ganglion neurons and molar tooth pulp of the rat.
The cell body size and coexpression of carbonic anhydrase (CA), calretinin (CR) and calcitonin gene-related peptide (CGRP) of primary neurons with calbindin-D28k (CB) was examined in the trigeminal ganglion (TG) of the rat. CB-immunoreactive (-ir) cells were mostly large and preferentially distributed in the maxillary and mandibular divisions of the TG. 48% of CB-ir TG cells exhibited enzyme CA activity. 10% of CB-ir TG cells contained CR-ir. Most TG cells coexpressing CB- and CR-irs were localized to the maxillary and mandibular divisions and exhibited CA activity. 6.5% of CB-ir TG cells coexisted with CGRP-ir. 46% of TG cells coexpressing CB and CGRP exhibited CA activity. The innervation of the molar tooth pulp by CB-ir TG primary neurons was also examined. CB-ir thick and smooth nerve fibers projected from the root pulp to the pulp horn and the roof of the pulp chamber, where they became thinner and rarely entered the subodontoblastic layer. However, they could not be traced to the odontoblastic layer, predentin or dentine. The distribution pattern of CB-ir pulpal fibers was different from that of CR-ir ones. The trigeminal neurons cells retrogradely labeled with fast blue (FB) from the maxillary molar tooth pulp contained CB- and CR-irs. 23% and 1% of the labeled cells were immunoreactive for CB and CR, respectively. The coexpression of CB- and CR-immunoreactivities (-irs) in FB-labeled cells was negligible. An immunoelectron microscopic method revealed that 21% of pulpal nerve fibers were immunoreactive for CB, and that all CB-ir nerve fibers in the root pulp were myelinated. The present study indicated that the tooth pulp primary neurons contained CB-ir but did not coexpress CB- and CR-irs and that these neurons projected their myelinated axons to the pulp.


Evaluation of pKa estimation methods on 211 druglike compounds.
The pK(a) values of 211 discovery (druglike) compounds were determined experimentally using capillary electrophoresis coupled with ultraviolet spectroscopy and a novel fitting algorithm. These values were compared to those predicted by five different commercially available pK(a) estimation packages: ACDLabs/pK(a), Marvin (ChemAxon), MoKa (Molecular Discovery), Epik (Schrodinger), and Pipeline Pilot (Accelrys). Even though the topological method MoKa was noticeably faster than ACD, the accuracy of those two methods and Marvin was statistically indistinguishable, with a root-mean-squared error of about 1 pK(a) unit compared to experiment. Pipeline Pilot and EpiK both produced pK(a) estimates in significantly worse agreement with the experiment. Interestingly, on a number of compounds, the predictions due to ACD v12 were in poorer agreement with the experiment than ACD v10. Microscopic and "apparent" pK(a) predictions were also compared using ACD v10. Microscopic pK(a)s gave significantly worse agreement with the experiment than the "apparent" values. In all cases, the errors appeared to be randomly distributed across chemical series.


C3 woody plant expansion in a C4 grassland: are grasses and shrubs functionally distinct?
The expansion of C(3) shrubs into C(4)-dominated tallgrass prairies represents a fundamental shift in growth-form dominance accompanied by changes in resource acquisition and use. We assessed these changes by comparing the ecophysiological traits of the dominant C(4) grass Andropogon gerardii, with traits of three C(3) invasive shrub species, Cornus drummondii, Prunus americana, and Rhus glabra. We tested the hypothesis that ecophysiological traits of the shrubs would be similar within this growth form but distinct from grasses and that these species would conform to the two-layer soil water model. Photosynthetic rates in R. glabra were similar to A. gerardii and higher than in the other two shrubs, while water use efficiency was markedly greater in A. gerardii. Among all species, midday xylem pressure potentials (XPP) were distinctly lower (70%) for P. americana, but were similar among the other species. Predawn XPP was related to soil water at shallow depths for A. gerardii (r(2) = 0.59) and P. americana (r(2) = 0.62), and to deeper soil moisture for R. glabra (r(2) = 0.63); there was no relationship for C. drummondii at any soil depth. Thus, a simple two-layer soil water model for partitioning shrub/grass resource acquisition was not appropriate for this grassland. We conclude that these shrubs could not be considered functional equivalents from an ecophysiological perspective, nor were they, as a group, distinct from A. gerardii in resource acquisition and use.


Glycans, Glycosite, and Intact Glycopeptide Analysis of N-Linked Glycoproteins Using Liquid Handling Systems.
Aberrant glycosylation has been shown to associate with disease progression, and with glycoproteins representing the major protein component of biological fluids this makes them attractive targets for disease monitoring. Leveraging glycoproteomic analysis via mass spectrometry (MS) could provide the insight into the altered glycosylation patterns that relate to disease progression. However, investigation of large sample cohorts requires rapid, efficient, and highly reproducible sample preparation. To address the limitation, we developed a high-throughput method for characterizing glycans, glycosites, and intact glycopeptides (IGPs) derived from N-linked glycoproteins. We combined disparate peptide enrichment strategies (i.e., hydrophilic and hydrophobic) and a liquid handling platform allowing for a high throughput and rapid enrichment of IGP in a 96-well plate format. The C18/MAX-Tip workflow reduced sample processing time and facilitated the selective enrichment of IGPs from complex samples. Furthermore, our approach enabled the analysis of deglycosylated peptides and glycans from enriched IGPs following PNGase F digest. Following development and optimization of the C18/MAX-Tip methodology using the standard glycoprotein, fetuin, we investigated normal urine samples to obtain N-linked glycoprotein information. Together, our method enables a high-throughput enrichment of glycan, glycosites, and IGPs from biological samples.


Screening breast cancer patients for ATM mutations and polymorphisms by using denaturing high-performance liquid chromatography.
All 62 coding exons of the ATM gene, along with 10-20 bases of the intronic region flanking each exon, were screened for DNA base sequence alterations by using denaturing high-performance liquid chromatography (DHPLC) in a series of 52 breast cancer patients. Six (12%) of these patients exhibited a total of eight different novel germ-line mutations that do not represent common polymorphisms. Of these, three patients possessed four nonconservative missense mutations while two conservative missense and two synonymous mutations were detected in the other three patients. In addition, 43 patients were found to have a total of 141 DNA sequence variations representing 21 different common polymorphisms and rare variants. An analysis of the relationship between the presence of a novel ATM mutation and either patient demographics or tumor properties demonstrated a significant difference between African Americans (3/7 = 43%) and other ethnic groups (3/45 = 7%, P = 0.026). None of the other characteristics examined was found to be related to mutation status.


Application of time-spatial labeling inversion pulse magnetic resonance imaging in the diagnosis of spontaneous intracranial hypotension due to high-flow cerebrospinal fluid leakage at C1-2.
Spontaneous intracranial hypotension (SIH) due to cerebrospinal fluid (CSF) leakage at C1-2 poses diagnostic and therapeutic challenges to spine surgeons. Although computed tomography (CT) myelography has been the diagnostic imaging modality of choice for identifying the CSF leakage point, extradural CSF collection at C1-2 on conventional CT myelography or magnetic resonance imaging (MRI) may often be a false localizing sign. The present study reports the successful application of time-spatial labeling inversion pulse (T-SLIP) MRI, which enabled the precise identification of the CSF leakage point at C1-2 in a 28-year-old woman with intractable SIH. After identifying the leakage point using both CT myelography and T-SLIP MRI, surgery was performed to seal the CSF leak. Intraoperatively, a pouch suggestive of an extradural arachnoid cyst around the left C2 nerve root was found, which was repaired by packing the pouch with muscle and fibrin glue. Clinical improvement was observed shortly after surgery, and postoperative imaging revealed the disappearance of the CSF leakage. T-SLIP MRI may provide useful information on the flow dynamics of CSF in SIH patients due to high-flow leakage. However, further experience is required to assess its sensitivity and specificity as an imaging modality for identifying CSF leakage points.


Discovery of a B-Cell Lymphoma 6 Protein-Protein Interaction Inhibitor by a Biophysics-Driven Fragment-Based Approach.
B-cell lymphoma 6 (BCL6) is a transcriptional factor that expresses in lymphocytes and regulates the differentiation and proliferation of lymphocytes. Therefore, BCL6 is a therapeutic target for autoimmune diseases and cancer treatment. This report presents the discovery of BCL6-corepressor interaction inhibitors by using a biophysics-driven fragment-based approach. Using the surface plasmon resonance (SPR)-based fragment screening, we successfully identified fragment 1 (SPR KD = 1200 μM, ligand efficiency (LE) = 0.28), a competitive binder to the natural ligand BCoR peptide. Moreover, we elaborated 1 into the more potent compound 7 (SPR KD = 0.078 μM, LE = 0.37, cell-free protein-protein interaction (PPI) IC50 = 0.48 μM (ELISA), cellular PPI IC50 = 8.6 μM (M2H)) by a structure-based design and structural integration with a second high-throughput screening hit.


Entry of US medical school graduates into family medicine residencies: 2006-2007 and 3-year summary.
This is the 26th report prepared by the American Academy of Family Physicians (AAFP) on the percentage of each US medical school's graduates entering family medicine residency programs. Approximately 8.5% of the 16,110 graduates of US medical schools between July 2005 and June 2006 were first-year family medicine residents in 2006, compared with 8.4% in 2005 and 9.2% in 2004. Medical school graduates from publicly funded medical schools were more likely to be first-year family medicine residents in October 2006 than were residents from privately funded schools, 10.1% compared with 6.0%. The West North Central and the Mountain regions reported the highest percentage of medical school graduates who were first-year residents in family medicine programs in October 2006 at 12.4% and 10.7%, respectively; the New England and Middle Atlantic regions reported the lowest percentages at 5.7% and 5.6%, respectively. Nearly half of the medical school graduates (49.2%) entering a family medicine residency program as first-year residents in October 2006 entered a program in the same state where they graduated from medical school. The percentages for each medical school have varied substantially from year to year since the AAFP began reporting this information. This article reports the average percentage for each medical school for the last 3 years. Also reported are the number and percentage of graduates from colleges of osteopathic medicine who entered Accreditation Council for Graduate Medical Education-accredited family medicine residency programs, based on estimates provided by the American Association of Colleges of Osteopathic Medicine.


Interaction of diabetes and smoking on stroke: a population-based cross-sectional survey in China.
Diabetes and smoking are known independent risk factors for stroke; however, their interaction concerning stroke is less clear. We aimed to explore such interaction and its influence on stroke in Chinese adults. Cross-sectional study. Community-based investigation in Xuzhou, China. A total of 39 887 Chinese adults who fulfilled the inclusion criteria were included. Participants were selected using a multistage stratified cluster method, and completed self-reported questionnaires on stroke and smoking. Type 2 diabetes mellitus (DM2) was assessed by fasting blood glucose or use of antidiabetic medication. Interaction, relative excess risk owing to interaction (RERI), attributable proportion (AP) and synergy index (S) were evaluated using a logistic regression model. After adjustment for age, sex, marital status, educational level, occupation, physical activity, body mass index, hypertension, family history of stroke, alcohol use and blood lipids, the relationships between DM2 and stroke, and between smoking and stroke, were still significant: ORs were 2.75 (95% CI 2.03 to 3.73) and 1.70 (95% CI 1.38 to 2.10), respectively. In subjects with DM2 who smoked, the RERI, AP and S values (and 95% CIs) were 1.80 (1.24 to 3.83), 0.52 (0.37 to 0.73) and 1.50 (1.18 to 1.84), respectively. The results suggest there are additive interactions between DM2 and smoking and that these affect stroke in Chinese adults.


Using tagging data and aerial surveys to incorporate availability bias in the abundance estimation of blue sharks (Prionace glauca).
There is worldwide concern about the status of elasmobranchs, primarily as a result of overfishing and bycatch with subsequent ecosystem effects following the removal of top predators. Whilst abundant and wide-ranging, blue sharks (Prionace glauca) are the most heavily exploited shark species having suffered marked declines over the past decades, and there is a call for robust abundance estimates. In this study, we utilized depth data collected from two blue sharks using pop-up satellite archival tags, and modelled the proportion of time the sharks were swimming in the top 1-meter layer and could therefore be detected by observers conducting aerial surveys. The availability models indicated that the tagged sharks preferred surface waters whilst swimming over the continental shelf and during daytime, with a model-predicted average proportion of time spent at the surface of 0.633 (SD = 0.094) for on-shelf, and 0.136 (SD = 0.075) for off-shelf. These predicted values were then used to account for availability bias in abundance estimates for the species over a large area in the Northeast Atlantic, derived through distance sampling using aerial survey data collected in 2015 and 2016 and modelled with density surface models. Further, we compared abundance estimates corrected with model-predicted availability to uncorrected estimates and to estimates that incorporated the average time the sharks were available for detection. The mean abundance (number of individuals) corrected with modelled availability was 15,320 (CV = 0.28) in 2015 and 11,001 (CV = 0.27) in 2016. Depending on the year, these estimates were ~7 times higher compared to estimates without the bias correction, and ~3 times higher compared to the abundances corrected with average availability. When the survey area contains habitat heterogeneity that may affect surfacing patterns of animals, modelling animals' availability provides a robust alternative to correcting for availability bias and highlights the need for caution when applying "average" correction factors.


[Acupuncture and insomnia].
40 patients with primary difficulties in either falling asleep or remaining asleep were diagnosed according to the traditional Chinese medicine, allocated to specific diagnostic subgroups and treated individually by a practitioner in his private practice. The patients were randomized into two groups, one receiving true acupuncture, the other needled at non-acupuncture points for 3-5 sessions at weekly intervals. The outcome of the therapy was assessed in several ways, first and foremost by an objective measurement of the sleep quality by polysomnography in a specialized sleep laboratory, performed once before and once after termination of the series of treatments. Additional qualitative results were obtained from several questionnaires. The objective measurement showed a statistically significant effect only in the patients who received the true acupuncture. The subjective, qualitative assessment was better in the proper treatment group than in the control group but was not calculated statistically for methodological reasons. Based on the results of this study, it can be concluded that true and individualized acupuncture indeed shows efficacy in primary sleep disorders. However, a direct influence by the therapist cannot be excluded.


Radiation-induced Chromosome Instability: The Role of Dose and Dose Rate.
Nontargeted effects include radiation-induced genomic instability (RIGI) which is observed in the progeny of cells exposed to ionizing radiation and can be manifested in different ways, including chromosomal instability and micronucleus (MN) formation. Since genomic instability is commonly observed in tumors and has a role in tumor progression, RIGI has the potential of being an important mechanism for radiation-induced cancer. The work presented explores the role of dose and dose rate on RIGI, determined using a MN assay, in normal primary human fibroblast (HF19) cells exposed to either 0.1 Gy or 1 Gy of X-rays delivered either as an acute (0.42 Gy/min) or protracted (0.0031 Gy/min) exposure. While the expected increase in MN was observed following the first mitosis of the irradiated cells compared to unirradiated controls, the results also demonstrate a significant increase in MN yields in the progeny of these cells at 10 and 20 population doublings following irradiation. Minimal difference was observed between the two doses used (0.1 and 1 Gy) and the dose rates (acute and protracted). Therefore, these nontargeted effects have the potential to be important for the low-dose and dose-rate exposure. The results also show an enhancement of the cellular levels of reactive oxygen species after 20 population doublings, which suggests that ionising radiation (IR) could potentially perturb the homeostasis of oxidative stress and so modify the background rate of endogenous DNA damage induction. In conclusion, the investigations have demonstrated that normal primary human fibroblast (HF19) cells are susceptible to the induction of early DNA damage and RIGI, not only after a high dose and high dose rate exposure to low linear energy transfer, but also following low dose, low dose rate exposures. The results suggest that the mechanism of radiation induced RIGI in HF19 cells can be correlated with the induction of reactive oxygen species levels following exposure to 0.1 and 1 Gy low-dose rate and high-dose rate x-ray irradiation.


Population dynamics of synthetic terraformation motifs.
Ecosystems are complex systems, currently experiencing several threats associated with global warming, intensive exploitation and human-driven habitat degradation. Because of a general presence of multiple stable states, including states involving population extinction, and due to the intrinsic nonlinearities associated with feedback loops, collapse in ecosystems could occur in a catastrophic manner. It has been recently suggested that a potential path to prevent or modify the outcome of these transitions would involve designing synthetic organisms and synthetic ecological interactions that could push these endangered systems out of the critical boundaries. In this paper, we investigate the dynamics of the simplest mathematical models associated with four classes of ecological engineering designs, named Terraformation motifs (TMs). These TMs put in a nutshell different ecological strategies. In this context, some fundamental types of bifurcations pervade the systems' dynamics. Mutualistic interactions can enhance persistence of the systems by means of saddle-node bifurcations. The models without cooperative interactions show that ecosystems achieve restoration through transcritical bifurcations. Thus, our analysis of the models allows us to define the stability conditions and parameter domains where these TMs must work.


Non classical risk factors for gestational diabetes mellitus: a systematic review of the literature.
Age, obesity and family history of diabetes are well known risk factors for gestational diabetes mellitus. Others are more controversial. The objective of this review is to find evidence in the literature that justifies the inclusion of these other conditions among risk factors. The MEDLINE, Cochrane, LILACS and Pan American Health Organization databases were searched, covering articles dating from between 1992 and 2006. Keywords were used in combination (AND) with gestational diabetes mellitus separately and with each one of the risk factors studied. The methodological quality of the studies included was assessed, resulting in the selection of 41 papers. Most studies investigating maternal history of low birth weight, low stature, and low level of physical activity have found positive associations with gestational diabetes mellitus. Low socioeconomic levels, smoking during pregnancy, high parity, belonging to minority groups, and excessive weight gain during pregnancy presented conflicting results. Publication bias cannot be ruled out. Standardization of techniques, cutoff points for screening and diagnosis, as well as studies involving larger sample sizes would allow future meta-analyses.


Probing the charging mechanisms of carbon nanomaterial polyelectrolytes.
Chemical charging of single-walled carbon nanotubes (SWCNTs) and graphenes to generate soluble salts shows great promise as a processing route for electronic applications, but raises fundamental questions. The reduction potentials of highly-charged nanocarbon polyelectrolyte ions were investigated by considering their chemical reactivity towards metal salts/complexes in forming metal nanoparticles. The redox activity, degree of functionalisation and charge utilisation were quantified via the relative metal nanoparticle content, established using thermogravimetric analysis (TGA), inductively coupled plasma atomic emission spectroscopy (ICP-AES) and X-ray photoelectron spectroscopy (XPS). The fundamental relationship between the intrinsic nanocarbon electronic density of states and Coulombic effects during charging is highlighted as an important area for future research.


Nonspecific behaviors as early indications of cerebral vasospasm.
This study investigated nonspecific behaviors as early indications of vasospasm following subarachnoid hemorrhage. Although symptoms of vasospasm (e.g., lowered level of consciousness, focal deficits such as hemiplegia or aphasia), are well recognized, the significance of early appearance of nonspecific symptoms such as restlessness, unusual behaviors, and impulsive behavior has not been investigated in detail. The study design included descriptive quantitative elements and a small qualitative component. Nonspecific behaviors were recorded, and the prevalence of those behaviors in individuals developing vasospasm was noted. Of 60 participants, 31 developed vasospasm; 24 of the 31 initially presented with nonspecific behaviors (p < .0001). Early detection of cerebral vasospasm allows prompt intervention and treatment, with the goal of preventing further ischemia or infarction.


Stroke is predicted by low visuospatial in relation to other intellectual abilities and coronary heart disease by low general intelligence.
Low intellectual ability is associated with an increased risk of coronary heart disease and stroke. Most studies have used a general intelligence score. We studied whether three different subscores of intellectual ability predict these disorders. We studied 2,786 men, born between 1934 and 1944 in Helsinki, Finland, who as conscripts at age 20 underwent an intellectual ability test comprising verbal, visuospatial (analogous to Raven's progressive matrices) and arithmetic reasoning subtests. We ascertained the later occurrence of coronary heart disease and stroke from validated national hospital discharge and death registers. 281 men (10.1%) had experienced a coronary heart disease event and 131 (4.7%) a stroke event. Coronary heart disease was predicted by low scores in all subtests, hazard ratios for each standard deviation (SD) lower score ranging from 1.21 to 1.30 (confidence intervals 1.08 to 1.46). Stroke was predicted by a low visuospatial reasoning score, the corresponding hazard ratio being 1.23 (95% confidence interval 1.04 to 1.46), adjusted for year and age at testing. Adjusted in addition for the two other scores, the hazard ratio was 1.40 (1.10 to 1.79). This hazard ratio was little affected by adjustment for socioeconomic status in childhood and adult life, whereas the same adjustments attenuated the associations between intellectual ability and coronary heart disease. The associations with stroke were also unchanged when adjusted for systolic blood pressure at 20 years and reimbursement for adult antihypertensive medication. Stroke is predicted by low visuospatial reasoning scores in relation to scores in the two other subtests. This association may be mediated by common underlying causes such as impaired brain development, rather than by mechanisms associated with risk factors shared by stroke and coronary heart disease, such as socio-economic status, hypertension and atherosclerosis.


Polymorphism in the innate immune receptor SIRPα controls CD47 binding and autoimmunity in the nonobese diabetic mouse.
The signal regulatory protein (SIRP) locus encodes a family of paired receptors that mediate both activating and inhibitory signals and is associated with type 1 diabetes (T1D) risk. The NOD mouse model recapitulates multiple features of human T1D and enables mechanistic analysis of the impact of genetic variations on disease. In this study, we identify Sirpa encoding an inhibitory receptor on myeloid cells as a gene in the insulin-dependent diabetes locus 13.2 (Idd13.2) that drives islet inflammation and T1D. Compared to T1D-resistant strains, the NOD variant of SIRPα displayed greater binding to its ligand CD47, as well as enhanced T cell proliferation and diabetogenic potency. Myeloid cell-restricted expression of a Sirpa transgene accelerated disease in a dose-dependent manner and displayed genetic and functional interaction with the Idd5 locus to potentiate insulitis progression. Our study demonstrates that variations in both SIRPα sequence and expression level modulate T1D immunopathogenesis. Thus, we identify Sirpa as a T1D risk gene and provide insight into the complex mechanisms by which disease-associated variants act in concert to drive defined stages in disease progression.


Evening versus morning dosing of antihypertensive drugs in hypertensive patients with sleep apnoea: a cross-over study.
Beneficial effects of continuous positive airway pressure (CPAP) on both blood pressure (BP) levels and variability have been documented in patients with obstructive sleep apnoea (OSA). We investigated the relevant impact of different dosing times of antihypertensive drugs beyond CPAP application. In this prospective, cross-over trial, we included 41 patients with newly diagnosed hypertension and never treated OSA (apnoea-hypopnea index ≥15/h), without increased daytime somnolence (Epworth Score ≤10 points). Patients first received treatment with valsartan or with a fixed combination of amlodipine and valsartan in a single morning dose for 8 weeks. In the following 8-week period, patients received the same therapeutic regimen in a single evening dose. Office and ambulatory BP were measured at baseline and after each treatment period. Compared with morning administration, evening dosing induced a greater decrease in office SBP (by 3.7 ± 6.5 mmHg, P = 0.001). The decrease in 24-h SBP/DBP was significant and similar after morning and evening dosing (-16.4 ± 11/11.0 ± 7.5 and -18.4 ± 11/12.1 ± 7.5 mmHg, respectively, P < 0.001 for both). Evening compared with morning dosing further reduced night-time SBP/DBP by 4.4 ± 8.6/2.9 ± 5.6 mmHg (P = 0.007 and P = 0.006, respectively). Night-time dippers increased from 24% at baseline to 34% with morning dosing and to 61% with evening dosing. There was no significant interaction between concurrent CPAP application and drugs dosing time on BP changes. Evening dosing of antihypertensive drugs improves night-time BP and dipping status in nonsleepy patients with OSA, irrespective of CPAP application.


Gene expression profile of patients with phadiatop-positive and -negative allergic rhinitis treated with acupuncture.
We assessed the therapeutic effect of acupuncture in patients with perennial allergic rhinitis. Acupuncture therapy corrects the equilibrium deviation using the bidirectional regulative actions in treating syndromes by inserting needles into acupoints. We studied the clinical outcomes and gene expression profiles of Phadiatop (Ph)-positive (+) and -negative (-) allergic rhinitis patients who were treated with acupuncture. Twenty-one (21) patients with allergic rhinitis [13 Ph(+), 8 Ph(-)] received 8 courses of acupuncture treatment over 4 weeks. Blood samples of the patients were collected during the course of acupuncture for global analysis of gene expression profiles by Affymetrix human U133A chips. Patients completed the rhinoconjunctivitis quality of life questionnaire (RQLQ) before and after the therapy to objectively measure the therapeutic effect of acupuncture. The gene expression profile in patients with Ph(+) and Ph(-) allergic rhinitis treated before and after acupuncture was analyzed by unsupervised and supervised clustering methods. The results of the RQLQ and the gene expression profiles were different between the Ph(+) and Ph(-) groups after receiving treatment with acupuncture. Activity, practical problems, and nasal symptoms showed significant improvement in the Ph(+) group versus the Ph(-) group. In addition, genes involved in active immune response, differential of Treg and cell apoptosis, were different in the Ph(+) and Ph(-) groups after acupuncture treatment. Differential gene expression profiles of patients with Ph(+) and Ph(-) allergic rhinitis indicate the distinct physiologic responses after receiving acupuncture treatment in these two groups. Our results suggest that personalized medical treatment should be essential for acupuncture treatment in patients with allergic rhinitis.


The number of genes changing expression after chronic exposure to code division multiple access or frequency DMA radiofrequency radiation does not exceed the false-positive rate.
Experiments with cultured C3H 10T 1/2 cells were performed to determine if exposure to cell phone radiofrequency (RF) radiations induce changes in gene expression. Following a 24 h exposure of 5 W/kg specific adsorption rate, RNA was extracted from the exposed and sham control cells for microarray analysis on Affymetrix U74Av2 Genechips. Cells exposed to 0.68 Gy of X-rays with a 4-h recovery were used as positive controls. The number of gene expression changes induced by RF radiation was not greater than the number of false positives expected based on a sham versus sham comparison. In contrast, the X-irradiated samples showed higher numbers of probe sets changing expression level than in the sham versus sham comparison.


[Approach to the Patient with Elevated Serum Ferritin].
An increase of the serum ferritin may appear as an incidental finding in asymptomatic patients in the routine laboratory examination. On the one hand, ferritin reflects the iron stores of the body and can therefore indicate an iron overload of various causes. On the other hand, it is an acute phase protein and thus increases in inflammatory and malignant diseases. We aim to describe an approach to the incidental finding hyperferritinemia with possible evaluation strategy and to explain the most important differential diagnoses.


Vision maintenance and retinal apoptosis reduction in RCS rats with Okayama University-type retinal prosthesis (OUReP™) implantation.
Photoelectric dye-coupled polyethylene film, designated Okayama University-type retinal prosthesis or OUReP™, generates light-evoked surface electric potentials and stimulates neurons. In this study, the vision was assessed by behavior tests in aged hereditary retinal dystrophic RCS rats with OUReP™, retinal apoptosis and electroretinographic responses were measured in dystrophic eyes with OUReP™. The dye-coupled films, or plain films as a control, were implanted in subretinal space of RCS rats. On behavior tests, RCS rats with dye-coupled films, implanted at the old age of 14 weeks, showed the larger number of head-turning, consistent with clockwise and anticlockwise rotation of a surrounding black-and-white-striped drum, compared with rats with plain films, under the dim (50 lux) and bright (150 lux) conditions in the observation period until the age of 22 weeks (n = 5, P < 0.05, repeated-measure ANOVA). The number of apoptotic cells in retinal sections at the site of dye-coupled film implantation was significantly smaller, compared with the other retinal sites, neighboring the film, or opposite to the film, 5 months after film implantation at the age of 6 weeks (P = 0.0021, Friedman test). The dystrophic eyes of RCS rats with dye-coupled films showed positive responses to maximal light stimulus at a significantly higher rate, compared with the eyes with no treatment (P < 0.05, Chi-square test). Electroretinograms in normal eyes of Wistar rats with dye-coupled or plain films showed significantly decreased amplitudes (n = 14, P < 0.05, repeated-measure ANOVA). In conclusions, vision was maintained in RCS rats with dye-coupled films implanted at the old age. The dystrophic eyes with dye-coupled films showed electroretinographic responses. Five-month film implantation caused no additional retinal changes.


Accuracy of the H2S test: a systematic review of the influence of bacterial density and sample volume.
The presence/absence hydrogen sulphide test (P/A H2S) is widely used as a low-cost alternative faecal indicator test in remote and resource-poor settings. The aim of the paper is to assess how bacterial density and sample volume affect its accuracy. Based on a systematic search, we identified studies that tested water samples (n = 2,034) using both the P/A H2S test and recognised tests for thermotolerant coliforms (TTC) or Escherichia coli. We calculated P/A H2S test specificity and sensitivity against a range of TTC and E. coli densities. For two studies, we compared this with sensitivity and specificity estimates for simulated 100 and 20 ml presence/absence tests. For most of the 19 included studies, as the threshold used to define contamination increased from 1 to 100 cfu/100 ml, P/A H2S test sensitivity increased but specificity decreased. Similarly, the simulation indicated that increasing test volumes from 20 to 100 ml increased sensitivity but reduced specificity. There was potential for bias, for example from lack of blinding during test interpretation, in most of the studies reviewed. In assessing the P/A H2S test as an alternative to standard methods, careful consideration of likely indicator bacteria levels and sample volume is required.


Enhanced phospholipase A2 activity in cultured cardiomyocytes from newborn spontaneously hypertensive rat.
1. Changes in membrane lipid composition and metabolism could participate in myocardial membrane dysfunction in essential or experimental hypertension. Phospholipid-bound fatty acid profile and metabolism are altered in cultured heart myocytes of newborn genetically hypertensive rats. The present study was designed to investigate the participation of phospholipase A2 in these modifications. 2. Phospholipase A2 activity of cultured cardiomyocytes of neonate spontaneously hypertensive rats and normotensive control Wistar-Kyoto rats was compared. The enzyme activity was measured using 2-[1-14C]arachidonyl-phosphatidylethanolamine as substrate. In both strains, Ca(2+)-dependent and independent phospholipase A2 activities were present. Only the Ca(2+)-dependent enzyme activity was altered in spontaneously hypertensive rat cardiomyocytes. With 0.2 mmol/l substrate and 5 mmol/l Ca2+, the phospholipase A2 activities were 79.0 +/- 13.4 and 26.0 +/- 3.6 nmol h-1 mg-1 of protein in spontaneously hypertensive and Wistar-Kyoto rat cardiomyocytes respectively (n = 10 in both cases, P = 0.001). The maximum velocity of the enzyme was three times higher in spontaneously hypertensive rat than in Wistar-Kyoto rat, without changes in the apparent affinity of the enzyme for its substrate. 3. The present results demonstrate an enhanced phospholipase A2 activity in cultured heart muscle cells of spontaneously hypertensive rats, which could be genetically determined.


Effect of "missed" pills on oral contraceptive effectiveness.
The purpose of this study was to determine whether missing pills in an oral contraceptive (OC) cycle resulted in folliculogenesis and eventual ovulation. Fifteen women selected from a population requesting tubal reanastomosis were randomized into three groups and issued pill packs missing four consecutive pills in specific sequences, as follows: group I, days 1-4; group II, days 3-6; and group III, days 6-9. Serum was drawn for assay of LH, FSH, estradiol (E2), and progesterone, and serial ovarian ultrasound examinations were done to study follicular development throughout the cycle at 4-day intervals. No subject ovulated, as suggested by serum progesterone concentrations (not exceeding 0.63 ng/mL for any woman) and ultrasound assessment of follicular development (no follicular diameter exceeding 13 mm). The highest (mean +/- standard deviation) serum concentrations of LH and FSH in any group (13.25 +/- 18.71 and 14.40 +/- 7.71 mIU/mL, respectively) and of E2 (44.35 +/- 26.79 pg/mL) were observed during or immediately after the pill-free interval. Ovarian ultrasound examinations suggested suppressed folliculogenesis in all groups. No functional ovarian cysts were detected. Oral contraceptives exerted a similar degree of pituitary and ovarian suppression even when the subjects missed four pills at varying times in a cycle. The anovulatory effect persisted when the OC pills were reinstituted and taken reliably after an interval of noncompliance.


Constructing irregular surfaces to enclose macromolecular complexes for mesoscale modeling using the discrete surface charge optimization (DISCO) algorithm.
Salt-mediated electrostatics interactions play an essential role in biomolecular structures and dynamics. Because macromolecular systems modeled at atomic resolution contain thousands of solute atoms, the electrostatic computations constitute an expensive part of the force and energy calculations. Implicit solvent models are one way to simplify the model and associated calculations, but they are generally used in combination with standard atomic models for the solute. To approximate electrostatics interactions in models on the polymer level (e.g., supercoiled DNA) that are simulated over long times (e.g., milliseconds) using Brownian dynamics, Beard and Schlick have developed the DiSCO (Discrete Surface Charge Optimization) algorithm. DiSCO represents a macromolecular complex by a few hundred discrete charges on a surface enclosing the system modeled by the Debye-Hückel (screened Coulombic) approximation to the Poisson-Boltzmann equation, and treats the salt solution as continuum solvation. DiSCO can represent the nucleosome core particle (>12,000 atoms), for example, by 353 discrete surface charges distributed on the surfaces of a large disk for the nucleosome core particle and a slender cylinder for the histone tail; the charges are optimized with respect to the Poisson-Boltzmann solution for the electric field, yielding a approximately 5.5% residual. Because regular surfaces enclosing macromolecules are not sufficiently general and may be suboptimal for certain systems, we develop a general method to construct irregular models tailored to the geometry of macromolecules. We also compare charge optimization based on both the electric field and electrostatic potential refinement. Results indicate that irregular surfaces can lead to a more accurate approximation (lower residuals), and the refinement in terms of the electric field is more robust. We also show that surface smoothing for irregular models is important, that the charge optimization (by the TNPACK minimizer) is efficient and does not depend on the initial assigned values, and that the residual is acceptable when the distance to the model surface is close to, or larger than, the Debye length. We illustrate applications of DiSCO's model-building procedure to chromatin folding and supercoiled DNA bound to Hin and Fis proteins. DiSCO is generally applicable to other interesting macromolecular systems for which mesoscale models are appropriate, to yield a resolution between the all-atom representative and the polymer level.


Residential Aged Care Medication Review to Improve the Quality of Medication Use: A Systematic Review.
Aging is often associated with various underlying comorbidities that warrant the use of multiple medications. Various interventions, including medication reviews, to optimize pharmacotherapy in older people residing in aged care facilities have been described and evaluated. Previous systematic reviews support the positive impact of various medication-related interventions but are not conclusive because of several factors. The current study aimed to assess the impact of medication reviews in aged care facilities, with additional focus on the types of medication reviews, using randomized controlled trials (RCTs) and observational studies. A systematic searching of English articles that examined the medication reviews conducted in aged care facilities was performed using the following databases: PubMed, CINAHL, IPA, TRiP, and the Cochrane Library, with the last update in December 2015. Extraction of articles and quality assessment of included articles were performed independently by 2 authors. Data on interventions and outcomes were extracted from the included studies. The SIGN checklist for observational studies and the Cochrane Collaboration's tool for assessing risk of bias in RCTs were applied. Outcomes assessed were related to medications, reviews, and adverse events. Because of the heterogeneity of the measurements, it was deemed inappropriate to conduct a meta-analysis and thus a narrative approach was employed. Twenty-two studies (10 observational studies and 12 controlled trials) were included from 1141 evaluated references. Of the 12 trials, 8 studies reported findings of pharmacist-led medication reviews and 4 reported findings of multidisciplinary team-based reviews. The medication reviews performed in the included trials were prescription reviews (n = 8) and clinical medication reviews (n = 4). In the case of the observational studies, the majority of the studies (8/12 studies) reported findings of pharmacist-led medication reviews, and only 2 studies reported findings of multidisciplinary team-based reviews. Similarly, 6 studies employed prescription reviews, whereas 4 studies employed clinical medication reviews. The majority of the recommendations put forward by the pharmacist or a multidisciplinary team were accepted by physicians. The number of prescribed medications, inappropriate medications, and adverse outcomes (eg, number of deaths, frequency of hospitalizations) were reduced in the intervention group. Medication reviews conducted by pharmacists, either working independently or with other health care professionals, appear to improve the quality of medication use in aged care settings. However, robust conclusions cannot be drawn because of significant heterogeneity in measurements and potential risk for biases.


A transitional extracellular matrix instructs cell behavior during muscle regeneration.
Urodele amphibians regenerate appendages through the recruitment of progenitor cells into a blastema that rebuilds the lost tissue. Blastemal formation is accompanied by extensive remodeling of the extracellular matrix. Although this remodeling process is important for appendage regeneration, it is not known whether the remodeled matrix directly influences the generation and behavior of blastemal progenitor cells. By integrating in vivo 3-dimensional spatiotemporal matrix maps with in vitro functional time-lapse imaging, we show that key components of this dynamic matrix, hyaluronic acid, tenascin-C and fibronectin, differentially direct cellular behaviors including DNA synthesis, migration, myotube fragmentation and myoblast fusion. These data indicate that both satellite cells and fragmenting myofibers contribute to the regeneration blastema and that the local extracellular environment provides instructive cues for the regenerative process. The fact that amphibian and mammalian myoblasts exhibit similar responses to various matrices suggests that the ability to sense and respond to regenerative signals is evolutionarily conserved.


Health Care Service and Outcomes Among an Estimated 6.7 Million Ambulatory Care Diabetic Foot Cases in the U.S.
To evaluate ambulatory clinical cases of diabetic foot ulcers (DFUs) and diabetic foot infections (DFIs) in the U.S. from 2007 to 2013 and to assess outcomes of emergency department or inpatient (ED/IP) admission, number of clinic visits per year, and physician time spent per visit. A cross-sectional historical cohort analysis was conducted by using the nationally representative Centers for Disease Control and Prevention National Ambulatory Medical Care Survey data from 2007 to 2013, including patients age ≥18 years with diabetes and either DFIs or DFUs. Study outcomes were analyzed by using generalized linear models controlling for key demographics and chronic conditions. Across the estimated 5.6 billion ambulatory care visits between 2007 and 2013, 784.8 million involved diabetes and ∼6.7 million (0.8%) were for DFUs (0.3%) or DFIs (0.5%). Relative to other ambulatory clinical cases, multivariable analyses indicated that DFUs were associated with a 3.4 times higher odds of direct ED/IP admission (CI 1.01-11.28; P = 0.049), 2.1 times higher odds of referral to another physician (CI 1.14-3.71; P = 0.017), 1.9 times more visits in the past 12 months (CI 1.41-2.42; P < 0.001), and 1.4 times longer time spent per visit with the physician (CI 1.03-1.87; P = 0.033). DFIs were independently associated with a 6.7 times higher odds of direct ED referral or IP admission (CI 2.25-19.51; P < 0.001) and 1.5 times more visits in the past 12 months (CI 1.14-1.90; P = 0.003). This investigation of an estimated 6.7 million diabetic foot cases indicates markedly greater risks for both ED/IP admissions and number of outpatient visits, with DFUs also associated with a higher odds of referrals to other physicians and longer physician visit times.


Modelling a full scale membrane bioreactor using Activated Sludge Model No.1: challenges and solutions.
A full-scale membrane bioreactor (1,600 m(3) d(-1)) was monitored for modelling purposes during the summer of 2006. A complete calibration of the ASM1 model is presented, in which the key points were the wastewater characterisation, the oxygen transfer and the biomass kinetics. Total BOD tests were not able to correctly estimate the biodegradable fraction of the wastewater. Therefore the wastewater fractionation was identified by adjusting the simulated sludge production rate to the measured value. MLVSS and MLSS were accurately predicted during both calibration and validation periods (20 and 30 days). Because the membranes were immerged in the aeration tank, the coarse bubble and fine bubble diffusion systems coexisted in the same tank. This allowed five different aeration combinations, depending whether the 2 systems were operating separately or simultaneously, and at low speed or high speed. The aeration control maintained low DO concentrations, allowing simultaneous nitrification and denitrification. This made it difficult to calibrate the oxygen transfer. The nitrogen removal kinetics were determined using maximum nitrification rate tests and an 8-hour intensive sampling campaign. Despite the challenges encountered, a calibrated set of parameters was identified for ASM1 that gave very satisfactory results for the calibration period. Matching simulated and measured data became more difficult during the validation period, mainly because the dominant aeration configuration had changed. However, the merit of this study is to be the first effort to simulate a full-scale MBR plant.


Assembly-free single-molecule sequencing recovers complete virus genomes from natural microbial communities.
Viruses are the most abundant biological entities on Earth and play key roles in host ecology, evolution, and horizontal gene transfer. Despite recent progress in viral metagenomics, the inherent genetic complexity of virus populations still poses technical difficulties for recovering complete virus genomes from natural assemblages. To address these challenges, we developed an assembly-free, single-molecule nanopore sequencing approach, enabling direct recovery of complete virus genome sequences from environmental samples. Our method yielded thousands of full-length, high-quality draft virus genome sequences that were not recovered using standard short-read assembly approaches. Additionally, our analyses discriminated between populations whose genomes had identical direct terminal repeats versus those with circularly permuted repeats at their termini, thus providing new insight into native virus reproduction and genome packaging. Novel DNA sequences were discovered, whose repeat structures, gene contents, and concatemer lengths suggest they are phage-inducible chromosomal islands, which are packaged as concatemers in phage particles, with lengths that match the size ranges of co-occurring phage genomes. Our new virus sequencing strategy can provide previously unavailable information about the genome structures, population biology, and ecology of naturally occurring viruses and viral parasites.


Preventative, but not post-stroke, inhibition of CD36 attenuates brain swelling in hyperlipidemic stroke.
The lack of inclusion of comorbidities in animal models of stroke may underlie the limited development of therapy in stroke. Previous studies in mice deficient of CD36, an immune receptor, indicated its contribution to stroke-induced inflammation and injury in hyperlipidemic conditions. The current study, therefore, tested whether pharmacological inhibition of CD36 provides neuroprotection in hyperlipidemic stroke. The hyperlipidemic mice subjected to stroke showed an exacerbation of infarct size and profound brain swelling. However, post-stroke treatment with CD36 inhibitors did not reduce, and in some cases worsened, acute stroke outcome, suggesting potential benefits of elevated CD36 in the post-stroke brain in a hyperlipidemic condition. On the other hand, chronic treatment of a CD36 inhibitor prior to stroke significantly reduced stroke-induced brain swelling. There was a trend toward infarct reduction, although it did not reach statistical significance. The observed benefit of preventative CD36 inhibition is in line with previously reported smaller infarct volume and swelling in CD36 KO mice. Thus, the current findings suggest that insights gained from the genetic models should be carefully considered before the implementation of pharmacological interventions, as a potential therapeutic strategy may depend on preventative treatment or a post-stroke acute treatment paradigm.


BGI-RIS: an integrated information resource and comparative analysis workbench for rice genomics.
Rice is a major food staple for the world's population and serves as a model species in cereal genome research. The Beijing Genomics Institute (BGI) has long been devoting itself to sequencing, information analysis and biological research of the rice and other crop genomes. In order to facilitate the application of the rice genomic information and to provide a foundation for functional and evolutionary studies of other important cereal crops, we implemented our Rice Information System (BGI-RIS), the most up-to-date integrated information resource as well as a workbench for comparative genomic analysis. In addition to comprehensive data from Oryza sativa L. ssp. indica sequenced by BGI, BGI-RIS also hosts carefully curated genome information from Oryza sativa L. ssp. japonica and EST sequences available from other cereal crops. In this resource, sequence contigs of indica (93-11) have been further assembled into Mbp-sized scaffolds and anchored onto the rice chromosomes referenced to physical/genetic markers, cDNAs and BAC-end sequences. We have annotated the rice genomes for gene content, repetitive elements, gene duplications (tandem and segmental) and single nucleotide polymorphisms between rice subspecies. Designed as a basic platform, BGI-RIS presents the sequenced genomes and related information in systematic and graphical ways for the convenience of in-depth comparative studies (http://rise.genomics.org.cn/).


Active transport, substrate specificity, and methylation of Hg(II) in anaerobic bacteria.
The formation of methylmercury (MeHg), which is biomagnified in aquatic food chains and poses a risk to human health, is effected by some iron- and sulfate-reducing bacteria (FeRB and SRB) in anaerobic environments. However, very little is known regarding the mechanism of uptake of inorganic Hg by these organisms, in part because of the inherent difficulty in measuring the intracellular Hg concentration. By using the FeRB Geobacter sulfurreducens and the SRB Desulfovibrio desulfuricans ND132 as model organisms, we demonstrate that Hg(II) uptake occurs by active transport. We also establish that Hg(II) uptake by G. sulfurreducens is highly dependent on the characteristics of the thiols that bind Hg(II) in the external medium, with some thiols promoting uptake and methylation and others inhibiting both. The Hg(II) uptake system of D. desulfuricans has a higher affinity than that of G. sulfurreducens and promotes Hg methylation in the presence of stronger complexing thiols. We observed a tight coupling between Hg methylation and MeHg export from the cell, suggesting that these two processes may serve to avoid the build up and toxicity of cellular Hg. Our results bring up the question of whether cellular Hg uptake is specific for Hg(II) or accidental, occurring via some essential metal importer. Our data also point at Hg(II) complexation by thiols as an important factor controlling Hg methylation in anaerobic environments.


Olfaction and psychiatry.
Recent clinical studies have identified significant olfactory deficits in several neuropsychiatric disorders, notably Alzheimer's disease and Parkinson's disease. These have correlated with neurochemical and neuropathological studies of the olfactory system. The presence of a specific sensory deficit may be related to the localisation of pathology within the brain. There is a need for incorporation of olfactory testing into routine clinical examination.


Investigation of the sludge reduction mechanism in the anaerobic side-stream reactor process using several control biological wastewater treatment processes.
To investigate the mechanism of sludge reduction in the anaerobic side-stream reactor (SSR) process, activated sludge with five different sludge reduction schemes were studied side-by-side in the laboratory. These are activated sludge with: 1) aerobic SSR, 2) anaerobic SSR, 3) aerobic digester, 4) anaerobic digester, and 5) no sludge wastage. The system with anaerobic SSR (system #2) was the focus of this study and four other systems served as control processes with different functions and purposes. Both mathematical and experimental approaches were made to determine solids retention time (SRT) and sludge yield for the anaerobic SSR process. The results showed that the anaerobic SSR process produced the lowest solids generation, indicating that sludge organic fractions degraded in this system are larger than other systems that possess only aerobic or anaerobic mode. Among three systems that involved long SRT (system #1, #2, and #5), it was only system #2 that showed stable sludge settling and effluent quality, indicating that efficient sludge reduction in this process occurred along with continuous generation of normal sludge flocs. This observation was further supported by batch anaerobic and aerobic digestion data. Batch digestion on sludges collected after 109 days of operation clearly demonstrated that both anaerobically and aerobically digestible materials were removed in activated sludge with anaerobic SSR. In contrast, sludge reduction in the aerobic SSR process or no wastage system was achieved by removal of mainly aerobically digestible materials. All these results led us to conclude that repeating sludge under both feast/fasting and anaerobic/aerobic conditions (i.e., activated sludge with anaerobic SSR) is necessary to achieve the highest biological solids reduction with normal wastewater treatment performance.


Comparative proteome analysis of psychrophilic versus mesophilic bacterial species: Insights into the molecular basis of cold adaptation of proteins.
Cold adapted or psychrophilic organisms grow at low temperatures, where most of other organisms cannot grow. This adaptation requires a vast array of sequence, structural and physiological adjustments. To understand the molecular basis of cold adaptation of proteins, we analyzed proteomes of psychrophilic and mesophilic bacterial species and compared the differences in amino acid composition and substitution patterns to investigate their likely association with growth temperatures. In psychrophilic bacteria, serine, aspartic acid, threonine and alanine are overrepresented in the coil regions of secondary structures, whilst glutamic acid and leucine are underrepresented in the helical regions. Compared to mesophiles, psychrophiles comprise a significantly higher proportion of amino acids that contribute to higher protein flexibility in the coil regions of proteins, such as those with tiny/small or neutral side chains. Amino acids with aliphatic, basic, aromatic and hydrophilic side chains are underrepresented in the helical regions of proteins of psychrophiles. The patterns of amino acid substitutions between the orthologous proteins of psychrophiles versus mesophiles are significantly different for several amino acids when compared to their substitutions in orthologous proteins of within the mesophiles or psychrophiles. Current results provide quantitative substitution preferences (or avoidance) of amino acids that lead to the adaptation of proteins to cold temperatures. These finding would help future efforts in selecting mutations for rational design of proteins with enhanced psychrophilic properties.


Health Insurance and Disclosure of Same-Sex Sexual Behaviors Among Gay and Bisexual Men in Same-Sex Relationships.
Gay and bisexual men (GBM) have poorer health outcomes than the general population. Improved health outcomes will require that GBM have access to healthcare and that healthcare providers are aware of their sexual behaviors. This study sought to examine factors associated with having health insurance and disclosure of same-sex sexual behaviors to primary care providers (PCPs) among GBM in primary same-sex relationships. We conducted an online survey of a national sample of 722 men in same-sex couples living in the United States. Logistic regression and multinomial regression models were conducted to assess whether characteristic differences existed between men who did and did not have health insurance, and between men who did and did not report that their PCP knew about their same-sex sexual activity. Our national sample of same-sex partnered men identified themselves predominantly as gay and white, and most reported having an income and health insurance. Having health insurance and disclosing sexual behavior to PCPs was associated with increasing age, higher education, and higher income levels. Insurance was less prevalent among nonwhite participants and those living in the south and midwest United States. Disclosure of sexual behavior was more common in urban respondents and in the western United States. In 25% of couples, one partner was insured, while the other was not. Having health insurance and disclosing one's sexual behavior to PCPs was suboptimal overall and occurred in patterns likely to exacerbate health disparities among those GBM already more heavily burdened with poorer health outcomes. These factors need to be considered by PCPs and health policymakers to improve the health of GBM. Patient- and provider-targeted interventions could also improve the health outcomes of GBM.


Simulating realistic fetal neurosonography images with appearance and growth change using cycle-consistent adversarial networks and an evaluation.
Purpose: We present an original method for simulating realistic fetal neurosonography images specifically generating third-trimester pregnancy ultrasound images from second-trimester images. Our method was developed using unpaired data, as pairwise data were not available. We also report original insights on the general appearance differences between second- and third-trimester fetal head transventricular (TV) plane images. Approach: We design a cycle-consistent adversarial network (Cycle-GAN) to simulate visually realistic third-trimester images from unpaired second- and third-trimester ultrasound images. Simulation realism is evaluated qualitatively by experienced sonographers who blindly graded real and simulated images. A quantitative evaluation is also performed whereby a validated deep-learning-based image recognition algorithm (ScanNav®) acts as the expert reference to allow hundreds of real and simulated images to be automatically analyzed and compared efficiently. Results: Qualitative evaluation shows that the human expert cannot tell the difference between real and simulated third-trimester scan images. 84.2% of the simulated third-trimester images could not be distinguished from the real third-trimester images. As a quantitative baseline, on 3000 images, the visibility drop of the choroid, CSP, and mid-line falx between real second- and real third-trimester scans was computed by ScanNav® and found to be 72.5%, 61.5%, and 67%, respectively. The visibility drop of the same structures between real second-trimester and simulated third-trimester was found to be 77.5%, 57.7%, and 56.2%, respectively. Therefore, the real and simulated third-trimester images were consider to be visually similar to each other. Our evaluation also shows that the third-trimester simulation of a conventional GAN is much easier to distinguish, and the visibility drop of the structures is smaller than our proposed method. Conclusions: The results confirm that it is possible to simulate realistic third-trimester images from second-trimester images using a modified Cycle-GAN, which may be useful for deep learning researchers with a restricted availability of third-trimester scans but with access to ample second trimester images. We also show convincing simulation improvements, both qualitatively and quantitatively, using the Cycle-GAN method compared with a conventional GAN. Finally, the use of a machine learning-based reference (in the case ScanNav®) for large-scale quantitative image analysis evaluation is also a first to our knowledge.


Association of severe insulin resistance with both loss of limb fat and elevated serum tumor necrosis factor receptor levels in HIV lipodystrophy.
HIV-lipodystrophy (HIV-LD) is characterized by the loss of body fat from the limbs and face, an increase in truncal fat, insulin resistance, and hyperlipidemia, factors placing affected patients at increased risk for vascular disease. This study evaluated insulin sensitivity and inflammatory status associated with HIV-LD and provides suggestions about its etiology. Insulin sensitivity and immune activation markers were assessed in 12 control subjects and 2 HIV-positive groups, 14 without and 15 with LD syndrome. Peripheral insulin sensitivity (mostly skeletal muscle) was determined with the hyperinsulinemic-euglycemic clamp. Circulating insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) and free fatty acid (FFA) levels, and their response to insulin infusion were indicative of insulin responsiveness of liver and adipose tissue, respectively. Serum levels of soluble type 2 tumor necrosis factor-alpha (TNF-alpha) receptor (sTNFR2) were used as an indicator of immune activation. HIV-LD study subjects had significantly reduced (twofold) peripheral insulin sensitivity, but normal levels of FFA and reduced levels of IGFBP-1, relative to the nonlipodystrophy groups, indicating that the loss of insulin sensitivity was more pronounced in skeletal muscle than in liver or fat. The significant loss of peripheral fat in the HIV-LD group (34%; p <.05) closely correlated with the reduced peripheral insulin sensitivity (p =. 0001). Levels of sTNFR2 were elevated in all HIV-infected study subjects, but they were significantly higher in those with lipodystrophy than without, and sTNFR2 levels strongly correlated with the reduction in insulin sensitivity (p =.0001). Loss of peripheral fat, normal levels of FFA, and reduced levels of IGFBP-1 indicate that insulin resistance in HIV-LD is distinct from type 2 diabetes and obesity. The relationship between the degree of insulin resistance and sTNFR2 levels suggests an inflammatory stimulus is contributing to the development of HIV-associated lipodystrophy.


Bud phenology and growth are subject to divergent selection across a latitudinal gradient in Populus angustifolia and impact adaptation across the distributional range and associated arthropods.
Temperate forest tree species that span large geographical areas and climatic gradients often have high levels of genetic variation. Such species are ideal for testing how neutral demographic factors and climate-driven selection structure genetic variation within species, and how this genetic variation can affect ecological communities. Here, we quantified genetic variation in vegetative phenology and growth traits in narrowleaf cottonwood, Populus angustifolia, using three common gardens planted with genotypes originating from source populations spanning the species' range along the Rocky Mountains of North America (ca. 1700 km). We present three main findings. First, we found strong evidence of divergent selection (Q ST > F ST) on fall phenology (bud set) with adaptive consequences for frost avoidance. We also found evidence for selection on bud flush duration, tree height, and basal diameter, resulting in population differentiation. Second, we found strong associations with climate variables that were strongly correlated with latitude of origin. More strongly differentiated traits also showed stronger climate correlations, which emphasizes the role that climate has played in divergent selection throughout the range. We found population × garden interaction effects; for some traits, this accounted for more of the variance than either factor alone. Tree height was influenced by the difference in climate of the source and garden locations and declined with increasing transfer distance. Third, growth traits were correlated with dependent arthropod community diversity metrics. Synthesis. Overall, we conclude that climate has influenced genetic variation and structure in phenology and growth traits and leads to local adaptation in P. angustifolia, which can then impact dependent arthropod species. Importantly, relocation of genotypes far northward or southward often resulted in poor growth, likely due to a phenological mismatch with photoperiod, the proximate cue for fall growth cessation. Genotypes moved too far southward suffer from early growth cessation, whereas those moved too far northward are prone to fall frost and winter dieback. In the face of current and forecasted climate change, habitat restoration, forestry, and tree breeding efforts should utilize these findings to better match latitudinal and climatic source environments with management locations for optimal future outcomes.


Cytotoxicity and Preliminary Analysis of the Pro-apoptotic and Cell Cycle Arrest Effects of Lantana ukambensis Against Colorectal Cancer Cells.
Lantana ukambensis (Vatke) Verdc. (Verbenaceae) is a seasonal herb widely spread in the West African region. The whole plant is used for the treatment of wounds, infections, and inflammatory pathologies. The purpose of this research is to evaluate the cytotoxicity and to analyze the probable pro-apototic, and cell cycle arrest effects of L. ukambensis methylene chloride extract and its fractions against HCT-116 and HT-29 colorectal cancer cells using preliminary tests in order to highlight the interest of this plant in the search of new anticancer molecules. The dried powder of the whole plant was extracted by methylene chloride maceration for 24 hours and the extract was divided into five fractions. The cytotoxicity of the crude extract and fractions were evaluated by the MTS assay. The most active fractions were subjected to some preliminary assays including crystal violet, Hoechst staining, cell cycle arrest, and annexin V/PI assays on the cancer cells to highlight the probable mechanism of action of these fractions. The methylene chloride, ethyl acetate, and 1-butanol fractions of L. ukambensis crude extract demonstrated significant antiproliferative effects on HCT-116 and HT-29 cell growth with IC50 values ranging between 2 to 15 μg/mL. 1-butanol and ethyl acetate fractions decreased the G1 phase by 20.53% and 28.47% and increased the G2/M by 23.47% and 25.90% respectively on HCT-116. Moreover, 1-butanol fraction increased the cumulative value of apoptotic cells by 49.77% on HCT-116 and ethyl acetate fraction increased this value by 53.37% at 15 μg/mL after 48 hours of exposure. The outcome of this study suggests the potential of 1-butanol and ethyl acetate fractions for the isolation of anticancer molecules against colorectal cancer.


Electrical microstimulation thresholds for behavioral detection and saccades in monkey frontal eye fields.
The frontal eye field (FEF) is involved in the transformation of visual signals into saccadic eye movements. Although it is often considered an oculomotor structure, several lines of evidence suggest that the FEF also contributes to visual perception and attention. To better understand the range of behaviors to which the FEF can contribute, we tested whether monkeys could detect activation of their FEF by electrical microstimulation with currents below those that cause eye movements. We found that stimulation of FEF neurons could almost always be detected at levels below those needed to generate saccades and that the electrical current needed for detection was highly correlated with that needed to generate a saccade. This relationship between detection and saccade thresholds can be explained if FEF neurons represent preparation to make particular saccades and subjects can be aware of such preparations without acting on them when the representation is not strong.