Comparative proteomic analysis of metabolically labelled proteins from Plasmodium falciparum isolates with different adhesion properties

The virulence of Plasmodium falciparum relates in part to the cytoadhesion characteristics of parasitized erythrocytes but the molecular basis of the different qualitative and quantitative binding phenotypes is incompletely understood. This paucity of information is due partly to the difficulty in working with membrane proteins, the variant nature of these surface antigens and their relatively low abundance. To address this two-dimensional (2D) protein profiles of closely related, but phenotypically different laboratory strains of P. falciparum have been characterized using proteomic approaches. Since the mature erythrocyte has no nucleus and no protein synthesis capability, metabolic labelling of proteins was used to selectively identify parasite proteins and increase detection sensitivity. A small number of changes (less than 10) were observed between four different P. falciparum laboratory strains with distinctive cytoadherence properties using metabolic labelling, with more parasite protein changes found in trophozoite iRBCs than ring stage. The combination of metabolic labelling and autoradiography can therefore be used to identify parasite protein differences, including quantitative ones, and in some cases to obtain protein identifications by mass spectrometry. The results support the suggestion that the membrane protein profile may be related to cytoadherent properties of the iRBCs. Most changes between parasite variants were differences in iso-electric point indicating differential protein modification rather than the presence or absence of a specific peptide

Lean mass, muscle strength, and physical function in a diverse population of men: a population-based cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Age-related declines in lean body mass appear to be more rapid in men than in women but our understanding of muscle mass and function among different subgroups of men and their changes with age is quite limited. The objective of this analysis is to examine racial/ethnic differences and racial/ethnic group-specific cross-sectional age differences in measures of muscle mass, muscle strength, and physical function among men.</p> <p>Methods</p> <p>Data were obtained from the Boston Area Community Health/Bone (BACH/Bone) Survey, a population-based, cross-sectional, observational survey. Subjects included 1,157 black, Hispanic, and white randomly-selected Boston men ages 30-79 y. Lean mass was assessed by dual-energy x-ray absorptiometry. Upper extremity (grip) strength was assessed with a hand dynamometer and lower extremity physical function was derived from walk and chair stand tests. Upper extremity strength and lower extremity physical function were also indexed by lean mass and lean mass was indexed by the square of height.</p> <p>Results</p> <p>Mean age of the sample was 47.5 y. Substantial cross-sectional age differences in grip strength and physical function were consistent across race/ethnicity. Racial/ethnic differences, with and without adjustment for covariates, were evident in all outcomes except grip strength. Racial differences in lean mass did not translate into parallel differences in physical function. For instance, multivariate modeling (with adjustments for age, height, fat mass, self-rated health and physical activity) indicated that whereas total body lean mass was 2.43 kg (approximately 5%) higher in black compared with white men, black men had a physical function score that was approximately 20% lower than white men.</p> <p>Conclusions</p> <p>In spite of lower levels of lean mass, the higher levels of physical function observed among white compared with non-white men in this study appear to be broadly consistent with known racial/ethnic differences in outcomes.</p

Eye Size at Birth in Prosimian Primates: Life History Correlates and Growth Patterns

BACKGROUND: Primates have large eyes relative to head size, which profoundly influence the ontogenetic emergence of facial form. However, growth of the primate eye is only understood in a narrow taxonomic perspective, with information biased toward anthropoids.\ud \ud METHODOLOGY/PRINCIPAL FINDINGS: We measured eye and bony orbit size in perinatal prosimian primates (17 strepsirrhine taxa and Tarsius syrichta) to infer the extent of prenatal as compared to postnatal eye growth. In addition, multiple linear regression was used to detect relationships of relative eye and orbit diameter to life history variables. ANOVA was used to determine if eye size differed according to activity pattern. In most of the species, eye diameter at birth measures more than half of that for adults. Two exceptions include Nycticebus and Tarsius, in which more than half of eye diameter growth occurs postnatally. Ratios of neonate/adult eye and orbit diameters indicate prenatal growth of the eye is actually more rapid than that of the orbit. For example, mean neonatal transverse eye diameter is 57.5% of the adult value (excluding Nycticebus and Tarsius), compared to 50.8% for orbital diameter. If Nycticebus is excluded, relative gestation age has a significant positive correlation with relative eye diameter in strepsirrhines, explaining 59% of the variance in relative transverse eye diameter. No significant differences were found among species with different activity patterns.\ud \ud CONCLUSIONS/SIGNIFICANCE: The primate developmental strategy of relatively long gestations is probably tied to an extended period of neural development, and this principle appears to apply to eye growth as well. Our findings indicate that growth rates of the eye and bony orbit are disassociated, with eyes growing faster prenatally, and the growth rate of the bony orbit exceeding that of the eyes after birth. Some well-documented patterns of orbital morphology in adult primates, such as the enlarged orbits of nocturnal species, mainly emerge during postnatal development.\ud \u

Cross-cultural adaptation and validation of a disease knowledge and self-care questionnaire for a brazilian sample of heart failure patients

To adapt a questionnaire that assesses knowledge about heart failure (HF) and self-care and to analyze its content validity and reproducibility for use in Brazil. The questionnaire was validated through translation, summary, back-translation, expert committee review, pretest and assessment of psychometric properties. The final version (14 questions) was applied at the university hospital to HF outpatients under multidisciplinary team care. Five questions showed total agreement; seven scored Kappa > 0.4; one Kappa = 0.4, and just one presented no agreement. A group of 153 patients within 1-4 years of outpatient follow-up was assessed (age 59±13, 61% male). In the knowledge assessment, right answers varied from 4 to 14 (average 9.9±2.1). Results indicate the validity of the questionnaire for use in Brazil.Se tuvo por objetivo realizar la adaptación transcultural de un cuestionario que evalúa el conocimiento sobre la insuficiencia cardíaca (IC) y el autocuidado y analizar su validez de contenido y la reproductibilidad para uso en Brasil. Se trata de un proceso de validación constituido de traducción, síntesis, retrotraducción, revisión por comité de expertos, prueba piloto y verificación de las propiedades psicométricas. La versión final adaptada con 14 preguntas fue aplicada a pacientes con IC en acompañamiento en ambulatorio con el equipo multidisciplinar de un hospital universitario. Cinco preguntas presentaron concordancia total; siete obtuvieron coeficiente Kappa > 0,4; una obtuvo Kappa 0,4 y apenas en una pregunta no hubo concordancia. Se evaluaron 153 pacientes, edad de 59±13; 61% sexo masculino; mediana de tiempo de acompañamiento en el ambulatorio 2 (1-4) años. En la evaluación del conocimiento, los aciertos variaron de cuatro a 14, promedio 9,9±2,1. Concluimos que los resultados indicaron que este cuestionario fue validado para ser usado en Brasil.Esta pesquisa teve como objetivos realizar a adaptação transcultural de um questionário que avalia o conhecimento sobre a insuficiência cardíaca (IC) e o autocuidado e analisar sua validade de conteúdo e a reprodutibilidade para uso no Brasil. O processo de validação constituiu-se de tradução, síntese, retrotradução, revisão por comitê de especialistas, pré-teste e verificação das propriedades psicométricas. A versão final adaptada com 14 questões foi aplicada a pacientes com IC em acompanhamento ambulatorial com a equipe multidisciplinar de um hospital universitário. Quanto aos resultados, cinco questões apresentaram concordância total, sete obtiveram coeficiente Kappa >0,4, uma obteve Kappa 0,4 e apenas em uma questão não houve concordância. Avaliaram-se 153 pacientes, idade de 59±13, sendo 64% sexo masculino; mediana do tempo de acompanhamento no ambulatório de 2 (1-4) anos. Na avaliação do conhecimento, os acertos variaram de quatro a 14, média 9,9±2,1. Conclui-se pelos resultados, que esse questionário foi validado para uso no Brasil

Effects of dairy intake on weight maintenance

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

GmFT2a, a Soybean Homolog of FLOWERING LOCUS T, Is Involved in Flowering Transition and Maintenance

BACKGROUND: Flowering reversion can be induced in soybean (Glycine max L. Merr.), a typical short-day (SD) dicot, by switching from SD to long-day (LD) photoperiods. This process may involve florigen, putatively encoded by FLOWERING LOCUS T (FT) in Arabidopsis thaliana. However, little is known about the potential function of soybean FT homologs in flowering reversion. METHODS: A photoperiod-responsive FT homologue GmFT (renamed as GmFT2a hereafter) was cloned from the photoperiod-sensitive cultivar Zigongdongdou. GmFT2a gene expression under different photoperiods was analyzed by real-time quantitative PCR. In situ hybridization showed direct evidence for its expression during flowering-related processes. GmFT2a was shown to promote flowering using transgenic studies in Arabidopsis and soybean. The effects of photoperiod and temperature on GmFT2a expression were also analyzed in two cultivars with different photoperiod-sensitivities. RESULTS: GmFT2a expression is regulated by photoperiod. Analyses of GmFT2a transcripts revealed a strong correlation between GmFT2a expression and flowering maintenance. GmFT2a transcripts were observed continuously within the vascular tissue up to the shoot apex during flowering. By contrast, transcripts decreased to undetectable levels during flowering reversion. In grafting experiments, the early-flowering, photoperiod-insensitive stock Heihe27 promotes the appearance of GmFT2a transcripts in the shoot apex of scion Zigongdongdou under noninductive LD conditions. The photothermal effects of GmFT2a expression diversity in cultivars with different photoperiod-sensitivities and a hypothesis is proposed. CONCLUSION: GmFT2a expression is associated with flowering induction and maintenance. Therefore, GmFT2a is a potential target gene for soybean breeding, with the aim of increasing geographic adaptation of this crop

Nuclear cGMP-Dependent Kinase Regulates Gene Expression via Activity-Dependent Recruitment of a Conserved Histone Deacetylase Complex

Elevation of the second messenger cGMP by nitric oxide (NO) activates the cGMP-dependent protein kinase PKG, which is key in regulating cardiovascular, intestinal, and neuronal functions in mammals. The NO-cGMP-PKG signaling pathway is also a major therapeutic target for cardiovascular and male reproductive diseases. Despite widespread effects of PKG activation, few molecular targets of PKG are known. We study how EGL-4, the Caenorhabditis elegans PKG ortholog, modulates foraging behavior and egg-laying and seeks the downstream effectors of EGL-4 activity. Using a combination of unbiased forward genetic screen and proteomic analysis, we have identified a conserved SAEG-1/SAEG-2/HDA-2 histone deacetylase complex that is specifically recruited by activated nuclear EGL-4. Gene expression profiling by microarrays revealed >40 genes that are sensitive to EGL-4 activity in a SAEG-1–dependent manner. We present evidence that EGL-4 controls egg laying via one of these genes, Y45F10C.2, which encodes a novel protein that is expressed exclusively in the uterine epithelium. Our results indicate that, in addition to cytoplasmic functions, active EGL-4/PKG acts in the nucleus via a conserved Class I histone deacetylase complex to regulate gene expression pertinent to behavioral and physiological responses to cGMP. We also identify transcriptional targets of EGL-4 that carry out discrete components of the physiological response

Introduction to “Binary Binds”: Deconstructing Sex and Gender Dichotomies in Archaeological Practice

YesGender archaeology has made significant strides toward deconstructing the hegemony of binary categorizations. Challenging dichotomies such as man/woman, sex/gender, and biology/culture, approaches informed by poststructuralist, feminist, and queer theories have moved beyond essentialist and universalist identity constructs to more nuanced configurations. Despite the theoretical emphasis on context, multiplicity, and fluidity, binary starting points continue to streamline the spectrum of variability that is recognized, often reproducing normative assumptions in the evidence. The contributors to this special issue confront how sex, gender, and sexuality categories condition analytical visibility, aiming to develop approaches that respond to the complexity of theory in archaeological practice. The papers push the ontological and epistemological boundaries of bodies, personhood, and archaeological possibility, challenging a priori assumptions that contain how sex, gender, and sexuality categories are constituted and related to each other. Foregrounding intersectional approaches that engage with ambiguity, variability, and difference, this special issue seeks to “de-contain” categories, assumptions, and practices from “binding” our analytical gaze toward only certain kinds of persons and knowledges, in interpretations of the past and practices in the present

Evidence-Based Annotation of the Malaria Parasite's Genome Using Comparative Expression Profiling

A fundamental problem in systems biology and whole genome sequence analysis is how to infer functions for the many uncharacterized proteins that are identified, whether they are conserved across organisms of different phyla or are phylum-specific. This problem is especially acute in pathogens, such as malaria parasites, where genetic and biochemical investigations are likely to be more difficult. Here we perform comparative expression analysis on Plasmodium parasite life cycle data derived from P. falciparum blood, sporozoite, zygote and ookinete stages, and P. yoelii mosquito oocyst and salivary gland sporozoites, blood and liver stages and show that type II fatty acid biosynthesis genes are upregulated in liver and insect stages relative to asexual blood stages. We also show that some universally uncharacterized genes with orthologs in Plasmodium species, Saccharomyces cerevisiae and humans show coordinated transcription patterns in large collections of human and yeast expression data and that the function of the uncharacterized genes can sometimes be predicted based on the expression patterns across these diverse organisms. We also use a comprehensive and unbiased literature mining method to predict which uncharacterized parasite-specific genes are likely to have roles in processes such as gliding motility, host-cell interactions, sporozoite stage, or rhoptry function. These analyses, together with protein-protein interaction data, provide probabilistic models that predict the function of 926 uncharacterized malaria genes and also suggest that malaria parasites may provide a simple model system for the study of some human processes. These data also provide a foundation for further studies of transcriptional regulation in malaria parasites

Evaluating genetic markers and neurobiochemical analytes for fluoxetine response using a panel of mouse inbred strains

RationaleIdentification of biomarkers that establish diagnosis or treatment response is critical to the advancement of research and management of patients with depression.ObjectiveOur goal was to identify biomarkers that can potentially assess fluoxetine response and risk to poor treatment outcome.MethodsWe measured behavior, gene expression, and the levels of 36 neurobiochemical analytes across a panel of genetically diverse mouse inbred lines after chronic treatment with water or fluoxetine.ResultsGlyoxylase 1 (GLO1) and guanine nucleotide-binding protein 1 (GNB1) mostly account for baseline anxiety-like and depressive-like behavior, indicating a common biological link between depression and anxiety. Fluoxetine-induced biochemical alterations discriminated positive responders, while baseline neurobiochemical differences differentiated negative responders (p < 0.006). Results show that glial fibrillary acidic protein, S100 beta protein, GLO1, and histone deacetylase 5 contributed most to fluoxetine response. These proteins are linked within a cellular growth/proliferation pathway, suggesting the involvement of cellular genesis in fluoxetine response. Furthermore, a candidate genetic locus that associates with baseline depressive-like behavior contains a gene that encodes for cellular proliferation/adhesion molecule (Cadm1), supporting a genetic basis for the role of neuro/gliogenesis in depression.ConclusionWe provided a comprehensive analysis of behavioral, neurobiochemical, and transcriptome data across 30 mouse inbred strains that has not been accomplished before. We identified biomarkers that influence fluoxetine response, which, altogether, implicate the importance of cellular genesis in fluoxetine treatment. More broadly, this approach can be used to assess a wide range of drug response phenotypes that are challenging to address in human samples.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-011-2574-z) contains supplementary material, which is available to authorized users