Patterns of biomedical science production in a sub-Saharan research center

<p>Abstract</p> <p>Background</p> <p>Research activities in sub-Saharan Africa may be limited to delegated tasks due to the strong control from Western collaborators, which could lead to scientific production of little value in terms of its impact on social and economic innovation in less developed areas. However, the current contexts of international biomedical research including the development of public-private partnerships and research institutions in Africa suggest that scientific activities are growing in sub-Saharan Africa. This study aims to describe the patterns of clinical research activities at a sub-Saharan biomedical research center.</p> <p>Methods</p> <p>In-depth interviews were conducted with a core group of researchers at the Medical Research Unit of the Albert Schweitzer Hospital from June 2009 to February 2010 in Lambaréné, Gabon. Scientific activities running at the MRU as well as the implementation of ethical and regulatory standards were covered by the interview sessions.</p> <p>Results</p> <p>The framework of clinical research includes transnational studies and research initiated locally. In transnational collaborations, a sub-Saharan research institution may be limited to producing confirmatory and late-stage data with little impact on economic and social innovation. However, ethical and regulatory guidelines are being implemented taking into consideration the local contexts. Similarly, the scientific content of studies designed by researchers at the MRU, if local needs are taken into account, may potentially contribute to a scientific production with long-term value on social and economic innovation in sub-Saharan Africa.</p> <p>Conclusion</p> <p>Further research questions and methods in social sciences should comprehensively address the construction of scientific content with the social, economic and cultural contexts surrounding research activities.</p

Structural characterization of suppressor lipids by high-resolution mass spectrometry

Rationale: Suppressor lipids were originally identified in 1993 and reported to encompass six lipid classes that enable Saccharomyces cerevisiae to live without sphingolipids. Structural characterization, using non-mass spectrometric approaches, revealed that these suppressor lipids are very long chain fatty acid (VLCFA)- containing glycerophospholipids with polar head groups that are typically incorporated into sphingolipids. Here we report, for the first time, the structural characterization of the yeast suppressor lipids using high-resolution mass spectrometry.Methods: Suppressor lipids were isolated by preparative chromatography and subjected to structural characterization using hybrid quadrupole time-of-flight and ion trap-orbitrap mass spectrometry.Results: Our investigation recapitulates the overall structural features of the suppressor lipids and provides an in-depth characterization of their fragmentation pathways. Tandem mass analysis identified the positionally defined molecular lipid species phosphatidylinositol (PI) 26:0/16:1, PI mannoside (PIM) 16:0/26:0 and PIM inositol-phosphate (PIMIP) 16:0/26:0 as abundant suppressor lipids. This finding differs from the original study that only inferred the positional isomer PI 16:0/26:0 and prompts new insight into the biosynthesis of suppressor lipids. Moreover, we also report the identification of a novel suppressor lipid featuring an amino sugar residue linked to a VLCFA-containing PI molecule.Conclusions: Fragmentation pathways of yeast suppressor lipids have been delineated. In addition, the fragmentation information has been added to our open source ALEX lipid database to support automated identification and quantitative monitoring of suppressor lipids in yeast and bacteria that produce similar lipid molecules

Whole blood gene expression in infants with respiratory syncytial virus bronchiolitis

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of viral bronchiolitis in infants worldwide, and environmental, viral and host factors are all of importance for disease susceptibility and severity. To study the systemic host response to this disease we used the microarray technology to measure mRNA gene expression levels in whole blood of five male infants hospitalised with acute RSV, subtype B, bronchiolitis versus five one year old male controls exposed to RSV during infancy without bronchiolitis. The gene expression levels were further evaluated in a new experiment using quantitative real-time polymerase chain reaction (QRT-PCR) both in the five infants selected for microarray and in 13 other infants hospitalised with the same disease. RESULTS: Among the 30 genes most differentially expressed by microarray nearly 50% were involved in immunological processes. We found the highly upregulated interferon, alpha-inducible protein 27 (IFI27) and the highly downregulated gene Charcot-Leyden crystal protein (CLC) to be the two most differentially expressed genes in the microarray study. When performing QRT-PCR on these genes IFI27 was upregulated in all but one infant, and CLC was downregulated in all 18 infants, and similar to that given by microarray. CONCLUSION: The gene IFI27 is upregulated and the gene CLC is downregulated in whole blood of infants hospitalised with RSV, subtype B, bronchiolitis and is not reported before. More studies are needed to elucidate the specificity of these gene expressions in association with host response to this virus in bronchiolitis of moderate severity

Jesus, Barabbas and the People: The Climax of Luke’s Trial Narrative and Lukan Christology (Luke 23.13-25)

This article argues that the nuance and function given to the Barabbas pericope in Luke’s trial narrative differs significantly from that expressed by the other evangelists. It submits that Luke depicts Jesus’ death to be the result of a substitution between the acquitted Jesus and the insurrectionist and murderer Barabbas. Furthermore, the third evangelist has crafted his trial narrative so as to highlight the representative nature of this death, thereby developing Jesus’ narrative identity as the Messiah. It is concluded that Luke’s crafting of his trial narrative raises questions for the prevalent view that the third evangelist has not integrated the idea of substitution into his understanding of Jesus’ death

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3–90 years

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Consortium to examine age‐related trajectories inferred from cross‐sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3–90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter‐individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age‐related morphometric patterns

Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large‐scale studies. In response, we used cross‐sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Consortium to infer age‐related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta‐analysis and one‐way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes

The Theology of St Luke

New York255 p.; 20 c

Hermeneia - A Critical and Historial commentary on the Bible : V.5: Acts of the Apostles

Philadelphia287 p. ; 24 c