Evolutionary Pressure on Mitochondrial Cytochrome b Is Consistent with a Role of CytbI7T Affecting Longevity during Caloric Restriction

Background: Metabolism of energy nutrients by the mitochondrial electron transport chain (ETC) is implicated in the aging process. Polymorphisms in core ETC proteins may have an effect on longevity. Here we investigate the cytochrome b (cytb) polymorphism at amino acid 7 (cytbI7T) that distinguishes human mitochondrial haplogroup H from haplogroup U. Principal Findings: We compared longevity of individuals in these two haplogroups during historical extremes of caloric intake. Haplogroup H exhibits significantly increased longevity during historical caloric restriction compared to haplogroup U(p = 0.02) while during caloric abundance they are not different. The historical effects of natural selection on the cytb protein were estimated with the software TreeSAAP using a phylogenetic reconstruction for 107 mammal taxa from all major mammalian lineages using 13 complete protein-coding mitochondrial gene sequences. With this framework, we compared the biochemical shifts produced by cytbI7T with historical evolutionary pressure on and near this polymorphic site throughout mammalian evolution to characterize the role cytbI7T had on the ETC during times of restricted caloric intake. Significance: Our results suggest the relationship between caloric restriction and increased longevity in human mitochondrial haplogroup H is determined by cytbI7T which likely enhances the ability of water to replenish the Q i binding site and decreases the time ubisemiquinone is at the Qo site, resulting in a decrease in the average production rate of radica

Using a simplified human immunodeficiency virus type 1 p24 antigen assay to diagnose pediatric HIV-infection in Malawi

There is a worldwide need for a pediatric HIV-1 diagnostic test that has a high diagnostic accuracy, is technically simple and cost efficient. The Up24 HIV-1 assay, which requires both the HIV-1 p24 ELISA and the ELAST signal amplification kit, has previously been shown to be a robust tool to diagnose pediatric HIV-1 from dried whole blood spots (DBS) (Cachafeiro et al., JCM 2009;47:459–6213). In order to make the assay more accessible to a resource-limited clinical setting, we eliminated the ELAST system, which simplified the Up24 assay, reduced its cost, and tested the accuracy of the modified assay in a rural Malawian hospital

A Forward Genetic Screen in Mice Identifies Mutants with Abnormal Cortical Patterning

Formation of a 6-layered cortical plate and axon tract patterning are key features of cerebral cortex development. Abnormalities of these processes may be the underlying cause for a range of functional disabilities seen in human neurodevelopmental disorders. To identify mouse mutants with defects in cortical lamination or corticofugal axon guidance, N-ethyl-N-nitrosourea (ENU) mutagenesis was performed using mice expressing LacZ reporter genes in layers II/III and V of the cortex (Rgs4-lacZ) or in corticofugal axons (TAG1-tau-lacZ). Four lines with abnormal cortical lamination have been identified. One of these was a splice site mutation in reelin (Reln) that results in a premature stop codon and the truncation of the C-terminal region (CTR) domain of reelin. Interestingly, this novel allele of Reln did not display cerebellar malformation or ataxia, and this is the first report of a Reln mutant without a cerebellar defect. Four lines with abnormal cortical axon development were also identified, one of which was found by whole-genome resequencing to carry a mutation in Lrp2. These findings demonstrated that the application of ENU mutagenesis to mice carrying transgenic reporters marking cortical anatomy is a sensitive and specific method to identify mutations that disrupt patterning of the developing brain

Decision making in child protection:An international comparative study on maltreatment substantiation, risk assessment and interventions recommendations, and the role of professionals’ child welfare attitudes

Item does not contain fulltextChild welfare professionals regularly make crucial decisions that have a significant impact on children and their families. The present study presents the Judgments and Decision Processes in Context model (JUDPIC) and uses it to examine the relationships between three independent domains: case characteristic (mother's wish with regard to removal), practitioner characteristic (child welfare attitudes), and protective system context (four countries: Israel, the Netherlands, Northern Ireland and Spain); and three dependent factors: substantiation of maltreatment, risk assessment, and intervention recommendation. The sample consisted of 828 practitioners from four countries. Participants were presented with a vignette of a case of alleged child maltreatment and were asked to determine whether maltreatment was substantiated, assess risk and recommend an intervention using structured instruments. Participants’ child welfare attitudes were assessed. The case characteristic of mother's wish with regard to removal had no impact on judgments and decisions. In contrast, practitioners’ child welfare attitudes were associated with substantiation, risk assessments and recommendations. There were significant country differences on most measures. The findings support most of the predictions derived from the JUDPIC model. The significant differences between practitioners from different countries underscore the importance of context in child protection decision making. Training should enhance practitioners’ awareness of the impact that their attitudes and the context in which they are embedded have on their judgments and decisions

Rise of the Earliest Tetrapods: An Early Devonian Origin from Marine Environment

Tetrapod fossil tracks are known from the Middle Devonian (Eifelian at ca. 397 million years ago - MYA), and their earliest bony remains from the Upper Devonian (Frasnian at 375–385 MYA). Tetrapods are now generally considered to have colonized land during the Carboniferous (i.e., after 359 MYA), which is considered to be one of the major events in the history of life. Our analysis on tetrapod evolution was performed using molecular data consisting of 13 proteins from 17 species and different paleontological data. The analysis on the molecular data was performed with the program TreeSAAP and the results were analyzed to see if they had implications on the paleontological data collected. The results have shown that tetrapods evolved from marine environments during times of higher oxygen levels. The change in environmental conditions played a major role in their evolution. According to our analysis this evolution occurred at about 397–416 MYA during the Early Devonian unlike previously thought. This idea is supported by various environmental factors such as sea levels and oxygen rate, and biotic factors such as biodiversity of arthropods and coral reefs. The molecular data also strongly supports lungfish as tetrapod's closest living relative

A Genome-Wide Gene Function Prediction Resource for Drosophila melanogaster

Predicting gene functions by integrating large-scale biological data remains a challenge for systems biology. Here we present a resource for Drosophila melanogaster gene function predictions. We trained function-specific classifiers to optimize the influence of different biological datasets for each functional category. Our model predicted GO terms and KEGG pathway memberships for Drosophila melanogaster genes with high accuracy, as affirmed by cross-validation, supporting literature evidence, and large-scale RNAi screens. The resulting resource of prioritized associations between Drosophila genes and their potential functions offers a guide for experimental investigations

Cell-specific microarray profiling experiments reveal a comprehensive picture of gene expression in the C. elegans nervous system

A novel strategy for profiling Caenorhabditis elegans cells identifies transcripts highly enriched in either the embryonic or larval C. elegans nervous system, including 19 conserved transcripts of unknown function that are also expressed in the mammalian brain