Kinetics and specificities of the T helper-cell response to gp120 in the asymptomatic stage of HIV-1 infection

Peripheral blood mononuclear cells from 36 asymptomatic HIV-1 seropositive individuals were tested longitudinally for in vitro T–cell proliferation and IL–2 production in response to synthetic peptides spanning the entire gp120 of HIV–1. At baseline, significant T–cell proliferation to pooled and individual peptides was observed in 15 of the 36 donors. After 12 months, proliferate responses to peptide pools were lost or decreased significantly in most donors. Responses appeared to fluctuate over time: at 12 months new recognition sites were detected in four of 10 donors showing T–cell proliferation at baseline, as well as in five of 15 donors with no previous proliferative responses. IL–2 production appeared to be a more sensitive and longer preserved parameter of T–helper cell function: at baseline the majority of donors with no T–cell proliferation produced IL–2 in response to pooled peptides. This response was not decreased significantly after 12 months. The overall patterns of response to both pooled and individual peptides were heterogeneous among donors. Multiple recognition sites were detected in both variable and conserved regions of gp120, but no pool or individual peptide was recognized by all responders. Functional T–cell responses were not statistically correlated to CD4° cell percentile and absolute numbers

Gli3 Controls Corpus Callosum Formation by Positioning Midline Guideposts During Telencephalic Patterning

The corpus callosum (CC) represents the major forebrain commissure connecting the 2 cerebral hemispheres. Midline crossing of callosal axons is controlled by several glial and neuronal guideposts specifically located along the callosal path, but it remains unknown how these cells acquire their position. Here, we show that the Gli3 hypomorphic mouse mutant Polydactyly Nagoya (Pdn) displays agenesis of the CC and mislocation of the glial and neuronal guidepost cells. Using transplantation experiments, we demonstrate that agenesis of the CC is primarily caused by midline defects. These defects originate during telencephalic patterning and involve an up-regulation of Slit2 expression and altered Fgf and Wnt/β-catenin signaling. Mutations in sprouty1/2 which mimic the changes in these signaling pathways cause a disorganization of midline guideposts and CC agenesis. Moreover, a partial recovery of midline abnormalities in Pdn/Pdn;Slit2−/− embryos mutants confirms the functional importance of correct Slit2 expression levels for callosal development. Hence, Gli3 controlled restriction of Fgf and Wnt/β-catenin signaling and of Slit2 expression is crucial for positioning midline guideposts and callosal developmen

Potential of RFID telemetry for monitoring ground-dwelling beetle movements: A Mediterranean dry grassland study

Better understanding insects’ movements could help preserve and restore the insect communities that are key to the functioning of grasslands. Recent technological advances have led to spectacular achievements in movement ecology, making it possible to track the individual movements of a wide variety of organisms, including the smallest. However, monitoring systems such as RFID tags may negatively impact an organism’s life history, with potential consequences on the reliability of data and conclusions. This study explored the potential of passive RFID tags to track the movements of three small ground-dwelling beetle species, a predator (Poecilus sericeus, Carabidae), a detritivore (Asida sericea, Tenebrionidae) and a granivore (Acinopus picipes, Carabidae), in a Mediterranean dry grassland degraded by years of cultivation. First, we tested whether carrying tags might impact individuals’ behaviour, using a before-and-after design under laboratory conditions. Despite a trend toward shorter displacements, we found no significant short-term effect of the tags on individuals’ movements. Second, we tracked a total of 25 tagged beetles in their natural environment every 4 h for 48 h. We highlight the principal limitation of using passive tags with small terrestrial beetles: the antenna has to pass over the tags to detect them, which restricts tracking to a few consecutive days after which the probability of locating an individual is low. However, the data obtained sheds light on the biological rhythms and daily movement capabilities of our target species: A. sericea is more mobile and P. sericeus less mobile than expected. Such knowledge could help predict the species’ ability to recolonise degraded areas, enabling appropriate restoration actions to be designed based on landscape ecology principles

Assessment of the Nutritional Status of Children Living in Orphanages in the City of Douala, Cameroon

Introduction: Malnutrition is characterised by metabolic disturbances identified by measurement of anthropometric and biological parameters. The purpose of this study was to determine the nutritional profile of children living in orphanages and to investigate the factors associated with malnutrition in these institutions. Methods: A cross-sectional study was conducted on subjects aged 0 to 18, living in 13 orphanages in Douala. Socio-demographic data, anthropometric and biological parameters were collected. The diagnosis of malnutrition at the clinical level was based on Z score <-2 for the different index and >2 for Weight-for-Height and Body Mass Index for Age. A blood sample permits the photometric assay of albumin, pre-albumin, and C Reactive Protein. The results were interpreted according to reference values for age. Results: Among the 176 children included, the average age was 10±4 years with a male predominance. The majority of children (51.1%) were placed in orphanages for lack of financial resources, and one or both parents orphaned were 42.1%. The wasting, underweight and stunting rates were 5.6%, 4.7%, and 18.2%, respectively. Hypo-pre-albuminemia and hypo-albuminemia were observed in 42.6% and 34.7% of children respectively. CRP was increased in 5.1% of cases. Stunting and orphanages with one caregiver for more than 5 children were predictive factors for hypo-albuminemia and Hypo-pre-albuminemia. Conclusion: Rates of wasting, stunting and underweight were high. Several children had sub-clinical malnutrition despite normal anthropometric index. These results recall the importance of biology for screening, in order to prevent the occurrence of clinical malnutrition

Aging in humid granular media

Aging behavior is an important effect in the friction properties of solid surfaces. In this paper we investigate the temporal evolution of the static properties of a granular medium by studying the aging over time of the maximum stability angle of submillimetric glass beads. We report the effect of several parameters on these aging properties, such as the wear on the beads, the stress during the resting period, and the humidity content of the atmosphere. Aging effects in an ethanol atmosphere are also studied. These experimental results are discussed at the end of the paper.Comment: 7 pages, 9 figure

Fine-specificity of cytotoxic T lymphocytes which recognize conserved epitopes of the Gag protein of human immunodeficiency virus type 1

Human immunodeficiency virus type 1 (HIV-1) Gag-specific cytotoxic T lymphocyte (CTL) responses were studied in seven seropositive long-term asymptomatic individuals (CDC A1)with stable CD4 counts for more than 8 years. Using a set of partially overlapping peptides covering the whole Gag, five 15-20-mer peptides were found to contain CTL epitopes. Further characterization of these epitopes revealed a new HLA-A25-restricted CTL epitope in p24, p24203-212 ETINEEAAEW. This region of Gag highly conserved in clades B and D of HIV-1. Naturally occurring amino acid sequences, containing p24203D (consensus HIV-1 clades A, C, F, G and H) or p24204I(HIV-2(ROD)) were not recognized by CTL recognizing the index peptide. No virus variants with mutations in this sequence were found in peripheral blood mononuclear cells from the HIV-1-infected individual concerned during the 8 year observation period, indicating that the virus had not escaped from the observed CTL response.</p

Stable isotope tagging of epitopes: a highly selective strategy for the identification of major histocompatibility complex class I-associated peptides induced upon viral infection.

Identification of peptides presented in major histocompatibility complex (MHC) class I molecules after viral infection is of strategic importance for vaccine development. Until recently, mass spectrometric identification of virus-induced peptides was based on comparative analysis of peptide pools isolated from uninfected and virus-infected cells. Here we report on a powerful strategy aiming at the rapid, unambiguous identification of naturally processed MHC class I-associated peptides, which are induced by viral infection. The methodology, stable isotope tagging of epitopes (SITE), is based on metabolic labeling of endogenously synthesized proteins during infection. This is accomplished by culturing virus-infected cells with stable isotope-labeled amino acids that are expected to be anchor residues (i.e. residues of the peptide that have amino acid side chains that bind into pockets lining the peptide-binding groove of the MHC class I molecule) for the human leukocyte antigen allele of interest. Subsequently these cells are mixed with an equal number of non-infected cells, which are cultured in normal medium. Finally peptides are acid-eluted from immunoprecipitated MHC molecules and subjected to two-dimensional nanoscale LC-MS analysis. Virus-induced peptides are identified through computer-assisted detection of characteristic, binomially distributed ratios of labeled and unlabeled molecules. Using this approach we identified novel measles virus and respiratory syncytial virus epitopes as well as infection-induced self-peptides in several cell types, showing that SITE is a unique and versatile method for unequivocal identification of disease-related MHC class I epitopes

A comprehensive assessment of demographic, environmental, and host genetic associations with gut microbiome diversity in healthy individuals.

BACKGROUND: The gut microbiome is an important determinant of human health. Its composition has been shown to be influenced by multiple environmental factors and likely by host genetic variation. In the framework of the Milieu Intérieur Consortium, a total of 1000 healthy individuals of western European ancestry, with a 1:1 sex ratio and evenly stratified across five decades of life (age 20-69), were recruited. We generated 16S ribosomal RNA profiles from stool samples for 858 participants. We investigated genetic and non-genetic factors that contribute to individual differences in fecal microbiome composition. RESULTS: Among 110 demographic, clinical, and environmental factors, 11 were identified as significantly correlated with α-diversity, ß-diversity, or abundance of specific microbial communities in multivariable models. Age and blood alanine aminotransferase levels showed the strongest associations with microbiome diversity. In total, all non-genetic factors explained 16.4% of the variance. We then searched for associations between > 5 million single nucleotide polymorphisms and the same indicators of fecal microbiome diversity, including the significant non-genetic factors as covariates. No genome-wide significant associations were identified after correction for multiple testing. A small fraction of previously reported associations between human genetic variants and specific taxa could be replicated in our cohort, while no replication was observed for any of the diversity metrics. CONCLUSION: In a well-characterized cohort of healthy individuals, we identified several non-genetic variables associated with fecal microbiome diversity. In contrast, host genetics only had a negligible influence. Demographic and environmental factors are thus the main contributors to fecal microbiome composition in healthy individuals. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01699893