The French Institute for Public Health Surveillance set up two communities based surveys which provide both Hepatitis B surface antigen (HBsAg). The first one, the ANRS-Coquelicot survey, studied in ...2011-2013 drug users (DUs) who attend specialized structures in health care and risk reduction. The second survey, Prevagay, concerned men who have sex with men (MSM) who attended Paris gay venues in 2009. Persons recruited for both surveys were invited to collect a fingerprick whole blood sample on filter paper, and to respond to a behavioral questionnaire. This questionnaire was anonymous and administered by interviewers for DUs, and self-completed for MSM. Blood samples were screened for the presence of HBs Ag using the Monolisa HBs Ag ULTRA (Biorad®) assay. Among the 647 DUs and the 876 MSM investigated in Paris and included in the analysis, 15 DUs and 12 MSM were diagnosed HBs Ag-positive, representing HBs Ag seroprevalence of 2.1% (IC95% 1.0-4.2) and 1.4%,respectively. In these two specific populations, different in terms of socio-demographic profiles, and both at risk of HBV transmission, due to their drug use practices or their sexual behaviors, HBs Ag seroprevalence was closeto the one observed in the general population.
L’Institut de veille sanitaire a mené deux études de séroprévalence de l’antigène HBs (AgHBs) en populations spécifiques. La première, l’enquête ANRS-Coquelicot, a étudié en 2011-2013 les usagers de drogue (UD) fréquentant les structures de prise en charge et de réduction des risques. La seconde, Prevagay, concernait les hommes ayant des rapports sexuels avec des hommes (HSH) fréquentant les lieux de convivialité gay parisiens en 2009. Les personnes recrutées pour ces deux études déposaient sur un papier buvard un échantillon de sang par auto-prélèvement capillaire au bout du doigt, puis répondaient à un questionnaire comportemental. Ce questionnaire était anonyme et passé en face-à face avec des enquêteurs pour les UD, et auto-administré pour les HSH. La recherche de l’AgHBs a été réalisée en laboratoire, à l’aide de la trousse Elisa Monolisa HBsAg ULTRA (Biorad®). Parmi les 647 hommes UD et les 876 HSH enquêtés à Paris et retenus pour l’analyse, 15 UD et 12 HSH étaient porteurs de l’AgHBs, soit des séroprévalences respectives de 2,1% (IC95% 1,0-4,2) et 1,4%. Ces deux populations spécifiques, différentes en termes de profils sociodémographiques, toutes deux exposées aux risques de transmission du VHB de par leurs pratiques d’usage de drogues ou leurs pratiques sexuelles, avaient des séroprévalences de l’AgHBs proches de celle de la population générale.
Background: Physical activity (PA) is responsible for a multitude of health benefits for girls and young women. Research on active transportation to school (ATS) shows that it is a known way to ...increase PA. However, girls do not regularly use ATS despite the many physical, mental, and community health benefits of an active commute. One route to improve girls’ ATS is by using a Social Marketing framework to discern critical messages for use in a public health marketing campaign. Methods: Focus groups with 79 girls between the ages of 7 and 15 were conducted in Spring 2017. Transcripts and poster data were a priori categorized by the SM ‘4Ps’ framework (Product, Price, Place and Promotion). Participant groups were segmented into three age categories for tailored messaging. Data were managed using NVivo 11 and were analyzed using Constant Comparative Method tools (Strauss & Corbin, 1998). Results: Two thematic areas, Price and Place, were particularly important to girls in defining and appropriate ‘marketing mix’ for an ATS campaign. Based on our findings, a Social Marketing initiative with girls as the priority audience should be built on empowering girls to overcome the barriers to ATS. Positive and lighthearted messaging emphasizing friendship and independence as promised benefits of ATS would resonate with girls across a broad age range. Further segmentation of the audience would result in more tailored messages based on the different core values and beliefs held by this diverse group.
Graduate
Tacrolimus, an immunosuppressive drug prescribed to a majority of organ transplant recipients is nephrotoxic, through still unclear mechanisms. This study on a lineage of proximal tubular cells using ...a multi-omics approach aims to detect off-target pathways modulated by tacrolimus that can explain its nephrotoxicity.
LLC-PK1 cells were exposed to 5 µM of tacrolimus for 24 h in order to saturate its therapeutic target FKBP12 and other high-affine FKBPs and favour its binding to less affine targets. Intracellular proteins and metabolites, and extracellular metabolites were extracted and analysed by LC-MS/MS. The transcriptional expression of the dysregulated proteins PCK-1, as well as of the other gluconeogenesis-limiting enzymes FBP1 and FBP2, was measured using RT-qPCR. Cell viability with this concentration of tacrolimus was further checked until 72 h.
In our cell model of acute exposure to a high concentration of tacrolimus, different metabolic pathways were impacted including those of arginine (e.g., citrulline, ornithine) (p < 0.0001), amino acids (e.g., valine, isoleucine, aspartic acid) (p < 0.0001) and pyrimidine (p < 0.01). In addition, it induced oxidative stress (p < 0.01) as shown by a decrease in total cell glutathione quantity. It impacted cell energy through an increase in Krebs cycle intermediates (e.g., citrate, aconitate, fumarate) (p < 0.01) and down-regulation of PCK-1 (p < 0.05) and FPB1 (p < 0.01), which are key enzymes in gluconeogenesis and acid-base balance control.
The variations found using a multi-omics pharmacological approach clearly point towards a dysregulation of energy production and decreased gluconeogenesis, a hallmark of chronic kidney disease which may also be an important toxicity pathway of tacrolimus.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Inflammation is a characteristic feature of Parkinson's disease (PD). We examined the role of TLR9 and its regulation by glucocorticoid receptors (GRs) in degeneration of substantia nigra dopamine ...neurons (DNs). TLR9 agonist, CpG-ODN, induced DN degeneration in mice lacking GR in microglia but not in controls. TLR9 deletion reduced DN loss in neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. GR regulates TLR9 activation during MPTP neurotoxicity as TLR9 antagonist suppressed increased DN loss in microglia/macrophage GR mutant mice. GR absence in microglia enhanced TLR9 translocation to endolysosomes and facilitated its cleavage leading to pro-inflammatory gene expression. GR-dependent TLR9 activation also triggered DN loss following intranigral injection of mitochondrial DNA. Finally, microglial GR sensitivity to A53T-alpha-synuclein induced DN degeneration as well as decreased microglial GR expression observed in SN of PD brain samples, all suggest that reduced microglial GR activity in SN can stimulate TLR9 activation and DN loss in PD pathology.
To establish reference values for the 6-minute walk test (6MWT) and 2-minute walk test (2MWT) distances, to investigate the correlation between these 2 tests, and to establish prediction equations ...for these distances in healthy populations of Belgium and Vietnam.
Cross-sectional study.
The 6MWT and 2MWT were administered to a convenience sample of 239 Belgian and 303 Vietnamese participants between the ages of 18 and 80 years.
The mean (standard deviation; SD) 2MWT distances were 215 (32.8) m for Belgian participants and 156 (25.5) m for Vietnamese participants. The mean (SD) 6MWT distances were 625 (90.7) m for Belgian participants and 449 (70.4) m for Vietnamese participants. The Pearson correlation coefficient between the 2 tests was 0.901 (p < 0.001) for Belgian participants and 0.871 (p < 0.001) for Vietnamese participants. Age and sex were the 2 most important predictors of walking distance, followed by body mass index for Belgium and height for Vietnam. The adjusted R² ranged from 0.31 to 0.49 across 4 predictive equations.
These results can be used to determine the presence of walking performance deficits and to guide future studies. The 2MWT is suggested as a useful and convenient alternative to the 6MWT for assessing walking performance in clinical practice.
The precise contribution of astrocytes in neuroinflammatory process occurring in Parkinson's disease (PD) is not well characterized. In this study, using GR
mice that are conditionally inactivated ...for glucocorticoid receptor (GR) in astrocytes, we have examined the actions of astrocytic GR during dopamine neuron (DN) degeneration triggered by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The results show significantly augmented DN loss in GR
mutant mice in substantia nigra (SN) compared to controls. Hypertrophy of microglia but not of astrocytes was greatly enhanced in SN of these astrocytic GR mutants intoxicated with MPTP, indicating heightened microglial reactivity compared to similarly-treated control mice. In the SN of GR astrocyte mutants, specific inflammation-associated transcripts ICAM-1, TNF-α and Il-1β as well as TNF-α protein levels were significantly elevated after MPTP neurotoxicity compared to controls. Interestingly, this paralleled increased connexin hemichannel activity and elevated intracellular calcium levels in astrocytes examined in acute midbrain slices from control and mutant mice treated with MPP+ . The increased connexin-43 hemichannel activity was found in vivo in MPTP-intoxicated mice. Importantly, treatment of MPTP-injected GR
mutant mice with TAT-Gap19 peptide, a specific connexin-43 hemichannel blocker, reverted both DN loss and microglial activation; in wild-type mice there was partial but significant survival effect. In the SN of post-mortem PD patients, a significant decrease in the number of astrocytes expressing nuclear GR was observed, suggesting the participation of astrocytic GR deregulation of inflammatory process in PD. Overall, these data provide mechanistic insights into GR-modulated processes in vivo, specifically in astrocytes, that contribute to a pro-inflammatory state and dopamine neurodegeneration in PD pathology.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The human pathogen Streptococcus pyogenes, or group A Streptococcus, is responsible for mild infections to life-threatening diseases. To facilitate the characterization of regulatory networks ...involved in the adaptation of this pathogen to its different environments and their evolution, we have determined the primary transcriptome of a serotype M1 S. pyogenes strain at single-nucleotide resolution and compared it with that of Streptococcus agalactiae, also from the pyogenic group of streptococci.
By using a combination of differential RNA-sequencing and oriented RNA-sequencing we have identified 892 transcription start sites (TSS) and 885 promoters in the S. pyogenes M1 strain S119. 8.6% of S. pyogenes mRNAs were leaderless, among which 81% were also classified as leaderless in S. agalactiae. 26% of S. pyogenes transcript 5' untranslated regions (UTRs) were longer than 60 nt. Conservation of long 5' UTRs with S. agalactiae allowed us to predict new potential regulatory sequences. In addition, based on the mapping of 643 transcript ends in the S. pyogenes strain S119, we constructed an operon map of 401 monocistrons and 349 operons covering 81.5% of the genome. One hundred fifty-six operons and 254 monocistrons retained the same organization, despite multiple genomic reorganizations between S. pyogenes and S. agalactiae. Genomic reorganization was found to more often go along with variable promoter sequences and 5' UTR lengths. Finally, we identified 117 putative regulatory RNAs, among which nine were regulated in response to magnesium concentration.
Our data provide insights into transcriptome evolution in pyogenic streptococci and will facilitate the analysis of genetic polymorphisms identified by comparative genomics in S. pyogenes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Nanocrystals' (NCs) band gap can be easily tuned over the infrared range, making them appealing for the design of cost-effective sensors. Though their growth has reached a high level of maturity, ...their doping remains a poorly controlled parameter, raising the need for post-synthesis tuning strategies. As a result, phototransistor device geometry offers an interesting alternative to photoconductors, allowing carrier density control. Phototransistors based on NCs that target integrated infrared sensing have to (i) be compatible with low-temperature operation, (ii) avoid liquid handling, and (iii) enable large carrier density tuning. These constraints drive the search for innovative gate technologies beyond traditional dielectric or conventional liquid and ion gel electrolytes. Here, we explore lithium-ion glass gating and apply it to channels made of HgTe narrow band gap NCs. We demonstrate that this all-solid gate strategy is compatible with large capacitance up to 2 µF·cm
and can be operated over a broad range of temperatures (130-300 K). Finally, we tackle an issue often faced by NC-based phototransistors:their low absorption; from a metallic grating structure, we combined two resonances and achieved high responsivity (10 A·W
or an external quantum efficiency of 500%) over a broadband spectral range.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In the 1980s, excess infrared emission was discovered around main-sequence stars; subsequent direct-imaging observations revealed orbiting disks of cold dust to be the source. These 'debris disks' ...were thought to be by-products of planet formation because they often exhibited morphological and brightness asymmetries that may result from gravitational perturbation by planets. This was proved to be true for the β Pictoris system, in which the known planet generates an observable warp in the disk. The nearby, young, unusually active late-type star AU Microscopii hosts a well-studied edge-on debris disk; earlier observations in the visible and near-infrared found asymmetric localized structures in the form of intensity variations along the midplane of the disk beyond a distance of 20 astronomical units. Here we report high-contrast imaging that reveals a series of five large-scale features in the southeast side of the disk, at projected separations of 10-60 astronomical units, persisting over intervals of 1-4 years. All these features appear to move away from the star at projected speeds of 4-10 kilometres per second, suggesting highly eccentric or unbound trajectories if they are associated with physical entities. The origin, localization, morphology and rapid evolution of these features are difficult to reconcile with current theories.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Clustered regularly interspaced short palindromic repeats (CRISPR) confer immunity against mobile genetic elements (MGEs) in prokaryotes. Streptococcus agalactiae, a leading cause of neonatal ...infections contains in its genome two CRISPR/Cas systems. We show that type 1‐C CRISPR2 is present in few strains but type 2‐A CRISPR1 is ubiquitous. Comparative sequence analysis of the CRISPR1 spacer content of 351 S. agalactiae strains revealed that it is extremely diverse due to the acquisition of new spacers, spacer duplications and spacer deletions that witness the dynamics of this system. The spacer content profile mirrors the S. agalactiae population structure. Transfer of a conjugative transposon targeted by CRISPR1 selected for spacer rearrangements, suggesting that deletions and duplications pre‐exist in the population. The comparison of protospacers located within MGE or the core genome and protospacer‐associated motif‐shuffling demonstrated that the GG motif is sufficient to discriminate self and non‐self and for spacer selection and integration. Strikingly more than 40% of the 949 different CRISPR1 spacers identified target MGEs found in S. agalactiae genomes. We thus propose that the S. agalactiae type II‐A CRISPR1/Cas system modulates the cohabitation of the species with its mobilome, as such contributing to the diversity of MGEs in the population.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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