State of genomics and epigenomics research in the perspective of HIV cure.

PURPOSE OF REVIEW: One of the seven key scientific priorities identified in the road map on HIV cure research is to 'determine the host mechanisms that control HIV replication in the absence of therapy'. This review summarizes the recent work in genomics and in epigenetic control of viral replication that is relevant for this mission. RECENT FINDINGS: New technologies allow the joint analysis of host and viral transcripts. They identify the patterns of antisense transcription of the viral genome and its role in gene regulation. High-throughput studies facilitate the assessment of integration at the genome scale. Integration site, orientation and host genomic context modulate the transcription and should also be assessed at the level of single cells. The various models of latency in primary cells can be followed using dynamic study designs to acquire transcriptome and proteome data of the process of entry, maintenance and reactivation of latency. Dynamic studies can be applied to the study of transcription factors and chromatin modifications in latency and upon reactivation. SUMMARY: The convergence of primary cell models of latency, new high-throughput quantitative technologies applied to the study of time series and the identification of compounds that reactivate viral transcription bring unprecedented precision to the study of viral latency.

Triiodothyronine stimulation of oligodendroglial differentiation and myelination. A developmental study.

The biochemical development of rotation-mediated aggregating brain cell cultures was studied in a serum-free chemically defined medium in the presence (complete medium) or the absence of triiodothyronine (T3). The expression of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) and myelin basic protein (MBP), two myelin components, was temporally dissociated in brain cell aggregating cultures grown in a complete medium. CNP increased from day 8 and reached a plateau around day 25. MBP accumulated rapidly from the third until the fourth week in culture. The total protein content increased gradually until day 25. The activity of ornithine decarboxylase (ODC) used as an index of cell growth and differentiation, showed two well-defined peaks of activity. The first peak reached a maximum at day 6 and correlated with both the highest DNA content and the peak of [3H]-thymidine incorporation. The second peak of ODC activity (from day 19 to 35) coincided with the differentiation of oligodendrocytes. These results confirm that aggregating fetal rat brain cells cultured in a serum-free chemically defined medium undergo extensive differentiation. Addition of T3 to the culture medium doubled the CNP activity by day 16. In contrast, MBP was only slightly increased by day 16, reaching at 25 and 35 days 8 to 10-fold higher values than the untreated cultures. When T3 was removed between day 16 and 25, CNP decreased almost to control values and MBP failed to accumulate. Moreover, when T3 was reintroduced into the medium (between day 25 and 35), CNP activity was restored and MBP content was partially corrected. T3 treatment produced a concentration-dependent increase in ODC activity which was observed only around day 19. The first peak of ODC activity observed at culture day 6 was independent of the presence of T3. These results obtained in brain cell cultures emphasize the direct effect of T3 on myelination.

A cnidarian homologue of an insect gustatory receptor functions in developmental body patterning.

Insect gustatory and odorant receptors (GRs and ORs) form a superfamily of novel transmembrane proteins, which are expressed in chemosensory neurons that detect environmental stimuli. Here we identify homologues of GRs (Gustatory receptor-like (Grl) genes) in genomes across Protostomia, Deuterostomia and non-Bilateria. Surprisingly, two Grls in the cnidarian Nematostella vectensis, NvecGrl1 and NvecGrl2, are expressed early in development, in the blastula and gastrula, but not at later stages when a putative chemosensory organ forms. NvecGrl1 transcripts are detected around the aboral pole, considered the equivalent to the head-forming region of Bilateria. Morpholino-mediated knockdown of NvecGrl1 causes developmental patterning defects of this region, leading to animals lacking the apical sensory organ. A deuterostome Grl from the sea urchin Strongylocentrotus purpuratus displays similar patterns of developmental expression. These results reveal an early evolutionary origin of the insect chemosensory receptor family and raise the possibility that their ancestral role was in embryonic development.

"Indemniser les planteurs pour abolir l'esclavage ? Entre économie, éthique et politique : une étude des débats parlementaires britanniques et français (1788-1848) dans une perspective comparée".

RESUME DE THESEUne majorité d'abolitions dans le Nouveau Monde (1777-1888) donne lieu à l'octroi d'indemnités aux propriétaires d'esclaves. Si cet aspect des émancipations n'a pas retenu l'attention des spécialistes jusqu'à présent, il s'agit d'un phénomène récurrent dans les Amériques. L'étude globale de la question de l'indemnité par l'examen des objectifs d'une telle mesure, de ses enjeux, ainsi que de son coût pour les Etats concernés, constitue ainsi l'ambition de cette recherche.L'originalité de la démarche adoptée réside dans le choix de la comparaison comme mode d'investigation et dans la sélection des débats parlementaires comme sources de travail. Une scène d'investigation sur deux niveaux a été construite. Les processus d'indemnisation britannique et français - jugés les plus représentatifs - ont été traités par le biais de sources, les autres cas par la littérature secondaire. Les discussions tenues de 1788 à 1848 aux Chambres des Communes et des députés ont été isolées comme bases d'investigation.Cette recherche démontre que la question de l'indemnité - bien que délaissée par les historiens qui ne l'ont pas perçue comme telle - constitue une cheville ouvrière d'une émancipation. Bien plus, l'étude du thème de l'indemnité - mesure s'inscrivant dans le concept d'économie morale - élargit l'angle de vue au-delà des seuls enjeux d'une abolition jusqu'à présent privilégiés. Outre des facteurs juridiques et économiques, des éléments sociaux et politiques doivent en effet être considérés, qui permettent de mieux cerner - par le biais de l'indemnité - la problématique complexe d'une abolition.

Predictors of developmental dyslexia in European orthographies with varying complexity.

Background:  The relationship between phoneme awareness, rapid automatized naming (RAN), verbal short-term/working memory (ST/WM) and diagnostic category is investigated in control and dyslexic children, and the extent to which this depends on orthographic complexity. Methods:  General cognitive, phonological and literacy skills were tested in 1,138 control and 1,114 dyslexic children speaking six different languages spanning a large range of orthographic complexity (Finnish, Hungarian, German, Dutch, French, English). Results:  Phoneme deletion and RAN were strong concurrent predictors of developmental dyslexia, while verbal ST/WM and general verbal abilities played a comparatively minor role. In logistic regression models, more participants were classified correctly when orthography was more complex. The impact of phoneme deletion and RAN-digits was stronger in complex than in less complex orthographies. Conclusions:  Findings are largely consistent with the literature on predictors of dyslexia and literacy skills, while uniquely demonstrating how orthographic complexity exacerbates some symptoms of dyslexia.

Nouveautés en médecine interne générale ambulatoire (2) [General internal medicine: review of year 2009 from the ambulatory perspective (2)]

Despite two international studies, there is still no consensus concerning prostate cancer screening. The results of a meta-analysis are making us question our convictions concerning pneumococcal vaccination. The preoperative work-up of cataract surgery can be simplified. When describing the efficacy of a treatment to a patient, relative risks are better understood than absolute risks. For rotator cuff syndrome, intramuscular corticosteroid injections are as efficient as intra-articular injections. In patients prescribed clopidogrel, a proton pump inhibitor is not absolutely necessary. The arrival of a anticoagulant that does not need blood monitoring is an interesting option in atrial fibrillation.

Multiple roles of mouse Numb in tuning developmental cell fates.

BACKGROUND: Notch signaling regulates multiple differentiation processes and cell fate decisions during both invertebrate and vertebrate development. Numb encodes an intracellular protein that was shown in Drosophila to antagonize Notch signaling at binary cell fate decisions of certain cell lineages. Although overexpression experiments suggested that Numb might also antagonize some Notch activity in vertebrates, the developmental processes in which Numb is involved remained elusive. RESULTS: We generated mice with a homozygous inactivation of Numb. These mice died before embryonic day E11.5, probably because of defects in angiogenic remodeling and placental dysfunction. Mutant embryos had an open anterior neural tube and impaired neuronal differentiation within the developing cranial central nervous system (CNS). In the developing spinal cord, the number of differentiated motoneurons was reduced. Within the peripheral nervous system (PNS), ganglia of cranial sensory neurons were formed. Trunk neural crest cells migrated and differentiated into sympathetic neurons. In contrast, a selective differentiation anomaly was observed in dorsal root ganglia, where neural crest--derived progenitor cells had migrated normally to form ganglionic structures, but failed to differentiate into sensory neurons. CONCLUSIONS: Mouse Numb is involved in multiple developmental processes and required for cell fate tuning in a variety of lineages. In the nervous system, Numb is required for the generation of a large subset of neuronal lineages. The restricted requirement of Numb during neural development in the mouse suggests that in some neuronal lineages, Notch signaling may be regulated independently of Numb.

Interaction analysis and psychology: A dialogical perspective

Interaction analysis is not a prerogative of any discipline in social sciences. It has its own history within each disciplinary field and is related to specific research objects. From the standpoint of psychology, this article first draws upon a distinction between factorial and dialogical conceptions of interaction. It then briefly presents the basis of a dialogical approach in psychology and focuses upon four basic assumptions. Each of them is examined on a theoretical and on a methodological level with a leading question: to what extent is it possible to develop analytical tools that are fully coherent with dialogical assumptions? The conclusion stresses the difficulty of developing methodological tools that are fully consistent with dialogical assumptions and argues that there is an unavoidable tension between accounting for the complexity of an interaction and using methodological tools which necessarily "monologise" this complexity.

Médecine interne hospitalière: l'année 2009 en revue (1). La perspective des chefs de clinique [Hospital based internal medicine: the year 2009 in review (I). The perspective of chief residents]

Internists must regularly adjust their patients care according to recent relevant publications. The chief residents from the Department of Internal Medicine of a university hospital present some major themes of internal medicine treated during the year 2009. Emphasis will be placed primarily on changes in the daily hospital practice induced by these recent studies. This variety of topics illustrates both the broad spectrum of the current internal medicine, and the many uncertainties associated with modern medical practice based on evidence.

Cost effectiveness and cost utility of risedronate for osteoporosis treatment and fracture prevention in women: a Swiss perspective.

OBJECTIVES: To assess the incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) of risedronate compared to no intervention in postmenopausal osteoporotic women in a Swiss perspective. METHODS: A previously validated Markov model was populated with epidemiological and cost data specific to Switzerland and published utility values, and run on a population of 1,000 women of 70 years with established osteoporosis and previous vertebral fracture, treated over 5 years with risedronate 35 mg weekly or no intervention (base case), and five cohorts (according to age at therapy start) with eight risk factor distributions and three lengths of residual effects. RESULTS: In the base case population, the ICER of averting a hip fracture and the ICUR per quality-adjusted life year gained were both dominant. In the presence of a previous vertebral fracture, the ICUR was below euro45,000 (pound30,000) in all the scenarios. For all osteoporotic women>or=70 years of age with at least one risk factor, the ICUR was below euro45,000 or the intervention may even be cost saving. Age at the start of therapy and the fracture risk profile had a significant impact on results. CONCLUSION: Assuming a 2-year residual effect, that ICUR of risedronate in women with postmenopausal osteoporosis is below accepted thresholds from the age of 65 and even cost saving above the age of 70 with at least one risk factor.