Quantification of lentiviral vector copy numbers in individual hematopoietic colony-forming cells shows vector dose-dependent effects on the frequency and level of transduction

Lentiviral vectors are effective tools for gene transfer and integrate variable numbers of proviral DNA copies in variable proportions of cells. The levels of transduction of a cellular population may therefore depend upon experimental parameters affecting the frequency and/or the distribution of vector integration events in this population. Such analysis would require measuring vector copy numbers (VCN) in individual cells. To evaluate the transduction of hematopoietic progenitor cells at the single-cell level, we measured VCN in individual colony-forming cell (CFC) units, using an adapted quantitative PCR (Q-PCR) method. The feasibility, reproducibility and sensitivity of this approach were tested with characterized cell lines carrying known numbers of vector integration. The method was validated by correlating data in CFC with gene expression or with calculated values, and was found to slightly underestimate VCN. In spite of this, such Q-PCR on CFC was useful to compare transduction levels with different infection protocols and different vectors. Increasing the vector concentration and re-iterating the infection were two different strategies that improved transduction by increasing the frequency of transduced progenitor cells. Repeated infection also augmented the number of integrated copies and the magnitude of this effect seemed to depend on the vector preparation. Thus, the distribution of VCN in hematopoietic colonies may depend upon experimental conditions including features of vectors. This should be carefully evaluated in the context of ex vivo hematopoietic gene therapy studies

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Common dysregulation of Wnt/Frizzled receptor elements in human hepatocellular carcinoma

Dysregulation of growth factors and their receptors is central to human hepatocellular carcinoma (HCC). We previously demonstrated that the Frizzled-7 membrane receptor mediating the Wnt signalling can activate the β-catenin pathway and promotes malignancy in human hepatitis B virus-related HCCs. Expression patterns of all the 10 Frizzled receptors, and their extracellular soluble autoparacrine regulators (19 Wnt activators and 4 sFRP inhibitors) were assessed by real-time RT–PCR in 62 human HCC of different etiologies and their matched peritumorous areas. Immunostaining was performed to localise Frizzled on cell types in liver tissues. Regulation of three known Frizzled-dependent pathways (β-catenin, protein kinase C, and C-Jun NH2-terminal kinase) was measured in tissues by western blot. We found that eight Frizzled-potentially activating events were pleiotropically dysregulated in 95% HCC and 68% peritumours as compared to normal livers (upregulations of Frizzled-3/6/7 and Wnt3/4/5a, or downregulation of sFRP1/5), accumulating gradually with severity of fibrosis in peritumours and loss of differentiation status in tumours. The hepatocytes supported the Wnt/Frizzled signalling since specifically overexpressing Frizzled receptors in liver tissues. Dysregulation of the eight Frizzled-potentially activating events was associated with differential activation of the three known Frizzled-dependent pathways. This study provides an extensive analysis of the Wnt/Frizzled receptor elements and reveals that the dysregulation may be one of the most common and earliest events described thus far during hepatocarcinogenesis

Particle and VOC emission factor measurements for anthropogenic sources in West Africa

A number of campaigns have been carried out to establish the emission factors of pollutants from fuel combustion in West Africa, as part of work package 2 ("Air Pollution and Health") of the DACCIWA (Dynamics-Aerosol-Chemistry-Cloud Interactions in West Africa) FP7 program. Emission sources considered here include wood (hevea and iroko) and charcoal burning, charcoal making, open trash burning, and vehicle emissions, including trucks, cars, buses and two-wheeled vehicles. Emission factors of total particulate matter (TPM), elemental carbon (EC), primary organic carbon (OC) and volatile organic compounds (VOCs) have been established. In addition, emission factor measurements were performed in combustion chambers in order to reproduce field burning conditions for a tropical hardwood (hevea), and obtain particulate emission factors by size (PM0.25, PM1, PM2.5 and PM10). Particle samples were collected on quartz fiber filters and analyzed using gravimetric method for TPM and thermal methods for EC and OC. The emission factors of 58 VOC species were determined using offline sampling on a sorbent tube. Emission factor results for two species of tropical hardwood burning of EC, OC and TPM are 0.98 ± 0.46 g kg-1 of fuel burned (g kg-1), 11.05 ± 4.55 and 41.12 ± 24.62 g kg-1, respectively. For traffic sources, the highest emission factors among particulate species are found for the two-wheeled vehicles with two-stroke engines (2.74 g kg-1 fuel for EC, 65.11 g kg-1 fuel for OC and 496 g kg-1 fuel for TPM). The largest VOC emissions are observed for two-stroke two-wheeled vehicles, which are up to 3 times higher than emissions from light-duty and heavy-duty vehicles. Isoprene and monoterpenes, which are usually associated with biogenic emissions, are present in almost all anthropogenic sources investigated during this work and could be as significant as aromatic emissions in wood burning (1 g kg-1 fuel). EC is primarily emitted in the ultrafine fraction, with 77 % of the total mass being emitted as particles smaller than 0.25 μm. The particles and VOC emission factors obtained in this study are generally higher than those in the literature whose values are discussed in this paper. This study underlines the important role of in situ measurements in deriving realistic and representative emission factors

Le Guomindang et ses relais dans la société shanghaïenne en 1923

The Guomindang and its Connections with the Shanghai Society in 1923. This paper examines the changing relations between the Guomindang and those associations — the National Salvation Ten People Groups (Zhonghua jiuguo shirentuan lianhehui), the Merchants' Street Associations (Ge jie shangjie lianhehui) — that lead, in Shanghai, the successive popular mobilizations during the first half of 1923 : the Liishun and Dalian leased territory recovery movement, and, after the coup d'État perpetrated by Cao Kun in Peking, the "people's self determination movement" (guomin zijue yundong), which ended, on June 23, with the formation by the General Chamber of Commerce of a committee enthrusted with establishing a "merchants' government." The Guomindang tried to seize control of these movements, but failed because of, first, the intervention of the main native-place associations (tongxianghui), but also, more generally, of the reticences of the associations, whose political orientation differed notably from the Guomindang's schemes. As judged by their leaders's pronouncements, or their members's activities, this political orientation partakes of an anarchist ethos, that characterizes the period, since the May Fourth Movement, and the "people's self-determination movement" may appear, to a certain extent, as a late expression of this tendency.Cet article examine les relations changeantes entre les associations — Fédération chinoise des Dizaines du salut national (Zhonghua jiuguo shirentuan lianhehui), Unions de marchands par rues (Ge jie shangjie lianhehui) — qui animent, à Shanghai, les diverses mobilisations populaires qui se déroulent au cours du premier semestre de 1923 : mouvement pour le recouvrement du territoire à bail de Liishun et Dalian, puis, après le coup d'État perpétré à Pékin par Cao Kun, «mouvement d'autodétermination populaire » (lequel débouche, le 23 juin, sur la formation par la Chambre générale de commerce d'un comité chargé de préparer la constitution d'un «gouvernement des marchands »), et le Guomindang. Celui-ci tente de prendre le contrôle de ces mobilisations, mais échoue du fait de l'intervention des principaux tongxianghui de la ville, d'abord, mais, plus généralement, des réticences des associations, dont le projet politique apparaît très différent de celui du Guomindang. Le projet politique de ces associations, tel qu'il peut être connu par les déclarations de leurs dirigeants ou les activités mêmes de leurs membres, participe en effet d'une tendance anarchisante, dont relèvent aussi, dans une certaine mesure, le projet d'autonomie locale des notables, tout comme le «mouvement d'autodétermination populaire », qui apparaît comme l'expression tardive de cette tendance, qui caractérise toute la période depuis le mouvement du 4 Mai.Galy Laurent. Le Guomindang et ses relais dans la société shanghaïenne en 1923. In: Études chinoises, vol. 17, n°1-2, Printemps-Automne 1998. pp. 233-294

2. Une trajectoire tianjinoise

Retraçant le parcours de Théodore Desorgues, l’auteur des paroles de l’Hymne à l’Être suprême, Michel Vovelle a livré en 1985 une enquête d’histoire, culturelle par ses interrogations (l’artiste dans la Révolution), sociale par sa démarche fondamentale (l’étude des différents milieux dont Desorgues avait été l’expression). Historien quantitativiste, ayant « frayé [sa] trace dans l’histoire sociale et celle des mentalités, en s’attaquant aux traces dormantes de ceux qui n’ont pas laissé de tém..

Isabelle Maynard, China Dreams : Growing Up Jewish in Tientsin , University press (« Singular Lives : The Iowa Series in North American Autobiography »), 1996

Galy Laurent. Isabelle Maynard, China Dreams : Growing Up Jewish in Tientsin , University press (« Singular Lives : The Iowa Series in North American Autobiography »), 1996. In: Études chinoises, vol. 21, n°1-2, Printemps-Automne 2002. pp. 305-306

Chronologies biographiques (nianpu 年谱) (Chine)

Les nianpu, « chronologies biographiques », constituent un genre biographique qui apparaît sous la dynastie Song (960‑1279) et illustrent la tradition annalistique de l’historiographie chinoise traditionnelle. Ce genre continue d’être cultivé aujourd’hui face à la forme plus moderne de la « biographie critique » (pingzhuan).The nianpu, “biographical chronologies”, are a Chinese traditional form of biographical writing, that appeared during the Song dynasty (960‑1279). They exemplify the annalistic form of Chinese traditional historiography. This biographical style still flourishes today along with the more modern form of “critical biography” (pingzhuan)

Isabelle Maynard, China Dreams : Growing Up Jewish in Tientsin , University press (« Singular Lives : The Iowa Series in North American Autobiography »), 1996

Galy Laurent. Isabelle Maynard, China Dreams : Growing Up Jewish in Tientsin , University press (« Singular Lives : The Iowa Series in North American Autobiography »), 1996. In: Études chinoises, vol. 21, n°1-2, Printemps-Automne 2002. pp. 305-306

Tables de parenté familiale (jiapu 家谱)

Documents établissant la filiation des familles d’un lignage à partir d’un premier ancêtre, les jiapu constituent le genre généalogique chinois traditionnel. L’émergence de ce genre sous la dynastie des Song (960‑1279) est liée à l’affermissement à ce moment de l’ordre rituel néoconfucéen et à l’apparition du lignage comme institution. Une vogue généalogique récente en Chine a consacré les jiapu comme troisièmes « grands documents historiques » à côté des histoires dynastiques et des monographies locales.Documents establishing the filiation of families of a lineage beginning with one first ancestor, the jiapu, constitute the traditional Chinese genealogical style. The emergence of this form at the time of the Song dynasty (960‑1279) is linked to the strengthening of the neo‑Confucianism ritual order, and the appearance of the lineage as an institution. A recent genealogical trend in China has established the jiapu as the third “greatest historical document”, next to dynastic histories and local monographs