Antigenic Properties of Recombinant Envelope Glycoproteins Derived from T-Cell-Line-Adapted Isolates or Primary Human Immunodeficiency Virus Isolates and Their Relationship to Immunogenicity

AbstractThe native envelope glycoproteins of primary HIV-1 virions have weaker antigenicity than do T-cell laboratory-adapted (TCLA) viruses. These antigenic properties require further evaluation if recombinant envelope glycoproteins are produced as part of a vaccine strategy. In this study, we compared the antigenicity of recombinant envelope glycoproteins derived from three primary isolates (PI) (HIV-1BX08, HIV-1CHA, and HIV-1133) and two TCLA viruses (HIV-1HXB2 and HIV-1MN) produced using the Semliki Forest virus (SFV) system. This analysis was performed by radioimmunoprecipitation assays and flow cytometry. The results suggest that the SFV produces envelope glycoproteins with features in common with the envelopes found in naturally occurring virions. In particular, the PI envelopes had weak heterogeneous antigenic properties. However, the cytometric analysis also showed that there was less envelope glycoprotein on the cell surface for the PI envelopes than for those of TCLA viruses, suggesting differences in their intracellular trafficking. The immunogenic properties of the various envelope glycoproteins were evaluated in mice using recombinant SFV particles as vaccine vectors. The PI envelopes were less immunogenic than the TCLA envelopes, probably due to both their low antigenicity and cell surface expression level. Thus, it may be difficult to design an effective vaccine based on native recombinant PI envelopes

The multinational second Diabetes, Attitudes, Wishes and Needs study: results of the French survey

International audienceAIM:The second Diabetes, Attitudes, Wishes and Needs (DAWN2™) multinational cross-sectional study was aimed at generating insights to facilitate innovative efforts by people with diabetes (PWD), family members (FMs), and health care professionals (HCPs) to improve self-management and psychosocial support in diabetes. Here, the French data from the DAWN2™ study are described.METHODS:In France, 500 PWD (80 with type 1 diabetes [T1] and 420 with type 2 diabetes [T2]), 120 FMs, and 288 HCPs were recruited. The questionnaires assessed the impact of diabetes on quality of life and mood, self-management, attitudes/beliefs, and care/support.RESULTS:Diabetes negatively impacted the emotional well-being of 59% of people with T1 versus 45% of people with T2 (P<0.05) and about half of FMs. A high level of distress was felt by about half of PWD and FMs. About half of HCPs reported assessing depression in their patients. Sixty-two percent of FMs considered managing diabetes to be a burden. Hypoglycemia was a source of concern for 64% of people with T1 and 73% of FMs of insulin users. About two-thirds of non-insulin-medicated people with T2 agreed to start insulin if prescribed, while half of HCPs preferred to delay insulin initiation. A discrepancy between HCPs' perceptions of their interactions with their patients and PWD's recollection of these interactions with regard to patients' personal needs and distress was also observed.CONCLUSION:While distress remains under-assessed by HCPs, the negative impact of diabetes on the lives of PWD and FMs clearly induces distress on both groups. These findings provide new understanding of barriers precluding optimal management of diabetes. Developing strategies to overcome these barriers is now warranted

The Relation Between Depressive Symptoms and Semantic Memory in Amnestic Mild Cognitive Impairment and in Late-Life Depression

Semantic deficits have been documented in the prodromal phase of Alzheimer’s disease, but it is unclear whether these deficits are associated with non-cognitive manifestations. For instance, recent evidence indicates that cognitive deficits in elders with amnestic mild cognitive impairment (aMCI) are modulated by concomitant depressive symptoms. The purposes of this study were to (i) investigate if semantic memory impairment in aMCI is modulated according to the presence (aMCI-D group) or absence (aMCI group) of depressive symptoms, and (ii) compare semantic memory performance of aMCI and aMCI-D groups to that of patients with late-life depression (LLD). Seventeen aMCI, 16 aMCI-D, 15 LLD, and 26 healthy control participants were administered a semantic questionnaire assessing famous person knowledge. Results showed that performance of aMCI-D patients was impaired compared to the control and LLD groups. However, in the aMCI group performance was comparable to that of all other groups. Overall, these findings suggest that semantic deficits in aMCI are somewhat associated with the presence of concomitant depressive symptoms. However, depression alone cannot account solely for the semantic deficits since LLD patients showed no semantic memory impairment in this study. Future studies should aim at clarifying the association between depression and semantic deficits in older adults meeting aMCI criteria.Instituts de recherche en santé du Canada (IRSC) IAO-8467

A roadmap to climate data rescue services

Quantitative approaches to climate risk management such as mapping or impact modelling rely on past meteorological data with daily or sub‐daily resolution, a large fraction of which have not yet been digitized. Over the last decade or so, a number of projects have contributed to the rescue of some of these data. Here we provide a summary of a survey we have undertaken of several meteorological and climate data rescue projects, in order to identify the needs of climate data rescue services. To make these efforts more sustainable, additional integrated activities are needed. We argue that meteorological and climate data rescue must be seen as a continuous, coordinated long‐term effort. Technical developments (e.g. data assimilation), new scientific questions (e.g. process understanding of extreme events) and new social (e.g. risk assessment, health) or economic (e.g. new renewable energy sources, agriculture and forestry, tourism, infrastructure, etc.) services are highlighting the immense value of data previously neglected or never considered. This continuous effort is currently undertaken by projects of various sizes, structure, funding and staffing, as well as by dedicated programmes, ranging from those within many national weather services down to “grassroots” initiatives. These activities are often not sufficiently coordinated, staffed, or funded at an international level and will benefit considerably from climate data rescue services being established within the Copernicus Climate Change Service (C3S) (https://climate.copernicus.eu/)

The International Surface Pressure Databank version 2

The International Surface Pressure Databank (ISPD) is the world's largest collection of global surface and sea-level pressure observations. It was developed by extracting observations from established international archives, through international cooperation with data recovery facilitated by the Atmospheric Circulation Reconstructions over the Earth (ACRE) initiative, and directly by contributing universities, organizations, and countries. The dataset period is currently 1768–2012 and consists of three data components: observations from land stations, marine observing systems, and tropical cyclone best track pressure reports. Version 2 of the ISPD (ISPDv2) was created to be observational input for the Twentieth Century Reanalysis Project (20CR) and contains the quality control and assimilation feedback metadata from the 20CR. Since then, it has been used for various general climate and weather studies, and an updated version 3 (ISPDv3) has been used in the ERA-20C reanalysis in connection with the European Reanalysis of Global Climate Observations project (ERA-CLIM). The focus of this paper is on the ISPDv2 and the inclusion of the 20CR feedback metadata. The Research Data Archive at the National Center for Atmospheric Research provides data collection and access for the ISPDv2, and will provide access to future versions

Deux tombes féminines, atypiques et privilégiées, de la nécropole du Bas-Empire d’Arcis-sur-Aube (Champagne-Ardenne)

En 2002, une nécropole a été partiellement fouillée au sud de la commune d’Arcis-sur-Aube (Aube, Champagne-Ardenne). Cette opération a permis d’exhumer vingt-deux tombes datées entre la fin du IIIe et le milieu du IVe siècle. Malgré des pratiques de dépôt partagées par la plupart des défunts, deux tombes se distinguent. Ces deux fosses, aménagées avec un double coffrage, accueillent deux défuntes qui possèdent des dépôts très similaires. La qualité des dépôts, leur disposition dans la fosse, ainsi que la proximité des creusements, signalent une volonté du groupe de mettre en exergue ces deux femmes. De plus, une particularité dentaire encourage à voir entre elles un possible apparentement.In 2002, a necropolis to the south of the commune of Arcis-sur-Aube (Aube, Champagne-Ardenne) was excavated. Twenty-two tombs were exhumed and dated to between the end of the 3rd and middle of the 4th century. While most of the deceased were deposited in the same manner, two tombs differ from the others. These two pits, constructed a double coffering, contained two individuals with very similar grave goods. The quality of these objects, their arrangement in the pits, and the proximity of the pits to each other indicate that the group intended to highlight these two women. Moreover, a shared dental feature could indicate a kinship relationship between them.2002 wurden im Süden der Gemeinde Arcis-sur-Aube (Departement Aube, Champagne-Ardenne) bei der teilweisen Ausgrabung einer Nekropole 22 Bestattungen freigelegt, die zwischen das Ende des 3. und die Mitte des 4. Jh. datierten. Die Beigaben sind in den meisten Gräbern identisch. Nur zwei doppelt verschalte Gräber weisen Unterschiede auf. Hier ruhten zwei weibliche Verstorbene mit sehr ähnlichen Grabbeigaben. Deren Qualität, Anordnung in der Grube sowie die Nähe der beiden Grabstätten zu einander zeugen von dem Sonderstatus der beiden Frauen innerhalb der Gruppe. Eine Eigentümlichkeit der Zähne legt eine verwandtschaftliche Beziehung zwischen den Frauen nah

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations