Localization of the N-terminal domain of cauliflower mosaic virus coat protein precursor

AbstractCauliflower mosaic virus (CaMV) open reading frame (ORF) IV encodes a coat protein precursor (pre-CP) harboring an N-terminal extension that is cleaved off by the CaMV-encoded protease. In transfected cells, pre-CP is present in the cytoplasm, while the processed form (p44) of CP is targeted to the nucleus, suggesting that the N-terminal extension might be involved in keeping the pre-CP in the cytoplasm for viral assembly. This study reports for the first time the intracellular localization of the N-terminal extension during CaMV infection in Brassica rapa. Immunogold-labeling electron microscopy using polyclonal antibodies directed to the N-terminal extension of the pre-CP revealed that this region is closely associated with viral particles present in small aggregates, which we called small bodies, adjacent to the main inclusion bodies typical of CaMV infection. Based on these results, we propose a model for viral assembly of CaMV

Synthesis of new para-aminobenzoic acid derivatives, in vitro biological evaluation and preclinical validation of DAB-2-28 as a therapeutic option for the treatment of bladder cancer

Chronic inflammation plays a crucial role in bladder cancer (BCa) development and progression. To offer a unique treatment opportunity for this type of cancer, a hydrazide derivative namely, DAB-1, was recently identified in our laboratory as a potential drug to target cancer-related inflammation. In preclinical models of murine BCa, this particular compound exhibited remarkable anticancer activities. Structurally, DAB-1 is made from para-aminobenzoic acid and bears two different components, a maleimide and a hydrazide moieties, which are critical for its anti-inflammatory activity and its anticancer properties. In order to improve its biological potential, the hydrazide moiety was further modified to provide 3 ​s-generation molecules named, DAB-2-28, DAB-2-31A, and DAB-2-31B, and two third-generation molecules named, DAB-3-27 and DAB-3-33. Data from in vitro studies revealed that, among the different DAB molecules under study, DAB-2-28 has less cytotoxic activity with greater efficiency than DAB-1 to inhibit the production of nitric oxide (NO) induced by the combination of IFNγ with TNFα, as well as the activation of pro-tumoral and pro-inflammatory signaling pathways IL6/STAT3 and TNFα/NFκB. Moreover, while DAB-2-28 exhibited similar anti-inflammatory activity in vivo to DAB-1 in a model of carrageenan-induced acute inflammation, it efficiently inhibited the expression of the enzymes iNOS and COX-2 induced by the combined activation of IFNγ with LPS in peritoneal macrophages. Notably, analysis of the growth kinetics of MB49-I tumors implanted subcutaneously in C57Bl/6 mice showed that DAB-2-28 was more efficient to inhibit tumor development. In conclusion, this study provided preclinical proof-of-principle for DAB-2-28 molecule in the treatment of BCa.Fil: Oufqir, Yassine. Université du Québec a Montreal; CanadáFil: Fortin, Laurie. Université du Québec a Montreal; CanadáFil: Girouard, Julie. Université du Québec a Montreal; CanadáFil: Cloutier, Francis. Université du Québec a Montreal; CanadáFil: Cloutier, Maude. Université du Québec a Montreal; CanadáFil: Leclerc, Marie France. Université du Québec a Montreal; CanadáFil: Belgorosky, Denise. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Eijan, Ana Maria. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bérubé, Gervais. Université du Québec a Montreal; CanadáFil: Reyes-Moreno, Carlos. Université du Québec a Montreal; Canad

Reporting rates of opioid-related adverse events since 1965 in Canada : a descriptive retrospective study

Background : Patients with chronic or acute/postoperative pain frequently use opioids. However, opioids may cause considerable adverse reactions (ARs), such as respiratory depression, which could be lethal. Unfortunately, only 5% of drug-related ARs (including those to opioids) are reported to health authorities. Therefore, little is known regarding the occurrence of opioid-related ARs at the population level. Objective : The aim of this study was to investigate how the rates of reported opioid-related ARs have changed in Canada since 1965. Methods : Our retrospective study examined trends of reported opioid-related ARs occurring in hospitalized and outpatients. Data on opioid-related ARs and mortality between 1965 and 2019 were obtained from the Canada Vigilance and Statistics Canada databases. Descriptive and Joinpoint regression analyses were performed. Results : Oxycodone and normethadone were the most and least involved opioid agents, respectively, among the 18,407 reported ARs. The highest rate of reported opioid ARs (3.8 per 100,000 person-years) was recorded in 2012, whereas the lowest was recorded in 1965 (0.1 per 100,000 person-years). Between 1965 and 2019, annual rates climbed by 4.2% (95% confidence interval [CI] 3.1–5.2), and many fluctuations were observed: 1965–1974: +22.3% (95% CI 12.0–33.6); 1974–2000: − 4.1% (95% CI − 5.3 to − 2.9); 2000–2008: +30.3% (95% CI 22.6–38.4); 2008–2014: +4.1% (95% CI − 1.5 to 10.1); 2014–2017: −26.0% (95% CI − 44.7 to − 0.9); and, finally, 2017–2019: +35.4% (95% CI 3.8–76.7). Conclusion : Reported opioid-related ARs have increased since 1965, although fluctuations were observed in recent decades. The absolute number of opioid-related ARs might be seriously underestimated. Future studies should look into how to close this gap

Low back pain around retirement age and physical occupational exposure during working life

<p>Abstract</p> <p>Background</p> <p>Physical occupational exposure is a risk factor for low back pain in workers but the long term effects of exposure remain unclear. As several countries consider increasing the retirement age, further information on this topic is relevant. This study aimed to describe the prevalence of low back pain among middle aged and aging individuals in the general French population according to physical occupational exposure and retirement status.</p> <p>Methods</p> <p>The study population originated from the French national survey 'Enquête décennale santé 2002'. Low back pain for more than 30 days within the previous twelve months (LBP) was assessed using a French version of the Nordic questionnaire. Occupational exposure was self assessed. Subjects were classified as "exposed" if they were currently or had previously been exposed to handling of heavy loads and/or to tiring postures. The weighted prevalence of LBP was computed separately for men and women, for active (aged 45-59) and retiree (aged 55-74), according to 5-year age group and past/present occupational exposure.</p> <p>Results</p> <p>For active men, the prevalence of LBP was significantly higher in those currently or previously exposed (n = 1051) compared with those never exposed (n = 1183), respectively over 20% versus less than 11%. Among retired men, the prevalence of LBP tended towards equivalence with increasing age among those previously exposed (n = 748) and those unexposed (n = 599).</p> <p>Patterns were quite similar for women with a higher prevalence in exposed active women (n = 741) compared to unexposed (n = 1260): around 25% versus 15%. Similarly, differences between previously exposed (n = 430) and unexposed (n = 489) retired women tended to reduce with age.</p> <p>Conclusion</p> <p>The prevalence of LBP in active workers was associated with occupational exposure. The link with past exposure among retirees decreased with age. These results should be considered for policies dealing with prevention at the workplace and retirement.</p

Frequency of low back pain among men and women aged 30 to 64 years in France. Results of two national surveys.

International audienceINTRODUCTION: In France, most studies of low back pain (LBP) have been carried out among workers or patients. Until very recently, the frequency of LBP in the general population was not known, because National Health Surveys did not include questions on LBP. OBJECTIVE: To estimate the prevalence of LBP in the French population aged 30 to 64 years. MATERIALS AND METHODS: The main data were from the National Health Survey 2002-2003 (n=14,248). LBP was assessed by an accompanying self-administered questionnaire asking details about duration of LBP in the previous 12 months. Weights were used to estimate the prevalence of LBP in the French population, with two definitions of LBP. Additional results dealing with chronic LBP, from another national survey (Handicap, Disability and Dependence), are also briefly presented. RESULTS: More than half of the French population in this age group experienced LBP at least one day in the previous 12 months (LBP1), with 17% experiencing LBP for more than 30 days in the previous 12 months (LBP30); prevalence differed between men and women and that of LBP30 increased with age. DISCUSSION-CONCLUSION: The prevalence of LBP as assessed by the National Health Survey is similar to that found in countries other than France. These estimates can be used as a reference for surveys in specific populations, provided that comparable methodologies are used

DiNAMO: Exact method for degenerate IUPAC motifs discovery, characterization of sequence-specific errors

National audienceNext generation sequencing technologies are still associated with relatively high error rates, about 1%, which correspond to thousands of errors in the scale of a complete genome. Each region needs therefore to be sequenced several times and variants are usually filtered based on depth criteria. The significant number of artifacts, in spite of those filters, shows the limit of conventional approaches and indicates that some sequencing artifacts are recurrent. This recurrence underlines that sequencing errors can depend on the upstream nucleotide sequence context. Our goal is to search for overrepresented motifs that tend to induce sequencing errors. Previous studies showed that some motifs, such as GGT [1,2], induce sequencing errors in the Illumina technologies. However, these studies were dedicated to exact motifs, and did not take into account approximate motifs, limiting the statistical power of such approaches. On the other hand, some tools, such as FIRE [3], DREME [4] and Discrover [5], were developed to search for degenerate motifs over the 15-letter IUPAC alphabet in the context of chip-seq studies. However, these tools use greedy algorithms, implying a lack of sensitivity. So we developed an exact algorithm to search for degenerate motifs by enumerating all possible IUPAC motifs. This algorithm is based on mutual information and uses hashtables with graphs data structure to store the motifs. It is independent from the sequencing technology. Experimental results on real data show that there are many overrepresented motifs upstream of sequencing artifacts. These latter are identified through the strand bias between forward and reverse reads. The homopoly-mer of length 3 CCC seems to be sufficient to induce errors on IonTorrent. On Illumina, motifs are mainly composed of GGC followed by GGT (like: TGGCNGGT) or homopolymers. We have also noticed a base quality fall after the detected motifs. Our exact algorithm requires less than one minute (Intel R Core TM i5-4570 CPU, 3.20GHz), and less than 2GB of RAM to search for full degenerate motifs of length 6 on a dataset of approximately 24000 sequences, extracted from 11 exomes sequenced on IonTorrent Proton

Offspring mass variation in tree swallows : a case of bet‐hedging?

The evolution of reproductive strategies is affected by the ability of organisms to deal with future environmental conditions. When environments are temporally unpredictable, however, it is difficult to anticipate optimal offspring phenotype. Diversification of offspring phenotypes, a strategy called diversified bet‐hedging, may allow parents to maximize their fitness by reducing between‐year variation in reproductive success. The link between diversification of offspring phenotypes and individual reproductive success, however, has rarely been documented empirically. We used an eight‐year dataset (1215 broods, 870 females) on individually marked tree swallows ( Tachycineta bicolor ) to assess whether intra‐brood mass variation was compatible with a diversified bet‐hedging strategy. Intra‐brood mass variation was weakly, but significantly repeatable within females, suggesting consistent individual differences. Greater intra‐brood mass variation, however, was not associated with reduced between‐year variation in reproductive success or increased female reproductive success. Moreover, contrary to diversified bet‐hedging expectations, fledging success of large broods was greater when hatchlings had similar rather than variable masses. Our results suggest that intra‐brood mass variation may not result from diversified bet‐hedging, but rather from complex interactions between environmental, brood, and maternal characteristics

Enhance quality care performance: Determination of the variables for establishing a common database in French paediatric critical care units

Abstract Selected variables for the French Paediatric Intensive Care registry. Rationale, aims, and objectives Providing quality care requires follow-up in regard to clinical and economic activities. Over the past decade, medical databases and patient registries have expanded considerably, particularly in paediatric critical care medicine (eg, the Paediatric Intensive Care Audit Network (PICANet) in the UK, the Australian and New Zealand Paediatric Intensive Care (ANZPIC) Registry in Australia and New Zealand, and the Virtual Paediatric Intensive Care Unit Performance System (VPS) in the USA). Such a registry is not yet available in France. The aim of this study was to determine variables that ought to be included in a French paediatric critical care registry. Methods Variables, items, and subitems from 3 foreign registries and 2 French local databases were used. Items described each variable, and subitems described items. The Delphi method was used to evaluate and rate 65 variables, 90 items, and 17 subitems taking into account importance or relevance based on input from 28 French physicians affiliated with the French Paediatric Critical Care Group. Two ratings were used between January and May 2013. Results Fifteen files from 10 paediatric intensive care units were included. Out of 65 potential variables, 48 (74%) were considered to be indispensable, 16 (25%) were considered to be optional, and 1 (2%) was considered to be irrelevant. Out of 90 potential items, 62 (69%) were considered to be relevant, 23 (26%) were considered to be of little relevance, and 5 (6%) were considered to be irrelevant. Out of 17 potential subitems, 9 (53%) were considered to be relevant, 6 (35%) were considered to be of little relevance, and 2 (12%) were considered to be irrelevant. Conclusions The necessary variables that ought to be included in a French paediatric critical care registry were identified. The challenge now is to develop the French registry for paediatric intensive care units