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Nucleotide diversity was assessed within nine candidate genes (in total 4.6 kb) for the time of bud burst in nine sessile oak (Quercus petraea) populations distributed in central and northern Europe. The sampled populations were selected on the basis of their contrasting time of bud burst observed in common garden experiments (provenance tests). The candidate genes were selected according to their expression profiles during the transition from quiescent to developing buds and/or their functional role in model plants. The overall nucleotide diversity was large (πtot=6.15 × 10−3; πsilent=11.2 × 10−3), but population differentiation was not larger than for microsatellites. No outlier single-nucleotide polymorphism (SNP), departing from neutral expectation, was found among the total of 125 SNPs. These results contrasted markedly with the significant associations that were observed between the candidate genes and bud burst in segregating populations. Quantitative trait loci (QTLs) for bud burst were identified for 13 year*site seasonal observations in a cloned mapping pedigree. Nineteen QTLs were detected, and QTLs located on linkage groups 2, 5 and 9 contributed repeatedly to more than 12% of the phenotypic variation of the trait. Eight genes were polymorphic in the two parents of the pedigree and could be mapped on the existing genetic map. Five of them located within the confidence intervals of QTLs for bud burst. Interestingly, four of them located within the three QTLs exhibiting the largest contributions to bud burst. [ABSTRACT FROM AUTHOR]

After neonatal hospitalization, our healthcare system offers multidisciplinary care for premature babies and their families during the first years of life. However, there are disparities and gaps, particularly in the case of medium prematurity. Maternal and child protection, a major player in early prevention and family follow-up, is a partner likely to be able to deploy post-hospital support perspectives in favor of child development and parenting support., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

In sweet cherry ( Prunus avium L.), large variability exists for various traits related to fruit quality. There is a need to discover the genetic architecture of these traits in order to enhance the efficiency of breeding strategies for consumer and producer demands. With this objective, a germplasm collection consisting of 116 sweet cherry accessions was evaluated for 23 agronomic fruit quality traits over 2-6 years, and characterized using a genotyping-by-sequencing approach. The SNP coverage collected was used to conduct a genome-wide association study using two multilocus models and three reference genomes. We identified numerous SNP-trait associations for global fruit size (weight, width, and thickness), fruit cracking, fruit firmness, and stone size, and we pinpointed several candidate genes involved in phytohormone, calcium, and cell wall metabolisms. Finally, we conducted a precise literature review focusing on the genetic architecture of fruit quality traits in sweet cherry to compare our results with potential colocalizations of marker-trait associations. This study brings new knowledge of the genetic control of important agronomic traits related to fruit quality, and to the development of marker-assisted selection strategies targeted towards the facilitation of breeding efforts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

In sweet cherry ( Prunus avium L.), flowering date is strongly dependent on the environment conditions and, therefore, is a trait of major interest for adaptation to climate change. Such trait can be influenced by genotype-by-environment interaction (G×E), that refers to differences in the response of genotypes to different environments. If not taken into account, G×E can reduce selection accuracy and overall genetic gain. However, little is known about G×E in fruit tree species. Flowering date is a highly heritable and polygenic trait for which many quantitative trait loci (QTLs) have been identified. As for the overall genetic performance, differential expression of QTLs in response to environment (QTL-by-environment interaction, QTL×E) can occur. The present study is based on the analysis of a multi-environment trial (MET) suitable for the study of G×E and QTL×E in sweet cherry. It consists of a sweet cherry F 1 full-sib family (n = 121) derived from the cross between cultivars 'Regina' and 'Lapins' and planted in two copies in five locations across four European countries (France, Italy, Slovenia and Spain) covering a large range of climatic conditions. The aim of this work was to study the effect of the environment on flowering date and estimate G×E, to carry QTL detection in different environments in order to study the QTL stability across environments and to estimate QTL×E. A strong effect of the environment on flowering date and its genetic control was highlighted. Two large-effect and environment-specific QTLs with significant QTL×E were identified on linkage groups (LGs) 1 and 4. This work gives new insights into the effect of the environment on a trait of main importance in one of the most economically important fruit crops in temperate regions. Moreover, molecular markers were developed for flowering date and a strategy consisting in using specific markers for warm or cold regions was proposed to optimize marker-assisted selection (MAS) in sweet cherry breeding programs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Branchereau, Hardner, Dirlewanger, Wenden, Le Dantec, Alletru, Parmentier, Ivančič, Giovannini, Brandi, Lopez-Ortega, Garcia-Montiel, Quilot-Turion and Quero-García.)

Objectives: To describe new-onset IBD (new IBD) in patients treated with IL-17 inhibitors (IL-17i), to assess their incidence and to identify their risk factors in real life., Methods: A French national registry (MISSIL) aimed to report all cases of new IBD in patients treated with IL-17i from January 2016 to December 2019. Using the estimated number of patients treated by IL-17 in France during the study period, the annual incidence rates of new IBD was reported in IL-17i-treated patients. A case-control study was performed with two controls per new IBD case matched by gender, age and underlying inflammatory disease., Results: Thirty-one cases of new IBD under IL-17i were collected: 27 patients treated for spondyloarthritis and four patients for psoriasis. All were observed with secukinumab (SEK). The median time to onset of new IBD symptoms was 4.0 (1.5-7.5) months. SEK was discontinued in all patients. The evolution was favourable with complete resolution (17/31), improvement (7/31) or stabilization (5/31). Two patients died: one due to a massive myocardial infarction and one due to post-colectomy complications. The incidence of new IBD decreased from 0.69/100 patient-years [PY] (7/1010) in 2016 to 0.08/100 PY (6/7951) in 2019. No previous treatment with etanercept (odds ratio [OR] = 0.33, 95% CI: 0.14-0.80, P = 0.014) and low number of previous biologic therapies (OR = 0.67, 95% CI: 0.47, 0.94, P = 0.021) were significantly associated with new IBD., Conclusion: The incidence of new IBD was low and decreased from 2016 to 2019. The outcome was favourable in 24 out of 31 patients, but two patients died., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Flowering date is an important trait in Prunus fruit species, especially for their adaptation in a global warming context. Numerous quantitative trait loci (QTLs) have been identified and a major one was previously located on LG4. The objectives of this study were to fine-map this QTL in sweet cherry, to identify robust candidate genes by using the new sweet cherry genome sequence of the cultivar 'Regina' and to define markers usable in marker-assisted selection (MAS). We performed QTL analyses on two populations derived from crosses using cultivars 'Regina' and 'Garnet' as parents. The first one (n = 117) was phenotyped over ten years, while the second one (n = 1386) was evaluated during three years. Kompetitive allele specific PCR (KASP) markers located within the QTL region on LG4 were developed and mapped within this region, consisting in the first fine mapping in sweet cherry. The QTL interval was narrowed from 380 kb to 68 kb and candidate genes were identified by using the genome sequence of 'Regina'. Their expression was analyzed from bud dormancy period to flowering in cultivars 'Regina' and 'Garnet'. Several genes, such as PavBOI-E3, PavSR45a and PavSAUR71, were differentially expressed in these two cultivars and could be then considered as promising candidate genes. Two KASP markers were validated using a population derived from a cross between cultivars 'Regina' and 'Lapins' and two collections, including landraces and modern cultivars. Thanks to the high synteny within the Prunus genus, these results give new insights into the control of flowering date in Prunus species and pave the way for the development of molecular breeding strategies., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved.)

Dormancy release and bloom time of sweet cherry cultivars depend on the environment and the genotype. The knowledge of these traits is essential for cultivar adaptation to different growing areas, and to ensure fruit set in the current climate change scenario. In this work, the major sweet cherry bloom time QTL qP-BT1.1 m (327 Kbs; Chromosome 1) was scanned for candidate genes in the Regina cv genome. Six MADS-box genes ( PavDAM s), orthologs to peach and Japanese apricot DAM s, were identified as candidate genes for bloom time regulation. The complete curated genomic structure annotation of these genes is reported. To characterize PavDAM s intra-specific variation, genome sequences of cultivars with contrasting chilling requirements and bloom times ( N = 13), were then mapped to the 'Regina' genome. A high protein sequence conservation (98.8-100%) was observed. A higher amino acid variability and several structural mutations were identified in the low-chilling and extra-early blooming cv Cristobalina. Specifically, a large deletion (694 bp) upstream of PavDAM1 , and various INDELs and SNPs in contiguous PavDAM4 and -5 UTRs were identified. PavDAM1 upstream deletion in 'Cristobalina' revealed the absence of several cis-acting motifs, potentially involved in PavDAM s expression. Also, due to this deletion, a non-coding gene expressed in late-blooming 'Regina' seems truncated in 'Cristobalina'. Additionally, PavDAM4 and - 5 UTRs mutations revealed different splicing variants between 'Regina' and 'Cristobalina' PavDAM5 . The results indicate that the regulation of PavDAM s expression and post-transcriptional regulation in 'Cristobalina' may be altered due to structural mutations in regulatory regions. Previous transcriptomic studies show differential expression of PavDAM genes during dormancy in this cultivar. The results indicate that 'Cristobalina' show significant amino acid differences, and structural mutations in PavDAM s, that correlate with low-chilling and early blooming, but the direct implication of these mutations remains to be determined. To complete the work, PCR markers designed for the detection of 'Cristobalina' structural mutations in PavDAM s, were validated in an F 2 population and a set of cultivars. These PCR markers are useful for marker-assisted selection of early blooming seedlings, and probably low-chilling, from 'Cristobalina', which is a unique breeding source for these traits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Calle, Grimplet, Le Dantec and Wünsch.)

In temperate trees, optimal timing and quality of flowering directly depend on adequate winter dormancy progression, regulated by a combination of chilling and warm temperatures. Physiological, genetic and functional genomic studies have shown that hormones play a key role in bud dormancy establishment, maintenance and release. We combined physiological and transcriptional analyses, quantification of abscisic acid (ABA) and gibberellins (GAs), and modeling to further investigate how these signaling pathways are associated with dormancy progression in the flower buds of two sweet cherry cultivars. Our results demonstrated that GA-associated pathways have distinct functions and may be differentially related with dormancy. In addition, ABA levels rise at the onset of dormancy, associated with enhanced expression of ABA biosynthesis PavNCED genes, and decreased prior to dormancy release. Following the observations that ABA levels are correlated with dormancy depth, we identified PavUG71B6, a sweet cherry UDP-GLYCOSYLTRANSFERASE gene that up-regulates active catabolism of ABA to ABA glucosyl ester (ABA-GE) and may be associated with low ABA content in the early cultivar. Subsequently, we modeled ABA content and dormancy behavior in three cultivars based on the expression of a small set of genes regulating ABA levels. These results strongly suggest the central role of ABA pathway in the control of dormancy progression and open up new perspectives for the development of molecular-based phenological modeling., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objectives: Assess the frequency of paradoxical reactions encountered in daily practice under tocilizumab, using the REGATE (Registry-RoActemra) registry. The secondary objectives were to determine the type of paradoxical reaction and the consequences of these reactions., Methods: The REGATE registry is an independent prospective registry, promoted by the French Society of Rheumatology, consisting of patients treated with tocilizumab for rheumatoid arthritis. The paradoxical reaction was retained if it was a paradoxical precipitation of a condition for which tocilizumab was indicated, if tocilizumab was being used for an alternative indication, and if it appeared after at least one tocilizumab infusion., Results: Among the 1491 patients included with at least one follow-up visit (3429 patient-years), a paradoxical reaction occurred in 9 patients (0.60% of patients; 2.62/1000 patient-years). These were 7 de novo pathologies (3 vasculitis, 3 uveitis, 1 lupus) and 2 exacerbations of pre-existing conditions (1 vasculitis, 1 lupus). Permanent discontinuation of tocilizumab was chosen for 5 patients., Conclusions: In the REGATE registry, the occurrence of paradoxical reactions in patients treated with tocilizumab was rare., (Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

The timing of flowering in perennial plants is crucial for their survival in temperate climates and is regulated by the duration of bud dormancy. Bud dormancy release and bud break depend on the perception of cumulative chilling during endodormancy and heat during the bud development. The objectives of this work were to identify candidate genes involved in dormancy and flowering processes in sweet cherry, their mapping in two mapping progenies 'Regina' × 'Garnet' and 'Regina' × 'Lapins', and to select those candidate genes which co-localized with quantitative trait loci (QTLs) associated with temperature requirements for bud dormancy release and flowering. Based on available data on flowering processes in various species, a list of 79 candidate genes was established. The peach and sweet cherry orthologs were identified and primers were designed to amplify sweet cherry candidate gene fragments. Based on the amplified sequences of the three parents of the mapping progenies, SNPs segregations in the progenies were identified. Thirty five candidate genes were genetically mapped in at least one of the two progenies and all were in silico mapped. Co-localization between candidate genes and QTLs associated with temperature requirements and flowering date were identified for the first time in sweet cherry. The allelic composition of the candidate genes located in the major QTL for heat requirements and flowering date located on linkage group 4 have a significant effect on these two traits indicating their potential use for breeding programs in sweet cherry to select new varieties adapted to putative future climatic conditions.

The present study investigated the genetic determinism of flowering date (FD), dissected into chilling (CR) and heat (HR) requirements. Elucidation of the genetic determinism of flowering traits is crucial to anticipate the increasing of ecological misalignment of adaptative traits with novel climate conditions in most temperate-fruit species. CR and HR were evaluated over 3 yr and FD over 5 yr in an intraspecific sweet cherry (Prunus avium) F1 progeny, and FD over 6 yr in a different F1 progeny. One quantitative trait locus (QTL) with major effect and high stability between years of evaluation was detected for CR and FD in the same region of linkage group (LG) 4. For HR, no stable QTL was detected. Candidate genes underlying the major QTL on LG4 were investigated and key genes were identified for CR and FD. Phenotypic dissection of FD and year repetitions allowed us to identify CR as the high heritable component of FD and a high genotype × environment interaction for HR. QTLs for CR reported in this study are the first described in this species. Our results provide a foundation for the identification of genes involved in CR and FD in sweet cherry which could be used to develop ideotypes adapted to future climatic conditions., (© 2014 INRA. New Phytologist © 2014 New Phytologist Trust.)

The nucleotide sequence of a 6863-bp Spiroplasma citri DNA fragment comprising the spiralin gene was determined. Sequence analysis revealed eight putative ORFs that encode ribosomal protein S2, elongation factor Ts, spiralin, 6-phosphofructokinase, pyruvate kinase, and three unidentified proteins (A, B, and X). The gene organization reported here is different from that previously published. Northern blot analysis of rpsB, tsf, and x transcripts indicates that these genes are organized into a single transcriptional unit (operon). However, the detection of an additional transcript corresponding to the rpsB gene alone suggests that a transcriptional mechanism should occur in the 3' region of the rpsB gene, allowing a conditional transcription termination.

A retrospective medical record-based study of cases of peripheral pyogenic arthritis diagnosed in a rheumatology department between 1966 and 1993 was conducted. Of the 197 cases, 179 were evaluable. Pyogenic arthritis accounted for 0.68% of admissions and 30.3% of bone and joint infections during the study period. Incidence rose gradually from 2.2 new cases per year between 1966 and 1970 up to 6 to 10 new cases per year since 1991. In 88% of cases a single joint was involved, with the most commonly affected sites being the knee (32.5%), hip (22.2%), shoulder (12%) and sacroiliac joint (11.4%). Of the 22 patients with polyarticular arthritis, 19 had involvement of two joints. A portal of entry was identified in 53% of cases. Of the 13% of iatrogenic cases, half occurred after a local corticosteroid injection. The pathogen was identified in 65% of cases. Staphylococcus aureus was the most common organism (56%) followed by streptococci (9.5%) and E. coli (7%). Only three patients had gonococcal arthritis. Mean duration of therapy was four months. Although complications were exceedingly rare, three patients died and three others developed septic shock. Our data suggest that the presentation of pyogenic arthritis has remained essentially unchanged. In particular, we found no increase in iatrogenic forms, in contrast to recent experience with vertebral osteomyelitis.