New insights into inflammatory osteoclast precursors as therapeutic targets for rheumatoid arthritis and periodontitis

Rheumatoid arthritis(RA)and periodontitis are chronic inflammatory diseases leading to increased bone resorption.Preventing this inflammatory bone resorption is a major health challenge.Both diseases share immunopathogenic similarities and a common inflammatory environment.The autoimmune response or periodontal infection stimulates certain immune actors,leading in both cases to chronic inflammation that perpetuates bone resorption.Moreover,RA and periodontitis have a strong epidemiological association that could be explained by periodontal microbial dysbiosis.This dysbiosis is believed to be involved in the initiation of RA via three mechanisms.(i)The dissemination of periodontal pathogens triggers systemic inflammation.(ii)Periodontal pathogens can induce the generation of citrullinated neoepitopes,leading to the generation of anti-citrullinated peptide autoantibodies.(iii)Intracellular danger-associated molecular patterns accelerate local and systemic inflammation.Therefore,periodontal dysbiosis could promote or sustain bone resorption in distant inflamed joints.Interestingly,in inflammatory conditions,the existence of osteoclasts distinct from“classical osteoclasts”has recently been reported.They have proinflammatory origins and functions.Several populations of osteoclast precursors have been described in RA,such as classical monocytes,a dendritic cell subtype,and arthritis-associated osteoclastogenic macrophages.The aim of this review is to synthesize knowledge on osteoclasts and their precursors in inflammatory conditions,especially in RA and periodontitis.Special attention will be given to recent data related to RA that could be of potential value in periodontitis due to the immunopathogenic similarities between the two diseases.Improving our understanding of these pathogenic mechanisms should lead to the identification of new therapeutic targets involved in the pathological inflammatory bone resorption associated with these diseases.

Diversity and selection of the continuous-flowering gene, RoKSN, in rose

Blooming seasonality is an important trait in ornamental plants and was selected by humans.Wild roses flower only in spring whereas most cultivated modern roses can flower continuously.This trait is explained by a mutation of a floral repressor gene,RoKSN,a TFL1 homologue.In this work,we studied the origin,the diversity and the selection of the RoKSN gene.We analyzed 270 accessions,including wild and old cultivated Asian and European roses as well as modern roses.By sequencing the RoKSN gene,we proposed that the allele responsible for continuous-flowering,RoKSN copia,originated from Chinese wild roses(Indicae section),with a recent insertion of the copia element.Old cultivated Asian roses with the RoKSN copia allele were introduced in Europe,and the RoKSN copia allele was progressively selected during the 19th and 20th centuries,leading to continuous-flowering modern roses.Furthermore,we detected a new allele,RoKSN A181,leading to a weak reblooming.This allele encodes a functional floral repressor and is responsible for a moderate accumulation of RoKSN transcripts.A transient selection of this RoKSN A181 allele was observed during the 19th century.Our work highlights the selection of different alleles at the RoKSN locus for recurrent blooming in rose.

Morphological studies of rose prickles provide new in sights

Prickles are common structures in plants that play a key role in defense against herbivores.In the Rosa genus,prickles are widely present with great diversity in terms of form and density.For cut rose production,prickles represent an important issue,as they can damage the flower and injure workers.Our objectives were to precisely describe the types of prickles that exist in roses,their tissues of origin and their development.We performed a detailed histological analysis of prickle initiation and development in a rose F1 population.Based on the prickle investigation of 110 roses,we proposed the fi rst categorization of prickles in the Rosa genus.They are mainly divided into two categories,nonglandular prickles(NGPs)and glandular prickles(GPs),and subcategories were defined based on the presence/absence of hairs and branches.We demonstrated that NGPs and GPs both originate from multiple cells ofthe ground meristem beneath the protoderm.For GPs,the gland cells originate from the protoderm of the GP at the early developmental stage.Our findings clearly demonstrate that prickles are notmodified trichomes(which originate from the protoderm).These conclusions are different from the current mainstream hypothesis.These results provide a foundation for further studies on prickle initiation and development in plants.

Paracetamol Sensitive Cellulose-Based Electrochemical Sensors

Electrochemical determination of paracetamol(PCT)was successfully performed using carbon paste electrodes(CPEs)modified with treated coffee husks(CHt)or cellulose powder(Ce).Scanning electron microscopy was used to characterize unmodified or modified CPEs prior to their use.The electrochemical oxidation of PCT was investigated using square wave voltammetry(SWV)and cyclic voltammetry(CV).The oxidation current density of PCT was two-fold higher with the CPE-CHt sensor and 30%higher with CPE-Ce in comparison with the unmodified CPE,and this correlated with the higher hydrophilicity of the modified electrodes.Using SWV for the electrochemical analysis of PCT,carbon paste electrode modified with raw coffee husks(CPE-CHr)showed the presence of impurities at+0.27 V/SCE,showing the interest in using pure cellulose for the present analytical application.Furthermore,CPE-Ce presented a higher real area compared to CPE-CHr,which explains the increase in the limit of saturation from 400 mg/L to 950 mg/L.The better saturation limit exhibited by CPE-Ce justifies its choice for electroanalysis of PCT in commercialized tablets.The proposed method was successfully applied in the determination of PCT in commercialized tablets(DolipraneR 500)with a recovery rate close to 100%,and no interference with the excipients contained in the tablets analyzed was observed.This novel sensor opens the way for sustainable development of electroanalytical control of drugs sold individually in developing countries.

Gaining access to acetyl-CoA by peroxisomal surface display

Synthetic biology is constantly making progress for producing compounds on demand.Recently,Yocum and collaborators have developed an outstanding approach based on the anchoring of biosynthetic enzymes to the peroxisomal membrane.This allowed access to an untapped resource of acetyl-CoA and stimulated the synthesis of a valuable polyketide.

Added value of molecular karyotype in childhood acute lymphoblastic leukemia

Background:Thanks to an improved therapeutic regimen in childhood B-cell precursor acute lymphoblastic leukemia(BCP-ALL),5 year-overall survival now exceeds 90%.Unfortunately,the 25%of children who relapse have an initial poor prognosis,potentially driven by pre-existing or emerging molecular anomalies.The latter are initially and essentially identified by cytogenetics.However,some subtle alterations are not visible through karyotyping.Methods:Single nucleotide polymorphisms(SNP)array is an alternative way of chromosomal analysis allowing for a more in-depth evaluation of chromosomal modifications such as the assessment of copy number alterations(CNA)and loss of heterozygosity(LOH).This method was applied here in retrospective diagnosis/relapse paired samples from seven children with BCP-ALL and in a prospective cohort of 38 newly diagnosed childhood cases.Results:In the matched study,compared to the initial karyotype,SNP array analysis reclassified two patients as poor prognosis cases.Modulation during relapse was seen for 4 CNA and 0.9 LOH.In the prospective study,SNP reclassified the 10 patients with intermediate karyotype as 7 good prognosis and 3 poor prognosis.Ultimately,in all the children tested,SNP array allowed to identify additional anomalies compared to conventional karyotype,refine its prognostic value and identify some druggable anomalies that could be used for precision medicine.Overall,the anomalies detected could be segregated in four groups respectively involved in B-cell development,cell proliferation,transcription and molecular pathways.Conclusion:SNP therefore appears to be a method of choice in the integrated diagnosis of BCP ALL,especially for patients initially classified as intermediate prognosis.This complementary method of both cytogenetics and high throughput sequencing allows to obtain further classified information and can be useful in case of failure of these techniques.

Self-assembly of peptide-based nanostructures： Synthesis and biological activity

Peptide-based nanostructures have received much attention in the field of drug targeting. In fact, peptides have many advantages such as simplicity of the structure, biocompatibility, and chemical diversity. Moreover, some peptides, which are called cell-penetrating peptides, can cross cellular membranes and carry small molecules, small interfering RNA, or viruses inside live cells. These molecules are often covalently or noncovalently linked to cargoes, thus forming amphiphilic conjugates that can self-assemble. Supramolecular nanostructures formed from peptides are used in nanomedicine as a carrier to protect a drug and to target cancer cells. This review explores aliphatic-chain-conjugated peptides and drug-conjugated peptides that can self-assemble. Special emphasis is placed on the synthesis procedure, nanostructure formation, and biological activity.