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During the 18th century, Faizābād and Lucknow became strategic centres of painting production in Northern India. Encouraged by the patronage of European collectors, but most probably by unnamed Indian patrons as well, the region experienced an intense period marked by the large number of albums and paintings in circulation. Based on the in-depth analysis of a selection of albums, paintings, and manuscripts, this article aims to highlight the evolution of compilation practices and painting productions. Full-page flower paintings, in particular, became increasingly popular in muraqqaʿ, to the point where calligraphic panels were completely replaced by colourful plants. Floral designs also appear in the margins, and the repetition of motives and patterns on several pages of different dimensions revealed an extensive commercialization based on a standardized production. In addition, the collections of European collectors such as Antoine-Louis Polier and Jean-Baptiste-Joseph Gentil bear the traces of commercial transactions between European and Indian collectors, as well as prices and possession marks. Together with their writings, correspondences, and memoirs, they bring new information on previously unknown Indian collectors, and more generally on the dynamism of the 18th-century book market.

Communication au congrès KES de 2021 qui s'est déroulé à Szczecin; International audience; Understanding the replication machinery of viruses contributes to suggest and try effective antiviral strategies. Exhaustive knowledge about the proteins structure, their function, or their interaction is one of the preconditions for successfully modeling it. In this context, modeling methods based on a formal representation with a high semantic expressiveness would be relevant to extract proteins and their nucleotide or amino acid sequences as an element from the replication process. Consequently, our approach relies on the use of semantic technologies to design the SARS-CoV-2 replication machinery. This provides the ability to infer new knowledge related to each step of the virus replication. More specifically, we developed an ontology-based approach enriched with reasoning process of a complete replication machinery process for SARS-CoV-2. We present in this paper a partial overview of our ontology OntoRepliCov to describe one step of this process, namely, the continuous translation or protein synthesis, through classes, properties, axioms, and SWRL (Semantic Web Rule Language) rules.

Recent publications describe various skin disorders in relation to phototypes and aging. The highest phototypes (III to VI) are more sensitive to acne, with the appearance of dark spots due to the inflammation induced by Cutibacterium acnes (previously Propionibacterium acnes). Dryness with aging is due to a lower activity of specific enzymes involved in the maturation of lipids in the stratum corneum. To observe and understand these cutaneous issues, tissue engineering is a perfect tool. Since several years, pigmented epidermis with melanocytes derived from specific phototypes allow to develop in vitro models for biological investigations. In the present study, several models were developed to study various skin disorders associated with phototypes and aging. These models were also used to evaluate selected ingredients’ ability to decrease the negative effects of acne, inflammation, and cutaneous dryness. Hyperpigmentation was observed on our reconstructed pigmented epidermis after the application of C. acnes, and pollutant (PM10) application induced increased inflammatory cytokine release. Tissue engineering and molecular biology offer the capability to modify genetically cells to decrease the expression of targeted proteins. In our case, GCase was silenced to decrease the maturation of lipids and in turn modify the epidermal barrier function. These in vitro models assisted in the development of ethnic skin-focused cosmetic ingredients.

International audience; Coronavirus (CoV) genomes consist of positive-sense single-stranded RNA and are among the largest viral RNAs known todate (30 kb). As a result, CoVs deploy sophisticated mecha-nisms to replicate these extraordinarily large genomes as wellas to transcribe subgenomic messenger RNAs. Since 2003, withthe emergence of three highly pathogenic CoVs (SARS-CoV,MERS-CoV, and SARS-CoV-2), significant progress has beenmade in the molecular characterization of the viral proteinsand key mechanisms involved in CoV RNA genome replication.For example, to allow for the maintenance and integrity of theirlarge RNA genomes, CoVs have acquired RNA proofreading 30-50 exoribonuclease activity (in nonstructural protein nsp14). Inorder to replicate the large genome, the viral-RNA–dependentRNA polymerase (RdRp; in nsp12) is supplemented by aprocessivity factor (made of the viral complex nsp7/nsp8),making it the fastest known RdRp. Lastly, a viral structuralprotein, the nucleocapsid (N) protein, which is primarilyinvolved in genome encapsidation, is required for efficient viralreplication and transcription. Therefore, CoVs are a paradoxamong positive-strand RNA viruses in the sense that they useboth a processivity factor and have proofreading activityreminiscent of DNA organisms in addition to structural pro-teins that mediate efficient RNA synthesis, commonly used bynegative-strand RNA viruses. In this review, we present a his-torical perspective of these unsuspected discoveries and detailthe current knowledge on the core replicative machinerydeployed by CoVs.

The discovery of a new coronavirus (CoV) as the causative agent of the severe acute respiratory syndrome (SARS) pandemic outbreak in 2003 has stimulated a number of studies on the molecular biology of SARS-CoV and related viruses. This research has provided significant new insight into functions and activities of the CoV replication-transcription complex, a multi-protein complex that directs coordinated processes of both continuous and discontinuous RNA synthesis to replicate and transcribe the large CoV genome, a single-stranded, positive-sense RNA of ∼30 kilobases. In this review, we summarize current understanding of the expression and functions of key replicative enzymes, such as RNA polymerases, ribonucleases, methyltransferases and other replicase gene encoded proteins involved in genome expression, virus-host interactions and other processes. Collectively, these recent studies reveal fascinating details of a huge enzymatic machinery unique in the RNA virus world.

RNA viruses encode dedicated protein machinery required through the viral life cycle. Some enzymatic activities are generally associated with RNA viruses such as RNA- or DNA-dependent RNA polymerases, RNA helicases or proteases. Some viral enzyme activities are however unique to some viral families. This is the case of two 3'-5' exoribonuclease activities identified in arenavirus and coronavirus proteomes. Arenaviruses have a segmented ambisense single stranded RNA genome of negative polarity while coronaviruses have a positive single-stranded genomic RNA. Although both enzymes belong to the same exo(ribo)nuclease superfamily, available data indicate that they are involved in very different pathways. Indeed, the exoribonuclease activity carried by the arenavirus nucleoprotein seems to counteract the innate immunity antiviral response while the exoribonuclease activity carried by the coronavirus nsp14 protein is likely involved in a unique RNA repair mechanism. In this review, we present our current knowledge about these two viral enzymes and their functions in the viral life cycle.

International audience; The large (L) protein of Ebola virus is a key protein for virus replication. Its N-terminal region harbors the RNA-dependent RNA polymerase activity, and its C terminus contains a cap assembling line composed of a capping domain and a methyltransferase domain (MTase) followed by a C-terminal domain (CTD) of unknown function. The L protein MTase catalyzes methylation at the 2'-O and N-7 positions of the cap structures. In addition, the MTase of Ebola virus can induce capin-dependent internal adenosine 2'-O-methylation. In this work, we investigated the CTD role in the regulation of the cap-dependent and cap-independent MTase activities of the L protein. We found that the CTD, which is enriched in basic amino acids, plays a key role in RNA binding and in turn regulates the different MTase activities. We demonstrated that the mutation of CTD residues modulates specifically the different MTase activities. Altogether, our results highlight the pivotal role of the L protein CTD in the control of viral RNA methylation, which is critical for Ebola virus replication and escape from the innate response in infected cells.IMPORTANCE Ebola virus infects human and nonhuman primates, causing severe infections that are often fatal. The epidemics, in West and Central Africa, emphasize the urgent need to develop antiviral therapies. The Ebola virus large protein (L), which is the central protein for viral RNA replication/transcription, harbors a methyltransferase domain followed by a C-terminal domain of unknown function. We show that the C-terminal domain regulates the L protein methyltransferase activities and consequently participates in viral replication and escape of the host innate immunity.

Resume Dans les pays developpes, la lepre est une pathologie rare et meconnue qui se manifeste habituellement par des lesions cutanees et des neuropathies peripheriques sensitives. Sa revelation par une polyarthrite peut entrainer une errance diagnostique. Nous rapportons le cas d’une lepre borderline lepromateuse avec reaction de reversion chez un homme de 26 ans originaire de Mayotte chez qui le diagnostic de sarcoidose avait initialement ete retenu devant le tableau clinique articulaire et cutane ainsi que l’anatomopathologie.

To describe the clinical and microbiological characteristics and outcomes after antibiotic treatment of a national cohort of patients with Lyme arthritis confirmed by PCR testing on synovial fluid and by serology, when available. Objectives To describe the clinical and microbiological characteristics and outcomes after antibiotic treatment of a national cohort of patients with Lyme arthritis confirmed by PCR testing on synovial fluid and by serology, when available. Methods Using the French National Reference Center for Borrelia database, patients with a positive PCR on synovial fluid for Borrelia were identified. Patient clinical and biological characteristics were reviewed from patient records. Long-term outcomes after treatment were studied through a questionnaire and with follow-up data. Results Among 357 synovial fluid testing by PCR between 2010 and 2016, 37 (10.4%) were positive for Borrelia. Patients’ median age was 36 years (range 6–78) with 61% of men and 28% patients under 18. The presentation was monoarticular in 92% and the knee was involved in 97%. Contrary to the Borrelia species repartition in European ticks, B. burgdorferi sensu stricto was the most prevalent species found in synovial fluid (54%) followed by B. azfelii (29%) and B. garinii (17%). Antibiotic treatments were mainly composed of doxycycline (n = 24), ceftriaxone (n = 10) and amoxicillin (n = 6), for a median duration of 4 weeks (range 3–12). Despite a properly conducted treatment, 34% of patients (n = 12) developed persistent synovitis for at least 2 months (median duration 3 months, range 2–16). Among those, 3 developed systemic inflammatory oligo- or polyarthritis in previously unaffected joints with no signs of persistent infection (repeated PCR testing negative), which mandated Disease-Modifying Antirheumatic Drugs (DMARD) introduction, leading to remission. Conclusion In France and contrary to ticks ecology, Lyme arthritis is mainly caused by B. burgdorferi sensu stricto. Despite proper antibiotic therapy, roughly one third of patients may present persistent inflammatory synovitis and a small proportion may develop systemic arthritis. In such cases, complete remission can be reached using DMARD. journal article 2019 06 2018 09 28 imported

introduction : les affections rhumatismales en Afrique sont souvent chroniques parfois aigues, mais surtout leur prise en charge reste aleatoire sur le plan therapeutique. Malgre tout, dans la derniere decennie, l’interet porte a la rhumatologie observee en zone tropicale, specialement dans la race noire, est croissant. De plus il apparait du plus grand interet d’etablir des comparaisons entre ce qui est observe dans la race noire et ce qui est connu dans d’autres races: ainsi, peut-on preciser la place des facteurs genetiques dans la physiopathologie souvent plurifactorielle de ces affections. Dans le contexte d’un continent encore en developpement, la pathologie infectieuse est encore frequente en Afrique Sub-saharienne. Methodes : dans ce travail, les auteurs passent en revue les polyarthrites de l’adulte en Afrique a travers le temps d’hier a aujourd’hui avant de presenter les particularites liees aux therapeutiques et a leur application en Afrique. Resultats : sur le plan contextuel, l’Afrique est une terre d’ambivalence d’une chose et de son contraire: unicite et diversite; melange et separation entre autres. En effet l’Afrique repose sur une plaque tectonique, c’est aussi et surtout un continent. L’Afrique est aussi une terre de diversites representees principalement par: des climats contrastes (mediterraneen, aride, tropical sec, tropical humide et equatorial), des populations tres inegalement reparties a dominante jeune, une tres grande diversite genetique et ethnoculturelle avec plus de 2000 groupes ethniques. L’environnement est aussi caracterise par une urbanisation tres anarchique avec des disparites enormes: 80% des populations sont encore rurales. Les etudes consacrees aux affections rhumatismales en Afrique Noire ont permis d’etablir que le continent n’en n’est pas epargne. Lorsque l’on evoque les particularites de la rhumatologie dans la race noire, il apparait que certaines affections dont le caractere genetique est clairement etabli, ont une frequence tres differente chez le caucasien. Les autres particularites majeures de la rhumatologie en Afrique est representee par les complications osteoarticulaires des hemoglobinopathies, specialement de la drepanocytose, determinee genetiquement et propre a la race noire et la fluorose osseuse hydro tellurique encore frequente en Afrique de l’ouest. L’Afrique est un vaste continent aux contrastes environnementaux, sociaux, culturels et genetiques. Conclusion : les polyarthrites de l’adulte en Afrique sont polymorphes, d’etiologies diverses. Elles sont frequentes, souvent diagnostiquees avec retard et a des stades evolues. Aujourd’hui les rhumatismes parasitaires ont quasi disparu. La prevalence des rhumatismes lies aux VIH est devenue plus importante. Enfin une autre preoccupation actuelle ou a venir est representee par l’emergence des rhumatismes metaboliques dans un contexte de changement de mode avec une urbanisation anarchique, une sedentarite, la «montee en puissance» du Syndrome. Au meme moment les therapeutiques sont toujours limitees et concurrencees par la contrefacon et le non-respect des regles de conservation des medicaments.

Highlights • This review summarizes coronavirus RNA biochemistry mechanisms. • A processivity factor for the viral RNA-dependent RNA polymerase. • RNA proofreading through a viral 3′–5′ exonuclease. • Viral capping regulator factors., The successive emergence of highly pathogenic coronaviruses (CoVs) such as the Severe Acute Respiratory Syndrome (SARS-CoV) in 2003 and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in 2012 has stimulated a number of studies on the molecular biology. This research has provided significant new insight into functions and activities of the replication/transcription multi-protein complex. The latter directs both continuous and discontinuous RNA synthesis to replicate and transcribe the large coronavirus genome made of a single-stranded, positive-sense RNA of ∼30 kb. In this review, we summarize our current understanding of SARS-CoV enzymes involved in RNA biochemistry, such as the in vitro characterization of a highly active and processive RNA polymerase complex which can associate with methyltransferase and 3′–5′ exoribonuclease activities involved in RNA capping, and RNA proofreading, respectively. The recent discoveries reveal fascinating RNA-synthesizing machinery, highlighting the unique position of coronaviruses in the RNA virus world.

Favipiravir (T-705) is a broad-spectrum antiviral agent that has been approved in Japan for the treatment of influenza virus infections. T-705 also inhibits the replication of various RNA viruses, including chikungunya virus (CHIKV). We demonstrated earlier that the K291R mutation in the F1 motif of the RNA-dependent RNA polymerase (RdRp) of CHIKV is responsible for low-level resistance to T-705. Interestingly, this lysine is highly conserved in the RdRp of positive-sense single-stranded RNA (+ssRNA) viruses. To obtain insights into the unique broad-spectrum antiviral activity of T-705, we explored the role of this lysine using another +ssRNA virus, namely, coxsackievirus B3 (CVB3). Introduction of the corresponding K-to-R substitution in the CVB3 RdRp (K159R) resulted in a nonviable virus. Replication competence of the K159R variant was restored by spontaneous acquisition of an A239G substitution in the RdRp. A mutagenesis analysis at position K159 identified the K159M variant as the only other viable variant which had also acquired the A239G substitution. The K159 substitutions markedly decreased the processivity of the purified viral RdRp, which was restored by the introduction of the A239G mutation. The K159R A239G and K159M A239G variants proved, surprisingly, more susceptible than the wild-type virus to T-705 and exhibited lower fidelity in polymerase assays. Furthermore, the K159R A239G variant was found to be highly attenuated in mice. We thus demonstrate that the conserved lysine in the F1 motif of the RdRp of +ssRNA viruses is involved in the broad-spectrum antiviral activity of T-705 and that it is a key amino acid for the proper functioning of the enzyme. IMPORTANCE In this study, we report the key role of a highly conserved lysine residue of the viral polymerase in the broad-spectrum antiviral activity of favipiravir (T-705) against positive-sense single-stranded RNA viruses. Substitutions of this conserved lysine have a major negative impact on the functionality of the RdRp. Furthermore, we show that this lysine is involved in the fidelity of the RdRp and that the RdRp fidelity influences the sensitivity of the virus for the antiviral efficacy of T-705. Consequently, these results provide insights into the mechanism of the antiviral activity of T-705 and may lay the basis for the design of novel chemical scaffolds that may be endowed with a more potent broad-spectrum antiviral activity than that of T-705.

ABSTRACT RNA viruses are important emerging pathogens that cause human and animal infectious diseases. Antiviral therapies have to deal with the high mutational capacity of RNA viruses, which quickly adapt to new environments. A primary target for antiviral drug development is the viral RNA-dependent RNA polymerase (RdRp), which is the central enzyme of the viral RNA replication/transcription machinery. Here, we review the current mechanistic and structural knowledge on RdRps of positive-strand RNA viruses gained through crystallography and biochemistry. In addition, we review the growing body of information on RdRp-mediated strategies, such as proofreading and genome end repair, used by positive-strand RNA viruses to maintain their genome integrity.

Highlights • This paper presents an in-depth review of coronavirus Orf1b enzymes. • It is organized in sections on RNA synthesis, RNA degradation, and RNA capping. • It discusses integration of these functions into the coronavirus replication/transcription complex. • It reviews published inhibitors of any of these functions., The SARS (severe acute respiratory syndrome) pandemic caused ten years ago by the SARS-coronavirus (SARS-CoV) has stimulated a number of studies on the molecular biology of coronaviruses. This research has provided significant new insight into many mechanisms used by the coronavirus replication-transcription complex (RTC). The RTC directs and coordinates processes in order to replicate and transcribe the coronavirus genome, a single-stranded, positive-sense RNA of outstanding length (∼27–32 kilobases). Here, we review the up-to-date knowledge on SARS-CoV replicative enzymes encoded in the ORF1b, i.e., the main RNA-dependent RNA polymerase (nsp12), the helicase/triphosphatase (nsp13), two unusual ribonucleases (nsp14, nsp15) and RNA-cap methyltransferases (nsp14, nsp16). We also review how these enzymes co-operate with other viral co-factors (nsp7, nsp8, and nsp10) to regulate their activity. These last ten years of research on SARS-CoV have considerably contributed to unravel structural and functional details of one of the most fascinating replication/transcription machineries of the RNA virus world. This paper forms part of a series of invited articles in Antiviral Research on “From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses”.

Joint Bone Spine - In Press.Proof corrected by the author Available online since jeudi 26 janvier 2017

Trente ans apres l’exposition organisee par Jeremiah Losty (The Art of the Book in India, Londres, 1982.), la British Library consacre une exposition aux productions de peinture durant le long regne la dynastie moghole. Le catalogue, richement illustre s’organise en quatre chapitres. Il s’ouvre sur une carte du sous-continent, une genealogie des souverains moghols et un glossaire. Le catalogue contient 167 entrees associees a une bibliographie exhaustive des publications. Le premier chapitre ...

Summary Telomere shortening is considered as one of the main characteristics of cellular aging by limiting cellular division. Besides the fundamental advances through the discoveries of telomere and telomerase, which were recognized by a Nobel Prize, telomere protection remains an essential area of research. Recently, it was evidenced that studying the cross-talks between the proteins associated with telomere should provide a better understanding of the mechanistic basis for telomere-associated aging phenotypes. In this review, we discuss the current knowledge on telomere shortening, telomerase activity, and the essential role of telomere binding proteins in telomere stabilization and telomere-end protection. This review highlights the capacity of telomere binding proteins to limit cellular senescence and to maintain skin tissue homeostasis, which is of key importance to reduce accelerated tissue aging. Future studies addressing telomere protection and limitation of DNA damage response in human skin should include investigations on telomere binding proteins. As little is known about the expression of telomere binding proteins in human skin and modulation of their expression with aging, it remains an interesting field of skin research and a key area for future skin protection and anti-aging developments.

Most viruses use the mRNA-cap dependent cellular translation machinery to translate their mRNAs into proteins. The addition of a cap structure at the 5' end of mRNA is therefore an essential step for the replication of many virus families. Additionally, the cap protects the viral RNA from degradation by cellular nucleases and prevents viral RNA recognition by innate immunity mechanisms. Viral RNAs acquire their cap structure either by using cellular capping enzymes, by stealing the cap of cellular mRNA in a process named "cap snatching", or using virus-encoded capping enzymes. Many viral enzymes involved in this process have recently been structurally and functionally characterized. These studies have revealed original cap synthesis mechanisms and pave the way towards the development of specific inhibitors bearing antiviral drug potential.

The replication/transcription complex of severe acute respiratory syndrome coronavirus is composed of at least 16 nonstructural proteins (nsp1–16) encoded by the ORF-1a/1b. This complex includes replication enzymes commonly found in positive-strand RNA viruses, but also a set of RNA-processing activities unique to some nidoviruses. The nsp14 protein carries both exoribonuclease (ExoN) and (guanine-N7)-methyltransferase (N7-MTase) activities. The nsp14 ExoN activity ensures a yet-uncharacterized function in the virus life cycle and must be regulated to avoid nonspecific RNA degradation. In this work, we show that the association of nsp10 with nsp14 stimulates >35-fold the ExoN activity of the latter while playing no effect on N7-MTase activity. Nsp10 mutants unable to interact with nsp14 are not proficient for ExoN activation. The nsp10/nsp14 complex hydrolyzes double-stranded RNA in a 3′ to 5′ direction as well as a single mismatched nucleotide at the 3′-end mimicking an erroneous replication product. In contrast, di-, tri-, and longer unpaired ribonucleotide stretches, as well as 3′-modified RNAs, resist nsp10/nsp14-mediated excision. In addition to the activation of nsp16-mediated 2′-O-MTase activity, nsp10 also activates nsp14 in an RNA processing function potentially connected to a replicative mismatch repair mechanism.

Joint Bone Spine - In Press.Proof corrected by the author Available online since jeudi 31 mars 2016