Xenopus: An in vivo model for studying skin response to ultraviolet B irradiation.

Ultraviolet B (UVB) in sunlight cause skin damage, ranging from wrinkles to photoaging and skin cancer. UVB can affect genomic DNA by creating cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidine (6-4) photoproducts (6-4PPs). These lesions are mainly repaired by the nucleotide excision repair (NER) system and by photolyase enzymes that are activated by blue light. Our main goal was to validate the use of Xenopus laevis as an in vivo model system for investigating the impact of UVB on skin physiology. The mRNA expression levels of xpc and six other genes of the NER system and CPD/6-4PP photolyases were found at all stages of embryonic development and in all adult tissues tested. When examining Xenopus embryos at different time points after UVB irradiation, we observed a gradual decrease in CPD levels and an increased number of apoptotic cells, together with an epidermal thickening and an increased dendricity of melanocytes. We observed a quick removal of CPDs when embryos are exposed to blue light versus in the dark, confirming the efficient activation of photolyases. A decrease in the number of apoptotic cells and an accelerated return to normal proliferation rate was noted in blue light-exposed embryos compared with their control counterparts. Overall, a gradual decrease in CPD levels, detection of apoptotic cells, thickening of epidermis, and increased dendricity of melanocytes, emulate human skin responses to UVB and support Xenopus as an appropriate and alternative model for such studies.

External validation of Glasgow-Blatchford, modified Glasgow-Blatchford and CANUKA scores to identify low-risk patients with upper gastrointestinal bleeding in emergency departments: a retrospective cohort study.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a medical emergency with an approximate mortality of 10%, which results in a high hospitalisation rate. The Glasgow-Blatchford score (GBS) is recommended to identify low-risk patients who can be discharged from the emergency department (ED). A modified GBS (mGBS) and CANUKA score have recently been proposed but have not been well studied. The aim of this study was to assess whether the use of GBS, mGBS or CANUKA score could identify patients at low risk of death or need for intervention. METHODS: A single-centre retrospective study was performed including patients with suspected UGIB visiting the ED of Saint-Antoine hospital (Paris, France) from January 2016 to December 2018. Demographic and medical data needed to calculate GBS and CANUKA were collected, as well as outcomes data. Need for intervention was defined as the need for blood transfusion, endoscopic haemostasis or rebleeding within 7 days. In-hospital mortality was also collected. Sensitivity, specificity and predictive values were measured for the score thresholds of interest. RESULTS: A total of 386 patients were included. Median age was 60 years (38-78), 65.3% (n=252) were male and 60% (n=233) were hospitalised. A GBS≤1, mGBS=0 and CANUKA≤2 categorised 24.9%, 18.2% and 18.9% of patients as low risk, respectively. There was a need for intervention in 2.2%, 4.6% and 0% of those patients categorised as low risk by GBS, mGBS and CANUKA, respectively. No deaths occurred in the patients identified as low risk, regardless of the score used. All scores had a high sensitivity and negative predictive value. CONCLUSIONS: In patients with UGIB, the use of a GBS≤1 or CANUKA score ≤2 appears to be safe for identifying patients at low risk of death or need for intervention.

Left atrial compression by a large hiatal hernia: A rare cause of cardiac dysfunction.

Symptomatic hiatal hernia (HH) is most often revealed by gastroesophageal reflux disease, but there are atypical presentations some of which are life-threatening. We report the case of a 57-year-old woman brought to the emergency department with isolated shortness of breath for 24 h. Initial explorations revealed unexplained hyperlactatemia (6.4 mmol/L) without clinical or biological evidence of hypovolemia, distributive, obstructive or cardiogenic shock. Two hours after admission, we observed a decreased of blood pressure and an increase of lactate level to 7.9 mmol/L. A bedside echocardiography revealed an extra-cardiac left atrial compression and thoracoabdominal computed tomography showed a large sliding HH compressing the left atrium. After an upper gastrointestinal endoscopy permitting the aspiration of gastric contents, a repair surgery was performed without complications and patient was discharge three days later. Emergency physicians should be aware that HH can be a rare cause of cardiac symptoms by heart compression and certainly use echocardiography for unexplained hemodynamic failure.

Leukemia inhibitory factor signaling in Xenopus embryo: Insights from gain of function analysis and dominant negative mutant of the receptor.

Leukemia inhibitory factor (LIF) is a cytokine member of the interleukin 6 family (IL6) of cytokines. It signals through a heterodimer receptor complex that consists of the LIF receptor (or LIFR formerly known as gp190) and the Interleukin 6 signal transducer (or IL6ST formerly known as gp130). LIF signaling is mediated mainly by signal transducer and activator of transcription 3 (STAT3) and has a wide variety of biological activities with pleiotropic effects on many cell types and organs among which are stem cell renewal and implantation process in mammalian embryo. Despite the wealth of data on LIF in mammalian cells, there is a paucity of information on its functions in lower vertebrates. Here, we provide information on the status and the function of LIF signaling in Xenopus amphibian. The IL6 cytokine family is highly conserved in Xenopus genome both at ligands and receptors levels. All cytokines and receptors of the family, except oncostatin M (OSM) and IL27, can be identified in the genome including the orthologs of LIF, cardiotrophin 1 (CTF1), ciliary neurotrophic factor (CNTF), cardiotrophin like cytokine factor 1 (CLCF1), LIFR, IL6ST, IL6R, IL11RA and CNTFR. Lif mRNA is zygotically expressed after midblastula transition while lifr and il6st are maternally expressed. We have investigated the functions of LIF in Xenopus early development with a gain-of-function analysis combined to the use of a dominant negative form of the receptor. The overexpression of Xenopus lif in embryo activates STAT3 phosphorylation and induces a dramatic phenotype where embryos are ventralised and show a reduction of anterior structures with microcephaly. This results mainly from BMP signal stimulation and antagonism towards IGF signals. In addition, most embryos develop tumor-like cell masses according to both autonomous and non-autonomous processes. Through the use of a dominant negative form of the receptor, we demonstrate for the first time that a functional LIF signaling is required for normal vertebrate kidney development. Owing to its experimental advantages, the Xenopus embryo constitutes a useful model to identify the molecular actors that may account for the pleiotropic functions of LIF and their role in vertebrate development.

General practitioner consultation after a visit to the emergency department: an observational study.

BACKGROUND: Some studies have demonstrated an association between poor continuity of care, high likelihood of 'inappropriate' use of emergency departments (EDs) and avoidable hospitalization. However, we lack data concerning primary care use after an ED visit. OBJECTIVE: Identify the determinants of a visit to the general practitioner (GP) after an ED visit.Methods. DESIGN: Observational study (single-centre cohort). SETTING: One emergency department in Paris, France. SUBJECTS: All adult patients who presented at the ED and were discharged. MAIN OUTCOME MEASURE: We collected data by the use of a standardized questionnaire, patients' medical records and a telephonic follow-up. Descriptive analyses were performed to compare individuals with and without a GP. Then, for those with a GP, multivariate logistic regression was used to identify the determinants of the GP consultation. RESULTS: We included 243 patients (mean age 45 years [±19]); 211 (87%) reported having a GP. Among those who reported having a GP, 52% had consulted their GP after the ED visit. Not having a GP was associated with young age, not having complementary health insurance coverage, and being single. GP consultation was associated with increasing age [adjusted odds ratios (aOR) = 1.03], poor self-reported health status (aOR = 2.25), medical complaints versus traumatic injuries (aOR = 2.24) and prescription for sick note (aOR = 5.74). CONCLUSION: Not having a GP was associated with factors of social vulnerability such as not having complementary health insurance coverage. For patients with a GP, consultation in the month after an ED visit seems appropriate, because it was associated with poor health status and medical complaints.

From vestigial to vestigial-like: the Drosophila gene that has taken wing.

The members of the vestigial-like gene family have been identified as homologs of the Drosophila vestigial, which is essential to wing formation. All members of the family are characterized by the presence of the TONDU domain, a highly conserved sequence that mediates their interaction with the transcription factors of the TEAD family. Mammals possess four vestigial-like genes that can be subdivided into two classes, depending on the number of Tondu domains present. While vestigial proteins have been studied in great depth in Drosophila, we still have sketchy knowledge of the functions of vestigial-like proteins in vertebrates. Recent studies have unveiled unexpected functions for some of these members and reveal the role they play in the Hippo pathway. Here, we present the current knowledge about vestigial-like family gene members and their functions, together with their identification in different taxa.

MRAS GTPase is a novel stemness marker that impacts mouse embryonic stem cell plasticity and Xenopus embryonic cell fate.

Pluripotent mouse embryonic stem cells (mESCs), maintained in the presence of the leukemia inhibitory factor (LIF) cytokine, provide a powerful model with which to study pluripotency and differentiation programs. Extensive microarray studies on cultured cells have led to the identification of three LIF signatures. Here we focus on muscle ras oncogene homolog (MRAS), which is a small GTPase of the Ras family encoded within the Pluri gene cluster. To characterise the effects of Mras on cell pluripotency and differentiation, we used gain- and loss-of-function strategies in mESCs and in the Xenopus laevis embryo, in which Mras gene structure and protein sequence are conserved. We show that persistent knockdown of Mras in mESCs reduces expression of specific master genes and that MRAS plays a crucial role in the downregulation of OCT4 and NANOG protein levels upon differentiation. In Xenopus, we demonstrate the potential of Mras to modulate cell fate at early steps of development and during neurogenesis. Overexpression of Mras allows gastrula cells to retain responsiveness to fibroblast growth factor (FGF) and activin. Collectively, these results highlight novel conserved and pleiotropic effects of MRAS in stem cells and early steps of development.

Comparative genomic and expression analysis of the adenosine signaling pathway members in Xenopus.

Adenosine is an endogenous molecule that regulates many physiological processes via the activation of four specific G-protein-coupled ADORA receptors. Extracellular adenosine may originate either from the hydrolysis of released ATP by the ectonucleotidases or from cellular exit via the equilibrative nucleoside transporters (SLC29A). Adenosine extracellular concentration is also regulated by its successive hydrolysis into uric acid by membrane-bound enzymes or by cell influx via the concentrative nucleoside transporters (SLC28A). All of these members constitute the adenosine signaling pathway and regulate adenosine functions. Although the roles of this pathway are quite well understood in adults, little is known regarding its functions during vertebrate embryogenesis. We have used Xenopus laevis as a model system to provide a comparative expression map of the different members of this pathway during vertebrate development. We report the characterization of the different enzymes, receptors, and nucleoside transporters in both X. laevis and X. tropicalis, and we demonstrate by phylogenetic analyses the high level of conservation of these members between amphibians and mammals. A thorough expression analysis of these members during development and in the adult frog reveals that each member displays distinct specific expression patterns. These data suggest potentially different developmental roles for these proteins and therefore for extracellular adenosine. In addition, we show that adenosine levels during amphibian embryogenesis are very low, confirming that they must be tightly controlled for normal development.

The grape aquaporin VvSIP1 transports water across the ER membrane.

Water diffusion through biological membranes is facilitated by aquaporins, members of the widespread major intrinsic proteins (MIPs). In the present study, the localization, expression, and functional characterization of a small basic intrinsic protein (SIP) from the grapevine were assessed. VvSIP1 was expressed in leaves and berries from field-grown vines, and in leaves and stems from in vitro plantlets, but not in roots. When expressed in tobacco mesophyll cells and in Saccharomyces cerevisiae, fluorescent-tagged VvSIP1 was localized at the endoplasmic reticulum (ER). Stopped-flow spectroscopy showed that VvSIP1-enriched ER membrane vesicles from yeast exhibited higher water permeability and lower activation energy for water transport than control vesicles, indicating the involvement of protein-mediated water diffusion. This aquaporin was able to transport water but not glycerol, urea, sorbitol, glucose, or inositol. VvSIP1 expression in Xenopus oocytes failed to increase the water permeability of the plasma membrane. VvSIP1-His-tag was solubilized and purified to homogeneity from yeast ER membranes and the reconstitution of the purified protein in phosphatidylethanolamine liposomes confirmed its water channel activity. To provide further insights into gene function, the expression of VvSIP1 in mature grapes was studied when vines were cultivated in different field conditions, but its transcript levels did not increase significantly in water-stressed plants and western-exposed berries. However, the expression of the aquaporin genes VvSIP1, VvPIP2;2, and VvTIP1;1 was up-regulated by heat in cultured cells.

Xenopus as a model system for studying pigmentation and pigmentary disorders.

Human pigmentary disorders encompass a broad spectrum of phenotypic changes arising from disruptions in various stages of melanocyte formation, the melanogenesis process, or the transfer of pigment from melanocytes to keratinocytes. A large number of pigmentation genes associated with pigmentary disorders have been identified, many of them awaiting in vivo confirmation. A more comprehensive understanding of the molecular basis of pigmentary disorders requires a vertebrate animal model where changes in pigmentation are easily observable in vivo and can be combined to genomic modifications and gain/loss-of-function tools. Here we present the amphibian Xenopus with its unique features that fulfill these requirements. Changes in pigmentation are particularly easy to score in Xenopus embryos, allowing whole-organism based phenotypic screening. The development and behavior of Xenopus melanocytes closely mimic those observed in mammals. Interestingly, both Xenopus and mammalian skins exhibit comparable reactions to ultraviolet radiation. This review highlights how Xenopus constitutes an alternative and complementary model to the more commonly used mouse and zebrafish, contributing to the advancement of knowledge in melanocyte cell biology and related diseases.

Evaluation of use and identification of predictive factors for nonuse of peripheral venous catheters in the emergency department.

The placement of peripheral venous catheters (PVC) is a frequent procedure in the emergency department (ED), which exposes patients to complications (hematoma, fluid leakage, phlebitis, edema, infection), increases hemolysis of blood samples, is time-consuming and costly. The main aim of this study is to analyze the rate of PVC nonuse in the ED and to identify predictive factors of their nonuse. This prospective single-center observational study was conducted in the ED of the Saint-Antoine Hospital in Paris, France between February and March 2022. Adult patients receiving a PVC were included. In addition to demographic and medical data, the reason for PVC prescription and the prescribing physician's expectation of PVC use were collected. A total of 304 patients were included, with a median age of 61.5 years (IQR: 43-79 years), of whom 152 (50%) were men. PVC were primarily prescribed for intravenous medication administration. Seventy-two (23.7%) PVC were not used. In multivariable analysis, the predictive factors of nonuse were the prescribing physician's expectation of nonuse [OR 6.35, CI 95% (2.64-15.29), for "no" and "not sure" vs. "yes" responses] and the reason for prescribing "just in case" [OR 3.54, CI 95% (1.37-9.17)]. PVC were not used in 23.7% of cases. Predictors of nonuse were the prescribing physician's expectation of nonuse and the reason for prescribing "just in case". A PVC should probably not be prescribed if the prescribing physician thinks it will not be used or prescribes it "just in case".

WD repeat-containing protein 5, a ubiquitously expressed histone methyltransferase adaptor protein, regulates smooth muscle cell-selective gene activation through interaction with pituitary homeobox 2.

WD repeat-containing protein 5 (WDR5) is a common component of mammalian mixed lineage leukemia methyltransferase family members and is important for histone H3 lysine 4 methylation (H3K4me), which has been implicated in control of activation of cell lineage genes during embryogenesis. However, WDR5 has not been considered to play a specific regulatory role in epigenetic programming of cell lineage because it is ubiquitously expressed. Previous work from our laboratory showed the appearance of histone H3K4me within smooth muscle cell (SMC)-marker gene promoters during the early stages of development of SMC from multipotential embryonic cells but did not elucidate the underlying mechanisms that mediate SMC-specific and locus-selective H3K4me. Results presented herein show that knockdown of WDR5 significantly decreased SMC-marker gene expression in cultured SMC differentiation systems and in Xenopus laevis embryos in vivo. In addition, we showed that WDR5 complexes within SMC progenitor cells contained H3K4 methyltransferase enzymatic activity and that knockdown of WDR5 selectively decreased H3K4me1 and H3K4me3 enrichment within SMC-marker gene promoter loci. Moreover, we present evidence that it is recruited to these gene promoter loci through interaction with a SMC-selective pituitary homeobox 2 (Pitx2). Taken together, studies provide evidence for a novel mechanism for epigenetic control of SMC-marker gene expression during development through interaction of WDR5, homeodomain proteins, and chromatin remodeling enzymes.

LIM Homeobox-2 Suppresses Hallmarks of Adult and Pediatric Liver Cancers by Inactivating MAPK/ERK and Wnt/Beta-Catenin Pathways.

Introduction: Hepatocellular carcinoma and hepatoblastoma are two liver cancers characterized by gene deregulations, chromosomal rearrangements, and mutations in Wnt/beta-catenin (Wnt) pathway-related genes. LHX2, a transcriptional factor member of the LIM homeobox gene family, has important functions in embryogenesis and liver development. LHX2 is oncogenic in many solid tumors and leukemia, but its role in liver cancer is unknown. Methods: We analyzed the expression of LHX2 in hepatocellular carcinoma and hepatoblastoma samples using various transcriptomic datasets and biological samples. The role of LHX2 was studied using lentiviral transduction, in vitro cell-based assays (growth, migration, senescence, and apoptosis), molecular approaches (phosphokinase arrays and RNA-seq), bioinformatics, and two in vivo models in chicken and Xenopus embryos. Results: We found a strong connection between LHX2 downregulation and Wnt activation in these two liver cancers. In hepatoblastoma, LHX2 downregulation correlated with multiple poor outcome parameters including higher patient age, intermediate- and high-risk tumors, and low patient survival. Forced expression of LHX2 reduced the proliferation, migration, and survival of liver cancer cells in vitro through the inactivation of MAPK/ERK and Wnt signals. In vivo, LHX2 impeded the development of tumors in chick embryos and repressed the Wnt pathway in Xenopus embryos. RNA-sequencing data and bioinformatic analyses confirmed the deregulation of many biological functions and molecular processes associated with cell migration, cell survival, and liver carcinogenesis in LHX2-expressing hepatoma cells. At a mechanistic level, LHX2 mediated the disassembling of beta-catenin/T-cell factor 4 complex and induced expression of multiple inhibitors of Wnt (e.g., TLE/Groucho) and MAPK/ERK (e.g., DUSPs) pathways. Conclusion: Collectively, our findings demonstrate a tumor suppressive function of LHX2 in adult and pediatric liver cancers.

Acute icteric hepatitis as the first isolated symptom of COVID-19.

Patients with COVID-19 may be asymptomatic or present with extrarespiratory symptoms, such as liver injury. It has been reported that 22.5%-46.2% of patients have moderate elevation of liver enzymes. To our knowledge, acute hepatitis has never been described as an isolated symptom of COVID-19 in a previously healthy patient. We report the case of a 53-year-old patient with COVID-19 whose first clinical presentation was acute icteric hepatitis, several days before the development of others symptoms. During the pandemic, we suggest that patients with acute hepatitis be considered as COVID-19 suspects, tested and isolated.

Alcohol consumption among French physicians: A cross-sectional study.

BACKGROUND: Data regarding French physicians' alcohol behaviours are scarce and most studies address this issue within the population of either medical students or residents. We aim to describe and assess the prevalence of hazardous alcohol consumption among French physicians. METHODS: A regional, cross-sectional, survey was conducted in 2018 using an online questionnaire among Parisian general practitioners and hospital doctors. Hazardous alcohol consumption was defined by an Alcohol Use Disorders Identification Test (AUDIT) score ≥ 8. Data were analysed in 2020. RESULTS: Five hundred fifteen physicians completed the survey: 108 general practitioners and 407 hospital physicians. The median age was 40 years [32-55] and 59 % were women. They considered their physical and mental health as average or bad in 10 % and 8% of cases, respectively. The prevalence of hazardous alcohol consumption was 12.6 %. Among the 65 physicians with hazardous alcohol consumption, 27 (41.5 %) did not considered it as risky and four (6.2 %) mentioned a potentially negative impact on patients' care. Factors independently associated with hazardous alcohol consumption were illegal drugs consumption (OR 4.62 [2.05-10.37]) and fixed term contract for hospital doctors (OR 2.69 [1.14-6.36]). CONCLUSIONS: The prevalence of hazardous alcohol consumption among French physicians was 12.6 %. Illegal substance users and fix-termed contract hospital doctors were more likely to have risky alcohol consumption. A large-scale national study would confirm the factors associated with hazardous alcohol consumption and could explore the efficacy of preventive measures to insure the safety and health of physicians and their patients.

Outpatient Management of Patients With COVID-19: Multicenter Prospective Validation of the Hospitalization or Outpatient Management of Patients With SARS-CoV-2 Infection Rule to Discharge Patients Safely.

BACKGROUND: The Hospitalization or Outpatient Management of Patients With SARS-CoV-2 Infection (HOME-CoV) rule is a checklist of eligibility criteria for home treatment of patients with COVID-19, defined using a Delphi method. RESEARCH QUESTION: Is the HOME-CoV rule reliable for identifying a subgroup of COVID-19 patients with a low risk of adverse outcomes who can be treated at home safely? STUDY DESIGN AND METHODS: We aimed to validate the HOME-CoV rule in a prospective, multicenter study before and after trial of patients with probable or confirmed COVID-19 who sought treatment at the ED of 34 hospitals. The main outcome was an adverse evolution, that is, invasive ventilation or death, occurring within the 7 days after patient admission. The performance of the rule was assessed by the false-negative rate. The impact of the rule implementation was assessed by the absolute differences in the rate of patients who required invasive ventilation or who died and in the rate of patients treated at home, between an observational and an interventional period after implementation of the HOME-CoV rule, with propensity score adjustment. RESULTS: Among 3,000 prospectively enrolled patients, 1,239 (41.3%) demonstrated a negative HOME-CoV rule finding. The false-negative rate of the HOME-CoV rule was 4 in 1,239 (0.32%; 95% CI, 0.13%-0.84%), and its area under the receiver operating characteristic curve was 80.9 (95% CI, 76.5-85.2). On the adjusted populations, 25 of 1,274 patients (1.95%) experienced an adverse evolution during the observational period vs 12 of 1,274 patients (0.95%) during the interventional period: -1.00 (95% CI, -1.86 to -0.15). During the observational period, 858 patients (67.35%) were treated at home vs 871 patients (68.37%) during the interventional period: -1.02 (95% CI, -4.46 to 2.26). INTERPRETATION: A large proportion of patients treated in the ED with probable or confirmed COVID-19 have a negative HOME-CoV rule finding and can be treated safely at home with a very low risk of complications. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04338841; URL: www.clinicaltrials.gov.

HDAC inhibition induces expression of scaffolding proteins critical for tumor progression in pediatric glioma: focus on EBP50 and IRSp53.

BACKGROUND: Diffuse midline glioma (DMG) is a pediatric malignancy with poor prognosis. Most children die less than one year after diagnosis. Recently, mutations in histone H3 have been identified and are believed to be oncogenic drivers. Targeting this epigenetic abnormality using histone deacetylase (HDAC) inhibitors such as panobinostat (PS) is therefore a novel therapeutic option currently evaluated in clinical trials. METHODS: BH3 profiling revealed engagement in an irreversible apoptotic process of glioma cells exposed to PS confirmed by annexin-V/propidium iodide staining. Using proteomic analysis of 3 DMG cell lines, we identified 2 proteins deregulated after PS treatment. We investigated biological effects of their downregulation by silencing RNA but also combinatory effects with PS treatment in vitro and in vivo using a chick embryo DMG model. Electron microscopy was used to validate protein localization. RESULTS: Scaffolding proteins EBP50 and IRSp53 were upregulated by PS treatment. Reduction of these proteins in DMG cell lines leads to blockade of proliferation and migration, invasion, and an increase of apoptosis. EBP50 was found to be expressed in cytoplasm and nucleus in DMG cells, confirming known oncogenic locations of the protein. Treatment of glioma cells with PS together with genetic or chemical inhibition of EBP50 leads to more effective reduction of cell growth in vitro and in vivo. CONCLUSION: Our data reveal a specific relation between HDAC inhibitors and scaffolding protein deregulation which might have a potential for therapeutic intervention for cancer treatment.

Smooth muscle cell differentiation from human bone marrow: variations in cell type specific markers and Id gene expression in a new model of cell culture.

Stromal cells follow a vascular smooth muscle differentiation pathway. However, cell culture models performed from human bone marrow do not allow the obtention of a large proportion of highly differentiated smooth muscle cells (SMC) and their differentiation pathways remain unclear. We have characterized a new model of SMC differentiation from human bone marrow stromal cells by using different factors (bFGF, EGF, insulin and BMP-4). A relative homogeneous population of differentiated SMC was reproducibly obtained in short-term culture with high expression of SMC markers. Id gene expression was investigated and showed that (1) Id2 mRNA expression was upregulated during SMC differentiation without change of Id1 mRNA and (2) Id1 gene expression highly increased concomitantly with a decrease of SMC markers while Id2 mRNA was slightly modulated. Our data suggested that Id genes are potentially implicated in the differentiation pathway of human SMC from bone marrow.

Structure and evolution of tropomyosin genes.

Tropomyosins constitute a family of highly related actin-binding proteins found in the animal kingdom from yeast to human. In vertebrates, they are encoded by a multigene family where each member can produce several isoforms through alternative splicing and for some of them with alternate promoters. Tropomyosin isoform diversity has considerably increased during evolution from invertebrates to vertebrates and stems from the duplication of ancestral genes. The advance ofgenomic sequence information on various animals has expanded our knowledge on the structure of tropomyosin genes in different phyla and subphyla. We present the organisation of tropomyosin genes in different major phyla and the phylogenetic comparison of their structure highlights the evolution of this multigene family.