Validating the Perceived Active School Travel Enablers and Barriers - Child (PASTEB-C) questionnaire.

OBJECTIVES: Presently, child-specific tools and instruments related to active school travel (AST) are lacking. This methodological shortcoming often contributes to suboptimal AST behaviour evaluations and intervention programming. The aim of this paper was to develop and validate a theoretically informed child-specific scale regarding multiple perceived barriers and enablers known to impact children's participation in AST. STUDY DESIGN: Mixed methods. METHODS: A mixed-methods and multistudy scale development approach featuring the application of social-ecological theory, a validation pilot study (n = 80), and test-retest study (n = 96) was conducted in collaboration with children in Ontario, Canada. In tandem with completing cognitive interviews and online surveys, multiple analyses, including a qualitative thematic analysis, along with weighted Cohen's kappa, Cronbach's alpha, and confirmatory factor analysis were undertaken. RESULTS: Qualitative analyses of the developed tool addressed face validity concerns related to the response options and definitions of terms used. Following the reliability analyses of 40 items, two confirmatory factor analyses were run to assess the construct validation of perceived AST barriers and enablers, and resulted in the development of the 24-item Perceived Active School Travel Enablers and Barriers - Child (PASTEB-C) questionnaire. CONCLUSION: The developed PASTEB-C questionnaire may be used to inform the programming and development of AST interventions, as well as conduct child-specific AST research.

Cutaneous sarcoidosis due to immune-checkpoint inhibition and exacerbated by a novel BRAF dimerization inhibitor.

Sarcoidosis is a non-infective granulomatous disorder of unknown aetiology, with cutaneous involvement affecting up to 30% of patients. Drug-induced sarcoidosis has been reported secondary to modern melanoma therapies including immune-checkpoint inhibitors and first generation BRAF inhibitors such as vemurafenib and dabrafenib. Herein, we report a case of cutaneous micropapular sarcoidosis that first developed on immune-checkpoint inhibition with ipilimumab and nivolumab for metastatic melanoma, which was exacerbated and further complicated by pityriasis rubra pilaris-like palmar plaques upon transition to a next-generation BRAF-dimerisation inhibitor. Both the micropapular eruption and palmar plaques rapidly resolved after cessation of the novel BRAF-inhibitor and concurrent commencement of hydroxychloroquine. It is unclear how inhibition of BRAF-dimerisation results in granuloma formation, though upregulation of TH1/TH17 T-cells and impairment of T-reg cells may be responsible. Clinicians should be aware of the potential for exacerbation of sarcoidosis when transitioning from immune-checkpoint inhibitors to these novel BRAF-dimerisation inhibitors, particularly as their uptake in treating cancers increases beyond clinical trials. Further studies are required to assess whether these next-generation agents can trigger sarcoidosis de-novo, or simply exacerbate pre-existing sarcoidosis.

Identification of naphthalene carboxylase subunits of the sulfate-reducing culture N47.

Expanding industrialization and the associated usage and production of mineral oil products has caused a worldwide spread of polycyclic aromatic hydrocarbons. These pollutants accumulate and persist under anoxic conditions but little is known about the biochemical reactions catalyzing their anaerobic degradation. Recently, carboxylation of naphthalene was demonstrated for the sulfate-reducing culture N47. Proteogenomic studies on N47 allowed the identification of a gene cluster with products suggested to be involved in the initial reaction of naphthalene degradation. Here, we performed comparative proteomic studies with N47 proteins extracted from naphthalene versus 2-methylnapththalene-grown cells on blue native PAGE. The analysis led to the identification of subunits of the naphthalene carboxylase of N47. Moreover, we show that the identified subunits are encoded in an operon structure within the previously mentioned naphthalene carboxylase gene cluster. These findings were supported by a pull-down experiment revealing in vitro interaction partners of a heterologously produced GST-tagged naphthalene carboxylase subunit. Based on these lines of evidence, naphthalene carboxylase is proposed to be a complex of about 750 kDa. Naphthalene carboxylase can be seen as a prototype of a new enzyme family of UbiD like de-/carboxylases catalyzing the anaerobic activation of non-substituted polycyclic aromatic hydrocarbons.

Giardia Colonizes and Encysts in High-Density Foci in the Murine Small Intestine.

Giardia lamblia is a highly prevalent yet understudied protistan parasite causing significant diarrheal disease worldwide. Hosts ingest Giardia cysts from contaminated sources. In the gastrointestinal tract, cysts excyst to become motile trophozoites, colonizing and attaching to the gut epithelium. Trophozoites later differentiate into infectious cysts that are excreted and contaminate the environment. Due to the limited accessibility of the gut, the temporospatial dynamics of giardiasis in the host are largely inferred from laboratory culture and thus may not mirror Giardia physiology in the host. Here, we have developed bioluminescent imaging (BLI) to directly interrogate and quantify the in vivo temporospatial dynamics of Giardia infection, thereby providing an improved murine model to evaluate anti-Giardia drugs. Using BLI, we determined that parasites primarily colonize the proximal small intestine nonuniformly in high-density foci. By imaging encystation-specific bioreporters, we show that encystation initiates shortly after inoculation and continues throughout the duration of infection. Encystation also initiates in high-density foci in the proximal small intestine, and high density contributes to the initiation of encystation in laboratory culture. We suggest that these high-density in vivo foci of colonizing and encysting Giardia likely result in localized disruption to the epithelium. This more accurate visualization of giardiasis redefines the dynamics of the in vivo Giardia life cycle, paving the way for future mechanistic studies of density-dependent parasitic processes in the host. IMPORTANCEGiardia is a single-celled parasite causing significant diarrheal disease in several hundred million people worldwide. Due to limited access to the site of infection in the gastrointestinal tract, our understanding of the dynamics of Giardia infections in the host has remained limited and largely inferred from laboratory culture. To better understand Giardia physiology and colonization in the host, we developed imaging methods to quantify Giardia expressing bioluminescent physiological reporters in two relevant animal models. We discovered that parasites primarily colonize and encyst in the proximal small intestine in discrete, high-density foci. We also show that high parasite density contributes to encystation initiation.

Analytical characteristics and comparative evaluation of Aptima HCV quant Dx assay with the Abbott RealTime HCV assay and Roche COBAS AmpliPrep/COBAS TaqMan HCV quantitative test v2.0.

BACKGROUND: The Aptima HCV Quant Dx assay (Aptima assay) is a fully automated quantitative assay on the Panther® system. This assay is intended for confirmation of diagnosis and monitoring of HCV RNA in plasma and serum specimens. The purpose of the testing described in this paper was to evaluate the performance of the Aptima assay. METHODS: The analytical sensitivity, analytical specificity, precision, and linearity of the Aptima assay were assessed. The performance of the Aptima assay was compared to two commercially available HCV assays; the Abbott RealTime HCV assay (Abbott assay, Abbott Labs Illinois, USA) and the Roche COBAS Ampliprep/COBAS Taqman HCV Quantitative Test v2.0 (Roche Assay, Roche Molecular Systems, Pleasanton CA, USA). The 95% Lower Limit of Detection (LoD) of the assay was determined from dilutions of the 2nd HCV WHO International Standard (NIBSC 96/798 genotype 1) and HCV positive clinical specimens in HCV negative human plasma and serum. Probit analysis was performed to generate the 95% predicted detection limits. The Lower Limit of Quantitation (LLoQ) was established for each genotype by diluting clinical specimens and the 2nd HCV WHO International Standard (NIBSC 96/798 genotype 1) in HCV negative human plasma and serum. Specificity was determined using 200 fresh and 536 frozen HCV RNA negative clinical specimens including 370 plasma specimens and 366 serum specimens. Linearity for genotypes 1 to 6 was established by diluting armored RNA or HCV positive clinical specimens in HCV negative serum or plasma from 8.08 log IU/mL to below 1 log IU/mL. Precision was tested using a 10 member panel made by diluting HCV positive clinical specimens or spiking armored RNA into HCV negative plasma and serum. A method comparison was conducted against the Abbott assay using 1058 clinical specimens and against the Roche assay using 608 clinical specimens from HCV infected patients. In addition, agreement between the Roche assay and the Aptima assay using specimens with low HCV concentrations (

Sequence conservation predicts T cell reactivity against ragweed allergens.

BACKGROUND: Ragweed is a major cause of seasonal allergy, affecting millions of people worldwide. Several allergens have been defined based on IgE reactivity, but their relative immunogenicity in terms of T cell responses has not been studied. OBJECTIVE: We comprehensively characterized T cell responses from atopic, ragweed-allergic subjects to Amb a 1, Amb a 3, Amb a 4, Amb a 5, Amb a 6, Amb a 8, Amb a 9, Amb a 10, Amb a 11, and Amb p 5 and examined their correlation with serological reactivity and sequence conservation in other allergens. METHODS: Peripheral blood mononuclear cells (PBMCs) from donors positive for IgE towards ragweed extracts after in vitro expansion for secretion of IL-5 (a representative Th2 cytokine) and IFN-γ (Th1) in response to a panel of overlapping peptides spanning the above-listed allergens were assessed. RESULTS: Three previously identified dominant T cell epitopes (Amb a 1 176-191, 200-215, and 344-359) were confirmed, and three novel dominant epitopes (Amb a 1 280-295, 304-319, and 320-335) were identified. Amb a 1, the dominant IgE allergen, was also the dominant T cell allergen, but dominance patterns for T cell and IgE responses for the other ragweed allergens did not correlate. Dominance for T cell responses correlated with conservation of ragweed epitopes with sequences of other well-known allergens. CONCLUSIONS AND CLINICAL RELEVANCE: These results provide the first assessment of the hierarchy of T cell reactivity in ragweed allergens, which is distinct from that observed for IgE reactivity and influenced by T cell epitope sequence conservation. The results suggest that ragweed allergens associated with lesser IgE reactivity and significant T cell reactivity may be targeted for T cell immunotherapy, and further support the development of immunotherapies against epitopes conserved across species to generate broad reactivity against many common allergens.

Epidemic Spread of Symbiotic and Non-Symbiotic Bradyrhizobium Genotypes Across California.

The patterns and drivers of bacterial strain dominance remain poorly understood in natural populations. Here, we cultured 1292 Bradyrhizobium isolates from symbiotic root nodules and the soil root interface of the host plant Acmispon strigosus across a >840-km transect in California. To investigate epidemiology and the potential role of accessory loci as epidemic drivers, isolates were genotyped at two chromosomal loci and were assayed for presence or absence of accessory "symbiosis island" loci that encode capacity to form nodules on hosts. We found that Bradyrhizobium populations were very diverse but dominated by few haplotypes-with a single "epidemic" haplotype constituting nearly 30 % of collected isolates and spreading nearly statewide. In many Bradyrhizobium lineages, we inferred presence and absence of the symbiosis island suggesting recurrent evolutionary gain and or loss of symbiotic capacity. We did not find statistical phylogenetic evidence that the symbiosis island acquisition promotes strain dominance and both symbiotic and non-symbiotic strains exhibited population dominance and spatial spread. Our dataset reveals that a strikingly few Bradyrhizobium genotypes can rapidly spread to dominate a landscape and suggests that these epidemics are not driven by the acquisition of accessory loci as occurs in key human pathogens.

Fast three-dimensional superimposition of cone beam computed tomography for orthopaedics and orthognathic surgery evaluation.

The aim of this study was to validate a method for fast three-dimensional (3D) superimposition of cone beam computed tomography (CBCT) in growing patients and adults (surgical cases). The sample consisted of CBCT scans of 18 patients. For 10 patients, as the gold standard, the spatial position of the pretreatment CBCT was reoriented, saved as a reoriented volume, and then superimposed on the original image. For eight patients, four non-growing and four growing, the pre- and post-treatment scans were superimposed. Fast voxel-based superimposition was performed, with registration at the anterior cranial base. This superimposition process took 10-15s. The fit of the cranial base superimposition was verified by qualitative visualization of the semi-transparent axial, sagittal, and coronal cross-sectional slices of all corresponding anatomical structures. Virtual 3D surface models of the skull were generated via threshold segmentation, and superimposition errors in the reoriented models and the results of treatment for the treated cases were evaluated by 3D surface distances on colour-coded maps. The superimposition error of the spatial reorientation and for growing and non-growing patients was <0.5mm, which is acceptable and clinically insignificant. The voxel-based superimposition method evaluated was reproducible in different clinical conditions, rapid, and applicable for research and clinical practice.

Definition of a pool of epitopes that recapitulates the T cell reactivity against major house dust mite allergens.

BACKGROUND: Allergens from house dust mites (HDM) are a common cause of asthma. Der p and Der f from Dermatophagoides sp. are strong immunogens in humans. Allergen extracts are used to study T helper (Th2) cell responses to HDM, which are implicated in the development and regulation of allergic disease. OBJECTIVE: To define an epitope mixture that recapitulates, and might substitute for, HDM extract in terms of detecting and characterizing Th2 cell responses. METHODS: Peripheral blood mononuclear cells (PBMC) from 52 HDM allergic and 10 non-allergic individuals were stimulated with HDM extracts and assayed with a set of 178 peptides spanning mite allergens group Der p 1, 2, 23 and Der f group 1 and 2 allergens. A pool of the most dominant T cell epitopes identified in the present study and from published literature was assembled and tested for ex vivo T cell responses. Correlation with HDM-specific IgE titres was examined. RESULTS: Patterns of T cell reactivity to Der p and Der f - derived peptides revealed a large number of epitopes. Clear patterns of immunodominance were apparent, with HDM allergen group 1 and 2 dominant over group 23. Furthermore, within a given antigen, 6-11 epitopes accounted for the vast majority of responses. Based on these results and published data, a comprehensive dust mite pool (DMP) of epitopes was designed and found to allow detection of ex vivo T cell responses. DMP ex vivo reactivity correlated with HDM-specific IgE titres and was similar to that detected with commonly used HDM extracts. Ex vivo DMP stimulation was associated with a predominant Th2 response in allergic donors, and minor reactivity of T cells producing IFNγ, IL17 and IL10. CONCLUSIONS & CLINICAL RELEVANCE: A detailed map of Der p and Der f antigens defined a pool of epitopes that can be used to detect ex vivo HDM responses.

Exome sequencing detection of two untranslated GFPT1 mutations in a family with limb-girdle myasthenia.

The term 'limb-girdle myasthenia' (LGM) was first used to describe three siblings with proximal limb weakness without oculobulbar involvement, but with EMG decrement and responsiveness to anticholinesterase medication. We report here that exome sequencing in the proband of this family revealed several sequence variations in genes linked to proximal limb weakness. However, the only mutations that cosegregated with disease were an intronic IVS7-8A>G mutation and the previously reported 3'-UTR c.*22C>A mutation in GFPT1, a gene linked to LGM. A minigene assay showed that IVS7-8A>G activates an alternative splice acceptor that results in retention of the last seven nucleotides of intron 7 and a frameshift leading to a termination codon 13 nucleotides downstream from the new splice site. An anconeus muscle biopsy revealed mild reduction of the axon terminal size and postsynaptic fold simplification. The amplitudes of miniature endplate potentials and quantal release were also diminished. The DNA of the mildly affected father of the proband showed only the intronic mutation along with sequence variations in other genes potentially relevant to LGM. Thus, this study performed in the family originally described with LGM showed two GFPT1 untranslated mutations, which may cause disease by reducing GFPT1 expression and ultimately impairing protein glycosylation.

Small-molecule inhibition of CBP/catenin interactions eliminates drug-resistant clones in acute lymphoblastic leukemia.

Drug resistance in acute lymphoblastic leukemia (ALL) remains a major problem warranting new treatment strategies. Wnt/catenin signaling is critical for the self-renewal of normal hematopoietic progenitor cells. Deregulated Wnt signaling is evident in chronic and acute myeloid leukemia; however, little is known about ALL. Differential interaction of catenin with either the Kat3 coactivator CREBBP (CREB-binding protein (CBP)) or the highly homologous EP300 (p300) is critical to determine divergent cellular responses and provides a rationale for the regulation of both proliferation and differentiation by the Wnt signaling pathway. Usage of the coactivator CBP by catenin leads to transcriptional activation of cassettes of genes that are involved in maintenance of progenitor cell self-renewal. However, the use of the coactivator p300 leads to activation of genes involved in the initiation of differentiation. ICG-001 is a novel small-molecule modulator of Wnt/catenin signaling, which specifically binds to the N-terminus of CBP and not p300, within amino acids 1-110, thereby disrupting the interaction between CBP and catenin. Here, we report that selective disruption of the CBP/ß- and γ-catenin interactions using ICG-001 leads to differentiation of pre-B ALL cells and loss of self-renewal capacity. Survivin, an inhibitor-of-apoptosis protein, was also downregulated in primary ALL after treatment with ICG-001. Using chromatin immunoprecipitation assay, we demonstrate occupancy of the survivin promoter by CBP that is decreased by ICG-001 in primary ALL. CBP mutations have been recently identified in a significant percentage of ALL patients, however, almost all of the identified mutations reported occur C-terminal to the binding site for ICG-001. Importantly, ICG-001, regardless of CBP mutational status and chromosomal aberration, leads to eradication of drug-resistant primary leukemia in combination with conventional therapy in vitro and significantly prolongs the survival of NOD/SCID mice engrafted with primary ALL. Therefore, specifically inhibiting CBP/catenin transcription represents a novel approach to overcome relapse in ALL.

[Donor site preserved skin grafts. A clinical study of 10 cases]. / La greffe de peau en nourrice. Étude clinique à propos de dix cas.

INTRODUCTION: In spite of a rigorous technique, a graft will not necessarily completely take on a burned area. We propose to preserve on the donor site the excess skin graft harvested during the excision-graft procedure. PATIENTS AND METHODS: A clinical study was carried out in nine patients who had their excess skin graft preserved at the time of excision-graft for deep burn. The unused fragments of skin graft were preserved on the donor site. In the event of a small skin graft failure, the preserved skin graft was separated from its donor site and used as a new skin graft during wound dressing. RESULTS: Nine patients required the use of 10 preserved skin grafts. The average age was 54years and the average burned third degree surface was 17% total body surface area. In seven procedures for six patients, the preserved skin graft was taken off without pain and was used with a complete take. In three cases, the preserved skin graft was not used because in two cases, the take of the initial skin graft was complete and in one case, a definitely insufficient take required reoperation. CONCLUSION: The preservation and use of the skin graft as a complement was simple and useful and made it possible to easily complete a skin graft when the initial take was incomplete. It would appear to be efficient in burn surgery since it accelerates cicatrisation and avoids the need for a new graft harvesting procedure.

[Corneal sensitivity in patients treated medically for glaucoma or ocular hypertension]. / Évaluation de la sensibilité cornéenne chez les patients traités médicalement pour un glaucome ou une hypertonie oculaire.

PURPOSE: To evaluate the corneal sensitivity in patients treated with intraocular pressure (IOP)-lowering medications. INTRODUCTION: Chronic administration of anti-glaucoma drops is associated with numerous tissue changes on the ocular surface. The purpose of this study was to investigate the effect of these medications and their preservative, benzalkonium chloride (BAK), on corneal sensitivity. PATIENTS AND METHODS: Thirty-nine patients treated for glaucoma or ocular hypertension (OHT) and nine untreated patients were included in this study. Treated patients were divided into three groups according to the daily number of preserved eyedrops (0, 1 and ≥2). Corneal sensitivity was assessed using the Cochet-Bonnet esthesiometer. All patients underwent a complete examination of the ocular surface including Schirmer testing, tear film breakup time (BUT) and corneal and conjunctival fluorescein staining. The Ocular Surface Disease Index (OSDI) questionnaire was used to evaluate symptoms. RESULTS: Corneal sensitivity was 58.8±2.8mm, 56.2±5.2mm, 50.3±12.5mm and 44.3±13.6mm in untreated patients, in patients treated with none, one and two or more instillations of preserved eyedrops, respectively. Corneal sensitivity in patients treated with preserved eyedrops was significantly lower as compared to untreated patients (P<0.001) and patients treated with preservative-free eyedrops (P=0.012). Corneal sensitivity of patients treated with intraocular pressure-lowering medications was negatively correlated to the number of instillations of preserved eyedrops (r=-0.390 ; P<0.001) as well as to the duration of treatment (R=-0.357 ; P=0.001). BUT and fluorescein staining were significantly altered in treated patients compared to the untreated control group ; however, no significant difference was observed between the treated groups. There was no significant difference for OSDI or Schirmer testing between the various groups. CONCLUSION: Chronic administration of BAK-containing anti-glaucoma eyedrops appears to alter corneal sensitivity. These results could explain the absence of correlation between clinical signs and symptoms sometimes observed in patients treated for glaucoma or OHT.

Effectiveness of low-temperature domestic laundry on the decontamination of healthcare workers' uniforms.

OBJECTIVE: Most professionals in the healthcare environment wear uniforms. For the purpose of this study, we concentrated on nurses' uniforms. In the United Kingdom, many nurses are expected to launder their uniforms at home by using a domestic washing machine that frequently has low-temperature wash cycles. We have investigated whether the use of low-temperature wash cycles results in a microbiologically acceptable product to wear on the wards. METHODS: We have assessed the bioburden on uniforms before and after laundry and the effectiveness of low-temperature wash cycles and ironing on removal of methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii. We did not assess the role of tumble drying. RESULTS: We demonstrate contamination of uniforms by gram-negative bacteria after wash, the removal of MRSA at low-temperature wash cycles in the presence of detergent, and the eradication of gram-negative bacteria after ironing. CONCLUSIONS: Our conclusions are that laundry in a domestic situation at 60°C (140°F) for 10 minutes is sufficient to decontaminate hospital uniforms and reduces the bacterial load by more than 7-log reduction, that items left in the pockets are decontaminated to the same extent, that the addition of either a biological detergent or a nonbiological detergent is beneficial in removing MRSA from experimentally contaminated swatches, and that uniforms become recontaminated with low numbers of principally gram-negative bacteria after laundry but that these are effectively removed by ironing.

Genetic structure of farmer-managed varieties in clonally-propagated crops.

The relative role of sexual reproduction and mutation in shaping the diversity of clonally propagated crops is largely unknown. We analyzed the genetic diversity of yam-a vegetatively-propagated crop-to gain insight into how these two factors shape its diversity in relation with farmers' classifications. Using 15 microsatellite loci, we analyzed 485 samples of 10 different yam varieties. We identified 33 different genotypes organized in lineages supported by high bootstrap values. We computed the probability that these genotypes appeared by sexual reproduction or mutation within and between each lineage. This allowed us to interpret each lineage as a product of sexual reproduction that has evolved by mutation. Moreover, we clearly noted a similarity between the genetic structure and farmers' classifications. Each variety could thus be interpreted as being the product of sexual reproduction having evolved by mutation. This highly structured diversity of farmer-managed varieties has consequences for the preservation of yam diversity.

Impact of past climatic and recent anthropogenic factors on wild yam genetic diversity.

Forests of the Dahomey Gap are considered as refugia for many species. They play a crucial role in providing ecosystem services in an area devoid of forests. However, the impact of the way they are managed on the biodiversity they host has barely been investigated. Wild yams existing in these forests play a crucial role in maintaining the genetic diversity of cultivated yams. Indeed, studies of farmer practices have shown that, by way of ennoblement, wild yams collected and selected in the forests and old fallow areas are integrated into the cultivated pool. However, the genetic structure of wild yams is poorly understood. Using nine microsatellite loci, we investigated the population genetics of Dioscorea praehensilis in five forests in Benin, involving different management strategies and bioclimatic areas. Populations of D. praehensilis were strongly differentiated, consistent with an ancient separation of the forests. While the D. praehensilis population in a holly forest was undergoing mutation and drift equilibrium, the population collected from the most conserved forest was in a bottleneck. Moreover, in two forests with different management strategies, accessions from other forests were found, resulting from the displacement of yams following farmer migrations. No isolation by distance was detected, but a differentiation was found between populations of the Sudano-Guinean climate and the Guineo-Congolian climate. Our findings suggest differentiation due to forest isolations under past climatic conditions and more recent tuber flow through anthropogenic impacts.

Epithelial or mesenchymal: Where to draw the line?

Epithelial and mesenchymal cells represent two of the main differentiated cell types in all vertebrates. However, their distinction is not always absolutely clear. Dozens of molecules have been used as markers for each cell type, while emerging evidence questions their validity. The aim of this study was to compare the molecular phenotype of these two cell types. Twenty-two commonly used molecular markers were evaluated by quantitative PCR and immunofluorescence in six lines of human and rat epithelial cells and fibroblasts. The epithelial cells were also examined for their responses to TGFbeta1 stimulation. All of the "markers" tested were found in both epithelial and mesenchymal cells. Some epithelial markers, such as CLDN5, OCLN, DSG1 and TJP1, were expressed even higher in fibroblasts than in epithelial cells. In comparison, mesenchymal markers showed more fidelity, but CDH2 and MMP9 were still significantly higher in epithelial cells than in mesenchymal cells. Furthermore, TGFbeta1 up-regulated epithelial markers CTNNB1 and CTNND1, but suppressed mesenchymal markers, such as S100A4, FGF1 and FGF2. In conclusion, no gene expression is cell-type restricted. Although some of these "markers" are expressed more in one cell type than in the other or differently localized, none of them shows a consistent pattern across species to make them universal markers. Nonetheless, some molecules appear to be better markers than others for a specific cell type. The information provided here is expected to serve as a reference for both basic and clinical researchers in the fields of epithelial-mesenchymal transition, molecular cell typing and cancer diagnosis.

Spatio-temporal dynamics of genetic diversity in Sorghum bicolor in Niger.

The dynamics of crop genetic diversity need to be assessed to draw up monitoring and conservation priorities. However, few surveys have been conducted in centres of diversity. Sub-Saharan Africa is the centre of origin of sorghum. Most Sahel countries have been faced with major human, environmental and social changes in recent decades, which are suspected to cause genetic erosion. Sorghum is the second staple cereal in Niger, a centre of diversity for this crop. Niger was submitted to recurrent drought period and to major social changes during these last decades. We report here on a spatio-temporal analysis of sorghum genetic diversity, conducted in 71 villages covering the rainfall gradient and range of agro-ecological conditions in Niger's agricultural areas. We used 28 microsatellite markers and applied spatial and genetic clustering methods to investigate change in genetic diversity over a 26-year period (1976-2003). Global genetic differentiation between the two collections was very low (F (st) = 0.0025). Most of the spatial clusters presented no major differentiation, as measured by F (st), and showed stability or an increase in allelic richness, except for two of them located in eastern Niger. The genetic clusters identified by Bayesian analysis did not show a major change between the two collections in the distribution of accessions between them or in their spatial location. These results suggest that farmers' management has globally preserved sorghum genetic diversity in Niger.