Hen's teeth with enamel cap: from dream to impossibility

<p>Abstract</p> <p>Background</p> <p>The ability to form teeth was lost in an ancestor of all modern birds, approximately 100-80 million years ago. However, experiments in chicken have revealed that the oral epithelium can respond to inductive signals from mouse mesenchyme, leading to reactivation of the odontogenic pathway. Recently, tooth germs similar to crocodile rudimentary teeth were found in a chicken mutant. These "chicken teeth" did not develop further, but the question remains whether functional teeth with enamel cap would have been obtained if the experiments had been carried out over a longer time period or if the chicken mutants had survived. The next odontogenetic step would have been tooth differentiation, involving deposition of dental proteins.</p> <p>Results</p> <p>Using bioinformatics, we assessed the fate of the four dental proteins thought to be specific to enamel (amelogenin, AMEL; ameloblastin, AMBN; enamelin, ENAM) and to dentin (dentin sialophosphoprotein, DSPP) in the chicken genome. Conservation of gene synteny in amniotes allowed definition of target DNA regions in which we searched for sequence similarity. We found the full-length chicken AMEL and the only N-terminal region of DSPP, and both are invalidated genes. AMBN and ENAM disappeared after chromosomal rearrangements occurred in the candidate region in a bird ancestor.</p> <p>Conclusion</p> <p>These findings not only imply that functional teeth with enamel covering, as present in ancestral Aves, will never be obtained in birds, but they also indicate that these four protein genes were dental specific, at least in the last toothed ancestor of modern birds, a specificity which has been questioned in recent years.</p

Factors Associated with Negative Direct Sputum Examination in Asian and African HIV-Infected Patients with Tuberculosis (ANRS 1260)

OBJECTIVE: To identify factors associated with negative direct sputum examination among African and Cambodian patients co-infected by Mycobacterium tuberculosis and HIV. DESIGN: Prospective multicenter study (ANRS1260) conducted in Cambodia, Senegal and Central African Republic. METHODS: Univariate and multivariate analyses (logistic regression) were used to identify clinical and radiological features associated with negative direct sputum examination in HIV-infected patients with positive M. tuberculosis culture on Lowenstein-Jensen medium. RESULTS: Between September 2002 and December 2005, 175 co-infected patients were hospitalized with at least one respiratory symptom and pulmonary radiographic anomaly. Acid-fast bacillus (AFB) examination was positive in sputum samples from 110 subjects (63%) and negative in 65 patients (37%). Most patients were at an advanced stage of HIV disease (92% at stage III or IV of the WHO classification) with a median CD4 cell count of 36/mm³. In this context, we found that sputum AFB negativity was more frequent in co-infected subjects with associated respiratory tract infections (OR = 2.8 [95%CI:1.1-7.0]), dyspnea (OR = 2.5 [95%CI:1.1-5.6]), and localized interstitial opacities (OR = 3.1 [95%CI:1.3-7.6]), but was less frequent with CD4 ≤ 50/mm³ (OR = 0.4 [95%CI:0.2-0.90), adenopathies (OR = 0.4 [95%CI:0.2-0.93]) and cavitation (OR = 0.1 [95%CI:0.03-0.6]). CONCLUSIONS: One novel finding of this study is the association between concomitant respiratory tract infection and negative sputum AFB, particularly in Cambodia. This finding suggests that repeating AFB testing in AFB-negative patients should be conducted when broad spectrum antibiotic treatment does not lead to complete recovery from respiratory symptoms. In HIV-infected patients with a CD4 cell count below 50/mm3 without an identified cause of pneumonia, systematic AFB direct sputum examination is justified because of atypical clinical features (without cavitation) and high pulmonary mycobacterial burden

Dipstick Test for Rapid Diagnosis of Shigella dysenteriae 1 in Bacterial Cultures and Its Potential Use on Stool Samples

International audienceBACKGROUND: We describe a test for rapid detection of S. dysenteriae 1 in bacterial cultures and in stools, at the bedside of patients. METHODOLOGY/PRINCIPAL FINDINGS: The test is based on the detection of S. dysenteriae 1 lipopolysaccharide (LPS) using serotype 1-specific monoclonal antibodies coupled to gold particles and displayed on a one-step immunochromatographic dipstick. A concentration as low as 15 ng/ml of LPS was detected in distilled water and in reconstituted stools in 10 minutes. In distilled water and in reconstituted stools, an unequivocal positive reaction was obtained with 1.6×10⁶ CFU/ml and 4.9×10⁶ CFU/ml of S. dysenteriae 1, respectively. Optimal conditions to read the test have been determined to limit the risk of ambiguous results due to appearance of a faint yellow test band in some negative samples. The specificity was 100% when tested with a battery of Shigella and unrelated strains in culture. When tested on 328 clinical samples in India, Vietnam, Senegal and France by laboratory technicians and in Democratic Republic of Congo by a field technician, the specificity (312/316) was 98.7% (95% CI:96.6-99.6%) and the sensitivity (11/12) was 91.7% (95% CI:59.8-99.6%). Stool cultures and the immunochromatographic test showed concordant results in 98.4 % of cases (323/328) in comparative studies. Positive and negative predictive values were 73.3% (95% CI:44.8-91.1%) and 99.7% (95% CI:98-100%). CONCLUSION: The initial findings presented here for a simple dipstick-based test to diagnose S. dysenteriae 1 demonstrates its promising potential to become a powerful tool for case management and epidemiological surveys

Evolutionary Analysis Predicts Sensitive Positions of MMP20 and Validates Newly- and Previously-Identified MMP20 Mutations Causing Amelogenesis Imperfecta

Amelogenesis imperfecta (AI) designates a group of genetic diseases characterized by a large range of enamel disorders causing important social and health problems. These defects can result from mutations in enamel matrix proteins or protease encoding genes. A range of mutations in the enamel cleavage enzyme matrix metalloproteinase-20 gene (MMP20) produce enamel defects of varying severity. To address how various alterations produce a range of AI phenotypes, we performed a targeted analysis to find MMP20 mutations in French patients diagnosed with non-syndromic AI. Genomic DNA was isolated from saliva and MMP20 exons and exon-intron boundaries sequenced. We identified several homozygous or heterozygous mutations, putatively involved in the AI phenotypes. To validate missense mutations and predict sensitive positions in the MMP20 sequence, we evolutionarily compared 75 sequences extracted from the public databases using the Datamonkey webserver. These sequences were representative of mammalian lineages, covering more than 150 million years of evolution. This analysis allowed us to find 324 sensitive positions (out of the 483 MMP20 residues), pinpoint functionally important domains, and build an evolutionary chart of important conserved MMP20 regions. This is an efficient tool to identify new- and previously-identified mutations. We thus identified six functional MMP20 mutations in unrelated families, finding two novel mutated sites. The genotypes and phenotypes of these six mutations are described and compared. To date, 13 MMP20 mutations causing AI have been reported, making these genotypes and associated hypomature enamel phenotypes the most frequent in AI

La phosphoglycoprotéine de la matrice extracellulaire, MEPE (origine, fonctions et évolution)

MEPE, la phosphoglycoprotéine de la matrice extracellulaire, appartient à la famille des SIBLINGs, dont les membres sont connus pour être impliqués dans la minéralisation de l'os et de la dentine. Deux régions de MEPE joueraient un rôle dans la régulation de la minéralisation : l'une, appelée dentonine, favoriserait la prolifération cellulaire ; l'autre, située à l'extrémité C-terminale, nommée ASARM, inhiberait la minéralisation et la réabsorption du phosphate au niveau rénal. L'analyse évolutive de MEPE a apporté un éclairage nouveau sur cette protéine. La dentonine serait apparue chez les placentaires et des régions très conservées, mais encore jamais étudiées, ont été mises en évidence. L'analyse étendue aux sauropsides a confirmé ces résultats ainsi que la présence du peptide ASARM chez l'ancêtre commun des amniotes, ce qui indique l'apparition de MEPE chez l'ancêtre commun de cette lignée. Chez les mammifères, MEPE est exprimé par les ostéoblastes, les ostéocytes, et les odontoblastes. Chez le poulet, l'ovocléidine 116 (OC-116), découverte pour son implication dans la minéralisation de la coquille d'oeuf, est l'orthologue de MEPE. L'étude de l'expression d'OC-116 dans les os de poulet au cours de l'ostéogenèse a mis en évidence la transcription de ce gène dans les mêmes types cellulaires que chez les mammifères. En parallèle, MEPE a été séquencé chez un lézard, Anolis carolinensis, et les transcrits ont été localisés dans les cellules osseuses et dans les odontoblastes au cours de la dentinogenèse.Chez l'ancêtre commun des amniotes MEPE/OC-116 était donc probablement impliquée dans la minéralisation de trois types de tissus : l'os, la dentine et la coquille d'oeuf.PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Odontogenèse chez l'amphibien caudate, Pleurodeles walt (connaissances actuelles, modifications morphologiques dentaires et transition émailloïde-émail au cours de l'ontogenèse, et caractérisation du gène de l'amélogénine)

Ce travail de thèse sur l odontogenèse de l amphibien caudate, Pleurodeles waltl, s inscrit dans un vaste programme de recherche centré sur l évolution et le développement du squelette dermique. Une revue bibliographique recueille toutes les informations obtenues au siècle dernier sur les dents d amphibiens (historique, structure, morphologie, remplacement et résorption dentaire). Chez P. waltl, nous avons étudié les modifications dentaires au cours de l ontogene se, de la larve à l adulte et établi la chronologie de développement d une famille dentaire (dent de première génération et ses remplaçantes). Nous avons ensuite décrit en détail la formation et le devenir de l émailloïde, tissu intermédiaire entre émail et dentine, et obtenu une séquence partielle du gène de l amélogénine chez P. waltl. Cette séquence sera utile pour visualiser l expression de l amélogénine lors de la formation de l émailloïde, en particulier lors des premiers stades de développement.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF