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131.
Srour M Schwartzentruber J Hamdan FF Ospina LH Patry L Labuda D Massicotte C Dobrzeniecka S Capo-Chichi JM Papillon-Cavanagh S Samuels ME Boycott KM Shevell MI Laframboise R Désilets V;FORGE Canada Consortium Maranda B Rouleau GA Majewski J Michaud JL 《American journal of human genetics》2012,90(4):693-700
Joubert syndrome (JBTS) is an autosomal-recessive disorder characterized by a distinctive mid-hindbrain malformation, developmental delay with hypotonia, ocular-motor apraxia, and breathing abnormalities. Although JBTS was first described more than 40 years ago in French Canadian siblings, the causal mutations have not yet been identified in this family nor in most French Canadian individuals subsequently described. We ascertained a cluster of 16 JBTS-affected individuals from 11 families living in the Lower St. Lawrence region. SNP genotyping excluded the presence of a common homozygous mutation that would explain the clustering of these individuals. Exome sequencing performed on 15 subjects showed that nine affected individuals from seven families (including the original JBTS family) carried rare compound-heterozygous mutations in C5ORF42. Two missense variants (c.4006C>T [p.Arg1336Trp] and c.4690G>A [p.Ala1564Thr]) and a splicing mutation (c.7400+1G>A), which causes exon skipping, were found in multiple subjects that were not known to be related, whereas three other truncating mutations (c.6407del [p.Pro2136Hisfs*31], c.4804C>T [p.Arg1602*], and c.7477C>T [p.Arg2493*]) were identified in single individuals. None of the unaffected first-degree relatives were compound heterozygous for these mutations. Moreover, none of the six putative mutations were detected among 477 French Canadian controls. Our data suggest that mutations in C5ORF42 explain a large portion of French Canadian individuals with JBTS. 相似文献
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134.
R.I. Samuels I.C. Paterson 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》1995,110(4):661-669
Insects degrade their own cuticle during moulting, a process which is catalysed by a complex mixture of enzymes. Entomopathogenic fungi infect the insect host by penetration of the cuticle, utilizing enzymatic and/or physical mechanisms. Protein is a major component of insect cuticle and a major recyclable resource for the insect and, therefore, represents a significant barrier to the invading fungus. To this end, both insects and entomopathogenic fungi produce a variety of cuticle degrading proteases. The aim of this paper is to review these proteases and to highlight their similarities, with particular reference to the tobacco hornworm, Manduca sexta, and the entomopathogenic fungus, Metarhizium anisopliae 相似文献
135.
Sasa Vukelic Olivera Stojadinovic Irena Pastar Constantinos Vouthounis Agata Krzyzanowska Sharmistha Das Herbert H. Samuels Marjana Tomic-Canic 《The Journal of biological chemistry》2010,285(3):1980-1988
Farnesyl pyrophosphate (FPP), a key intermediate in the mevalonate pathway and protein farnesylation, can act as an agonist for several nuclear hormone receptors. Here we show a novel mechanism by which FPP inhibits wound healing acting as an agonist for glucocorticoid receptor (GR). Elevation of endogenous FPP by the squalene synthetase inhibitor zaragozic acid A (ZGA) or addition of FPP to the cell culture medium results in activation and nuclear translocation of the GR, a known wound healing inhibitor. We used functional studies to evaluate the effects of FPP on wound healing. Both FPP and ZGA inhibited keratinocyte migration and epithelialization in vitro and ex vivo. These effects were independent of farnesylation and indicate that modulation of FPP levels in skin may be beneficial for wound healing. FPP inhibition of keratinocyte migration and wound healing proceeds, in part, by repression of the keratin 6 gene. Furthermore, we show that the 3-hydroxy-3-methylglutaryl-CoA-reductase inhibitor mevastatin, which blocks FPP formation, not only promotes epithelialization in acute wounds but also reverses the effect of ZGA on activation of the GR and inhibition of epithelialization. We conclude that FPP inhibits wound healing by acting as a GR agonist. Of special interest is that FPP is naturally present in cells prior to glucocorticoid synthesis and that FPP levels can be further altered by the statins. Therefore, our findings may provide a better understanding of the pleiotropic effects of statins as well as molecular mechanisms by which they may accelerate wound healing. 相似文献
136.
H W Taylor M Vázquez-Geffroy S J Samuels D M Taylor 《Journal of biosocial science》1999,31(3):289-310
The hypothesis that the month-specific rate of return to ovarian cyclicity after childbirth is causally related to suckling pattern was tested for a population of New Mexican women recruited within the service area of New Mexico Highlands University and for a nationwide USA subpopulation of women recruited through membership of the Couple to Couple League (CCL). Survival analysis for time-dependent covariates was used, and significant predictors of the first postpartum menses were found. Important differences were detected in the suckling pattern for the two groups and a 5:2 differential was found in their respective rates of menstrual cycle recovery. Although the two groups were comparable perinatally, daily and time-windowed breast-feeding performance fell off at twice the rate for the New Mexico population when contrasted with the CCL sample. For both populations, the introduction of solid feeds was a strong and significant predictor of returning menstrual cyclicity, independent of suckling pattern. 相似文献
137.
Peptaibol,Secondary‐Metabolite,and Hydrophobin Pattern of Commercial Biocontrol Agents Formulated with Species of the Trichoderma harzianum Complex 下载免费PDF全文
Thomas Degenkolb Kristian Fog Nielsen Ralf Dieckmann Fabiano Branco‐Rocha Priscila Chaverri Gary J. Samuels Ulf Thrane Hans von Döhren Andreas Vilcinskas Hans Brückner 《化学与生物多样性》2015,12(4):662-684
The production of bioactive polypeptides (peptaibiotics) in vivo is a sophisticated adaptation strategy of both mycoparasitic and saprotrophic Trichoderma species for colonizing and defending their natural habitats. This feature is of major practical importance, as the detection of peptaibiotics in plant‐protective Trichoderma species, which are successfully used against economically relevant bacterial and fungal plant pathogens, certainly contributes to a better understanding of these complex antagonistic interactions. We analyzed five commercial biocontrol agents (BCAs), namely Canna®, Trichosan®, Vitalin®, Promot® WP, and TrichoMax®, formulated with recently described species of the Trichoderma harzianum complex, viz. T. afroharzianum, T. simmonsii, and T. guizhouense. By using the well‐established, HPLC/MS‐based peptaibiomics approach, it could unequivocally be demonstrated that all of these formulations contained new and recurrent peptaibols, i.e., peptaibiotics carrying an acetylated N‐terminus, the C‐terminus of which is reduced to a 1,2‐amino alcohol. Their chain lengths, including the amino alcohol, were 11, 14, and 18 residues, respectively. Peptaibols were also to be the dominating secondary metabolites in plate cultures of the four strains obtained from four of the Trichoderma‐ based BCAs, contributing 95% of the UHPLC‐UV/VIS peak areas and 99% of the total ion count MS peak area from solid media. Furthermore, species‐specific hydrophobins, as well as non‐peptaibiotic secondary metabolites, were detected, the latter being known for their antifungal, siderophore, or plant‐growth‐promoting activities. Notably, none of the isolates produced low‐molecular weight mycotoxins. 相似文献
138.
Leshinsky-Silver E Landau Z Unlubay S Bistrizer T Zung A Tenenbaum-Rakover Y Devries L Lev D Hanukoglu A 《Hormone research》2006,66(2):73-78
BACKGROUND/AIMS: Isolated aldosterone biosynthesis defect causing congenital hyperreninemic hypoaldosteronism with otherwise normal adrenal function usually results from aldosterone synthase deficiency. Patients present with manifestations of mineralocorticoid deficiency during the first weeks of life. The largest numbers of cases have been described in Iranian Jews, who carried concomitantly two homozygous missense mutations (R181W and V386A). In a few cases with presumed aldosterone synthase deficiency no mutations in CYP11B2 gene have been identified. We describe a molecular and endocrine evaluation of seven cases of congenital hyperreninemic hypoaldosteronism in Israel. PATIENTS/METHODS: Two of the six Jewish patients are of Iranian origin. The parents of five other patients originated from Yemen, Syria and Morocco. One patient is a Muslim-Arab. CYP11B2's exons, exon-intron boundaries and promoter region were sequenced by multiple PCR amplifications. Gene size determination was performed either by long-range PCR or by Southern blot analysis. RESULTS: Only two patients (Iranian Jews) carried a known homozygous R181W, V386A mutations, other two were compound heterozygotes for either the R181W or V386A and one additional novel amino acid substitution (A319V or D335G), and one patient was found to be a carrier of the two novel variations (A319V and D335G). We could not find a molecular defect in 2 patients: one was a carrier of the D335G mutation and the other had no detectable molecular change in the coding and promoter regions. CONCLUSION: The genetic and molecular basis of congenital hyperreninemic hypoaldosteronism is more heterogeneous than previously described. The significance of amino acid substitutions identified in this study remains to be determined. 相似文献
139.
Growth hormone receptor sequence changes do not play a role in determining height in children with idiopathic short stature 总被引:3,自引:0,他引:3
BACKGROUND/AIMS: In children with short stature, in whom growth hormone deficiency has been excluded, the presence of a normal or elevated growth hormone concentration concomitant with low insulin-like growth factor I suggests growth hormone insensitivity (GHI). Previous reports suggest that heterozygous mutations in the growth hormone receptor gene (GHR) may account for about 5% of children with idiopathic short stature (ISS). In the present study we have attempted to determine whether mutations in the GHR explain the short stature and growth retardation in a cohort of children with ISS and characteristics suggesting GHI. METHODS: For the present study 33 children with clinical and biochemical characteristics of GHI were selected from a cohort of 150 children of short stature. Molecular analysis of the GHR was performed using a single-strand conformation polymorphism technique and sequencing. Ten different sequence changes in 19 (58%) out of 33 children were identified, 9 of them novel and 1 that had been described previously. RESULTS: Two changes were found in exons 2 and 6. The known polymorphism of exon 6 (G168) was significantly more common in the control subjects than in our study group (63.5 vs. 30%; p < 0.0001). In the intronic sequences 8 previously undescribed DNA changes were found. The screening of the affected children's family members revealed that both normal and short stature members carried the same variants. The study group did not significantly differ from the controls in retention (GHRfl) or exclusion (GHRd3) of exon 3. CONCLUSION: Our study suggests that sequence changes of the GHR are common in children with ISS. The presence of these sequence changes in the control subjects as well as in normal stature family members indicates that these changes represent a simple polymorphism of the GHR. Such DNA changes are more prevalent than previously recognized, and they do not seem to play a contributory role in the etiology of short stature. 相似文献
140.
Martin Samuels Gaurav Gulati Jae-Ho Shin Rejoice Opara Elizabeth McSweeney Matt Sekedat Stephen Long Zvi Kelman David Jeruzalmi 《Nucleic acids research》2009,37(13):4441-4452
The mini-chromosome maintenance (MCM) proteins serve as the replicative helicases in archaea and eukaryotes. Interestingly, an MCM homolog was identified, by BLAST analysis, within a phage integrated in the bacterium Bacillus cereus (Bc). BcMCM is only related to the AAA region of MCM-helicases; the typical amino-terminus is missing and is replaced by a segment with weak homology to primases. We show that BcMCM displays 3′→5′ helicase and ssDNA-stimulated ATPase activity, properties that arise from its conserved AAA domain. Isolated BcMCM is a monomer in solution but likely forms the functional oligomer in vivo. We found that the BcMCM amino-terminus can bind ssDNA and harbors a zinc atom, both hallmarks of the typical MCM amino-terminus. No BcMCM-catalyzed primase activity could be detected. We propose that the divergent amino-terminus of BcMCM is a paralog of the corresponding region of MCM-helicases. A divergent amino terminus makes BcMCM a useful model for typical MCM-helicases since it accomplishes the same function using an apparently unrelated structure. 相似文献