Bone scaffolds loaded with siRNA-Semaphorin4d for the treatment of osteoporosis related bone defects.

Osteoporosis is a prominent disorder affecting over 200 million people worldwide. Recently, semaphorins have been implicated in the cell-cell communication between osteoclasts and osteoblasts and have been associated with the progression of osteoporosis. Previously, we demonstrated that knockdown of semaphorin4d (Sema4d) using siRNA delivered with a bone-targeting system prevented bone loss in an osteoporotic animal model. Here, we used this bone-specific technology containing siRNA-Sema4d and fabricated a PLLA scaffold capable of enhancing bone repair following fracture. We investigated the ability of the implant to release siRNA-Sema4d into the surrounding tissues over time and to influence new bone formation in a 3 mm femur osteoporotic defect model in ovariectomized rats. Delivery of the bone-targeting system released from PLLA scaffolds began 2 hours post-implantation, peaked at 1 day, and was sustained over a 21 day period. μCT analysis demonstrated a significantly higher bone volume/total volume bone mineral density and number of osteoblasts in the rats that were transplanted with scaffolds loaded with siRNA-Sema4d. These results confirm the specific role of Sema4d in bone remodeling and demonstrate that significant increases in the speed and quality of new bone formation occur when siRNA-Sema4d is delivered via a PLLA scaffold

Vitamin C Prevents Hypogonadal Bone Loss

Epidemiologic studies correlate low vitamin C intake with bone loss. The genetic deletion of enzymes involved in de novo vitamin C synthesis in mice, likewise, causes severe osteoporosis. However, very few studies have evaluated a protective role of this dietary supplement on the skeleton. Here, we show that the ingestion of vitamin C prevents the low-turnover bone loss following ovariectomy in mice. We show that this prevention in areal bone mineral density and micro-CT parameters results from the stimulation of bone formation, demonstrable in vivo by histomorphometry, bone marker measurements, and quantitative PCR. Notably, the reductions in the bone formation rate, plasma osteocalcin levels, and ex vivo osteoblast gene expression 8 weeks post-ovariectomy are all returned to levels of sham-operated controls. The study establishes vitamin C as a skeletal anabolic agent. © 2012 Zhu et al

Vitamin C Prevents Hypogonadal Bone Loss

Abstract Epidemiologic studies correlate low vitamin C intake with bone loss. The genetic deletion of enzymes involved in de novo vitamin C synthesis in mice, likewise, causes severe osteoporosis. However, very few studies have evaluated a protective role of this dietary supplement on the skeleton. Here, we show that the ingestion of vitamin C prevents the low-turnover bone loss following ovariectomy in mice. We show that this prevention in areal bone mineral density and micro-CT parameters results from the stimulation of bone formation, demonstrable in vivo by histomorphometry, bone marker measurements, and quantitative PCR. Notably, the reductions in the bone formation rate, plasma osteocalcin levels, and ex vivo osteoblast gene expression 8 weeks post-ovariectomy are all returned to levels of sham-operated controls. The study establishes vitamin C as a skeletal anabolic agent

Метод расчета зависимости динамики доходов работников от уровня образования в Республике Беларусь

We report a study of the process e(+)e(-) -&gt; (D*(D) over bar*)(0)pi(0) using e(+)e(-) collision data samples with integrated luminosities of 1092 pb(-1) at root s = 4.23 GeV and 826 pb(-1) at root s = 4.26 GeV collected with the BESIII detector at the BEPCII storage ring. We observe a new neutral structure near the (D*(D) over bar*)(0) mass threshold in the pi(0) recoil mass spectrum, which we denote as Z(c)(4025)(0). Assuming a Breit-Wigner line shape, its pole mass and pole width are determined to be (4025.5(-4.7)(+2.0) +/- 3.1) MeV/c(2) and (23.0 +/- 6.0 +/- 1.0) MeV, respectively. The Born cross sections of e(+)e(-) -&gt; Z(c)(4025)(0)pi(0) -&gt; (D*(D) over bar*)(0)pi(0) are measured to be (61.6 +/- 8.2 +/- 9.0) pb at root s = 4.23 GeV and (43.4 +/- 8.0 +/- 5.4) pb at root s = 4.26 GeV. The first uncertainties are statistical and the second are systematic.Funding: The BESIII Collaboration thanks the staff of BEPCII and the IHEP computing center for their strong support. This work is supported in part by the National Key Basic Research Program of China under Contract No. 2015CB856700; the National Natural Science Foundation of China (NSFC) under Contracts No. 11125525, No. 11235011, No. 11275266, No. 11322544, No. 11335008, and No. 11425524; the Chinese Academy of Sciences (CAS) Large-Scale Scientific Facility Program; the CAS Center for Excellence in Particle Physics (CCEPP); the Collaborative Innovation Center for Particles and Interactions (CICPI); the Joint Large-Scale Scientific Facility Funds of the NSFC and the CAS under Contracts No. 11179007, No. U1232201, and No. U1332201; the CAS under Contracts No. KJCX2-YW-N29 and No. KJCX2-YW-N45; the 100 Talents Program of the CAS; INPAC and the Shanghai Key Laboratory for Particle Physics and Cosmology; German Research Foundation DFG under Contract No. Collaborative Research Center CRC-1044; the Istituto Nazionale di Fisica Nucleare, Italy; the Ministry of Development of Turkey under Contract No. DPT2006K-120470; the Russian Foundation for Basic Research under Contract No. 14-07-91152; the U.S. Department of Energy under Contracts No. DE-FG02-04ER41291, No. E-FG02-05ER41374, No. DE-FG02-94ER40823, and No. DESC0010118; the U.S. National Science Foundation; the University of Groningen (RuG) and the Helmholtzzentrum fuer Schwerionenforschung GmbH (GSI), Darmstadt; and the WCU Program of National Research Foundation of Korea under Contract No. R32-2008-000-10155-0.</p

Mutation detection and prenatal diagnosis of XLHED pedigree

Background The phenotypic characters of X -linked Hypohidrotic Ectodermal Dysplasia (XLHED) are the dysplasia of epithelial- and mesenchymal-derived organs. Ectodysplasin (EDA) is the causative gene of XLHED. Methods The current study reported a large Chinese XLHED pedigree. The genomic DNA of adult and fetus was extracted from peripheral blood and shed chorion cell respectively. The nucleotide variation in EDA gene was screened through direct sequencing the coding sequence. The methylation state of EDA gene’s promoter was evaluated by pyrosequencing. Results This Chinese XLHED family had two male patients and three carriers. All of them were with a novel EDA frameshift mutation. The mutation, c.172-173insGG, which leads to an immediate premature stop codon in exon one caused severe structural changes of EDA. Prenatal diagnosis suggested that the fetus was a female carrier. The follow-up observation of this child indicated that she had mild hypodontia of deciduous teeth at age six. The methylation level of EDA gene’s promoter was not related to carriers’ phenotype changes in this family. Discussion We reported a new frameshift mutation of EDA gene in a Chinese family. Prenatal diagnosis can help to predict the disease status of the fetus

Genotypic and allelic distributions of rs2486668 in NSOFC cases and controls.

<p>Genotypic and allelic distributions of rs2486668 in NSOFC cases and controls.</p

Lack of Association between Missense Variants in <i>GRHL3</i> (rs2486668 and rs545809) and Susceptibility to Non-Syndromic Orofacial Clefts in a Han Chinese Population

<div><p>Background</p><p>Grainyhead-like-3 (<i>GRHL3</i>) was recently identified as the second gene that, when mutated, can leads to Van der Woude syndrome, which is characterized by orofacial clefts (OFC) and lower lip pits. In addition, a missense variant (rs41268753) in <i>GRHL3</i> confers risk for non-syndromic cleft palate cases of European ancestry. Together with interferon regulatory factor 6 (<i>IRF6</i>), <i>GRHL3</i> may be associated with the risk of NSOFC which awaits for being verified across different ethnic populations.</p><p>Objective</p><p>The aim of this study was to investigate the possible relationship between common functional variants in <i>GRHL3</i> and susceptibility to NSOFC, especially cleft palate cases, in a Han Chinese population, one of the ethnic groups with the highest birth prevalence of orofacial clefting.</p><p>Methods</p><p>Because the allele frequency for rs41268753 minor alleles was zero in our Chinese population, we selected functional single nucleotide polymorphisms (SNPs) spanning <i>GRHL3</i> with minor allele frequencies (MAFs) > 5% in the Han Chinese population. Two SNPs which meet the above criteria were then genotyped in a case-control cohort comprising 1145 individuals using the TaqMan 5′-exonuclease allelic discrimination assay.</p><p>Results</p><p>SNPs rs2486668 and rs545809 were used in this study. Overall genotype and allele distributions of both SNPs in general and stratified genotyping analyses revealed no statistically significant differences between cases and controls. Further logistic regression analyses using different genetic models failed to reveal any evidence that these markers influence risk to NSOFC.</p><p>Conclusions</p><p>The variant rs41268753 in <i>GRHL3</i> increases the risk for cleft palate in European population, but our findings failed to detect the link between two <i>GRHL3</i> SNPs (rs2486668 and rs545809) and risk to NSOFC in the Han Chinese cohort. Although the present study did not provide any evidence that common functional variants in <i>GRHL3</i> may contribute to NSOFC etiology in this Chinese population, further studies with a larger sample size, additional SNPs, and a more diverse ethnic cohort are still warranted.</p></div

Genotypic and allelic distributions of rs545809 in NSOFC cases and controls.

<p>Genotypic and allelic distributions of rs545809 in NSOFC cases and controls.</p

Methylation state of the EDA gene promoter in Chinese X-linked hypohidrotic ectodermal dysplasia carriers.

Hypodontia, hypohidrosis, sparse hair and characteristic faces are the main characters of X-linked hypohidrotic ectodermal dysplasia (XLHED) which is caused by genetic ectodysplasin A (EDA) deficiency. Heterozygous female carriers tend to have mild to moderate XLHED phenotype, even though 30% of them present no obvious symptom.A large Chinese XLHED family was reported and the entire coding region and exon-intron boundaries of EDA gene were sequenced. To elucidate the mechanism for carriers' tempered phenotype, we analyzed the methylation level on four sites of the promoter of EDA by the pyrosequencing system.A known frameshift mutation (c.573-574 insT) was found in this pedigree. Combined with the pedigrees we reported before, 120 samples comprised of 23 carrier females from 11 families and 97 healthy females were analyzed for the methylation state of EDA promoter. Within 95% confidence interval (CI), 18 (78.26%) carriers were hypermethylated at these 4 sites.Chinese XLHED carriers often have a hypermethylated EDA promoter

Two novel mutations in MSX1 causing oligodontia.

Tooth agenesis is one of the most common developmental anomalies in humans and can affect dental occlusion and speech pronunciation. Research has identified an association between mutations in MSX1, PAX9, EDA, AXIN2, WNT10A, WNT10B and LRP6 and human tooth agenesis. Two unrelated individuals with non-syndromic tooth agenesis and their families were enrolled in this study. Using Sanger sequencing of the candidate genes, we identified two novel mutations: a missense mutation c.572 T>C and a frameshift mutation c.590_594 dup TGTCC, which were both detected in the homeodomain of MSX1. After identifying the mutations, structural modeling and bioinformatics analysis were used to predict the resulting conformational changes in the MSX1 homeodomain. Combined with 3D-structural analysis of other MSX1 mutations, we propose that there is a correlation between the observed phenotypes and alterations in hydrogen bond formation, thereby potentially affecting protein binding