A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism

We recently reported a deletion of exon 2 of the trimethyllysine hydroxylase epsilon (TMLHE) gene in a proband with autism. TMLHE maps to the X chromosome and encodes the first enzyme in carnitine biosynthesis, 6-N-trimethyllysine dioxygenase. Deletion of exon 2 of TMLHE causes enzyme deficiency, resulting in increased substrate concentration (6-N-trimethyllysine) and decreased product levels (3-hydroxy-6-N-trimethyllysine and γ-butyrobetaine) in plasma and urine. TMLHE deficiency is common in control males (24 in 8,787 or 1 in 366) and was not significantly increased in frequency in probands from simplex autism families (9 in 2,904 or 1 in 323). However, it was 2.82-fold more frequent in probands from male-male multiplex autism families compared with controls (7 in 909 or 1 in 130; P = 0.023). Additionally, six of seven autistic male siblings of probands in male-male multiplex families had the deletion, suggesting that TMLHE deficiency is a risk factor for autism (metaanalysis Z-score = 2.90 and P = 0.0037), although with low penetrance (2-4%). These data suggest that dysregulation of carnitine metabolism may be important in nondysmorphic autism; that abnormalities of carnitine intake, loss, transport, or synthesis may be important in a larger fraction of nondysmorphic autism cases; and that the carnitine pathway may provide a novel target for therapy or prevention of autism.     

The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations

The small intestine epithelium undergoes rapid and continuous regeneration supported by crypt intestinal stem cells (ISCs). Bmi1 and Lgr5 have been independently identified to mark long-lived multipotent ISCs by lineage tracing in mice; however, the functional distinctions between these two populations remain undefined. Here, we demonstrate that Bmi1 and Lgr5 mark two functionally distinct ISCs in vivo. Lgr5 marks mitotically active ISCs that exhibit exquisite sensitivity to canonical Wnt modulation, contribute robustly to homeostatic regeneration, and are quantitatively ablated by irradiation. In contrast, Bmi1 marks quiescent ISCs that are insensitive to Wnt perturbations, contribute weakly to homeostatic regeneration, and are resistant to high-dose radiation injury. After irradiation, however, the normally quiescent Bmi1(+) ISCs dramatically proliferate to clonally repopulate multiple contiguous crypts and villi. Clonogenic culture of isolated single Bmi1(+) ISCs yields long-lived self-renewing spheroids of intestinal epithelium that produce Lgr5-expressing cells, thereby establishing a lineage relationship between these two populations in vitro. Taken together, these data provide direct evidence that Bmi1 marks quiescent, injury-inducible reserve ISCs that exhibit striking functional distinctions from Lgr5(+) ISCs and support a model whereby distinct ISC populations facilitate homeostatic vs. injury-induced regeneration.     

Complement factor H genotypes impact risk of age-related macular degeneration by interaction with oxidized phospholipids

The rs1061170T/C variant encoding the Y402H change in complement factor H (CFH) has been identified by genome-wide association studies as being significantly associated with age-related macular degeneration (AMD). However, the precise mechanism by which this CFH variant impacts the risk of AMD remains largely unknown. Oxidative stress plays an important role in many aging diseases, including cardiovascular disease and AMD. A large amount of oxidized phospholipids (oxPLs) are generated in the eye because of sunlight exposure and high oxygen content. OxPLs bind to the retinal pigment epithelium and macrophages and strongly activate downstream inflammatory cascades. We hypothesize that CFH may impact the risk of AMD by modulating oxidative stress. Here we demonstrate that CFH binds to oxPLs. The CFH 402Y variant of the protective rs1061170 genotype binds oxPLs with a higher affinity and exhibits a stronger inhibitory effect on the binding of oxPLs to retinal pigment epithelium and macrophages. In addition, plasma from non-AMD subjects with the protective genotype has a lower level of systemic oxidative stress measured by oxPLs per apolipoprotein B (oxPLs/apoB). We also show that oxPL stimulation increases expression of genes involved in macrophage infiltration, inflammation, and neovascularization in the eye. OxPLs colocalize with CFH in drusen in the human AMD eye. Subretinal injection of oxPLs induces choroidal neovascularization in mice. In addition, we show that the CFH risk allele confers higher complement activation and cell lysis activity. Together, these findings suggest that CFH influences AMD risk by modulating oxidative stress, inflammation, and abnormal angiogenesis.     

Detection of p53 gene mutation by using a novel biosensor based on localized surface plasmon resonance

Few studies to date have reported on the development and application of a nanobiosensor based on localized surface plasmon resonance (LSPR) for detecting gene mutations. This study aimed to develop a novel LSPR biosensor used for detecting p53 mutation. Nanosphere lithography was used to fabricate the silver nanoparticles. The DNA probe was designed to recognize the target sequence and immobilized on the chip surface by a covalent-coupling method using amine-group ligands. Synthetic oligonucleotides or PCR products were amplified from genomic DNA taken from blood samples and hybridized with the immobilized probe. Wild-type and mutant p53 was detected by measuring shifts in peak of LSPR extinction spectra. The low detection limit of the sensor for target sequence was 10 nM, and detection occurred over a wide dynamic range (10 nM - 10 μM). Importantly, the differences in measuring signal between wild-type and mismatched p53 DNA was significant, allowing for this sensor to effectively discriminate against single base mutations. In conclusion, we developed a biosensor with potential as a rapid, label-free, sensitive, and low-cost method for detecting p53 mutation. Our results suggest that such an LSPR-based biosensor provides an attractive alternative for clinical detection of genetic mutation.     

Enhanced bone regeneration around dental implant with bone morphogenetic protein 2 gene and vascular endothelial growth factor protein delivery

Objective: To evaluate the synergistic effect of bone morphogenetic protein 2 (BMP‐2) and vascular endothelial growth factor (VEGF) on the repair of bone defects around dental implants. Material and methods: Five groups of scaffold were fabricated by a freeze‐drying method, including pure chitosan/collagen scaffold; scaffold loaded with adenoviruses expressing BMP‐2, adenoviruses expressing VEGF, both adenoviruses expressing BMP‐2 and VEGF, VEGF protein and adenovirus expressing BMP‐2. In vitro studies examined whether bone marrow stromal cells were responsive to these scaffolds over time. Bone formation capacity, bone‐to‐implant contact, as well as removal torque values were investigated in vivo. Differences between the various groups were statistically analyzed using the one‐way analysis of variance test. Results: The in vitro study revealed a burst and rapid release of VEGF with a sustained high‐level expression of BMP‐2 in scaffold combined with VEGF protein and adenoviruses expressing BMP‐2. Histomorphometry demonstrated that scaffolds expressing BMP‐2 enhanced more bone formation compared with other groups; VEGF alone is insufficient to promote bone formation. New bone formation in the bone defects around dental implants, bone‐to‐implant contact and mean peak removal torque showed statistically significant difference for the adenoviral vector encoding human bone morphogenetic protein 2 (Ad‐BMP‐2) and VEGF protein and adenovirus expressing BMP‐2 groups. Furthermore, scaffold combined with VEGF protein and Ad‐BMP‐2 represented the best outcomes in this model. Conclusions: A combination of BMP‐2 gene and VEGF protein could have a synergistic effect in promoting bone healing. To cite this article:
Luo T, Zhang W, Shi B, Cheng X, Zhang Y. Enhanced bone regeneration around dental implant with bone morphogenetic protein 2 gene and vascular endothelial growth factor protein delivery.
Clin. Oral Impl. Res. 23 , 2012 467–474.
doi: 10.1111/j.1600‐0501.2011.02164.x     

温控型镍钛弓丝力学性能的时效变化

目的:比较不同品牌温控型镍钛弓丝力学性能的长期变化。方法:利用Instron万能材料力学实验机在37℃人工唾液中对4种品牌温控型镍钛圆丝(直径0.016英寸)在3个时间点(0、4、8周)进行改良部分牙弓弯曲实验,绘制加载、卸载的载荷-挠曲曲线,计算各时间点卸载1.5mm的载荷值、卸载2.5～0.5mm之间的刚度平均值和标准差。采用SPSS11.5软件包对数据进行统计学分析。结果:A、B、D 3种温控型镍钛圆丝0周与4周载荷-挠曲曲线很相近,而在8周时加载曲线明显增高,但卸载曲线无显著变化,C弓丝在3个时间点的载荷-挠曲曲线之间均有显著差异。A、B、D 3种弓丝在所有时间点卸载1.5mm载荷值的波动很小,C弓丝8周时卸载力值有所增大。B与D弓丝不同时间点的卸载刚度波动较小,而A与C弓丝卸载刚度随着时间延长有减小趋势。结论:温控型镍钛弓丝随着加载时间的延长,其力学性能有所变化,但其超弹性及形状记忆性能并未改变。     

Classification and reconstruction of posttraumatic ear deformity

The diversity of posttraumatic auricular deformity caused by various factors often makes reconstruction exacting for the surgeon. During the past 10 years (from 2001 to 2010), a total of 60 patients (75 ears) were treated. The etiology of the deformities included burns (n = 35), traffic accidents (n = 10), cuts during fight (n = 8), and human bite injuries (n = 7). Based on previously published ones, we set a classification taking into consideration the involved tissue components, size of defects, and status of surrounding soft tissues, which categorized posttraumatic auricular deformities into 5 types. Different reconstruction modalities used for each type are described and discussed with examples. During follow-up, the degree of patients' satisfaction was high, and most reconstructed ears were accepted, barring a few complications. It must be admitted that achieving satisfactory outcome in the treatment of posttraumatic ear deformity similar to that of microtia is difficult, especially in the presence of extensive scar. Our 10-year experience suggested that proper classification and careful selection of techniques would be helpful.     

降低垂直距离在老年全口义齿修复中的应用

目的:观察适当降低垂直距离对老年人全口义齿修复效果的影响。方法:采用传统法和降低3mm垂直距离法,为40例老年患者分别制作完成2副全口义齿。适应3个月后,测定咀嚼效能和压痛点。采用SAS6.04软件包对数据进行统计学分析。结果:降低3mm垂直距离制作的全口义齿咀嚼效能与传统法比较,无显著差异(P>0.05),但压痛点显著少于传统法(P<0.05)。结论:降低3mm垂直距离法是临床上可行的老年人全口义齿修复方法。