Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments.

International audienceSHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice

Study of hadronic event-shape variables in multijet final states in pp collisions at √s=7 TeV

Peer reviewe

Constraints on parton distribution functions and extraction of the strong coupling constant from the inclusive jet cross section in pp collisions at √s=7 TeV

Peer reviewe

Clinical Practice Guideline for Cardiac Rehabilitation in Korea

OBJECTIVE: Though clinical practice guidelines (CPGs) for cardiac rehabilitation (CR) are an effective and widely used treatment method worldwide, they are as yet not widely accepted in Korea. Given that cardiovascular disease is the second leading cause of death in Korea, it is urgent that CR programs be developed. In 2008, the Government of Korea implemented CR programs at 11 university hospitals as part of its Regional Cardio-Cerebrovascular Center Project, and three additional medical facilities will be added in 2019. In addition, owing to the promotion of CR nationwide and the introduction of CR insurance benefits, 40 medical institutions nationwide have begun CR programs even as a growing number of medical institutions are preparing to offer CR. The purpose of this research was to develop evidence-based CPGs to support CR implementation in Korea. METHODS: This study is based on an analysis of CPGs elsewhere in the world, an extensive literature search, a systematic analysis of multiple randomized control trials, and a CPG management, development, and assessment committee comprised of 33 authors-primarily rehabilitation specialists, cardiologists, and thoracic surgeons in 21 university hospitals and two general hospitals. Twelve consultants, primarily rehabilitation, sports medicine, and preventive medicine specialists, CPG experts, nurses, physical therapists, clinical nutritionists, and library and information experts participated in the research and development of these CPGs. After the draft guidelines were developed, three rounds of public hearings were held with staff members from relevant academic societies and stakeholders, after which the guidelines were further reviewed and modified. PRINCIPAL CONCLUSIONS: CR involves a more cost-effective use of healthcare resources relative to that of general treatments, and the exercise component of CR lowers cardiovascular mortality and readmission rates, regardless of the type of coronary heart disease and type and setting of CR. Individualized CR programs should be considered together with various factors, including differences in heart function and lifestyle, and doing so will boost participation and adherence with the CR program, ultimately meeting the final goals of the program, namely reducing the recurrence of myocardial infarction and mortality rates

Clinical Practice Guideline for Cardiac Rehabilitation in Korea: Recommendations for Cardiac Rehabilitation and Secondary Prevention after Acute Coronary Syndrome

Though clinical practice guidelines (CPGs) for cardiac rehabilitation (CR) are an effective and widely used treatment method worldwide, they are as yet not widely accepted in Korea. Given that cardiovascular (CV) disease is the second leading cause of death in Korea, it is urgent that CR programs be developed. In 2008, the Government of Korea implemented CR programs at 11 university hospitals as part of its Regional Cardio-Cerebrovascular Center Project, and 3 additional medical facilities will be added in 2019. In addition, owing to the promotion of CR nationwide and the introduction of CR insurance benefits, 40 medical institutions nationwide have begun CR programs even as a growing number of medical institutions are preparing to offer CR. The purpose of this research was to develop evidence-based CPGs to support CR implementation in Korea. This study is based on an analysis of CPGs elsewhere in the world, an extensive literature search, a systematic analysis of multiple randomized control trials, and a CPG management, development, and assessment committee comprised of thirty-three authors-primarily rehabilitation specialists, cardiologists, and thoracic surgeons in 21 university hospitals and 2 general hospitals. Twelve consultants, primarily rehabilitation, sports medicine, and preventive medicine specialists, CPG experts, nurses, physical therapists, clinical nutritionists, and library and information experts participated in the research and development of these CPGs. After the draft guidelines were developed, 3 rounds of public hearings were held with staff members from relevant academic societies and stakeholders, after which the guidelines were further reviewed and modified. CR involves a more cost-effective use of healthcare resources relative to that of general treatments, and the exercise component of CR lowers CV mortality and readmission rates, regardless of the type of coronary heart disease and type and setting of CR. Individualized CR programs should be considered together with various factors, including differences in heart function and lifestyle, and doing so will boost participation and adherence with the CR program, ultimately meeting the final goals of the program, namely reducing the recurrence of myocardial infarction and mortality rates

Histone deacetylase controls adult stem cell aging by balancing the expression of polycomb genes and jumonji domain containing 3

Aging is linked to loss of the self-renewal capacity of adult stem cells. Here, we observed that human multipotent stem cells (MSCs) underwent cellular senescence in vitro. Decreased expression of histone deacetylases (HDACs), followed by downregulation of polycomb group genes (PcGs), such as BMI1, EZH2 and SUZ12, and by upregulation of jumonji domain containing 3 (JMJD3), was observed in senescent MSCs. Similarly, HDAC inhibitors induced cellular senescence through downregulation of PcGs and upregulation of JMJD3. Regulation of PcGs was associated with HDAC inhibitor-induced hypophosphorylation of RB, which causes RB to bind to and decrease the transcriptional activity of E2F. JMJD3 expression regulation was dependant on histone acetylation status at its promoter regions. A histone acetyltransferase (HAT) inhibitor prevented replicative senescence of MSCs. These results suggest that HDAC activity might be important for MSC self-renewal by balancing PcGs and JMJD3 expression, which govern cellular senescence by p16INK4A regulation

Outer Membrane Vesicles as a Candidate Vaccine against Edwardsiellosis

Infection with Edwardsiella tarda, a Gram-negative bacterium, causes high morbidity and mortality in both marine and freshwater fish. Outer membrane vesicles (OMVs) released from Gram-negative bacteria are known to play important roles in bacterial pathogenesis and host immune responses, but no such roles for E. tarda OMVs have yet been described. In the present study, we investigated the proteomic composition of OMVs and the immunostimulatory effect of OMVs in a natural host, as well as the efficacy of OMVs when used as a vaccine against E. tarda infection. A total of 74 proteins, from diverse subcellular fractions, were identified in OMVs. These included a variety of important virulence factors, such as hemolysin, OmpA, porin, GAPDH, EseB, EseC, EseD, EvpC, EvpP, lipoprotein, flagellin, and fimbrial protein. When OMVs were administrated to olive flounder, significant induction of mRNAs encoding IL-1β, IL-6, TNFα, and IFNγ was observed, compared with the levels seen in fish injected with formalin-killed E. tarda. In a vaccine trial, olive flounder given OMVs were more effectively protected (p<0.0001) than were control fish. Investigation of OMVs may be useful not only for understanding the pathogenesis of E. tarda but also in development of an effective vaccine against edwardsiellosis

Status and Prospects of ZnO-Based Resistive Switching Memory Devices

In the advancement of the semiconductor device technology, ZnO could be a prospective alternative than the other metal oxides for its versatility and huge applications in different aspects. In this review, a thorough overview on ZnO for the application of resistive switching memory (RRAM) devices has been conducted. Various efforts that have been made to investigate and modulate the switching characteristics of ZnO-based switching memory devices are discussed. The use of ZnO layer in different structure, the different types of filament formation, and the different types of switching including complementary switching are reported. By considering the huge interest of transparent devices, this review gives the concrete overview of the present status and prospects of transparent RRAM devices based on ZnO. ZnO-based RRAM can be used for flexible memory devices, which is also covered here. Another challenge in ZnO-based RRAM is that the realization of ultra-thin and low power devices. Nevertheless, ZnO not only offers decent memory properties but also has a unique potential to be used as multifunctional nonvolatile memory devices. The impact of electrode materials, metal doping, stack structures, transparency, and flexibility on resistive switching properties and switching parameters of ZnO-based resistive switching memory devices are briefly compared. This review also covers the different nanostructured-based emerging resistive switching memory devices for low power scalable devices. It may give a valuable insight on developing ZnO-based RRAM and also should encourage researchers to overcome the challenges