Increased exonic de novo mutation rate in individuals with schizophrenia

Schizophrenia is a severe psychiatric disorder that profoundly affects cognitive, behavioral and emotional processes. The wide spectrum of symptoms and clinical variability in schizophrenia suggest a complex genetic etiology, which is consistent with the numerous loci thus far identified by linkage, copy number variation and association studies. Although schizophrenia heritability may be as high as ～80%, the genes responsible for much of this heritability remain to be identified. Here we sequenced the exomes of 14 schizophrenia probands and their parents. We identified 15 de novo mutations (DNMs) in eight probands, which is significantly more than expected considering the previously reported DNM rate. In addition, 4 of the 15 identified DNMs are nonsense mutations, which is more than what is expected by chance. Our study supports the notion that DNMs may account for some of the heritability reported for schizophrenia while providing a list of genes possibly involved in disease pathogenesis.     

Lysophosphatidic acid up-regulates vascular endothelial growth factor-C and lymphatic marker expressions in human endothelial cells

Lysophosphatidic acid (LPA) is a low-molecular-weight lipid growth factor, which binds to G-protein-coupled receptors. Previous studies have shown that LPA enhances vascular endothelial growth factor-A (VEGF-A) expression in cancer cells and promotes angiogenesis process. However, the roles of LPA in lymphatic vessel formation and lymphangiogenesis have not been investigated. Here, we demonstrated that LPA up-regulated VEGF-C mRNA and protein expressions in human umbilical vein endothelial cells (HUVECs). Furthermore, the expression levels of lymphatic markers, including Prox-1, LYVE-1 and podoplanin, were enhanced in LPA-stimulated tube forming endothelial cells in vitro and in vivo. Moreover, we showed that pretreatment with MAZ51, a VEGFR-3 kinase inhibitor, and introduction of VEGFR-3 siRNA suppressed LPA-induced HUVEC tube formation and lymphatic marker expressions. These results demonstrated that LPA enhances expression of lymphatic markers through activating VEGF-C receptors in endothelial cells. This study provides basic information that LPA might be a target for therapeutics against lymphangiogenesis and tumor metastasis.     

Preface： Advanced Thin Film Developments and Nano Structures

In this special issue, we invited a few leading materials researchers to present topics in thin films, coatings, and nano structures. Readers will find most recent developments in topics, including recent advances in hard, tough, and low friction nanocomposite coatings; thin films for coating nanomaterials; electroless plating of silver thin films on porous Al2O3 substrate; CrN/Nano Cr interlayer coatings; nano-structured carbide derived carbon （CDC） films and their tribology; predicting interdiffusion in high-temperature coatings; gallium-catalyzed silica nanowire growth; and corrosion protection properties of organofunctional silanes. Authors are from both national laboratories and academia.     

掺稻壳灰与纤维素纤维混凝土抗氯离子渗透和抗冻性试验研究

为了研究水胶比、稻壳灰和纤维素纤维对混凝土耐久性能的影响,以稻壳灰掺量（0、10%和20%）、纤维素纤维掺量（0.7 kg/m3、1.1 kg/m3和1.6 kg/m3）和水胶比（0.37、0.41和0.45）为变量,通过9组正交试验得到3种因素对混凝土抗氯离子渗透性能和抗冻性能的影响规律,并分别建立了掺稻壳灰纤维混凝土质量损失率与相对动弹性模量的冻融预测模型. 结果表明：各因素对混凝土抗氯离子渗透性能和抗冻性能影响显著程度依次为：水胶比＞稻壳灰掺量＞纤维素纤维掺量;混凝土的抗氯离子渗透性能和抗冻性能随稻壳灰掺量的增加显著增强,随纤维素纤维掺量的增加呈先增强后减弱的趋势,在水胶比为0.37时最优;稻壳灰掺量为20%时,混凝土抗氯离子渗透性能最佳,抗冻性能最优;纤维素纤维掺量为1.1 kg/m3时,混凝土抗氯离子渗透性能最好,抗冻性能最强;增加稻壳灰掺量、添加适量的纤维素纤维可以提高混凝土基体的密实度、减少微裂缝,进而增强混凝土的耐久性能;所建立的掺稻壳灰纤维混凝土质量损失率与相对动弹性模量的冻融预测模型与试验结果吻合较好,具有一定的适用性,可为制备绿色高性能混凝土提供理论依据和支撑.     

A Simulation Research Towards Better Leverage of Sales Ranking

As a kind of the most significantly popular information in markets,the sales ranking has great impacts on consumer choice.However,there are few discussions on how sales ranking should be provided to consumers in the literature.This paper aims to answer the following two questions:1)To what extent does the sales ranking influence consumer choices;2)When the sales ranking should be provided to consumers.To do so,this paper first constructs a sales ranking model and then provides detailed simulation experiments to demonstrate the model.The experimental results show that for markets where consumer preferences are dramatically different,such as music and movie markets,sales rankings do not have significant influences on consumer choices and should not be provided to consumers until a large number of early independent consumer choices have been accumulated.But for markets in which consumer preferences are similar,such as markets for official supplies,sales rankings have more influences on consumer choices and should be provided to consumers earlier.Furthermore,an evolution strategy is proposed to ascertain the most suitable sales rankings(characterised by suitable influence strength and suitable release time)for some specified online markets.The comparison results show that the optimized sales rankings not only can help consumers discover higher-quality products but also can improve overall sales.     

High-throughput oncogene mutation profiling in human cancer

Systematic efforts are underway to decipher the genetic changes associated with tumor initiation and progression. However, widespread clinical application of this information is hampered by an inability to identify critical genetic events across the spectrum of human tumors with adequate sensitivity and scalability. Here, we have adapted high-throughput genotyping to query 238 known oncogene mutations across 1,000 human tumor samples. This approach established robust mutation distributions spanning 17 cancer types. Of 17 oncogenes analyzed, we found 14 to be mutated at least once, and 298 (30%) samples carried at least one mutation. Moreover, we identified previously unrecognized oncogene mutations in several tumor types and observed an unexpectedly high number of co-occurring mutations. These results offer a new dimension in tumor genetics, where mutations involving multiple cancer genes may be interrogated simultaneously and in 'real time' to guide cancer classification and rational therapeutic intervention.     

Homozygous L-SIGN (CLEC4M) plays a protective role in SARS coronavirus infection

Severe acute respiratory syndrome (SARS) is caused by infection of a previously undescribed coronavirus (CoV). L-SIGN, encoded by CLEC4M (also known as CD209L), is a SARS-CoV binding receptor that has polymorphism in its extracellular neck region encoded by the tandem repeat domain in exon 4. Our genetic risk association study shows that individuals homozygous for CLEC4M tandem repeats are less susceptible to SARS infection. L-SIGN is expressed in both non-SARS and SARS-CoV-infected lung. Compared with cells heterozygous for L-SIGN, cells homozygous for L-SIGN show higher binding capacity for SARS-CoV, higher proteasome-dependent viral degradation and a lower capacity for trans infection. Thus, homozygosity for L-SIGN plays a protective role during SARS infection.     

Pretrained Models and Evaluation Data for the Khmer Language

Trained on a large corpus, pretrained models(PTMs) can capture different levels of concepts in context and hence generate universal language representations, which greatly benefit downstream natural language processing(NLP) tasks. In recent years, PTMs have been widely used in most NLP applications, especially for high-resource languages, such as English and Chinese. However, scarce resources have discouraged the progress of PTMs for low-resource languages. Transformer-based PTMs for the Khmer l...     

Fabrication of flexible α-MnO_2 nanowire membranes with superior mechanical strength

The Assembly of one-dimensional （1D） nano- structures such as nanowires/nanorods/nanotubes into two- dimensional （2D） macrostructured films is attracting considerable research interest because of their unique properties and wide applications. In this study, flexible membranes were successfully fabricated using α-MnO2 nanowires synthesized through a hydrothermal method. The effects of thickness and post-annealing temperature on the mechanical properties of the membranes were investigated in detail. Nano-indentation measurements showed that the modulus of the as-prepared 11.75 μm-thick membrane reached 5.765 GPa, and the modulus increased with the increasing post-annealing temperature. Thus, the fabricated membranes with superior mechanical strength can have potential applications such as in photocatalysis, filtering, and supporting substrates.