Ku80 cooperates with CBP to promote COX-2 expression and tumor growth.

Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Overexpression of Ku80 was associated with poor prognosis in patients with lung cancers. We conclude that Ku80 promotes COX-2 expression and tumor growth and is a potential therapeutic target in lung cancer

Docking rings in a solid: reversible assembling of pseudorotaxanes inside a zirconium metal–organic framework

An unprecedented zirconium metal–organic framework featuring a T-shaped benzimidazole strut was constructed and employed as a sponge-like material for selective absorption of macrocyclic guests. The neutral benzimidazole domain of the as-synthesized framework can be readily protonated and fully converted to benzimidazolium. Mechanical threading of [24]crown-8 ether wheels onto recognition sites to form pseudorotaxanes was evidenced by solution nuclear magnetic resonance, solid-state fluorescence, and infrared spectroscopy. Selective absorption of [24]crown-8 ether rather than its dibenzo counterpart was also observed. Further study reveals that this binding process is reversible and acid–base switchable. The success of docking macrocyclic guests in crystals via host–guest interactions provides an alternative route to complex functional materials with interpenetrated structures

HTRA1 variant increases risk to neovascular age-related macular degeneration in Chinese population

AbstractAge-related macular degeneration (AMD) is a leading cause of irreversible visual impairment in the world. Advanced AMD can be divided into wet AMD (choroidal neovascularization) and dry AMD (geographic atrophy, GA). Drusen is characterized by deposits in the macula without visual loss and is an early AMD sign in the Caucasian population. rs11200638 in the promoter of HTRA1 has recently been shown to increases the risk for wet AMD in both Caucasian and Hong Kong Chinese populations. In order to replicate these results in a different cohort, we genotyped rs11200638 for 164 Chinese patients (90 wet AMD and 74 drusen) and 106 normal controls in a Han Mainland Chinese cohort. The genotypes were compared using chi square analysis for an additive allelic model. rs11200638 was significantly associated with wet AMD (p=5.00×10−12). Unlike in the Caucasian population, the risk allele of rs11200638 was not associated with drusen in our Chinese population. These findings confirm the association of HTRA1 with wet AMD

De novo transcriptome analysis of Medicago falcata reveals novel insights about the mechanisms underlying abiotic stress-responsive pathway

BACKGROUND: The entire world is facing a deteriorating environment. Understanding the mechanisms underlying plant responses to external abiotic stresses is important for breeding stress-tolerant crops and herbages. Phytohormones play critical regulatory roles in plants in the response to external and internal cues to regulate growth and development. Medicago falcata is one of the stress-tolerant candidate leguminous species and is able to fix atmospheric nitrogen. This ability allows leguminous plants to grow in nitrogen deficient soils. METHODS: We performed Illumina sequencing of cDNA prepared from abiotic stress treated M. falcata. Sequencedreads were assembled to provide a transcriptome resource. Transcripts were annotated using BLASTsearches against the NCBI non-redundant database and gene ontology definitions were assigned. Acomparison among the three abiotic stress treated samples was carried out. The expression of transcriptswas confirmed with qRT-PCR. RESULTS: We present an abiotic stress-responsive M. falcata transcriptome using next-generation sequencing data from samples grown under standard, dehydration, high salinity, and cold conditions. We combined reads from all samples and de novo assembled 98,515 transcripts to build the M. falcata gene index. A comprehensive analysis of the transcriptome revealed abiotic stress-responsive mechanisms underlying the metabolism and core signalling components of major phytohormones. We identified nod factor signalling pathways during early symbiotic nodulation that are modified by abiotic stresses. Additionally, a global comparison of homology between the M. falcata and M. truncatula transcriptomes, along with five other leguminous species, revealed a high level of global sequence conservation within the family. CONCLUSIONS: M. falcata is shown to be a model candidate for studying abiotic stress-responsive mechanisms in legumes. This global gene expression analysis provides new insights into the biochemical and molecular mechanisms involved in the acclimation to abiotic stresses. Our data provides many gene candidates that might be used for herbage and crop breeding. Additionally, FalcataBase (http://bioinformatics.cau.edu.cn/falcata/) was built for storing these data. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2019-x) contains supplementary material, which is available to authorized users

The diploid genome sequence of an Asian individual

Here we present the first diploid genome sequence of an Asian individual. The genome was sequenced to 36-fold average coverage using massively parallel sequencing technology. We aligned the short reads onto the NCBI human reference genome to 99.97% coverage, and guided by the reference genome, we used uniquely mapped reads to assemble a high-quality consensus sequence for 92% of the Asian individual's genome. We identified approximately 3 million single-nucleotide polymorphisms (SNPs) inside this region, of which 13.6% were not in the dbSNP database. Genotyping analysis showed that SNP identification had high accuracy and consistency, indicating the high sequence quality of this assembly. We also carried out heterozygote phasing and haplotype prediction against HapMap CHB and JPT haplotypes (Chinese and Japanese, respectively), sequence comparison with the two available individual genomes (J. D. Watson and J. C. Venter), and structural variation identification. These variations were considered for their potential biological impact. Our sequence data and analyses demonstrate the potential usefulness of next-generation sequencing technologies for personal genomics

Aluminium alloys and nanocomposites manufactured via friction stirring and 3D printing processes

In recent years, fabricating aluminium matrix composites (AMCs) reinforced with nanoparticles via Selective laser melting (SLM) has drawn attention due to the potential in improving mechanical properties. However, the formation of undesirable intermetallic phases and porosity defects are challenging to overcome. Also, joining of AMCs is also important for industrial applications. Friction stir welding (FSW) is a solid-state joining technique capable of producing good mechanical properties. This study paves the way for the fabrication of new novel AMCs via FSP as well as the joining of SLM fabricated AMCs. The main findings are: i. A new Al-based nano-composite reinforced with uniformly dispersed Al2O3 and carbon nanotubes (CNTs) have been successfully fabricated using FSP. Grain refinement was observed in friction stir processing with/ without the addition of nano-sized reinforcement particles. The presence of nano-sized reinforcement led to more pronounced grain refinement as pinning effect of the nano-particles have retarded the grain growth rate in the dynamic recrystallisation process. The micro-hardness and tensile strengths were increased significantly through the addition of Al2O3 and CNTs nanoparticles. In particular, the yield strength of the composites increased 70% compared with that of FSPed Al when both Al2O3 and CNTs were added in the matrix. Multiple reinforcements with different shapes can be an effective method to increase the tensile strengths, especially yield strength of metal matrix composites. ii. SLM fabricated AlSi10Mg, and AlSi10Mg-nAl2O3 composites were studied. The addition of nAl2O3 resulted in the increasing formation of porosity in SLM fabricated AMCs. Hence, higher laser energy input was required to improve the wettability properties. Columnar grain structure along the thermal gradient was observed. Significant grain refinement was achieved with the addition of nAl2O3 via Zener pinning effect by exerting pinning pressure. The use of AlSi10Mg has resulted in the fabrication of AlSi10Mg-nAl2O3 composites with superior mechanical properties compared to Al-nAl2O3 composites using pure aluminium. iii. FSW had successfully joined SLM fabricated AlSi10Mg parts together without the presence of welding defects with rotational speed = 1200 rpm, travel speed = 1 mm/s, tilt angle = 4.5°. Grain refinement was observed in the FSW region due to dynamic recrystallisation process together with a significant increase in the fraction of high-angle grain boundaries during FSW. Significant decreases in the hardness and tensile strength were observed in the weld region due to the precipitation of Si. The increase in rotation speed or reduction in travel speed increased in grain size and slight reduction of hardness. Ductility was improved after FSW, and tensile strength is comparable to FSW of AA6061-T6 rolled sheets. iv. FSW was successfully used to joined SLM fabricated AlSi10Mg and its composites together achieving fine grains in the FSW region. Agglomerated and sintered nAl2O3 was observed to have broken down and dispersed in the matrix after FSW. It was observed that the use of higher tool rotational speed resulted in larger grains. The addition of nAl2O3 contributed to finer grains and higher hardness due to Zener pinning effect. FSW can generate porosity-free welds while 18% porosity density was received from as-printed substrates. These favourable findings ascertained the feasibility of using FSW to join SLM fabricated Al-Al2O3 composites and contributed to the scientific knowledge that FSW can produce a weld with desirable results for actual applications.Doctor of Philosoph

A comparison between cannulated and non-cannulated cancellous screws used in the fixation of a simulated femoral neck fracture : a finite element study

Femoral neck fractures are a common form of injury amongst the elderly and cannulated screws are the preferred choice for fixation. Previous studies have researched the performance of various screw design and configurations based on pull-out strength as well as the best fixation based on displacement, load and stiffness characteristic. However, little attention was given to the use of finite element method to aid in the investigation of the performance of various fixations. In this study, ABAQUS was used to investigate the performance between cannulated and non-cannulated screws used in an inferior triangular fixation on Pauwel’s type-2 vertical femoral neck fracture with normal Sawbones femur. The von Mises stresses were analysed and the results suggested that the femur with cannulated screws experienced lower stresses.Bachelor of Engineering (Mechanical Engineering

Comprehensively benchmarking applications for detecting copy number variation.

MOTIVATION:Recently, copy number variation (CNV) has gained considerable interest as a type of genomic variation that plays an important role in complex phenotypes and disease susceptibility. Since a number of CNV detection methods have recently been developed, it is necessary to help investigators choose suitable methods for CNV detection depending on their objectives. For this reason, this study compared ten commonly used CNV detection applications, including CNVnator, ReadDepth, RDXplorer, LUMPY and Control-FREEC, benchmarking the applications by sensitivity, specificity and computational demands. Taking the DGV gold standard variants as a standard dataset, we evaluated the ten applications with real sequencing data at sequencing depths from 5X to 50X. Among the ten methods benchmarked, LUMPY performs the best for both high sensitivity and specificity at each sequencing depth. For the purpose of high specificity, Canvas is also a good choice. If high sensitivity is preferred, CNVnator and RDXplorer are better choices. Additionally, CNVnator and GROM-RD perform well for low-depth sequencing data. Our results provide a comprehensive performance evaluation for these selected CNV detection methods and facilitate future development and improvement in CNV prediction methods

Aluminium-carbon nanotubes composites produced from friction stir processing and selective laser melting

Aluminium reinforced with multi-wall carbon nanotubes was produced using friction stir processing and selective laser melting. Very fine grains were successfully achieved in both methods with high Vickers hardness values. Cavities were present in selective laser melting of AlSi10Mg reinforced with multi-wall carbon nanotubes parts resulting in higher stress concentration brittle fracture appearance. The high laser absorption and higher thermal conductivity of multi-wall carbon nanotubes resulted in the formation of the cavities in the melted parts. However, the fractography images showed dimpled like appearance indicating a ductile fracture mechanism. Multi-wall carbon nanotubes were observed at the fracture sites indicating the presence of a crack-bridging mechanism. In comparison to carbon nanotubes reinforced aluminium by friction stir processing, selective laser melting produces aluminium reinforced aluminium with better mechanical properties.Accepted versio