Indicators of the molecular pathogenesis of virulent Newcastle disease virus in chickens revealed by transcriptomic profiling of spleen

Newcastle disease virus (NDV) has caused significant outbreaks in South-East Asia, particularly in Indonesia in recent years. Recently emerged genotype VII NDVs (NDV-GVII) have shifted their tropism from gastrointestinal/respiratory tropism to a lymphotropic virus, invading lymphoid organs including spleen and bursa of Fabricius to cause profound lymphoid depletion. In this study, we aimed to identify candidate genes and biological pathways that contribute to the disease caused by this velogenic NDV-GVII. A transcriptomic analysis based on RNA-Seq of spleen was performed in chickens challenged with NDV-GVII and a control group. In total, 6361 genes were differentially expressed that included 3506 up-regulated genes and 2855 down-regulated genes. Real-Time PCR of ten selected genes validated the RNA-Seq results as the correlation between them is 0.98. Functional and network analysis of Differentially Expressed Genes (DEGs) showed altered regulation of ElF2 signalling, mTOR signalling, proliferation of cells of the lymphoid system, signalling by Rho family GTPases and synaptogenesis signalling in spleen. We have also identified modified expression of IFIT5, PI3K, AGT and PLP1 genes in NDV-GVII infected chickens. Our findings in activation of autophagy-mediated cell death, lymphotropic and synaptogenesis signalling pathways provide new insights into the molecular pathogenesis of this newly emerged NDV-GVII

Wafer-scale Fabrication of Non-Polar Mesoporous GaN Distributed Bragg Reflectors via Electrochemical Porosification

Distributed Bragg reflectors (DBRs) are essential components for the development of optoelectronic devices. For many device applications, it is highly desirable to achieve not only high reflectivity and low absorption, but also good conductivity to allow effective electrical injection of charges. Here, we demonstrate the wafer-scale fabrication of highly reflective and conductive non-polar gallium nitride (GaN) DBRs, consisting of perfectly lattice-matched non-polar (11–20) GaN and mesoporous GaN layers that are obtained by a facile one-step electrochemical etching method without any extra processing steps. The GaN/mesoporous GaN DBRs exhibit high peak reflectivities (>96%) across the entire visible spectrum and wide spectral stop-band widths (full-width at half-maximum >80nm), while preserving the material quality and showing good electrical conductivity. Such mesoporous GaN DBRs thus provide a promising and scalable platform for high performance GaN-based optoelectronic, photonic, and quantum photonic devices.This research was supported by the UK Engineering and Physical Sciences Research Council Grants EP/J003603/1 and EP/M011682/1. The microscopy studies were supported by the European Research Council under the European Community’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no 279361 (MACONS). Dr. T. Ding acknowledges the support from Leverhulme Early Career Fellowship (ECF-2016-606)

Primary skin fibroblasts as a model of Parkinson's disease

Parkinson's disease is the second most frequent neurodegenerative disorder. While most cases occur sporadic mutations in a growing number of genes including Parkin (PARK2) and PINK1 (PARK6) have been associated with the disease. Different animal models and cell models like patient skin fibroblasts and recombinant cell lines can be used as model systems for Parkinson's disease. Skin fibroblasts present a system with defined mutations and the cumulative cellular damage of the patients. PINK1 and Parkin genes show relevant expression levels in human fibroblasts and since both genes participate in stress response pathways, we believe fibroblasts advantageous in order to assess, e.g. the effect of stressors. Furthermore, since a bioenergetic deficit underlies early stage Parkinson's disease, while atrophy underlies later stages, the use of primary cells seems preferable over the use of tumor cell lines. The new option to use fibroblast-derived induced pluripotent stem cells redifferentiated into dopaminergic neurons is an additional benefit. However, the use of fibroblast has also some drawbacks. We have investigated PARK6 fibroblasts and they mirror closely the respiratory alterations, the expression profiles, the mitochondrial dynamics pathology and the vulnerability to proteasomal stress that has been documented in other model systems. Fibroblasts from patients with PARK2, PARK6, idiopathic Parkinson's disease, Alzheimer's disease, and spinocerebellar ataxia type 2 demonstrated a distinct and unique mRNA expression pattern of key genes in neurodegeneration. Thus, primary skin fibroblasts are a useful Parkinson's disease model, able to serve as a complement to animal mutants, transformed cell lines and patient tissues

Epstein-Barr virus infection and chronic lymphocytic leukemia: a possible progression factor?

Epstein-Barr virus is pathogenically associated with a well defined group of lymphoid and epithelial tumors in which the virus directly drives transformation of infected cells. Recent evidence however indicates that this virus may infect a subpopulation of tumor cells in patients with chronic lymphocytic leukemia (CLL) and EBV infection has been also associated with Richter transformation in a fraction of cases. We herein review available data suggesting a possible role of EBV as a direct or micro-environmental progression factor in a subset of CLL

Etiology and Clinical Characterization of Respiratory Virus Infections in Adult Patients Attending an Emergency Department in Beijing

BACKGROUND: Acute respiratory tract infections (ARTIs) represent a serious global health burden. To date, few reports have addressed the prevalence of respiratory viruses (RVs) in adults with ARTIs attending an emergency department (ED). Therefore, the potential impact of respiratory virus infections on such patients remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: To determine the epidemiological and clinical profiles of common and recently discovered respiratory viruses in adults with ARTIs attending an ED in Beijing, a 1-year consecutive study was conducted from May, 2010, to April, 2011. Nose and throat swab samples from 416 ARTI patients were checked for 13 respiratory viruses using multiple reverse transcription polymerase chain reaction(RT-PCR) assays for common respiratory viruses, including influenza viruses (Flu) A, B, and adenoviruses (ADVs), picornaviruses (PICs), respiratory syncytial virus (RSV), parainfluenza viruses (PIVs) 1-3, combined with real-time RT-PCR for human metapneumovirus (HMPV) and human coronaviruses (HCoVs, -OC43, -229E, -NL63, and -HKU1). Viral pathogens were detected in 52.88% (220/416) of patient samples, and 7.21% (30/416) of patients tested positive for more than one virus. PICs (17.79%) were the dominant agents detected, followed by FluA (16.11%), HCoVs (11.78%), and ADV (11.30%). HMPV, PIVs, and FluB were also detected (<3%), but not RSV. The total prevalence and the dominant virus infections detected differed significantly between ours and a previous report. Co-infection rates were high for HCoV-229E (12/39, 30.76%), PIC (22/74, 29.73%), ADV (12/47, 25.53%) and FluA (15/67, 22.39%). Different patterns of clinical symptoms were associated with different respiratory viruses. CONCLUSIONS: The pattern of RV involvement in adults with ARTIs attending an ED in China differs from that previously reported. The high prevalence of viruses (PIC, FluA, HCoVs and ADV) reported here strongly highlight the need for the development of safe and effective therapeutic approaches for these viruses

Lymph node infarction – a rare complication associated with disseminated intra vascular coagulation in a case of dengue fever

BACKGROUND: Lymph node infarction is known to occur in association with many non-neoplastic and neoplastic conditions however its occurrence in association with DIC is not reported hitherto in the literature. CASE PRESENTATION: We describe an unusual case of lymph node infarction in a twenty seven year old male following disseminated intravascular coagulation (DIC) in a case of dengue fever. Multiple sections of the infarcted and the surrounding non-infarcted lymph nodes failed to reveal any predisposing condition. How ever the parahilar vessels showed thrombotic occlusion, which must have been responsible for the infarction. CONCLUSION: Global infarction of the lymph node may mask the underlying pathology. Any malignancy especially lymphoma may coexist or follow lymph node infarction, therefore the patient needs constant surveillance

Systematic Two-Hybrid and Comparative Proteomic Analyses Reveal Novel Yeast Pre-mRNA Splicing Factors Connected to Prp19

Prp19 is the founding member of the NineTeen Complex, or NTC, which is a spliceosomal subcomplex essential for spliceosome activation. To define Prp19 connectivity and dynamic protein interactions within the spliceosome, we systematically queried the Saccharomyces cerevisiae proteome for Prp19 WD40 domain interaction partners by two-hybrid analysis. We report that in addition to S. cerevisiae Cwc2, the splicing factor Prp17 binds directly to the Prp19 WD40 domain in a 1∶1 ratio. Prp17 binds simultaneously with Cwc2 indicating that it is part of the core NTC complex. We also find that the previously uncharacterized protein Urn1 (Dre4 in Schizosaccharomyces pombe) directly interacts with Prp19, and that Dre4 is conditionally required for pre-mRNA splicing in S. pombe. S. pombe Dre4 and S. cerevisiae Urn1 co-purify U2, U5, and U6 snRNAs and multiple splicing factors, and dre4Δ and urn1Δ strains display numerous negative genetic interactions with known splicing mutants. The S. pombe Prp19-containing Dre4 complex co-purifies three previously uncharacterized proteins that participate in pre-mRNA splicing, likely before spliceosome activation. Our multi-faceted approach has revealed new low abundance splicing factors connected to NTC function, provides evidence for distinct Prp19 containing complexes, and underscores the role of the Prp19 WD40 domain as a splicing scaffold

Nanometer Sized Silver Particles Embedded Silica Particles—Spray Method

Spherical shaped, nanometer to micro meter sized silica particles were prepared in a homogeneous nature by spray technique. Silver nanoparticles were produced over the surface of the silica grains in a harmonized manner. The size of silver and silica particles was effectively controlled by the precursors and catalysts. The electrostatic repulsion among the silica spheres and the electro static attraction between silica spheres and silver particles make the synchronized structure of the synthesized particles and the morphological images are revealed by transmission electron microscope. The silver ions are reduced by sodium borohydride. Infra red spectroscopy and X-ray photoelectron spectroscopy analysis confirm the formation of silver–silica composite particles. Thermal stability of the prepared particles obtained from thermal analysis ensures its higher temperature applications. The resultant silver embedded silica particles can be easily suspended in diverse solvents and would be useful for variety of applications

Parametric design optimisation of proximal humerus plates based on finite element method

Optimal treatment of proximal humerus fractures remains controversial. Locking plates offer theoretical advantages but are associated with complications in the clinic. This study aimed to perform parametric design optimisation of proximal humerus plates to enhance their mechanical performance. A finite element (FE) model was developed that simulated a two-part proximal humerus fracture that had been treated with a Spatial Subchondral Support (S3) plate and subjected to varus bending. The FE model was validated against in vitro biomechanical test results. The predicted load required to apply 5 mm cantilever varus bending was only 0.728% lower. The FE model was then used to conduct a parametric optimisation study to determine the orientations of inferomedial plate screws that would yield minimum fracture gap change (i.e. optimal stability). The feasible design space was automatically identified by imposing clinically relevant constraints, and the creation process of each FE model for the design optimisation was automated. Consequently, 538 FE models were generated, from which the obtained optimal model had 4.686% lower fracture gap change (0.156 mm) than that of the manufacturer’s standard plate. Whereas its screws were oriented towards the inferomedial region and within the range of neck-shaft angle of a healthy subject. The methodology presented in this study promises future applications in patient-specific design optimisation of implants for other regions of the human body