Classic swine fever virus NS2 protein leads to the induction of cell cycle arrest at S-phase and endoplasmic reticulum stress

<p>Abstract</p> <p>Background</p> <p>Classical swine fever (CSF) caused by virulent strains of Classical swine fever virus (CSFV) is a haemorrhagic disease of pigs, characterized by disseminated intravascular coagulation, thrombocytopoenia and immunosuppression, and the swine endothelial vascular cell is one of the CSFV target cells. In this report, we investigated the previously unknown subcellular localization and function of CSFV NS2 protein by examining its effects on cell growth and cell cycle progression.</p> <p>Results</p> <p>Stable swine umbilical vein endothelial cell line (SUVEC) expressing CSFV NS2 were established and showed that the protein localized to the endoplasmic reticulum (ER). Cellular analysis revealed that replication of NS2-expressing cell lines was inhibited by 20-30% due to cell cycle arrest at S-phase. The NS2 protein also induced ER stress and activated the nuclear transcription factor kappa B (NF-κB). A significant increase in cyclin A transcriptional levels was observed in NS2-expressing cells but was accompanied by a concomitant increase in the proteasomal degradation of cyclin A protein. Therefore, the induction of cell cycle arrest at S-phase by CSFV NS2 protein is associated with increased turnover of cyclin A protein rather than the down-regulation of cyclin A transcription.</p> <p>Conclusions</p> <p>All the data suggest that CSFV NS2 protein modulate the cellular growth and cell cycle progression through inducing the S-phase arrest and provide a cellular environment that is advantageous for viral replication. These findings provide novel information on the function of the poorly characterized CSFV NS2 protein.</p

Malignant mesenchymal tumor with leiomyosarcoma, rhabdomyosarcoma, chondrosarcoma, and osteosarcoma differentiation: case report and literature review

A case of malignant mesenchymoma of the bladder containing leiomyosarcoma, rhabdomyosarcoma, chondrosarcoma, osteosarcoma, and myxomatous components is described. The primary pedunculated tumor measuring 14 × 13 × 7 cm and weighing 343 g arose from the left trigone of the bladder and was treated by total cystectomy. The histogenesis of malignant mesenchymomas and their optimal management strategy and prognosis remain uncertain. Herein, we present the fifth case of malignant mesenchymoma of the urinary bladder to be reported in the literature, which presented five unrelated differentiated tissues more than did previously reported cases

Halide-Assisted Atmospheric Pressure Growth of Large WSe2 and WS2 Monolayer Crystals

Chemical vapor deposition (CVD) of two-dimensional (2D) tungsten dichalcogenide crystals requires steady flow of tungsten source in the vapor phase. This often requires high temperature and low pressure due to the high sublimation point of tungsten oxide precursors. We demonstrate atmospheric pressure CVD of WSe2 and WS2 monolayers at moderate temperatures (700 ~ 850 oC) using alkali metal halides (MX where M= Na or K and X=Cl, Br or I) as the growth promoters. We attribute the facilitated growth to the formation of volatile tungsten oxyhalide species during growth, which leads to efficient delivery of the precursor to the growth substrates. The monolayer crystals were found to be free of unintentional doping with alkali metal and halogen atoms. Good field-effect transistor (FET) performances with high current on/off ratio ~10 7, hole and electron mobilities up to 102 and 26 cm2 V 1 s-1 for WSe2 and electron mobility of ~14 cm2 V-1 s-1 for WS2 devices were achieved.Comment: 21 pages, 4 figures in manuscript & 10 pages, 6 figures in supplementary materia

Heteroepitaxial Growth of Single-Walled Carbon Nanotubes from Boron Nitride

The growth of single-walled carbon nanotubes (SWCNTs) with predefined structure is of great importance for both fundamental research and their practical applications. Traditionally, SWCNTs are grown from a metal catalyst with a vapor-liquid-solid mechanism, where the catalyst is in liquid state with fluctuating structures, and it is intrinsically unfavorable for the structure control of SWCNTs. Here we report the heteroepitaxial growth of SWCNTs from a platelet boron nitride nanofiber (BNNF), which is composed of stacked (002) planes and is stable at high temperatures. SWCNTs are found to grow epitaxially from the open (002) edges of the BNNFs, and the diameters of the SWCNTs are multiples of the BN (002) interplanar distance. In situ transmission electron microscopy observations coupled with first principles calculations reveal that the growth of SWCNTs from the BNNFs follows a vapor-solid-solid mechanism. Our work opens opportunities for the control over the structure of SWCNTs by hetero-crystallographic epitaxy.Peer reviewe

Neutralization of Diverse Human Cytomegalovirus Strains Conferred by Antibodies Targeting Viral gH/gL/pUL128-131 Pentameric Complex

Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection, and developing a prophylactic vaccine is of high priority to public health. We recently reported a replication-defective human cytomegalovirus with restored pentameric complex glycoprotein H (gH)/gL/pUL128-131 for prevention of congenital HCMV infection. While the quantity of vaccine-induced antibody responses can be measured in a viral neutralization assay, assessing the quality of such responses, including the ability of vaccine-induced antibodies to cross-neutralize the field strains of HCMV, remains a challenge. In this study, with a panel of neutralizing antibodies from three healthy human donors with natural HCMV infection or a vaccinated animal, we mapped eight sites on the dominant virus-neutralizing antigen-the pentameric complex of glycoprotein H (gH), gL, and pUL128, pUL130, and pUL131. By evaluating the site-specific antibodies in vaccine immune sera, we demonstrated that vaccination elicited functional antiviral antibodies to multiple neutralizing sites in rhesus macaques, with quality attributes comparable to those of CMV hyperimmune globulin. Furthermore, these immune sera showed antiviral activities against a panel of genetically distinct HCMV clinical isolates. These results highlighted the importance of understanding the quality of vaccine-induced antibody responses, which includes not only the neutralizing potency in key cell types but also the ability to protect against the genetically diverse field strains. IMPORTANCE HCMV is the leading cause of congenital viral infection, and development of a preventive vaccine is a high public health priority. To understand the strain coverage of vaccine-induced immune responses in comparison with natural immunity, we used a panel of broadly neutralizing antibodies to identify the immunogenic sites of a dominant viral antigen-the pentameric complex. We further demonstrated that following vaccination of a replication-defective virus with the restored pentameric complex, rhesus macaques can develop broadly neutralizing antibodies targeting multiple immunogenic sites of the pentameric complex. Such analyses of site-specific antibody responses are imperative to our assessment of the quality of vaccine-induced immunity in clinical studies