bluuebunny/crossref_metadata_2025 huggingface dataset:
Infectious Bronchitis Coronavirus Inhibits STAT1 Signaling and Requires Accessory Proteins for Resistance to Type I Interferon Activity
Authors: Kint Joeri , Dickhout Annemiek , Kutter Jasmin , Maier Helena J. , Britton Paul , Koumans Joseph , Pijlman Gorben P. , Fros Jelke J. , Wiegertjes Geert F. , Forlenza Maria
Published: September 2015

The innate immune response is the first line of defense against viruses, and type I interferon (IFN) is a critical component of this response. Similar to other viruses, the gammacoronavirus infectious bronchitis virus (IBV) has evolved under evolutionary pressure to evade and counteract the IFN response to enable its survival. Previously, we reported that IBV induces a delayed activation of the IFN response. In the present work, we describe the resistance of IBV to IFN and the potential role of accessory proteins herein. We show that IBV is fairly resistant to the antiviral state induced by IFN and identify that viral accessory protein 3a is involved in resistance to IFN, as its absence renders IBV less resistant to IFN treatment. In addition to this, we found that independently of its accessory proteins, IBV inhibits IFN-mediated phosphorylation and translocation of STAT1. In summary, we show that IBV uses multiple strategies to counteract the IFN response.

IMPORTANCE
In the present study, we show that infectious bronchitis virus (IBV) is resistant to IFN treatment and identify a role for accessory protein 3a in the resistance against the type I IFN response. We also demonstrate that, in a time-dependent manner, IBV effectively interferes with IFN signaling and that its accessory proteins are dispensable for this activity. This study demonstrates that the gammacoronavirus IBV, similar to its mammalian counterparts, has evolved multiple strategies to efficiently counteract the IFN response of its avian host, and it identifies accessory protein 3a as multifaceted antagonist of the avian IFN system.
Modulation of MicroRNA Cluster miR-183-96-182 Expression by Epstein-Barr Virus Latent Membrane Protein 1
Authors: Oussaief Lassad , Fendri Ali , Chane-Woon-Ming Béatrice , Poirey Remy , Delecluse Henri-Jacques , Joab Irène , Pfeffer Sébastien
Published: September 2015

Epstein-Barr virus (EBV) is an oncogenic human herpesvirus involved in the pathogenesis of Burkitt's lymphoma (BL) and various other lymphoproliferative disorders. In BL, EBV protein expression is restricted to EBV nuclear antigen 1 (EBNA1), but small noncoding RNAs such as EBV-encoded small RNAs (EBERs) and microRNAs (miRNAs) can also be detected. miRNAs play major roles in crucial processes such as proliferation, differentiation, and cell death. It has recently become clear that alterations in the expression profile of miRNAs contribute to the pathogenesis of a number of malignancies. During latent infection, EBV expresses 25 viral pre-miRNAs and modulates the expression of specific cellular miRNAs, such as miR-155 and miR-146, which potentially play a role in oncogenesis. Here, we established the small-RNA expression profiles of three BL cell lines. Using large-scale sequencing coupled to Northern blotting and real-time reverse transcription-PCR (RT-PCR) analysis validation, we demonstrated the differential expression of some cellular and viral miRNAs. High-level expression of the miR-183-96-182 cluster and EBV miR-BamHI A rightward transcript (miR-BART) cluster was significantly associated with EBV type I latency. This expression was not affected by viral reactivation since transforming growth factor β1 (TGF-β1) stimulation did not significantly change the miRNA profiles. However, using several approaches, including
de novo
infection with a mutant virus, we present evidence that the expression of latent membrane protein 1 (LMP-1) triggered downregulation of the expression of the miR-183-96-182 cluster. We further show that this effect involves the Akt signaling pathway.

IMPORTANCE
In addition to expressing their own miRNAs, herpesviruses also impact the expression levels of cellular miRNAs. This regulation can be either positive or negative and usually results in the perturbation of pathways to create a cellular environment that is more “virus-friendly.” For example, EBV induces the expression of miR-155, a well-characterized oncomiR, which leads to increased cell proliferation and decreased cell death. Here, we show that EBV-encoded LMP-1 is also involved in the downregulation of a cluster of three miRNAs, miR-183, -96, and -182, which are known to be also repressed in several cancers. We therefore identify yet another potential player in EBV-induced oncogenesis.
The U4 Antibody Epitope on Human Papillomavirus 16 Identified by Cryo-electron Microscopy
Authors: Guan Jian , Bywaters Stephanie M. , Brendle Sarah A. , Lee Hyunwook , Ashley Robert E. , Christensen Neil D. , Hafenstein Susan
Published: September 2015

The human papillomavirus (HPV) major structural protein L1 composes capsomers that are linked together through interactions mediated by the L1 C terminus to constitute a T=7 icosahedral capsid. H16.U4 is a type-specific monoclonal antibody recognizing a conformation-dependent neutralizing epitope of HPV thought to include the L1 protein C terminus. The structure of human papillomavirus 16 (HPV16) complexed with H16.U4 fragments of antibody (Fab) was solved by cryo-electron microscopy (cryo-EM) image reconstruction. Atomic structures of virus and Fab were fitted into the corresponding cryo-EM densities to identify the antigenic epitope. The antibody footprint mapped predominately to the L1 C-terminal arm with an additional contact point on the side of the capsomer. This footprint describes an epitope that is presented capsid-wide. However, although the H16.U4 epitope suggests the presence of 360 potential binding sites exposed in the capsid valley between each capsomer, H16.U4 Fab bound only to epitopes located around the icosahedral five-fold vertex of the capsid. Thus, the binding characteristics of H16.U4 defined in this study showed a distinctive selectivity for local conformation-dependent interactions with specific L1 invading arms between five-fold related capsomers.

IMPORTANCE
Human papillomavirus 16 (HPV16) is the most prevalent oncogenic genotype in HPV-associated anogenital and oral cancers. Here we use cryo-EM reconstruction techniques to solve the structures of the HPV16 capsid complexes using H16.U4 fragment of antibody (Fab). Different from most other antibodies directed against surface loops, H16.U4 monoclonal antibody is unique in targeting the C-terminal arm of the L1 protein. This monoclonal antibody (MAb) is used throughout the HPV research community in HPV serological and vaccine development and to define mechanisms of HPV uptake. The unique binding mode of H16.U4 defined here shows important conformation-dependent interactions within the HPV16 capsid. By targeting an important structural and conformational epitope, H16.U4 may identify subtle conformational changes in different maturation stages of the HPV capsid and provide a key probe to analyze the mechanisms of HPV uptake during the early stages of virus infection. Our analyses precisely define important conformational epitopes on HPV16 capsids that are key targets for successful HPV prophylactic vaccines.
Vpr Enhances Tumor Necrosis Factor Production by HIV-1-Infected T Cells
Authors: Roesch Ferdinand , Richard Léa , Rua Réjane , Porrot Françoise , Casartelli Nicoletta , Schwartz Olivier
Published: September 2015

The HIV-1 accessory protein Vpr displays different activities potentially impacting viral replication, including the arrest of the cell cycle in the G2phase and the stimulation of apoptosis and DNA damage response pathways. Vpr also modulates cytokine production by infected cells, but this property remains partly characterized. Here, we investigated the effect of Vpr on the production of the proinflammatory cytokine tumor necrosis factor (TNF). We report that Vpr significantly increases TNF secretion by infected lymphocytes.De novoproduction of Vpr is required for this effect. Vpr mutants known to be defective for G2cell cycle arrest induce lower levels of TNF secretion, suggesting a link between these two functions. Silencing experiments and the use of chemical inhibitors further implicated the cellular proteins DDB1 and TAK1 in this activity of Vpr. TNF secreted by HIV-1-infected cells triggers NF-κB activity in bystander cells and allows viral reactivation in a model of latently infected cells. Thus, the stimulation of the proinflammatory pathway by Vpr may impact HIV-1 replicationin vivo.

IMPORTANCEThe role of the HIV-1 accessory protein Vpr remains only partially characterized. This protein is important for viral pathogenesis in infected individuals but is dispensable for viral replication in most cell culture systems. Some of the functions described for Vpr remain controversial. In particular, it remains unclear whether Vpr promotes or instead prevents proinflammatory and antiviral immune responses. In this report, we show that Vpr promotes the release of TNF, a proinflammatory cytokine associated with rapid disease progression. Using Vpr mutants or inhibiting selected cellular genes, we show that the cellular proteins DDB1 and TAK1 are involved in the release of TNF by HIV-infected cells. This report provides novel insights into how Vpr manipulates TNF production and helps clarify the role of Vpr in innate immune responses and inflammation.
First and only symptom of undiagnosed diabetes mellitus: eruptive xanthoma
Authors: Solak Berna , Kara Rabia Oztas , Acikgoz Seyyid Bilal , Kosem Mustafa
Published: September 2015

Eruptive xanthoma (EX) is a very rare dermatosis mostly occurring due to high levels of serum triglycerides or uncontrolled diabetes mellitus. When EX is encountered, it is important to keep in mind that it could be a sign of severe underlying metabolic derangements. Early recognition can help avoid serious complications such as pancreatitis. After treatment of the underlying metabolic disorders, lesions mostly disappear without leaving scars. We present a case of a 55-year-old woman who presented with solely EX lesions and who was eventually diagnosed with diabetes mellitus and severe hypertriglyceridaemia.
Larval dispersal underlies demographically important intersystem connectivity in a Great Lakes yellow perch (Perca flavescens) population
Authors: Brodnik Reed M. , Fraker Michael E. , Anderson Eric J. , Carreon-Martinez Lucia , DeVanna Kristen M. , Heath Daniel D. , Reichert Julie M. , Roseman Edward F. , Ludsin Stuart A.
Published: September 2015

Ability to quantify connectivity among spawning subpopulations and their relative contribution of recruits to the broader population is a critical fisheries management need. By combining microsatellite and age information from larval yellow perch (Perca flavescens) collected in the Lake St. Clair – Detroit River system (SC-DRS) and western Lake Erie with a hydrodynamic backtracking approach, we quantified subpopulation structure, connectivity, and contributions of recruits to the juvenile stage in western Lake Erie during 2006–2007. After finding weak (yet stable) genetic structure between the SC-DRS and two western Lake Erie subpopulations, microsatellites also revealed measurable recruitment of SC-DRS larvae to the juvenile stage in western Lake Erie (17%–21% during 2006–2007). Consideration of precollection larval dispersal trajectories, using hydrodynamic backtracking, increased estimated contributions to 65% in 2006 and 57% in 2007. Our findings highlight the value of complementing subpopulation discrimination methods with hydrodynamic predictions of larval dispersal by revealing the SC-DRS as a source of recruits to western Lake Erie and also showing that connectivity through larval dispersal can affect the structure and dynamics of large lake fish populations.
THE SIZE OF FOREIGN EXCHANGE RESERVES AND LOCAL CURRENCY INTERNATIONALIZATION: CROSS-COUNTRY EVIDENCE
Authors: ZHANG ZHIWEN
Published: September 2015

This paper produces the first cross-country evidence on the relationship between the size of foreign exchange reserves and local currency internationalization using a sample of Switzerland, Japan and the UK. It finds that a high ratio of foreign exchange reserves to international reserves has a significant, but negative, impact on local currency internationalization during the period 1976–2009. After controlling for interest rate differential, different indicators for long-run depreciation and volatility of exchange rates, as well as the once-in-a-century global financial crisis of 2007–2009, the above conclusion still holds. Additionally, these results are robust to different methods (Pooled OLS and Pooled IV/2SLS) and measures of the scale of foreign exchange reserves. This study is informative for any policy decisions and will provide a strategic reference for the Chinese government as it optimizes the composition of its international reserves, promotes the process of renminbi (RMB) internationalization and becomes a major power through financial development.
The Lower Old Red Sandstone at Balmaha–Aberfoyle and its bearing on the nature of the Highland Boundary and Gualann Faults
Authors: Bluck B. J.
Published: September 2015

The final stages of the emplacement of the Dalradian block into Scotland are recorded in the Old Red Sandstone rocks that lie faulted against the main Dalradian belt. In the case of the Balmaha–Queen Elizabeth Forest sequence this involves the Gualann Fault, a splay of the Highland Boundary Fault, which transects
c
. 6.5 km of Lower Old Red Sandstone conglomerates and sandstones between Balmaha and Aberfoyle. A sequence of coarse conglomerates at Balmaha, near the top of the succession, derived from the SE, was deposited unconformably on the Highland Border Complex. This conglomerate has been studied in detail and the sequence is interpreted as an oblique section through an alluvial fan. Fitting the average dimensions of other alluvial fans to the unfolded cross-section suggests that it once extended some 5 km to the north, over the position of the Dalradian block. The conglomerate–sandstone sequence beneath was also deposited in alluvial fans that accumulated in a strike-slip, extensional basin in which units of conglomerate become progressively younger to the SW. Immediately NW of the Gualann Fault, in the Queen Elizabeth Forest, sub-horizontal red sandstones and breccias rest unconformably on the Highland Border Complex and were probably deposited beyond the reach of the coarse conglomerates.

It is suggested that the Gualann Fault was initially a very low-angle or flat thrust, which was rotated in mid-Devonian times during the development of the steep NW limb of the Strathmore Syncline. It brought sub-horizontal breccias and sandstones, originally deposited 10–15 km to the NW, well out of the influence of the conglomerates on the SE side of the fault, into juxtaposition with folded coarse conglomerates south of the Fault. As the Gualann Fault is a splay of the Highland Boundary Fault this implies that the latter may also be a thrust that brought the Dalradian block over the Highland Border rocks.

The whole sequence, from Balmaha to the Queen Elizabeth Forest, reflects the unroofing of an existing source of conglomerates to eventually erode their quartzite basement. The Highland Boundary Fault, although a fairly straight and prominent feature to the NE, becomes displaced and difficult to follow in the area to the SW where it is accompanied by many splays trending roughly N–S. The area, in and around the Firth of Clyde, has been regarded as the product of a locked phase of the fault movement that produced an extensional basin in Upper Old Red Sandstone times, but is also likely to have generated the more northern basins seen here.

There are a few records of conglomerates and associated rocks cut by the Highland Boundary Fault to the NE, suggesting that Old Red Sandstone basins extended well beyond the present Highland Boundary Fault. These basins may also have relevance to the timing of the incoming of the Dalradian block, absent from Scotland during earlier periods.
Placental ischemia-induced increases in brain water content and cerebrovascular permeability: role of TNF-α
Authors: Warrington Junie P. , Drummond Heather A. , Granger Joey P. , Ryan Michael J.
Published: September 2015

Cerebrovascular complications and increased risk of encephalopathies are characteristic of preeclampsia and contribute to 40% of preeclampsia/eclampsia-related deaths. Circulating tumor necrosis factor-α (TNF-α) is elevated in preeclamptic women, and infusion of TNF-α into pregnant rats mimics characteristics of preeclampsia. While this suggests that TNF-α has a mechanistic role to promote preeclampsia, the impact of TNF-α on the cerebral vasculature during pregnancy remains unclear. We tested the hypothesis that TNF-α contributes to cerebrovascular abnormalities during placental ischemia by first infusing TNF-α in pregnant rats (200 ng/day ip, from gestational day 14 to 19) at levels to mimic those reported in preeclamptic women. TNF-α increased mean arterial pressure (MAP, P < 0.05) and brain water content in the anterior cerebrum ( P < 0.05); however, TNF-α infusion had no effect on blood-brain barrier (BBB) permeability in the anterior cerebrum or posterior cerebrum. We then assessed the role of endogenous TNF-α in mediating these abnormalities in a model of placental ischemia induced by reducing uterine perfusion pressure followed by treatment with the soluble TNF-α receptor (etanercept, 0.8 mg/kg sc) on gestational day 18. Etanercept reduced placental ischemia-mediated increases in MAP, anterior brain water content ( P < 0.05), and BBB permeability (202 ± 44% in placental ischemic rats to 101 ± 28% of normal pregnant rats). Our results indicate that TNF-α mechanistically contributes to cerebral edema by increasing BBB permeability and is an underlying factor in the development of cerebrovascular abnormalities associated with preeclampsia complicated by placental ischemia.
The long noncoding RNA landscape in hypoxic and inflammatory renal epithelial injury
Authors: Lin Jennie , Zhang Xuan , Xue Chenyi , Zhang Hanrui , Shashaty Michael G. S. , Gosai Sager J. , Meyer Nuala , Grazioli Alison , Hinkle Christine , Caughey Jennifer , Li Wenjun , Susztak Katalin , Gregory Brian D. , Li Mingyao , Reilly Muredach P.
Published: September 2015

Long noncoding RNAs (lncRNAs) are emerging as key species-specific regulators of cellular and disease processes. To identify potential lncRNAs relevant to acute and chronic renal epithelial injury, we performed unbiased whole transcriptome profiling of human proximal tubular epithelial cells (PTECs) in hypoxic and inflammatory conditions. RNA sequencing revealed that the protein-coding and noncoding transcriptomic landscape differed between hypoxia-stimulated and cytokine-stimulated human PTECs. Hypoxia- and inflammation-modulated lncRNAs were prioritized for focused followup according to their degree of induction by these stress stimuli, their expression in human kidney tissue, and whether exposure of human PTECs to plasma of critically ill sepsis patients with acute kidney injury modulated their expression. For three lncRNAs (MIR210HG, linc-ATP13A4-8, and linc-KIAA1737-2) that fulfilled our criteria, we validated their expression patterns, examined their loci for conservation and synteny, and defined their associated epigenetic marks. The lncRNA landscape characterized here provides insights into novel transcriptomic variations in the renal epithelial cell response to hypoxic and inflammatory stress.
MiR-423-3p Enhances Cell Growth Through Inhibition of p21Cip1/Waf1 in Colorectal Cancer
Authors: Li Hong-tao , Zhang Hui , Chen Yong , Liu Xian-fu , Qian Jun
Published: September 2015

Background/Aims: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths globally, with many oncogenes and tumor suppressors involved. The miRNAs are small non-coding RNAs known to play a vital role in the pathogenesis of CRC. The miR-423-3p was reported to act as an oncogene; however, its role in CRC growth remains unknown. Methods: qPCR assay was used to detect miR-423-3p expression in CRC specimens. Cell proliferation assay and transwell assay were conducted to evaluate CRC cell proliferation and migration. Luciferase reporter assay was to identify the target gene of miR-423-3p. And tumorigenesis model was established to test the role of miR-423-3p in CRC development in vivo. Results: Here, we showed that miR-423-3p was significantly up regulated in CRC tissues and cells compared with normal tissues and cells. Overexpression of miR-423-3p promoted CRC cell proliferation via enhancing the G1/S transition phase of the cell cycle, while inhibition of miR-423-3p repressed cell growth. Further studies showed that p21Cip1/Waf1 mediated the function of miR-423-3p, and overexpression of p21Cip1/Waf1 reversed the augmented effect of miR-423-3p on cell proliferation. Importantly, all these data were validated in the tumorigenesis assay in vivo. Conclusions: In conclusion, our findings demonstrated a critical impact of miR-423-3p on CRC growth.
8-oxoG DNA Glycosylase-1 Inhibition Sensitizes Neuro-2a Cells to Oxidative DNA Base Damage Induced by 900 MHz Radiofrequency Electromagnetic Radiation
Authors: Wang Xiaoya , Liu Chuan , Ma Qinglong , Feng Wei , Yang Lingling , Lu Yonghui , Zhou Zhou , Yu Zhengping , Li Wei , Zhang Lei
Published: September 2015

Background/Aims: The purpose of this study was to explore the in vitro putative genotoxicity during exposure of Neuro-2a cells to radiofrequency electromagnetic fields (RF-EMFs) with or without silencing of 8-oxoG DNA glycosylase-1 (OGG1). Methods: Neuro-2a cells treated with or without OGG1 siRNA were exposed to 900 MHz Global System for Mobile Communication (GSM) Talk signals continuously at a specific absorption rate (SAR) of 0, 0.5, 1 or 2 W/kg for 24 h. DNA strand breakage and DNA base damage were measured by the alkaline comet assay and a modified comet assay using formamidopyrimidine DNA glycosylase (FPG), respectively. Reactive oxygen species (ROS) levels and cell viability were monitored using the non-fluorescent probe 2, 7-dichlorofluorescein diacetate (DCFH-DA) and CCK-8 assay. Results: Exposure to 900 MHz RF-EMFs with insufficient energy could induce oxidative DNA base damage in Neuro-2a cells. These increases were concomitant with similar increases in the generation of reactive oxygen species (ROS). Without OGG1 siRNA, 2 W/kg RF-EMFs induced oxidative DNA base damage in Neuro-2a cells. Interestingly, with OGG1 siRNA, RF-EMFs could cause DNA base damage in Neuro-2a cells as low as 1 W/kg. However, neither DNA strand breakage nor altered cell viability was observed. Conclusion: Even if further studies remain conducted we support the hypothesis that OGG1 is involved in the process of DNA base repair and may play a pivotal role in protecting DNA bases from RF-EMF induced oxidative damage.
Tripterine Treatment Improves Endothelial Progenitor Cell Function via Integrin-Linked Kinase
Authors: Lu Chenhui , Yu Xixiang , Zuo Keqiang , Zhang Xiaoping , Cao Chuanwu , Xu Jichong , Wang Shi , Tang Tao , Ye Meng , Pei Erli , Uzan Georges , Zhi Kangkang , Li Maoquan
Published: September 2015

Background/Aims: Atherosclerosis is associated with dysfunction of endothelial progenitor cells (EPCs). Tripterine, a chemical compound derived from the Chinese medicinal plant Tripterygium wilfordii Hook, displays anti-inflammatory properties in several animal models. We hypothesized that tripterine can improve EPC function and thus the efficiency of EPC transplantation. Methods and Results: Tripterine preconditioning (2.5 μM, 4 h) improved EPC proliferation, tube formation, migration, and adhesion, and reduced apoptosis in cells cultured in ox-LDL (200 µg/ml). Tripterine restored integrin-linked kinase (ILK) levels downregulated by ox-LDL in EPCs, suggesting the involvement of the ILK/Akt pathway. Small interfering RNA-mediated depletion of ILK and dominant-negative ILK transduction inhibited the phosphorylation of the ILK downstream signaling targets protein kinase B/Akt and glycogen synthase kinase 3-beta (GSK-3β), and reduced β-catenin and cyclin D1 expression. In atherosclerotic mice injected with green fluorescent protein-labeled EPCs to evaluate EPC function, tripterine decreased aortic lesions and plaque deposition, and injection of tripterine-treated EPCs restored ILK levels. Conclusion: The present results suggest that tripterine improves vascular function in atherosclerosis by enhancing EPC function through a mechanism involving the ILK signaling pathway.
Placental Growth Factor Promotes Metastases of Ovarian Cancer Through MiR-543-Regulated MMP7
Authors: Song Ning , Liu Hao , Ma Xiaoxin , Zhang Shulan
Published: September 2015

Background/Aims: Elucidation of the molecular mechanisms underlying ovarian cancer (OC) cell invasion and migration may provide important evidence for developing efficient therapy. Recently, Matrix metalloproteinase (MMP) has been shown to be regulated by vascular endothelial growth factor family members, especially placental growth factor (PLGF), as a potential mechanism underlying cancer invasion. Here, we studied the molecular relationship between PLGF and MMP7 in the OC. Methods: We examined the levels of PLGF and MMP7 in the resected OC specimens and compared to paired adjacent non-tumor ovarian tissue. We also examined the correlation between PLGF and MMP7. We modified PLGF levels in a human OC cell line, OVCAR3, and analyzed the effects on MMP7. Prediction of microRNA (miRNA) binding to 3'-UTR of MMP7 mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay using miR-543-modifed OC cells. The levels of miR-543 were examined in the OC specimens, and the correlation between miR-543 and PLGF or MMP7 was performed. Results: PLGF and MMP7 both significantly increased in the OC specimens, compared to paired adjacent non-tumor ovarian tissue. PLGF significantly increased MMP7 in the OC cells at protein level, but not at mRNA level. In OC cells, PLGF significantly decreased the levels of miR-543, which suppressed the translation of MMP7 mRNA via 3'-UTR binding. In OC specimen, miR-543 significantly decreased, compared to paired adjacent non-tumor ovarian tissue. An inverse correlation was detected between the levels of miR-543 and PLGF or MMP7 in the OC specimens. Conclusion: MiR-543 inhibits translation of MMP7 through binding to the 3'-UTR of MMP7 mRNA in OC. PLGF suppresses miR-543, which activates MMP7-mediated cancer invasion.
MicroRNA-140-5p Inhibits the Progression of Colorectal Cancer by Targeting VEGFA
Authors: Zhang Wenbo , Zou Chen , Pan Lei , Xu Ying , Qi Weidong , Ma Gui , Hou Yongzhong , Jiang Pengcheng
Published: September 2015

Background: microRNAs (miRNAs) are small non-coding RNAs and have been shown to play a crucial role in the colorectal cancer (CRC) tumorigenesis and progression. The aim of this study was to investigate the clinical significance and prognostic value of miR-140-5p in CRC. The exact functions and the underlying molecular mechanisms of miR-140-5p in CRC was further determined. Methods: miR-140-5p expression was detected in CRC samples, their adjacent nontumor tissues as well as CRC cell lines by RT-qPCR. Cell proliferation was detected using CCK-8, and cell invasion and migration were evaluated using Transwell assay. The direct regulation of VEGFA by miR-140-5p was identified using luciferase reporter assay. Results: miR-140-5p was significantly dowregulated in CRC tissues and cell lines. Downregulation of miR-140-5p was significantly correlated with advanced CRC stage and poorer overall survival. Both gain-of-function and loss of function studies demonstrated that miR-140-5p acted as a tumor suppressor by inhibiting cell proliferation, migration and invasion. Integrated analysis identified VEGFA as a direct and functional target gene of miR-140-5p. Silencing VEGFA by small interfering RNA (siRNA) resembled the phenotype resulting from ectopic miR-140-5p expression, while overexpression of VEGFA attenuated the effect of miR-140-5p on CRC cells. Conclusions: Our results suggested a tumor suppressive role of miR-140-5p in CRC tumorigenesis and progression by targeting VEGFA.
Inhibition of Autophagy by Chloroquine Stimulates Nitric Oxide Production and Protects Endothelial Function during Serum Deprivation
Authors: Pestana Cezar Rangel , Oishi Jorge Camargo , Salistre-Araújo Heloísa Sobreiro , Rodrigues Gerson Jhonatan
Published: September 2015

Background/Aims: Autophagy plays a fundamental role in cell survival under stress conditions such as nutrient deprivation. Decreased nitric oxide (NO) production, which may contribute to vascular dysfunction, is one of the consequences of autophagy in endothelial cells. The antimalarial drug chloroquine (CLQ) inhibits autophagy by blocking autophagosome formation and has been proposed as adjuvant chemotherapy in other diseases. Methods: Autophagy was induced by serum deprivation in Human Umbilical Vascular Endothelial Cells (HUVEC) as demonstrated by formation of Acidic Vesicular Organelles (AVOs), conversion of Microtubule-associated protein 1 light chain (LC3), and Sequestosome-1 (SQTM1/p62) degradation. Using endothelium-dependent vasorelaxation assays, intracellular NO production in an ex vivo rat aortic ring model pre-constricted with phenylephrine was estimated along with DAF-2 DA cell membrane-permeable NO sensitive fluorescent dye. Results: The inhibition of autophagy by CLQ restored NO levels, protected against superoxide generation and preserved morphology as well as proliferation of HUVEC under serum deprivation. Interestingly, the incubation of rat aortic rings with CLQ resulted in endothelium-dependent relaxation mediated by the increase of NO. Conclusion: These findings emphasize the importance of autophagy in endothelial function and demonstrate the potential use of autophagy inhibitors to protect vascular function during nutrient deprivation.
Treatment of Acute Hepatitis C Infection with Pegylated Interferon and Ribavirin in Patients Coinfected with Human Immunodeficiency Virus: A Systematic Review and Meta-Analysis
Authors: Zhang Bing , Nguyen Nghia H. , Yee Brittany E. , Yip Benjamin , Ayoub Walid S. , Lutchman Glen A. , Nguyen Mindie H.
Published: September 2015

Background/Aims: Of the 35 million human immunodeficiency virus (HIV)-positive patients worldwide, 10-40% are coinfected with chronic hepatitis C virus (HCV). Compared to HCV-monoinfected patients, those coinfected experience decreased spontaneous HCV clearance, accelerated liver fibrosis, and a decreased response to anti-HCV therapy. We conducted a meta-analysis to estimate the efficacy of treating acute HCV in HIV-positive patients with peginterferon and ribavirin combination therapy. Methods: Two authors independently searched MEDLINE and EMBASE (2014) for English articles, and reviewed bibliographies and abstracts from major liver and HIV conferences (2011-2013). Original studies featuring at least 10 treatment-naive, HIV-positive adults infected with acute HCV and treated with peginterferon and ribavirin were included. Analyses were calculated using a random-effects model. Heterogeneity was assessed using the Cochrane Q test (p < 0.05) and the I2 statistic (>50%). Results: From 12 studies (450 patients), the pooled sustained virological response (SVR) was 71.4% (95% CI 64.7-77.4; Q statistic = 22.20, p = 0.023, I2 = 50.44). The rapid virological response (RVR; 7 studies, 196 patients) was 47.4% (95% CI 40.6-54.7), and the early virological response (EVR; 9 studies, 283 patients) was 82.8% (95% CI 67.0-92.0). The probability of an SVR was 93.1% (95% CI 84.9-97.0) in those who obtained an RVR (6 studies, 82 patients) and 85.9% (95% CI 78.7-91.0) if an EVR (7 studies, 168 patients) was reached. Conclusion: Peginterferon with ribavirin is an effective option for treating acute HCV in HIV-positive patients, especially if they achieve an RVR or an EVR.
Review of Positive Psychology Outcome Measures for Chronic Illness, Traumatic Brain Injury and Older Adults: Adaptability in Dementia?
Authors: Stoner Charlotte R. , Orrell Martin , Spector Aimee
Published: September 2015

Background: Despite positive psychology being increasingly recognised as an important agent in well-being, there is a lack of standardised outcome measures for psychosocial dementia research. This review assessed positive psychology outcome measures using standardised criterion in populations that were identified as having shared characteristics. It aimed to identify robust measures that were suitable for potential adaption or use within a dementia population. Summary: The review identified 16 positive psychology outcome measures (and 8 further psychometric assessments of these) within the constructs of resilience, self-efficacy, religiousness/spirituality, life valuation, sense of coherence, autonomy, resourcefulness and a combined measure (CASP-19). Scale development studies were subject to a quality assessment, and most were found to be lacking information on reproducibility and responsiveness. Key Messages: A wide range of measures within the constructs of positive psychology was identified as having potential utility for psychosocial research within a dementia population. Examples included the CD-RISC, GSWB, SWLS, MPAQ, RSOA and CASP-19. It is recommended that such scales are further adapted or validated for people with dementia. Underreporting of appropriate psychometric analyses hampered this review, and it is recommended that future authors endeavour to report such analyses.
Beauty and the Biologic: Artistic Documentation of Scientific Breakthrough in Psoriasis
Authors: Maul Julia-Tatjana , Carraro Sabina , Stierlin Johanna , Geiges Michael L. , Navarini Alexander A.
Published: September 2015

The making of wax moulages was an exclusive and sought-after art that was primarily used for teaching, but also to document clinical and laboratory research during the first half of the 20th century. Applying the technique of moulage-making to document a case of psoriasis improvement for posterity, a moulage of the trunk of a patient with psoriasis vulgaris was taken prior to treatment with biologics - adalimumab, a TNF-α antagonist - and again 3 month after adalimumab was first given. Our modern moulage shows in the most realistic way the science-driven improvement of psoriasis achievable nowadays with biologics. However, the real clinical picture of the disease is shrouded by showing only one detail of the patient - by accident the one with the best clinical improvement. All available techniques to document skin disease have advantages and limitations and nothing beats seeing live patients.
Детермінантно-основана класифікація тяжкості гострого панкреатиту (Міжнародний мультидисциплінарний консиліум) (українська версія)
Authors: ЧУКЛІН С. М.
Published: September 2015

Визначення тяжкості гострого панкреатиту, прийняте в Атланті, вкоренилося в лексиконі панкреатологів, але не є оптимальним, тому що воно основане на емпіричному описі явищ, які лише пов’язані з тяжкістю.
Нестандартні ситуації при проведенні реконструктивно-відновних операційних втручань на стравоході
Authors: ШАПРИНСЬКИЙ В. О. , КРИВЕЦЬКИЙ В. Ф. , ШАПРИНСЬКИЙ Є. В.
Published: September 2015

Стаття присвячена вирішенню нестандартних ситуацій при виконанні реконструктивно-відновних операцій на стравоході. Проведено аналіз операційного лікування 160 хворих на стенозувальні захворювання стравоходу. Встановлено показання до кожного конкретного способу виконання езофагопластики. Запропоновано інфузійну терапію з метою профілактики ішемічних розладів у трансплантаті, пластику шлунком у модифікації клініки та пластику ілеоцекальним сегментом.
Морфологічні зміни мозкового та кіркового шару нирок у щурів з тяжкою та комбінованою травмою після корекції препаратами ксеношкіри
Authors: ПІДРУЧНА С. Р.
Published: September 2015

В експериментальних умовах моделювання тяжкої та комбінованої травми у щурів досліджено морфологічні зміни в тканині нирок після тижневого використання ліофілізованого субстрату ксеношкіри свині. У кірковій та мозковій зоні нирок піддослідних тварин з моделлю тяжкої травми мають місце гемодинамічні та запальні зміни, а комбінована травма супроводжується наявністю ще й структурних змін. Тижневе використання ліофілізованої ксеношкіри супроводжувалося частковим відновленням структурно-функціональних змін у тканині нирок.
Обгрунтування способу та об’єму резекції підшлункової залози при хронічному панкреатиті
Authors: КАНІКОВСЬКИЙ О. Є. , ПАВЛИК І. В.
Published: September 2015

Проаналізовано результати хірургічного лікування 181 хворого на хронічний панкреатит, ускладнений синдромом панкреатичної гіпертензії. У 128 виконано трансабдомінальну операційну корекцію панкреатичної гіпертензії. У 53 пацієнтів ми застосували малоінвазивні операційні втручання. Тканинний тиск опору підшлункової залози вище 200 мм рт. ст., наявність протокової гіпертензії, конкрементів підшлункової залози, розширення панкреатичної потоки за типом низки озер, на нашу думку, є показанням до широкого висічення паренхіми підшлункової залози з розкриттям проток третинного порядку (операція Фрея—Ізбіцького), яка дозволяє зменшити кількість рецидивів панкреатичної гіпертензії на 11,1 %.
Ефективність своєчасної та якісної догоспітальної електричної дефібриляції при раптовій зупинці кровообігу
Authors: ЛЯХОВИЧ Р. М. , ДЖУС М. Я. , ПРОЦЮК І. А.
Published: September 2015

У статті висвітлено основні види зупинки кровообігу при ЕКГ-моніторуванні потерпілих, які перебувають у стані клінічної смерті. Доведено ефективність своєчасної та якісної догоспітальної дефібриляції на тлі підтвердженої фібриляції шлуночків та шлуночкової тахікардії без пульсу.
Literture review: urban noise as an environmental pollutant.
Authors: Garcia Natasha Paltrinieri , Felisberto Rafael Florêncio Dias , Sanches Felipe Marquesini , Suzuki Danilo Henrique da Silva , Bento Ricardo Ferreira
Published: September 2015

Objetivo: Analisar os estudos sobre o ruído como poluição ambiental nos centros urbanos, com foco em suas fontes e os níveis sonoros na tentativa de entender se modelo urbano atual é adequado para a saúde individual e coletiva. Material e Métodos: BVS, Pubmed e Cochrane foram usados para pesquisar artigos originais de pesquisa relacionados com o ruído ambiente. Resultados: Este artigo de revisão analisa 19 estudos relacionados ao ruído como um poluente ambiental. Conclusão: Muitos estudos estão sendo conduzidos para quantificar o ruído urbano e seu potencial de perturbação causada na população, utilizando-se diferentes metodologias. Nosso trabalho demonstra que o ruído está presente no ambiente urbano e geralmente extrapola os atuais níveis tolerados pela lei, sendo um estressor em potencial. Portanto, a sua presença em várias atividades humanas, especialmente no trânsito, reflete um modelo de cidade atual que precisa ser repensado.Os resultados deste estudo podem ser úteis para o desenvolvimento de novas pesquisas sobre o ruído urbano e desenvolvimento de políticas públicas.
O uso do crack durante a gestao e suas repercusses biopsicossociais e espirituais
Authors: Reis Fernando Teixeira , Loureiro Rubens José
Published: September 2015

O objetivo deste estudo foi identificar as repercusses biopsicossociais e espirituais do uso do crack durante a gestao. Trata-se de um estudo descritivo com abordagem qualitativa onde foi feito um relato de caso de uma paciente de 33 anos, purpera e multpara que fez uso do crack at o sexto ms de gestao. Aps coleta e anlise dos dados, as desordens encontradas foram classificadas e inseridas em trs categorias temticas, que so: repercusses biolgicas; repercusses psicolgicas e repercusses sociais e espirituais. Os resultados deste estudo reforam a necessidade de estratgias holsticas tanto de abordagem quanto de interveno para esse segmento especifico da populao.
Probabilidades de internação psiquiátrica de pacientes de um ambulatório de saúde mental
Authors: Reis Leonardo Naves dos , Simplicio Julio Cesar Ribeiro , Gherardi-Donato Edilaine Cristina da Silva , Zanetti Ana Carolina Guidorizzi
Published: September 2015

Objetivou-se avaliar fatores de predio (diagnsticos e caractersticas sociodemogrficas) referentes  internao psiquitrica entre usurios ambulatoriais de sade mental. O estudo foi realizado a partir de dados secundrios, extrados dos pronturios e analisados por regresso logstica, para obteno da equao de predio da probabilidade de internao psiquitrica. Os diagnsticos que apresentaram significncia estatstica (p<0,05) foram transtorno afetivo bipolar, esquizofrenia, distrbios ansiosos e depresso, e os dois primeiros apresentaram associao de alta magnitude com a necessidade de internao. A idade foi inversamente proporcional  necessidade de internao. Os resultados encontrados podem incitar aes especficas substitutivas e de preveno  internao psiquitrica aos pacientes mais jovens com esquizofrenia e transtorno afetivo bipolar.
Risco de suicídio em dependentes de cocaína com episódio depressivo atual: sentimentos e vivências
Authors: Rocha Caroline Neubser , Silveira Danille Bernardi , Camargo Roger Santos , Fernandes Simone , Ferigolo Maristela , Barros Helena Maria Tannhauser
Published: September 2015

A morte por suicdio passou a ocupar a terceira posio entre as mais frequentes na populao de 15 a 44 anos de idade. A morte autoinfligida possui significados que requerem compreenso e ateno. O objetivo deste estudo foi conhecer as vivncias e os sentimentos dos usurios de cocana dentro da relao dependncia qumica e suicdio. Este  um estudo qualitativo, realizado de agosto de 2012 a fevereiro de 2013. Os 18 indivduos que preencheram os critrios para episdio depressivo responderam  entrevista semiestruturada para risco de suicdio, pelo Mini International Neuropsychiatric Interview. Na anlise dos contedos narrados, estabeleceram-se trs categorias: histria pregressa, tentativas de suicdio e depresso. Os resultados foram avaliados procurando refletir e compreender as vivncias expostas pelos usurios. Este estudo auxilia a compreenso dos significados das vivncias e sentimentos dos usurios de cocana/crack ante o risco de suicdio.
TRAF6-Mediated SM22α K21 Ubiquitination Promotes G6PD Activation and NADPH Production, Contributing to GSH Homeostasis and VSMC Survival In Vitro and In Vivo
Authors: Dong Li-Hua , Li Liang , Song Yu , Duan Zhi-Li , Sun Shao-Guang , Lin Yan-Ling , Miao Sui-Bing , Yin Ya-Juan , Shu Ya-Nan , Li Huan , Chen Peng , Zhao Li-Li , Han Mei
Published: September 2015

Rationale:

Vascular smooth muscle cell (VSMC) survival under stressful conditions is integral to promoting vascular repair, but facilitates plaque stability during the development of atherosclerosis. The cytoskeleton-associated smooth muscle (SM) 22α protein is involved in the regulation of VSMC phenotypes, whereas the pentose phosphate pathway plays an essential role in cell proliferation through the production of dihydronicotinamide adenine dinucleotide phosphate.

Objective:

To identify the relationship between dihydronicotinamide adenine dinucleotide phosphate production and SM22α activity in the development and progression of vascular diseases.

Methods and Results:

We showed that the expression and activity of glucose-6-phosphate dehydrogenase (G6PD) are promoted in platelet-derived growth factor (PDGF)-BB–induced proliferative VSMCs. PDGF–BB induced G6PD membrane translocation and activation in an SM22α K21 ubiquitination–dependent manner. Specifically, the ubiquitinated SM22α interacted with G6PD and mediated G6PD membrane translocation. Furthermore, we found that tumor necrosis factor receptor–associated factor (TRAF) 6 mediated SM22α K21 ubiquitination in a K63-linked manner on PDGF-BB stimulation. Knockdown of TRAF6 decreased the membrane translocation and activity of G6PD, in parallel with reduced SM22α K21 ubiquitination. Elevated levels of activated G6PD consequent to PDGF-BB induction led to increased dihydronicotinamide adenine dinucleotide phosphate generation through stimulation of the pentose phosphate pathway, which enhanced VSMC viability and reduced apoptosis in vivo and in vitro via glutathione homeostasis.

Conclusions:

We provide evidence that TRAF6-induced SM22α ubiquitination maintains VSMC survival through increased G6PD activity and dihydronicotinamide adenine dinucleotide phosphate production. The TRAF6–SM22α–G6PD pathway is a novel mechanism underlying the association between glucose metabolism and VSMC survival, which is beneficial for vascular repair after injury but facilitates atherosclerotic plaque stability.
Sensitivity to Referential Ambiguity in Discourse: The Role of Attention, Working Memory, and Verbal Ability
Authors: Boudewyn Megan A. , Long Debra L. , Traxler Matthew J. , Lesh Tyler A. , Dave Shruti , Mangun George R. , Carter Cameron S. , Swaab Tamara Y.
Published: September 2015

The establishment of reference is essential to language comprehension. The goal of this study was to examine listeners' sensitivity to referential ambiguity as a function of individual variation in attention, working memory capacity, and verbal ability. Participants listened to stories in which two entities were introduced that were either very similar (e.g., two oaks) or less similar (e.g., one oak and one elm). The manipulation rendered an anaphor in a subsequent sentence (e.g., oak) ambiguous or unambiguous. EEG was recorded as listeners comprehended the story, after which participants completed tasks to assess working memory, verbal ability, and the ability to use context in task performance. Power in the alpha and theta frequency bands when listeners received critical information about the discourse entities (e.g., oaks) was used to index attention and the involvement of the working memory system in processing the entities. These measures were then used to predict an ERP component that is sensitive to referential ambiguity, the Nref, which was recorded when listeners received the anaphor. Nref amplitude at the anaphor was predicted by alpha power during the earlier critical sentence: Individuals with increased alpha power in ambiguous compared with unambiguous stories were less sensitive to the anaphor's ambiguity. Verbal ability was also predictive of greater sensitivity to referential ambiguity. Finally, increased theta power in the ambiguous compared with unambiguous condition was associated with higher working-memory span. These results highlight the role of attention and working memory in referential processing during listening comprehension.