bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soluble CD163 and soluble mannose receptor predict survival and decompensation in patients with liver cirrhosis, and correlate with gut permeability and bacterial translocation
Authors: Rainer F. , Horvath A. , Sandahl T. D. , Leber B. , Schmerboeck B. , Blesl A. , Groselj‐Strele A. , Stauber R. E. , Fickert P. , Stiegler P. , Møller H. J. , Grønbæk H. , Stadlbauer V. 
Published: December 2017

SummaryBackgroundActivated hepatic macrophages play a key role in inflammation and fibrosis progression in chronic liver disease.AimTo assess the prognostic value of soluble (s)CD163 and mannose receptor (sMR) in cirrhotic patients and explore associations with markers of intestinal permeability (lactulose‐mannitol ratio, diamine oxidase), bacterial translocation (endotoxin, lipopolysaccharide‐binding protein) and markers of systemic immune activation (interleukin‐6, interleukin‐8, sCD14).MethodsWe prospectively investigated 101 cirrhotic patients (Child‐Pugh class A: n = 72, Child‐Pugh classes B and C: n = 29) and 31 healthy controls. Patients were observed for a median follow‐up of 37 months.ResultsMedian plasma levels of sCD163 and soluble mannose receptor were significantly elevated in cirrhotic patients (P < .001) and increased with disease severity (sCD163 in healthy controls = 1.3, Child‐Pugh class A = 4.2, Child‐Pugh classes B and C = 8.4 mg/L; sMR in healthy controls = 15.8, Child‐Pugh class A = 36.5, Child‐Pugh classes B and C = 66.3 μg/dL). A total of 21 patients died during the observation period. Patients with sCD163 levels above 5.9 mg/L showed significantly reduced survival (survival rate after 36 months: 71% versus 98%, P < .001). Patients with soluble mannose receptor levels above 45.5 μg/dL developed significantly more complications of cirrhosis within 12 months (73% versus 9%, P < .001). Furthermore, both variables correlated with the lactulose‐mannitol ratio, diamine oxidase, lipopolysaccharide and interleukin‐8.ConclusionOur data demonstrate the prognostic value of sCD163 in predicting long‐term survival in patients with liver cirrhosis and identify soluble mannose receptor as a prognostic marker for occurrence of cirrhosis‐associated complications. The correlation between gut barrier dysfunction and activation of macrophages points towards a link between them.
Sistem Kenaikan Pangkat dan Kepuasan Kerja : Satu Kajian Kes Ke atas Perkhidmatan Awam Persekutuan Di Malaysia
Authors: Chin Mohammad , Syed Khalid Wafa Syed Azizi Wafa , Hassan Ramraini Ali 
Published: December 2017

This research is a case study exploring the relationship between the promotion system and job satisfaction among federal civil servants in federal departments and agencies in Malaysia. The samples involved in this study are government officers serving in federal departments and agencies in the state of Sabah, Malaysia. A quantitative method was used in this study. A total of 700 questionnaires were distributed among federal civil servants in grades 41 to grades 54. A total of 420 questionnaires were returned but after screening only 380 questionnaires were found useable and analysed in the study. Questionnaires were distributed to respondents based on purposive sampling methods. A significant positive relationship was found between the promotion system and job satisfaction. This study will contribute knowledge through the empirical data obtained as well as gaining a better understanding of the relationship between the promotion system and the level of job satisfaction among federal public servants in Malaysia. From a practical perspective, the findings of this study can be used by policy makers, managers and researchers who are interested in improving the policy of human resource management within the public sector in Malaysia.
Cellular Stoichiometry of Methyl-Accepting Chemotaxis Proteins in Sinorhizobium meliloti
Authors: Zatakia Hardik M. , Arapov Timofey D. , Meier Veronika M. , Scharf Birgit E. 
Published: December 2017

ABSTRACT

The chemosensory system in
Sinorhizobium meliloti
has several important deviations from the widely studied enterobacterial paradigm. To better understand the differences between the two systems and how they are optimally tuned, we determined the cellular stoichiometry of the methyl-accepting chemotaxis proteins (MCPs) and the histidine kinase CheA in
S. meliloti
. Quantitative immunoblotting was used to determine the total amount of MCPs and CheA per cell in
S. meliloti
. The MCPs are present in the cell in high abundance (McpV), low abundance (IcpA, McpU, McpX, and McpW), and very low abundance (McpY and McpZ), whereas McpT was below the detection limit. The approximate cellular ratio of these three receptor groups is 300:30:1. The chemoreceptor-to-CheA ratio is 23.5:1, highly similar to that seen in
Bacillus subtilis
(23:1) and about 10 times higher than that in
Escherichia coli
(3.4:1). Different from
E. coli
, the high-abundance receptors in
S. meliloti
are lacking the carboxy-terminal NWETF pentapeptide that binds the CheR methyltransferase and CheB methylesterase. Using transcriptional
lacZ
fusions, we showed that chemoreceptors are positively controlled by the master regulators of motility, VisNR and Rem. In addition, FlbT, a class IIA transcriptional regulator of flagellins, also positively regulates the expression of most chemoreceptors except for McpT and McpY, identifying chemoreceptors as class III genes. Taken together, these results demonstrate that the chemosensory complex and the adaptation system in
S. meliloti
deviates significantly from the established enterobacterial paradigm but shares some similarities with
B. subtilis
.

IMPORTANCE
The symbiotic soil bacterium
Sinorhizobium meliloti
is of great agricultural importance because of its nitrogen-fixing properties, which enhances growth of its plant symbiont, alfalfa. Chemotaxis provides a competitive advantage for bacteria to sense their environment and interact with their eukaryotic hosts. For a better understanding of the role of chemotaxis in these processes, detailed knowledge on the regulation and composition of the chemosensory machinery is essential. Here, we show that chemoreceptor gene expression in
S. meliloti
is controlled through the main transcriptional regulators of motility. Chemoreceptor abundance is much lower in
S. meliloti
than in
Escherichia coli
and
Bacillus subtilis
. Moreover, the chemoreceptor-to-kinase CheA ratio is different from that of
E. coli
but similar to that of
B. subtilis
.
Deficiency of the IRE1α-Autophagy Axis Enhances the Antitumor Effects of the Oncolytic Virus M1
Authors: Li Kai , Hu Cheng , Xing Fan , Gao Mingshi , Liang Jiankai , Xiao Xiao , Cai Jing , Tan Yaqian , Hu Jun , Zhu Wenbo , Yin Wei , Li Yuan , Chen Wenli , Lu Bingzheng , Mai Jialuo , Qiu Pengxin , Su Xingwen , Yan Guangmei , Zhang Haipeng , Lin Yuan 
Published: December 2017

ABSTRACT

Oncolytic virotherapy is an emerging treatment modality that uses replication-competent viruses to destroy cancer cells. M1 is a naturally occurring alphavirus (
Togaviridae
) which shows potent oncolytic activities against many cancers. Accumulation of unfolded proteins during virus replication leads to a transcriptional/translational response known as the unfolded protein response (UPR), which might counteract the antitumor effect of the oncolytic virus. In this report, we show that either pharmacological or biological inhibition of IRE1α or PERK, but not ATF6, substantially increases the oncolytic effects of the M1 virus. Moreover, inhibition of IRE1α blocks M1 virus-induced autophagy, which restricts the antitumor effects of the M1 virus through degradation of viral protein, in glioma cells. In addition, IRE1α suppression significantly increases the oncolytic effect of M1 virus in an orthotopic glioma model. From a molecular pathology study, we found that IRE1α is expressed at lower levels in higher-grade gliomas, suggesting greater antitumor efficacy of the oncolytic virus M1. Taken together, these findings illustrate a defensive mechanism of glioma cells against the oncolytic virus M1 and identify possible approaches to enhance the oncolytic viral protein accumulation and the subsequent lysis of tumor cells.

IMPORTANCE
Although oncolytic virotherapy is showing great promise in clinical applications, not all patients are benefiting. Identifying inhibitory signals in refractory cancer cells for each oncolytic virus would provide a good chance to increase the therapeutic effect. Here we describe that infection with the oncolytic virus M1 triggers the unfolded protein response (UPR) and subsequent autophagy, while blocking the UPR-autophagy axis significantly potentiates the antitumor efficacy of M1
in vitro
and
in vivo
. A survey of cancer tissue banks revealed that IRE1α, a key element in the UPR pathway, is commonly downregulated in higher-grade human gliomas, suggesting favorable prospects for the application of M1. Our work provides a potential predictor and target for enhancement of the therapeutic effectiveness of the M1 virus. We predict that the mechanism-based combination therapy will promote cancer virotherapy in the future.
Identification of a Conserved Interface of Human Immunodeficiency Virus Type 1 and Feline Immunodeficiency Virus Vifs with Cullin 5
Authors: Gu Qinyong , Zhang Zeli , Gertzen Christoph G. W. , Häussinger Dieter , Gohlke Holger , Münk Carsten 
Published: December 2017

ABSTRACT

Members of the apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC3 [A3]) family of DNA cytidine deaminases are intrinsic restriction factors against retroviruses. In felids such as the domestic cat (
Felis catus
), the A3 genes encode the A3Z2, A3Z3, and A3Z2Z3 antiviral cytidine deaminases. Only A3Z3 and A3Z2Z3 inhibit viral infectivity factor (Vif)-deficient feline immunodeficiency virus (FIV). The FIV Vif protein interacts with Cullin (CUL), Elongin B (ELOB), and Elongin C (ELOC) to form an E3 ubiquitination complex to induce the degradation of feline A3s. However, the functional domains in FIV Vif for the interaction with Cullin are poorly understood. Here, we found that the expression of dominant negative CUL5 prevented the degradation of feline A3s by FIV Vif, while dominant negative CUL2 had no influence on the degradation of A3. In coimmunoprecipitation assays, FIV Vif bound to CUL5 but not CUL2. To identify the CUL5 interaction site in FIV Vif, the conserved amino acids from positions 47 to 160 of FIV Vif were mutated, but these mutations did not impair the binding of Vif to CUL5. By focusing on a potential zinc-binding motif (K175-C161-C184-C187) of FIV Vif, we found a conserved hydrophobic region (174IR175) that is important for the CUL5 interaction. Mutation of this region also impaired the FIV Vif-induced degradation of feline A3s. Based on a structural model of the FIV Vif-CUL5 interaction, the 52LW53 region in CUL5 was identified as mediating binding to FIV Vif. By comparing our results to the human immunodeficiency virus type 1 (HIV-1) Vif-CUL5 interaction surface (120IR121, a hydrophobic region that is localized in the zinc-binding motif), we suggest that the CUL5 interaction surface in the diverse HIV-1 and FIV Vifs is evolutionarily conserved, indicating a strong structural constraint. However, the FIV Vif-CUL5 interaction is zinc independent, which contrasts with the zinc dependence of HIV-1 Vif.

IMPORTANCE
Feline immunodeficiency virus (FIV), which is similar to human immunodeficiency virus type 1 (HIV-1), replicates in its natural host in T cells and macrophages that express the antiviral restriction factor APOBEC3 (A3). To escape A3s, FIV and HIV induce the degradation of these proteins by building a ubiquitin ligase complex using the viral protein Vif to connect to cellular proteins, including Cullin 5. Here, we identified the protein residues that regulate this interaction in FIV Vif and Cullin 5. While our structural model suggests that the diverse FIV and HIV-1 Vifs use conserved residues for Cullin 5 binding, FIV Vif binds Cullin 5 independently of zinc, in contrast to HIV-1 Vif.
The Human Papillomavirus E6 Oncoprotein Targets USP15 and TRIM25 To Suppress RIG-I-Mediated Innate Immune Signaling
Authors: Chiang Cindy , Pauli Eva-Katharina , Biryukov Jennifer , Feister Katharina F. , Meng Melissa , White Elizabeth A. , Münger Karl , Howley Peter M. , Meyers Craig , Gack Michaela U. 
Published: December 2017

ABSTRACT
Retinoic acid-inducible gene I (RIG-I) is a key pattern recognition receptor that senses viral RNA and interacts with the mitochondrial adaptor MAVS, triggering a signaling cascade that results in the production of type I interferons (IFNs). This signaling axis is initiated by K63-linked ubiquitination of RIG-I mediated by the E3 ubiquitin ligase TRIM25, which promotes the interaction of RIG-I with MAVS. USP15 was recently identified as an upstream regulator of TRIM25, stabilizing the enzyme through removal of degradative K48-linked polyubiquitin, ultimately promoting RIG-I-dependent cytokine responses. Here, we show that the E6 oncoprotein of human papillomavirus type 16 (HPV16) as well as of other HPV types form a complex with TRIM25 and USP15 in human cells. In the presence of E6, the K48-linked ubiquitination of TRIM25 was markedly increased, and in line with this, TRIM25 degradation was enhanced. Our results further showed that E6 inhibited the TRIM25-mediated K63-linked ubiquitination of RIG-I and its CARD-dependent interaction with MAVS. HPV16 E6, but not E7, suppressed the RIG-I-mediated induction of IFN-β, chemokines, and IFN-stimulated genes (ISGs). Finally, CRISPR-Cas9 gene targeting in human keratinocytes showed that the TRIM25-RIG-I-MAVS triad is important for eliciting an antiviral immune response to HPV16 infection. Our study thus identifies a novel immune escape mechanism that is conserved among different HPV strains and further indicates that the RIG-I signaling pathway plays an important role in the innate immune response to HPV infection.

IMPORTANCE
Persistent infection and tumorigenesis by HPVs are known to require viral manipulation of a variety of cellular processes, including those involved in innate immune responses. Here, we show that the HPV E6 oncoprotein antagonizes the activation of the cytoplasmic innate immune sensor RIG-I by targeting its upstream regulatory enzymes TRIM25 and USP15. We further show that the RIG-I signaling cascade is important for an antiviral innate immune response to HPV16 infection, providing evidence that RIG-I, whose role in sensing RNA virus infections has been well characterized, also plays a crucial role in the antiviral host response to small DNA viruses of the
Papillomaviridae
family.
Asian Elephant T Cell Responses to Elephant Endotheliotropic Herpesvirus
Authors: Fuery Angela , Leen Ann M. , Peng Rongsheng , Wong Matthew C. , Liu Hao , Ling Paul D. 
Published: December 2017

ABSTRACT

Elephant endotheliotropic herpesvirus (EEHV) can cause lethal hemorrhagic disease in juvenile Asian elephants, an endangered species. One hypothesis to explain this vulnerability of some juvenile elephants is that they fail to mount an effective T cell response to the virus. To our knowledge, there have been no studies of Asian elephant T cell responses to EEHV. To address this deficiency, we validated the gamma interferon (IFN-γ) enzyme-linked immunospot assay for tracking antigen-directed T cell activity by monitoring rabies-specific responses in vaccinated elephants. In addition, we generated monoclonal antibodies to Asian elephant CD4 and CD8 to facilitate phenotypic T cell profiling. Using these tools, we screened healthy elephants with a history of EEHV infection for reactivity against nine EEHV proteins whose counterparts in other herpesviruses are known to induce T cell responses in their natural hosts. We identified glycoprotein B (gB) and the putative regulatory protein E40 as the most immunogenic T cell targets (IFN-γ responses in five of seven elephants), followed by the major capsid protein (IFN-γ responses in three of seven elephants). We also observed that IFN-γ responses were largely from CD4
+
T cells. We detected no activity against the predicted major immediate early (E44) and large tegument (E34) proteins, both immunodominant T cell targets in humans latently infected with cytomegalovirus. These studies identified EEHV-specific T cells in Asian elephants for the first time, lending insight into the T cell priming that might be required to protect against EEHV disease, and will guide the design of effective vaccine strategies.

IMPORTANCE
Endangered Asian elephants are facing many threats, including lethal hemorrhagic disease from elephant endotheliotropic herpesvirus (EEHV). EEHV usually establishes chronic, benign infections in mature Asian elephants but can be lethal to juvenile elephants in captivity and the wild. It is the leading cause of death in captive Asian elephants in North America and Europe. Despite the availability of sensitive tests and protocols for treating EEHV-associated illness, these measures are not always effective. The best line of defense would be a preventative vaccine. We interrogated normal healthy elephants previously infected with EEHV for T cell responses to nine EEHV proteins predicted to induce cellular immune responses. Three proteins elicited IFN-γ responses, suggesting their potential usefulness as vaccine candidates. Our work is the first to describe T cell responses to a member of the proposed fourth subfamily of mammalian herpesviruses, the
Deltaherpesvirinae
, within a host species in the clade Afrotheria. An EEHV vaccine would greatly contribute to the health care of Asian and African elephants that are also susceptible to this disease.
Albumin improves stability and longevity of perfluorochemical-perfused hearts
Authors: Segel L. D. , Ensunsa J. L. 
Published: December 2017

Page H1107: L. D. Segel and J. L. Ensunsa. “Albumin improves stability and longevity of perfluorochemical-perfused hearts.” The stroke work data and CVR units in Table 2 should appear as follows. (See PDF)
Characterization of pulmonary arterial input impedance with lumped parameter models
Authors: Grant B. J. B. , Paradowski L. J. 
Published: December 2017

Page H587: B. J. B. Grant and L. J. Paradowski. “Characterization of pulmonary arterial input impedance with lumped parameter models.” Equations 5 and 6 should appear as the following. (See PDF)
Rate of oxygen loss from arterioles is an order of magnitude higher than expected
Authors: Popel Aleksander S. , Pittman Roland N. , Ellsworth Mary L. 
Published: December 2017

Pages H921–H924: Aleksander S. Popel, Roland N. Pittman, and Mary L. Ellsworth. “Rate of oxygen loss from arterioles is an order of magnitude higher than expected.“ Page H922: Table 1 should appear as the following: (See PDF)
Myoglobin function and energy metabolism of isolated cardiac myocytes: effect of sodium nitrite
Authors: Doeller Jeannette E. , Wittenberg Beatrice A. 
Published: December 2017

Pages H53–H62, 1991: Jeannette E. Doeller and Beatrice A. Wittenberg. “Myoglobin function and energy metabolism of isolated cardiac myocytes: effect of sodium nitrite.” We regret that the following references were inadvertently dropped during printing. 26. Wittenberg, B. A., J. E. Doeller, R. K. Gupta, and R. L. White. Measurement of sarcolemmal permeability and intracellular pH, free magnesium, and high energy phosphates of isolated heart cells. In: Biology of Isolated Adult Cardiac Myocytes, edited by W. A. Clark, R. S. Decker, and T. K. Borg. New York: Elsevier, 1988, p. 188–130. 27. Wittenberg, B. A., and T. F. Robinson. Oxygen requirements, morphology, cell coat and membrane permeability of calcium tolerant myocytes from hearts of adult rats. Cell Tissue Res. 216: 231–251, 1981. 28. Wittenberg, B. A., and J. B. Wittenberg. Oxygen pressure gradients in isolated cardiac myocytes. J. Biol. Chem. 260: 6548–6554, 1985. 29. Wittenberg, B. A., and J. B. Wittenberg. Myoglobin-mediated oxygen delivery to mitochondria of isolated cardiac myocytes. Proc. Natl. Acad. Sci. USA 84: 7503–7607, 1987. 30. Wittenberg, B. A., and J. B. Wittenberg. Transport of oxygen in muscle. Annu. Rev. Physiol. 51: 857–878, 1989. 31. Wittenberg, B. A., J. B. Wittenberg, and P. R. B. Caldwell. Role of myoglobin in the oxygen supply to red skeletal muscle. J. Biol. Chem. 250: 9038–9043, 1975. 32. Wittenberg, J. B., and B. A. Wittenberg. Preparation of myoglobins. In: Methods of Enzymology, edited by S. P. Colowick and N. O. Kaplan. New York: Academic, 1981, vol. 76, p. 29–42. 33. Wittenberg, J. B., and B. A. Wittenberg. Mechanisms of cytoplasmic hemoglobin and myoglobin function. Annu. Reu. Biophys. Biophys. Chem. 19: 217–241, 1990.
Phenotypic changes of human aortic smooth muscle cells during development and in the adult vessel
Authors: Glukhova Marina A. , Frid Maria G. , Koteliansky Victor E. 
Published: December 2017

To characterize phenotypic expression of human aortic smooth muscle cells (SMCs), we have studied the content of cytodifferentiation-related cytoskeletal proteins, and of fibronectin (FN) variants in the samples of media from the fetal, child, and adult aorta and in the subendothelial intima of the normal and atherosclerotic aorta. Mature SMCs from the adult aortic media contained high amounts of -SM-actin, SM-myosin heavy chains, meta-vinculin, and 150 kDa caldesmon. Cytokeratin 8 and extra domain-containing variants of FN (A-FN and B-FN) were not found in these cells. The SMCs from the aortic media of 10-wk-old fetus contained low amounts of the SM markers, expressed cytokeratin 8, A-FN, and B-FN. In 25-wk-old fetus, as well as in 2- and 6-mo-old child, aortic medial SMCs expressed an intermediate phenotype, and only in 18-mo-old child were the cells found to be similar to those from adult media. SMCs from the normal adult subendothelial intima contained reduced amounts of meta-vinculin and of 150 kDa caldesmon, and they expressed A-FN. In addition, the SMCs from atherosclerotic fibrous plaque contained a decreased proportion of -SM-actin and of SM-myosin heavy chains, whereas cytokeratin 8 was found. Therefore we conclude that the SMCs from intimal thickenings appear to express a less mature phenotype than that of the medial cells from adult aorta. Rather, these SMCs contain reduced amounts of the SM markers and express proteins typical of the fetal SMC phenotype, A-FN and cytokeratin 8. cytodifferentiation; cytoskeletal proteins; fibronectin variant forms
Free radical metabolites in myocardium during ischemia and reperfusion
Authors: Ruuge Enno K. , Ledenev Alexander N. , Lakomkin Vladimir L. , Konstantinov Alexander A. , Ksenzenko Marina Yu. 
Published: December 2017

Low-temperature electron paramagnetic resonance (EPR) spectroscopy and spin traps were used to measure paramagnetic species generation in rat hearts and isolated mitochondria. The hearts were freeze-clamped at 77 K during control perfusion by the Langendorff procedure, after 20–30 min of normothermic ischemia or 10–30 s of reperfusion with oxygenated perfusate. All EPR spectra measured at 4.5–50 K exhibited signals of both mitochondrial free radical centers and FeS proteins. The analysis of spectral parameters measured at 243 K showed that free radicals in heart tissue were semiquinones of coenzyme Q10 and flavins. The appearance of a typical “doublet” signal at g = 1.99 in low-temperature spectra indicated that a part of ubisemiquinones formed a complex with a high potential FeS protein of succinate dehydrogenase. Ischemia decreased the free radical species in myocardium 50%; the initiation of reflow of perfusate resulted in quick increase of the EPR signal. Mitochondria isolated from hearts during control perfusion and after 20–30 min of ischemia were able to produce superoxide radicals in both the NADH-coenzyme Q10 reductase and the bc1 segments of the respiratory chain. The rate of oxyradical generation was significantly higher in mitochondria isolated from ischemic heart. electron paramagnetic resonance; oxygen paradox; oxyradicals; rat heart; semiquinones