bluuebunny/crossref_metadata_2025_split huggingface dataset:
High, Broad, Polyfunctional, and Durable T Cell Immune Responses Induced in Mice by a Novel Hepatitis C Virus (HCV) Vaccine Candidate (MVA-HCV) Based on Modified Vaccinia Virus Ankara Expressing the Nearly Full-Length HCV Genome
Authors: Gómez Carmen E. , Perdiguero Beatriz , Cepeda María Victoria , Mingorance Lidia , García-Arriaza Juan , Vandermeeren Andrea , Sorzano Carlos Óscar S. , Esteban Mariano 
Published: April 2013

ABSTRACT

A major goal in the control of hepatitis C infection is the development of a vaccine. Here, we have developed a novel HCV vaccine candidate based on the highly attenuated poxvirus vector MVA (referred to as MVA-HCV) expressing the nearly full-length (7.9-kbp) HCV sequence, with the aim to target almost all of the T and B cell determinants described for HCV. In infected cells, MVA-HCV produces a polyprotein that is subsequently processed into the structural and nonstructural HCV proteins, triggering the cytoplasmic accumulation of dense membrane aggregates. In both C57BL/6 and transgenic HLA-A2-vaccinated mice, MVA-HCV induced high, broad, polyfunctional, and long-lasting HCV-specific T cell immune responses. The vaccine-induced T cell response was mainly mediated by CD8 T cells; however, although lower in magnitude, the CD4
+
T cells were highly polyfunctional. In homologous protocol (MVA-HCV/MVA-HCV) the main CD8
+
T cell target was p7+NS2, whereas in heterologous combination (DNA-HCV/MVA-HCV) the main target was NS3. Antigenic responses were also detected against other HCV proteins (Core, E1-E2, and NS4), but the magnitude of the responses was dependent on the protocol used. The majority of the HCV-induced CD8
+
T cells were triple or quadruple cytokine producers. The MVA-HCV vaccine induced memory CD8
+
T cell responses with an effector memory phenotype. Overall, our data showed that MVA-HCV induced broad, highly polyfunctional, and durable T cell responses of a magnitude and quality that might be associated with protective immunity and open the path for future considerations of MVA-HCV as a prophylactic and/or therapeutic vaccine candidate against HCV.
A Case for the Ancient Origin of Coronaviruses
Authors: Wertheim Joel O. , Chu Daniel K. W. , Peiris Joseph S. M. , Kosakovsky Pond Sergei L. , Poon Leo L. M. 
Published: April 2013

ABSTRACTCoronaviruses are found in a diverse array of bat and bird species, which are believed to act as natural hosts. Molecular clock dating analyses of coronaviruses suggest that the most recent common ancestor of these viruses existed around 10,000 years ago. This relatively young age is in sharp contrast to the ancient evolutionary history of their putative natural hosts, which began diversifying tens of millions of years ago. Here, we attempted to resolve this discrepancy by applying more realistic evolutionary models that have previously revealed the ancient evolutionary history of other RNA viruses. By explicitly modeling variation in the strength of natural selection over time and thereby improving the modeling of substitution saturation, we found that the time to the most recent ancestor common for all coronaviruses is likely far greater (millions of years) than the previously inferred range.
Canine Distemper Virus Associated with a Lethal Outbreak in Monkeys Can Readily Adapt To Use Human Receptors
Authors: Sakai Kouji , Yoshikawa Tomoki , Seki Fumio , Fukushi Shuetsu , Tahara Maino , Nagata Noriyo , Ami Yasushi , Mizutani Tetsuya , Kurane Ichiro , Yamaguchi Ryoji , Hasegawa Hideki , Saijo Masayuki , Komase Katsuhiro , Morikawa Shigeru , Takeda Makoto 
Published: April 2013

ABSTRACT
A canine distemper virus (CDV) strain, CYN07-dV, associated with a lethal outbreak in monkeys, used human signaling lymphocyte activation molecule as a receptor only poorly but readily adapted to use it following a P541S substitution in the hemagglutinin protein. Since CYN07-dV had an intrinsic ability to use human nectin-4, the adapted virus became able to use both human immune and epithelial cell receptors, as well as monkey and canine ones, suggesting that CDV can potentially infect humans.
Sodium Taurocholate Cotransporting Polypeptide Mediates Woolly Monkey Hepatitis B Virus Infection of Tupaia Hepatocytes
Authors: Zhong Guocai , Yan Huan , Wang Haimin , He Wenhui , Jing Zhiyi , Qi Yonghe , Fu Liran , Gao Zhenchao , Huang Yi , Xu Guangwei , Feng Xiaofeng , Sui Jianhua , Li Wenhui 
Published: April 2013

ABSTRACT

Primary
Tupaia
hepatocytes (PTHs) are susceptible to woolly monkey hepatitis B virus (WMHBV) infection, but the identity of the cellular receptor(s) mediating WMHBV infection of PTHs remains unclear. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was identified as a functional receptor for human hepatitis B virus (HBV) infection of primary human and
Tupaia
hepatocytes. In this study, a synthetic pre-S1 peptide from WMHBV was found to bind specifically to cells expressing
Tupaia
NTCP (tsNTCP) and it efficiently blocked WMHBV entry into PTHs; silencing of tsNTCP in PTHs significantly inhibited WMHBV infection. Ectopic expression of tsNTCP rendered HepG2 cells susceptible to WMHBV infection. These data demonstrate that tsNTCP is a functional receptor for WMHBV infection of PTHs. The result also indicates that NTCP's orthologs likely act as a common cellular receptor for all known primate hepadnaviruses.
Serum 25-hydroxyvitamin D3and the risk of pneumonia in an ageing general population
Authors: Aregbesola Alex , Voutilainen Sari , Nurmi Tarja , Virtanen Jyrki K , Ronkainen Kimmo , Tuomainen Tomi-Pekka 
Published: April 2013

BackgroundVitamin D has been suggested to have a role in infection defence and on the immune system. We therefore investigated the effect of serum 25-hydroxyvitamin D3(25(OH)D3) on the risk of incident hospitalised pneumonia in an ageing general population in eastern Finland.MethodsThe study population included 723 men and 698 women aged 53–73 years from the prospective population-based Kuopio Ischemic Heart Disease Risk Factor study who were free of pneumonia, other pulmonary diseases and cancer at baseline in 1998–2001. Incident pneumonia episodes leading to hospitalisation were collected by record linkage to the hospital discharge register. The serum vitamin D status was assayed as 25(OH)D3concentration. Cox proportional hazards regression models were used to analyse the effect of serum 25(OH)D3on the risk of incident pneumonia.ResultsThe mean (SD) serum 25(OH)D3concentration of the study population was 43.5 (17.8) nmol/l. 73 subjects had at least one hospitalisation episode due to pneumonia during an average follow-up of 9.8 years. After multivariable adjustments, the subjects in the lowest serum 25(OH)D3tertile had a 2.6-fold (95% CI 1.4 to 5.0, p trend across tertiles=0.005) higher risk of developing pneumonia compared with the subjects in the highest tertile. This significant result remained even after adjustment for the determinants of serum 25-hydroxyvitamin D3.ConclusionsThese data suggest an inverse effect of serum 25(OH)D3concentration on the risk of incident pneumonia in the general ageing population.
Proximal myopathy: diagnostic approach and initial management
Authors: Suresh Ernest , Wimalaratna Sunil 
Published: April 2013

Abstract
Proximal myopathy presents as symmetrical weakness of proximal upper and/or lower limbs. There is a broad range of underlying causes including drugs, alcohol, thyroid disease, osteomalacia, idiopathic inflammatory myopathies (IIM), hereditary myopathies, malignancy, infections and sarcoidosis. Clinical assessment should aim to distinguish proximal myopathy from other conditions that can present similarly, identify patients who need prompt attention, like those with cardiac, respiratory or pharyngeal muscle involvement, and determine underlying cause of myopathy. Initial evaluation should include simple tests, like creatine kinase, thyroid function and (25)OH vitamin D levels, but further evaluation including neurophysiological studies, muscle imaging and muscle biopsy should be considered for patients in whom no toxic, metabolic or endocrine cause is found, and in those with clinical features suggestive of inflammatory or hereditary myopathy. Additionally, screening for malignancy and testing for anti-Jo1 antibody is indicated for selected patients with IIM. Management depends on underlying cause, and includes measures, such as removal of offending agent, correction of endocrine or metabolic problem, corticosteroids and immunosuppressive therapy for IIM, and physical therapy, rehabilitation and genetic counselling for muscular dystrophies.
Cf.Wortmaniafrom the early Paleocene of Montana and an evaluation of the fossil record of the initial diversification of the Taeniodonta (Mammalia)
Authors: Clemens William A. 
Published: April 2013

The Garbani Channel deposits, part of the Tullock Formation exposed in northeastern Montana, have yielded a large sample of vertebrates that probably lived during the Puercan 3 North American Land Mammal Age (NALMA). Four fossils in this sample — three isolated teeth and a medial phalanx — document the presence of a stylinodontid taeniodont, cf. Wortmania. Discovery of cf. Wortmania in the Tullock Formation extends the documented range of taeniodonts during Puercan 3 approximately 500 miles (800 km) northward from the San Juan Basin, New Mexico. Evaluation of the oldest records of taeniodonts, from the Lancian, Puercan, and Torrejonian NALMAs, highlights biases warranting future research. Recent phylogenetic analyses that resulted in numerous ghost lineages indicate that the available fossil record is far from complete. They open the possibility that the origin and initial radiation of taeniodonts occurred in areas yet to be sampled and their first occurrences might reflect immigration of invasive species. The available fossil record of taeniodonts is biased with significantly more abundant and complete specimens discovered in the San Juan Basin than at localities to the north. This bias is also apparent in the available samples of two other lineages of large Puercan mammals, the multituberculate Taeniolabis and the “triisodontid” Eoconodon. Where they occur, taeniodonts are relatively rare members of any local fauna. Is their rarity a product of an ecological bias or a reflection of decreasing population size related to increasing body size?
Resveratrol Induces Differentiation Markers Expression in Anaplastic Thyroid Carcinoma via Activation of Notch1 Signaling and Suppresses Cell Growth
Authors: Yu Xiao-Min , Jaskula-Sztul Renata , Ahmed Kamal , Harrison April D. , Kunnimalaiyaan Muthusamy , Chen Herbert 
Published: April 2013

Abstract
Anaplastic thyroid carcinoma (ATC) is an extremely aggressive malignancy with undifferentiated features, for which conventional treatments, including radioactive iodine ablation, are usually not effective. Recent evidence suggests that the Notch1 pathway is important in the regulation of thyroid cancer cell growth and expression of thyrocyte differentiation markers. However, drug development targeting Notch1 signaling in ATC remains largely underexplored. Previously, we have identified resveratrol out of over 7,000 compounds as the most potent Notch pathway activator using a high-throughput screening method. In this study, we showed that resveratrol treatment (10–50 μmol/L) suppressed ATC cell growth in a dose-dependent manner for both HTh7 and 8505C cell lines via S-phase cell-cycle arrest and apoptosis. Resveratrol induced functional Notch1 protein expression and activated the pathway by transcriptional regulation. In addition, the expression of thyroid-specific genes including TTF1, TTF2, Pax8, and sodium iodide symporter (NIS) was upregulated in both ATC cell lines with resveratrol treatment. Notch1 siRNA interference totally abrogated the induction of TTF1 and Pax8 but not of TTF2. Moreover, Notch1 silencing by siRNA decreased resveratrol-induced NIS expression. In summary, our data indicate that resveratrol inhibits cell growth and enhances redifferentiation in ATC cells dependent upon the activation of Notch1 signaling. These findings provide the first documentation for the role of resveratrol in ATC redifferentiation, suggesting that activation of Notch1 signaling could be a potential therapeutic strategy for patients with ATC and thus warrants further clinical investigation. Mol Cancer Ther; 12(7); 1276–87. ©2013 AACR.
Interactions between SAP155 and FUSE-Binding Protein-Interacting Repressor Bridges c-Myc and P27Kip1 Expression
Authors: Matsushita Kazuyuki , Tamura Mai , Tanaka Nobuko , Tomonaga Takeshi , Matsubara Hisahiro , Shimada Hideaki , Levens David , He Liusheng , Liu Juhong , Yoshida Minoru , Nomura Fumio 
Published: April 2013

Abstract
Oncogenic c-Myc plays a critical role in cell proliferation, apoptosis, and tumorigenesis, but the precise mechanisms that drive this activity remain largely unknown. P27Kip1 (CDKN1B) arrests cells in G1, and SAP155 (SF3B1), a subunit of the essential splicing factor 3b (SF3b) subcomplex of the spliceosome, is required for proper P27 pre-mRNA splicing. FUSE-binding protein-interacting repressor (FIR), a splicing variant of PUF60 lacking exon5, is a c-Myc transcriptional target that suppresses the DNA helicase p89 (ERCC3) and is alternatively spliced in colorectal cancer lacking the transcriptional repression domain within exon 2 (FIRΔexon2). FIR and FIRΔexon2 form a homo- or hetero-dimer that complexes with SAP155. Our study indicates that the FIR/FIRΔexon2/SAP155 interaction bridges c-Myc and P27 expression. Knockdown of FIR/FIRΔexon2 or SAP155 reduced p27 expression, inhibited its pre-mRNA splicing, and reduced CDK2/Cyclin E expression. Moreover, spliceostatin A, a natural SF3b inhibitor, markedly inhibited P27 expression by disrupting its pre-mRNA splicing and reduced CDK2/Cyclin E expression. The expression of P89, another FIR target, was increased in excised human colorectal cancer tissues. Knockdown of FIR reduced P89; however, the effects on P27 and P89 expression are not simply or directly related to altered FIR expression levels, indicating that the mechanical or physical interaction of the SAP155/FIR/FIRΔexon2 complex is potentially essential for sustained expression of both P89 and P27. Together, the interaction between SAP155 and FIR/FIRΔexon2 not only integrates cell-cycle progression and c-Myc transcription by modifying P27 and P89 expression but also suggests that the interaction is a potential target for cancer screening and treatment. Mol Cancer Res; 11(7); 689–98. ©2013 AACR.
The pro- and anticoagulant role of blood-borne phagocytes in patients with acute coronary syndrome
Authors: Frissen Mick , Huts Mark , Kragten Johannes , Jie Kon-Siong , Leers Math , Keuren Jeffrey 
Published: April 2013

SummaryThis study was performed to gain further insight in pro- and anticoagulant characteristics of leukocytes in acute coronary syndrome (ACS). For this purpose, patients presenting on the emergency department (ED) with anginal chest pain were included in this study. In peripheral blood, procoagulant tissue factor (TF) expression was measured in the different blood-borne phagocytes, i.e. neutrophilic granulocytes and the three different monocyte subsets based on expression of CD14 and CD16. Simultaneously, intracellular presence of platelet-(CD41) and/or endothelial cell-remnants (CD62e) was analysed in these different leukocyte subsets. Neutrophils showed a weak intracellular staining of CD62e and CD41 that increased with severity of ACS. Monocytes, and especially the classical (CD14++CD16-) and intermediate monocytes (CD14++CD16+) showed a clear and significant increase in intracellular CD41-staining after coronary damage. The different monocyte subsets showed an increase in expression of TF in severe ACS. Finally, it appeared that also neutrophils showed a significant increase in expression of TF on their membrane. In conclusion, this study showed an increased intracellular staining in blood-borne phagocytes for CD62e and CD41 in patients with ACS compared to non-cardiac related control patients. This indicates that at least in the acute phase of ACS phagocytosis of platelet and endothelial cell-remnants is increased. These data support the recent hypothesis that neutrophils protect against further thrombotic processes by clearing platelet and endothelial cell-remnants. In addition, this study shows that the different monocyte subsets are also involved in this process. Furthermore, both monocytes and neutrophils show increased TF expression in ACS.
Adipose tissue angiogenesis in obesity
Authors: Lemoine Amal Y. , Ledoux Séverine , Larger Etienne 
Published: April 2013

summaryAdipose tissue is the most plastic tissue in all multicellular organisms, being constantly remodelled along with weight gain and weight loss. Expansion of adipose tissue must be accompanied by that of its vascularisation, through processes of angiogenesis, whereas weight loss is associated with the regression of blood vessels. Adipose tissue is thus among the tissues that have the highest angiogenic capacities. These changes of the vascular bed occur through close interactions of adipocytes with blood vessels, and involve several angiogenic factors. This review presents studies that are the basis of our understanding of the regulation of adipose tissue angiogenesis. The growth factors that are involved in the processes of angiogenesis and vascular regression are discussed with a focus on their potential modulation for the treatment of obesity. The hypothesis that inflammation of adipose tissue and insulin resistance could be related to altered angiogenesis in adipose tissue is presented, as well as the beneficial or deleterious effect of inhibition of adipose tissue angiogenesis on metabolic diseases.
Screening to identify unknown atrial fibrillation
Authors: Lowres Nicole , Neubeck Lis , Redfern Julie , Freedman S. Ben 
Published: April 2013

SummaryAtrial fibrillation (AF) is associated with a significantly increased stroke risk which is highly preventable with appropriate oral anticoagulant therapy (OAC). However, AF may be asymptomatic and unrecognised prior to stroke. We aimed to determine if single time-point screening for AF could identify sufficient numbers with previously undiagnosed AF, to be effective for stroke prevention. This is a systematic review of clinical trials, by searching electronic medical databases, reference lists and grey literature. Studies were included if they evaluated a general ambulant adult population, using electrocardiography or pulse palpation to identify AF. We identified 30 individual studies (n=122,571, mean age 64 years, 54% male) in nine countries. Participants were recruited either from general practitioner and outpatient clinics (12 studies) or population screening/community advertisements (18 studies). Prevalence of AF across all studies was 2.3% (95% CI, 2.2–2.4%), increasing to 4.4% (CI, 4.1–4.6%) in those ≥65 years (16 studies, n= 27,884). Overall incidence of previously unknown AF (14 studies, n=67,772) was 1.0% (CI, 0.89–1.04%), increasing to 1.4% (CI, 1.2–1.6%) in those ≥65 years (8 studies, n= 18,189) in whom screening setting did not influence incidence identified. Of those with previously unknown AF, 67% were at high risk of stroke. Screening can identify 1.4% of the population ≥65 years with previously undiagnosed AF. Many of those identified would be eligible for, and benefit from OAC to prevent stroke. Given this incidence, community AF screening strategies in at risk older age groups could potentially reduce the overall health burden associated with AF.
Intracoronary Injection of Bone Marrow–Derived Mononuclear Cells Early or Late After Acute Myocardial Infarction
Authors: Sürder Daniel , Manka Robert , Lo Cicero Viviana , Moccetti Tiziano , Rufibach Kaspar , Soncin Sabrina , Turchetto Lucia , Radrizzani Marina , Astori Giuseppe , Schwitter Juerg , Erne Paul , Zuber Michel , Auf der Maur Christoph , Jamshidi Peiman , Gaemperli Oliver , Windecker Stephan , Moschovitis Aris , Wahl Andreas , Bühler Ines , Wyss Christophe , Kozerke Sebastian , Landmesser Ulf , Lüscher Thomas F. , Corti Roberto 
Published: April 2013

Background—
Intracoronary administration of autologous bone marrow–derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction. The optimal time point of administration of BM-MNC is still uncertain and has rarely been addressed prospectively in randomized clinical trials.

Methods and Results—

In a multicenter study, we randomized 200 patients with large, successfully reperfused ST-segment elevation myocardial infarction in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were administered either early (ie, 5 to 7 days) or late (ie, 3 to 4 weeks) after acute myocardial infarction. Cardiac magnetic resonance imaging was performed at baseline and after 4 months. The primary end point was the change from baseline to 4 months in global LV ejection fraction between the 2 treatment groups and the control group. The absolute change in LV ejection fraction from baseline to 4 months was −0.4±8.8% (mean±SD;
P
=0.74 versus baseline) in the control group, 1.8±8.4% (
P
=0.12 versus baseline) in the early group, and 0.8±7.6% (
P
=0.45 versus baseline) in the late group. The treatment effect of BM-MNC as estimated by ANCOVA was 1.25 (95% confidence interval, −1.83 to 4.32;
P
=0.42) for the early therapy group and 0.55 (95% confidence interval, −2.61 to 3.71;
P
=0.73) for the late therapy group.

Conclusions—
Among patients with ST-segment elevation myocardial infarction and LV dysfunction after successful reperfusion, intracoronary infusion of BM-MNC at either 5 to 7 days or 3 to 4 weeks after acute myocardial infarction did not improve LV function at 4-month follow-up.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00355186.
Population dynamics of Meloidogyne graminicola and Hirschmanniella oryzae in a double rice-cropping sequence in the lowlands of Myanmar
Authors: Win Pa Pa , Kyi Pyone Pyone , Maung Zin Thu Zar , De Waele Dirk 
Published: April 2013

The rice root-knot nematode, Meloidogyne graminicola, and the rice root nematode, Hirschmanniella oryzae, are considered potentially important nematode pathogens in lowland rice. A study was undertaken from December 2009 until December 2010 in the Ayeyarwady River Delta, the major lowland rice-producing area of Myanmar, to monitor the population dynamics of M. graminicola and H. oryzae in a naturally infested field. Root samples of the two rice varieties Yatanartoe and Taungpyan that are commonly cultivated in double rice-cropping sequences in Myanmar and represent irrigated and rainfed lowland rice varieties, respectively, were obtained for nematode analysis. During the summer-irrigated rice-growing season the root population density of second-stage juveniles (J2) of M. graminicola showed two distinct peaks – at the maximum tillering stage of the rice plants in January and at the heading stage of the rice plants in March 2010. With the onset of the monsoon rains, the J2 population densities in the roots of ratoon rice plants gradually decreased in May. During the rainfed monsoon rice-growing season, very low population densities of M. graminicola J2 were detected in the roots of rice plants, while the root population density of H. oryzae juveniles and adults showed two distinct peaks – at the maximum tillering stage of the rice plants in August and at the heading stage of the rice plants in October 2010. With the onset of the dry season, population density of H. oryzae in the roots reached the lowest density at harvest in November. Root galling caused by M. graminicola followed the same trend as the J2 population densities throughout the irrigated season. No root galls were observed during the monsoon season. Our results can be used for practical purposes aimed at a better management of both M. graminicola and H. oryzae.