bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ORF61 Protein Encoded by Simian Varicella Virus and Varicella-Zoster Virus Inhibits NF-κB Signaling by Interfering with IκBα Degradation
Authors: Whitmer Travis , Malouli Daniel , Uebelhoer Luke S. , DeFilippis Victor R. , Früh Klaus , Verweij Marieke C. 
Published: June 2015

ABSTRACT

Varicella-zoster virus (VZV) causes chickenpox upon primary infection and establishes latency in ganglia. Reactivation from latency causes herpes zoster, which may be complicated by postherpetic neuralgia. Innate immunity mediated by interferon and proinflammatory cytokines represents the first line of immune defense upon infection and reactivation. VZV is known to interfere with multiple innate immune signaling pathways, including the central transcription factor NF-κB. However, the role of these inhibitory mechanisms
in vivo
is unknown. Simian varicella virus (SVV) infection of rhesus macaques recapitulates key aspects of VZV pathogenesis, and this model thus permits examination of the role of immune evasion mechanisms
in vivo
. Here, we compare SVV and VZV with respect to interference with NF-κB activation. We demonstrate that both viruses prevent ubiquitination of the NF-κB inhibitor IκBα, whereas SVV additionally prevents IκBα phosphorylation. We show that the ORF61 proteins of VZV and SVV are sufficient to prevent IκBα ubiquitination upon ectopic expression. We further demonstrate that SVV ORF61 interacts with β-TrCP, a subunit of the SCF ubiquitin ligase complex that mediates the degradation of IκBα. This interaction seems to inactivate SCF-mediated protein degradation in general, since the unrelated β-TrCP target Snail is also stabilized by ORF61. In addition to ORF61, SVV seems to encode additional inhibitors of the NF-κB pathway, since SVV with ORF61 deleted still prevented IκBα phosphorylation and degradation. Taken together, our data demonstrate that SVV interferes with tumor necrosis factor alpha (TNF-α)-induced NF-κB activation at multiple levels, which is consistent with the importance of these countermechanisms for varicella virus infection.

IMPORTANCE
The role of innate immunity during the establishment of primary infection, latency, and reactivation by varicella-zoster virus (VZV) is incompletely understood. Since infection of rhesus macaques by simian varicella virus (SVV) is used as an animal model of VZV infection, we characterized the molecular mechanism by which SVV interferes with innate immune activation. Specifically, we studied how SVV prevents activation of the transcription factor NF-κB, a central factor in eliciting proinflammatory responses. The identification of molecular mechanisms that counteract innate immunity might ultimately lead to better vaccines and treatments for VZV, since overcoming these mechanisms, either by small-molecule inhibition or by genetic modification of vaccine strains, is expected to reduce the pathogenic potential of VZV. Moreover, using SVV infection of rhesus macaques, it will be possible to study how increasing the vulnerability of varicella viruses to innate immunity will impact viral pathogenesis.
Health trajectories in regeneration areas in England: the impact of the New Deal for Communities intervention
Authors: Walthery Pierre , Stafford Mai , Nazroo James , Whitehead Margaret , Dibben Christopher , Halliday Emma , Povall Sue , Popay Jennie 
Published: June 2015

BackgroundA large body of evidence documents the adverse relationship between concentrated deprivation and health. Among the evaluations of regeneration initiatives to tackle these spatial inequalities, few have traced the trajectories of individuals over time and fewer still have employed counterfactual comparison. We investigate the impact of one such initiative in England, the New Deal for Communities (NDC), which ran from 1999 to 2011, on socioeconomic inequalities in health trajectories.MethodsLatent Growth Curve modelling of within-person changes in self-rated health, mental health and life satisfaction between 2002 and 2008 of an analytical cohort of residents of 39 disadvantaged areas of England in which the NDC was implemented, compared with residents of comparator, non-intervention areas, focusing on: (1) whether differences over time in outcomes can be detected between NDC and comparator areas and (2) whether interventions may have altered socioeconomic differences in outcomes.ResultsNo evidence was found for an overall improvement in the three outcomes, or for significant differences in changes in health between respondents in NDC versus comparator areas. However, we found a weakly significant gap in life satisfaction and mental health between high and low socioeconomic status individuals in comparator areas which widened over time to a greater extent than in NDC areas. Change over time in the three outcomes was non-linear: individual improvements among NDC residents were largest before 2006.ConclusionsThere is limited evidence that the NDC moderated the impact of socioeconomic factors on mental health and life satisfaction trajectories. Furthermore, any NDC impact was strongest in the first 6 years of the programmes.
Sex Differences in the Rate, Timing, and Principal Diagnoses of 30-Day Readmissions in Younger Patients with Acute Myocardial Infarction
Authors: Dreyer Rachel P. , Ranasinghe Isuru , Wang Yongfei , Dharmarajan Kumar , Murugiah Karthik , Nuti Sudhakar V. , Hsieh Angela F. , Spertus John A. , Krumholz Harlan M. 
Published: June 2015

Background—
Young women (<65 years) experience a 2- to 3-fold greater mortality risk than younger men after an acute myocardial infarction. However, it is unknown whether they are at higher risk for 30-day readmission, and if this association varies by age. We examined sex differences in the rate, timing, and principal diagnoses of 30-day readmissions, including the independent effect of sex following adjustment for confounders.

Methods and Results—

We included patients aged 18 to 64 years with a principal diagnosis of acute myocardial infarction. Data were used from the Healthcare Cost and Utilization Project-State Inpatient Database for California (07–09). Readmission diagnoses were categorized by using an aggregated version of the Centers for Medicare and Medicaid Services’ Condition Categories, and readmission timing was determined from the day after discharge. Of 42 518 younger patients with acute myocardial infarction (26.4% female), 4775 (11.2%) had at least 1 readmission. The 30-day all-cause readmission rate was higher for women (15.5% versus 9.7%,
P
<0.0001). For both sexes, readmission risk was highest on days 2 to 4 after discharge and declined thereafter, and women were more likely to present with noncardiac diagnoses (44.4% versus 40.6%,
P
=0.01). Female sex was associated with a higher rate of 30-day readmission, which persisted after adjustment (hazard ratio, 1.22; 95% confidence interval, 1.15–1.30). There was no significant interaction between age and sex on readmission.

Conclusions—
In comparison with men, younger women have a higher risk for readmission, even after the adjustment for confounders. The timing of 30-day readmission was similar in women and men, and both sexes were susceptible to a wide range of causes for readmission.
Preoperative transaortic forward flow: Prediction of surgical outcomes in patients with DCM and mitral regurgitation
Authors: Hirota Masanori , Yoshida Minoru , Hoshino Joji , Kondo Taichi , Isomura Tadashi 
Published: June 2015

Background In patients with dilated cardiomyopathy and mitral regurgitation, preoperative prognostic factors are very important. Methods We hypothesized that preoperative transaortic forward flow might be related to postoperative survival, despite mitral regurgitant volume. We retrospectively evaluated surgical outcomes and echocardiographic parameters, including forward flow through the aortic valve. Results Seventy-nine patients (54 males, 25 females; mean age 59 ± 12 years) with dilated cardiomyopathy and mitral regurgitation were divided into two groups according to postoperative outcome: 19 patients in group A suffered cardiac death, 60 in group B survived or died of another cause. In group A, death occurred after 227 ± 116 days, group B patients survived (except one who died of infection) for 505 ± 446 days; p < 0.01. Preoperatively, there was no significant difference in ejection fraction, end-diastolic and end-systolic volume index, mitral regurgitant volume, effective regurgitant orifice area, or right ventricular systolic pressure. Preoperative transaortic forward flow was significantly lower in group A vs. group B (1.57 ± 0.33 vs. 1.81 ± 0.46 L m−2; p 0.04). In group B, transaortic forward flow was increased significantly before discharge (1.81 ± 0.51 vs. 2.43 ± 0.62 L m−2; p < 0.01). Ejection fraction was significantly alleviated before discharge (28% ± 9% vs. 23% ± 8%; p < 0.01) and recovered to the preoperative value without repeat dilation of the left ventricle in late follow-up. Conclusions Preoperative transaortic forward flow may be a predictor of survival in patients with dilated cardiomyopathy and mitral regurgitation, irrespective of mitral regurgitant volume.
Cerebrospinal fluid amounts of HLA-G in dimeric form are strongly associated to patients with MRI inactive multiple sclerosis
Authors: Fainardi Enrico , Bortolotti Daria , Bolzani Silvia , Castellazzi Massimiliano , Tamborino Carmine , Roversi Gloria , Baldi Eleonora , Caniatti Maria Luisa , Casetta Ilaria , Gentili Valentina , Granieri Enrico , Rizzo Roberta ,   the ERMES study group, Granieri E , Castellazzi M , Casetta I , Tola MR , Fainardi E , Dallocchio F , Bellini T , Rizzo R , Rotola A , Di Luca D , Seraceni S , Contini C , Sabbioni S , Negrini M , Tognon M , Antonelli T , Groppo E , Gentile M , Baldi E , Caniatti ML , Ceruti S , Manfrinato MR , Trentini A , Bortolotti D , Miotto E , Ferracin M , Mazzoni E , Pietrobon S , Masini I , Rotondo JC , Martini F , Baruzzi A , Roberto D’Alessandro R , Michelucci R , Salvi F , Stecchi S , Scandellari C , Terzano G , Granella F , Nichelli P , Sola P , Ferraro D , Vitetta F , Simone AM , Bedin R , Marcello N , Motti L , Montepietra S , Guidetti D , Immovilli P , Montanari E , Pesci I , Guareschi A , Greco G , Santangelo M , Mauro AM , Malagù S , Rasi F , Spadoni M , Galeotti M , Fiorani L , Neri W , Ravasio A , Pasquinelli M , Gutman S , Monaldini C 
Published: June 2015

Background: The relevance of human leukocyte antigen (HLA)-G in dimeric form in multiple sclerosis (MS) is still unknown. Objective: To investigate the contribution of cerebrospinal fluid (CSF) HLA-G dimers in MS pathogenesis. Methods: CSF amounts of 78-kDa HLA-G dimers were measured by western blot analysis in 80 MS relapsing–remitting MS (RRMS) patients and in 81 inflammatory and 70 non-inflammatory controls. Results: CSF amounts of 78kDa HLA-G dimers were more frequent in RRMS than in inflammatory ( p<0.01) and non-inflammatory controls ( p<0.001) and in magnetic resonance imaging (MRI) inactive than in MRI active RRMS ( p<0.00001). Conclusion: Our findings suggest that HLA-G dimers may be implicated in termination of inflammatory response occurring in MS.
A comparison study of cognitive deficits in radiologically and clinically isolated syndromes
Authors: Labiano-Fontcuberta Andrés , Martínez-Ginés Mª Luisa , Aladro Yolanda , Ayuso Lucía , Mitchell Alex J , Puertas-Martín Verónica , Cerezo Marta , Higueras Yolanda , Benito-León Julián 
Published: June 2015

Up until now, no information has existed regarding a comparison of the pattern and frequency of cognitive deficits between radiologically isolated syndrome (RIS) and clinically isolated syndrome (CIS) patients. Within this objective, Rao’s Brief Repeatable Battery and Stroop test were administered to 28 RIS patients, 25 CIS patients, and 22 healthy controls. Conclusions: The prevalence of cognitive deficits in RIS was similar to that of CIS. Cognitive deficits seem to be present in RIS patients regardless of the presence of risk factors for a future symptomatic demyelinating event.
Enhanced uplink scheduling algorithm for efficient resource management in IEEE 802.16
Authors: Oad Aneel , Subramaniam Shamala K , Zukarnain Zuriati Ahmad 
Published: June 2015

Abstract
Worldwide interoperability for Microwave Access (WiMAX) is based on the IEEE 802.16 standard. This technology provides broadband wireless last-mile access in a Metropolitan Area Network (MAN). The IEEE 802.16-2004 standard (i.e. Fixed WiMAX) provides specification for the Medium Access Control (MAC) and Physical (PHY) layers for WiMAX. A critical part of the MAC layer specification is scheduling, which resolves contention for bandwidth and determines the transmission order of users. The algorithms are researched under different mixes of traffic and for various characteristics of the IEEE 802.16 MAC layer. In this research the focus is on the WiMAX uplink traffic scheduling. A scheduling algorithm’s task in a multi-class network is also to categorize the users into one of the pre-defined classes. In this research, the algorithms are tailored at enhancing the collective performance of hybrid algorithms in the WiMAX domains which complement the assigned priorities. The spectrum of constraints which have been extracted from the hybrid Earliest Deadline First(EDF) + Weighted Fair Queuing (WFQ) + First in First out (FIFO) EDF+WFQ+FIFO algorithm include the static nature by which priorities are assigned and maintained during the entire duration of a transmission time and the core attributes of absolute dependence on deadline. The second constraint is embedded within the EDF scheduling algorithm and the perseverance of pursuing deadline associated weightages. In this research, the reengineering of the scheduling mechanics governing the EDF algorithms has been pursued. The dominance of the pre-stipulated deadline of the EDF algorithm is indeed acknowledged in the proposed and developed enhanced algorithm. The simulation results indicate that the legacy algorithms are not suitable for the multi-class traffic systems of WiMAX. This is because these algorithms do not explicitly incorporate the WiMAX QoS parameters into their mechanisms and are highly static. Extensive discrete – event simulation experiments have been done for the purpose of performance analysis. The performance metrics used are average throughput, average delay, missed deadline ratio and average queue size utilization ratio. The acquired results have proven that the proposed algorithms have successfully enhanced the static constrained algorithm.
The threshold of a stochastic SIQS epidemic model
Authors: Pang Yanni , Han Yuecai , Li Wenjin 
Published: June 2015

Abstract
In this paper, we discuss the dynamics of a stochastic SIQS epidemic model. When the noise is large, the infective decays exponentially to zero regardless of the magnitude of

R
0

. When the noise is small, sufficient conditions for extinction exponentially and persistence in the mean are established. The results are illustrated by computer simulations.

MSC:34F05, 37H10, 60H10, 92D25, 92D30.
Positive solution of singular fractional differential system with nonlocal boundary conditions
Authors: Wu Jing , Zhang Xinguang , Liu Lishan , Wu Yonghong 
Published: June 2015

Abstract
In this paper, we consider the existence of positive solutions for a singular fractional differential system involving a nonlocal boundary condition which is given by a linear functional on

C
[
0
,
1
]

with a signed measure. By looking for the upper and lower solutions of the system, the sufficient condition of the existence of positive solutions is established; some further cases are discussed. This is proved in the case of strong singularity and with a signed measure.

MSC:34B15, 34B25.
Grain iron and zinc density in pearl millet: combining ability, heterosis and association with grain yield and grain size
Authors: Kanatti Anand , Rai Kedar N , Radhika Kommineni , Govindaraj Mahalingam , Sahrawat Kanwar L , Rao Aluri S 
Published: June 2015

Abstract
Genetics of micronutrients and their relationships with grain yield and other traits have a direct bearing on devising effective strategies for breeding biofortified crop cultivars. A line × tester study of 196 hybrids and their 28 parental lines of pearl millet (Pennisetum glaucum (L.) R.Br.) showed large genetic variability for Fe and Zn densities with predominantly additive gene action and no better-parent heterosis. Hybrids with high levels of Fe and Zn densities, involved both parental lines having significant positive general combining ability (GCA), and there were highly significant and high positive correlations between performance per se of parental lines and their GCAs. There was highly significant and high positive correlation between the Fe and Zn densities, both for performance per se and GCA. Fe and Zn densities had highly significant and negative, albeit weak, correlations with grain yield and highly significant and moderate positive correlation with grain weight in hybrids. These correlations, however, were non-significant in the parental lines. Thus, to breed hybrids with high Fe and Zn densities would require incorporating these micronutrients in both parental lines. Also, simultaneous selection for Fe and Zn densities based on performance per se would be highly effective in selecting for GCA. Breeding for high Fe and Zn densities with large grain size will be highly effective. However, combining high levels of these micronutrients with high grain yield would require growing larger breeding populations and progenies than breeding for grain yield alone, to make effective selection for desirable recombinants.
Wnt5a regulates dental follicle stem/progenitor cells of the periodontium
Authors: Xiang Lusai , Chen Mo , He Ling , Cai Bin , Du Yu , Zhang Xinchun , Zhou Chen , Wang Chenglin , Mao Jeremy J , Ling Junqi 
Published: June 2015

Abstract
Introduction
Dental follicle gives rise to one or several tissues of the periodontium including the periodontal ligament, cementum and/or alveolar bone. Whether Wnt5a is expressed in the postnatal periodontium or regulates dental follicle stem/progenitor cells is unknown.

Methods
Dental follicle stem/progenitor cells were isolated from postnatal day 1 (p1) to p11 from rat mandibular first molars. Immunolocalization mapped Wnt5a expression in the alveolar bone, periodontal ligament, and the developing ameloblast and odontoblast layers. Mononucleated and adherent cells were isolated from p7 dental follicle. Wnt5a was overexpressed in dental follicle stem/progenitor cells to study their proliferation, osteogenic differentiation and migration behavior, with subpopulations of native dental follicle stem/progenitor cells as controls, using real-time PCR (Taqman), Lenti-viral transfection, Western blotting and immunofluorescence.

Results
Wnt5a was expressed consistently in p1 to p11 rat peridontium. Native, p7 dental follicle stem/progenitor cells had modest ability to mineralize in the tested 14 days. Even in chemically defined osteogenesis medium, dental follicle stem/progenitor cells only showed modest mineralization. Upon addition of 300 ng/mL Wnt5a protein in osteogenesis medium, dental follicle stem/progenitor cells displayed mineralization that was still unremarkable. Chemically induced or Wnt5a-induced mineralization of dental follicle cells only occurred sparsely. Combination of Wnt5a with 100 ng/mL BMP2 finally prompted dental follicle stem/progenitor cells to produce robust mineralization with elevated expression of Runx2, alkaline phosphatase, collagen 1α1 and osteocalcin. Thus, native dental follicle stem/progenitor cells or some of their fractions may be somewhat modest in mineralization. Strikingly, Wnt5a protein significantly augmented RANKL ligand, suggesting putative regulatory roles of dental follicle stem/progenitor cells for the monocyte/osteoclast lineage and potential involvement in alveolar bone remodeling and/or resorption. P-Jnk1/2 was activated in Wnt5a overexpressed dental follicle cells; conversely, exposure to SP600125, a c-Jun N-terminal kinase (JNK) inhibitor attenuated Runx2, collagen 1α1 and osteocalcin expression either in the presence or absence of Wnt5a. Wnt5a overexpression in dental follicle stem/progenitor cells significantly reduced their proliferation rates, but robustly augmented their migration capacity.

Conclusions
These findings provide a glimpse of Wnt5a’s putative roles in dental follicle stem/progenitor cells and the periodontium with implications in periodontal disease, tooth eruption, dental implant bone healing and orthodontic tooth movement.
Mesenchymal stem cell-mediated suppression of hypertrophic scarring is p53 dependent in a rabbit ear model
Authors: Liu Yi-Lun , Liu Wei-Hua , Sun Jin , Hou Tuan-Jie , Liu Yue-Ming , Liu Hai-Rong , Luo Yong-Hui , Zhao Ning-Ning , Tang Ying , Deng Feng-Mei 
Published: June 2015

Abstract
Introduction
Mesenchymal stem cells (MSCs) are considered to play important roles in wound repair and tissue remodeling. Hypertrophic scar (HTS) is a cutaneous condition characterized by deposits of excessive amount of collagen after an acute skin injury. However, currently there is little knowledge about the direct relationship between MSCs and HTS.

Methods
The hypertrophic scar model was established on rabbit ears. MSCs were isolated from rabbit femur bone marrow and transplanted through ear artery injection. Hypertrophic scar formation was examined using frozen-section analysis, hematoxylin and eosin (HE) staining, Masson’s trichrome staining, and scar elevation index. The role of p53 in the MSCs-mediated anti-scarring effect was examined by gene knockdown using p53 shRNA.

Results
In this study, MSCs engraftment through ear artery injection significantly inhibited the hypertrophic scarring in a rabbit ear hypertrophic scar model, while this anti-scarring function could be abrogated by p53 gene knockdown in MSCs. Additionally, we found that MSCs down-regulated the expression of TGF-β receptor I (TβRI) and alpha-smooth muscle actin (α-SMA) at both mRNA and protein levels in a paracrine manner, and this down-regulation was rescued by p53 gene knockdown. Moreover, our results showed that MSCs with p53 gene knockdown promoted the proliferation of fibroblasts through increasing nitric oxide (NO) production.

Conclusions
These results suggest that MSCs inhibit the formation of HTS in a p53 dependent manner through at least two mechanisms: inhibition of the transformation of HTS fibroblast to myofibroblast; and inhibition of the proliferation of fibroblasts through inhibition of NO production.