bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin‐6 receptor alpha blockade improves skin lesions in a murine model of systemic lupus erythematosus
Authors: Birner Peter , Heider Susanne , Petzelbauer Peter , Wolf Peter , Kornauth Christoph , Kuroll Madeleine , Merkel Olaf , Steiner Günter , Kishimoto Tadamitsu , Rose‐John Stefan , Soleiman Afschin , Moriggl Richard , Kenner Lukas 
Published: January 2016

AbstractSystemic lupus erythematosus (SLE) is an autoimmune disease, characterized by antinuclear autoantibodies (ANA) and immunocomplexes, commonly affecting kidneys, skin, heart, lung or even the brain. We have shown that JunBΔep mice develop a SLE phenotype linked to increased epidermal Interleukin (IL)‐6 secretion. Blocking of IL‐6 receptor alpha (IL‐6Rα) is considered as therapeutic strategy for the treatment of SLE. JunBΔep and wild‐type mice were treated for short (5 weeks) or long term (21 weeks) with the IL‐6Rα‐blocking antibody MR16‐1. Skin and kidney of mice were investigated by histology and immunofluorescence, and in addition, kidneys were analysed by electron microscopy. Furthermore, soluble IL‐6R (sIL‐6R), antihistone and antinucleosome antibodies levels were measured and associated with disease parameters. Treatment with MR16‐1 resulted in significant improvement of SLE‐like skin lesions in JunBΔep mice, compared to untreated mice. The sIL‐6R amount upon long‐term treatment with MR16‐1 was significantly higher in JunBΔep versus untreated JunBΔep (P = 0.034) or wild‐type mice (P = 0.034). MR16‐1 treatment over these time spans did not significantly improve kidney pathology of immunoglobulin deposits causing impaired function. Significantly higher antihistone (P = 0.028) and antinucleosome antibody levels (P = 0.028) were measured in MR16‐1‐treated JunBΔep mice after treatment compared to levels before therapy. In conclusion, blockade of IL‐6Rα improves skin lesions in a murine SLE model, but does not have a beneficial effect on autoimmune‐mediated kidney pathology. Inhibition of IL‐6R signalling might be helpful in lupus cases with predominant skin involvement, but combinatorial treatment might be required to restrain autoantibodies.
Anatomy, morphology and evolution of the patella in squamate lizards and tuatara (Sphenodon punctatus)
Authors: Regnault Sophie , Jones Marc E. H. , Pitsillides Andrew A. , Hutchinson John R. 
Published: January 2016

AbstractThe patella (kneecap) is the largest and best‐known of the sesamoid bones, postulated to confer biomechanical advantages including increasing joint leverage and reinforcing the tendon against compression. It has evolved several times independently in amniotes, but despite apparently widespread occurrence in lizards, the patella remains poorly characterised in this group and is, as yet, completely undescribed in their nearest extant relative Sphenodon (Rhynchocephalia). Through radiography, osteological and fossil studies we examined patellar presence in diverse lizard and lepidosauromorph taxa, and using computed tomography, dissection and histology we investigated in greater depth the anatomy and morphology of the patella in 16 lizard species and 19 Sphenodon specimens. We have found the first unambiguous evidence of a mineralised patella in Sphenodon, which appears similar to the patella of lizards and shares several gross and microscopic anatomical features. Although there may be a common mature morphology, the squamate patella exhibits a great deal of variability in development (whether from a cartilage anlage or not, and in the number of mineralised centres) and composition (bone, mineralised cartilage or fibrotendinous tissue). Unlike in mammals and birds, the patella in certain lizards and Sphenodon appears to be a polymorphic trait. We have also explored the evolution of the patella through ancestral state reconstruction, finding that the patella is ancestral for lizards and possibly Lepidosauria as a whole. Clear evidence of the patella in rhynchocephalian or stem lepidosaurian fossil taxa would clarify the evolutionary origin(s) of the patella, but due to the small size of this bone and the opportunity for degradation or loss we could not definitively conclude presence or absence in the fossils examined. The pattern of evolution in lepidosaurs is unclear but our data suggest that the emergence of this sesamoid may be related to the evolution of secondary ossification centres and/or changes in knee joint conformation, where enhancement of extensor muscle leverage would be more beneficial.
Repeated exposure to whole cigarette smoke promotes primary human gingival epithelial cell growth and modulates keratin expression
Authors: Alharbi I. A. , Rouabhia M. 
Published: January 2016

Background and ObjectiveThe gingiva is the first oral tissue directly exposed to cigarette smoke (CS). Exposure to CS compromises the structure and function of gingival tissue. Damaging or altering the gingival epithelium leads to a compromised protective barrier of the periodontium, resulting in several diseases. The aim of this study was to assess the effect of repeated exposure to CS on gingival epithelial cell growth and on expression of apoptotic protein and keratin.Material and MethodsPrimary human gingival epithelial cells were seeded on a collagen scaffold for 5 d to allow growth and stratification. The cells were then exposed for 5 min to whole CS for 3, 6 and 9 d. At the end of each exposure period, cell proliferation [using (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide) (MTT) and 5‐bromo‐2′‐deoxyuridine (BrdU) assays], gene expression [by quantitative reverse transcription polymerase chain reaction (qRT‐PCR)] and protein production (by western blot analysis) were investigated.ResultsHigher metabolic activity was found in the CS‐exposed cells than in the nonexposed cells, specifically after 3 and 6 d of exposure to CS. At 9 d there was no significant difference between CS‐exposed and nonexposed cells. Metabolic activity was supported by the BrdU cell‐proliferation analyses, which showed increased cell growth at 3 d compared with the control. However, at 6 and 9 d, cell proliferation in the CS‐exposed culture was comparable to that in the nonexposed culture. Interestingly, the Bax/Bcl‐2 protein ratios decreased with increased CS exposure, suggesting cell resistance. Moreover, protein analyses showed that CS decreased expression of keratin(K) 5 at 3, 6 and 9 d, and increased expression of K14 at 6 and 9 d. Finally, mRNA analyses showed significant decreases of K1, K6, K10 and K16 in CS‐exposed cultures, correlating, at times, with a decrease of protein production.ConclusionCS was shown to increase epithelial cell proliferation, which may involve cell resistance to apoptosis. This is supported by the modulation of expression of different keratin genes and proteins. Altogether, these data may explain the hyperplasia reported in gingival tissue, as well as periodontal disease, in smokers.
Breed Distribution and Clinical Characteristics of B Cell Chronic Lymphocytic Leukemia in Dogs
Authors: Bromberek J.L. , Rout E.D. , Agnew M.R. , Yoshimoto J. , Morley P.S. , Avery A.C. 
Published: January 2016

BackgroundB‐cell chronic lymphocytic leukemia (B‐CLL) is the most common hematopoietic malignancy in humans in the developed world and the primary risk factor is genetic. Dogs also develop B‐CLL, but there is no systematic description of the disease in dogs. Understanding the epidemiology of B‐CLL in dogs may help practitioners recognize the disease and position the dog as a model for future genetic studies.ObjectivesTo describe B‐CLL presentation in dogs, its clinicopathologic findings, and breed predisposition.AnimalsFour hundred and ninety‐one dogs with B‐CLL and 5,673 control dogs with suspicion of a lymphoproliferative disorder (LPD).MethodsRetrospective cross‐sectional study of dogs for which samples were submitted to the Colorado State University Clinical Immunology Laboratory for immunophenotyping between 2010 and 2014. To assess breed predilection, dogs with B‐CLL were compared to those with suspicion of other LPDs using logistic regression.ResultsThe median age was 11 years with no sex predilection. Half of the dogs presented with peripheral lymphadenopathy or splenomegaly and 26% had anemia. Eleven small‐breed dogs had significantly increased odds of B‐CLL. In addition, English Bulldogs had an increased risk and a unique presentation: these dogs were diagnosed at a median of 6 years and expressed lower class II MHC and CD25.ConclusionsB‐cell chronic lymphocytic leukemia is overrepresented in small‐breed dogs. Future genetic studies of these breeds may identify genetic risk factors. The unique presentation of English Bulldogs provides evidence of multiple forms of this disease. Additional studies are necessary to determine whether presenting signs are associated with survival.
Gestational Age, Birthweight for Gestational Age, and Childhood Hospitalisations for Asthma and Other Wheezing Disorders
Authors: Leung June Y. Y. , Lam Hugh S. , Leung Gabriel M. , Schooling C. Mary 
Published: January 2016

AbstractBackgroundPreterm birth, early term birth, and low birthweight are associated with childhood wheezing disorders in developed Western settings, but observed associations could be confounded by socio‐economic position. This study aims to clarify such associations in a developed non‐Western setting with a different confounding structure.MethodsUsing Cox regression, we examined the adjusted associations of gestational age and birthweight for gestational age with time to first public hospital admission for asthma, bronchitis, and bronchiolitis (International Classification of Diseases, Ninth Version Clinical Modification 466, 490, and 493) from 9 days to 12 years in a population‐representative birth cohort of 8327 Chinese children in Hong Kong, a developed setting with less clear social patterning of prematurity or birthweight. Analyses were adjusted for infant and parental characteristics and socio‐economic position.ResultsChildren born late preterm (34 to <37 weeks) had higher risk of hospitalisation for asthma and other wheezing disorders [hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.48, 2.67] than children born full term (39 to <41 weeks). Early term births (37 to <39 weeks) had HR 1.01 (95% CI 0.84, 1.22), late term births (41 to <42 weeks) had HR 0.77 (95% 0.59, 1.01), and post‐term births (≥42 weeks) had HR 0.56 (95% CI 0.32, 0.98). Large for gestational age was associated with lower risk of hospitalisation (HR 0.76, 95% CI 0.57, 0.99).ConclusionThe association of preterm birth with childhood wheezing could be biologically mediated. We cannot rule out an association for early term births.
Understanding the Lives of Mothers after Incarceration: Moving Beyond Socially Constructed Definitions of Motherhood
Authors: Garcia Janet 
Published: January 2016

AbstractIn the wake of mass incarceration, an increasing number of women are going through the penal system. A fair number of these women are mothers, yet the intersection of motherhood and prison may contradict conceptions of femininity and challenge traditional views of appropriate mothering. The contradiction between notions of criminality and femininity contributes to stigmatized perceptions of formerly incarcerated mothers, which drastically shapes their ability to reintegrate into society post‐incarceration. While reentry efforts tackle gender differences through the implementation of gender‐responsive programs that cater to women's needs, failure to adequately account for unique maternal experiences may hinder attempts to address obstacles faced by mothers in particular, such as regaining child custody and paying for day care. This article argues for special attention to the post‐incarceration experiences of mothers without imposing socially constructed definitions of motherhood like having custody and living with children, which may not coincide with the realities mothers face after imprisonment. Ideas are also discussed for the inclusive consideration of formerly incarcerated mothers and their post‐incarceration experiences.
Detection of Atypical H-Type Bovine Spongiform Encephalopathy and Discrimination of Bovine Prion Strains by Real-Time Quaking-Induced Conversion
Authors: Masujin Kentaro , Orrú Christina D. , Miyazawa Kohtaro , Groveman Bradley R. , Raymond Lynne D. , Hughson Andrew G. , Caughey Byron 
Published: January 2016

ABSTRACTPrion diseases of cattle include the classical bovine spongiform encephalopathy (C-BSE) and the atypical H-type BSE (H-BSE) and L-type BSE (L-BSE) strains. Although the C- and L-BSE strains can be detected and discriminated by ultrasensitive real-time quaking-induced conversion (RT-QuIC) assays, no such test has yet been described for the detection of H-BSE or the discrimination of each of the major bovine prion strains. Here, we demonstrate an RT-QuIC assay for H-BSE that can detect as little as 10−9dilutions of brain tissue and neat cerebrospinal fluid samples from clinically affected cattle. Moreover, comparisons of the reactivities with different recombinant prion protein substrates and/or immunoblot band profiles of proteinase K-treated RT-QuIC reaction products indicated that H-, L-, and C-BSE have distinctive prion seeding activities and can be discriminated by RT-QuIC on this basis.
Comparison of Performance Characteristics of Aspergillus PCR in Testing a Range of Blood-Based Samples in Accordance with International Methodological Recommendations
Authors: Springer Jan , White P. Lewis , Hamilton Shanna , Michel Denise , Barnes Rosemary A. , Einsele Hermann , Löffler Juergen 
Published: January 2016

ABSTRACT

Standardized methodologies for the molecular detection of invasive aspergillosis (IA) have been established by the European
Aspergillus
PCR Initiative for the testing of whole blood, serum, and plasma. While some comparison of the performance of
Aspergillus
PCR when testing these different sample types has been performed, no single study has evaluated all three using the recommended protocols. Standardized
Aspergillus
PCR was performed on 423 whole-blood pellets (WBP), 583 plasma samples, and 419 serum samples obtained from hematology patients according to the recommendations. This analysis formed a bicenter retrospective anonymous case-control study, with diagnosis according to the revised European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) consensus definitions (11 probable cases and 36 controls). Values for clinical performance using individual and combined samples were calculated. For all samples, PCR positivity was significantly associated with cases of IA (for plasma,
P
= 0.0019; for serum,
P
= 0.0049; and for WBP,
P
= 0.0089). Plasma PCR generated the highest sensitivity (91%); the sensitivities for serum and WBP PCR were 80% and 55%, respectively. The highest specificity was achieved when testing WBP (96%), which was significantly superior to the specificities achieved when testing serum (69%,
P
= 0.0238) and plasma (53%,
P
= 0.0002). No cases were PCR negative in all specimen types, and no controls were PCR positive in all specimens. This study confirms that
Aspergillus
PCR testing of plasma provides robust performance while utilizing commercial automated DNA extraction processes. Combining PCR testing of different blood fractions allows IA to be both confidently diagnosed and excluded. A requirement for multiple PCR-positive plasma samples provides similar diagnostic utility and is technically less demanding. Time to diagnosis may be enhanced by testing multiple contemporaneously obtained sample types.
Prolactin Regulatory Element Binding Protein Is Involved in Hepatitis C Virus Replication by Interaction with NS4B
Authors: Kong Lingbao , Fujimoto Akira , Nakamura Mariko , Aoyagi Haruyo , Matsuda Mami , Watashi Koichi , Suzuki Ryosuke , Arita Minetaro , Yamagoe Satoshi , Dohmae Naoshi , Suzuki Takehiro , Sakamaki Yuriko , Ichinose Shizuko , Suzuki Tetsuro , Wakita Takaji , Aizaki Hideki 
Published: January 2016

ABSTRACT

It has been proposed that the hepatitis C virus (HCV) NS4B protein triggers the membranous HCV replication compartment, but the underlying molecular mechanism is not fully understood. Here, we screened for NS4B-associated membrane proteins by tandem affinity purification and proteome analysis and identified 202 host proteins. Subsequent screening of replicon cells with small interfering RNA identified prolactin regulatory element binding (PREB) to be a novel HCV host cofactor. The interaction between PREB and NS4B was confirmed by immunoprecipitation, immunofluorescence, and proximity ligation assays. PREB colocalized with double-stranded RNA and the newly synthesized HCV RNA labeled with bromouridine triphosphate in HCV replicon cells. Furthermore, PREB shifted to detergent-resistant membranes (DRMs), where HCV replication complexes reside, in the presence of NS4B expression in Huh7 cells. However, a PREB mutant lacking the NS4B-binding region (PREBd3) could not colocalize with double-stranded RNA and did not shift to the DRM in the presence of NS4B. These results indicate that PREB locates at the HCV replication complex by interacting with NS4B. PREB silencing inhibited the formation of the membranous HCV replication compartment and increased the protease and nuclease sensitivity of HCV replicase proteins and RNA in DRMs, respectively. Collectively, these data indicate that PREB promotes HCV RNA replication by participating in the formation of the membranous replication compartment and by maintaining its proper structure by interacting with NS4B. Furthermore, PREB was induced by HCV infection
in vitro
and
in vivo
. Our findings provide new insights into HCV host cofactors.

IMPORTANCE
The hepatitis C virus (HCV) protein NS4B can induce alteration of the endoplasmic reticulum and the formation of a membranous web structure, which provides a platform for the HCV replication complex. The molecular mechanism by which NS4B induces the membranous HCV replication compartment is not understood. We screened for NS4B-associated membrane proteins by tandem affinity purification and proteome analysis, followed by screening with small interfering RNA. We identified prolactin regulatory element binding (PREB) to be a novel HCV host cofactor. PREB is induced by HCV infection and recruited into the replication complex by interaction with NS4B. Recruited PREB promotes HCV RNA replication by participating in the formation of the membranous HCV replication compartment. To our knowledge, the effect of NS4B-binding protein on the formation of the membranous HCV replication compartment is newly described in this report. Our findings are expected to provide new insights into HCV host cofactors.
The Synthetic Antiviral Drug Arbidol Inhibits Globally Prevalent Pathogenic Viruses
Authors: Pécheur Eve-Isabelle , Borisevich Viktoriya , Halfmann Peter , Morrey John D. , Smee Donald F. , Prichard Mark , Mire Chad E. , Kawaoka Yoshihiro , Geisbert Thomas W. , Polyak Stephen J. 
Published: January 2016

ABSTRACT

Arbidol (ARB) is a synthetic antiviral originally developed to combat influenza viruses. ARB is currently used clinically in several countries but not in North America. We have previously shown that ARB inhibits
in vitro
hepatitis C virus (HCV) by blocking HCV entry and replication. In this report, we expand the list of viruses that are inhibited by ARB and demonstrate that ARB suppresses
in vitro
infection of mammalian cells with Ebola virus (EBOV), Tacaribe arenavirus, and human herpesvirus 8 (HHV-8). We also confirm suppression of hepatitis B virus and poliovirus by ARB. ARB inhibited EBOV Zaire Kikwit infection when added before or at the same time as virus infection and was less effective when added 24 h after EBOV infection. Experiments with recombinant vesicular stomatitis virus (VSV) expressing the EBOV Zaire glycoprotein showed that infection was inhibited by ARB at early stages, most likely at the level of viral entry into host cells. ARB inhibited HHV-8 replication to a similar degree as cidofovir. Our data broaden the spectrum of antiviral efficacy of ARB to include globally prevalent viruses that cause significant morbidity and mortality.

IMPORTANCE
There are many globally prevalent viruses for which there are no licensed vaccines or antiviral medicines. Some of these viruses, such as Ebola virus or members of the arenavirus family, rapidly cause severe hemorrhagic diseases that can be fatal. Other viruses, such as hepatitis B virus or human herpesvirus 8 (HHV-8), establish persistent infections that cause chronic illnesses, including cancer. Thus, finding an affordable, effective, and safe drug that blocks many viruses remains an unmet medical need. The antiviral drug arbidol (ARB), already in clinical use in several countries as an anti-influenza treatment, has been previously shown to suppress the growth of many viruses. In this report, we expand the list of viruses that are blocked by ARB in a laboratory setting to include Ebola virus, Tacaribe arenavirus, and HHV-8, and we propose ARB as a broad-spectrum antiviral drug that may be useful against hemorrhagic viruses.
Requirement for the E1 Helicase C-Terminal Domain in Papillomavirus DNA Replication
In Vivo
Authors: Bergvall Monika , Gagnon David , Titolo Steve , Lehoux Michaël , D'Abramo Claudia M. , Melendy Thomas , Archambault Jacques 
Published: January 2016

ABSTRACT

The papillomavirus (PV) E1 helicase contains a conserved C-terminal domain (CTD), located next to its ATP-binding site, whose function
in vivo
is still poorly understood. The CTD is comprised of an alpha helix followed by an acidic region (AR) and a C-terminal extension termed the C-tail. Recent biochemical studies on bovine papillomavirus 1 (BPV1) E1 showed that the AR and C-tail regulate the oligomerization of the protein into a double hexamer at the origin. In this study, we assessed the importance of the CTD of human papillomavirus 11 (HPV11) E1
in vivo
, using a cell-based DNA replication assay. Our results indicate that combined deletion of the AR and C-tail drastically reduces DNA replication, by 85%, and that further truncation into the alpha-helical region compromises the structural integrity of the E1 helicase domain and its interaction with E2. Surprisingly, removal of the C-tail alone or mutation of highly conserved residues within the domain still allows significant levels of DNA replication (55%). This is in contrast to the absolute requirement for the C-tail reported for BPV1 E1
in vitro
and confirmed here
in vivo
. Characterization of chimeric proteins in which the AR and C-tail from HPV11 E1 were replaced by those of BPV1 indicated that while the function of the AR is transferable, that of the C-tail is not. Collectively, these findings define the contribution of the three CTD subdomains to the DNA replication activity of E1
in vivo
and suggest that the function of the C-tail has evolved in a PV type-specific manner.

IMPORTANCE
While much is known about hexameric DNA helicases from superfamily 3, the papillomavirus E1 helicase contains a unique C-terminal domain (CTD) adjacent to its ATP-binding site. We show here that this CTD is important for the DNA replication activity of HPV11 E1
in vivo
and that it can be divided into three functional subdomains that roughly correspond to the three conserved regions of the CTD: an alpha helix, needed for the structural integrity of the helicase domain, followed by an acidic region (AR) and a C-terminal tail (C-tail) that have been shown to regulate the oligomerization of BPV1 E1
in vitro
. Characterization of E1 chimeras revealed that, while the function of the AR could be transferred from BPV1 E1 to HPV11 E1, that of the C-tail could not. These results suggest that the E1 CTD performs multiple functions in DNA replication, some of them in a virus type-specific manner.