bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis B Virus Polymerase Disrupts K63-Linked Ubiquitination of STING To Block Innate Cytosolic DNA-Sensing Pathways
Authors: Liu Yinghui , Li Jianhua , Chen Jieliang , Li Yaming , Wang Weixia , Du Xiaoting , Song Wuhui , Zhang Wen , Lin Li , Yuan Zhenghong 
Published: December 2014

ABSTRACT
The cellular innate immune system recognizing pathogen infection is essential for host defense against viruses. In parallel, viruses have developed a variety of strategies to evade the innate immunity. The hepatitis B virus (HBV), a DNA virus that causes chronic hepatitis, has been shown to inhibit RNA helicase RIG-I-mediated interferon (IFN) induction. However, it is still unknown whether HBV could affect the host DNA-sensing pathways. Here we report that in transiently HBV-transfected Huh7 cells, the stably HBV-producing cell line HepAD38, and HBV-infected HepaRG cells and primary human hepatocytes, HBV markedly interfered with IFN-β induction and antiviral immunity mediated by the stimulator of interferon genes (STING), which has been identified as a central factor in foreign DNA recognition and antiviral innate immunity. Screening analysis demonstrated that the viral polymerase (Pol), but not other HBV-encoded proteins, was able to inhibit STING-stimulated interferon regulatory factor 3 (IRF3) activation and IFN-β induction. Moreover, the reverse transcriptase (RT) and the RNase H (RH) domains of Pol were identified to be responsible for the inhibitory effects. Furthermore, Pol was shown to physically associate with STING and dramatically decrease the K63-linked polyubiquitination of STING via its RT domain without altering the expression level of STING. Taken together, these observations suggest that besides its inherent catalytic function, Pol has a role in suppression of IFN-β production by direct interaction with STING and subsequent disruption of its K63-linked ubiquitination, providing a new mechanism for HBV to counteract the innate DNA-sensing pathways.

IMPORTANCE
Although whether and how HBV infection induces the innate immune responses are still controversial, it has become increasingly clear that HBV has developed strategies to counteract the pattern recognition receptor-mediated signaling pathways. Previous studies have shown that type I IFN induction activated by the host RNA sensors could be inhibited by HBV. However, it remains unknown whether HBV as a DNA virus utilizes evasion mechanisms against foreign DNA-elicited antiviral signaling. In recent years, the cytosolic DNA sensor and key adaptor STING has been demonstrated to be essential in multiple foreign DNA-elicited innate immune signalings. Here, for the first time, we report STING as a new target of HBV to antagonize IFN induction and identify the viral polymerase responsible for the inhibitory effect, thus providing an additional molecular mechanism by which HBV evades the innate immunity; this implies that in addition to its inherent catalytic function, HBV polymerase is a multifunctional immunomodulatory protein.
Expanding the Role of the Virome: Commensalism in the Gut
Authors: Cadwell Ken 
Published: December 2014

ABSTRACT
Viruses affect host physiology beyond causing acute disease, thereby giving rise to the concept that the virome is a component of the microbiome. However, the role of the enteric virome is understudied relative to the fast-paced research examining commensal bacteria in the intestine. In this article, I discuss our recent work on murine norovirus indicating that an animal virus in the intestine can provide many of the signals to the host that have been attributed to commensal bacteria. Our findings suggest that the surge in microbiome research should incorporate examination of the enteric virome.
Characterization of Novel Transcripts of Human Papillomavirus Type 16 Using Cap Analysis Gene Expression Technology
Authors: Taguchi Ayumi , Nagasaka Kazunori , Kawana Kei , Hashimoto Kosuke , Kusumoto-Matsuo Rika , Plessy Charles , Thomas Miranda , Nakamura Hiroe , Bonetti Alessandro , Oda Katsutoshi , Kukimoto Iwao , Carninci Piero , Banks Lawrence , Osuga Yutaka , Fujii Tomoyuki 
Published: December 2014

ABSTRACT
We have performed cap-analysis gene expression (CAGE) sequencing to identify the regulatory networks that orchestrate genome-wide transcription in human papillomavirus type 16 (HPV16)-positive cervical cell lines of different grades: W12E, SiHa, and CaSki. Additionally, a cervical intraepithelial neoplasia grade 1 (CIN1) lesion was assessed for identifying the transcriptome expression profile. Here we have precisely identified a novel antisense noncoding viral transcript in HPV16. In conclusion, CAGE sequencing should pave the way for understanding a diversity of viral transcript expression.
Mutations within the Pathogenic Region of Herpes Simplex Virus 1 gK Signal Sequences Alter Cell Surface Expression and Neurovirulence
Authors: Matundan Harry H. , Mott Kevin R. , Akhtar Aslam Abbasi , Breunig Joshua J. , Ghiasi Homayon 
Published: December 2014

ABSTRACT

To investigate the role of the signal sequences of herpes simplex virus 1 (HSV-1) gK on virus replication and viral pathogenesis, we constructed recombinant viruses with or without mutations within the signal sequences of gK. These recombinant viruses expressed two additional copies of the mutated (MgK) or native (NgK) form of the gK gene in place of the latency-associated transcript with a myc epitope tag to facilitate detection at their 3′ ends. The replication of MgK virus was similar to that of NgK both
in vitro
and
in vivo
, as well as in the trigeminal ganglia (TG) of latently infected mice. The levels of gB and gK transcripts in the corneas, TG, and brains of infected mice on days 3 and 5 postinfection were markedly virus and time dependent, as well as tissue specific. Mutation in the signal sequence of gK in MgK virus blocked cell surface expression of gK-myc in rabbit skin cells, increased 50% lethal dose, and decreased corneal scarring in ocularly infected mice compared to the NgK or revertant (RgK) virus. MgK and NgK viruses, and not the RgK virus, showed a reduced extent of explant reactivation at the lower dose of ocular infection but not at the higher dose. However, the time of reactivation was not affected by overexpression of the different forms of gK. Taken together, these results strongly suggest that the 8mer peptide (ITAYGLVL) within the signal sequence of gK promotes cell surface expression of gK in infected cells and ocular pathogenesis in infected mice.

IMPORTANCE
In this study, we show for the first time that mutations within the signal sequence of gK blocked cell surface expression of inserted recombinant gK
in vitro
. Furthermore, this blockage in cell surface expression was correlated with higher 50% lethal dose and less corneal scarring
in vivo
. Thus, these studies point to a key role for the 8mer within the signal sequence of gK in HSV-1-induced pathogenicity.
Clinician-friendly lower extremity physical performance measures in athletes: a systematic review of measurement properties and correlation with injury, part 1. The tests for knee function including the hop tests
Authors: Hegedus Eric J , McDonough Suzanne , Bleakley Chris , Cook Chad E , Baxter G David 
Published: December 2014

ObjectiveTo review the measurement properties of physical performance tests (PPTs) of the knee as each pertain to athletes, and to determine the relationship between PPTs and injury in athletes age 12 years to adult.MethodsA search strategy was constructed by combining the terms ‘lower extremity’ and synonyms for ‘performance test’, and names of performance tests with variants of the term ‘athlete’. In this, part 1, we report on findings in the knee. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed and theConsensus-basedStandards for the selection of healthMeasurementInstruments (COSMIN) checklist was used to critique the methodological quality of each paper. A second measure was used to analyse the quality of the measurement properties of each test.ResultsIn the final analysis, we found 29 articles pertinent to the knee detailing 19 PPTs, of which six were compiled in a best evidence synthesis. The six tests were: one leg hop for distance (single and triple hop), 6 m timed hop, crossover hop for distance, triple jump and single leg vertical jump. The one leg hop for distance is the most often studied PPT. There is conflicting evidence regarding the validity of the hop and moderate evidence that the hop test is responsive to changes during rehabilitation. No test has established reliability or measurement error as assessed by the minimal important change or smallest detectable change. No test predicts knee injury in athletes.ConclusionsDespite numerous published articles addressing PPTs at the knee, there is predominantly limited and conflicting evidence regarding the reliability, agreement, construct validity, criterion validity and responsiveness of commonly used PPTs. There is a great opportunity for further study of these tests and the measurement properties of each in athletes.
A district general hospital experience of palliative biliary stenting
Authors: Thomas S E , Lee M J , Sivaramakrishnan N , Lambert K 
Published: December 2014

BackgroundPalliative management of malignant pancreaticobiliary (PB) disease typically takes the form of endoscopic biliary stenting with a covered metal stent. We set out to assess outcomes from endoscopic biliary stenting (endoscopic retrograde cholangiopancreatography, ERCP) for malignant disease in our district general hospital (DGH).MethodsWe identified patients with malignant PB disease who underwent primary ERCP between 2011 and 2012. Case notes were reviewed for clinical outcomes and involvement of palliative care.Results38 patients underwent biliary stenting in this period. Median age was 75.6 years (53.6–99.8 years). 35 stents were placed for primary PB malignancy. 31 of these stents were covered metal stents and 6 were uncovered. Bilirubin decreased from a median of 218 to 112 µmol/L (median decrease 55 µmol/L). Complications occurred in the following 13 cases: 7 blocked stents (18.9%), 2 of which were associated with sepsis; 2 cases of stent migration (8.1%); 3 cases of biliary sepsis (8.1%) and 1 episode of pancreatitis (2.7%). Subsequently, 12 patients underwent a single repeat ERCP and 1 patient underwent 3 further ERCPs. Median survival following ERCP and stent was 78 days (10–806). 28 patients (76%) were known to the hospital palliative care team.ConclusionsOur DGH provides local service with complication rates comparable to those described in the literature. This allows care of patients with limited prognosis to be treated close to home. The majority of stent complications and mortality occur within 3 months. Input from the palliative care team is useful when considering whether a patient has a prognosis long enough to benefit from the procedure.
Controls on deltaic sedimentation in glacio-eustatic cycles of late Marsdenian (Namurian R
2b
4 to R
2c
1, Pennsylvanian) age in the UK Central Pennine Basin
Authors: Jones C. M. 
Published: December 2014

Summary

Evolution of the succession between the
Bilinguites eometabilinguis
(R
2b
4) and
Verneulites sigma
(R
2c
2) marine bands of Marsdenian (Pennsylvanian) age in the Central Pennine Basin, and its offshore extension into the North Sea Basin, is discussed. Five separate marine bands are now recognized. Two closely spaced marine bands,
B. eometabilinguis
and
B. metabilinguis
, occur at the base of the R
2b
4 cycle and a higher
B. metabilinguis
band occurs at the base of the R
2b
5 cycle. The overlying
B. superbilinguis
and
V. sigma
marine bands define an additional thinner and much simpler cycle (R
2c
1). These three cycles are all of glacio-eustatic origin. A new sequence-stratigraphic interpretation examines the relationship between the constituent sandstone units (currently named the Hazel Greave Grit, Beacon Hill Flags, Guiseley Grit, Ashover Grit, Roaches Grit, plus local names and unnamed units). Different types of fluvial-deltaic sequences were deposited in different phases of the cycle and some cycles lack coarse clastic lithologies. The succession in parts of Yorkshire and Lancashire contains a major non-sequence in the R
2b
5 cycle. A revised interpretation of the incised deep channels in the Roaches Grit in Staffordshire, suggesting river channel adjustment to a post-glacial climate rather than infill of a pre-eroded palaeovalley, is also presented. Many of these different features can be explained by climatic variations associated with the Carboniferous Ice Age. Variations in basin bathymetry and fault related subsidence exercised more localized controls.
Geology and geomorphology of the Palaeolithic site at High Lodge, Mildenhall, Suffolk, England
Authors: West R.G. , Gibbard P.L. , Boreham S. , Rolfe C. 
Published: December 2014

Summary

The geology of the High Lodge site at Mildenhall is described and re-interpreted as a sequence of deposits related to a doline formed in the underlying Chalk. Doline development in the area is considered in detail. Lacustrine sediments filling the depression contain a Palaeolithic industry and pollen assemblages that indicate contemporaneous coniferous woodland. The High Lodge sequence, at the northern end of the Warren Hill ridge, is related to the Three Hills site at the southern end of the ridge and to recent exposures near the Beech Clump, midway on the ridge. The geology of the three sites combines to demonstrate a series of ice-marginal proglacial successions along the west and south side of the Warren Hill ridge, marking a glacial limit. This Skertchly Line limit, on the eastern flank of the Fenland, resulted from the Tottenhill ice advance into Fenland late in the Wolstonian Stage (
c
. 160 ka; during Marine Isotope Stage [MIS] 6). Structural evidence indicates that the doline filling was initially thrust glaciotectonically by the glacial ice. These sediments were subsequently disturbed by diapirism arising from loading by meltwater deposits and possibly by periglacial processes. The doline strata predate the ice advance and represent a period of cool temperate vegetation, probably of interstadial character, earlier in the Wolstonian, during MIS 7. The High Lodge Palaeolithic industry is associated with this cool temperate period, not with pre-Anglian times as formerly proposed. At Three Hills, artefacts occur within the proglacial deposits and are reworked from an earlier period. The geomorphology of the Warren Hill ridge is described and an interpretation of the ice front presented. The relation of the area to the wider Fenland landscape development is discussed.
Multiresolution Analysis Based on Coalescence Hidden-Variable Fractal Interpolation Functions
Authors: Kapoor G. P. , Prasad Srijanani Anurag 
Published: December 2014

Multiresolution analysis arising from Coalescence Hidden-variable Fractal Interpolation Functions (CHFIFs) is developed. The availability of a larger set of free variables and constrained variables with CHFIF in multiresolution analysis based on CHFIFs provides more control in reconstruction of functions in L2(R) than that provided by multiresolution analysis based only on Affine Fractal Interpolation Functions (AFIFs). Our approach consists of introduction of the vector space of CHFIFs, determination of its dimension and construction of Riesz bases of vector subspaces Vk, k∈Z, consisting of certain CHFIFs in L2(R)∩C0(R).
Immune-Related Conditions and Acute Leukemia in Children with Down Syndrome: A Children's Oncology Group Report
Authors: Linabery Amy M. , Li Wenchao , Roesler Michelle A. , Spector Logan G. , Gamis Alan S. , Olshan Andrew F. , Heerema Nyla A. , Ross Julie A. 
Published: December 2014

Abstract
Background: Children with Down syndrome have unique immune profiles and increased leukemia susceptibility.
Methods: Mothers of 158 children with Down syndrome diagnosed with acute leukemia at 0 to 19 years in 1997 to 2002 and 173 children with Down syndrome but no leukemia were interviewed. Associations were evaluated via multivariable unconditional logistic regression.
Results: No associations were detected for asthma, eczema, allergies, or hypothyroidism. Diabetes mellitus associated with leukemia (OR = 9.23; 95% confidence interval 2.33–36.59); however, most instances occurred concurrent with or after the leukemia diagnosis.
Conclusions and Impact: Children with Down syndrome who develop leukemia have increased diabetes risk, likely due to treatment and underlying susceptibility factors. Cancer Epidemiol Biomarkers Prev; 24(2); 454–8. ©2014 AACR.
A Comparative Study of Wave Forcing Derived from the ERA-40 and ERA-Interim Reanalysis Datasets
Authors: Lu Hua , Bracegirdle Thomas J. , Phillips Tony , Turner John 
Published: December 2014

Abstract
The Eliassen–Palm (E-P) flux divergences derived from ERA-40 and ERA-Interim show significant differences during northern winter. The discrepancies are marked by vertically alternating positive and negative anomalies at high latitudes and are manifested via a difference in the climatology. The magnitude of the discrepancies can be greater than the interannual variability in certain regions. These wave forcing discrepancies are only partially linked to differences in the residual circulation but they are evidently related to the static stability in the affected regions. Thus, the main cause of the discrepancies is most likely an imbalance of radiative heating.
Two significant sudden changes are detected in the differences between the eddy heat fluxes derived from the two reanalyses. One of the changes may be linked to the bias corrections applied to the infrared radiances from the NOAA-12 High-Resolution Infrared Radiation Sounder in ERA-40, which is known to be contaminated by volcanic aerosol from the 1991 eruption of Mt. Pinatubo. The other change may be due in part to the use of uncorrected radiances from the NOAA-15 Advanced Microwave Sounding Units by ERA-Interim since 1998. These sudden changes have the potential to alter the wave forcing trends in the affected reanalysis, suggesting that extreme care is needed when one comes to extract trends from the highly derived wave forcing quantities.
Percutaneous endoscopic gastrostomy (PEG) site infections: a clinical and microbiological study from university teaching hospital, India
Authors: Krishna Sushma , Singh Sanjeev , Dinesh Kavitha R , KP Remya , Siyad Ismail , Karim Shamsul 
Published: December 2014

Background: Percutaneous endoscopic gastrostomy (PEG) is used to provide enteral access in patients who are unable to swallow. Infection of the stoma is an important complication and there is little data from India on this problem, which can be used to inform infection prevention and prophylactic strategies. Aim: The objective was to assess the prevalence and the role of contributory factors in PEG site infections. Methods: A total of 173 patients underwent PEG insertion from January 2011 to May 2012. Clinical and microbiological data were collected for culture-positive cases. Insertion was performed using a standard sterile pull-through technique. Infections were defined as two of: peristomal erythema, induration, and purulent discharge. Results: A total of 54 PEG infections occurred in 43 patients (28.85%). Seventy-seven organisms were isolated. Pseudomonas aeruginosa was the most common ( n=29) followed by coliforms ( n=21) and meticillin resistant Staphylococcus aureus (MRSA) ( n=6). Thirty-one (72%) received amoxicillin-clavulanic acid as prophylaxis and 12 (28%) were receiving concomitant antibiotics for their underlying conditions. The occurrence of PEG site infections was statistically independent of the administered prophylactic antibiotics ( p=0.3). Conclusions: This study has demonstrated the importance of PEG sites as a cause of healthcare associated infections. Educating patients on wound care practices would play a significant role in prevention of PEG site infections.
Evaluation of silica nanoparticle binding to major human blood proteins
Authors: Hata Katsutomo , Higashisaka Kazuma , Nagano Kazuya , Mukai Yohei , Kamada Haruhiko , Tsunoda Shin-ichi , Yoshioka Yasuo , Tsutsumi Yasuo 
Published: December 2014

Abstract
Nanomaterials are used for various biomedical applications because they are often more effective than conventional materials. Recently, however, it has become clear that the protein corona that forms on the surface of nanomaterials when they make contact with biological fluids, such as blood, influences the pharmacokinetics and biological responses induced by the nanomaterials. Therefore, when evaluating nanomaterial safety and efficacy, it is important to analyze the interaction between nanomaterials and proteins in biological fluids and to evaluate the effects of the protein corona. Here, we evaluated the interaction of silica nanoparticles, a commonly used nanomaterial, with the human blood proteins albumin, transferrin, fibrinogen, and IgG. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that the amount of albumin, transferrin, and IgG binding to the silica particles increased as the particle size decreased under conditions where the silica particle mass remained the same. However, under conditions in which the specific surface area remained constant, there were no differences in the binding of human plasma proteins to the silica particles tested, suggesting that the binding of silica particles with human plasma proteins is dependent on the specific surface area of the silica particles. Furthermore, the amount of albumin, transferrin, and IgG binding to silica nanoparticles with a diameter of 70 nm (nSP70) and a functional amino group was lower than that with unmodified nSP70, although there was no difference in the binding between nSP70 with the surface modification of a carboxyl functional group and nSP70. These results suggest that the characteristics of nanomaterials are important for binding with human blood proteins; this information may contribute to the development of safe and effective nanomaterials.
Oxidation Reactivity of a Structurally and Spectroscopically Well-defined Mononuclear Peroxocarbonato–Iron(III) Complex
Authors: Tsugawa Tomohiro , Furutachi Hideki , Marunaka Megumi , Endo Taichi , Hashimoto Koji , Fujinami Shuhei , Akine Shigehisa , Sakata Yoko , Nagatomo Shigenori , Tosha Takehiko , Nomura Takashi , Kitagawa Teizo , Ogura Takashi , Suzuki Masatatsu 
Published: December 2014

Abstract
A mononuclear peroxocarbonato–iron(III) complex [Fe(6Me-pic)2(O2C(O)O)]− (1-O2C(O)O) with bidentate ligands (6Me-pic), prepared by the reaction of a carbonato–iron(III) complex [Fe(6Me-pic)2(CO3)]− (1-CO3) with H2O2, was fully characterized. 1-O2C(O)O showed reversible O–O bond cleavage and reformation of the peroxo group under CO2 at 25 °C. 1-O2C(O)O is capable of not only oxidizing the C=C bond of cyclooctene but also the C–H bond of toluene. As for cyclooctene, epoxidation is favorable under CO2 in the presence of H2O, while cis-dihydroxylation precedes under N2, indicating that the oxidation reactivity of 1-O2C(O)O toward cyclooctene can be tuned by changing the concentration of CO2 and H2O.