bluuebunny/crossref_metadata_2025_split huggingface dataset:
BGLF4 Kinase Modulates the Structure and Transport Preference of the Nuclear Pore Complex To Facilitate Nuclear Import of Epstein-Barr Virus Lytic Proteins
Authors: Chang Chou-Wei , Lee Chung-Pei , Su Mei-Tzu , Tsai Ching-Hwa , Chen Mei-Ru 
Published: November 2014

ABSTRACT

BGLF4 kinase, the only Ser/Thr protein kinase encoded by the Epstein-Barr virus (EBV) genome, phosphorylates multiple viral and cellular substrates to optimize the cellular environment for viral DNA replication and the nuclear egress of nucleocapsids. Previously, we found that nuclear targeting of BGLF4 is through direct interaction with the FG repeat-containing nucleoporins (FG-Nups) Nup62 and Nup153 independently of cytosolic transport factors. Here, we investigated the regulatory effects of BGLF4 on the structure and biological functions of the nuclear pore complex (NPC). In EBV-positive NA cells, the distribution of FG-Nups was modified during EBV reactivation. In transfected cells, BGLF4 changed the staining pattern of Nup62 and Nup153 in a kinase activity-dependent manner. Detection with anti-phospho-Ser/Thr-Pro MPM-2 antibody demonstrated that BGLF4 induced the phosphorylation of Nup62 and Nup153. The nuclear targeting of importin β was attenuated in the presence of BGLF4, leading to inhibition of canonical nuclear localization signal (NLS)-mediated nuclear import. An
in vitro
nuclear import assay revealed that BGLF4 induced the nuclear import of larger molecules. Notably, we found that BGLF4 promoted the nuclear import of several non-NLS-containing EBV proteins, including the viral DNA-replicating enzymes BSLF1, BBLF2/3, and BBLF4 and the major capsid protein (VCA), in cotransfected cells. The data presented here suggest that BGLF4 interferes with the normal functions of Nup62 and Nup153 and preferentially helps the nuclear import of viral proteins for viral DNA replication and assembly. In addition, the nuclear import-promoting activity was found in cells expressing the BGLF4 homologs of another two gammaherpesviruses but not those from alpha- and betaherpesviruses.

IMPORTANCE
During lytic replication, many EBV genome-encoded proteins need to be transported into the nucleus, not only for viral DNA replication but also for the assembly of nucleocapsids. Because nuclear pore complexes are effective gateways that control nucleocytoplasmic traffic, most EBV proteins without canonical NLSs are retained in the cytoplasm until they form complexes with their NLS-containing partners for nuclear targeting. In this study, we found that EBV BGLF4 protein kinase interacts with the Nup62 and Nup153 and induces the redistribution of FG-Nups. BGLF4 modulates the function of the NPC to inhibit the nuclear import of host NLS-containing proteins. Simultaneously, the nuclear import of non-NLS-containing EBV lytic proteins was enhanced, possibly through phosphorylation of Nup62 and Nup153, nuclear pore dilation, or microtubule reorganization. Overall, our data suggest that BGLF4-induced modification of nuclear pore transport may block nuclear targeting of cellular proteins and increase the import of viral proteins to promote viral lytic replication.
The HIV-1 Nucleocapsid Protein Recruits Negatively Charged Lipids To Ensure Its Optimal Binding to Lipid Membranes
Authors: Kempf Noémie , Postupalenko Viktoriia , Bora Saurabh , Didier Pascal , Arntz Youri , de Rocquigny Hugues , Mély Yves 
Published: November 2014

ABSTRACT

The HIV-1 Gag polyprotein precursor composed of the matrix (MA), capsid (CA), nucleocapsid (NC), and p6 domains orchestrates virus assembly via interactions between MA and the cell plasma membrane (PM) on one hand and NC and the genomic RNA on the other hand. As the Gag precursor can adopt a bent conformation, a potential interaction of the NC domain with the PM cannot be excluded during Gag assembly at the PM. To investigate the possible interaction of NC with lipid membranes in the absence of any interference from the other domains of Gag, we quantitatively characterized by fluorescence spectroscopy the binding of the mature NC protein to large unilamellar vesicles (LUVs) used as membrane models. We found that NC, either in its free form or bound to an oligonucleotide, was binding with high affinity (∼10
7
M
−1
) to negatively charged LUVs. The number of NC binding sites, but not the binding constant, was observed to decrease with the percentage of negatively charged lipids in the LUV composition, suggesting that NC and NC/oligonucleotide complexes were able to recruit negatively charged lipids to ensure optimal binding. However, in contrast to MA, NC did not exhibit a preference for phosphatidylinositol-(4,5)-bisphosphate. These results lead us to propose a modified Gag assembly model where the NC domain contributes to the initial binding of the bent form of Gag to the PM.

IMPORTANCE
The NC protein is a highly conserved nucleic acid binding protein that plays numerous key roles in HIV-1 replication. While accumulating evidence shows that NC either as a mature protein or as a domain of the Gag precursor also interacts with host proteins, only a few data are available on the possible interaction of NC with lipid membranes. Interestingly, during HIV-1 assembly, the Gag precursor is thought to adopt a bent conformation where the NC domain may interact with the plasma membrane. In this context, we quantitatively characterized the binding of NC, as a free protein or as a complex with nucleic acids, to lipid membranes and showed that the latter constitute a binding platform for NC. Taken together, our data suggest that the NC domain may play a role in the initial binding events of Gag to the plasma membrane during HIV-1 assembly.
Islet autoantibody status in a multi-ethnic UK clinic cohort of children presenting with diabetes
Authors: Perchard R , MacDonald D , Say J , Pitts J , Pye S , Allgrove J , Banerjee K , Amin R 
Published: November 2014

ObjectiveWe prospectively determined islet autoantibody status in children presenting with diabetes to a single UK region in relation to ethnicity.Design316 (68.0% non-white) children presenting with diabetes between 2006 and 2013 were tested centrally for islet cell autoantibodies (ICA) and glutamic acid decarboxylase autoantibodies (GAD-65) at diagnosis, and if negative for both, tested for insulin autoantibodies (IAA). The assay used to measure GAD-65 autoantibodies changed from an in-house to a standardised ELISA method during the study.ResultsEven with use of the standardised ELISA method, 25.8% of children assigned a diagnosis of type 1 diabetes still tested negative for all three autoantibodies. 30% of children assigned a diagnosis of type 2 diabetes were autoantibody positive, and these had the highest glycated haemoglobin (HbA1c) levels at 12 months follow-up compared with other groups (p value for analysis of variance <0.001), although the sample size was small. Autoantibody positivity was similar between non-white and white children regardless of assay used (60.0% (n=129) vs 56.4% (n=57), χ2=0.9, p=0.35), as was mean GAD-65 autoantibody levels, but fewer non-white children had two or more autoantibodies detectable (13% (n=28) vs 27.7% (n=28), χ2=12.1, p=0.001).ConclusionsIslet autoantibody positivity was associated with a more severe phenotype, as demonstrated by poorer glycaemic control, regardless of assigned diabetes subtype. Positivity did not differ by ethnic group.
SRT1720 Induces Lysosomal-Dependent Cell Death of Breast Cancer Cells
Authors: Lahusen Tyler J. , Deng Chu-Xia 
Published: November 2014

Abstract
SRT1720 is an activator of SIRT1, a NAD+-dependent protein and histone deacetylase that plays an important role in numerous biologic processes. Several studies have illustrated that SRT1720 treatment could improve metabolic conditions in mouse models and in a study in cancer SRT1720 caused increased apoptosis of myeloma cells. However, the effect of SRT1720 on cancer may be complex, as some recent studies have demonstrated that SRT1720 may not directly activate SIRT1 and another study showed that SRT1720 treatment could promote lung metastasis. To further investigate the role of SRT1720 in breast cancer, we treated SIRT1 knockdown and control breast cancer cell lines with SRT1720 both in vitro and in vivo. We showed that SRT1720 more effectively decreased the viability of basal-type MDA-MB-231 and BT20 cells as compared with luminal-type MCF-7 breast cancer cells or nontumorigenic MCF-10A cells. We demonstrated that SRT1720 induced lysosomal membrane permeabilization and necrosis, which could be blocked by lysosomal inhibitors. In contrast, SRT1720-induced cell death occurred in vitro irrespective of SIRT1 status, whereas in nude mice, SRT1720 exhibited a more profound effect in inhibiting the growth of allograft tumors of SIRT1 proficient cells as compared with tumors of SIRT1-deficient cells. Thus, SRT1720 causes lysosomal-dependent necrosis and may be used as a therapeutic agent for breast cancer treatment. Mol Cancer Ther; 14(1); 183–92. ©2014 AACR.
Detection of Bursaphelenchus xylophilus infection in Pinus massoniana from hyperspectral data
Authors: Ju Yunwei , Pan Jie , Wang Xiaotang , Zhang Heng 
Published: November 2014

Hyperspectral remote sensing has great potential for accurate detection of forest pests and diseases. The main objectives of this research were: i) to determine the best hyperspectral wavelengths or their combinations to discriminate Pinus massoniana trees infected by Bursaphelenchus xylophilus disease from healthy trees over the spectral range of 350-1000 nm; and ii) to assess the chlorophyll content of infected trees using the hyperspectral algorithm. We also discuss the possibility of an early detection method of B. xylophilus disease dynamics by combining the spectral characteristics and the chlorophyll content of trees. The hyperspectral data were gathered for six stages of healthy to infected trees using a 1-nm-wide handheld spectroradiometer. First derivative (FD) spectra and vegetation indices were used for data dimensionality reduction and to select the most effective wavelengths for detection. The most effective FD spectrum in 759 nm was selected to discriminate the infected and healthy P. massoniana plants. The normalised difference vegetation index (NDVI)(810,450) value in the fully infected stage correlated with the variation of chlorophyll content (). We conclude that the combination of specific spectral characteristics and chlorophyll content is a reliable method for confirming infection about 30 days after B. xylophilus inoculation.
The Community Earth System Model (CESM) Large Ensemble Project: A Community Resource for Studying Climate Change in the Presence of Internal Climate Variability
Authors: Kay J. E. , Deser C. , Phillips A. , Mai A. , Hannay C. , Strand G. , Arblaster J. M. , Bates S. C. , Danabasoglu G. , Edwards J. , Holland M. , Kushner P. , Lamarque J.-F. , Lawrence D. , Lindsay K. , Middleton A. , Munoz E. , Neale R. , Oleson K. , Polvani L. , Vertenstein M. 
Published: November 2014

Abstract
While internal climate variability is known to affect climate projections, its influence is often underappreciated and confused with model error. Why? In general, modeling centers contribute a small number of realizations to international climate model assessments [e.g., phase 5 of the Coupled Model Intercomparison Project (CMIP5)]. As a result, model error and internal climate variability are difficult, and at times impossible, to disentangle. In response, the Community Earth System Model (CESM) community designed the CESM Large Ensemble (CESM-LE) with the explicit goal of enabling assessment of climate change in the presence of internal climate variability. All CESM-LE simulations use a single CMIP5 model (CESM with the Community Atmosphere Model, version 5). The core simulations replay the twenty to twenty-first century (1920–2100) 30 times under historical and representative concentration pathway 8.5 external forcing with small initial condition differences. Two companion 1000+-yr-long preindustrial control simulations (fully coupled, prognostic atmosphere and land only) allow assessment of internal climate variability in the absence of climate change. Comprehensive outputs, including many daily fields, are available as single-variable time series on the Earth System Grid for anyone to use. Early results demonstrate the substantial influence of internal climate variability on twentieth- to twenty-first-century climate trajectories. Global warming hiatus decades occur, similar to those recently observed. Internal climate variability alone can produce projection spread comparable to that in CMIP5. Scientists and stakeholders can use CESM-LE outputs to help interpret the observational record, to understand projection spread and to plan for a range of possible futures influenced by both internal climate variability and forced climate change.
Extended Reconstructed Sea Surface Temperature Version 4 (ERSST.v4): Part II. Parametric and Structural Uncertainty Estimations
Authors: Liu Wei , Huang Boyin , Thorne Peter W. , Banzon Viva F. , Zhang Huai-Min , Freeman Eric , Lawrimore Jay , Peterson Thomas C. , Smith Thomas M. , Woodruff Scott D. 
Published: November 2014

Abstract
Described herein is the parametric and structural uncertainty quantification for the monthly Extended Reconstructed Sea Surface Temperature (ERSST) version 4 (v4). A Monte Carlo ensemble approach was adopted to characterize parametric uncertainty, because initial experiments indicate the existence of significant nonlinear interactions. Globally, the resulting ensemble exhibits a wider uncertainty range before 1900, as well as an uncertainty maximum around World War II. Changes at smaller spatial scales in many regions, or for important features such as Niño-3.4 variability, are found to be dominated by particular parameter choices.
Substantial differences in parametric uncertainty estimates are found between ERSST.v4 and the independently derived Hadley Centre SST version 3 (HadSST3) product. The largest uncertainties are over the mid and high latitudes in ERSST.v4 but in the tropics in HadSST3. Overall, in comparison with HadSST3, ERSST.v4 has larger parametric uncertainties at smaller spatial and shorter time scales and smaller parametric uncertainties at longer time scales, which likely reflects the different sources of uncertainty quantified in the respective parametric analyses. ERSST.v4 exhibits a stronger globally averaged warming trend than HadSST3 during the period of 1910–2012, but with a smaller parametric uncertainty. These global-mean trend estimates and their uncertainties marginally overlap.
Several additional SST datasets are used to infer the structural uncertainty inherent in SST estimates. For the global mean, the structural uncertainty, estimated as the spread between available SST products, is more often than not larger than the parametric uncertainty in ERSST.v4. Neither parametric nor structural uncertainties call into question that on the global-mean level and centennial time scale, SSTs have warmed notably.
An Interdecadal Change in the Relationship between Boreal Spring Arctic Oscillation and the East Asian Summer Monsoon around the Early 1970s
Authors: Chen Shangfeng , Chen Wen , Wu Renguang 
Published: November 2014

Abstract
Previous studies suggested that the boreal spring Arctic Oscillation (AO) exerts a pronounced influence on the following East Asian summer monsoon (EASM) variability. This study reveals that the relationship of spring AO with the following EASM experienced a significant interdecadal change in the early 1970s. The influence of spring AO on the following EASM is weak during the 1950s and 1960s but strong and significant during the mid-1970s through the mid-1990s. The spring AO-related sea surface temperature (SST), atmospheric circulation, and heating anomalies are compared between 1949–71 and 1975–97. Results show that the spring AO-related cyclonic circulation anomaly over the tropical western North Pacific is weaker and located more northward in the former epoch than in the latter epoch. Correspondingly, SST, atmospheric circulation, and heating anomalies over the tropical North Pacific are located more northeastward in the former than latter epoch from spring to summer. In the following summer, the spring AO-related cyclonic circulation anomalies over the tropical North Pacific are located farther away from East Asia in the former epoch. This interdecadal change in the AO–EASM connection may be attributed to a significant change in the intensity of spring North Pacific synoptic-scale eddy activity around the early 1970s from a weak regime to a strong regime, which induces a stronger eddy feedback to the low-frequency mean flow after the early 1970s. This may explain a stronger spring AO-related cyclonic circulation over the tropical western North Pacific and thus a closer relationship between the spring AO and the following EASM in the latter than former epoch.
Spontaneous hemopneumothorax: Our experience with surgical management
Authors: Tay Cheong Kiat Julian , Yee Yong Chen , Asmat Atasha 
Published: November 2014

Background Spontaneous hemopneumothorax is rare, accounting for only 1%–12% of patients presenting with spontaneous pneumothorax. The optimal management of these patients remains controversial with no definitive guidelines on patient selection and timing of surgery. The aim of this study was to review our institution’s surgical experience in the management of patients with spontaneous hemopneumothorax. Methods We performed a retrospective review of all patients with spontaneous hemopneumothorax who underwent surgery from January 2000 to June 2013. Patient data were obtained from our institution’s primary spontaneous pneumothorax database. Results Of 510 patients who underwent surgery for spontaneous pneumothorax, 33 (6.4%) developed spontaneous hemopneumothorax. The mean age was 24.0 years (range 16–40 years). In 30 (90.9%) patients, it was their first presentation of pneumothorax. There were 25 (75.8%) patients with Vanderschueren stage III spontaneous pneumothorax. Blood loss ranged from 250 to 3000 mL (mean 1280 mL). In 28 patients, a torn adhesion band was the source of bleeding. Thoracotomy was the surgical approach in 9 (27.3%) patients, and video-assisted thoracic surgery was used in 24 (72.7%). One patient required reoperation for retained clots. There was no mortality. Conclusion Our results suggest that surgical management of spontaneous hemopneumothorax can be undertaken with minimal morbidity and mortality. With the increasing use of video-assisted thoracic surgery, definitive surgical management of spontaneous hemopneumothorax can be instituted earlier.
Arterial Anatomy of the Tibialis Posterior Tendon
Authors: Manske Mary Claire , McKeon Kathleen E. , Johnson Jeffrey E. , McCormick Jeremy J. , Klein Sandra E. 
Published: November 2014

Background: Tibialis posterior tendon dysfunction is a common disorder leading to pain, deformity, and disability, although its pathogenesis is unclear. A vascular etiology has been proposed, but there is controversy regarding the existence of a hypovascular region that may render the tendon vulnerable. The purpose of this study was to provide a description of the arterial anatomy supplying the tibialis posterior tendon. Methods: Sixty adult cadaveric lower extremities were obtained from a university-affiliated body donation program. Thirty specimens obtained within 72 hours of death were used for microscopic analysis. Thirty specimens were previously frozen and used for macroscopic analysis. The tibialis anterior, tibialis posterior, and peroneal arteries were injected with India Ink and Ward’s Blue Latex. The specimens used for macroscopic analysis were debrided with sodium hypochlorite to expose the extratendinous anatomy. For the microscopic analysis, the tendon was cleared using a modified Spälteholz technique to expose the intratendinous vascular anatomy. Results: Macroscopically, an average of 2.5 ± 0.7 vessels entered the tendon proximal to the navicular insertion. In all, 28/30 (93.3%) specimens had a vessel entering 4.1 ± 0.6 cm proximal to the medial malleolus and 24/30 (80.0%) specimens had a vessel entering 1.7 ± 0.9 cm distal to the medial malleolus. Microscopically, an average of 1.9 ± 0.3 vessels entered each tendon proximal to the navicular insertion. In total, 27/30 (90%) specimens had a vessel entering the tendon 4.8 ± 0.8 cm proximal to the medial malleolus and 30/30 (100%) specimens had a vessel entering the tendon 1.9 ± 0.8 cm distal to the medial malleolus. In all specimens, a hypovascular region was observed, starting 2.2 ± 0.8 cm proximal to the medial malleolus and ending 0.6 ± 0.6 cm proximal to the medial malleolus with an average length of 1.5 ± 1.0 cm. The insertion of the tendon was well vascularized both on microscopic and macroscopic specimens. Conclusion: The tibialis posterior tendon was supplied by 2 vessels entering the tendon approximately 4.5 cm proximal and 2.0 cm distal to the medial malleolus. A retromalleolar hypovascular region was observed. Clinical Relevance: Improved understanding of the vascularity of the tibialis posterior tendon may be helpful in clinical practice and potentially provides a basis for further evaluation of the causative factors of tibialis posterior tendinopathy.
Lipoatrophy in Children With Type 1 Diabetes
Authors: Kordonouri Olga , Biester Torben , Schnell Kerstin , Hartmann Reinhard , Tsioli Christiana , Fath Maryam , Datz Nicolin , Danne Thomas 
Published: November 2014

Objectives: The objectives were to evaluate the current prevalence of lipoatrophy at insulin injection sites in young patients with type 1 diabetes. Methods: Standardized examination of insulin injection sites in all 678 patients with type 1 diabetes treated in 2013 in our outpatient clinic were conducted. In case of lipoatrophy photo documentation and standardized interview with parents and patients were performed. Methods: We identified a total of 16 patients (43.8% male) with lipoatrophy (overall prevalence 2.4%). The current mean age (±SD) of the affected patients was 14.4 ± 3.9 years, age and diabetes duration at onset of lipoatrophy were 11.5 ± 3.8 years and 5.4 ± 3.6 years, respectively. All patients were using analogs at the onset of lipoatrophy. In all, 14 of 16 patients (87.5%) were on insulin pump compared with 52% without lipoatrophy ( P = .0018). The use of steel needle and Teflon catheter was equal between the pump patients. Concomitant autoimmune diseases were present in 37.5% of the patients (thyroiditis: n = 3, thyroiditis and celiac disease: n = 2, celiac disease: n = 1) compared with 15.0% in those without lipoatrophy ( P = .0128). Conclusions: Lipoatrophy was present in young patients treated with modern insulins and pumps; however, the prevalence was relatively low as expected with the use of modern insulins. Our data may support the hypothesis that a constant mechanical element such as a subcutaneous catheter may trigger the development of lipoatrophy, particularly in those patients with more than 1 autoimmune disease.