bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural Single-Nucleotide Variations in the HIV-1 Genomic SA1prox Region Can Alter Viral Replication Ability by Regulating Vif Expression Levels
Authors: Nomaguchi Masako , Doi Naoya , Sakai Yosuke , Ode Hirotaka , Iwatani Yasumasa , Ueno Takamasa , Matsumoto Yui , Miyazaki Yasuyuki , Masuda Takao , Adachi Akio 
Published: February 2016

ABSTRACT

We previously found that natural single-nucleotide variations located within a proximal region of splicing acceptor 1 (SA1prox) in the HIV-1 genome could alter the viral replication potential and mRNA expression pattern, especially the
vif
mRNA level. Here, we studied the virological and molecular basis of nucleotide sequence variations in SA1prox for alterations of viral replication ability. Consistent with our previous findings, variant clones indeed expressed Vif at different levels and grew distinctively in cells with various APOBEC3G expression levels. Similar effects were observed for natural variations found in HIV-2 SA1prox, suggesting the importance of the SA1prox sequence. To define nucleotides critical for the regulation of HIV-1 Vif expression, effects of natural SA1prox variations newly found in the HIV Sequence Compendium database on
vif
mRNA/Vif protein levels were examined. Seven out of nine variations were found to produce Vif at lower, higher, or more excessive levels than wild-type NL4-3. Combination experiments of variations giving distinct Vif levels suggested that the variations mutually affected
vif
transcript production. While low and high producers of Vif grew in an APOBEC3G-dependent manner, excessive expressers always showed an impeded growth phenotype due to defects in single-cycle infectivity and/or virion production levels. The phenotype of excessive expressers was not due primarily to inadequate expression of Tat or Rev, although SA1prox variations altered the overall HIV-1 mRNA expression pattern. Collectively, our results demonstrate that HIV SA1prox regulates Vif expression levels and suggest a relationship between SA1prox and viral adaptation/evolution given that variations occurred naturally.

IMPORTANCE
While human cells possess restriction factors to inhibit HIV-1 replication, HIV-1 encodes antagonists to overcome these barriers. Conflicts between host restriction factors and viral counterparts are critical driving forces behind mutual evolution. The interplay of cellular APOBEC3G and viral Vif proteins is a typical example. Here, we demonstrate that naturally occurring single-nucleotide variations in the proximal region of splicing acceptor 1 (SA1prox) of the HIV-1 genome frequently alter Vif expression levels, thereby modulating viral replication potential in cells with various ABOBEC3G levels. The results of the present study reveal a previously unidentified and important way for HIV-1 to compete with APOBEC3G restriction by regulating its Vif expression levels. We propose that SA1prox plays a regulatory role in Vif counteraction against APOBEC3G in order to contribute to HIV-1 replication and evolution, and this may be applicable to other primate lentiviruses.
Nonstructural Protein NP1 of Human Bocavirus 1 Plays a Critical Role in the Expression of Viral Capsid Proteins
Authors: Zou Wei , Cheng Fang , Shen Weiran , Engelhardt John F. , Yan Ziying , Qiu Jianming 
Published: February 2016

ABSTRACT

A novel chimeric parvoviral vector, rAAV2/HBoV1, in which the recombinant adeno-associated virus 2 (rAAV2) genome is pseudopackaged by the human bocavirus 1 (HBoV1) capsid, has been shown to be highly efficient in gene delivery to human airway epithelia (Z. Yan et al., Mol Ther 21:2181–2194, 2013,
http://dx.doi.org/10.1038/mt.2013.92
). In this vector production system, we used an HBoV1 packaging plasmid, pHBoV1NSCap, that harbors HBoV1 nonstructural protein (
NS
) and capsid protein (
Cap
) genes. In order to simplify this packaging plasmid, we investigated the involvement of the HBoV1 NS proteins in capsid protein expression. We found that NP1, a small NS protein encoded by the middle open reading frame, is required for the expression of the viral capsid proteins (VP1, VP2, and VP3). We also found that the other NS proteins (NS1, NS2, NS3, and NS4) are not required for the expression of VP proteins. We performed systematic analyses of the HBoV1 mRNAs transcribed from the pHBoV1NSCap packaging plasmid and its derivatives in HEK 293 cells. Mechanistically, we found that NP1 is required for both the splicing and the read-through of the proximal polyadenylation site of the HBoV1 precursor mRNA, essential functions for the maturation of capsid protein-encoding mRNA. Thus, our study provides a unique example of how a small viral nonstructural protein facilitates the multifaceted regulation of capsid gene expression.

IMPORTANCE
A novel chimeric parvoviral vector, rAAV2/HBoV1, expressing a full-length cystic fibrosis transmembrane conductance regulator (CFTR) gene, is capable of correcting CFTR-dependent chloride transport in cystic fibrosis human airway epithelium. Previously, an HBoV1 nonstructural and capsid protein-expressing plasmid, pHBoV1NSCap, was used to package the rAAV2/HBoV1 vector, but yields remained low. In this study, we demonstrated that the nonstructural protein NP1 is required for the expression of capsid proteins. However, we found that the other four nonstructural proteins (NS1 to -4) are not required for expression of capsid proteins. By mutating the
cis
elements that function as internal polyadenylation signals in the capsid protein-expressing mRNA, we constructed a simple HBoV1 capsid protein-expressing gene that expresses capsid proteins as efficiently as pHBoV1NSCap does, and at similar ratios, but independently of NP1. Our study provides a foundation to develop a better packaging system for rAAV2/HBoV1 vector production.
Diseases Transmitted by Domestic Livestock: Perils of the Petting Zoo
Authors: Dunn John R. , Behravesh Casey Barton , Angulo Frederick J. 
Published: February 2016

ABSTRACT
Petting zoo venues encourage or permit public contact with animals which provide opportunities for education and entertainment. These venues vary but are common at county or state fairs, zoos, and aquariums. In addition to these common petting zoo settings, animals are present in many other venues where the public is permitted to contact them and their environment. Thus, humans may have contact with animals in a wide range of settings, and transmission of infectious diseases from animals to humans may occur at any of these venues, creating perils associated with petting zoos.
There are many considerations when evaluating perils associated with the wide range of venues where animal contact can occur. First, many venues or events draw large numbers of people; some operate during a short time frame, while others, such as zoos and aquariums, operate year round. Second, petting zoos and other animal contact venues are particularly popular with children, who compared with adults, commonly have less stringent hygienic practices and are more susceptible to severe disease outcomes. Finally, there is remarkable variability in the physical layout of venues that permit animal contact and in the types of animals that may be contacted. Animal contact areas range from well-designed permanent exhibits targeting risk reduction to various temporary or seasonal exhibits established without detailed planning. Many petting zoos house only small ruminant species such as sheep and goats, but other venues house a wide variety of mammalian species, exotic animals, poultry and other avian species, reptiles and amphibians, and aquatic animals.
Potassium Channel Subfamily K Member 3 (KCNK3) Contributes to the Development of Pulmonary Arterial Hypertension
Authors: Antigny Fabrice , Hautefort Aurélie , Meloche Jolyane , Belacel-Ouari Milia , Manoury Boris , Rucker-Martin Catherine , Péchoux Christine , Potus François , Nadeau Valérie , Tremblay Eve , Ruffenach Grégoire , Bourgeois Alice , Dorfmüller Peter , Breuils-Bonnet Sandra , Fadel Elie , Ranchoux Benoît , Jourdon Philippe , Girerd Barbara , Montani David , Provencher Steeve , Bonnet Sébastien , Simonneau Gérald , Humbert Marc , Perros Frédéric 
Published: February 2016

Background—

Mutations in the
KCNK3
gene have been identified in some patients suffering from heritable pulmonary arterial hypertension (PAH).
KCNK3
encodes an outward rectifier K
+
channel, and each identified mutation leads to a loss of function. However, the pathophysiological role of potassium channel subfamily K member 3 (KCNK3) in PAH is unclear. We hypothesized that loss of function of KCNK3 is a hallmark of idiopathic and heritable PAH and contributes to dysfunction of pulmonary artery smooth muscle cells and pulmonary artery endothelial cells, leading to pulmonary artery remodeling: consequently, restoring KCNK3 function could alleviate experimental pulmonary hypertension (PH).

Methods and Results—
We demonstrated that KCNK3 expression and function were reduced in human PAH and in monocrotaline-induced PH in rats. Using a patch-clamp technique in freshly isolated (not cultured) pulmonary artery smooth muscle cells and pulmonary artery endothelial cells, we found that KCNK3 current decreased progressively during the development of monocrotaline-induced PH and correlated with plasma-membrane depolarization. We demonstrated that KCNK3 modulated pulmonary arterial tone. Long-term inhibition of KCNK3 in rats induced distal neomuscularization and early hemodynamic signs of PH, which were related to exaggerated proliferation of pulmonary artery endothelial cells, pulmonary artery smooth muscle cell, adventitial fibroblasts, and pulmonary and systemic inflammation. Lastly, in vivo pharmacological activation of KCNK3 significantly reversed monocrotaline-induced PH in rats.

Conclusions—
In PAH and experimental PH, KCNK3 expression and activity are strongly reduced in pulmonary artery smooth muscle cells and endothelial cells. KCNK3 inhibition promoted increased proliferation, vasoconstriction, and inflammation. In vivo pharmacological activation of KCNK3 alleviated monocrotaline-induced PH, thus demonstrating that loss of KCNK3 is a key event in PAH pathogenesis and thus could be therapeutically targeted.
China as the Guardian of the International Seabed Area in the Central Arctic Ocean
Authors: Magnússon Bjarni Már 
Published: February 2016

China has been engaging more actively in the Arctic, as echoed by the Arctic Council’s admittance of China as a permanent observer in May 2013. China’s interest in the Arctic can to a large extent be explained by climate change shrinking the ice cover of the Arctic Ocean, which has sparked interest with respect to possible exploitation of natural resources and new shipping routes. One aspect of the possible exploitation of natural resources concerns the International Seabed Area. The Stockholm International Peace Research Institute’s policy paper on China’s Arctic aspirations stated that “many Chinese scholars believe that UNCLOS does not entirely safeguard China’s perceived Arctic interests” concerning the continental shelf beyond 200 nautical miles. One scholar noted that “[i]f the Arctic states succeed in their claims to extend their outer continental shelves, the international community’s and China’s right to fairly benefit from Arctic resources will be weakened”.
This article asks whether China can act as a watchdog against excessive continental shelf claims beyond 200 nautical miles by the littoral states and shield the idea of the common heritage of mankind, as enshrined in the Area. More precisely, the article will ask whether China can bring a case before an international court or tribunal against one of the littoral states if it establishes the outer limits of the extended continental shelf beyond what they are entitled to according to UNCLOS.
Susceptibility to Hamstring Injuries in Soccer
Authors: Schuermans Joke , Van Tiggelen Damien , Danneels Lieven , Witvrouw Erik 
Published: February 2016

Background: Running-related hamstring strain injuries remain a delicate issue in several sports such as soccer. Their unremittingly high incidence and recurrence rates indicate that the underlying risk has not yet been fully identified. Among other factors, the importance of neuromuscular coordination and the quality of interplay between the different hamstring muscle bellies is thought to be a key determinant within the intrinsic injury risk. Muscle functional magnetic resonance imaging (mfMRI) is one of the tools that has been proven to be valid for evaluating intermuscular coordination. Purpose: To investigate the risk of sustaining an index or recurring soccer-related hamstring injury by exploring metabolic muscle characteristics using mfMRI. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 27 healthy male soccer players and 27 soccer players with a history of hamstring injuries underwent standardized mfMRI. The mfMRI protocol consisted of a resting scan, a strenuous bilateral eccentric hamstring exercise, and a postexercise scan. The exercise-related T2 change, or the signal intensity shift between both scans, was used to detect differences in metabolic characteristics between (1) the different hamstring muscle bellies and (2) the prospective cohorts based on the (re)occurrence of hamstring injuries during a follow-up period of 18 months. Results: The risk of sustaining a first hamstring injury was associated with alterations in the intermuscular hierarchy in terms of the magnitude of the metabolic response after a heavy eccentric effort, with the dominant role of the semitendinosus set aside for a higher contribution of the biceps femoris ( P = .017). Receiver operating characteristic (ROC) curve analysis demonstrated that this variable was significantly able to predict the occurrence of index injuries with a sensitivity of 100% and a specificity of 70% when the metabolic activity of the biceps femoris exceeded 10%. The risk of sustaining a reinjury was associated with a substantial deficit in hamstring strength endurance ( P = .031). Soccer players who sustained a reinjury were only able to perform prone leg curls for a mean duration of 146.50 ± 76.16 seconds, whereas those with an injury history but no recurrence during follow-up were able to continue for a mean of 237.45 ± 110.76 seconds (95% CI, 11.9-230.5 seconds; P = .031). Conclusion: This was the first study to assess the causal relation between the intramuscular recruitment pattern and the risk of sustaining an index or secondary hamstring strain. Changes in intermuscular interplay seem to significantly increase the risk of sustaining index hamstring injuries in male amateur soccer players. Inadequate eccentric muscle endurance could be associated with an increased risk of sustaining a recurring hamstring injury.
Effect of Hypercholesterolemia on Fatty Infiltration and Quality of Tendon-to-Bone Healing in a Rabbit Model of a Chronic Rotator Cuff Tear
Authors: Chung Seok Won , Park HaeBong , Kwon Jieun , Choe Ghee Young , Kim Sae Hoon , Oh Joo Han 
Published: February 2016

Background: The incidence of healing failure after rotator cuff repair is high, and fatty infiltration is a crucial factor in healing failure. Purpose: To verify the effect of hypercholesterolemia on fatty infiltration and the quality of tendon-to-bone healing and its reversibility by lowering the cholesterol level in a chronic tear model using the rabbit supraspinatus. Study Design: Controlled laboratory study. Methods: Forty-eight rabbits were randomly allocated into 4 groups (n = 12 each). After 4 weeks of a high-cholesterol diet (groups A and B) and a regular diet (groups C and D), the supraspinatus tendon was detached and left alone for 6 weeks and then was repaired in a transosseous manner (groups A, B, and C). Group D served as a control. Group A continued to receive the high-cholesterol diet until the final evaluation (6 weeks after repair); however, at the time of repair, group B was changed to a general diet with administration of a cholesterol-lowering agent (simvastatin). Histological evaluation of the fat-to-muscle proportion was performed twice, at the time of repair and the final evaluation, and an electromyographic (EMG) test, mechanical test, and histological test of tendon-to-bone healing were performed at the final evaluation. Results: For the EMG test, group A showed a significantly smaller area of compound muscle action potential compared with groups C and D (all P <.01), and group B showed a larger area than group A, almost up to the level of group C ( P = .312). Similarly, group A showed significantly lower mechanical properties both in load-to-failure and stiffness compared with groups C and D (all P <.05). In addition, although not significantly different, the mechanical properties of group B were higher than those of group A (mean load-to-failure: group A = 42.01 N, group B = 58.23 N [ P = .103]; mean stiffness: group A = 36.32 N/mm, group B = 47.22 N/mm [ P = .153]). For the histological test, groups A and B showed a significantly higher fat-to-muscle proportion than did groups C and D at 6 weeks after detachment (all P <.05), but at the final evaluation, group B showed a decreased fat-to-muscle proportion (mean ± SD: from 64.02% ± 11.87% to 54.68% ± 10.47%; P = .146) compared with group A, which showed increased fat-to-muscle proportion (from 59.26% ± 17.80% to 78.23% ± 10.87%; P = .015). Groups B and C showed better tendon-to-bone interface structures than did group A, which showed coarse and poorly organized collagen fibers with fat interposition. Conclusion: Hypercholesterolemia had a deleterious effect on fatty infiltration and the quality of tendon-to-bone repair site, and lowering hypercholesterolemia seemed to halt or reverse these harmful effects in this experimental model. Clinical Relevance: Systemic diseases such as hypercholesterolemia should be tightly controlled during the perioperative period of rotator cuff repair.
Prospective Comparison of Acute Kidney Injury During Treatment With the Combination of Piperacillin-Tazobactam and Vancomycin Versus the Combination of Cefepime or Meropenem and Vancomycin
Authors: Peyko Vincent , Smalley Samantha , Cohen Henry 
Published: February 2016

Purpose: To prospectively evaluate the observed incidence of acute kidney injury (AKI) in adult patients receiving the combination of piperacillin-tazobactam and vancomycin versus the combination of cefepime or meropenem and vancomycin for greater than 72 hours. Methods: This was a prospective, open-label cohort study at a community academic medical center involving adult patients over a 3-month time period who received either the combination of piperacillin-tazobactam and vancomycin or the combination of cefepime or meropenem and vancomycin for greater than 72 hours. The patients were evaluated for AKI, defined using specific criteria introduced by Kidney Disease: Improving global outcomes (KDIGO) acute kidney injury work group in 2012. Results: A total of 85 patients receiving either antimicrobial combination were evaluated for AKI. The incidence of AKI was significantly higher in the piperacillin-tazobactam and vancomycin group (37.3%) compared with the cefepime or meropenem and vancomycin group (7.7%; χ2 = 7.80, P = .005). Conclusion: The result of this study suggests that the risk of developing AKI is increased in patients receiving the combination of piperacillin-tazobactam and vancomycin versus those receiving the combination of cefepime or meropenem and vancomycin.
Consensus statement on the role of Accredited Exercise Physiologists within the treatment of mental disorders: a guide for mental health professionals
Authors: Lederman Oscar , Grainger Kristine , Stanton Robert , Douglas Angela , Gould Kirrily , Perram Amy , Baldeo Rishi , Fokas Theodora , Nauman Fiona , Semaan Amanda , Hewavasam Jude , Pontin Louise , Rosenbaum Simon 
Published: February 2016

Objective: The aim is to identify the role and scope of Accredited Exercise Physiologist (AEP) services in the mental health sector and to provide insight as to how AEPs can contribute to the multidisciplinary mental health team. Methods: A modified Delphi approach was utilised. Thirteen AEPs with experience in mental health contributed to the iterative development of a national consensus statement. Six mental health professionals with expertise in psychiatry, mental health nursing, general practice and mental health research participated in the review process. Reviewers were provided with a template to systematically provide feedback on the language, content, structure and relevance to their professional group. Results: This consensus statement outlines how AEPs can contribute to the multidisciplinary mental health team, the aims and scope of AEP-led interventions in mental health services and examples of such interventions, the range of physical and mental health outcomes possible through AEP-led interventions and common referral pathways to community AEP services. Outcome: AEPs can play a key role in the treatment of individuals experiencing mental illness. The diversity of AEP interventions allows for a holistic approach to care, enhancing both physical and mental health outcomes.
Holographic femtosecond laser manipulation for advanced material processing
Authors: Hasegawa Satoshi , Hayasaki Yoshio 
Published: February 2016

Abstract
Parallel femtosecond laser processing using a computer-generated hologram displayed on a spatial light modulator, known as holographic femtosecond laser processing, provides the advantages of high throughput and high-energy use efficiency. Therefore, it has been widely used in many applications, including laser material processing, two-photon polymerization, two-photon microscopy, and optical manipulation of biological cells. In this paper, we review the development of holographic femtosecond laser processing over the past few years from the perspective of wavefront and polarization modulation. In particular, line-shaped and vector-wave femtosecond laser processing are addressed. These beam-shaping techniques are useful for performing large-area machining in laser cutting, peeling, and grooving of materials and for high-speed fabrication of the complex nanostructures that are applied to material-surface texturing to control tribological properties, wettability, reflectance, and retardance. Furthermore, issues related to the nonuniformity of diffraction light intensity in optical reconstruction and wavelength dispersion from a computer-generated hologram are addressed. As a result, large-scale holographic femtosecond laser processing over 1000 diffraction spots was successfully demonstrated on a glass sample.
Towards microstructure-cytocompatibility relationship in ultralight Mg-4Li-1Ca (LX41) alloy for degradable implant applications
Authors: Nene Saurabh Sanjay , Estrin Yuri , Kashyap Bhagawati Prasad , Prabhu Nithyananad , Al-Samman Talal , Luthringer Berengere J.C. , Willumeit Regine 
Published: February 2016

AbstractCytocompatibility and biodegradation behaviour were investigated for a newly developed ultralight Mg-4Li-1Ca (LX41) alloy with different starting microstructures. This established the important role of microstructure in determining the pH variation, H
Cross-linked enzyme aggregates (CLEA) in enzyme improvement – a review
Authors: Velasco-Lozano Susana , López-Gallego Fernando , Mateos-Díaz Juan C. , Favela-Torres Ernesto 
Published: February 2016

AbstractStructural and functional catalytic characteristics of cross-linked enzyme aggregates (CLEA) are reviewed. Firstly, advantages of enzyme immobilization and existing types of immobilization are described. Then, a wide description of the factors that modify CLEA activity, selectivity and stability is presented. Nowadays CLEA offers an economic, simple and easy tool to reuse biocatalysts, improving their catalytic properties and stability. This immobilization methodology has been widely and satisfactorily tested with a great variety of enzymes and has demonstrated its potential as a future tool to optimize biocatalytic processes.