bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biochemical and Structural Insights into the Preference of Nairoviral DeISGylases for Interferon-Stimulated Gene Product 15 Originating from Certain Species
Authors: Deaton M. K. , Dzimianski J. V. , Daczkowski C. M. , Whitney G. K. , Mank N. J. , Parham M. M. , Bergeron E. , Pegan S. D. 
Published: July 2016

ABSTRACT
The regulation of the interferon type I (IFN-I) response has been shown to rely on posttranslational modification by ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15) to stabilize, or activate, a variety of IFN-I signaling and downstream effector proteins. Unlike Ub, which is almost perfectly conserved among eukaryotes, ISG15 is highly divergent, even among mammals. Since zoonotic viruses rely on viral proteins to recognize, or cleave, ISG15 conjugates in order to evade, or suppress, innate immunity, the impact of ISG15 biodiversity on deISGylating proteases of the ovarian tumor family (vOTU) from nairoviruses was evaluated. The enzymatic activities of vOTUs originating from the Crimean-Congo hemorrhagic fever virus, Erve virus, and Nairobi sheep disease virus were tested against ISG15s from humans, mice, shrews, sheep, bats, and camels, which are mammalian species known to be infected by nairoviruses. This along with investigation of binding by isothermal titration calorimetry illustrated significant differences in the abilities of nairovirus deISGylases to accommodate certain species of ISG15. To investigate the molecular underpinnings of species preferences of these vOTUs, a structure was determined to 2.5 Å for a complex of Erve virus vOTU protease and a mouse ISG15 domain. This structure revealed the molecular basis of Erve virus vOTU's preference for ISG15 over Ub and the first structural insight into a nonhuman ISG15. This structure also revealed key interactions, or lack thereof, surrounding three amino acids that may drive a viral deISgylase to prefer an ISG15 from one species over that of another.

IMPORTANCE
Viral ovarian tumor domain proteases (vOTUs) are one of the two principal classes of viral proteases observed to reverse posttranslational modification of host proteins by ubiquitin and interferon-stimulated gene product 15 (ISG15), subsequently facilitating downregulation of IFN-I signaling pathways. Unlike the case with ubiquitin, the amino acid sequences of ISG15s from various species are notably divergent. We illustrate that vOTUs have clear preferences for ISG15s from certain species. In addition, these observations are related to the molecular insights acquired via the first X-ray structure of the vOTU from the Erve nairovirus in complex with the first structurally resolved nonhuman ISG15. This information implicates certain amino acids that drive the preference of vOTUs for ISG15s from certain species.
High-Throughput Small Interfering RNA Screening Identifies Phosphatidylinositol 3-Kinase Class II Alpha as Important for Production of Human Cytomegalovirus Virions
Authors: Polachek William S. , Moshrif Hanan F. , Franti Michael , Coen Donald M. , Sreenu Vattipally B. , Strang Blair L. 
Published: July 2016

ABSTRACT

High-throughput small interfering RNA (siRNA) screening is a useful methodology to identify cellular factors required for virus replication. Here we utilized a high-throughput siRNA screen based on detection of a viral antigen by microscopy to interrogate cellular protein kinases and phosphatases for their importance during human cytomegalovirus (HCMV) replication and identified the class II phosphatidylinositol 3-kinase class II alpha (PI3K-C2A) as being involved in HCMV replication. Confirming this observation, infected cells treated with either pooled or individual siRNAs targeting
PI3K-C2A
mRNA produced approximately 10-fold less infectious virus than the controls. Western blotting and quantitative PCR analysis of infected cells treated with siRNAs indicated that depletion of PI3K-C2A slightly reduced the accumulation of late but not immediate early or early viral antigens and had no appreciable effect on viral DNA synthesis. Analysis of siRNA-treated cells by electron microscopy and Western blotting indicated that PI3K-C2A was not required for the production of viral capsids but did lead to increased numbers of enveloped capsids in the cytoplasm that had undergone secondary envelopment and a reduction in the amount of viral particles exiting the cell. Therefore, PI3K-C2A is a factor important for HCMV replication and has a role in the production of HCMV virions.

IMPORTANCE
There is limited information about the cellular factors required for human cytomegalovirus (HCMV) replication. Therefore, to identify proteins involved in HCMV replication, we developed a methodology to conduct a high-throughput siRNA screen of HCMV-infected cells. From our screening data, we focused our studies on the top hit from our screen, the lipid kinase phosphatidylinositol 3-kinase class II alpha (PI3K-C2A), as its role in HCMV replication was unknown. Interestingly, we found that PI3K-C2A is important for the production of HCMV virions and is involved in virion production after secondary envelopment of viral capsids, the encapsidation of HCMV capsids by a lipid bilayer that occurs before virions exit the cell.
Complexities in Ferret Influenza Virus Pathogenesis and Transmission Models
Authors: Belser Jessica A. , Eckert Alissa M. , Tumpey Terrence M. , Maines Taronna R. 
Published: July 2016

SUMMARY
Ferrets are widely employed to study the pathogenicity, transmissibility, and tropism of influenza viruses. However, inherent variations in inoculation methods, sampling schemes, and experimental designs are often overlooked when contextualizing or aggregating data between laboratories, leading to potential confusion or misinterpretation of results. Here, we provide a comprehensive overview of parameters to consider when planning an experiment using ferrets, collecting data from the experiment, and placing results in context with previously performed studies. This review offers information that is of particular importance for researchers in the field who rely on ferret data but do not perform the experiments themselves. Furthermore, this review highlights the breadth of experimental designs and techniques currently available to study influenza viruses in this model, underscoring the wide heterogeneity of protocols currently used for ferret studies while demonstrating the wealth of information which can benefit risk assessments of emerging influenza viruses.
Acute Whiplash Injury Study (AWIS): a protocol for a cluster randomised pilot and feasibility trial of an Active Behavioural Physiotherapy Intervention in an insurance private setting
Authors: Wiangkham Taweewat , Duda Joan , Haque M Sayeed , Price Jonathan , Rushton Alison 
Published: July 2016

IntroductionWhiplash-associated disorder (WAD) causes substantial social and economic burden internationally. Up to 60% of patients with WAD progress to chronicity. Research therefore needs to focus on effective management in the acute stage to prevent the development of chronicity. Approximately 93% of patients are classified as WADII (neck complaint and musculoskeletal sign(s)), and in the UK, most are managed in the private sector. In our recent systematic review, a combination of active and behavioural physiotherapy was identified as potentially effective in the acute stage. An Active Behavioural Physiotherapy Intervention (ABPI) was developed through combining empirical (modified Delphi study) and theoretical (social cognitive theory focusing on self-efficacy) evidence. This pilot and feasibility trial has been designed to inform the design of an adequately powered definitive randomised controlled trial.Methods and analysisTwo parallel phases. (1) An external pilot and feasibility cluster randomised double-blind (assessor and participants), parallel two-arm (ABPI vs standard physiotherapy) clinical trial to evaluate procedures and feasibility. Six UK private physiotherapy clinics will be recruited and cluster randomised by a computer-generated randomisation sequence. Sixty participants (30 each arm) will be assessed at recruitment (baseline) and at 3 months postbaseline. The planned primary outcome measure is the neck disability index. (2) An embedded exploratory qualitative study using semistructured indepth interviews (n=3–4 physiotherapists) and a focus group (n=6–8 patients) and entailing the recruitment of purposive samples will explore perceptions of the ABPI. Quantitative data will be analysed descriptively. Qualitative data will be coded and analysed deductively (identify themes) and inductively (identify additional themes).Ethics and disseminationThis trial is approved by the University of Birmingham Ethics Committee (ERN_15-0542).Trial registration numberISRCTN84528320.
Novel pharmacological inhibitors demonstrate the role of the tyrosine kinase Pyk2 in adhesion and aggregation of human platelets
Authors: Zarà Marta , Canobbio Ilaria , Visconte Caterina , Di Nunzio Giada , Torti Mauro , Guidetti Gianni 
Published: July 2016

SummaryPyk2 is a Ca2+-regulated kinase predominantly expressed in neuronal and in haematopoietic cells. Previous studies on Pyk2-null mice have demonstrated that Pyk2 plays a crucial role in platelet activation and thrombus formation, thus representing a possible target for antithrombotic therapy. Very limited information is available about the role of Pyk2 in human platelets, mainly because of the lack of specific pharmacological inhibitors. In this work, we have tested two novel Pyk2 inhibitors, PF-4594755 and PF-4520440, to validate their specificity and to investigate their ability to modulate platelet activation. Both molecules were able to efficiently block Pyk2 activity in human and mouse platelets stimulated with thrombin or with the Ca2+-ionophore. In wild-type murine platelets, PF-4594755 and PF-4520440 reduced thrombin-induced aggregation to the level observed in Pyk2 knockout platelets, but did not affect aggregation induced by GPVI stimulation. Importantly, neither compounds affected the residual thrombin-induced aggregation of Pyk2-null platelets, thus excluding possible off-target effects. In human platelets, PF-4594755 and PF-4520440 significantly reduced aggregation stimulated by thrombin, but not by the GPVI agonist convulxin. Both inhibitors reduced platelet adhesion on fibrinogen and prevented Akt phosphorylation in adherent cells, indicating that Pyk2 regulates PI3K and cell spreading downstream of integrins in human platelets. Finally, the Pyk2 inhibitors significantly inhibited thrombus formation upon blood perfusion on immobilized collagen under arterial flow rate. These results demonstrate that PF-4594755 and PF-4520440 are specific inhibitors of Pyk2 in intact platelets and allowed to reliably document that this kinase plays a relevant role in human platelet activation.Supplementary Material to this article is available online at www.thrombosis-online.com.
Performance Analysis of MTD64, our Tiny Multi-Threaded DNS64 Server Implementation: Proof of Concept
Authors: Lencse Gábor 
Published: July 2016

In the current stage of IPv6 deployment, the combination of DNS64 and NAT64 is an important IPv6 transition technology, which can be used to enable IPv6 only clients to communicate with IPv4 only servers. In addition to the existing free software DNS64 implementations, we proposed a tiny multithreaded one, MTD64.In this paper, the performance of MTD64 is measured and compared to that of the industry standard BIND in order to check the correctness of the design concepts of MTD64, especially of the one that we use a new thread for each request. For the performance measurements, our earlier proposed dns64perf program is enhanced as dns64perf2, which one is also documented in this paper. We found that MTD64 seriously outperformed BIND and hence our design principles may be useful for the design of a high performance production class DNS64 server. As an additional test, we have also examined the effect of dynamic CPU frequency scaling to the performance of the implementations.
Pigment Epithelium‐Derived Factor (PEDF) Improves Ischemic Cardiac Functional Reserve Through Decreasing Hypoxic Cardiomyocyte Contractility Through PEDF Receptor (PEDF‐R)
Authors: Lu Peng , Zhang Yi‐Qian , Zhang Hao , Li Yu‐Feng , Wang Xiao‐Yu , Xu Hao , Liu Zhi‐Wei , Li Lei , Dong Hong‐Yan , Zhang Zhong‐Ming 
Published: July 2016

Background

Pigment epithelium‐derived factor (
PEDF
), which belongs to the noninhibitory serpin family, has shown the ability to stimulate several physiological processes, such as antiangiogenesis, anti‐inflammation, and antioxidation. In the present study, the effects of
PEDF
on contractility and calcium handling of rat ventricular myocytes were investigated.

Methods and Results

Adult Sprague‐Dawley rat models of acute myocardial infarction (
AMI
) were surgically established.
PEDF
‐lentivirus was delivered into the myocardium along and away from the infarction border to overexpress
PEDF
. Video edge detection was used to measure myocyte shortening in vitro. Intracellular Ca
2+
was measured in cells loaded with the Ca
2+
sensitive fluorescent indicator, Fura‐2‐acetoxymethyl ester.
PEDF
local overexpression enhanced cardiac functional reserve in
AMI
rats and reduced myocardial contracture bordering the infracted area. Exogenous
PEDF
treatment (10 nmol/L) caused a significant decrease in amplitudes of isoproterenol‐stimulated myocyte shortening, Ca
2+
transients, and caffeine‐evoked Ca
2+
transients in vitro. We then tested a potential role for PEDF receptor‐mediated effects on upregulation of protein kinase C (
PKC
) and found evidence of signaling through the diacylglycerol/
PKC
α pathway. We also confirmed that pretreatment of cardiomyocytes with
PEDF
exhibited dephosphorylation of phospholamban at Ser
16
, which could be attenuated with
PKC
inhibition.

Conclusions

The results suggest that
PEDF
depresses myocyte contractility by suppressing phosphorylation of phospholamban and Ca
2+
transients in a
PKC
α‐dependent manner through its receptor, PEDF receptor, therefore improving cardiac functional reserve during AMI.
Influence of bacterial density and mating on life history traits of Heterorhabditis bacteriophora
Authors: Addis Temesgen , Demissie Shiferaw , Strauch Olaf , Ehlers Ralf-Udo 
Published: July 2016

Heterorhabditis bacteriophora, associated with Photorhabdus luminescens, is commonly used against insect pests. Dauer juveniles (DJ) develop into self-fertilising hermaphrodites that lay eggs until juveniles hatch inside the uterus and feed on the body content of the mother (endotokia matricida). The life history traits of H. bacteriophora were studied at 2.5 × 109, 5 × 109, 10 × 109 and 20 × 109 cells ml−1 of P. luminescens at 25°C using a hanging drop technique. The number of offspring produced per hermaphrodite increased from 50 at 2.5 × 109 cells ml−1 to 269 at 20 × 109 cells ml−1 of P. luminescens. The bacterial density did not influence the beginning of endotokia matricida, hermaphrodite death, DJ release from the maternal carcass and the percentage of juveniles obtained through endotokia matricida. Mating of automictic females could not increase offspring production and survival. Endotokia matricida is an obligatory developmental step in H. bacteriophora.
The Anonymisation of Research Data — A Pyric Victory for Privacy that Should Not Be Pushed Too Hard by the eu Data Protection Framework?
Authors: Quinn Paul 
Published: July 2016

Abstract
Personal health data is essential to many forms of scientific research. Such data may come from a large variety of sources including electronic health records (ehrs), datasets used for previous research and from data linked to biobanks. European data protection law recognises that in addition to using consent as a legal basis for the processing of personal health data for scientific research, such data may be used without consent where it is in the ‘public interest’. Despite the existence of such a legal option, ethics bodies in a number of states have shown reticence to utilise it, often pushing researchers into either obtaining consent or anonymising the data in question. Whilst the latter option may be appealing from a legal point of view, if carried out properly, the result may be that the research value of the data is reduced or even destroyed.
Two Types of Interannual Variability of South China Sea Summer Monsoon Onset Related to the SST Anomalies before and after 1993/94
Authors: Liu Boqi , Zhu Congwen , Yuan Yuan , Xu Kang 
Published: July 2016

Abstract
An advance in the timing of the onset of the South China Sea (SCS) summer monsoon (SCSSM) during the period 1980–2014 can be detected after 1993/94. In the present study, the interannual variability of the SCSSM onset is classified into two types for the periods before and after 1993/94, based on their different characteristics of vertical coupling between the upper- and lower-tropospheric circulation and the differences in their related sea surface temperature anomalies (SSTAs). On the interannual time scale, type-I SCSSM onset is characterized by anomalous low-level circulation over the northern SCS during 1980–93, whereas type-II SCSSM onset is associated with anomalies of upper-level circulation in the tropics during 1994–2014. The upper-tropospheric thermodynamic field and circulation structures over the SCS are distinct between the two types of SCSSM onset, and this investigation shows the importance of the role played by the spring SSTAs in the southern Indian Ocean (SIO) and that of ENSO events in type-I and type-II SCSSM onset, respectively. In the early episode, the warming SIO SSTAs can induce an anomalous low-level anticyclone over the northern SCS that affects local monsoonal convection and rainfall over land to its north, demonstrating a high sensitivity of subtropical systems in type-I SCSSM onset. However, in type-II SCSSM onset during the later episode, the winter warm ENSO events and subsequent warming in the tropical Indian Ocean can influence the SCSSM onset by modulating the spring tropical temperature and upper-level pumping effect over the SCS.
Representation of Snow in the Canadian Seasonal to Interannual Prediction System. Part II: Potential Predictability and Hindcast Skill
Authors: Sospedra-Alfonso Reinel , Merryfield William J. , Kharin Viatcheslav V. 
Published: July 2016

Abstract
This paper examines potential predictability (PP) and actual skill for snow water equivalent (SWE) in the Canadian Seasonal to Interannual Prediction System (CanSIPS). A significant PP is found for SWE, with potentially predictable variance over 50% of the total variance at up to a 5-month lead in mid- to high latitudes in forecasts initialized after snow onset. Much, though not all, of this PP stems from a tendency for SWE anomalies to persist through the snow season. Although the spring melt acts as a PP barrier regardless of initialization date, in some regions significant PP reemerges in the following snow season. This is due primarily to ENSO teleconnections that are modeled realistically by CanSIPS, particularly in northwestern North America. Actual skill of CanSIPS in forecasting SWE is assessed using several verification datasets. Highest skills are obtained using a blend of five such datasets, consistent with the hypothesis that skill scores are degraded by errors in the verification data as well as by forecast errors, and that observational errors can be reduced by blending multiple datasets, much as forecast errors can be reduced by averaging across different models. Actual skill for SWE is comparable to, though generally lower than, that implied by PP. This is due in part to the similar autocorrelation properties of the forecast and observed SWE anomalies, which provide skill through anomaly persistence, combined with reasonably accurate initialization of SWE by CanSIPS. Long-lead skill across snow seasons is found to be linked to ENSO, particularly in western North America, much as for PP.
Clinical Translation of Tissue Engineered Trachea Grafts
Authors: Chiang Tendy , Pepper Victoria , Best Cameron , Onwuka Ekene , Breuer Christopher K 
Published: July 2016

Objective: To provide a state-of-the-art review discussing recent achievements in tissue engineered tracheal reconstruction. Data Sources and Review Methods: A structured PubMed search of the current literature up to and including October 2015. Representative articles that discuss the translation of tissue engineered tracheal grafts (TETG) were reviewed. Conclusions: The integration of a biologically compatible support with autologous cells has resulted in successful regeneration of respiratory epithelium, cartilage, and vascularization with graft patency, although the optimal construct composition has yet to be defined. Segmental TETG constructs are more commonly complicated by stenosis and delayed epithelialization when compared to patch tracheoplasty. Implications for Practice: The recent history of human TETG recipients represents revolutionary proof of principle studies in regenerative medicine. Application of TETG remains limited to a compassionate use basis; however, defining the mechanisms of cartilage formation, epithelialization, and refinement of in vivo regeneration will advance the translation of TETG from the bench to the bedside.
The weight of a portrait: Caricatura and industrial violence after the Charlie Hebdo attack
Authors: Morel Olivier 
Published: July 2016

‘It’s vital’, Luz told his friend the publisher Alain David in mid-February 2015, when he called him. Luz’s book Catharsis, written in the aftermath of the Charlie Hebdo attacks, was completed in record time. The book revolves around an impossible drawing. It is the proper name of the event called ‘attack on Charlie Hebdo, January 7, 2015’. ‘The’ drawing, ‘ le dessin’ is what Luz cannot draw and translate, cannot express and figure without re-engaging the very nature of figurability. Luz converses with ghostly visitations, and while doing so, he re-enacts a foundation of the figuration process that Georges Didi-Huberman calls the ‘dialectique du visuel’ (1992: 53–84). The image breaks down the usual distinction between watching and being watched. This powerful act of refiguring after a violent de-figuration, this artistic redemption, is a political response to a political assassination that targets a regime of visibility while raising central questions about what it means to create a portrait in the age of industrial violence. In a way, Luz’s Catharsis is not a ‘testimony’: it is an attempt to redeem a visual horizon that was torn by the attackers of 7 January.