bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ubiquitination of the Cytoplasmic Domain of Influenza A Virus M2 Protein Is Crucial for Production of Infectious Virus Particles
Authors: Su Wen-Chi , Yu Wen-Ya , Huang Shih-Han , Lai Michael M. C. 
Published: November 2017

ABSTRACT
Virus replication is mediated by interactions between the virus and host. Here, we demonstrate that influenza A virus membrane protein 2 (M2) can be ubiquitinated. The lysine residue at position 78, which is located in the cytoplasmic domain of M2, is essential for M2 ubiquitination. An M2-K78R (Lys78→Arg78) mutant, which produces ubiquitination-deficient M2, showed a severe defect in the production of infectious virus particles. M2-K78R mutant progeny contained more hemagglutinin (HA) proteins, less viral RNAs, and less internal viral proteins, including M1 and NP, than the wild-type virus. Furthermore, most of the M2-K78R mutant viral particles lacked viral ribonucleoproteins upon examination by electron microscopy and exhibited slightly lower densities. We also found that mutant M2 colocalized with the M1 protein to a lesser extent than for the wild-type virus. These findings may account for the reduced incorporation of viral ribonucleoprotein into virions. By blocking the second round of virus infection, we showed that the M2 ubiquitination-defective mutant exhibited normal levels of virus replication during the first round of infection, thereby proving that M2 ubiquitination is involved in the virus production step. Finally, we found that the M2-K78R mutant virus induced autophagy and apoptosis earlier than did the wild-type virus. Collectively, these results suggest that M2 ubiquitination plays an important role in infectious virus production by coordinating the efficient packaging of the viral genome into virus particles and the timing of virus-induced cell death.

IMPORTANCE
Annual epidemics and recurring pandemics of influenza viruses represent very high global health and economic burdens. The influenza virus M2 protein has been extensively studied for its important roles in virus replication, particularly in virus entry and release. Rimantadine, one of the most commonly used antiviral drugs, binds to the channel lumen near the N terminus of M2 proteins. However, viruses that are resistant to rimantadine have emerged. M2 undergoes several posttranslational modifications, such as phosphorylation and palmitoylation. Here, we reveal that ubiquitination mediates the functional role of M2. A ubiquitination-deficient M2 mutant predominately produced virus particles either lacking viral ribonucleoproteins or containing smaller amounts of internal viral components, resulting in lower infectivity. Our findings offer insights into the mechanism of influenza virus morphogenesis, particularly the functional role of M1-M2 interactions in viral particle assembly, and can be applied to the development of new influenza therapies.
Spin–orbit splitting in graphene, silicene and germanene: Dependence on buckling
Authors: Singh Ranber 
Published: November 2017

The spin–orbit splitting (E[Formula: see text]) of valence band maximum at the [Formula: see text] point is significantly smaller in 2D planner honeycomb structures of graphene, silicene, germanene and BN than that in the corresponding 3D bulk counterparts. For 2D planner honeycomb structure of SiC, it is almost same as that for 3D bulk cubic SiC. The bandgap which opens at the K and K[Formula: see text] points due to spin–orbit coupling (SOC) is very small in flat honeycomb structures of graphene and silicene, while in germanene it is about 2 meV. The buckling in these structures of graphene, silicene and germanene increases the bandgap opened at the K and K[Formula: see text] points due to SOC quadratically, while the E[Formula: see text] of valence band maximum at the [Formula: see text] point decreases quadratically with an increase in the magnitude of buckling.
New perspectives on pterosaur palaeobiology
Authors: Hone David W. E. , Witton Mark P. , Martill David M. 
Published: November 2017

Abstract
Pterosaurs were the first vertebrates to evolve powered flight and occupied the skies of the Mesozoic for 160 million years. They occurred on every continent, evolved their incredible proportions and anatomy into well over 100 species, and included the largest flying animals of all time among their ranks. Pterosaurs are undergoing a long-running scientific renaissance that has seen elevated interest from a new generation of palaeontologists, contributions from scientists working all over the world and major advances in our understanding of their palaeobiology. They have especially benefited from the application of new investigative techniques applied to historical specimens and the discovery of new material, including detailed insights into their fragile skeletons and their soft tissue anatomy. Many aspects of pterosaur science remain controversial, mainly due to the investigative challenges presented by their fragmentary, fragile fossils and notoriously patchy fossil record. With perseverance, these controversies are being resolved and our understanding of flying reptiles is increasing. This volume brings together a diverse set of papers on numerous aspects of the biology of these fascinating reptiles, including discussions of pterosaur ecology, flight, ontogeny, bony and soft tissue anatomy, distribution and evolution, as well as revisions of their taxonomy and relationships.
FOXF1 Defines the Core-Regulatory Circuitry in Gastrointestinal Stromal Tumor
Authors: Ran Leili , Chen Yuedan , Sher Jessica , Wong Elissa W.P. , Murphy Devan , Zhang Jenny Q. , Li Dan , Deniz Kemal , Sirota Inna , Cao Zhen , Wang Shangqian , Guan Youxin , Shukla Shipra , Li Katie Yang , Chramiec Alan , Xie Yuanyuan , Zheng Deyou , Koche Richard P. , Antonescu Cristina R. , Chen Yu , Chi Ping 
Published: November 2017

Abstract
The cellular context that integrates upstream signaling and downstream nuclear response dictates the oncogenic behavior and shapes treatment responses in distinct cancer types. Here, we uncover that in gastrointestinal stromal tumor (GIST), the forkhead family member FOXF1 directly controls the transcription of two master regulators, KIT and ETV1, both required for GIST precursor-interstitial cells of Cajal lineage specification and GIST tumorigenesis. Further, FOXF1 colocalizes with ETV1 at enhancers and functions as a pioneer factor that regulates the ETV1-dependent GIST lineage-specific transcriptome through modulation of the local chromatin context, including chromatin accessibility, enhancer maintenance, and ETV1 binding. Functionally, FOXF1 is required for human GIST cell growth in vitro and murine GIST tumor growth and maintenance in vivo. The simultaneous control of the upstream signaling and nuclear response sets up a unique regulatory paradigm and highlights the critical role of FOXF1 in enforcing the GIST cellular context for highly lineage-restricted clinical behavior and treatment response.
Significance: We uncover that FOXF1 defines the core-regulatory circuitry in GIST through both direct transcriptional regulation and pioneer factor function. The unique and simultaneous control of signaling and transcriptional circuitry by FOXF1 sets up an enforced transcriptional addiction to FOXF1 in GIST, which can be exploited diagnostically and therapeutically. Cancer Discov; 8(2); 234–51. ©2017 AACR.
See related commentary by Lee and Duensing, p. 146.
This article is highlighted in the In This Issue feature, p. 127
Falling Poverty, Rising Privations: Trends over a Quarter Century in a Slum and a Village near Delhi
Authors: Vijay Devesh 
Published: November 2017

The need to track multi-dimensional poverty in place of just subsistence is being widely recognised by policy makers. However, the challenge of quantifying deficits in housing and sanitation as well as ‘freedoms’ is immense and a number of dearths that bring maximum suffering to people (like risks spawned by contaminated water and food supplies) remain uncharted in common counts of ‘poverties’ and deprivations. In this context, long-term, multi-disciplinary accounts of urban and rural poverty in a range of communities can be of help. As a contribution, this article offers an analysis of changing indices of material poverty as well as ‘privations’ like the worsening health environment, in the microcosm of a village and a slum from Delhi’s periphery, observed over a quarter century through observations, surveys, group discussions and semi-structured interviews. The study shows that ‘absolute poverty’ has declined, in both the sites, since late 1980s but ‘privations’ have risen on many fronts.
Indian Politics: Haunted by Spectre of Post-democracy?
Authors: Verma Ravindra Kumar 
Published: November 2017

The dawn of 21st century has witnessed some new features of democratic politics that seem to be shifting away from what we call democratic. The impact of globalisation has created such a nexus among elites of politics–corporates–media that has made political regimes to ignore the democratic norms and well-being of common masses and overemphasise economic growth and corporate-friendly policy priorities. Besides, the approach of the political actors (parties and politicians), in the process of power-seeking, has shown unconventional trends. These features do not resemble either dictatorship or totalitarianism; rather they depict trends of aristocratic mode of decision-making by using democratic framework and institutions. Such trends have been termed as ‘post-democracy’ by recent Western scholarship. Indian politics is not an exception. These trends have created an imbalance between interest of social classes and corporative interests which has prompted political regimes to take tough decisions, in despotic ways. Though the present article does not posit that Indian democracy is on the brink, it attempts to underline the post-democratic features visible in Indian politics through examination of (a) party politics in terms of democratic framework, ideology, policy initiations and reforms, electioneering, etc.; (b) politicians–corporates–media nexus; and (c) modes and trends of politicians in communicating and relating with the electorate.
Political instability and the ability of local government to respond to reputational threats in unison
Authors: Grøn Caroline Howard , Salomonsen Heidi Houlberg 
Published: November 2017

This article investigates whether local governments are able to act in a unified manner when responding to reputational threats posed by negative media coverage. Based on an argument that local governments facing political instability are less able to perform in unison, the article investigates a number of expectations, including various types of political instability (council, agenda and policy area instability) and their relation to different types of responses to negative media coverage from the political and administrative actors (communication behaviour, responsibility and blame-avoidant behaviour, and sanctioning behaviour). The article finds such relationships for some of these aspects. The analysis also indicates that the reputational history of a local government is related to the degree of unified behaviour. The empirical analysis is primarily based on a survey sent to all Danish public managers in the three upper levels of the local government hierarchy. Point for practitioners Reputation management has become an area for strategic management in the public sector, not least in local governments. This article demonstrates that public managers need to pay attention to the degree of political instability characterizing their local governments when dealing with reputational threats. If the local government is characterized by political instability, the need to address potential disagreements between administrative and political actors becomes vital. Furthermore, public managers need to take into account the reputational history of their organization as it may challenge the ability to coordinate a unified response across the political and administrative leadership during reputational threats.
Lying to patients with dementia: Attitudes versus behaviours in nurses
Authors: Cantone Daniela , Attena Francesco , Cerrone Sabrina , Fabozzi Antonio , Rossiello Riccardo , Spagnoli Laura , Pelullo Concetta Paola 
Published: November 2017

Background: Using lies, in dementia care, reveals a common practice far beyond the diagnosis and prognosis, extending to the entire care process. Objectives: In this article, we report results about the attitude and the behaviour of nurses towards the use of lies to patients with dementia. Research design: An epidemiological cross-sectional study was conducted between September 2016 and February 2017 in 12 elderly residential facilities and in the geriatric, psychiatric and neurological wards of six specialised hospitals of Italy’s Campania Region. Participants: In all, 106 nurses compiled an attitude questionnaire (A) where the main question was ‘Do you think it is ethically acceptable to use lies to patients with dementia?’, instead 106 nurses compiled a behaviour questionnaire (B), where the main question was ‘Have you ever used lies to patients with dementia?’ Ethical considerations: Using lies in dementia care, although topic ethically still controversial, reveals a common practice far beyond the diagnosis and prognosis, extending to the entire care process. Findings: Only a small percentage of the interviewed nurses stated that they never used lies/that it is never acceptable to use lies (behaviour 10.4% and attitude 12.3%; p = 0.66). The situation in which nurses were more oriented to use lies was ‘to prevent or reduce aggressive behaviors’. Indeed, only the 6.7% in the attitude group and 3.8% in the behaviour group were against using lies. On the contrary, the case in which the nurses were less oriented to use lies was ‘to avoid wasting time giving explanations’, in this situation were against using lies the 51.0% of the behaviour group and the 44.6% of the attitude group. Conclusion: Our results, according to other studies, support the hypothesis of a low propensity of nurses to ethical reflection about use of lies. In our country, the implementation of guidelines about a correct use of lie in the relationship between health operators and patients would be desirable.
Effect of non-steroidal anti-inflammatory drugs on postoperative respiratory and heart rate in cats subjected to ovariohysterectomy
Authors: Höglund Odd V , Dyall Barbara , Gräsman Victoria , Edner Anna , Olsson Ulf , Höglund Katja 
Published: November 2017

Objectives The use of physiological parameters such as respiratory rate and heart rate to assess pain has long been discussed. The aim of the study was to compare postoperative respiratory rate and heart rate in cats subjected to flank ovariohysterectomy treated with a preoperative non-steroidal anti-inflammatory drug (NSAID) or no NSAID, and determine whether these parameters are suitable for postoperative pain assessment in cats. We hypothesised that cats without an NSAID would experience more postoperative pain, which may increase heart rate and respiratory rate. Methods A total of 168 female privately owned cats were studied. All cats were premedicated with medetomidine (0.08 mg/kg) and butorphanol (0.4 mg/kg) subcutaneously and anaesthesia was induced with intramuscular ketamine (5 mg/kg). Cats were divided into subgroups; controls (no NSAID) or cats given an NSAID, carprofen (4 mg/kg) or meloxicam (0.3 mg/kg), at premedication or induction of anaesthesia. Cats were subjected to flank ovariohysterectomy by the same surgeon. Atipamezole was administered 2.5 h after induction of anaesthesia. Respiratory rate and heart rate were measured 3.5 h after the induction of anaesthesia. Data were analysed using one-way ANOVA with mixed procedure and Tukey’s adjustment method for multiplicity. Results The postoperative respiratory rate and heart rate per minute for all cats were 34.0 ± 8.6 and 167.5 ± 27.4, respectively. Neither respiratory rate nor heart rate differed significantly between the control group and the NSAID groups or between different time points of administration of NSAIDs. Conclusion and relevance Assuming there was less postoperative pain in the group administered NSAIDs, the results of the study presented no support for use of respiratory rate and heart rate as parameters for postoperative pain assessment in individual cats. Study limitations included a lack of pain scoring and baseline data for respiratory rate and heart rate.
Endovascular Renal Artery Stent Retriever Embolectomy in a Young Patient With Cardiac Myxoma: Case Report and Review of the Literature
Authors: Silva Michael A. , See Alfred P. , Shah Samir K. , Khandelwal Priyank , Patel Nirav J. , Lyu Heather , Menard Matthew T. , Aziz-Sultan Mohammad Ali 
Published: November 2017

Purpose: Cardiac myxomas are common tumors of the heart with disproportionate impact on young patients, occasionally with dramatic systemic dissemination of tumor emboli with catastrophic multiorgan system ischemia. The coincident comorbidities can increase the risk of traditional treatments for tumor embolus in each region. Case report: A young patient with previously unknown cardiac myxoma presented with seizure and was found to have stress cardiomyopathy, multiple cerebral large vessel occlusions with acute ischemic stroke, bilateral lower extremity tumor emboli and rhabdomyolysis, and renal tumor embolus with acute tubular necrosis. We describe a multidisciplinary approach applying cerebrovascular stent retriever devices in tumor embolectomy of the renal artery of a young patient with systemic morbidity, preventing safe laparotomy for open surgical tumor embolectomy. Conclusion: We describe 2-month renal function outcomes and the considerations in applying a neuroendovascular mechanical thrombectomy device within the renal artery. This was a radiographically successful technique and her renal function appears to be improving at the 2-month follow-up, although this is complicated by other renal insults and support.
An agent-based modeling framework for cybersecurity in mobile tactical networks
Authors: Thompson Brian , Morris-King James 
Published: November 2017

Mobile tactical networks facilitate communication, coordination, and information dissemination between soldiers in the field. Their increasing use provides important benefits, yet also makes them a prime enemy target. Furthermore, their dynamic, distributed, and ad-hoc nature makes them particularly vulnerable to cyber attack. Unfortunately, most existing research on cybersecurity in mobile ad-hoc networks either uses simplistic mobility models that are easier to analyze mathematically or focuses on modeling the dynamics of civilian networks. In this work, we present an agent-based modeling framework to study malware spread in mobile tactical networks. Our framework includes military-inspired models of hierarchical command structure, unit movement, communication over short-range radio, self-propagating malware, and cyber defense mechanisms. We implement several example scenarios representing military units engaged in tactical operations on a synthetic battlefield. Finally, we conduct a case study, using agent-based simulation to analyze the impact of hierarchy and cybersecurity policies on malware spread. Our results support the claim that agent-based modeling is particularly well-suited for representing the complex organizational and spatial structures inherent to military operations, and we urge others to incorporate the key elements of our framework into existing modeling tools when performing studies of cyber attacks on mobile tactical networks and corresponding cybersecurity measures.
Fixation of proximal pole scaphoid nonunion with non-vascularized cancellous autograft
Authors: Luchetti Timothy J. , Rao Allison J. , Fernandez John J. , Cohen Mark S. , Wysocki Robert W. 
Published: November 2017

We present 20 patients with established proximal pole scaphoid nonunions treated with curettage and cancellous autograft from the distal radius and screw fixation. Fractures with significant proximal pole fragmentation were excluded. Patients were treated at a mean of 26 weeks after injury (range 12–72). Union occurred in 18 of 20 patients (90%) based on computed tomographic imaging. The two nonunions that did not heal were treated with repeat curettage and debridement and iliac crest bone grafting without revision of fixation. Union was achieved in both at a mean of 11 weeks after the revision procedures. Our findings suggest that non-vascularized cancellous autograft and antegrade fixation is a useful option for the treatment of proximal pole scaphoid nonunions. Level of evidence: IV
Pharmacokinetic and pharmacodynamic comparison of subcutaneous versus intramuscular leuprolide acetate formulations in male subjects
Authors: Saltzstein Daniel , Shore Neal D. , Moul Judd W. , Chu Franklin , Concepcion Raoul , de la Motte Stephan , McLane John A. , Atkinson Stuart , Yang Alex , Crawford E. David 
Published: November 2017

Background: The aim of this study was to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of two distinct formulations of leuprolide acetate (LA); subcutaneous (SC) injection and intramuscular (IM) injection. Methods: A total of 32 healthy men were randomized to receive a single 7.5 mg injection of SC-LA ( n = 16) or IM-LA ( n = 16) in this phase I, open-label, parallel-group study. PK was assessed via LA concentrations, and PD via serum luteinizing hormone (LH) and testosterone (T) concentrations. Results: The initial surge of LA was higher for IM-LA than SC-LA (Cmax 27 ± 4.9 versus 19 ± 8.0 ng/ml, respectively), with a shorter tmax (1.0 ± 0.4 versus 2.1 ± 0.8 h). The duration of quantifiable LA concentration was longer for SC-LA (up to 56 versus 42 days for SC-LA and IM-LA, respectively). Median LH concentrations in both groups rapidly increased, followed by gradual decrease. However, SC-LA demonstrated a longer duration of LH suppression, with median levels remaining below 1.0 IU/l through Day 56 compared with IM-LA where LH started to rise by Day 35. Consequently, serum T began to increase by Day 42 in the IM-LA group, with only four subjects maintaining levels ⩽50 ng/dl, compared with 14 subjects in the SC-LA group. By Day 56, 13 SC-LA subjects maintained serum T levels ⩽50 ng/dl. Both SC-LA and IM-LA were well tolerated. Conclusions: Both formulations demonstrated consistent delivery of drug over 1 month; however, SC-LA provided a longer duration of action than expected based on the dosing interval. This profile suggests that SC-LA will provide effective suppression of T over a longer period of time, permitting greater injection scheduling flexibility.