bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Contributions of Tacaribe Arenavirus Nucleoprotein N-Terminal and C-Terminal Residues to Nucleocapsid Functional Activity
Authors: D'Antuono Alejandra , Loureiro Maria Eugenia , Foscaldi Sabrina , Marino-Buslje Cristina , Lopez Nora 
Published: April 2014

ABSTRACT

The arenavirus nucleoprotein (NP) is the main protein component of viral nucleocapsids and is strictly required for viral genome replication mediated by the L polymerase. Homo-oligomerization of NP is presumed to play an important role in nucleocapsid assembly, albeit the underlying mechanism and the relevance of NP-NP interaction in nucleocapsid activity are still poorly understood. Here, we evaluate the contribution of the New World Tacaribe virus (TCRV) NP self-interaction to nucleocapsid functional activity. We show that alanine substitution of N-terminal residues predicted to be available for NP-NP interaction strongly affected NP self-association, as determined by coimmunoprecipitation assays, produced a drastic inhibition of transcription and replication of a TCRV minigenome RNA, and impaired NP binding to RNA. Mutagenesis and functional analysis also revealed that, while dispensable for NP self-interaction, key amino acids at the C-terminal domain were essential for RNA synthesis. Furthermore, mutations at these C-terminal residues rendered NP unable to bind RNA both
in vivo
and
in vitro
but had no effect on the interaction with the L polymerase. In addition, while all oligomerization-defective variants tested exhibited unaltered capacities to sustain NP-L interaction, NP deletion mutants were fully incompetent to bind L, suggesting that, whereas NP self-association is dispensable, the integrity of both the N-terminal and C-terminal domains is required for binding the L polymerase. Overall, our results suggest that NP self-interaction mediated by the N-terminal domain may play a critical role in TCRV nucleocapsid assembly and activity and that the C-terminal domain of NP is implicated in RNA binding.

IMPORTANCE
The mechanism of arenavirus functional nucleocapsid assembly is still poorly understood. No detailed information is available on the nucleocapsid structure, and the regions of full-length NP involved in binding to viral RNA remain to be determined. In this report, novel findings are provided on critical interactions between the viral ribonucleoprotein components. We identify several amino acid residues in both the N-terminal and C-terminal domains of TCRV NP that differentially contribute to NP-NP and NP-RNA interactions and analyze their relevance for binding of NP to the L polymerase and for nucleocapsid activity. Our results provide insight into the contribution of NP self-interaction to RNP assembly and activity and reveal the involvement of the NP C-terminal domain in RNA binding.
Novel Roles of Focal Adhesion Kinase in Cytoplasmic Entry and Replication of Influenza A Viruses
Authors: Elbahesh Husni , Cline Troy , Baranovich Tatiana , Govorkova Elena A. , Schultz-Cherry Stacey , Russell Charles J. 
Published: April 2014

ABSTRACT
Viruses modulate cellular signaling pathways at almost every step of the infection cycle. Cellular signaling pathways activated at later times of influenza infection have previously been investigated; however, early influenza virus-host cell interactions remain understudied. Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that regulates phosphatidylinositol 3-kinase (PI3K) activation and actin reorganization, two critical processes during influenza A virus (IAV) infection in most cell types. Using 6 influenza A virus strains (A/Puerto Rico/8/1934, A/Aichi/2/1968 × A/Puerto Rico/8/1934 reassortant [X-31], A/California/04/2009, mouse-adapted A/California/04/2009, A/WSN/1933, and A/New Caledonia/20/1999), we examined the role of FAK during IAV entry. We found that influenza virus attachment induced PI3K-dependent FAK-Y397 phosphorylation. Pharmacological FAK inhibition or expression of a kinase-dead mutant of FAK led to disruption of the actin meshwork that resulted in sequestration of IAV at the cell periphery and reduced virion localization to early endosomes. Additionally, FAK inhibition impeded viral RNA replication at later times of infection and ultimately resulted in significantly reduced viral titers in both A549 and differentiated normal human bronchial epithelial (NHBE) cells. Although not all tested strains activated FAK, all of them exhibited a reduction in viral replication in response to inhibition of FAK signaling. These findings highlight novel biphasic roles of FAK activation during IAV infection and indicate that FAK serves as a central link between receptor-mediated PI3K activation and actin reorganization during IAV infection.

IMPORTANCE
We found that FAK links early activation of PI3K and actin reorganization, thereby regulating influenza virus entry. Surprisingly, we also found that FAK can regulate viral RNA replication independently of its role in entry. Our study addresses a knowledge gap in the understanding of signaling events triggered by influenza virus that mediate its internalization and initiation of the infection cycle. Understanding of these fundamental molecular events will be necessary to identify novel host targets, such as FAK, and development of future anti-influenza virus therapeutics.
Overexpression of integrin αv correlates with poor prognosis in colorectal cancer
Authors: Ha Sang Yun , Shin Juyoun , Kim Jeong Hoon , Kang Myung Soo , Yoo Hae-Yong , Kim Hyeon-Ho , Um Sung-Hee , Kim Seok-Hyung 
Published: April 2014

AimsIntegrin αv subunits are involved in tumour angiogenesis and tumour progression in various types of cancers. Clinical trials evaluating agents targeting integrin αv are ongoing. Integrin αv expression has been reported in several cancers in association with tumour progression or poor survival. However, no study has addressed the prognostic influence of integrin αv expression on survival of patients with colorectal cancer (CRC).MethodsImmunohistochemical staining of integrin αv was performed in 198 CRC samples to evaluate its prognostic significance.ResultsHigh expression of integrin αv was observed in 58.1% (115/189) of colorectal adenocarcinoma samples, while only in 11.5% (3/26) of tubular adenoma samples and in none of normal mucosa or hyperplastic polyp samples. It was more frequently found in female patients and less frequently observed in well differentiated tumours. The proportion of cases with high expression of integrin αv showed an increasing trend with increased T stage (p=0.032), N stage (p=0.006) and TNM stage (p=0.001). Patients displaying exuberant expression of integrin αv showed shorter overall survival (p=0.001) and disease-free survival (p=0.004). Elevated integrin αv expression was an independent prognostic factor for overall survival (HR: 2.04, 95% CI 1.16 to 3.56; p=0.013) and disease-free survival (HR: 2.19, 95% CI 1.16 to 4.13; p=0.015).ConclusionsOverexpression of integrin αv is associated with advanced T and N stage and as an independent prognostic factor in CRC.
Aspirin and Other NSAIDs as Chemoprevention Agents in Melanoma
Authors: Goodman James R. , Grossman Douglas 
Published: April 2014

Abstract
Melanoma incidence is increasing and, despite recent therapeutic advances, the prognosis for patients with metastatic disease remains poor. Thus, early detection and chemoprevention are promising strategies for improving patient outcomes. Aspirin (acetylsalicylic acid) and other nonsteroidal anti-inflammatory drugs (NSAID) have demonstrated chemoprotective activity in several other cancers, and have been proposed as chemopreventive agents for melanoma. Throughout the last decade, however, a number of case–control, prospective, and interventional studies of NSAIDs and melanoma risk have yielded conflicting results. These inconsistent findings have led to uncertainty about the clinical utility of NSAIDs for melanoma chemoprevention. This mini-review highlights current knowledge of NSAID mechanisms of action and rationale for use in melanoma, provides a comparative review of outcomes and limitations of prior studies, and discusses the future challenges in demonstrating that these drugs are effective agents for mitigating melanoma risk. Cancer Prev Res; 7(6); 557–64. ©2014 AACR.
Sustained pro-haemostatic activity of rFVIIa in plasma and platelets in non-bleeding pigs may explain the efficacy of a once-daily prophylaxis in humans
Authors: Schut Anne Marieke , Hyseni Agon , Adelmeijer Jelle , Meijers Joost C. M. , de Groot Philip G. , Lisman Ton 
Published: April 2014

SummaryRecombinant factor VIIa (rFVIIa) is registered for treatment of inhibitor-complicated haemophilia, and a once-daily prophylactic administration of rFVIIa is successful in reducing the number of bleeding events. This suggests that a single rFVIIa dose has a pro-haemostatic effect up to 24 hours (h), which is difficult to explain given its half-life of 2 h. In this study, six pigs received a 90 µg/kg rFVIIa bolus. Plasma was collected and platelets were isolated at various time points up to 48 h, and analysed for FVIIa levels and associated haemostatic activity. Elevated plasma FVIIa levels were detected up to 24 h post-administration (36 (32–56) mU/ml [median (interquartile range [IQR]), 24 h] vs 2 (2–14) mU/ml [baseline]). Corresponding prothrombin time (PT) values remained shortened compared to baseline until 24 h post-administration (9.4 (9.3–9.9) seconds (s) [24 h] vs 10.5 (10.2–11.0) s [baseline], p ≤0.01). The lag time in thrombin generation testing as well as clotting times in plasma-based assays were shortened up to 12 or 24 h post-administration, respectively (lag times 1.8 (1.7–2.1) minutes (min) [12 h] vs 2.3 (2.3–2.6) min [baseline], p ≤0.01 and clotting times 3.8 (3.2–3.9) min [24 h] vs 5.2 (4.6–5.5) min [baseline], p ≤0.001). Platelet FVIIa levels were elevated up to 48 h (7.7 (3.4–9.0) ng VIIa/mg actin [48 h] vs 2.5 (0.7–4.8) ng VIIa/mg actin [baseline]). In conclusion, elevated and haemostatically active plasma and platelet FVIIa levels are detectable up to 24–48 h following rFVIIa administration in pigs. This prolonged pro-haemostatic effect of FVIIa may explain the prophylactic efficacy of a once-daily rFVIIa treatment.
Electrophysiological Evidence for the Involvement of the Approximate Number System in Preschoolers' Processing of Spoken Number Words
Authors: Pinhas Michal , Donohue Sarah E. , Woldorff Marty G. , Brannon Elizabeth M. 
Published: April 2014

Abstract
Little is known about the neural underpinnings of number word comprehension in young children. Here we investigated the neural processing of these words during the crucial developmental window in which children learn their meanings and asked whether such processing relies on the Approximate Number System. ERPs were recorded as 3- to 5-year-old children heard the words one, two, three, or six while looking at pictures of 1, 2, 3, or 6 objects. The auditory number word was incongruent with the number of visual objects on half the trials and congruent on the other half. Children's number word comprehension predicted their ERP incongruency effects. Specifically, children with the least number word knowledge did not show any ERP incongruency effects, whereas those with intermediate and high number word knowledge showed an enhanced, negative polarity incongruency response (Ninc) over centroparietal sites from 200 to 500 msec after the number word onset. This negativity was followed by an enhanced, positive polarity incongruency effect (Pinc) that emerged bilaterally over parietal sites at about 700 msec. Moreover, children with the most number word knowledge showed ratio dependence in the Pinc (larger for greater compared with smaller numerical mismatches), a hallmark of the Approximate Number System. Importantly, a similar modulation of the Pinc from 700 to 800 msec was found in children with intermediate number word knowledge. These results provide the first neural correlates of spoken number word comprehension in preschoolers and are consistent with the view that children map number words onto approximate number representations before they fully master the verbal count list.
Human Rights and Reproductive Choices in the Case-law of Italian and European Courts
Authors: Valongo Alessia 
Published: April 2014

Abstract
The major issues regarding human fertilisation and embryology are addressed in a comparative perspective and in the light of relevant rulings of the European Court for Human Rights: the relationship between artificial procreation and parental responsibilities, the legal nature of the unborn child, the human right to reproduce and to have a healthy child. The article focuses on the key data of the latest Italian regulation regarding assisted conception, especially compared with British law. Particular attention is paid to the contribution given by recent European decisions to the protection of new human rights. National and international judgements ensure the right to private life and to health that are not always guaranteed by law. Converging developments in case-law panorama make the right to have children, to responsible procreation, to information about medical treatments, much less disharmonic realities than the Member States legislation suggests.
A Physically Based Algorithm for Non-Blackbody Correction of Cloud-Top Temperature and Application to Convection Study
Authors: Wang Chunpeng , Luo Zhengzhao Johnny , Chen Xiuhong , Zeng Xiping , Tao Wei-Kuo , Huang Xianglei 
Published: April 2014

AbstractCloud-top temperature (CTT) is an important parameter for convective clouds and is usually different from the 11-μm brightness temperature due to non-blackbody effects. This paper presents an algorithm for estimating convective CTT by using simultaneous passive [Moderate Resolution Imaging Spectroradiometer (MODIS)] and active [CloudSat + Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO)] measurements of clouds to correct for the non-blackbody effect. To do this, a weighting function of the MODIS 11-μm band is explicitly calculated by feeding cloud hydrometer profiles from CloudSat and CALIPSO retrievals and temperature and humidity profiles based on ECMWF analyses into a radiation transfer model. Among 16 837 tropical deep convective clouds observed by CloudSat in 2008, the averaged effective emission level (EEL) of the 11-μm channel is located at optical depth ~0.72, with a standard deviation of 0.3. The distance between the EEL and cloud-top height determined by CloudSat is shown to be related to a parameter called cloud-top fuzziness (CTF), defined as the vertical separation between −30 and 10 dBZ of CloudSat radar reflectivity. On the basis of these findings a relationship is then developed between the CTF and the difference between MODIS 11-μm brightness temperature and physical CTT, the latter being the non-blackbody correction of CTT. Correction of the non-blackbody effect of CTT is applied to analyze convective cloud-top buoyancy. With this correction, about 70% of the convective cores observed by CloudSat in the height range of 6–10 km have positive buoyancy near cloud top, meaning clouds are still growing vertically, although their final fate cannot be determined by snapshot observations.
Extreme Precipitation and Climate Gradients in Patagonia Revealed by High-Resolution Regional Atmospheric Climate Modeling
Authors: Lenaerts Jan T. M. , van den Broeke Michiel R. , van Wessem Jan M. , van de Berg Willem Jan , van Meijgaard Erik , van Ulft Lambertus H. , Schaefer Marius 
Published: April 2014

Abstract
This study uses output of a high-resolution (5.5 km) regional atmospheric climate model to describe the present-day (1979–2012) climate of Patagonia, with a particular focus on the surface mass balance (SMB) of the Patagonian ice fields. Through a comparison with available in situ observations, it is shown that the model is able to simulate the sharp climate gradients in western Patagonia. The southern Andes are an efficient barrier for the prevalent atmospheric flow, generating strong orographic uplift and precipitation throughout the entire year. The model suggests extreme orographic precipitation west of the Andes divide, with annual precipitation rates of &gt;5 to 34 m w.e. (water equivalent), and a clear rain shadow east of the divide. These modeled precipitation rates are supported qualitatively by available precipitation stations and SMB estimates on the ice fields derived from firn cores. For the period 1979–2012, a slight atmospheric cooling at upper ice field elevations is found, leading to a small but insignificant increase in the ice field SMB.
Did birth relative attendance at adoption panels assist decision-making? Evaluating the Suffolk experience
Authors: Clifton John , Horne Jane , Smith Christine 
Published: April 2014

This article evaluates an adoption agency’s scheme to encourage birth relative attendance at adoption panels considering whether their child required adoption. Using qualitative evaluations of panel minutes and adoption agency statistics, it was found that birth relative attendance generally enhanced the thoroughness and sensitivity of panel deliberations. Having met birth relatives, panel members were usually more confident about the need for adoption, but thought carefully about how they highlighted parental deficits, showing appreciation of birth relatives’ feelings for their child. The child’s heritage appeared to figure more prominently in discussions. There were rare instances of birth relative representations leading to diversion from the adoption proposal, usually in favour of kinship care. Birth parents appeared to use attendance to record a construction of themselves for their child to discover in future, including their own perspective on the adoption plan (usually opposition) and expressions of love and good wishes. Vivid accounts of these parental interactions with panels could prove an important source for adopted people who search for their birth heritage. Independent facilitation of birth relative attendances emerged as crucial to successful attendance, providing emotional support at the meeting and improving the uptake of adoption support services.
Monitoring and management of metabolic abnormalities: mixed-method evaluation of a successful intervention
Authors: Wilson Eleanor , Randall Christopher , Patterson Sue , Emmerson Brett , Moudgil Vikas , Weaver Tim 
Published: April 2014

Objective: To describe the process and impact of a service-level intervention on metabolic monitoring and follow-up of patients of a mental health service who were prescribed clozapine, and describe the metabolic health of these patients. Methods: The intervention − Let’s Get Physical − involved designating two months annually as ‘physical health months’, during which revised service protocol required metabolic monitoring for all eligible patients. Mixed methods were used to assess rates of monitoring at baseline, during the two physical health months, and follow-up and factors influencing practice. Data was analysed using a descriptive statistics and framework approach. Results: Monitoring was completed for around two thirds of eligible patients during each physical health month, representing a statistically significant increase (approximately fourfold) from baseline. Perceptions regarding scope of practice and perceived competency managing metabolic abnormalities were key determinants of clinicians’ practice. Low rates and inconsistency of follow-up were observed. Conclusion: Let’s Get Physical is cost effective in enhancing adherence to monitoring guidelines. The use of clinical algorithms supporting timely response to abnormalities should be considered. Ongoing education, role clarity and dedicated resources are required if psychiatrists are to contribute meaningfully to improving the physical health of people with mental illness.
Solution structure of the major factor VIII binding region on von Willebrand factor
Authors: Shiltagh Nuha , Kirkpatrick John , Cabrita Lisa D. , McKinnon Tom A. J. , Thalassinos Konstantinos , Tuddenham Edward G. D. , Hansen D. Flemming 
Published: April 2014

Key PointsThe high-resolution structure of the complex disulfide-bonded TIL′E′ (D′) region of VWF is presented. The major factor VIII binding site is localized around a flexible region on the TIL′ domain.
Fast anodization fabrication of AAO and barrier perforation process on ITO glass
Authors: Liu Sida , Xiong Zuzhou , Zhu Changqing , Li Ma , Zheng Maojun , Shen Wenzhong 
Published: April 2014

Abstract
Thin films of porous anodic aluminum oxide (AAO) on tin-doped indium oxide (ITO) substrates were fabricated through evaporation of a 1,000- to 2,000-nm-thick Al, followed by anodization with different durations, electrolytes, and pore widening. A faster method to obtain AAO on ITO substrates has been developed, which with 2.5 vol.% phosphoric acid at a voltage of 195 V at 269 K. It was found that the height of AAO films increased initially and then decreased with the increase of the anodizing time. Especially, the barrier layers can be removed by extending the anodizing duration, which is very useful for obtaining perforation AAO and will broaden the application of AAO on ITO substrates.
Documentation of delirium in the VA electronic health record
Authors: Hope Carol , Estrada Nicollete , Weir Charlene , Teng Chia-Chen , Damal Kavitha , Sauer Brian C 
Published: April 2014

Abstract

Background
Delirium is a life-threatening, clinical syndrome common among the elderly and hospitalized patients. Delirium is under-recognized and misdiagnosed, complicating efforts to study the epidemiology and construct appropriate decision support to improve patient care. This study was primarily conducted to realize how providers documented confirmed cases of delirium in electronic health records as a preliminary step for using computerized methods to identify patients with delirium from electronic health records.

Methods
The Mental Health Consult (MHC) team reported cases of delirium to the study team during a 6-month study period (December 1, 2009 - May 31, 2010). A chart extraction tool was developed to abstract documentation of diagnosis, signs and symptoms and known risk factors of delirium. A nurse practitioner, and a clinical pharmacist independently reviewed clinical notes during each patients hospital stay to determine if delirium and or sign and symptoms of delirium were documented.

Results
The MHC team reported 25 cases of delirium. When excluding MHC team notes, delirium was documented for 5 of the 25 patients (one reported case in a physician’s note, four in discharge summaries). Delirium was ICD-9 Coded for 7 of the 25 cases. Signs and symptoms associated with delirium were characterized in 8 physician notes, 11 discharge summaries, and 14 nursing notes, accounting for 16 of the 25 cases with identified delirium.

Conclusions
Documentation of delirium is highly inconsistent even with a confirmed diagnosis. Hence, efforts to use existing data to precisely estimate the prevalence of delirium or to conduct epidemiological studies based on medical records will be challenging.