bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Transmembrane Domain of the Adenovirus E3/19K Protein Acts as an Endoplasmic Reticulum Retention Signal and Contributes to Intracellular Sequestration of Major Histocompatibility Complex Class I Molecules
Authors: Sester Martina , Ruszics Zsolt , Mackley Emma , Burgert Hans-Gerhard 
Published: March 2013

ABSTRACTThe human adenovirus E3/19K protein is a type I transmembrane glycoprotein of the endoplasmic reticulum (ER) that abrogates cell surface transport of major histocompatibility complex class I (MHC-I) and MHC-I-related chain A and B (MICA/B) molecules. Previous data suggested that E3/19K comprises two functional modules: a luminal domain for interaction with MHC-I and MICA/B molecules and a dilysine motif in the cytoplasmic tail that confers retrieval from the Golgi apparatus back to the ER. This study was prompted by the unexpected phenotype of an E3/19K molecule that was largely retained intracellularly despite having a mutated ER retrieval motif. To identify additional structural determinants responsible for ER localization, chimeric molecules were generated containing the luminal E3/19K domain and the cytoplasmic and/or transmembrane domain (TMD) of the cell surface protein MHC-I Kd. These chimeras were analyzed for transport, cell surface expression, and impact on MHC-I and MICA/B downregulation. As with the retrieval mutant, replacement of the cytoplasmic tail of E3/19K allowed only limited transport of the chimera to the cell surface. Efficient cell surface expression was achieved only by additionally replacing the TMD of E3/19K with that of MHC-I, suggesting that the E3/19K TMD may confer static ER retention. This was verified by ER retention of an MHC-I Kdmolecule with the TMD replaced by that of E3/19K. Thus, we have identified the E3/19K TMD as a novel functional element that mediates static ER retention, thereby increasing the concentration of E3/19K in the ER. Remarkably, the ER retrieval signal alone, without the E3/19K TMD, did not mediate efficient HLA downregulation, even in the context of infection. This suggests that the TMD is required together with the ER retrieval function to ensure efficient ER localization and transport inhibition of MHC-I and MICA/B molecules.
Polyprotein Context Regulates the Activity of Poliovirus 2C
ATPase
Bound to Bilayer Nanodiscs
Authors: Springer Courtney L. , Huntoon Harrison P. , Peersen Olve B. 
Published: March 2013

ABSTRACT

Positive-strand RNA viruses generally replicate in large membrane-associated complexes. For poliovirus, these replication complexes are anchored to the membrane via the viral 2B, 2C, and 3A proteins. 2C is an AAA+ family ATPase that plays a key role in host cell membrane rearrangement, is a putative helicase, and is implicated in virion assembly and packaging. However, the membrane-binding characteristics of all of these viral proteins have made it difficult to elucidate their exact roles in virus replication. We show here that small lipid bilayers known as nanodiscs can be used to chaperone the
in vitro
expression of soluble poliovirus 2C, 2BC, and 2BC3AB polyproteins in a membrane-bound form. ATPase assays on these proteins show that the activity of the core 2C domain is stimulated ∼60-fold compared to the larger 2BC3AB polyprotein, with most of this stimulation occurring upon removal of 2B. The proteins are active over a wide range of salt concentrations, exhibit slight lipid headgroup dependence, and show significant stimulation by acetate. Our data lead to a model wherein the replication complex can be assembled with a minimally active form of 2C that then becomes fully activated by proteolytic cleavage from the adjacent 2B viroporin domain.
New Strategies in the Treatment of Multiple Myeloma
Authors: Munshi Nikhil C. , Anderson Kenneth C. 
Published: March 2013

AbstractMultiple myeloma is the second most common hematologic malignancy affecting terminally differentiated plasma cells. Although high-dose chemotherapy and autologous stem cell transplantation have improved survival in younger patients, the natural history of multiple myeloma has been changed with the availability of six new agents approved in the past 10 years (thalidomide, bortezomib, lenalidomide, liposomal doxorubicin, carfilzomib, and pomalidomide). Despite this significant improvement in the overall outcome, multiple myeloma remains incurable in the majority of patients, prompting a continued search for additional therapeutic options. Extensive molecular and genomic characterization of multiple myeloma cells in their bone marrow milieu, which affects myeloma cell growth and survival, has provided a number of novel drugable targets and pathways. Perturbation of protein catabolism at multiple levels has become an important target in multiple myeloma. Similarly, improvements in monoclonal antibody generation and vaccine development, along with identification of a number of cell surface and cellular targets, have led to the development of various strategies, including antibodies and antibody–drug conjugates that are under investigation preclinically and in early clinical studies. We propose that eventually, molecularly informed multiagent combination therapies will be required to eliminate the multiple myeloma cell clone for long-term disease control. Clin Cancer Res; 19(13); 3337–44. ©2013 AACR.
Neoadjuvant Chemotherapy with or without Zoledronic Acid in Early Breast Cancer—A Randomized Biomarker Pilot Study
Authors: Winter Matthew C. , Wilson Caroline , Syddall Stuart P. , Cross Simon S. , Evans Alyson , Ingram Christine E. , Jolley Ingrid J. , Hatton Matthew Q. , Freeman Jennifer V. , Mori Stefano , Holen Ingunn , Coleman Robert E. 
Published: March 2013

Abstract
Purpose: To investigate the short-term biologic effects of neoadjuvant chemotherapy +/− zoledronic acid (ZOL) in invasive breast cancer.
Experimental Design: Forty patients were randomized to receive a single 4 mg infusion of ZOL 24 hours after the first cycle of FE100C chemotherapy, or chemotherapy alone. Randomization was stratified for tumor stage, ER, HER2, and menopausal status. All patients had repeat breast core biopsy at day 5 (D5) ± day 21 (D21). Effects on apoptotic index, proliferation (Ki67), growth index, surrogate serum markers of angiogenesis (VEGF), and serum reproductive hormones within the TGFβ family (activin-A, TGFβ1, inhibin-A, and follistatin) were evaluated and compared.
Results: Baseline clinicopathologic characteristics were well balanced. Cell growth index (increased apoptosis and reduced proliferation) fell at D5 in both groups but recovered more rapidly with chemotherapy + ZOL compared with chemotherapy alone by D21 (P = 0.006). At D5, a greater reduction in serum VEGF occurred with chemotherapy + ZOL compared with chemotherapy: median percentage change −23.8% [interquartile range (IQR): −32.9 to −15.8] versus −8.4% (IQR: −27.3 to +8.9; P = 0.02), but these effects were lost by D21. Postmenopausal women showed a decrease in follistatin levels from baseline in the chemotherapy + ZOL group at D5 and D21, compared with chemotherapy alone (Pinteraction = 0.051).
Conclusions: In this pilot study, short-term changes in biomarkers suggest potentially relevant interactions between tumor biology, chemotherapy, modification of the bone microenvironment, and the endocrine status of the host. Larger studies with more frequent dosing of zoledronic acid are needed to assess these complex interactions more thoroughly. Clin Cancer Res; 19(10); 2755–65. ©2013 AACR.
Effects of Obstructive Sleep Apnea and its Treatment on Signal-Averaged P-Wave Duration in Men
Authors: Maeno Ken-ichi , Kasagi Satoshi , Ueda Azusa , Kawana Fusae , Ishiwata Sugao , Ohno Minoru , Yamaguchi Tetsu , Narui Koji , Kasai Takatoshi 
Published: March 2013

Background—
Prolonged P-wave duration, indicating atrial conduction delay, is a potent precursor of atrial fibrillation. Obstructive sleep apnea (OSA) is a risk factor for atrial fibrillation development. We investigated the association of P-wave duration with OSA and its treatment.

Methods and Results—

We enrolled 80 consecutive men with normal sinus rhythms who underwent polysomnography, had no history of atrial fibrillation or ischemic heart disease, and no evidence of heart failure. Signal-averaged P-wave duration (SAPWD) was measured in all participants. Multivariable regression analysis showed that age, hypertension, and log-transformed apnea–hypopnea index were significantly and independently correlated with SAPWD. SAPWD was repeatedly measured after 1 month of continuous positive airway pressure (CPAP) therapy in 62 patients with moderate-to-severe OSA. As controls, 18 patients with moderate-to-severe OSA were enrolled. Their SAPWD was also measured at baseline and after 1 month without CPAP therapy. No significant change in SAPWD was found between baseline and after 1 month in the controls. However, SAPWD was significantly shortened after 1 month of CPAP therapy (from 137.5±8.6 to 129.7±8.5 ms;
P
<0.001), and the SAPWD change was significantly different in patients with CPAP therapy compared with controls (
P
<0.001). In addition, the SAPWD change in patients with CPAP therapy correlated inversely with nightly CPAP usage (
r
=−0.52;
P
<0.001).

Conclusions—
OSA severity was significantly associated with prolonged SAPWD. CPAP therapy significantly shortened SAPWD in patients with moderate-to-severe OSA. Thus, OSA may cause atrial conduction disturbances, leading to an increased risk of atrial fibrillation development, which may be modifiable by alleviating OSA with CPAP therapy.
Effects of rainfall and geography on the comparative diets of eight rainbow lizard populations across Togo, Benin and Nigeria (West Africa)
Authors: Akani Godfrey C. , Akani Godfrey C. , Petrozzi Fabio , Akani Godfrey C. , Petrozzi Fabio , Rugiero Lorenzo , Akani Godfrey C. , Petrozzi Fabio , Rugiero Lorenzo , Segniagbeto Gabriel H. , Akani Godfrey C. , Petrozzi Fabio , Rugiero Lorenzo , Segniagbeto Gabriel H. , Luiselli Luca 
Published: March 2013

The diet composition of rainbow lizards (Agama agama complex) populations was studied by feces analysis at eight distant places across a mega-transect in the Gulf of Guinea (West Africa), covering three countries: Togo, Benin and Nigeria. The effects of geography (= linear distance between study sites) and local conditions (using the mean annual rainfall as a proxy of the site-specific conditions) on dietary similarity of rainbow lizards were tested. Rainbow lizards were mainly insectivorous at all sites. Multivariate analyses identified four main groups of localities in terms of diet diversity indexes, with populations inhabiting forest towns tending to have less prey taxa richness than conspecifics from more arid areas, which instead had higher dietary evenness. Food niche overlap between populations was high among populations (range 0.631-0.940, ), and decreased with increases in the difference of mean annual rainfall between sites. There was no effect of the geographic distance on the similarity in diet composition between populations. A UPGMA dendrogram revealed a geographic trend in terms of presence/absence of the various prey types in the diets, with all the Nigerian study sites forming one cluster, whereas Lomé and Cotonou, two cities situated within the Dahomey Gap, being grouped apart. Overall, rainfall of the various sites seems to be more important than geographic distance for determining the taxonomic diet composition similarity of these lizards.
The Diurnal Cycle of Cloud-Top Height and Cloud Cover over the Southeastern Pacific as Observed by GOES-10
Authors: Painemal David , Minnis Patrick , O'Neill Larry 
Published: March 2013

AbstractThe diurnal cycles in cloud-top height Htop and cloud fraction (CF) in the southeastern Pacific stratocumulus region were determined for October–November 2008 by analyzing data from Geostationary Operational Environmental Satellite-10 (GOES-10) according to a diurnal/semidiurnal harmonic fitting technique. The value of Htop was obtained by applying a formula based on a linear regression of the differences between GOES-10 cloud-top temperature and Tropical Rainfall Measuring Mission (TRMM) Microwave Imager (TMI) satellite sea surface temperature, with a common 0.25° × 0.25° spatial resolution. A satellite liquid water path (LWP) climatology complemented this dataset.Southwestward transects of Htop and LWP anomalies reveal a coherent propagating signal from the coast in the afternoon, with a typical phase speed of 25 m s−1. This pattern is preceded by a subsidence wave that reaches its peak a few hours before the maximum in Htop and LWP anomalies. Coincident increases in LWP and Htop after the subsidence wave passes suggest that the boundary layer deepening promotes cloud thickening and increased LWP, which are likely maintained through a well-mixed boundary layer and sufficient moisture fluxes that can counteract the effect of dry air entrainment. The interference between the radiatively and subsidence wave–driven cycles gives rise to a semidiurnal cycle in Htop along the coast. While the semidiurnal amplitude is near 80 m close to the coast with a fraction of explained variance greater than 0.4, it decreases to 30 m offshore (80°W). Similar to Htop, CF also exhibits contrasting zonal differences, but with a smaller semidiurnal component. The phase of the semidiurnal harmonic resembles the subsidence propagation westward, and the noticeable land–sea breeze circulation at 26°S that extends 200 km offshore.
Knowledge, beliefs and behaviours related to STD risk, prevention, and screening among a sample of African American men and women
Authors: Uhrig Jennifer D , Friedman Allison , Poehlman Jon , Scales Monica , Forsythe Ann 
Published: March 2013

Objective: Current data on sexually transmitted disease (STD) among African Americans show significant racial/ethnic disparities. The purpose of this study was to explore knowledge, attitudes, beliefs, and behaviours related to STD risk, prevention, and testing among African American adults to help inform the development of a health communication intervention to address the high rates of STDs in this community. Design: Cross-sectional survey. Setting: Four United States (US) communities with high cumulative incidence of STDs. Method: We administered a 44-item structured survey. Results: Participants were 185 sexually active heterosexual African Americans aged 18 to 45. Most participants (84.2%) had been tested for an STD at least once. Most participants (75.8%) perceived STDs to be a problem in their community, and almost all (91.2%) felt that people needed education to learn how to avoid STDs. Nonetheless, only half of participants (49.5%) agreed that they should get tested for STDs because they may be at risk. Misconceptions related to STD prevention and testing were identified. Results suggest that STDs remain highly stigmatized with concerns related to social and interpersonal consequences. Participants’ perceived personal risk was low, despite acknowledging high STD rates in their communities. Conclusion: Findings suggest that health communication may play an important role in addressing STD disparities by increasing perceptions of personal risk, minimizing STD-associated stigma, and marketing STD prevention and testing behaviours.
Rethinking the ‘Public Service Bargain’: the changing (legal) position of civil servants in Europe
Authors: van der Meer Frits M , van den Berg Caspar F , Dijkstra Gerrit SA 
Published: March 2013

It can be argued that because of the rise of New Public Management and the growing dominance of labor law and HRM practices, the so-called ‘traditional’ public law formulation of the position of civil servants has come under pressure in a number of Western European countries in recent decades and have shaken the ‘bargain’ agreed between the political and administrative leaders since the Second World War. By contrast, in Central and Eastern Europe and Britain, new Weberian-type civil service legislation has been introduced. In this analysis, we examine both apparent opposites from a public sector bargains perspective and find that European countries are at a crossroads in their reflection on the ‘bargain’. Points for practitioners For practitioners in this field two considerations are important to note. The first is that while the discussion about the (legal) position of civil servants within their political-administrative system may seem to be a national debate, in essence it forms part of a more general debate that is conducted all across Europe. The second is that both theoretically and empirically, two dimensions of the bargain have to be distinguished, namely on the one hand the material labor conditions (pay, job protection, etc.) and on the other hand the values of bureaucracy (impartiality, integrity, loyalty, etc.). As our empirical analysis shows, these two dimensions have become increasingly independent from each other in the discussions and reforms in various countries over recent decades. In other words, managerial reforms in terms of material labor conditions have in practice been paired with the renewed emphasis on Weberian values of bureaucracy. Whether this decoupling is sustainable from a policy point of view in the long run (i.e. whether Weberian-style labor conditions are or are not conditional for high levels of Weberian values of bureaucracy), remains to be seen.
Performance management systems for senior civil servants: how strong is the managerial public service bargain?
Authors: Hondeghem Annie , Dorpe Karolien Van 
Published: March 2013

During the past couple of decades we have witnessed important reforms in the public sector in OECD countries. Various forms of performance management systems have been introduced. This had an impact on the role and position of senior civil servants. The traditional public service bargain (PSB) came under pressure and was replaced by – at least partially – a managerial PSB. This article looks at the performance management systems that have been introduced for senior civil servants in five countries (Canada, the UK, the Netherlands, Denmark, and Belgium) and their impact on the managerial PSB. When there is strong result-based control in the different phases of the performance management cycle, we assume a strong managerial PSB. The finding is that the Anglo-Saxon countries have stronger result-based control systems than the European continental countries. Therefore we conclude that in the former countries the managerial PSBs are stronger than in the latter countries. Points for practitioners Performance management systems for senior civil servants show a different degree of result-based control. Following the four steps in a control process (plan, do, check, act) we can divide the performance management cycle into four phases: planning, monitoring, evaluation, and acting. When there is strong result-based control in each stage, we can speak of a strong managerial public service bargain (PSB). When there is moderate or weak result-based control, there is a moderate or weak managerial PSB, respectively. Each country can make its own choices regarding the performance management system for senior civil servants, but one must be aware that this has an impact on political-administrative relations.
Managerial reforms, Public Service Bargains and top civil servant identity
Authors: Bourgault Jacques , Van Dorpe Karolien 
Published: March 2013

In the past couple of decades, a wide range of managerial reforms have been witnessed in many OECD countries. These reforms may have significantly affected the identity of top civil servants. This change in identity may, in turn, have an impact on the performance of top officials, their roles, their views, their relations with political personnel and their expected competencies. Within a sample of countries (Belgium, Canada, Denmark, and the Netherlands) we explore these reforms, the changes that have occurred in top officials’ identity (personal, role and social) with document analysis and a series of interviews. We conclude that in all cases, regardless of the goals or the intensity of the reforms, there is now more individualization, more mobility, fixed-term contracts and more accountability. We did not find a full-blown managerial or any unambiguous evolution towards a pure managerial identity. Points for practitioners Managerial reforms certainly affect the relationships between politicians and top civil servants. Role perceptions of top civil servants are, depending on the context, more resistant to change than expected. Despite the omnipresent managerial discourse, the role of policy advisor remains very important. Corporate management designs tend to facilitate corporate identification, the type of employment relationship, contract and level of goals, thus affecting the social identity of top civil servants.
Beneficial influence of topical extra virgin olive oil application on an experimental model of penile fracture in rats
Authors: Gunes Mustafa , Ozkol Halil , Pirincci Necip , Gecit Ilhan , Bilici Salim , Yildirim Serkan 
Published: March 2013

Penile fracture (PF) is known as a traumatic rupture of the tunica albuginea of corpus cavernosum. In this study, we aimed to investigate the healing influence of topical extra virgin olive oil (EVOO) on PF through evaluating levels of some oxidative stress biomarkers for the first time. Histopathological evaluation was also realized. A total of 18 male Sprague-Dawley albino rats were divided into three groups of six rats each as control group, in PF (alone) group, and PF + EVOO group. Experimental PF was formed via incising from the proximal dorsal side of the penis in the rats of all groups except control. While in PF (alone) group, fracture was formed and the incision was primarily closed, in PF + EVOO group in addition to foregoing processes, EVOO was also administrated topically twice a day for 3 weeks. At the end of the experiment, all rats were killed and penectomy was carried out. While malondialdehyde, myeloperoxidase, lipid hyroperoxide, and total oxidant status significantly ( p < 0.05) increased, reduced glutathione and total free sulfhydryl groups markedly ( p < 0.05) decreased in PF (alone) group when compared with PF + EVOO group. Levels of these parameters were reversed to nearly normal values by topical EVOO application. Protection by EVOO is further substantiated via the improved histological findings in PF + EVOO group as against degenerative changes in the rats of PF (alone) group. Our data revealed that EVOO has protective effect in penile cavernosal tissue through probably its antioxidant, free radical defusing, anti-inflammatory, and antimicrobial effects.
Involvement of serotonin mechanism in methamphetamine-induced chronic pulmonary toxicity in rats
Authors: Wang Y. , Liu M. , Wang H.M. , Bai Y. , Zhang X.H. , Sun Y.X. , Wang H.L. 
Published: March 2013

The widest distribution and the highest uptake of methamphetamine (MA) in the human body occurred in the lungs, so that more and more attention should be paid to MA-induced pulmonary toxicity. MA induces the release of serotonin, which is an important mediator in pulmonary disease. The purpose of this study is to investigate the chronic response of the lung to MA and its potential mechanism in rats. Models of the chronic toxicity of MA were established with MA of 5 mg/kg and 10 mg/kg (intraperitoneally, twice per day) for 5 weeks. It was found that the high dose of MA induced rat pulmonary toxicity: crowded lung parenchyma, thickened septum, reduced number of alveolar sacs, inflammatory cell infiltration, and pulmonary arteriolar remodeling. In addition, MA resulted in a significant increase in the lung serotonin concentration and the marked upregulation of tryptophan hydroxylase 1, vesicular monoamine transporter 2, serotonin transporter, and downregulation of monoamine oxidase-A. These findings suggest that MA induced chronic pulmonary toxicity, which is concerned with the elevated serotonin concentration in rat lungs by increased synthesis, reduced metabolism, augmented accumulation, and promoted release of serotonin.