bluuebunny/crossref_metadata_2025 huggingface dataset:
Downturn Credit Portfolio Risk, Regulatory Capital and Prudential Incentives*
Authors: RÖSCH DANIEL , SCHEULE HARALD
Published: May 2010

This paper analyzes the level and cyclicality of bank capital requirement in relation to (i) the model methodologies through‐the‐cycle and point‐in‐time, (ii) four distinct downturn loss rate given default concepts, and (iii) US corporate and mortgage loans. The major finding is that less accurate models may lead to a lower bank capital requirement for real estate loans. In other words, the current capital regulations may not support the development of credit portfolio risk measurement models as these would lead to higher capital requirements and hence lower lending volumes. The finding explains why risk measurement techniques in real estate lending may be less developed than in other credit risk instruments. In addition, various policy recommendations for prudential regulators are made.
Financial Liberalization and Banking Crises: A Cross‐Country Analysis*
Authors: ANGKINAND APANARD P. , SAWANGNGOENYUANG WANVIMOL , WIHLBORG CLAS
Published: May 2010

Several studies indicate that financial liberalization contributes to the likelihood of a financial crisis. We focus on banking crises and argue that they are most likely to occur after an intermediate degree of liberalization. Using a recently updated dataset for financial reforms in 48 countries between 1973 and 2005, we find an inverted U‐shaped relationship between liberalization and the likelihood of crisis. We ask whether the relationship remains when institutional characteristics of countries and dynamic effects of liberalization are considered. The empirical results indicate that the relationship between liberalization and banking crises depends strongly on the strength of capital regulation and supervision. With very weak regulation and supervision, the probability of banking crises is increasing with liberalization but this relationship is reversed as regulation and supervision become stricter. The most important type of liberalization in relation to banking crises seems to be behavioral (a relaxation of interest and credit controls). A policy implication is that positive growth effects of liberalization can be achieved without increasing the risk of a banking crisis if appropriate institutions are developed.
First‐trimester ultrasound dating of twin pregnancy: are singleton charts reliable?
Authors: Dias T , Mahsud‐Dornan S , Thilaganathan B , Papageorghiou A , Bhide A
Published: May 2010

Please cite this paper as: Dias T, Mahsud‐Dornan S, Thilaganathan B, Papageorghiou A, Bhide A. First‐trimester ultrasound dating of twin pregnancy: are singleton charts reliable? BJOG 2010;117:979–984.

Objective  The aim of this study was to assess the performance of validated singleton crown–rump length (CRL) formulae in dating twin pregnancies at 11–14 weeks of gestation.

Design  Retrospective cohort study.

Setting  Fetal medicine unit of a London teaching hospital.

Sample  Three hundred and eighty‐four pregnancies with known dates of conception.

Methods  Retrospective analysis of 266 singletons and 118 twin pregnancies conceived by in vitro fertilisation (IVF), with a known date of conception. The gestation calculated from the date of conception was compared with the expected gestation from fetal size using a number of different CRL formulae.

Main outcome measures  Difference in gestational age computed from fetal size (CRL) of the bigger and smaller fetus in twin pregnancies and singleton pregnancies using three formulae.

Results  Two of the three studied CRL formulae systematically underestimated the mean gestational age and size of singleton IVF pregnancies (Robinson formula: gestation = 1.4 days, size = 2.7 mm). Twin CRL measurements straddled those of singletons, regardless of the CRL formula used (Robinson formula: larger twin gestation = 2.4 days, size = 4.7 mm; smaller twin gestation = 0.8 days, size = 1.7 mm). These underestimates in gestation and size for IVF singleton and twin pregnancies are well within the known limits of accuracy of first = trimester ultrasound measurements, and are of limited clinical significance.

Conclusions  Currently available CRL charts underestimate both the age and size of IVF singleton pregnancies by a clinically insignificant amount. This difference is similar for twin pregnancies, suggesting that singleton CRL charts can be used to date twin pregnancies accurately.
Pentobarbital inhibition of human recombinant α1AP/Q‐type voltage‐gated calcium channels involves slow, open channel block
Authors: Schober A , Sokolova E , Gingrich KJ
Published: May 2010

BACKGROUND AND PURPOSEPre‐synaptic neurotransmitter release is largely dependent on Ca2+entry through P/Q‐type (CaV2.1) voltage‐gated Ca2+channels (PQCCs) at most mammalian, central, fast synapses. Barbiturates are clinical depressants and inhibit pre‐synaptic Ca2+entry. PQCC barbiturate pharmacology is generally unclear, specifically in man. The pharmacology of the barbiturate pentobarbital (PB) in human recombinant α1APQCCs has been characterized.

EXPERIMENTAL APPROACHPB effects on macroscopic Ca2+(ICa) and Ba2+(IBa) currents were studied using whole‐cell patch clamp recording in HEK‐293 cells heterologously expressing (α1A)human(β2aα2δ‐1)rabbitPQCCs.

KEY RESULTSPB reversibly depressed peak current (Ipeak) and enhanced apparent inactivation (fractional current at 800 ms,r800) in a concentration‐dependent fashion irrespective of charge carrier (50% inhibitory concentration:Ipeak, 656 µM;r800, 104 µM). Rate of mono‐exponentialIBadecay was linearly dependent on PB concentration. PB reduced channel availability by deepening non‐steady‐state inactivation curves without altering voltage dependence, slowed recovery from activity‐induced unavailable states and produced use‐dependent block. PB (100 µM) induced use‐dependent block during physiological, high frequency pulse trains and overall depressed PQCC activity by two‐fold.

CONCLUSION AND IMPLICATIONSThe results support a PB pharmacological mechanism involving a modulated receptor with preferential slow, bimolecular, open channel block (Kd= 15 µM). Clinical PB concentrations (<200 µM) inhibit PQCC during high frequency activation that reduces computed neurotransmitter release by 16‐fold and is comparable to the magnitude of Ca2+‐dependent facilitation, G‐protein modulation and intrinsic inactivation that play critical roles in PQCC modulation underlying synaptic plasticity. The results are consistent with the hypothesis that PB inhibition of PQCCs contributes to central nervous system depression underlying anticonvulsant therapy and general anaesthesia.
The Indian informal sector: The impact of globalization and reform
Authors: Siggel Eckhard
Published: May 2010

Globalization and economic reforms typically affect the formal sector, the informal sector existing outside regulation. Yet, numerous links between them mean the informal sector is variously affected. Traditionally, the model used to explain the impact of these forces was labour market segmentation and migration: workers laid off in the formal sector increase informal labour supply, leading to wage decline and increased poverty. The author examines whether this pattern applies in India following economic reforms in the 1990s, and finds a more appropriate model, driven by expansion both in labour supply and in demand, through outsourcing, skill transfers and new enterprises.
Hungary's experiment in legalizing casual employment
Authors: Tésits Róbert , Szenoradszki Endre
Published: May 2010

Hungary's 1997 Casual Employment Act was originally meant to formalize ad hoc employment relationships entered into by private individual employers through simplified administrative procedures. After being widely abused, however, this flexible regulatory framework was eventually opened up to all employers, with a higher ceiling on the number of days workable on this basis, drastically reduced social security contributions and strong tax incentives. The aim was then to reduce unemployment and the incidence of illegal work by stretching the boundaries of formal employment, but neither of these objectives was attained. Instead, the authors argue, the attempted flexicurity has greatly increased workers' vulnerability.
State‐dependent dynamics of cycles in red grouse abundance
Authors: Kerlin Douglas H. , Thirgood Simon J. , Miller David R. , Aebischer Nicholas J. , Smith A. Adam , Haydon Daniel T.
Published: May 2010

Fluctuating populations are frequently demonstrated to co‐vary in abundance over space, but the dynamics of coupling between populations that gives rise to this synchrony are poorly understood. Synchrony may arise through coupling that is weak and continuous, but in populations that cycle with a characteristic period, synchrony can be maintained through stronger coupling that acts only intermittently. Here, we apply a discrete Markov model that describes the state of a population trajectory to be in one of four possible states. The Markov model reveals the nature of the coupling that gives rise to the weakly synchronous cycles of red grouse abundance. Using time‐series data from 287 populations across the species range in the UK, we show that grouse populations appear mostly uncoupled through time, but that approximately one year in six, “collective forcing events” occur, where populations in a region are forced into synchrony to a significantly greater degree than would be expected if their dynamics proceeded independently. In the absence of these events, synchrony between populations dissipates within ~3 yr. Smaller, low abundance populations tend to make the less probable phase shifts required to synchronize with nearby high abundance populations, suggesting that these low abundance populations are more susceptible to the perturbations responsible for phase shifts than larger populations.
K16 is a further new candidate for homotypic intermediate filament protein interactions
Authors: Trost Andrea , Costa Ivano , Jakab Martin , Ritter Markus , Haim Martina , Hintner Helmut , Bauer Johann W. , Önder Kamil
Published: May 2010

Please cite this paper as: K16 is a further new candidate for homotypic intermediate filament protein interactions. Experimental Dermatology 2010; 19: e241–e250.

Abstract:  Keratin filaments form obligatory heterodimers consisting of one type I and one type II keratin that build the intermediate filaments (IF). These filaments mediate resilience and mechanical strength to epithelial cells and maintain tissue integrity. Specific type I/type II pairs are co‐expressed in vivo and serve as markers for distinct tissue layers and cell differentiation states. Heterodimerization has been regarded the undisrupted hallmark of IF. We show now that recombinantly expressed cytokeratin 16 (K16) interacts with itself and forms homodimers even in denaturating SDS–PAGE analysis. Detailed FRET experiments in HaCaT keratinocytes were in accordance with our in vitro observations and showed clearly that K16 is able to form strong homodimers. Homotypic keratin interactions has been previously shown for keratin 17 (K17) and keratin 18 (K18) by Schnabel et al. (Biochim Biophys Acta, 1998: 1403: 158), and we now proved K16 to be the third type I keratin that is able to form homodimers.
EPA supplementation improves teacher‐rated behaviour and oppositional symptoms in children with ADHD
Authors: Gustafsson Per A , Birberg‐Thornberg Ulrika , Duchén Karel , Landgren Magnus , Malmberg Kerstin , Pelling Henrik , Strandvik Birgitta , Karlsson Thomas
Published: May 2010

Aim:  Measure efficacy of eicosapentaenoic acid (EPA) in children with attention deficit hyperactivity disorder (ADHD).

Methods:  Randomized controlled trial (RCT) of 0.5 g EPA or placebo (15 weeks) in 92 children (7–12 years) with ADHD. Efficacy measure was Conners’ Parent/Teacher Rating Scales (CPRS/CTRS). Fatty acids were analysed in serum phospholipids and red blood cell membranes (RBC) at baseline and endpoint with gas chromatography.

Results:  EPA improved CTRS inattention/cognitive subscale (p = 0.04), but not Conners’ total score. In oppositional children (n = 48), CTRS total score improved ≥25% in 48% of the children receiving EPA vs. 9% for placebo [effect size (ES) 0.63, p = 0.01]. In less hyperactive/impulsive children (n = 44), ≥25% improvement was seen in 36% vs. 18% (ES 0.41, n.s.), and with both these types of symptoms 8/13 with EPA vs. 1/9 for placebo improved ≥25% (p = 0.03). Children responding to treatment had lower EPA concentrations (p = 0.02), higher AA/EPA (p = 0.005) and higher AA/DHA ratios (p = 0.03) in serum at baseline. Similarly, AA/EPA (p = 0.01), AA/DHA (p = 0.038) and total omega‐6/omega‐3 ratios (p = 0.028) were higher in RBC, probably because of higher AA (p = 0.011).

Conclusion:  Two ADHD subgroups (oppositional and less hyperactive/impulsive children) improved after 15‐week EPA treatment. Increasing EPA and decreasing omega‐6 fatty acid concentrations in phospholipids were related to clinical improvement.
Erectile Dysfunction in the Community: Trends over Time in Incidence, Prevalence, GP Consultation and Medication Use—the Krimpen Study: Trends in ED
Authors: Schouten Boris W.V. , Bohnen Arthur M. , Groeneveld Frans P.M.J. , Dohle Gert R. , Thomas Siep , Ruud Bosch J.L.H.
Published: May 2010

Introduction

In the general population, erectile dysfunction (ED) is surrounded by a “taboo.” Epidemiologists studying this problem have to be aware of the phenomenon of the “tip-of-the-iceberg.”

Aims

Our aim is to describe the iceberg phenomenon for ED and their help-seeking behavior in the general population during a period when public interest in ED heightened and waned after the introduction of the drug sildenafil.

Methods

The data were obtained as part of a large longitudinal community-based study, i.e., the Krimpen study. With four rounds of data collection with an approximate 2.1 years interval, the local pharmacists provided data on medication use, whereas abstracts from the medical record and history were provided by the local general practitioners (GPs). The data from the questionnaires were entered into the Krimpen study database but were not communicated to the GPs.

Main Outcome Measures

ED: according to the ICS-questionnaire, GP consultation: search of electronic medical dossier for ED or reports from any specialist, use of ED medication as delivered by the pharmacy.

Results

The age-standardized prevalence of ED is stable, i.e., around 40%. During the period 1995 to 2000, the incidence increased from 5% to 6.5%, then it stabilizes around 5% per year. The first-time use of ED medication increases exponentially between 1995 and 2000, then it stabilizes at about 3.5% per year. The number of GP consultations by men with ED increases up to 1999, after which it stabilizes at about 1.8% per year.

Conclusion

We suggest that the availability and awareness of a new pharmacological option induced a change of behavior among GPs and their patients.
THE CHANGES AND DIFFICULTIES EXPERIENCED BY PATIENTS USING STEROIDS
Authors: Alparslan Guler Balcı , Kapucu Sevgi Sun
Published: May 2010

Aim: The purpose of this study is to determine the changes and difficulties experienced by patients because of the side effects of steroids and the effects on their life styles.

Method: This descriptive analytical study was carried out through interviews using a questionnaire for data collection. The study was conducted in Rheumatology and Nephrology Polyclinic of Hacettepe University Adult Hospital in Ankara, Turkey. There were 146 rheumatology and nephrology patients in the study.

Results: The findings indicated that 68.4% of patients experienced changes in body appearance, and 60.4% of these said they had difficulties. It was determined that changes in the digestive system occurred in 40.4% of the patients, and 44.1% of them had a number of difficulties. Changes occurred in the bone/muscle system of 39% of the patients, and 63.2% of them had difficulties. Psychological changes were observed in 48.6% of the patients, 63.3% of whom said they experienced difficulties.

Conclusion: It was determined that patients using steroids had difficulties due to the side effects of the drug.
CE: Continuing Education Article MANAGEMENT OF ANAEMIA IN CHRONIC KIDNEY DISEASE
Authors: Chamney Melissa , Pugh‐Clarke Karen , Kafkia Theodora , Wittwer Iain
Published: May 2010

Anaemia is an almost universal issue that develops in the later stages of chronic kidney disease (CKD) primarily due to a lack of erythropoietin (EPO) and the depressed EPO response in bone marrow. This can have a profound effect on the patient's lifestyle and quality of life. Knowledge of both the psychosocial and clinical areas of CKD is imperative for healthcare professionals so that they can be at the forefront of improvements of CKD patient care.
EFFECTS OF TEACHING PROGRAMME ON QUALITY OF LIFE FOR PATIENTS WITH END‐STAGE RENAL DISEASE
Authors: Bayoumi Magda , El‐Fouly Yasmin
Published: May 2010

End‐stage renal disease and its treatments negatively affect quality of life. Self‐care is an important approach for helping the patients deal with their problems. The aim of this study was to improve self‐care and quality of life of haemodialysis patients through teaching and evaluating their quality of life. This cross‐section design with pre‐post assessment was conducted in the dialysis unit of Suez Canal University Hospitals, participants were 50 patients receiving maintenance haemodialysis. Data were collected using a structured interview questionnaire, and the Kidney Disease Quality of Life Scale Short Form. Statistically the results show significant improvements that were revealed in the scores of many domains of quality of life, p < 0.001, except the physical domain. Statistically significant associations were revealed between pre‐ and postprogramme improvement in the total quality‐of‐life scores. The statistically significant independent predictors of quality‐of‐life improvement were programme attendance, dialysis duration and marital status.
CARDIOVASCULAR DISEASE IN RENAL TRANSPLANT RECIPIENTS
Authors: McQuarrie Emily P. , Fellström Bengt C. , Holdaas Hallvard , Jardine Alan G.
Published: May 2010

Renal transplant recipients have a markedly increased risk of premature cardiovascular disease (CVD) compared with the general population, although considerably lower than that of patients receiving maintenance haemodialysis. CVD in transplant recipients is poorly characterised and differs from the nonrenal population, with a much higher proportion of fatal to nonfatal cardiac events. In addition to traditional ischaemic heart disease risk factors such as age, gender, diabetes and smoking, there are additional factors to consider in this population such as the importance of hypertension, left ventricular hypertrophy and uraemic cardiomyopathy. There are factors specific to transplantation such immunosuppressive therapies and graft dysfunction which contribute to this altered risk profile. However, understanding and treatment is limited by the absence of large randomised intervention trials addressing risk factor modification, with the exception of the ALERT study. The approach to managing these patients should begin early and be multifactorial in nature.
ATHEROSCLEROTIC RENOVASCULAR DISEASE AND THE HEART
Authors: Chrysochou Constantina , Kalra Philip A.
Published: May 2010

The detrimental link between cardiac and renal pathophysiology in atherosclerotic renovascular disease (ARVD) is well described. Patients with ARVD usually have significant atherosclerotic disease in other vascular beds including the coronary circulation, and structural and functional cardiac changes are highly prevalent. This excess cardiovascular burden probably contributes to the increased cardiac morbidity and mortality seen in these patients.

In this review we describe the associations of cardiovascular disease and ARVD and treatment thereof. The clinical debate of which patients are offered any additional advantage by revascularisation over medications alone remains to be answered. The close link between cardiac and renal pathophysiology in ARVD raises the possibility that renal revascularisation might confer a benefit to cardiac morphology and function. This is the subject of ongoing randomised controlled trials.
THE DIABETIC CKD PATIENT—A MAJOR CARDIOVASCULAR CHALLENGE
Authors: Van Der Meer Irene M. , Ruggenenti Piero , Remuzzi Giuseppe
Published: May 2010

The diabetic patient with chronic kidney disease (CKD) is at very high risk of cardiovascular disease (CVD). Primary and secondary CVD prevention is of major importance and should be targeted at both traditional cardiovascular risk factors and risk factors specific for patients with CKD, such as albuminuria, anaemia and CKD—mineral and bone disorder. However, treatment goals have largely been derived from clinical trials including patients with no or only mild CKD and may not be generalisable to patients with advanced renal disease. Moreover, in patients on renal replacement therapy, the association between traditional CVD risk factors and the incidence of CVD may be reversed, and pharmaceutical interventions that are beneficial in the general population may be ineffective or even harmful in this high‐risk population. Those involved in the delivery of care to patients with diabetes and CKD need to be aware of these issues and should adopt an individualised approach to treatment.
Differences of genetic diversity and antibiotics susceptibility of Pseudomonas aeruginosa isolated from hospital, river and coastal seawater
Authors: Nonaka Lisa , Inubushi Ayumi , Shinomiya Hiroto , Murase Mitsuharu , Suzuki Satoru
Published: May 2010

Pseudomonas aeruginosa is an opportunistic pathogen, and ubiquitously found in natural environments. However, details on difference between clinical and environmental isolates have not been reported enough. In this study, we defined existence of marine specific genogroup and different drug susceptibility among isolates from clinical, river and coastal seawaters. Pseudomonas aeruginosa were isolated by using cetrimide kanamycin nalidixic acid agar media and incubation at 42°C, which was specific selection method of this bacterium from the natural aquatic samples. Pulse field gel electrophoresis analysis showed that the levels of genetic variation within P. aeruginosa were different among environmental sites. Pulse field gel electrophoresis also showed a lower diversity within P. aeruginosa in the coastal waters; and coastal strains isolated different sampling points were positioned closely in the same cluster. Most of the aquatic isolates were sensitive to most of the drugs tested and ‘intermediate’ to panipenem on the contrast to the clinical isolates, suggesting that the clinical use of antibiotics affect significantly to the emergence of the drug‐resistant P. aeruginosa.
EXPERIENCES AS COMPLEX EVENTS
Authors: Jacovides Michael
Published: May 2010

abstract

It is argued that experiences are complex events that befall their subjects. Each experience has a single subject and depends on the state or the event that it is of. The constituents of an experience are (or underlie) its subject, its grounding event or state, and everything that the subject is aware of during that time that's relevant to the telling of the story of how it was to participate in that event or be put in that state. The experience occurs where the person having the experience is. An experience of an event or state occurs when that event or state makes a difference to its possessor's conscious life, where this difference is either a matter of really knowing what's happening or merely a matter of being affected.
POLITICAL LIBERALISM, BASIC LIBERTIES, AND LEGAL PATERNALISM
Authors: Glod William
Published: May 2010

abstract

This essay argues that neutral paternalism (NP) is problematic for antiperfectionist liberal theories. Section 2 raises textual evidence that Rawlsian liberalism does not oppose and may even support NP. In section 3, I cast doubt on whether NP should have a place in political liberalism by defending a partially comprehensive conception of the good I call “moral capacity at each moment,” or MCEM, that is inconsistent with NP. I then explain why MCEM is a reasonable conception on Rawls's account of reasonableness. In section 4, I handle concerns that showing NP fails the test of Rawlsian public justification is a nonstarter since NP does not threaten any of our basic liberties. I sketch an argument that, if this is so, the burden is on political liberalism to defend its particular account of basic liberties, since MCEM is reasonable on Rawlsian grounds. More precisely, MCEM is a conception that challenges the way Rawls characterizes basic liberties; that is, his list of basic liberties should be more inclusive by political liberalism's own structural commitments, including Rawls's “liberal principle of legitimacy.” On this revised account, political liberalism can mount a strong opposition to hard legal paternalism.
Preparation of light-atom tips for scanning probe microscopy by explosive delamination
Authors: Hofmann T. , Welker J. , Giessibl F. J.
Published: May 2010

To obtain maximal resolution in scanning tunneling microscopy (STM) and atomic force microscopy, the size of the protruding tip orbital has to be minimized. Beryllium as tip material is a promising candidate for enhanced resolution because a beryllium atom has just four electrons, leading to a small covalent radius of only 96 pm. Besides that, beryllium is conductive and has a high elastic modulus, which is a necessity for a stable tip apex. However, beryllium tips that are prepared ex situ are covered with a robust oxide layer, which cannot be removed by just heating the tip. Here, the authors present a successful preparation method that combines the heating of the tip by field emission and a mild collision with a clean metal plate. That method yields a clean, oxide-free tip surface as proven by a work function of Φexpt=5.5 eV as deduced from a current-distance curve. Additionally, a STM image of the Si-(111)-(7×7) is presented to prove the single-atom termination of the beryllium tip.
Open source scanning probe microscopy control software package GXSM
Authors: Zahl Percy , Wagner Thorsten , Möller Rolf , Klust Andreas
Published: May 2010

GXSM is a full featured and modern scanning probe microscopy (SPM) software. It can be used for powerful multidimensional image/data processing, analysis, and visualization. Connected to an instrument, it is operating many different flavors of SPM, e.g., scanning tunneling microscopy and atomic force microscopy or, in general, two-dimensional multichannel data acquisition instruments. The GXSM core can handle different data types, e.g., integer and floating point numbers. An easily extendable plug-in architecture provides many image analysis and manipulation functions. A digital signal processor subsystem runs the feedback loop, generates the scanning signals, and acquires the data during SPM measurements. The programmable GXSM vector probe engine performs virtually any thinkable spectroscopy and manipulation task, such as scanning tunneling spectroscopy or tip formation. The GXSM software is released under the GNU general public license and can be obtained via the internet.
Internal damping for noncontact atomic force microscopy cantilevers
Authors: Zypman Fredy
Published: May 2010

In this article the authors build a practical modification to the standard Euler–Bernoulli equation for flexural modes of cantilever vibrations relevant for operation of noncontact atomic force microscopy in high vacuum conditions. This is done by first introducing an internal dissipation based on basic physical grounds. Second, this dissipation is written explicitly for the case of a cantilever in terms of the flexural deflection. Third, the equation is used to simulate the response of a free-end atomic force microscopy cantilever under harmonic excitation. Finally, this theoretical signal is compared to corresponding extant high vacuum experiments. They demonstrate that a single parameter is enough to reproduce the first two experimental flexural resonances. For comparison, they also show that the standard dissipation term proportional to the velocity, cannot fit the two peaks with a single parameter. They argue that the new term introduced here has a mesoscopic origin in the relative angular motion between consecutive layers inside the cantilever.
Weight Loss with Magnesium Alloys
Authors: Pollock Tresa M.
Published: May 2010

New design and processing approaches for magnesium-based alloys are offering a variety of opportunities in lightweight and energy-efficient applications.
Adaptive Evolution of an sRNA That Controls
Myxococcus
Development
Authors: Yu Yuen-Tsu N. , Yuan Xi , Velicer Gregory J.
Published: May 2010

Mutation of a small noncoding RNA drives adaptive evolution in a social bacterium.
Signaling Through Cooperation
Authors: Levy Emmanuel D. , Landry Christian R. , Michnick Stephen W.
Published: May 2010

Protein kinases and phosphatases may form a collaborative network of interactions to mediate cellular responses.
Five Questions on the Spill
Authors: Kerr Richard A. , Kintisch Eli , Schenkman Lauren , Stokstad Erik
Published: May 2010

Sizing up the weeks-long spill in the Gulf of Mexico and its impacts is proving a challenge for marine and coastal scientists. Scientists will be trying to answer five key questions over the coming months and years.
Animal Communication Helps Reveal Roots of Language
Authors: Balter Michael
Published: May 2010

An interdisciplinary gathering marks a turning point for a field historically richer in talk than data, but which now is increasingly embracing studies of animals.
Aichi Virus IgG Seroprevalence in Tunisia Parallels Genomic Detection and Clinical Presentation in Children with Gastroenteritis
Authors: Sdiri-Loulizi Khira , Hassine Mouna , Bour Jean-Baptiste , Ambert-Balay Katia , Mastouri Maha , Aho Ludwig-Serge , Gharbi-Khelifi Hakima , Aouni Zaidoun , Sakly Nabil , Chouchane Slaheddine , Neji-Guédiche Mohamed , Pothier Pierre , Aouni Mahjoub
Published: May 2010

Aichi virus has been described as a novel causative agent of gastroenteritis in humans. In this study, we report the seroprevalence distribution of Aichi virus in Tunisia. A panel of 1,000 sera was screened by applying an enzyme-linked immunosorbent assay for immunoglobulin G specific for Aichi virus. A considerable prevalence (92%) of antibody to Aichi virus was found across all age groups. The specific anti-Aichi virus antibodies increased with age, from a high rate (68.8%) in children under 10 years old to about 100% in persons more than 60 years old. We found a statistically significant increase in levels of antibody to Aichi virus according to the age of patients. Immunoglobulin M antibodies were detected among five children. A high frequency of Aichi virus monoinfections in hospitalized children with severe gastroenteritis was previously observed in Tunisia. Aichi virus causes diarrhea with dehydration, fever, and vomiting. This work is the first to establish a correlation between the high seroprevalence of specific Aichi virus antibodies, clinical presentation, and a high frequency of isolation of Aichi virus by genomic characterization in stools of children suffering from gastroenteritis. Our data show the importance and emerging character of Aichi virus in the viral etiology of pediatric gastroenteritis.
Interacting Roles of Immune Mechanisms and Viral Load in the Pathogenesis of Crimean-Congo Hemorrhagic Fever
Authors: Saksida Ana , Duh Darja , Wraber Branka , Dedushaj Isuf , Ahmeti Salih , Avšič-Županc Tatjana
Published: May 2010

Until now, the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) has not been well described. However, it has been hypothesized that it could be a result of the direct injury of virus-infected tissues in combination with the indirect effects of host immune responses, including cytokines. To shed more light on the role of viral load and cytokines, differential influences of CCHF virus (CCHFV) RNA load, antibody response, and cytokine production on severity and outcome of the disease were studied in sera of 46 patients with confirmed acute CCHF from Kosovo. In this study, viral load proved to be strongly related to the severity and outcome of the disease, with higher viral loads detected in patients with fatal outcomes than in surviving patients. Also, patients with fatal outcome had on average a weaker antibody response, if one was present at all. High levels of interleukin-10 (IL-10), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) were associated with poor outcome, since detected concentrations were highest in patients with fatal outcome and lowest in patients with moderate disease course. Additionally, a positive linear dependence between viral load and these cytokines was observed. Interestingly, reduced levels of IL-12 were detected in all CCHF patients. Our study favors the hypothesis that CCHF could be a result of a delayed and downregulated immune response caused by IL-10, which leads to an increased replication and spread of CCHFV throughout the body. This consequently triggers increased production of IFN-γ and TNF-α, cytokines mediating vascular dysfunction, disseminated intravascular coagulation, organ failure, and shock.
Differential Activation of NK Cells by Influenza A Pseudotype H5N1 and 1918 and 2009 Pandemic H1N1 Viruses
Authors: Du Ning , Zhou Jianfang , Lin Xiaojing , Zhang Yonghui , Yang Xiaoxing , Wang Yue , Shu Yuelong
Published: May 2010

Natural killer (NK) cells are the effectors of innate immunity and are recruited into the lung 48 h after influenza virus infection. Functional NK cell activation can be triggered by the interaction between viral hemagglutinin (HA) and natural cytotoxicity receptors NKp46 and NKp44 on the cell surface. Recently, novel subtypes of influenza viruses, such as H5N1 and 2009 pandemic H1N1, transmitted directly to the human population, with unusual mortality and morbidity rates. Here, the human NK cell responses to these viruses were studied. Differential activation of heterogeneous NK cells (upregulation of CD69 and CD107a and gamma interferon [IFN-γ] production as well as downregulation of NKp46) was observed following interactions with H5N1, 1918 H1N1, and 2009 H1N1 pseudotyped particles (pps), respectively, and the responses of the CD56dimsubset predominated. Much stronger NK activation was triggered by H5N1 and 1918 H1N1 pps than by 2009 H1N1 pps. The interaction of pps with NK cells and subsequent internalization were mediated by NKp46 partially. The NK cell activation by pps showed a dosage-dependent manner, while an increasing viral HA titer attenuated NK activation phenotypes, cytotoxicity, and IFN-γ production. The various host innate immune responses to different influenza virus subtypes or HA titers may be associated with disease severity.
Proteasome-Dependent Degradation of Daxx by the Viral E1B-55K Protein in Human Adenovirus-Infected Cells
Authors: Schreiner Sabrina , Wimmer Peter , Sirma Hüseyin , Everett Roger D. , Blanchette Paola , Groitl Peter , Dobner Thomas
Published: May 2010

The death-associated protein Daxx found in PML (promyelocytic leukemia protein) nuclear bodies (PML-NBs) is involved in transcriptional regulation and cellular intrinsic antiviral resistence against incoming viruses. We found that knockdown of Daxx in a nontransformed human hepatocyte cell line using RNA interference (RNAi) techniques results in significantly increased adenoviral (Ad) replication, including enhanced viral mRNA synthesis and viral protein expression. This Daxx restriction imposed upon adenovirus growth is counteracted by early protein E1B-55K (early region 1B 55-kDa protein), a multifunctional regulator of cell-cycle-independent Ad5 replication. The viral protein binds to Daxx and induces its degradation through a proteasome-dependent pathway. We show that this process is independent of Ad E4orf6 (early region 4 open reading frame 6), known to promote the proteasomal degradation of cellular p53, Mre11, DNA ligase IV, and integrin α3 in combination with E1B-55K. These results illustrate the importance of the PML-NB-associated factor Daxx in virus growth restriction and suggest that E1B-55K antagonizes innate antiviral activities of Daxx and PML-NBs to stimulate viral replication at a posttranslational level.
Redirecting Lentiviral Vectors Pseudotyped with Sindbis Virus-Derived Envelope Proteins to DC-SIGN by Modification of N-Linked Glycans of Envelope Proteins
Authors: Morizono Kouki , Ku Amy , Xie Yiming , Harui Airi , Kung Sam K. P. , Roth Michael D. , Lee Benhur , Chen Irvin S. Y.
Published: May 2010

Redirecting the tropism of viral vectors enables specific transduction of selected cells by direct administration of vectors. We previously developed targeting lentiviral vectors by pseudotyping with modified Sindbis virus envelope proteins. These modified Sindbis virus envelope proteins have mutations in their original receptor-binding regions to eliminate their natural tropisms, and they are conjugated with targeting proteins, including antibodies and peptides, to confer their tropisms on target cells. We investigated whether our targeting vectors interact with DC-SIGN, which traps many types of viruses and gene therapy vectors by binding to the N-glycans of their envelope proteins. We found that these vectors do not interact with DC-SIGN. When these vectors were produced in the presence of deoxymannojirimycin, which alters the structures of N-glycans from complex to high mannose, these vectors used DC-SIGN as their receptor. Genetic analysis demonstrated that the N-glycans at E2 amino acid (aa) 196 and E1 aa 139 mediate binding to DC-SIGN, which supports the results of a previous report of cryoelectron microscopy analysis. In addition, we investigated whether modification of the N-glycan structures could activate serum complement activity, possibly by the lectin pathway of complement activation. DC-SIGN-targeted transduction occurs in the presence of human serum complement, demonstrating that high-mannose structure N-glycans of the envelope proteins do not activate human serum complement. These results indicate that the strategy of redirecting viral vectors according to alterations of their N-glycan structures would enable the vectors to target specific cells types expressing particular types of lectins.
The Ubiquitin-Proteasome System Plays an Important Role during Various Stages of the Coronavirus Infection Cycle
Authors: Raaben Matthijs , Posthuma Clara C. , Verheije Monique H. , te Lintelo Eddie G. , Kikkert Marjolein , Drijfhout Jan W. , Snijder Eric J. , Rottier Peter J. M. , de Haan Cornelis A. M.
Published: May 2010

The ubiquitin-proteasome system (UPS) is a key player in regulating the intracellular sorting and degradation of proteins. In this study we investigated the role of the UPS in different steps of the coronavirus (CoV) infection cycle. Inhibition of the proteasome by different chemical compounds (i.e., MG132, epoxomicin, and Velcade) appeared to not only impair entry but also RNA synthesis and subsequent protein expression of different CoVs (i.e., mouse hepatitis virus [MHV], feline infectious peritonitis virus, and severe acute respiratory syndrome CoV). MHV assembly and release were, however, not appreciably affected by these compounds. The inhibitory effect on CoV protein expression did not appear to result from a general inhibition of translation due to induction of a cellular stress response by the inhibitors. Stress-induced phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) generally results in impaired initiation of protein synthesis, but the sensitivity of MHV infection to proteasome inhibitors was unchanged in cells lacking a phosphorylatable eIF2α. MHV infection was affected not only by inhibition of the proteasome but also by interfering with protein ubiquitination. Viral protein expression was reduced in cells expressing a temperature-sensitive ubiquitin-activating enzyme E1 at the restrictive temperature, as well as in cells in which ubiquitin was depleted by using small interfering RNAs. Under these conditions, the susceptibility of the cells to virus infection was, however, not affected, excluding an important role of ubiquitination in virus entry. Our observations reveal an important role of the UPS in multiple steps of the CoV infection cycle and identify the UPS as a potential drug target to modulate the impact of CoV infection.
Role of the Endoplasmic Reticulum Chaperone BiP, SUN Domain Proteins, and Dynein in Altering Nuclear Morphology during Human Cytomegalovirus Infection
Authors: Buchkovich Nicholas J. , Maguire Tobi G. , Alwine James C.
Published: May 2010

The process of assembly and egress of human cytomegalovirus (HCMV) virions requires significant morphological alterations of the nuclear and cytoplasmic architecture. In the studies presented we show that the nuclear periphery is dramatically altered, especially near the cytoplasmic assembly compartment, where the nuclear lamina is specifically rearranged, the outer nuclear membrane is altered, and the nucleus becomes permeable to large molecules. In addition, the tethering of the inner and outer nuclear membranes is lost during infection due to a decrease in levels of the SUN domain proteins. We previously demonstrated that the endoplasmic reticulum protein BiP functions as a component of the assembly compartment and disruption of BiP causes the loss of assembly compartment integrity. In this study we show that the depletion of BiP, and the loss of assembly compartment integrity, results in the loss of virally induced lamina rearrangement and morphology of the nucleus that is characteristic of HCMV infection. BiP functions in lamina rearrangement through its ability to affect lamin phosphorylation. Depletion of BiP and disruption of the assembly compartment result in the loss of lamin phosphorylation. The dependency of lamin phosphorylation on BiP correlates with an interaction between BiP and UL50. Finally, we confirm previous data (S. V. Indran, M. E. Ballestas, and W. J. Britt, J. Virol. 84:3162-3177, 2010) suggesting an involvement of dynein in assembly compartment formation and extend this observation by showing that when dynein is inhibited, the nuclear morphology characteristic of an HCMV infection is lost. Our data suggest a highly integrated assembly-egress continuum.
Safety and Immunogenicity of Novel Recombinant BCG and Modified Vaccinia Virus Ankara Vaccines in Neonate Rhesus Macaques
Authors: Rosario Maximillian , Fulkerson John , Soneji Shamit , Parker Joe , Im Eung-Jun , Borthwick Nicola , Bridgeman Anne , Bourne Charles , Joseph Joan , Sadoff Jerald C. , Hanke Tomáš
Published: May 2010

Although major inroads into making antiretroviral therapy available in resource-poor countries have been made, there is an urgent need for an effective vaccine administered shortly after birth, which would protect infants from acquiring human immunodeficiency virus type 1 (HIV-1) through breast-feeding.BacillusCalmette-Guérin (BCG) is given to most infants at birth, and its recombinant form could be used to prime HIV-1-specific responses for a later boost by heterologous vectors delivering the same HIV-1-derived immunogen. Here, two groups of neonate Indian rhesus macaques were immunized with either novel candidate vaccine BCG.HIVA401or its parental strain AERAS-401, followed by two doses of recombinant modified vaccinia virus Ankara MVA.HIVA. The HIVA immunogen is derived from African clade A HIV-1. All vaccines were safe, giving local reactions consistent with the expected response at the injection site. No systemic adverse events or gross abnormality was seen at necropsy. Both AERAS-401 and BCG.HIVA401induced high frequencies of BCG-specific IFN-γ-secreting lymphocytes that declined over 23 weeks, but the latter failed to induce detectable HIV-1-specific IFN-γ responses. MVA.HIVA elicited HIV-1-specific IFN-γ responses in all eight animals, but, except for one animal, these responses were weak. The HIV-1-specific responses induced in infants were lower compared to historic data generated by the two HIVA vaccines in adult animals but similar to other recombinant poxviruses tested in this model. This is the first time these vaccines were tested in newborn monkeys. These results inform further infant vaccine development and provide comparative data for two human infant vaccine trials of MVA.HIVA.
Feline Lectin Activity Is Critical for the Cellular Entry of Feline Infectious Peritonitis Virus
Authors: Regan Andrew D. , Ousterout David G. , Whittaker Gary R.
Published: May 2010

Feline infectious peritonitis is a lethal disease of felids caused by systemic infection with a feline coronavirus. Here, we report identification and analysis of the feline homologue to the human lectin DC-SIGN and show that it is a coreceptor for virulent strains of serotype 1 and serotype 2 feline coronaviruses.
Intradermal Vaccination with Influenza Virus-Like Particles by Using Microneedles Induces Protection Superior to That with Intramuscular Immunization
Authors: Quan Fu-Shi , Kim Yeu-Chun , Vunnava Aswani , Yoo Dae-Goon , Song Jae-Min , Prausnitz Mark R. , Compans Richard W. , Kang Sang-Moo
Published: May 2010

Influenza virus-like particles (VLPs) are a promising cell culture-based vaccine, and the skin is considered an attractive immunization site. In this study, we examined the immunogenicity and protective efficacy of influenza VLPs (H1N1 A/PR/8/34) after skin vaccination using vaccine dried on solid microneedle arrays. Coating of microneedles with influenza VLPs using an unstabilized formulation was found to decrease hemagglutinin (HA) activity, whereas inclusion of trehalose disaccharide preserved the HA activity of influenza VLP vaccines after microneedles were coated. Microneedle vaccination of mice in the skin with a single dose of stabilized influenza VLPs induced 100% protection against challenge infection with a high lethal dose. In contrast, unstabilized influenza VLPs, as well as intramuscularly injected vaccines, provided inferior immunity and only partial protection (≤40%). The stabilized microneedle vaccination group showed IgG2a levels that were 1 order of magnitude higher than those of other groups and had the lowest lung viral titers after challenge. Also, levels of recall immune responses, including hemagglutination inhibition titers, neutralizing antibodies, and antibody-secreting plasma cells, were significantly higher after skin vaccination with stabilized formulations. Therefore, our results indicate that HA stabilization, combined with vaccination via the skin using a vaccine formulated as a solid microneedle patch, confers protection superior to that with intramuscular injection and enables potential dose-sparing effects which are reflected by pronounced increases in rapid recall immune responses against influenza virus.