bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gastrointestinal Delivery of Baculovirus Displaying Influenza Virus Hemagglutinin Protects Mice against Heterologous H5N1 Infection
Authors: Prabakaran Mookkan , Madhan Selvaraj , Prabhu Nayana , Qiang Jia , Kwang Jimmy 
Published: January 2010

ABSTRACT

The recent outbreaks of influenza A H5N1 virus in birds and humans have necessitated the development of potent H5N1 vaccines. In this study, we evaluated the protective potential of an immediate-early promoter-based baculovirus displaying hemagglutinin (BacHA) against highly pathogenic avian influenza (HPAI) H5N1 virus infection in a mouse model. Gastrointestinal delivery of BacHA significantly enhanced the systemic immune response in terms of HA-specific serum IgG and hemagglutination inhibition (HI) titers. In addition, BacHA vaccine was able to significantly enhance the mucosal IgA level. The inclusion of recombinant cholera toxin B subunit as a mucosal adjuvant along with BacHA vaccine did not influence either the systemic or mucosal immunity. Interestingly, an inactivated form of BacHA was able to induce only a negligible level of immune responses compared to its live counterpart. Microneutralization assay also indicated that live BacHA vaccine was able to induce strong cross-clade neutralization against heterologous H5N1 strains (clade 1.0, clade 2.1, and clade 8.0) compared to the inactivated BacHA. Viral challenge studies showed that live BacHA was able to provide 100% protection against 5 50% mouse lethal doses (MLD
50
) of homologous (clade 2.1) and heterologous (clade 1) H5N1. Moreover, histopathological examinations revealed that mice vaccinated with live BacHA had only minimal bronchitis in lungs and regained their body weight more rapidly postchallenge. Furthermore, immunohistochemistry results demonstrated that the live BacHA was able to transduce and express HA in the intestinal epithelial cells
in vitro
and
in vivo
. We have demonstrated that recombinant baculovirus with a white spot syndrome virus (WSSV) immediate-early promoter 1 (ie1) acted as a vector as well as a protein vaccine and will enable the rapid production of prepandemic and pandemic vaccines without any biosafety concerns.
MicroRNA Expression and Virulence in Pandemic Influenza Virus-Infected Mice
Authors: Li Yu , Chan Eric Y. , Li Jiangning , Ni Chester , Peng Xinxia , Rosenzweig Elizabeth , Tumpey Terrence M. , Katze Michael G. 
Published: January 2010

ABSTRACT
The worst known H1N1 influenza pandemic in history resulted in more than 20 million deaths in 1918 and 1919. Although the underlying mechanism causing the extreme virulence of the 1918 influenza virus is still obscure, our previous functional genomics analyses revealed a correlation between the lethality of the reconstructed 1918 influenza virus (r1918) in mice and a unique gene expression pattern associated with severe immune responses in the lungs. Lately, microRNAs have emerged as a class of crucial regulators for gene expression. To determine whether differential expression of cellular microRNAs plays a role in the host response to r1918 infection, we compared the lung cellular “microRNAome” of mice infected by r1918 virus with that of mice infected by a nonlethal seasonal influenza virus, A/Texas/36/91. We found that a group of microRNAs, including miR-200a and miR-223, were differentially expressed in response to influenza virus infection and that r1918 and A/Texas/36/91 infection induced distinct microRNA expression profiles. Moreover, we observed significant enrichment in the number of predicted cellular target mRNAs whose expression was inversely correlated with the expression of these microRNAs. Intriguingly, gene ontology analysis revealed that many of these mRNAs play roles in immune response and cell death pathways, which are known to be associated with the extreme virulence of r1918. This is the first demonstration that cellular gene expression patterns in influenza virus-infected mice may be attributed in part to microRNA regulation and that such regulation may be a contributing factor to the extreme virulence of the r1918.
Ecoepidemiology and Complete Genome Comparison of Different Strains of Severe Acute Respiratory Syndrome-Related
Rhinolophus
Bat Coronavirus in China Reveal Bats as a Reservoir for Acute, Self-Limiting Infection That Allows Recombination Events
Authors: Lau Susanna K. P. , Li Kenneth S. M. , Huang Yi , Shek Chung-Tong , Tse Herman , Wang Ming , Choi Garnet K. Y. , Xu Huifang , Lam Carol S. F. , Guo Rongtong , Chan Kwok-Hung , Zheng Bo-Jian , Woo Patrick C. Y. , Yuen Kwok-Yung 
Published: January 2010

ABSTRACT

Despite the identification of severe acute respiratory syndrome-related coronavirus (SARSr-CoV) in
Rhinolophus
Chinese horseshoe bats (SARSr-Rh-BatCoV) in China, the evolutionary and possible recombination origin of SARSr-CoV remains undetermined. We carried out the first study to investigate the migration pattern and SARSr-Rh-BatCoV genome epidemiology in Chinese horseshoe bats during a 4-year period. Of 1,401 Chinese horseshoe bats from Hong Kong and Guangdong, China, that were sampled, SARSr-Rh-BatCoV was detected in alimentary specimens from 130 (9.3%) bats, with peak activity during spring. A tagging exercise of 511 bats showed migration distances from 1.86 to 17 km. Bats carrying SARSr-Rh-BatCoV appeared healthy, with viral clearance occurring between 2 weeks and 4 months. However, lower body weights were observed in bats positive for SARSr-Rh-BatCoV, but not Rh-BatCoV HKU2. Complete genome sequencing of 10 SARSr-Rh-BatCoV strains showed frequent recombination between different strains. Moreover, recombination was detected between SARSr-Rh-BatCoV Rp3 from Guangxi, China, and Rf1 from Hubei, China, in the possible generation of civet SARSr-CoV SZ3, with a breakpoint at the nsp16/spike region. Molecular clock analysis showed that SARSr-CoVs were newly emerged viruses with the time of the most recent common ancestor (tMRCA) at 1972, which diverged between civet and bat strains in 1995. The present data suggest that SARSr-Rh-BatCoV causes acute, self-limiting infection in horseshoe bats, which serve as a reservoir for recombination between strains from different geographical locations within reachable foraging range. Civet SARSr-CoV is likely a recombinant virus arising from SARSr-CoV strains closely related to SARSr-Rh-BatCoV Rp3 and Rf1. Such frequent recombination, coupled with rapid evolution especially in ORF7b/ORF8 region, in these animals may have accounted for the cross-species transmission and emergence of SARS.
Sustainability of Virulence in a Phage-Bacterial Ecosystem
Authors: Heilmann Silja , Sneppen Kim , Krishna Sandeep 
Published: January 2010

ABSTRACT
Virulent phages and their bacterial hosts represent an unusual sort of predator-prey system where each time a prey is eaten, hundreds of new predators are born. It is puzzling how, despite the apparent effectiveness of the phage predators, they manage to avoid driving their bacterial prey to extinction. Here we consider a phage-bacterial ecosystem on a two-dimensional (2-d) surface and show that homogeneous space in itself enhances coexistence. We analyze different behavioral mechanisms that can facilitate coexistence in a spatial environment. For example, we find that when the latent times of the phage are allowed to evolve, selection favors “mediocre killers,” since voracious phage rapidly deplete local resources and go extinct. Our model system thus emphasizes the differences between short-term proliferation and long-term ecosystem sustainability.
Evolutionary Dynamics of Multiple Sublineages of H5N1 Influenza Viruses in Nigeria from 2006 to 2008
Authors: Fusaro Alice , Nelson Martha I. , Joannis Tony , Bertolotti Luigi , Monne Isabella , Salviato Annalisa , Olaleye Olufemi , Shittu Ismaila , Sulaiman Lanre , Lombin Lami H. , Capua Ilaria , Holmes Edward C. , Cattoli Giovanni 
Published: January 2010

ABSTRACT
Highly pathogenic A/H5N1 avian influenza (HPAI H5N1) viruses have seriously affected the Nigerian poultry industry since early 2006. Previous studies have identified multiple introductions of the virus into Nigeria and several reassortment events between cocirculating lineages. To determine the spatial, evolutionary, and population dynamics of the multiple H5N1 lineages cocirculating in Nigeria, we conducted a phylogenetic analysis of whole-genome sequences from 106 HPAI H5N1 viruses isolated between 2006 and 2008 and representing all 25 Nigerian states and the Federal Capital Territory (FCT) reporting outbreaks. We identified a major new subclade in Nigeria that is phylogenetically distinguishable from all previously identified sublineages, as well as two novel reassortment events. A detailed analysis of viral phylogeography identified two major source populations for the HPAI H5N1 virus in Nigeria, one in a major commercial poultry area (southwest region) and one in northern Nigeria, where contact between wild birds and backyard poultry is frequent. These findings suggested that migratory birds from Eastern Europe or Russia may serve an important role in the introduction of HPAI H5N1 viruses into Nigeria, although virus spread through the movement of poultry and poultry products cannot be excluded. Our study provides new insight into the genesis and evolution of H5N1 influenza viruses in Nigeria and has important implications for targeting surveillance efforts to rapidly identify the spread of the virus into and within Nigeria.
Mutations Abrogating VP35 Interaction with Double-Stranded RNA Render Ebola Virus Avirulent in Guinea Pigs
Authors: Prins Kathleen C. , Delpeut Sebastien , Leung Daisy W. , Reynard Olivier , Volchkova Valentina A. , Reid St. Patrick , Ramanan Parameshwaran , Cárdenas Washington B. , Amarasinghe Gaya K. , Volchkov Viktor E. , Basler Christopher F. 
Published: January 2010

ABSTRACT

Ebola virus (EBOV) protein VP35 is a double-stranded RNA (dsRNA) binding inhibitor of host interferon (IFN)-α/β responses that also functions as a viral polymerase cofactor. Recent structural studies identified key features, including a central basic patch, required for VP35 dsRNA binding activity. To address the functional significance of these VP35 structural features for EBOV replication and pathogenesis, two point mutations, K319A/R322A, that abrogate VP35 dsRNA binding activity and severely impair its suppression of IFN-α/β production were identified. Solution nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography reveal minimal structural perturbations in the K319A/R322A VP35 double mutant and suggest that loss of basic charge leads to altered function. Recombinant EBOVs encoding the mutant VP35 exhibit, relative to wild-type VP35 viruses, minimal growth attenuation in IFN-defective Vero cells but severe impairment in IFN-competent cells. In guinea pigs, the VP35 mutant virus revealed a complete loss of virulence. Strikingly, the VP35 mutant virus effectively immunized animals against subsequent wild-type EBOV challenge. These
in vivo
studies, using recombinant EBOV viruses, combined with the accompanying biochemical and structural analyses directly correlate VP35 dsRNA binding and IFN inhibition functions with viral pathogenesis. Moreover, these studies provide a framework for the development of antivirals targeting this critical EBOV virulence factor.
Acquisition of Complement Resistance through Incorporation of CD55/Decay-Accelerating Factor into Viral Particles Bearing Baculovirus GP64
Authors: Kaname Yuuki , Tani Hideki , Kataoka Chikako , Shiokawa Mai , Taguwa Shuhei , Abe Takayuki , Moriishi Kohji , Kinoshita Taroh , Matsuura Yoshiharu 
Published: January 2010

ABSTRACTA major obstacle to gene transduction by viral vectors is inactivation by human complementin vivo. One way to overcome this is to incorporate complement regulatory proteins, such as CD55/decay accelerating factor (DAF), into viral particles. Lentivirus vectors pseudotyped with the baculovirus envelope protein GP64 have been shown to acquire more potent resistance to serum inactivation and longer transgene expression than those pseudotyped with the vesicular stomatitis virus (VSV) envelope protein G. However, the molecular mechanisms underlying resistance to serum inactivation in pseudotype particles bearing the GP64 have not been precisely elucidated. In this study, we generated pseudotype and recombinant VSVs bearing the GP64. Recombinant VSVs generated in human cell lines exhibited the incorporation of human DAF in viral particles and were resistant to serum inactivation, whereas those generated in insect cells exhibited no incorporation of human DAF and were sensitive to complement inactivation. The GP64 and human DAF were detected on the detergent-resistant membrane and were coprecipitated by immunoprecipitation analysis. A pseudotype VSV bearing GP64 produced in human DAF knockdown cells reduced resistance to serum inactivation. In contrast, recombinant baculoviruses generated in insect cells expressing human DAF or carrying the human DAF gene exhibited resistance to complement inactivation. These results suggest that the incorporation of human DAF into viral particles by interacting with baculovirus GP64 is involved in the acquisition of resistance to serum inactivation.
Rapid Escape from Preserved Cross-Reactive Neutralizing Humoral Immunity without Loss of Viral Fitness in HIV-1-Infected Progressors and Long-Term Nonprogressors
Authors: van Gils Marit J. , Bunnik Evelien M. , Burger Judith A. , Jacob Yodit , Schweighardt Becky , Wrin Terri , Schuitemaker Hanneke 
Published: January 2010

ABSTRACT

A substantial proportion of human immunodeficiency virus type 1 (HIV-1)-infected individuals has cross-reactive neutralizing activity in serum, with a similar prevalence in progressors and long-term nonprogressors (LTNP). We studied whether disease progression in the face of cross-reactive neutralizing serum activity is due to fading neutralizing humoral immunity over time or to viral escape. In three LTNP and three progressors, high-titer cross-reactive HIV-1-specific neutralizing activity in serum against a multiclade pseudovirus panel was preserved during the entire clinical course of infection, even after AIDS diagnosis in progressors. However, while early HIV-1 variants from all six individuals could be neutralized by autologous serum, the autologous neutralizing activity declined during chronic infection. This could be attributed to viral escape and the apparent inability of the host to elicit neutralizing antibodies to the newly emerging viral escape variants. Escape from autologous neutralizing activity was not associated with a reduction in the viral replication rate
in vitro
. Escape from autologous serum with cross-reactive neutralizing activity coincided with an increase in the length of the variable loops and in the number of potential N-linked glycosylation sites in the viral envelope. Positive selection pressure was observed in the variable regions in envelope, suggesting that, at least in these individuals, these regions are targeted by humoral immunity with cross-reactive potential. Our results may imply that the ability of HIV-1 to rapidly escape cross-reactive autologous neutralizing antibody responses without the loss of viral fitness is the underlying explanation for the absent effect of potent cross-reactive neutralizing humoral immunity on the clinical course of infection.
Comparison of the history obtained by patient-completed questionnaires with doctors’ standard notes for patients with acute abdominal pain
Authors: Saravanan B , Muhammad R , Geach R , Jenkinson L R 
Published: January 2010

Abstract

Background
Studies have shown that proformas improve the information recorded by junior doctors when they clerk patients with acute abdominal pain. This increases their diagnostic accuracy, but doctors are reluctant to use them. Patient-completed questionnaires are being used in elective surgery, but can they be used for patients with acute abdominal pain?

Objective
To evaluate the history obtained by patient-completed questionnaires in patients with acute abdominal pain and compare this with the history recorded by the admitting junior doctors.

Design
Prospective observational study.

Subjects
116 adult patients aged 17–90 admitted as an emergency to the Department of Surgery at Ysbyty Gwynedd in North Wales.

Main outcome measures
Differences in the amount of information collected using patient-completed questionnaires and the history recorded by junior doctors. The questionnaires contained 17 points relating to general symptoms of the acute abdomen and five points related to gynaecological symptoms.

Results
Of the 116 patients studied, 100 (86.2%) completed the questionnaires. There were 60 female and 40 male patients and the median age was 49 years (range 17–90). Doctors recorded fewer than 50% of the general symptoms for acute abdominal pain and patients recorded 90% or more (p&lt;0.0001). Doctors’ documentation of gynaecological symptoms was better, but still less detailed than patients’ (52–76% vs 92–100%).

Conclusion
Patient-completed questionnaires can be used to obtain a more accurate history than junior doctors for most patients admitted with acute abdominal pain.
Specialist practice in the community: chest medicine
Authors: O’Kelly N , Ghosh S , Smith J ,   Long-Term Conditions Team
Published: January 2010

Abstract
The impact of long term conditions (LTCs) is an issue for all health care systems in the world today. With an aging population and the incidence of LTCs subsequently increasing, the impact on health economics is a challenging burden on all societies. Thus, delivering cost effective high quality care for all LTCs is a major challenge to both health payers and providers alike. This review discusses the various models of care adopted in health systems. It then focuses on community specialist services for respiratory disease in the context of this changing health environment and concentrates on the scope and evidence to support specialist respiratory community services. The review concludes with discussions surrounding the implementation of such services across two large primary care trusts in the UK, with particular focus on the arguments for their future development and incorporation with strategies that are cost effective, while helping older people with LTCs to maintain their health, functional ability and quality of care.
An overview of the management of morbid obesity
Authors: Monkhouse S J W , Morgan J D T , Bates S E , Norton S A 
Published: January 2010

Abstract
Obesity is a modern-day epidemic with serious physical, psychological and economic implications for the patients. Tackling obesity is now a priority for most healthcare providers. Managing such patients can be complex, emotional, time consuming and often frustrating. Obesity surgery, in its various forms, has revolutionised this struggle. With appropriate selection of patients, adequate resources and a multidisciplinary team involvement, obesity can now effectively be “cured”. It is vital that those who deal with obese patients know how to access these services and understand the processes involved in the journey from initial assessment to postoperative follow-up. Obesity surgery has a major impact in reducing obesity-related comorbidities such as diabetes and hypertension and contributes to society by returning patients to work. Prevention must be at the heart of any strategy to manage obesity, but, for established cases, surgery is taking centre stage and will continue to flourish as new techniques and procedures are developed.
PORTRAITS OF RUSSIAN WOMEN ENTREPRENEURS: IDENTIFICATION AND WAYS OF LEADERSHIP
Authors: AALTIO IIRIS , PELTONEN HANNA 
Published: January 2010

Entrepreneurship has developed in Russia during the past two decades, which is a short time to develop a firm business culture. Women are still a minority among entrepreneurs globally, also in Russia [Verhovskaya, O. and Dorokhina, M. (2008) GEM. Global Entrepreneurship Monitor, Executive Summary, Russia 2007, www.gemconsortium.org, 30.9.2008]. Our study focuses on Russian women entrepreneurship by means of an interview and photographs of 10 women entrepreneurs in the St. Petersburg area. We ask, how do they identify themselves in the current economic situation. Further, we ask if there is a specifically Russian type of women entrepreneurship and entrepreneurial identification. Finally, in the study it is also elaborated the interviewed women entrepreneurs' perceptions concerning the Russian market economy and its transition, as well as their views for the future.This study results show that the women entrepreneurs make sense of their identity as leaders using expressions of autocracy and democracy. Moreover, they express a subjectively rich sense of their own entrepreneurship with no signs of marginality, and had an optimistic outlook on the future with wishes to expand and develop their businesses. Methodologically, the study contributes in combining the interview data and photograph analysis.
FEMALE ENTREPRENEURS' AUTHORITY: IS THE CREATIVE ASPECT OF AUTHORITY A MASCULINE FICTION IN MANAGERIAL AND ENTREPRENEURIAL PARADIGMS?
Authors: REDIEN-COLLOT RENAUD 
Published: January 2010

Authority is the confirmation of the control an individual has over norms and codes (Sennet, 1981). It stimulates the development of social capital. Gender shapes authority. Bourdieu (1994) stresses that in traditional societies men can interpret and produce norms whereas women reproduce them and consequently may experience difficulties in constructing their authority. Butler (1990) confirms that this dichotomy is still effective in post-modern contexts.In the literature on women entrepreneurs, scholars stress their lack of social capital as an impediment to growing the business and suggest that they should follow the male model (Aldrich et al., 1997; Ban et al., 1996). However, if one examines carefully the process of production of social capital, one would see that it is the result of a strict gender labor-division. In spite of their agentivity, female entrepreneurs fail to overcome this. Many of them may thus be tempted to adapt male patterns of authority.The present study examines how women entrepreneurs and minority business owners assimilate authority that is encapsulated in the traditional male entrepreneurial discourse. Then it analyses the perception of women entrepreneurs on authority and its impact on their style of internal management and their strategies of networking. The results reveal that either female entrepreneurs adopt authority as a repressive tool of management that helps them to develop their social capital in restricted circles of influence or they scorn authority as the display of norms that may endanger the reputation of their firms and their social influence without proposing a clear alternative. Apparently, women entrepreneurs deny the creative aspects of authority that Sennet and his Foucaldian followers have detected in managers' behaviors in the context of organizational sociology.