bluuebunny/crossref_metadata_2025_split huggingface dataset:
Second-Site Compensatory Mutations of HIV-1 Capsid Mutations
Authors: Noviello Colleen M. , López Claudia S. , Kukull Ben , McNett Henry , Still Amelia , Eccles Jacob , Sloan Rachel , Barklis Eric 
Published: March 2011

ABSTRACT

The human immunodeficiency virus (HIV) capsid (CA) protein assembles into a hexameric lattice that forms the mature virus core. Contacts between the CA N-terminal domain (NTD) of one monomer and the C-terminal domain (CTD) of the adjacent monomer are important for the assembly of this core. In this study, we have examined the effects of mutations in the NTD region associated with this interaction. We have found that such mutations yielded modest reductions of virus release but major effects on viral infectivity. Cell culture and
in vitro
assays indicate that the infectivity defects relate to abnormalities in the viral cores. We have selected second-site compensatory mutations that partially restored HIV infectivity. These mutations map to the CA CTD and to spacer peptide 1 (SP1), the portion of the precursor Gag protein immediately C terminal to the CTD. The compensatory mutations do not locate to the molecularly modeled intermolecular NTD-CTD interface. Rather, the compensatory mutations appear to act indirectly, possibly by realignment of the C-terminal helix of the CA CTD, which participates in the NTD-CTD interface and has been shown to serve an important role in the assembly of infectious virus.
The C-Terminal 42 Residues of the Tula Virus Gn Protein Regulate Interferon Induction
Authors: Matthys Valery , Gorbunova Elena E. , Gavrilovskaya Irina N. , Pepini Timothy , Mackow Erich R. 
Published: March 2011

ABSTRACT
Hantaviruses primarily infect the endothelial cell lining of capillaries and cause two vascular permeability-based diseases. The ability of pathogenic hantaviruses to regulate the early induction of interferon determines whether hantaviruses replicate in endothelial cells. Tula virus (TULV) and Prospect Hill virus (PHV) are hantaviruses which infect human endothelial cells but fail to cause human disease. PHV is unable to inhibit early interferon (IFN) responses and fails to replicate within human endothelial cells. However, TULV replicates successfully in human endothelial cells, suggesting that TULV is capable of regulating cellular IFN responses. We observed a >300-fold reduction in the IFN-stimulated genes (ISGs) MxA and ISG56 following TULV versus PHV infection of endothelial cells 1 day postinfection. Similar to results with pathogenic hantaviruses, expressing the TULV Gn protein cytoplasmic tail (Gn-T) blocked RIG-I- and TBK1-directed transcription from IFN-stimulated response elements (ISREs) and IFN-β promoters (>90%) but not transcription directed by constitutively active IFN regulatory factor-3 (IRF3). In contrast, expressing the PHV Gn-T had no effect on TBK1-induced transcriptional responses. Analysis of Gn-T truncations demonstrated that the C-terminal 42 residues of the Gn-T (Gn-T-C42) from TULV, but not PHV, inhibited IFN induction >70%. These findings demonstrate that the TULV Gn-T inhibits IFN- and ISRE-directed responses upstream of IRF3 at the level of the TBK1 complex and further define a 42-residue domain of the TULV Gn-T that inhibits IFN induction. In contrast to pathogenic hantavirus Gn-Ts, the TULV Gn-T lacks a C-terminal degron domain and failed to bind tumor necrosis factor (TNF) receptor-associated factor 3 (TRAF3), a TBK1 complex component required for IRF3 activation. These findings indicate that the nonpathogenic TULV Gn-T regulates IFN induction but accomplishes this via unique interactions with cellular TBK1 complexes. These findings fundamentally distinguish nonpathogenic hantaviruses, PHV and TULV, and demonstrate that IFN regulation alone is insufficient for hantaviruses to cause disease. Yet regulating the early IFN response is necessary for hantaviruses to replicate within human endothelial cells and to be pathogenic. Thus, in addition to IFN regulation, hantaviruses contain discrete virulence determinants which permit them to be human pathogens.
Nuclear Envelope Disruption Involving Host Caspases Plays a Role in the Parvovirus Replication Cycle
Authors: Cohen Sarah , Marr Alexandra K. , Garcin Pierre , Panté Nelly 
Published: March 2011

ABSTRACT
Parvoviruses are small, nonenveloped, single-stranded DNA viruses which replicate in the nucleus of the host cell. We have previously found that early during infection the parvovirus minute virus of mice (MVM) causes small, transient disruptions of the nuclear envelope (NE). We have now investigated the mechanism used by MVM to disrupt the NE. Here we show that the viral phospholipase A2, the only known enzymatic domain on the parvovirus capsid, is not involved in causing NE disruption. Instead, the virus utilizes host cell caspases, which are proteases involved in causing NE breakdown during apoptosis, to facilitate these nuclear membrane disruptions. Studies with pharmacological inhibitors indicate that caspase-3 in particular is involved. A caspase-3 inhibitor prevents nuclear lamin cleavage and NE disruption in MVM-infected mouse fibroblast cells and reduces nuclear entry of MVM capsids and viral gene expression. Caspase-3 is, however, not activated above basal levels in MVM-infected cells, and other aspects of apoptosis are not triggered during early MVM infection. Instead, basally active caspase-3 is relocalized to the nuclei of infected cells. We propose that NE disruption involving caspases plays a role in (i) parvovirus entry into the nucleus and (ii) alteration of the compartmentalization of host proteins in a way that is favorable for the virus.
The Helical Domains of the Stem Region of Dengue Virus Envelope Protein Are Involved in both Virus Assembly and Entry
Authors: Lin Su-Ru , Zou Gang , Hsieh Szu-Chia , Qing Min , Tsai Wen-Yang , Shi Pei-Yong , Wang Wei-Kung 
Published: March 2011

ABSTRACT
The envelope (E) of dengue virus (DENV) is a determinant of tropism and virulence. At the C terminus of E protein, there is a stem region containing two amphipathic α-helical domains (EH1 and EH2) and a stretch of conserved sequences in between. The crystal structure of E protein at the postfusion state suggested the involvement of the stem during the fusion; however, the critical domains or residues involved remain unknown. Site-directed mutagenesis was carried out to replace each of the stem residues at the hydrophobic face with an alanine or proline in a DENV serotype 4 (DENV4) precursor membrane (prM)/E expression construct. Most of the 15 proline mutations at either EH1 or EH2 severely affected the assembly of virus-like particles (VLPs). Radioimmunoprecipitation and membrane flotation assays revealed that EH1 mutations primarily affect prM-E heterodimerization and EH2 mutations affect the membrane binding of the stem. Introducing four proline mutations at either EH1 or EH2 into a DENV2 replicon packaging system greatly affects assembly and entry. Moreover, introducing these mutations into a DENV2 infectious clone confirmed the impairment in assembly and infectivity. Sequencing analysis of adaptive mutations in passage 5 viruses revealed a change to a leucine or wild-type residue at the original site, suggesting the importance of maintaining the helical structure. Collectively, these findings suggest that the EH1 and EH2 domains are involved in both assembly and entry steps of the DENV replication cycle; this feature, together with the high degree of sequence conservation, suggests that the stem region is a potential target of antiviral strategies.
Deletion of Major Nonessential Genomic Regions in the Vaccinia Virus Lister Strain Enhances Attenuation without Altering Vaccine Efficacy in Mice
Authors: Dimier Julie , Ferrier-Rembert Audrey , Pradeau-Aubreton Karine , Hebben Matthias , Spehner Danièle , Favier Anne-Laure , Gratier Danielle , Garin Daniel , Crance Jean-Marc , Drillien Robert 
Published: March 2011

ABSTRACT
The vaccinia virus (VACV) Lister strain was one of the vaccine strains that enabled smallpox eradication. Although the strain is most often harmless, there have been numerous incidents of mild to life-threatening accidents with this strain and others. In an attempt to further attenuate the Lister strain, we investigated the role of 5 genomic regions known to be deleted in the modified VACV Ankara (MVA) genome in virulence in immunodeficient mice, immunogenicity in immunocompetent mice, and vaccine efficacy in a cowpox virus challenge model. Lister mutants were constructed so as to delete each of the 5 regions or various combinations of these regions. All of the mutants replicated efficiently in tissue culture except region I mutants, which multiplied more poorly in human cells than the parental strain. Mutants with single deletions were not attenuated or only moderately so in athymic nude mice. Mutants with multiple deletions were more highly attenuated than those with single deletions. Deleting regions II, III, and V together resulted in total attenuation for nude mice and partial attenuation for SCID mice. In immunocompetent mice, the Lister deletion mutants induced VACV specific humoral responses equivalent to those of the parental strain but in some cases lower cell-mediated immune responses. All of the highly attenuated mutants protected mice from a severe cowpox virus challenge at low vaccine doses. The data suggest that several of the Lister mutants combining multiple deletions could be used in smallpox vaccination or as live virus vectors at doses equivalent to those used for the traditional vaccine while displaying increased safety.
Oxidative Stress Resistance inDeinococcus radiodurans
Authors: Slade Dea , Radman Miroslav 
Published: March 2011

SUMMARYDeinococcus radioduransis a robust bacterium best known for its capacity to repair massive DNA damage efficiently and accurately. It is extremely resistant to many DNA-damaging agents, including ionizing radiation and UV radiation (100 to 295 nm), desiccation, and mitomycin C, which induce oxidative damage not only to DNA but also to all cellular macromolecules via the production of reactive oxygen species. The extreme resilience ofD. radioduransto oxidative stress is imparted synergistically by an efficient protection of proteins against oxidative stress and an efficient DNA repair mechanism, enhanced by functional redundancies in both systems.D. radioduransassets for the prevention of and recovery from oxidative stress are extensively reviewed here. Radiation- and desiccation-resistant bacteria such asD. radioduranshave substantially lower protein oxidation levels than do sensitive bacteria but have similar yields of DNA double-strand breaks. These findings challenge the concept of DNA as the primary target of radiation toxicity while advancing protein damage, and the protection of proteins against oxidative damage, as a new paradigm of radiation toxicity and survival. The protection of DNA repair and other proteins against oxidative damage is imparted by enzymatic and nonenzymatic antioxidant defense systems dominated by divalent manganese complexes. Given that oxidative stress caused by the accumulation of reactive oxygen species is associated with aging and cancer, a comprehensive outlook onD. radioduransstrategies of combating oxidative stress may open new avenues for antiaging and anticancer treatments. The study of the antioxidation protection inD. radioduransis therefore of considerable potential interest for medicine and public health.
Change Is Good: Variations in Common Biological Mechanisms in the Epsilonproteobacterial GeneraCampylobacterandHelicobacter
Authors: Gilbreath Jeremy J. , Cody William L. , Merrell D. Scott , Hendrixson David R. 
Published: March 2011

SUMMARYMicrobial evolution and subsequent species diversification enable bacterial organisms to perform common biological processes by a variety of means. The epsilonproteobacteria are a diverse class of prokaryotes that thrive in diverse habitats. Many of these environmental niches are labeled as extreme, whereas other niches include various sites within human, animal, and insect hosts. Some epsilonproteobacteria, such asCampylobacter jejuniandHelicobacter pylori, are common pathogens of humans that inhabit specific regions of the gastrointestinal tract. As such, the biological processes of pathogenicCampylobacterandHelicobacterspp. are often modeled after those of common enteric pathogens such asSalmonellaspp. andEscherichia coli. While many exquisite biological mechanisms involving biochemical processes, genetic regulatory pathways, and pathogenesis of disease have been elucidated from studies ofSalmonellaspp. andE. coli, these paradigms often do not apply to the same processes in the epsilonproteobacteria. Instead, these bacteria often display extensive variation in common biological mechanisms relative to those of other prototypical bacteria. In this review, five biological processes of commonly studied model bacterial species are compared to those of the epsilonproteobacteriaC. jejuniandH. pylori. Distinct differences in the processes of flagellar biosynthesis, DNA uptake and recombination, iron homeostasis, interaction with epithelial cells, and protein glycosylation are highlighted. Collectively, these studies support a broader view of the vast repertoire of biological mechanisms employed by bacteria and suggest that future studies of the epsilonproteobacteria will continue to provide novel and interesting information regarding prokaryotic cellular biology.
Eukaryote-Like Serine/Threonine Kinases and Phosphatases in Bacteria
Authors: Pereira Sandro F. F. , Goss Lindsie , Dworkin Jonathan 
Published: March 2011

SUMMARY
Genomic studies have revealed the presence of Ser/Thr kinases and phosphatases in many bacterial species, although their physiological roles have largely been unclear. Here we review bacterial Ser/Thr kinases (eSTKs) that show homology in their catalytic domains to eukaryotic Ser/Thr kinases and their partner phosphatases (eSTPs) that are homologous to eukaryotic phosphatases. We first discuss insights into the enzymatic mechanism of eSTK activation derived from structural studies on both the ligand-binding and catalytic domains. We then turn our attention to the identified substrates of eSTKs and eSTPs for a number of species and to the implications of these findings for understanding their physiological roles in these organisms.
Pedestrian death in Morelos State, Mexico, 1998–2007
Authors: Rodriguez-Hernndez J M , Hijar-Medina M , Campuzano-Rincn J C 
Published: March 2011

AimDescribe main characteristics associated with mortality in pedestrian injuries in Morelos, Mexico between 1998 and 2007.MethodsWe made a descriptive cross-sectional study of pedestrian fatalities occurred in 33 municipalities of Morelos State, Mexico, data were collected from official death certificates available in the National Institute of Geography and Statistics (INEGI) between 1998 and 2007; variables such as sex, age, marital status, education, occupation, time and place of occurrence of the event were included in analysis. Trend analysis was obtained, specific rates by age and sex.Results703 pedestrian fatalities occurred on the period selected in Morelos, with a rate of 4.1/100 000 inhabitants. Was three times higher in men than in women; although the average age was 25 years, the rate increased with age; more than 60% of affected were single, widowed or separated, 70% had no healthcare; most of the deaths occurred in people with low education, they were unemployed, workers or peasants; the frequency of events were (34.7%) from 2:00 to 7:00 and (46%) from 7:00 to 13:00. 60% of deaths occurred in cities over 100 000 inhabitants, 58% in Cuernavaca and Cuautla, metropolitan areas.ConclusionsPedestrian fatalities rate remained constant for a 10-year period; they were concentrated in urban centres, the mortality risk increased with age and most affected were people without social security. At the time of the study were not designed public policies that had promoted road safety, to control or prevent this public health problem.
Knowledge, attitudes and practices of women pillion riders in two of the major cities of Pakistan, Karachi and Lahore
Authors: Waseem H , Shahbaz S , Khan U 
Published: March 2011

BackgroundEach year nearly 1.2 million people die and millions more are injured or disabled as a result of road traffic injuries. Wearing helmets is the single most effective way of reducing head injuries in motored two wheeled vehicles.ObjectiveThe objective of the study is to identify the knowledge, attitudes and practices of women pillion riders in the two major cities of Pakistan, Karachi and Lahore.MethodThis is a case-control study, in a selected female population. The inclusion criteria were working women and students between the ages of 18 and 45 with 10 years of education. A questionnaire was distributed focusing on awareness of helmet use and reasons why they are not used.ResultsThe results are derived from the sample size of 400. Among the many reasons for not wearing a helmet in the female Pakistani population, it emerged that while most of them were aware of the importance of helmets and their protective role, they had not thought that it was important for them as a pillion driver. Some respondents also thought they were not very fashionable and others blamed the hot and humid climate. Most of them thought that if there was a risk of being penalised they will probably wear them.ConclusionOur study is still in the process of data analysis, but it is very clear that the use of helmets especially in females is near to none.
Parents child safety behaviour on the prevention of unintentional injuries
Authors: Van Beelen M E J , Beirens T M J , Hertog P Den , Struijk M K , Van Beeck E F , Raat H 
Published: March 2011

BackgroundIn the Netherlands each year 30 children aged 0–4 years die, as result of unintentional injuries in or around the home. Additionally 57 000 children are medically treated, of which 46 000 children at the emergency room of a hospital. In order to reduce these numbers, parents' child safety behaviour is promoted. The aim of this study is to assess demographic correlates of parents' child safety behaviour.MethodsParents with a 7.5-month-old child, who were part of a sample of 30 Dutch child health clinics, urban and rural, were invited by their preventive healthcare provider to participate in the study. Parents fill in a questionnaire on either paper or through the Internet. Parents were informed that the study was about home safety and the prevention of injuries.The questionnaire contains items on pregnancy, birth, gender, ethnicity of the child and the parents, educational level of the parents, household and family composition, safety measures taken, determinants of safety behaviour on safety topics, like falling, poisoning, drowning and burning. Sum-scores for safety behaviour will be calculated.ResultsPreliminary results (n=132 parents) show that 91.7% of participants are mothers, 50.0% have at least one stair gate and 78.0% of children are exposed to unsafe storage of poisonings.ConclusionThe results of this study will provide information about parents' child safety behaviour which will be used to improve health education to parents of young children.
Can the theory of planned behaviour predict coach intentions to implement a safe landing program during netball training sessions?
Authors: White P , Ullah S , Romiti M , Finch C 
Published: March 2011

IntroductionIt is currently unknown whether the Theory of Planned Behaviour (TPB) can predict intentions to engage in sports safety behaviours and what particular TPB constructs are important in this prediction. The purpose of this study was to determine whether TPB can predict coach intentions to teach correct landing technique to junior players and what particular constructs are most important in this prediction.MethodsFifty-one coaches completed a 12-item survey to measure their attitudes, subjective norm and perceived behavioural control around the behaviour of teaching correct landing technique during junior netball training. Coaches were also asked about their intention to teach correct landing technique at netball training sessions. Factor analysis was used to identify the factors in relation to the TPB. Structural equation modelling was used to determine whether TPB could be used to predict the intention to teach correct landing technique.ResultsThe factor analysis identified that the three factors were sufficient to describe the 12 statements. These three factors were consistent with the attitudes, subjective norm and perceived behavioural control dimensions of the TPB, explaining 21%, 19% and 14% of the total variability respectively. Structural equation modelling revealed that none of the TPB factors were significant predictors to explain the intention of teaching correct landing technique.ConclusionsAlthough the three factors attitudes, subjective norm and perceived behavioural control were sufficient for describing the data, TPB may not be an appropriate theory to apply to the prediction of sports safety behaviour.
On-line survey with story sharing on risky behaviour for home safety
Authors: Cui M Y , Wang L 
Published: March 2011

ProblemIn China, injury is the leading killer of children aged under 14; around 43% child injury occurs at home (1 survey of childhood unintentional injury patterns and parental awareness in three cities in China (Beijing, Guangzhou and Shanghai 2004, Safe Kids Worldwide-China and National Center Chronic and Non-communicable Disease Control and Prevention, China CDC)).Objectives(1) To understand home injury among children through moms stories. (2) To educate moms about home safety by sharing real stories related to injuries photos among moms.Method(1) On-line collection of household child injuries by moms telling stories and how she could change her behaviour to avoid such injuries. (2) Analyse the risky behaviours in each story. (3) Share moms stories through Internet to educate more parents.Results(1) 5000 stories were collected with how the child was injuries and what mom could do to avoid such injuries later. (2) 2280 stories from 14 cities were quality enough for behaviour analysis. (3) The top four household injuries are falls (25%); burns including electric shocks (16.7%); cuts (9.1%) and poison (2.6%). (4) No-household injuries: injuries related to traffic is 71%; drowning is 5%.Conclusion(1) The survey got the quality data on household injuries as moms are giving the real stories. (2) On-line story sharing made the survey as a kind of education intervention, too as moms also tell how they should do in further to avoid such injuries. (3) The survey made a great use of limited resources through on-line platform and combining survey and education intervention together.