bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of Type I Interferon Secretion through Recombinant Newcastle Disease Virus Expressing Measles Virus Hemagglutinin Stimulates Antibody Secretion in the Presence of Maternal Antibodies
Authors: Kim Dhohyung , Martinez-Sobrido Luis , Choi Changsun , Petroff Natasha , García-Sastre Adolfo , Niewiesk Stefan , Carsillo Thomas 
Published: October 2010

ABSTRACTMeasles virus (MV) vaccine effectively protects seronegative individuals against infection. However, inhibition of vaccine-induced seroconversion by maternal antibodies after vaccination remains a problem, as it leaves infants susceptible to MV infection. In cotton rats, passive transfer of MV-specific IgG mimics maternal antibodies and inhibits vaccine-induced seroconversion. Here, we report that immunization in the presence of passively transferred IgG inhibits the secretion of neutralizing antibodies but not the generation of MV-specific B cells. This finding suggested that MV-specific B cells require an additional stimulus to mature into antibody-secreting plasma cells. In order to provide such a stimulus, we generated a recombinant Newcastle disease virus (NDV) expressing the MV hemagglutinin (NDV-H). In contrast to MV, NDV-H induced high levels of type I interferon in plasmacytoid dendritic cells and in lung tissue. In cotton rats immunized with NDV-H, neutralizing antibodies were also generated in the presence of passively transferred antibodies. In the latter case, however, the level and kinetics of antibody generation were reduced.In vitro, alpha interferon stimulated the activation of MV-specific B cells from MV-immune spleen cells. NDV infection (which induces alpha interferon) had the same effect, and stimulation could be abrogated by antibodies neutralizing alpha interferon, but not interleukin 6 (IL-6).In vivo, coapplication of UV-inactivated MV with NDV led to increased MV-specific antibody production in the presence and absence of passively transferred antibodies. These data indicate that MV-specific B cells are being generated after immunization in the presence of maternal antibodies and that the provision of alpha interferon as an additional signal leads to antibody secretion.
Poliovirus-Mediated Disruption of Cytoplasmic Processing Bodies
Authors: Dougherty Jonathan D. , White James P. , Lloyd Richard E. 
Published: October 2010

ABSTRACTMetazoan cells form cytoplasmic mRNA granules such as stress granules (SG) and processing bodies (P bodies) that are proposed to be sites of aggregated, translationally silenced mRNAs and mRNA degradation. Poliovirus (PV) is a plus-strand RNA virus containing a genome that is a functional mRNA; thus, we investigated if PV antagonizes the processes that lead to formation of these structures. We have previously shown that PV infection inhibits the ability of cells to form stress granules by cleaving RasGAP-SH3-binding protein (G3BP). Here, we show that P bodies are also disrupted during PV infection in cells by 4 h postinfection. The disruption of P bodies is more rapid and more complete than disruption of stress granules. The kinetics of P body disruption correlated with production of viral proteinases and required substantial viral gene product expression. The organizing mechanism that forms P body foci in cells is unknown; however, potential scaffolding, aggregating, or other regulatory proteins found in P bodies were investigated for degradation. Two factors involved in 5′-end mRNA decapping and degradation, Xrn1 and Dcp1a, and the 3′ deadenylase complex component Pan3 underwent accelerated degradation during infection, and Dcp1a may be a direct substrate of PV 3C proteinase. Several other key factors proposed to be essential for P body formation, GW182, Edc3, and Edc4, were unaffected by poliovirus infection. Since deadenylation has been reported to be required for P body formation, viral inhibition of deadenylation, through Pan3 degradation, is a potential mechanism of P body disruption.
Identification and Structural Characterization of the ALIX-Binding Late Domains of Simian Immunodeficiency Virus SIV
mac239
and SIV
agmTan-1
Authors: Zhai Qianting , Landesman Michael B. , Robinson Howard , Sundquist Wesley I. , Hill Christopher P. 
Published: October 2010

ABSTRACT

Retroviral Gag proteins contain short late-domain motifs that recruit cellular ESCRT pathway proteins to facilitate virus budding. ALIX-binding late domains often contain the core consensus sequence YPX
n
L (where X
n
can vary in sequence and length). However, some simian immunodeficiency virus (SIV) Gag proteins lack this consensus sequence, yet still bind ALIX. We mapped divergent, ALIX-binding late domains within the p6
Gag
proteins of SIV
mac239
(
40
SREK
P
YKE
VT
ED
L
LHLNSLF
59
) and SIV
agmTan-1
(
24
AAG
A
YDP
AR
KL
L
EQYAKK
41
). Crystal structures revealed that anchoring tyrosines (in lightface) and nearby hydrophobic residues (underlined) contact the ALIX V domain, revealing how lentiviruses employ a diverse family of late-domain sequences to bind ALIX and promote virus budding.
Variola and Monkeypox Viruses Utilize Conserved Mechanisms of Virion Motility and Release That Depend on Abl and Src Family Tyrosine Kinases
Authors: Reeves Patrick M. , Smith Scott K. , Olson Victoria A. , Thorne Steve H. , Bornmann William , Damon Inger K. , Kalman Daniel 
Published: October 2010

ABSTRACT

Vaccinia virus (VacV) enters mammalian cells, replicates extranuclearly, and produces virions that move to the cell surface along microtubules, fuse with the plasma membrane, and move from infected cells toward apposing cells on actin-filled membranous protrusions or actin tails. To form actin tails, cell-associated enveloped virions (CEV) require Abl and Src family tyrosine kinases. Furthermore, release of CEV from the cell requires Abl but not Src family tyrosine kinases and is blocked by imatinib mesylate (STI-571; Gleevec), an Abl family kinase inhibitor used to treat chronic myelogenous leukemia in humans. Here we demonstrate that the
Poxviridae
family members monkeypox virus (MPX) and variola virus (VarV) use conserved mechanisms for actin motility and extracellular enveloped virion (EEV) release. Furthermore, we show that imatinib mesylate is effective in a mouse model of infection with VacV, whether delivered prophylactically or postinfection, and restricts spread of virions from the site of inoculation. While inhibitors of both Src and Abl family kinases, such as dasatinib (BMS-354825; Sprycel), are effective in limiting dissemination of VacV, VarV, and MPX
in vitro
, members of this class of drugs appear to have immunosuppressive effects
in vivo
that preclude their use as anti-infectives. Together, these data suggest a possible utility for imatinib mesylate in treating smallpox or MPX infections or complications associated with vaccination.
Referrals from a primary care-based sports medicine department to an orthopaedic department: a retrospective cohort study
Authors: Menzies Robert D , Young Richard A 
Published: October 2010

ObjectiveTo describe the impact of an expanded primary care-based sports medicine clinic on referrals to an orthopaedics clinic and to describe the patients seen and procedures performed.DesignRetrospective cohort study.SettingPrimary care-based sports medicine clinic and orthopaedics clinic at a tax-supported American safety net healthcare system.ParticipantsAll patients referred to the sports medicine clinic by other primary care physicians over a 1-year time period of July 2006–June 2007.Main outcome measuresThe referral rate from sports medicine clinic to orthopaedics clinic, the percentage of referred patients who were recommended surgery by the orthopaedists, the change in average waiting time to be seen in orthopaedics clinic and the most common conditions and procedures.Results4925 patients were seen by the sports medicine department; 118 (2.4%) of those patients were referred to the orthopaedic department. Of the referred patients, surgery was offered by orthopaedists to 80 (68%) patients. The average wait for initial consultation by the orthopaedic spine clinic decreased from 199 to 70 days; the wait for general orthopaedic clinic decreased from 97 to 19 days. No single patient complaint or musculoskeletal pathology predominated: knee degenerative joint disease (25.3%), mechanical low back pain (21.6%) and lumbar disc disease (19.9%). Knee injections and epidural steroid injections were the most common procedures performed.ConclusionsVery few patients with musculoskeletal pathology were referred by a primary care-based sports medicine clinic to an orthopaedics clinic. Of the referred patients, sports medicine physicians and orthopaedists frequently agreed on the need for surgery. Expansion of a primary care-based sports medicine service could help relieve overburdened orthopaedics departments of patients with conditions not requiring surgery.
Clustered metabolic risk and leisure-time physical activity in adolescents: effect of dose?
Authors: Pahkala Katja , Heinonen Olli J , Lagström Hanna , Hakala Paula , Hakanen Maarit , Hernelahti Miika , Ruottinen Soile , Sillanmäki Lauri , Rönnemaa Tapani , Viikari Jorma , Raitakari Olli T , Simell Olli 
Published: October 2010

ObjectivesThe authors studied the association of leisure-time physical activity (LTPA) with clustered and individual metabolic risk factors in adolescents taking into account diet and pubertal status. The authors also studied whether screen time was associated with clustered risk.MethodsSelf-reported LTPA and screen time, lipids, lipoproteins, apolipoproteins, high-sensitivity C reactive protein, blood pressure, body mass index (BMI), pubertal status and diet were assessed in 13-year-old adolescents (n=542) participating in an atherosclerosis prevention study (Special Turku Coronary Risk Factor Intervention Project for Children). Activity groups were formed according to sex-specific LTPA index tertile cut-off points. BMI, high-density lipoprotein cholesterol (HDL-C), triglycerides and blood pressure comprised the cluster.ResultsAn increase in LTPA was associated with a decreased risk for clustered metabolic risk in girls. When sedentary and highly active adolescents were compared, an increase in LTPA decreased clustering of risk factors in boys as well. Little extra benefit on clustered risk was obtained by increasing LTPA from 30 MET h/week (eg, 4–5 h/week bicycling or playing soccer) to 50 MET h/week (eg, 7–8 h/week bicycling or playing soccer). LTPA was beneficially associated with BMI, HDL-C, systolic blood pressure and HDL-C/total cholesterol in girls and HDL-C in boys. Diet and pubertal status were similar in all activity groups. In girls, screen time >2 h/day was associated with an increased risk for clustered risk, independent of LTPA.ConclusionSedentary adolescents had an increased risk for clustered metabolic risk compared with physically more active peers. Only minor extra benefit was obtained when LTPA increased over 30 MET h/week. Focus in the prevention of clustered risk should especially be on avoiding sedentary lifestyle.
The epidemiology of injuries in English youth community rugby union
Authors: Haseler Christine M , Carmont Michael R , England Michael 
Published: October 2010

IntroductionRecent studies report the incidence and epidemiology of injury in professional rugby union; however, there is limited research in amateur and youth rugby. Injuries in youth rugby may have consequences for sports participation and physical development. The authors performed a prospective cohort study of injuries during youth community rugby.MethodsAn injury surveillance programme was established for the 2008–2009 season (9 months, 1636 player-hours) of an English community rugby club. The study included 210 players, all males, in Under 9 to Under 17 (U9–U17) age groups. These were categorised into mini, junior, pubertal and school participation age groupings. Injuries were defined according to the International Rugby Board consensus statements.ResultsThere were 39 injuries reported (overall injury rate 24/1000 player-hours). Injury rates ranged from 0 to 49.3/1000 player-hours. More injuries occurred in junior (34.2/1000 player-hours) than in minis (11.9/1000 player-hours) (p<0.025). Higher numbers of moderate (20.6/1000 player-hours, p<0.005) and severe (9.5/1000 player-hours, p<0.05) injuries occurred in the U16–U17 age groups compared with younger age groups (U9–U10) where only minor injuries were reported. Most injuries occurred in the tackle (59%). The knee (4.9/1000 player-hours), shoulder (4.9/1000 player-hours) and head (4.3/1000 player-hours) were the most commonly affected areas. Concussion (1.8/1000 player-hours) affected half of the head injuries.ConclusionsInjuries in youth rugby occur infrequently and are lower than in adult series. The risk of injury and severity of injury increases with age. This study highlights the need for further research into injury risk factors around puberty and the need for first aid provision.
Injury risk of playing football in Futsal World Cups
Authors: Junge Astrid , Dvorak Jiri 
Published: October 2010

BackgroundWhile injuries in football (soccer) have been the subject of numerous publications, little information is available about the injury risk in futsal.ObjectiveAnalysis of the incidence and characteristics of injury in futsal players during top-level international tournaments.DesignProspective survey.MethodsPlayer injuries during three consecutive Futsal World Cups were analysed using an established injury report system. The physicians of all participating teams reported all injuries after each match on a standardised injury report form. The average response rate was 93%.ResultsA total of 165 injuries were reported from 127 matches, which is equivalent to an incidence of 195.6 injuries per 1000 player hours (95% CI 165.8 to 225.6) or 130.4 injuries per 1000 player matches (95% CI 110.5 to 150.3). The majority of injuries were caused by contact with another player, and 36% of the injuries occurred during non-contact activities. Most injuries affected the lower extremity (70%), followed by head and neck (13%), upper extremity (10%) and trunk (7%). The most frequent diagnoses were contusion of the lower leg (11%), ankle sprain (10%) and groin strain (8%). On average, one time-loss injury in every two matches was reported.ConclusionWhile the location and diagnosis of injuries were similar in the two types of football, fewer injuries in futsal than in football were caused by contact with another player and by foul play. More information on injury mechanisms in futsal is needed to develop specific injury preventive interventions.
Clinicopathological evaluation of 100 cases of mucinous carcinoma of breast with emphasis on axillary staging and special reference to a micropapillary pattern
Authors: Ranade Aditi , Batra Rashmi , Sandhu Gagangeet , Chitale Rohit A , Balderacchi Jasminka 
Published: October 2010

BackgroundPure mucinous breast carcinoma (PMBC) is uncommon and associated with better prognosis than mixed mucinous breast carcinoma (MMBC). A micropapillary pattern in PMBC has been identified although its prognostic significance is questionable.MethodsA retrospective review of 100 cases of mucinous carcinoma diagnosed between 2000 and 2009 was conducted. Two broad categories were studied: PMBC (more than 90% mucinous component; n=45) and MMBC (less than 90% mucinous component; n=55). PMBC was further subclassified as hypocellular/type A (n=37) and cellular/type B (n=8). Receptor status, clinicomorphological and prognostic features were compared without patient follow-up.ResultsMean age at diagnosis in PMBC and MMBC was 60 and 63 years, while mean tumour size was 1.65 and 2.5 cm, respectively. Mean age in type A and type B PMBC patients was 75 and 55 years, respectively. The majority of PMBCs were well differentiated, with two poorly differentiated cases as well. The majority of MMBCs were moderately differentiated. A micropapillary pattern was seen in 20% of PMBCs. Sentinel lymph nodes were positive in 18.5% of PMBCs and 16% of MMBCs. Non-sentinel lymph nodes were positive in 14% of PMBCs and 39% of MMBCs. A micropapillary pattern was seen in 60% of LN positive PMBCs and 14% of LN negative PMBCs. Furthermore, 95% of PMBCs were ER(+), 84% were PR(+) and 9% were Her-2(+); 91% of MMBCs were ER(+), 87% were PR(+) and 33% were Her-2(+).ConclusionsPMBCs with a micropapillary pattern were more frequently associated with nodal disease. PMBCs with axillary disease had one or more of the following: micropapillary pattern, high nuclear grade, Her-2 positivity, smaller tumour size or younger age. Hence, axillary staging by sentinel lymph node biopsy is recommended in PMBCs.
Mortality related to temperature and persistent extreme temperatures: a study of cause-specific and age-stratified mortality
Authors: Rocklöv Joacim , Ebi Kristie , Forsberg Bertil 
Published: October 2010

ObjectivesHigh and low ambient temperatures are associated with large numbers of deaths annually. Many studies show higher mortalities during heatwaves. However, such effects are rarely explicitly incorporated in models of temperature and mortality, although dehydration followed by cardiovascular stress is more likely to occur. The authors aim to establish time-series models in which the effects of persistent extreme temperature and temperature in general can be disentangled.MethodsThe authors established time-series Poisson regression models based on cause-specific mortality and age-stratified mortality in Stockholm County (Sweden), 1990–2002, adjusting for time trends and potential confounders, and studied the effects of temperature and persistence of extreme temperature.ResultsPersistent extremely high temperature was associated with additional deaths, and the risk of death increased significantly per day of extended heat exposure. Extreme exposure to heat was associated with higher death rates in adults and for cardiovascular causes of death, compared with a rise in temperature. Warmer temperatures increase daily mortality from natural causes, while decreasing colder temperatures increase the risk of cardiovascular deaths. Furthermore, the impact of warm and cold temperatures decreases within the season, while the impact of persistent extremely high temperatures remains similar throughout the summer.ConclusionsThe authors found the mortality impact of persistence of extreme high temperatures to increase proportionally to the length of the heat episode in addition to the effects of temperature based on the temperature–mortality relationship. Thus, the additional effect of persistent extreme heat was found to be important to incorporate for models of mortality related to ambient temperatures to avoid negatively biased attributed risks, especially for cardiovascular mortality. Moreover, the effects associated with non-extreme temperatures may decline as the pool of fragile individuals shrink as well as due to acclimatisation/adaptation. However, a similar decline was not observed for the effects associated with extreme heat episodes.
Combinatorial Regulation of Neuroblastoma Tumor Progression by N-Myc and Hypoxia Inducible Factor HIF-1α
Authors: Qing Guoliang , Skuli Nicolas , Mayes Patrick A. , Pawel Bruce , Martinez Daniel , Maris John M. , Simon M. Celeste 
Published: October 2010

Abstract
In human neuroblastoma, amplification of the MYCN gene predicts poor prognosis and resistance to therapy. Because hypoxia contributes to aggressive tumor phenotypes, predominantly via two structurally related hypoxia inducible factors, HIF-1α and HIF-2α, we examined hypoxia responses in MYCN-amplified neuroblastoma cells. We demonstrate here that HIF-1α, but not HIF-2α, is preferentially expressed in both MYCN-amplified neuroblastoma cells and primary tumors in comparison to samples without MYCN amplification. Our results showed that interplay between N-Myc and HIF-1α plays critical roles in neuroblastoma. For example, high levels of N-Myc override HIF-1α inhibition of cell cycle progression, enabling continued proliferation under hypoxia. Furthermore, both HIF-1α and N-Myc are essential for the Warburg effect (aerobic glycolysis) in neuroblastomas by activating the transcription of multiple glycolytic genes. Of note, expressions of Phosphoglycerate Kinase 1 (PGK1), Hexokinase 2 (HK2), and Lactate Dehydrogenase A (LDHA) were each significantly higher in MYCN-amplified neuroblastomas than in tumors without MYCN amplification. Interestingly, MYCN-amplified neuroblastoma cells are “addicted” to LDHA enzymatic activity, as its depletion completely inhibits tumorigenesis in vivo. Thus, our results provide mechanistic insights explaining how MYCN-amplified neuroblastoma cells contend with hypoxic stress and paradoxically how hypoxia contributes to neuroblastoma aggressiveness through combinatorial effects of N-Myc and HIF-1α. These results also suggest that LDHA represents a novel, pharmacologically tractable target for neuroblastoma therapeutics. Cancer Res; 70(24); 10351–61. ©2010 AACR.
Hypoxia and Hypoxia-Inducible Factors: Master Regulators of Metastasis
Authors: Lu Xin , Kang Yibin 
Published: October 2010

Abstract
Hypoxia is a common condition found in a wide range of solid tumors and is often associated with poor prognosis. Hypoxia increases tumor glycolysis, angiogenesis, and other survival responses, as well as invasion and metastasis by activating relevant gene expressions through hypoxia-inducible factors (HIF). HIF-1α and HIF-2α undergo oxygen-dependent regulation, and their overexpression is frequently associated with metastasis and poor clinical outcomes. Recent studies show that each step of the metastasis process, from the initial epithelial-mesenchymal transition to the ultimate organotropic colonization, can potentially be regulated by hypoxia, suggesting a master regulator role of hypoxia and HIFs in metastasis. Furthermore, modulation of cancer stem cell self-renewal by HIFs may also contribute to the hypoxia-regulated metastasis program. The hypoxia-induced metastatic phenotype may be one of the reasons for the modest efficacy of antiangiogenic therapies and may well explain the recent provocative findings that antiangiogenic therapy increased metastasis in preclinical models. Multiple approaches to targeting hypoxia and HIFs, including HIF inhibitors, hypoxia-activated bioreductive prodrugs, and gene therapies may become effective treatments to prevent or reduce metastasis. Clin Cancer Res; 16(24); 5928–35 ©2010 AACR.
From 'Sovereignty as Responsibility' to the 'Responsibility to Protect'
Authors: Deng Francis 
Published: October 2010

AbstractThis essay examines the origins and evolution of the concepts of 'sovereignty as responsibility' and the 'responsibility to protect'. In particular, it considers the role and duty of states and how ideas of sovereignty have evolved since the modern nation-state was conceived by the European Treaty of Westphalia of 1648. It then examines the responsibility of states towards their own citizens and traces the development of the R2P norm in Africa as it has related to conflict prevention, management, and resolution since the end of the Cold War. The essay further considers the responsibilities of national democratic governments in Africa and beyond. Recent developments that have widened the scope and helped the acceptance and application of the concept of 'sovereignty as responsibility' are discussed, and the essay concludes with an examination of the accountability and enforcement challenges faced by R2P.