bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of the HIV-1 Spike by Single-PG9/16-Antibody Binding Suggests a Coordinated-Activation Model for Its Three Protomeric Units
Authors: Löving Robin , Sjöberg Mathilda , Wu Shang-Rung , Binley James M. , Garoff Henrik 
Published: April 2013

ABSTRACT
The HIV-1 spike is composed of three protomeric units, each containing a peripheral gp120 and a transmembrane gp41 subunit. Binding to the CD4 and the chemokine receptors triggers them to mediate virus entry into cells by membrane fusion. The spikes also represent the major target for neutralizing antibodies (Abs) against the virus. We have studied how two related broadly neutralizing Abs, PG9 and PG16, react with the spike. Unexpectedly, this also suggested how the functions of the individual protomers in the spike depend on each other. The Abs have been shown to bind the V1/V2 loops of gp120, located at the top of the spike. Using blue native-polyacrylamide gel electrophoresis (BN-PAGE), we show that only single Abs or antigen-binding fragments could bind to the spikes of HIV-1 virus-like particles. Apparently, binding to one gp120 sterically interferes with binding to the other two subunits in the spike top. Despite this constraint, all of the protomers of the spike became resistant to CD4 binding and subsequent formation of the coreceptor binding site. These activities were measured by monitoring the sequential complex formation of the spike first with Abs and then with soluble 2d- or 4d-CD4 or with soluble CD4 and the CD4 inducible coreceptor binding site Ab 17b in BN-PAGE. The inhibition of the spike by single-Ab binding suggested that the activation reactions of the individual protomeric units are linked to each other in a coordinated activation process.
Simultaneous Neutralization and Innate Immune Detection of a Replicating Virus by TRIM21
Authors: Watkinson R. E. , Tam J. C. H. , Vaysburd M. J. , James L. C. 
Published: April 2013

ABSTRACT

Tripartite motif-containing 21 (TRIM21) is a cytosolic immunoglobulin receptor that mediates antibody-dependent intracellular neutralization (ADIN). Here we show that TRIM21 potently inhibits the spreading infection of a replicating cytopathic virus and activates innate immunity. We used a quantitative PCR (qPCR)-based assay to measure
in vitro
replication of mouse adenovirus type 1 (MAV-1), a virus that causes dose-dependent hemorrhagic encephalitis in mice. Using this assay, we show that genetic ablation of TRIM21 or chemical inhibition of either the AAA ATPase p97/valosin-containing protein (VCP) or the proteasome results in a >1,000-fold increase in the relative level of infection in the presence of immune serum. Moreover, the TRIM21-mediated ability of antisera to block replication was a consistent feature of the humoral immune response in immunized mice. In the presence of immune sera and upon infection, TRIM21 also activates a proinflammatory response, resulting in secretion of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). These results demonstrate that TRIM21 provides a potent block to spreading infection and induces an antiviral state.
Differing Effects of Herpes Simplex Virus 1 and Pseudorabies Virus Infections on Centrosomal Function
Authors: Pasdeloup David , Labetoulle Marc , Rixon Frazer J. 
Published: April 2013

ABSTRACT
Efficient intracellular transport of the capsid of alphaherpesviruses, such as herpes simplex virus 1 (HSV-1), is known to be dependent upon the microtubule (MT) network. Typically, the MT network radiates from an MT-organizing center (MTOC), which is, in most cases, the centrosome. During herpesvirus egress, it has been assumed that capsids travel first from the nucleus to the centrosome and then from the centrosome to the site of envelopment. Here we report that the centrosome is no longer a primary MTOC in HSV-1-infected cells, but it retains this function in cells infected by another alphaherpesvirus, pseudorabies virus (PrV). As a result, MTs formed at late times after infection with PrV grow from a major, centralized MTOC, while those formed after HSV-1 infection arise from dispersed locations in the cytoplasm, indicating the presence of alternative and minor MTOCs. Thus, loss of the principal MT nucleating center in cells following HSV-1 infection raises questions about the mechanism of HSV-1 capsid egress. It is possible that, rather than passing via the centrosome, capsids may travel directly to the site of envelopment after exiting the nucleus. We suggest that, in HSV-1-infected cells, the disruption of centrosomal functions triggers reorganization of the MT network to favor noncentrosomal MTs and promote efficient viral spread.
Interleukin-22 Reduces Lung Inflammation during Influenza A Virus Infection and Protects against Secondary Bacterial Infection
Authors: Ivanov Stoyan , Renneson Joelle , Fontaine Josette , Barthelemy Adeline , Paget Christophe , Fernandez Elodie Macho , Blanc Fany , De Trez Carl , Van Maele Laurye , Dumoutier Laure , Huerre Michel-René , Eberl Gérard , Si-Tahar Mustapha , Gosset Pierre , Renauld Jean Christophe , Sirard Jean Claude , Faveeuw Christelle , Trottein François 
Published: April 2013

ABSTRACT

Interleukin-22 (IL-22) has redundant, protective, or pathogenic functions during autoimmune, inflammatory, and infectious diseases. Here, we addressed the potential role of IL-22 in host defense and pathogenesis during lethal and sublethal respiratory H3N2 influenza A virus (IAV) infection. We show that IL-22, as well as factors associated with its production, are expressed in the lung tissue during the early phases of IAV infection. Our data indicate that retinoic acid receptor-related orphan receptor-γt (RORγt)-positive αβ and γδ T cells, as well as innate lymphoid cells, expressed enhanced
Il22
transcripts as early as 2 days postinfection. During lethal or sublethal IAV infections, endogenous IL-22 played no role in the control of IAV replication and in the development of the IAV-specific CD8
+
T cell response. During lethal infection, where wild-type (WT) mice succumbed to severe pneumonia, the lack of IL-22 did not accelerate or delay IAV-associated pathogenesis and animal death. In stark contrast, during sublethal IAV infection, IL-22-deficient animals had enhanced lung injuries and showed a lower airway epithelial integrity relative to WT littermates. Of importance, the protective effect of endogenous IL-22 in pulmonary damages was associated with a more controlled secondary bacterial infection. Indeed, after challenge with
Streptococcus pneumoniae
, IAV-experienced
Il22
−/−
animals were more susceptible than WT controls in terms of survival rate and bacterial burden in the lungs. Together, IL-22 plays no major role during lethal influenza but is beneficial during sublethal H3N2 IAV infection, where it limits lung inflammation and subsequent bacterial superinfections.
Attenuated and Replication-Competent Vaccinia Virus Strains M65 and M101 with Distinct Biology and Immunogenicity as Potential Vaccine Candidates against Pathogens
Authors: Sánchez-Sampedro Lucas , Gómez Carmen Elena , Mejías-Pérez Ernesto , Pérez-Jiménez Eva , Oliveros Juan Carlos , Esteban Mariano 
Published: April 2013

ABSTRACT

Replication-competent poxvirus vectors with an attenuation phenotype and with a high immunogenic capacity of the foreign expressed antigen are being pursued as novel vaccine vectors against different pathogens. In this investigation, we have examined the replication and immunogenic characteristics of two vaccinia virus (VACV) mutants, M65 and M101. These mutants were generated after 65 and 101 serial passages of persistently infected Friend erythroleukemia (FEL) cells. In cultured cells of different origins, the mutants are replication competent and have growth kinetics similar to or slightly reduced in comparison with those of the parental Western Reserve (WR) virus strain. In normal and immune-suppressed infected mice, the mutants showed different levels of attenuation and pathogenicity in comparison with WR and modified vaccinia Ankara (MVA) strains. Wide genome analysis after deep sequencing revealed selected genomic deletions and mutations in a number of viral open reading frames (ORFs). Mice immunized in a DNA prime/mutant boost regimen with viral vectors expressing the LACK (
Leishmania
homologue for receptors of activated C kinase) antigen of
Leishmania infantum
showed protection or a delay in the onset of cutaneous leishmaniasis. Protection was similar to that triggered by MVA-LACK. In immunized mice, both polyfunctional CD4
+
and CD8
+
T cells with an effector memory phenotype were activated by the two mutants, but the DNA-LACK/M65-LACK protocol preferentially induced CD4
+
whereas DNA-LACK/M101-LACK preferentially induced CD8
+
T cell responses. Altogether, our findings showed the adaptive changes of the WR genome during long-term virus-host cell interaction and how the replication competency of M65 and M101 mutants confers distinct biological properties and immunogenicity in mice compared to those of the MVA strain. These mutants could have applicability for understanding VACV biology and as potential vaccine vectors against pathogens and tumors.
HIV-1 Envelope Glycoprotein Trimers Display Open Quaternary Conformation When Bound to the gp41 Membrane-Proximal External-Region-Directed Broadly Neutralizing Antibody Z13e1
Authors: Harris Audray K. , Bartesaghi Alberto , Milne Jacqueline L. S. , Subramaniam Sriram 
Published: April 2013

ABSTRACT
We describe cryo-electron microscopic studies of the interaction between the ectodomain of the trimeric HIV-1 envelope glycoprotein (Env) and Z13e1, a broadly neutralizing antibody that targets the membrane-proximal external region (MPER) of the gp41 subunit. We show that Z13e1-bound Env displays an open quaternary conformation similar to the CD4-bound conformation. Our results support the idea that MPER-directed antibodies, such as Z13e1, block viral entry by interacting with Env at a step after CD4 activation.
Intraduct papillary mucinous neoplasm of the pancreas: a tumour linked with IgG4-related disease?
Authors: Bateman Adrian C , Culver Emma L , Sommerlad Matthew , Chetty Runjan 
Published: April 2013

ObjectivesIntraduct papillary mucinous neoplasm (IPMN) is a pancreatic tumour that is often associated with chronic pancreatitis (CP) in the surrounding pancreas. Type 1 autoimmune pancreatitis (AIP) is a fibro-inflammatory condition with characteristic histological features and prominent IgG4+ plasma cells and is part of the spectrum of IgG4-related disease (IgG4-RD). The aim of this study was to determine whether CP associated with pancreatic IPMN commonly represents AIP.MethodsWe identified two consecutive ‘index’ cases of pancreatic IPMN during routine reporting in which the adjacent pancreas showed morphological features suggestive of AIP. These cases were investigated using the Boston criteria for the histopathological diagnosis of IgG4-RD and the HISORt criteria for the clinical and histopathological diagnosis of AIP. Using the same criteria, we proceeded to a clinical review of 12 extra cases of IPMN in which the tumour or the surrounding pancreas showed significant lymphoplasmacytic inflammation and/or fibrosis.ResultsBoth of the ‘index’ cases fulfilled the HISORt criteria for AIP and both had morphological features characteristic of IgG4-RD using the Boston criteria, although only one possessed features ‘highly suggestive of IgG4-RD’ after immunohistochemistry. Additionally, both ‘index’ cases had radiological features that could represent extrapancreatic manifestations. Review of the 12 additional cases of IPMN revealed no further examples showing co-existent AIP.ConclusionWhile pancreatic IPMN and AIP may co-exist, most CP associated with IPMN does not represent AIP.
Endocarditis in Adults With Bacterial Meningitis
Authors: Lucas Marjolein J. , Brouwer Matthijs C. , van der Ende Arie , van de Beek Diederik 
Published: April 2013

Background—
Endocarditis may precede or complicate bacterial meningitis, but the incidence and impact of endocarditis in bacterial meningitis are unknown.

Methods and Results—

We assessed the incidence and clinical characteristics of patients with meningitis and endocarditis from a nationwide cohort study of adults with community-acquired bacterial meningitis in the Netherlands from 2006 to 2012. Endocarditis was identified in 24 of 1025 episodes (2%) of bacterial meningitis. Cultures yielded
Streptococcus pneumoniae
in 13 patients,
Staphylococcus aureus
in 8 patients, and
Streptococcus agalactiae
,
Streptococcus pyogenes
, and
Streptococcus salivarius
in 1 patient each. Clues leading to the diagnosis of endocarditis were cardiac murmurs, persistent or recurrent fever, a history of heart valve disease, and
S aureus
as the causative pathogen of bacterial meningitis. Treatment consisted of prolonged antibiotic therapy in all patients and surgical valve replacement in 10 patients (42%). Two patients were treated with oral anticoagulants, and both developed life-threatening intracerebral hemorrhage. Systemic (70%) and neurological (54%) complications occurred frequently, leading to a high proportion of patients with unfavorable outcome (63%). Seven of 24 patients (29%) with meningitis and endocarditis died.

Conclusions—
Endocarditis is an uncommon coexisting condition in bacterial meningitis but is associated with a high rate of unfavorable outcome.
Income inequality and schizophrenia: Increased schizophrenia incidence in countries with high levels of income inequality
Authors: Burns Jonathan K , Tomita Andrew , Kapadia Amy S 
Published: April 2013

Background: Income inequality is associated with numerous negative health outcomes. There is evidence that ecological-level socio-environmental factors may increase risk for schizophrenia. Aims: The aim was to investigate whether measures of income inequality are associated with incidence of schizophrenia at the country level. Method: We conducted a systematic review of incidence rates for schizophrenia, reported between 1975 and 2011. For each country, national measures of income inequality (Gini coefficient) along with covariate risk factors for schizophrenia were obtained. Multi-level mixed-effects Poisson regression was performed to investigate the relationship between Gini coefficients and incidence rates of schizophrenia controlling for covariates. Results: One hundred and seven incidence rates (from 26 countries) were included. Mean incidence of schizophrenia was 18.50 per 100,000 (SD = 11.9; range = 1.7–67). There was a significant positive relationship between incidence rate of schizophrenia and Gini coefficient ( β = 1.02; Z = 2.28; p = .02; 95% CI = 1.00, 1.03). Conclusions: Countries characterized by a large rich–poor gap may be at increased risk of schizophrenia. We suggest that income inequality impacts negatively on social cohesion, eroding social capital, and that chronic stress associated with living in highly disparate societies places individuals at risk of schizophrenia.
Approximation of linear mappings in Banach modules over "Equation missing"-algebras
Authors: Park Choonkil , Cho Yeol Je , Saadati Reza 
Published: April 2013

AbstractLetX,Ybe Banach modules over aC∗-algebra and letr1,…,rn∈Rbe given. Using fixed-point methods, we prove the stability of the following functional equation in Banach modules over a unitalC∗-algebra:∑j=1nf(12∑1≤i≤n,i≠jrixi−12rjxj)+∑i=1nrif(xi)=nf(12∑i=1nrixi).As an application, we investigate homomorphisms in unitalC∗-algebras.MSC:39B72, 46L05, 47H10, 46B03, 47B48.
Dynamic recruitment of microRNAs to their mRNA targets in the regenerating liver
Authors: Schug Jonathan , McKenna Lindsay B , Walton Gabriel , Hand Nicholas , Mukherjee Sarmistha , Essuman Kow , Shi Zhongjie , Gao Yan , Markley Karen , Nakagawa Momo , Kameswaran Vasumathi , Vourekas Anastassios , Friedman Joshua R , Kaestner Klaus H , Greenbaum Linda E 
Published: April 2013

Abstract

Background
Validation of physiologic miRNA targets has been met with significant challenges. We employed HITS-CLIP to identify which miRNAs participate in liver regeneration, and to identify their target mRNAs.

Results
miRNA recruitment to the RISC is highly dynamic, changing more than five-fold for several miRNAs. miRNA recruitment to the RISC did not correlate with changes in overall miRNA expression for these dynamically recruited miRNAs, emphasizing the necessity to determine miRNA recruitment to the RISC in order to fully assess the impact of miRNA regulation. We incorporated RNA-seq quantification of total mRNA to identify expression-weighted Ago footprints, and developed a microRNA regulatory element (MRE) prediction algorithm that represents a greater than 20-fold refinement over computational methods alone. These high confidence MREs were used to generate candidate ‘competing endogenous RNA’ (ceRNA) networks.

Conclusion
HITS-CLIP analysis provide novel insights into global miRNA:mRNA relationships in the regenerating liver.
Data dissemination with rateless coding in a grid vehicular topology
Authors: Salkuyeh Mostafa Asgharpoor , Hendessi Faramarz , Gulliver T Aaron 
Published: April 2013

Abstract
Vehicular ad hoc networks are an important new class of wireless networks with applications ranging from safety and crash avoidance to Internet access and multimedia distribution. In this article, an efficient method of message dissemination using rateless coding is proposed. Both vehicle-to-vehicle and vehicle-to-infrastructure data transfer are allowed. By employing rateless coding at road side units and using vehicles as data carriers, messages can be propagated efficiently. To limit the buffer capacity required in vehicles, buffer management is employed. The network considered has a grid topology. The effects of vehicle speed, number of lanes, broadcast interval, and decoding distance on the performance are examined.
Rubella epidemic caused by genotype 1E rubella viruses in Beijing, China, in 2007–2011
Authors: Chen Meng , Zhu Zhen , Liu Donglei , Huang Guohong , Huang Fang , Wu Jiang , Zhang Tiegang , Xu Wenbo , Pang Xinghuo 
Published: April 2013

Abstract

Background
A series of different rubella vaccination strategies were implemented to control rubella and prevent congenital rubella virus infection in Beijing, China. The rubella vaccine was available in 1995 in Beijing, and was introduced into the Beijing immunization program (vaccine recipients at their own expense vaccination) in 2000, and was introduced into the National Expanded Program on Immunization (vaccine recipients free vaccination) in 2006. Rubella virological surveillance started in Beijing in 2007.

Results
The reported rubella incidence rate has decreased dramatically due to the introduction of the vaccine in Beijing since 1995. However, rubella epidemics occurred regardless in 2001 and 2007. The incidence rate among the floating population has gradually increased since 2002, reaching 2 or more times that in the permanent resident population. The peak age of rubella cases gradually changed from <15 years of age to adults after 2005. Phylogenetic analysis was performed and a phylogenetic tree was constructed based on the World Health Organization standard sequence window for rubella virus isolates. All Beijing rubella virus isolates belong to genotype 1E/cluster1 and were clustered interspersed with viruses from other provinces in China. The effective number of infections indicated by a Bayesian skyline plot remained constant from 2007 to 2011.

Conclusions
The proportion of rubella cases among the floating population has increased significantly in Beijing since 2002, and the disease burden gradually shifted to the older age group (15- to 39-year olds), which has become a major group with rubella infection since 2006. Genotype 1E rubella virus continuously caused a rubella epidemic in Beijing in 2007–2011 and was the predominant virus, and all Beijing genotype 1E viruses belong to cluster 1, which is also widely circulated throughout the country.
Peripheral Nerve Injury is Accompanied by Chronic Transcriptome-Wide Changes in the Mouse Prefrontal Cortex
Authors: Alvarado Sebastian , Tajerian Maral , Millecamps Magali , Suderman Mathew , Stone Laura S , Szyf Moshe 
Published: April 2013

Background Peripheral nerve injury can have long-term consequences including pain-related manifestations, such as hypersensitivity to cutaneous stimuli, as well as affective and cognitive disturbances, suggesting the involvement of supraspinal mechanisms. Changes in brain structure and cortical function associated with many chronic pain conditions have been reported in the prefrontal cortex (PFC). The PFC is implicated in pain-related co-morbidities such as depression, anxiety and impaired emotional decision-making ability. We recently reported that this region is subject to significant epigenetic reprogramming following peripheral nerve injury, and normalization of pain-related structural, functional and epigenetic abnormalities in the PFC are all associated with effective pain reduction. In this study, we used the Spared Nerve Injury (SNI) model of neuropathic pain to test the hypothesis that peripheral nerve injury triggers persistent long-lasting changes in gene expression in the PFC, which alter functional gene networks, thus providing a possible explanation for chronic pain associated behaviors. Results SNI or sham surgery where performed in male CD1 mice at three months of age. Six months after injury, we performed transcriptome-wide sequencing (RNAseq), which revealed 1147 differentially regulated transcripts in the PFC in nerve-injured vs. control mice. Changes in gene expression occurred across a number of functional gene clusters encoding cardinal biological processes as revealed by Ingenuity Pathway Analysis. Significantly altered biological processes included neurological disease, skeletal muscular disorders, behavior, and psychological disorders. Several of the changes detected by RNAseq were validated by RT-QPCR and included transcripts with known roles in chronic pain and/or neuronal plasticity including the NMDA receptor (glutamate receptor, ionotropic, NMDA; grin1), neurite outgrowth (roundabout 3; robo3), gliosis (glial fibrillary acidic protein; gfap), vesicular release (synaptotagmin 2; syt2), and neuronal excitability (voltage-gated sodium channel, type I; scn1a). Conclusions This study used an unbiased approach to document long-term alterations in gene expression in the brain following peripheral nerve injury. We propose that these changes are maintained as a memory of an insult that is temporally and spatially distant from the initial injury.