bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bayesian Inference for Palaeoclimate with time Uncertainty and Stochastic Volatility
Authors: Parnell Andrew C. , Sweeney James , Doan Thinh K. , Salter-Townshend Michael , Allen Judy R. M. , Huntley Brian , Haslett John 
Published: July 2014

SummaryWe propose and fit a Bayesian model to infer palaeoclimate over several thousand years. The data that we use arise as ancient pollen counts taken from sediment cores together with radiocarbon dates which provide (uncertain) ages. When combined with a modern pollen–climate data set, we can calibrate ancient pollen into ancient climate. We use a normal–inverse Gaussian process prior to model the stochastic volatility of palaeoclimate over time, and we present a novel modularized Markov chain Monte Chain algorithm to enable fast computation. We illustrate our approach with a case-study from Sluggan Moss, Northern Ireland, and provide an R package, Bclim, for use at other sites.
Impact of recipient ABH secretor status on outcome in minor ABO‐incompatible hematopoietic stem cell transplantation
Authors: Holbro Andreas , Stern Martin , Infanti Laura , O'Meara Alix , Drexler Beatrice , Frey Beat M. , Tiercy Jean‐Marie , Passweg Jakob R. , Gassner Christoph , Buser Andreas , Sigle Joerg‐Peter 
Published: July 2014

BackgroundThe impact of ABO incompatibility on hematopoietic stem cell transplantation (HSCT) outcome is controversial. As ABH substances are expressed on tissues and secreted in body fluids, they could drive an immune response in minor ABO‐incompatible HSCT. The aim of the study was to investigate the prognostic role of the recipients' ABH secretor status.Study Design and MethodsPatients who underwent minor ABO‐incompatible HSCT were included. Secretor status was determined either serologically or by molecular genetics.ResultsBetween March 1996 and June 2012, a total of 176 patients received minor ABO‐incompatible HSCT and 150 (85%) were secretors. Incidence and severity of acute graft‐versus‐host disease (GVHD) and chronic GVHD did not differ between secretors and nonsecretors (cumulative incidences ± standard errors: acute GVHD on Day 100, 41 ± 11 and 46 ± 5%, p = 0.59; chronic GVHD at 2 years, 52 ± 13 and 56 ± 5%, p = 0.62, for secretors and nonsecretors, respectively). Additionally, nonrelapse mortality (NRM) and overall survival (OS) were similar in the two groups (2‐year NRM, 27 ± 9 and 23 ± 3%, p = 0.45; 4‐year OS, 64 ± 10 and 55 ± 4%, p = 0.28, for secretors and nonsecretors, respectively).ConclusionThe recipients' ABH secretor status in minor ABO‐incompatible HSCT has no prognostic impact on major transplant outcomes.
Erythema multiforme, Stevens–Johnson syndrome and toxic epidermal necrolysis: a comparative review
Authors: Yager Julie A. 
Published: July 2014

BackgroundHuman erythema multiforme (EM) and Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are separate conditions. There is no consensus on classification criteria for the eponymous diseases in animals.ResultsAnimalEMis very different from 90% of humanEM, which is herpes virus associated (HAEM). Animals lack acrally distributed, typical raised targets. Unlike canine parvovirus ‘EM’,HAEMis not an active infection. AnimalEMis often attributed to drugs, but this is rarely proved. Conversely, human and animalSJS/TENare almost identical, life‐threatening disorders of epidermal necrosis and detachment, typically triggered by drugs (occasionally by infectious agents). BothEMandSJS/TENare mediated by cytotoxic lymphocyte responses against altered keratinocytes (infectious agents or drugs). Apoptosis results from direct cytotoxicity or through soluble mediators, namely Fas ligand, granzymes, perforin and granulysin. Diagnosis in humans is clinicopathological, with emphasis on clinical lesions; histopathology confirms the pathological process as interface (cytotoxic) dermatitis. HumanEMis self‐limiting; only recurrent and rare persistent cases require antiviral/immunosuppressive therapies. Drug‐inducedEMresponds to drug withdrawal. Idiopathic canineEM(>40%) is usually chronic, refractory to treatment and may represent heterogeneous conditions. Early identification and removal of the causative drug and high‐quality supportive care are critical inSJS/TEN. Mortality rate is nevertheless high.Conclusions and clinical importance(1) Histopathological lesions do not reliably differentiateEM,SJSandTEN. (2) A multicentre study to develop a consensus set of clinical criteria forEMandSJS/TENin animals is overdue. (3) No adjunctive therapies, including intravenous immunoglobulin and ciclosporin, have met evidence‐based standards.
Regioselective ketone α-alkylation with simple olefins via dual activation
Authors: Mo Fanyang , Dong Guangbin 
Published: July 2014

Carbon-carbon bonds without byproducts
Environmental and cost concerns are spurring development of chemical methods that minimize byproduct formation. In this vein, Mo and Dong present a catalyst that inserts olefins such as ethylene directly into the C-H bonds of ketones. Traditional methods to form such products rely on the preliminary reaction of the ketone with a base, followed by subsequent reaction with an alkyl halide. The authors used a ligand that simultaneously activates the ketone and guides the catalytic rhodium to the right location. This approach removes the need for the other reagents and eliminates the associated halide salt byproducts.

Science
, this issue p.
68
Bloodstream Infections Are an Improbable Cause of Positive Serum (1,3)-β-d-Glucan in Hematology Patients
Authors: Furfaro E. , Mikulska M. , Del Bono V. , Guolo F. , Minetto P. , Gobbi M. , Ghiso A. , Bacigalupo A. , Viscoli C. 
Published: July 2014

ABSTRACTNinety-one serum samples from 51 hematology patients with bacteremia infections were tested for (1,3)-β-d-glucan (BG). Eleven samples (15%) from 7 patients (14%) were positive for BG. Of these 7 patients with positive BG results, 4 (8%) had invasive aspergillosis and 3 (6%) had no invasive fungal disease. Bacteremia was an unlikely cause of the false-positive BG results.
Detection of Antibodies to Varicella-Zoster Virus in Recipients of the Varicella Vaccine by Using a Luciferase Immunoprecipitation System Assay
Authors: Cohen Jeffrey I. , Ali Mir A. , Bayat Ahmad , Steinberg Sharon P. , Park Hosun , Gershon Anne A. , Burbelo Peter D. 
Published: July 2014

ABSTRACTA high-throughput test to detect varicella-zoster virus (VZV) antibodies in varicella vaccine recipients is not currently available. One of the most sensitive tests for detecting VZV antibodies after vaccination is the fluorescent antibody to membrane antigen (FAMA) test. Unfortunately, this test is labor-intensive, somewhat subjective to read, and not commercially available. Therefore, we developed a highly quantitative and high-throughput luciferase immunoprecipitation system (LIPS) assay to detect antibody to VZV glycoprotein E (gE). Tests of children who received the varicella vaccine showed that the gE LIPS assay had 90% sensitivity and 70% specificity, a viral capsid antigen enzyme-linked immunosorbent assay (ELISA) had 67% and 87% specificity, and a glycoprotein ELISA (not commercially available in the United States) had 94% sensitivity and 74% specificity compared with the FAMA test. The rates of antibody detection by the gE LIPS and glycoprotein ELISA were not statistically different. Therefore, the gE LIPS assay may be useful for detecting VZV antibodies in varicella vaccine recipients. (This study has been registered at ClinicalTrials.gov under registration no. NCT00921999.)
First Report of Endocarditis Caused by a Pseudoclavibacter Species
Authors: Pailhoriès Hélène , Lemarié Carole , Quinqueneau Catherine , Eveillard Matthieu , Baufreton Christophe , Rouleau Frédéric , Mahaza Chetaou , Joly-Guillou Marie-Laure , Kempf Marie 
Published: July 2014

ABSTRACT

We describe the first case of
Pseudoclavibacter
species endocarditis in a 44-year-old patient. This genus, rarely isolated from humans, confirms here its role as a human pathogen.
Necrotizing Fasciitis Caused by Haemophilus influenzae Serotype f
Authors: Arnold Christopher J. , Garrigues Grant , St. Geme Joseph W. , Sexton Daniel J. 
Published: July 2014

ABSTRACT

Haemophilus influenzae
is a rare cause of soft tissue infection. In this report, we present a case of multifocal necrotizing fasciitis in a healthy adult patient, secondary to
Haemophilus influenzae
serotype f infection, and we review literature on this rare cause of necrotizing fasciitis.
Advances in Laboratory Methods for Detection and Typing of Norovirus
Authors: Vinjé Jan 
Published: July 2014

ABSTRACT
Human noroviruses are the leading cause of epidemic and sporadic gastroenteritis across all age groups. Although the disease is usually self-limiting, in the United States norovirus gastroenteritis causes an estimated 56,000 to 71,000 hospitalizations and 570 to 800 deaths each year. This minireview describes the latest data on laboratory methods (molecular, immunological) for norovirus detection, including real-time reverse transcription-quantitative PCR (RT-qPCR) and commercially available immunological assays as well as the latest FDA-cleared multi-gastrointestinal-pathogen platforms. In addition, an overview is provided on the latest nomenclature and molecular epidemiology of human noroviruses.
High-Resolution Structure of a Virally Encoded DNA-Translocating Conduit and the Mechanism of DNA Penetration
Authors: Sun Lei , Rossmann Michael G. , Fane Bentley A. 
Published: July 2014

ABSTRACT

Although ϕX174 DNA pilot protein H is monomeric during procapsid assembly, it forms an oligomeric tube on the host cell surface. Reminiscent of a double-stranded DNA phage tail in form and function, the H tube transports the single-stranded ϕX174 genome across the
Escherichia coli
cell wall. The 2.4-Å resolution H-tube crystal structure suggests functional and energetic mechanisms that may be common features of DNA transport through virally encoded conduits.
SnRK1 Phosphorylation of AL2 Delays Cabbage Leaf Curl Virus Infection in Arabidopsis
Authors: Shen Wei , Dallas Mary Beth , Goshe Michael B. , Hanley-Bowdoin Linda 
Published: July 2014

ABSTRACT

Geminivirus AL2/C2 proteins play key roles in establishing infection and causing disease in their plant hosts. They are involved in viral gene expression, counter host defenses by suppressing transcriptional gene silencing, and interfere with the host signaling involved in pathogen resistance. We report here that begomovirus and curtovirus AL2/C2 proteins interact strongly with host geminivirus Rep-interacting kinases (GRIKs), which are upstream activating kinases of the protein kinase SnRK1, a global regulator of energy and nutrient levels in plants. We used an
in vitro
kinase system to show that GRIK-activated SnRK1 phosphorylates recombinant AL2/C2 proteins from several begomoviruses and to map the SnRK1 phosphorylation site to serine-109 in the AL2 proteins of two New World begomoviruses:
Cabbage Leaf Curl Virus
(CaLCuV)
and
Tomato mottle virus
. A CaLCuV AL2 S109D phosphomimic mutation did not alter viral DNA levels in protoplast replication assays. In contrast, the phosphomimic mutant was delayed for symptom development and viral DNA accumulation during infection of
Arabidopsis thaliana
, demonstrating that SnRK1 contributes to host defenses against CaLCuV. Our observation that serine-109 is not conserved in all AL2/C2 proteins that are SnRK1 substrates
in vitro
suggested that phosphorylation of viral proteins by plant kinases contributes to the evolution of geminivirus-host interactions.

IMPORTANCE
Geminiviruses are single-stranded DNA viruses that cause serious diseases in many crops. Dicot-infecting geminiviruses carry genes that encode multifunctional AL2/C2 proteins that are essential for infection. However, it is not clear how AL2/C2 proteins are regulated. Here, we show that the host protein kinase SnRK1, a central regulator of energy balance and nutrient metabolism in plants, phosphorylates serine-109 in AL2 proteins of three subgroups of New World begomoviruses, resulting in a delay in viral DNA accumulation and symptom appearance. Our results support SnRK1's antiviral role and reveal a novel mechanism underlying this function. Phylogenetic analysis suggested that AL2 S109 evolved as begomoviruses migrated from the Old World to the New World and may have provided a selective advantage as begomoviruses adapted to a different environment and different plant hosts. This study provides new insights into the interaction of viral pathogens with their plant hosts at the level of viral protein modification by the host.
Unexpected Structural Features of the Hepatitis C Virus Envelope Protein 2 Ectodomain
Authors: Sabahi Ali , Uprichard Susan L. , Wimley William C. , Dash Srikanta , Garry Robert F. 
Published: July 2014

ABSTRACT

Hepatitis C virus (HCV), a member of the family
Flaviviridae
, is a leading cause of chronic liver disease and cancer. Recent advances in HCV therapeutics have resulted in improved cure rates, but an HCV vaccine is not available and is urgently needed to control the global pandemic. Vaccine development has been hampered by the lack of high-resolution structural information for the two HCV envelope glycoproteins, E1 and E2. Recently, Kong and coworkers (Science 342:1090–1094, 2013, doi:10.1126/science.1243876) and Khan and coworkers (Nature 509[7500]:381–384, 2014, doi:10.1038/nature13117) independently determined the structure of the HCV E2 ectodomain core with some unexpected and informative results. The HCV E2 ectodomain core features a globular architecture with antiparallel β-sheets forming a central β sandwich. The residues comprising the epitopes of several neutralizing and nonneutralizing human monoclonal antibodies were also determined, which is an essential step toward obtaining a fine map of the human humoral response to HCV. Also clarified were the regions of E2 that directly bind CD81, an important HCV cellular receptor. While it has been widely assumed that HCV E2 is a class II viral fusion protein (VFP), the newly determined structure suggests that the HCV E2 ectodomain shares structural and functional similarities only with domain III of class II VFPs. The new structural determinations suggest that the HCV glycoproteins use a different mechanism than that used by class II fusion proteins for cell fusion.
Tobacco etch virus Protein P1 Traffics to the Nucleolus and Associates with the Host 60S Ribosomal Subunits during Infection
Authors: Martínez Fernando , Daròs José-Antonio 
Published: July 2014

ABSTRACT

The genus
Potyvirus
comprises a large group of positive-strand RNA plant viruses whose genome encodes a large polyprotein processed by three viral proteinases. P1 protein, the most amino-terminal product of the polyprotein, is an accessory factor stimulating viral genome amplification whose role during infection is not well understood. We infected plants with
Tobacco etch virus
(TEV; genus
Potyvirus
) clones in which P1 was tagged with a fluorescent protein to track its expression and subcellular localization or with an affinity tag to identify host proteins involved in complexes in which P1 also takes part during infection. Our results showed that TEV P1 exclusively accumulates in infected cells at an early stage of infection and that the protein displays a dynamic subcellular localization, trafficking in and out of the nucleus and nucleolus during infection. Inside the nucleolus, P1 particularly targets the dense granular component. Consistently, we found functional nucleolar localization and nuclear export signals in TEV P1 sequence. Our results also indicated that TEV P1 physically interacts with the host 80S cytoplasmic ribosomes and specifically binds to the 60S ribosomal subunits during infection.
In vitro
translation assays of reporter proteins suggested that TEV P1 stimulates protein translation, particularly when driven from the TEV internal ribosome entry site. These
in vitro
assays also suggested that TEV helper-component proteinase (HC-Pro) inhibits protein translation. Based on these findings, we propose that TEV P1 stimulates translation of viral proteins in infected cells.

IMPORTANCE
In this work, we researched the role during infection of tobacco etch virus P1 protease. P1 is the most mysterious protein of potyviruses, a relevant group of RNA viruses infecting plants. Our experiments showed that the viral P1 protein exclusively accumulates in infected cells at an early stage of infection and moves in and out of the nucleus of infected cells, particularly targeting the nucleolus. Our experiments also showed that P1 protein binds host ribosomes during infection. Based on these findings and other
in vitro
experiments we propose that P1 protein stimulates translation of viral proteins during infection.
Late Endosomal Trafficking of Alternative Serotype Adenovirus Vaccine Vectors Augments Antiviral Innate Immunity
Authors: Teigler Jeffrey E. , Kagan Jonathan C. , Barouch Dan H. 
Published: July 2014

ABSTRACT
Adenovirus (Ad) vaccine vectors have found widespread use as vaccine platforms against multiple infections and cancers, and multiple serotypes have been shown to differ significantly in their biological properties and immune phenotypes. Our laboratory and others have previously described differential innate immune stimulation elicited by various Ad serotypes. Here, we show that Ad serotype 5 (Ad5) traffics rapidly to the nucleus following infection, whereas Ad35 and Ad26 accumulate in late endosomes 2 to 8 h postinfection. Innate immune cytokine elicitation by all Ad serotypes was abrogated by blockade of endosomal acidification, cathepsin B, and caspase 1, suggesting that virus interactions with acid-dependent sensors, such as Toll-like receptor- and cathepsin-dependent inflammasome activation in late endosomes, may trigger innate immunity. These data suggest a mechanism by which Ad vectors from various serotypes differentially trigger innate antiviral pathways via distinct intracellular trafficking to late endosomes.

IMPORTANCE
Adenoviruses (Ad) are widely used for vaccination and gene therapy applications. Importantly, Ad vectors have been shown to differ significantly in their innate immune profiles both
in vivo
and
in vitro
. The molecular mechanism that underlies these observed differences has important implications for the development of improved vaccines. In this study, we propose a mechanism in which the degree of late endosomal trafficking of Ad vectors results in differential stimulation of late endosomal pattern recognition receptors.
Interferon-Induced Protein Ifit2 Protects Mice from Infection of the Peripheral Nervous System by Vesicular Stomatitis Virus
Authors: Fensterl Volker , Wetzel Jaime L. , Sen Ganes C. 
Published: July 2014

ABSTRACT

The interferon system provides the first line of host defense against virus infection. Mouse pathogenesis studies have revealed the importance of specific interferon-induced proteins in providing protection against specific viruses. We have previously reported that one such protein, Ifit2, protects neurons of the central nervous system from intranasal infection by the neurotropic rhabdovirus, vesicular stomatitis virus (VSV). Here, we demonstrate that Ifit2 protects the peripheral nervous system from VSV infection as well. In
Ifit2
−/−
mice, VSV, injected subcutaneously into the footpad, entered the proximal lymph node, where it replicated and infected the nodal nerve endings. The infection spread to the sciatic nerve, the spinal cord, and the brain, causing paralysis. In contrast, in the wild-type mice, although VSV replicated equally well in the lymph node, infection of the sciatic nerve and the rest of the nervous system was impaired, thus preventing paralysis. Ifit2 protected only the nervous system from VSV infection; other tissues were well protected even in
Ifit2
−/−
mice. These results indicate that Ifit2 is the interferon-induced protein that prevents VSV infection of neurons of both the peripheral and the central nervous systems, thus inhibiting the consequent neuropathy, but it is dispensable for protecting the cells of other tissues from VSV infection.

IMPORTANCE
Although viral infection is quite common, the immune system effectively protects us from viral diseases. A major part of this protection is mediated by interferon, the antiviral cytokine secreted by virus-infected cells. To empower the neighboring uninfected cells in combating the oncoming infection, interferon induces the synthesis of more than 200 new proteins, many of which have antiviral activities. The virus studied here, vesicular stomatitis virus (VSV), like its relative, rabies virus, can cause neuropathy in mice if it enters the peripheral nervous system through skin lesions; however, interferon can protect neurons from VSV infection. We have identified a specific interferon-induced protein, Ifit2, as the protein that protects neurons from VSV infection. Surprisingly, Ifit2 was not needed to protect other cell types from VSV. Our results indicate that the effector antiviral proteins of the interferon system have highly specialized functions.
Contribution of Glutamine Residues in the Helix 4-5 Loop to Capsid-Capsid Interactions in Simian Immunodeficiency Virus of Macaques
Authors: Tipper Christopher , Sodroski Joseph G. 
Published: July 2014

ABSTRACT
Following retrovirus entry, the viral capsid (CA) disassembles into its component capsid proteins. The rate of this uncoating process, which is regulated by CA-CA interactions and by the association of the capsid with host cell factors like cyclophilin A (CypA), can influence the efficiency of reverse transcription. Inspection of the CA sequences of lentiviruses reveals that several species of simian immunodeficiency viruses (SIVs) have lost the glycine-proline motif in the helix 4-5 loop important for CypA binding; instead, the helix 4-5 loop in these SIVs exhibits an increase in the number of glutamine residues. In this study, we investigated the role of these glutamine residues in SIVmac239 replication. Changes in these residues, particularly glutamine 89 and glutamine 92, resulted in a decreased efficiency of core condensation, decreased stability of the capsids in infected cells, and blocks to reverse transcription. In some cases, coexpression of two different CA mutants produced chimeric virions that exhibited higher infectivity than either parental mutant virus. For this complementation of infectivity, glutamine 89 was apparently required on one of the complementing pair of mutants and glutamine 92 on the other. Modeling suggests that glutamines 89 and 92 are located on the distal face of hexameric capsid spokes and thus are well positioned to contribute to interhexamer interactions. Requirements to evade host restriction factors like TRIMCyp may drive some SIV lineages to evolve means other than CypA binding to stabilize the capsid. One solution used by several SIV strains consists of glutamine-based bonding.

IMPORTANCE
The retroviral capsid is an assembly of individual capsid proteins that surrounds the viral RNA. After a retrovirus enters a cell, the capsid must disassemble, or uncoat, at a proper rate. The interactions among capsid proteins contribute to this rate of uncoating. We found that some simian immunodeficiency viruses use arrays of glutamine residues, which can form hydrogen bonds efficiently, to keep their capsids stable. This strategy may allow these viruses to forego the use of capsid-stabilizing factors from the host cell, some of which have antiviral activity.