bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molluscan Community Recovery in a New England Back‐Barrier Salt Marsh Lagoon 10 Years after Partial Restoration
Authors: Thiet Rachel K. , Kidd Erica , Wennemer Jodie M. , Smith Stephen M. 
Published: January 2014

AbstractLike many Eastern U.S. salt marshes, East Harbor salt marsh lagoon on Cape Cod was isolated from tidal flow in the 1800s, resulting in near‐freshwater conditions and loss of native salt marsh species. After its partial restoration in 2002, a variety of marine and estuarine fauna recolonized East Harbor, and soft shell clam (Mya arenaria) recolonization was particularly prolific. The goal of our study was to evaluate molluscan community composition, density, and distribution at regular intervals for 10 years following restoration, and to relate molluscan community recovery to various physical properties at the site. In 2007, 2008, and 2011, we sampled mollusks at several points across East Harbor, and we also recorded water salinity and temperature, particle size distribution, and submerged aquatic vegetation density. In 2007 and 2008, we encountered 12 and 11 mollusk species, respectively; M. arenaria was the most abundant species in 2007 and the second most abundant species in 2008. In 2011, we encountered eight mollusk species and M. arenaria was the most abundant species. Mollusk species richness declined from 12 to 8 species between 2008 and 2011. Our results show that mollusk species richness and density have declined significantly since the first few years following restoration; related studies attribute this to high summer water temperatures in the Main Lagoon and severe macroalgal blooms during 2005–2006. This suggests that East Harbor is still equilibrating to baseline conditions and that full tidal restoration may be necessary to sustain a diverse mollusk community at East Harbor.
50th Anniversary Article: Review on Interface Fracture and Delamination of Composites
Authors: Banks‐Sills L. 
Published: January 2014

ABSTRACTIn this review paper, a methodology for measuring the interface fracture toughness of a crack between two isotropic, homogeneous materials and a delamination between two laminae of unidirectional composite materials of differing directions is presented. Four cases are considered. Two isotropic material pairs are described: glass/epoxy and two ceramic clays. Similar studies are presented for two cross‐ply laminates: 0°/90° and +45°/−45. The Brazilian disk specimen was used to carry out mixed mode fracture tests. The load and crack or delamination length at fracture were measured and used in a finite element analysis to determine the displacement field. An interaction energy orM‐integral was used to obtain the stress intensity factors at failure. These in turn were employed to calculate the critical interface energy release rateand two phase anglesψandφ, which measure the mode mixity. For theM‐integral and for each interface crack or delamination, the first term of the asymptotic solution of the fields is required. For two isotropic materials, these solutions are well known. For the laminates described here, they were determined by the Stroh and Lekhnittski formalisms. A failure criterion determined from first principles is presented. The values of,ψandφare used to specify the criterion for each material pair. A statistical analysis is presented, which predicts a 5% probability of failure.
Quantum Cognition: Key Issues and Discussion
Authors: Busemeyer Jerome R. , Wang Zheng 
Published: January 2014

AbstractQuantum cognition is an emerging field that uses mathematical principles of quantum theory to help formalize and understand cognitive systems and processes. The topic on the potential of using quantum theory to build models of cognition (Volume 5, issue 4) introduces and synthesizes its new development through an introduction and six core articles. The current issue presents 14 commentaries on the core articles. Five key issues surface, some of which are interestingly controversial and debatable as expected for a new emerging field.
Comparative Analysis of Bacillus subtilis Spores and Monophosphoryl Lipid A as Adjuvants of Protein-Based Mycobacterium tuberculosis-Based Vaccines: Partial Requirement for Interleukin-17A for Induction of Protective Immunity
Authors: Esparza-Gonzalez Sandra C. , Troy Amber R. , Izzo Angelo A. 
Published: January 2014

ABSTRACTThe development of adjuvants for vaccines has become an important area of research as the number of protein-based vaccines against infectious pathogens increases. Currently, there are a number of adjuvant-basedMycobacterium tuberculosisvaccines in clinical trials that have shown efficacy in animal models. Despite these novel adjuvants, there is still a need to design new and more versatile adjuvants that have minimal adverse side effects but produce robust long-lasting adaptive immune responses. To this end, we hypothesized thatBacillus subtilisspores may provide the appropriate innate signals that are required to generate such vaccine-mediated responses, which would be sufficient to reduce the mycobacterial burden after infection withM. tuberculosis. In addition, we compared the response generated byB. subtilisspores to that generated by monophosphoryl lipid A (MPL), which has been used extensively to test tuberculosis vaccines. The well-characterized, 6-kDa early secretory antigenic target ofM. tuberculosis(ESAT-6; Rv3875) was used as a test antigen to determine the T cell activation potential of each adjuvant. Inoculated into mice,B. subtilisspores induced a strong proinflammatory response and Th1 immunity, similar to MPL; however, unlike MPL formulated with dimethyldioctadecylammonium (DDA) bromide, it failed to induce significant levels of interleukin-17A (IL-17A) and was unable to significantly reduce the mycobacterial burden after pulmonary infection withM. tuberculosis. Further analysis of the activity of MPL-DDA suggested that IL-17A was required for protective immunity. Taken together, the data emphasize the requirement for a network of cytokines that are essential for protective immunity.
Fatal Fulminant Hepatitis E Associated with Autoimmune Hepatitis and Excessive Paracetamol Intake in Southeastern France
Authors: Doudier Barbara , Vencatassin Hugues , Aherfi Sarah , Colson Philippe 
Published: January 2014

ABSTRACT
We present, to our knowledge, the first case of fatal fulminant liver failure associated with hepatitis E virus infection, autoimmune hepatitis, and excessive paracetamol intake, which occurred in a 77-year-old woman. Hepatitis E testing should be performed in severe acute liver failure cases, even when another cause has been identified.
Evaluation of a Short, On-Plate Formic Acid Extraction Method for Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry-Based Identification of Clinically Relevant Yeast Isolates
Authors: Gorton Rebecca L. , Seaton Shila , Ramnarain Purnima , McHugh Timothy D. , Kibbler Christopher C. 
Published: January 2014

ABSTRACT
This report describes a short, on-plate formic acid (FA) extraction method for the identification of clinical yeast isolates using matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF MS). A total of 41.1% (78/190) and 63.7% (121/190) of yeasts were identified using species log score thresholds of >2.0 and >1.9, respectively. Overall, 97.4% (185/190) of yeasts were identified in combination with conventional FA extraction.
Abdominal Abscess Caused by Mycobacterium llatzerense
Authors: Cárdenas Ana María , Gomila Margarita , Lalucat Jorge , Edelstein Paul H. 
Published: January 2014

ABSTRACT

Mycobacterium llatzerense
was cultured from a subdiaphragmatic abscess. To our knowledge, this is the first report of isolation of this rapidly growing mycobacterium from a human. Growth characteristics and antimicrobial susceptibilities different from those previously reported for environmental isolates were observed.
Activation of the Interferon Induction Cascade by Influenza A Viruses Requires Viral RNA Synthesis and Nuclear Export
Authors: Killip Marian J. , Smith Matt , Jackson David , Randall Richard E. 
Published: January 2014

ABSTRACT

We have examined the requirements for virus transcription and replication and thus the roles of input and progeny genomes in the generation of interferon (IFN)-inducing pathogen-associated molecular patterns (PAMPs) by influenza A viruses using inhibitors of these processes. Using IFN regulatory factor 3 (IRF3) phosphorylation as a marker of activation of the IFN induction cascade that occurs upstream of the IFN-β promoter, we demonstrate strong activation of the IFN induction cascade in A549 cells infected with a variety of influenza A viruses in the presence of cycloheximide or nucleoprotein (NP) small interfering RNA (siRNA), which inhibits viral protein synthesis and thus complementary ribonucleoprotein (cRNP) and progeny viral RNP (vRNP) synthesis. In contrast, activation of the IFN induction cascade by influenza viruses was very effectively abrogated by treatment with actinomycin D and other transcription inhibitors, which correlated with the inhibition of the synthesis of all viral RNA species. Furthermore, 5,6-dichloro-1-β-
d
-ribofuranosyl-benzimidazole, an inhibitor that prevents viral RNA export from the nucleus, was also a potent inhibitor of IRF3 activation; thus, both viral RNA synthesis and nuclear export are required for IFN induction by influenza A viruses. While the exact nature of the viral PAMPs remains to be determined, our data suggest that in this experimental system the major influenza A virus PAMPs are distinct from those of incoming genomes or progeny vRNPs.

IMPORTANCE
The host interferon system exerts an extremely potent antiviral response that efficiently restricts virus replication and spread; the interferon response can thus dictate the outcome of a virus infection, and it is therefore important to understand how viruses induce interferon. Both input and progeny genomes have been linked to interferon induction by influenza viruses. However, our experiments in tissue culture cells show that viral RNA synthesis and nuclear export are required to activate this response. Furthermore, the interferon induction cascade is activated under conditions in which the synthesis of progeny genomes is inhibited. Therefore, in tissue culture cells, input and progeny genomes are not the predominant inducers of interferon generated by influenza A viruses; the major viral interferon inducer(s) still remains to be identified.
Inhibition of Dengue and Chikungunya Virus Infections by RIG-I-Mediated Type I Interferon-Independent Stimulation of the Innate Antiviral Response
Authors: Olagnier David , Scholte Florine E. M. , Chiang Cindy , Albulescu Irina C. , Nichols Carmen , He Zhong , Lin Rongtuan , Snijder Eric J. , van Hemert Martijn J. , Hiscott John 
Published: January 2014

ABSTRACT

RIG-I is a cytosolic sensor critically involved in the activation of the innate immune response to RNA virus infection. In the present study, we evaluated the inhibitory effect of a RIG-I agonist on the replication of two emerging arthropod-borne viral pathogens, dengue virus (DENV) and chikungunya virus (CHIKV), for which no therapeutic options currently exist. We demonstrate that when a low, noncytotoxic dose of an optimized 5′triphosphorylated RNA (5′pppRNA) molecule was administered, RIG-I stimulation generated a robust antiviral response against these two viruses. Strikingly, 5′pppRNA treatment before or after challenge with DENV or CHIKV provided protection against infection. In primary human monocytes and monocyte-derived dendritic cells, the RIG-I agonist blocked both primary infection and antibody-dependent enhancement of DENV infection. The protective response against DENV and CHIKV induced by 5′pppRNA was dependent on an intact RIG-I/MAVS/TBK1/IRF3 axis and was largely independent of the type I IFN response. Altogether, this
in vitro
analysis of the antiviral efficacy of 5′pppRNA highlights the therapeutic potential of RIG-I agonists against emerging viruses such as DENV and CHIKV.

IMPORTANCE
DENV and CHIKV are two reemerging mosquito-borne viruses for which no therapeutic options currently exist. Both viruses overlap geographically in tropical regions of the world, produce similar fever-like symptoms, and are difficult to diagnose. This study investigated the inhibitory effect of a RIG-I agonist on the replication of these two viruses. RIG-I stimulation using 5′pppRNA before or after DENV or CHIKV infection generated a protective antiviral response against both pathogens in immune and nonimmune cells; interestingly, the protective response against the viruses was largely independent of the classical type I interferon response. The antiviral efficacy of 5′pppRNA highlights the therapeutic potential of RIG-I agonists against emerging viruses such as DENV and CHIKV.
Large-Scale Nucleotide Optimization of Simian Immunodeficiency Virus Reduces Its Capacity To Stimulate Type I Interferon
In Vitro
Authors: Vabret Nicolas , Bailly-Bechet Marc , Lepelley Alice , Najburg Valérie , Schwartz Olivier , Verrier Bernard , Tangy Frédéric 
Published: January 2014

ABSTRACT

Lentiviral RNA genomes present a strong bias in their nucleotide composition with extremely high frequencies of A nucleotide in human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV). Based on the observation that human optimization of RNA virus gene fragments may abolish their ability to stimulate the type I interferon (IFN-I) response, we identified the most biased sequences along the SIV genome and showed that they are the most potent IFN-I stimulators. With the aim of designing an attenuated SIV genome based on a reduced capacity to activate the IFN-I response, we synthesized artificial SIV genomes whose biased sequences were optimized toward macaque average nucleotide composition without altering their regulatory elements or amino acid sequences. A synthetic SIV optimized with 169 synonymous mutations in
gag
and
pol
genes showed a 100-fold decrease in replicative capacity. Interestingly, a synthetic SIV optimized with 70 synonymous mutations in
pol
had a normal replicative capacity. Its ability to stimulate IFN-I was reduced when infected cells were cocultured with reporter cells. IFN regulatory factor 3 (IRF3) transcription factor was required for IFN-I stimulation, implicating cytosolic sensors in the detection of SIV-biased RNA in infected cells. No reversion of introduced mutations was observed for either of the optimized viruses after 10 serial passages. In conclusion, we have designed large-scale nucleotide-modified SIVs that may display attenuated pathogenic potential.

IMPORTANCE
In this study, we synthesized artificial SIV genomes in which the most hyperbiased sequences were optimized to bring them closer to the nucleotide composition of the macaque SIV host. Interestingly, we generated a stable synthetic SIV optimized with 70 synonymous mutations in
pol
gene, which had a normal replicative capacity but a reduced ability to stimulate type I IFN. This demonstrates the possibility to rationally change viral nucleotide composition to design replicative and genetically stable lentiviruses with attenuated pathogenic potentials.
Surfactant-Modified Nanoclay Exhibits an Antiviral Activity with High Potency and Broad Spectrum
Authors: Liang Jian-Jong , Wei Jiun-Chiou , Lee Yi-Ling , Hsu Shan-hui , Lin Jiang-Jen , Lin Yi-Ling 
Published: January 2014

ABSTRACTNanomaterials have the characteristics associated with high surface-to-volume ratios and have been explored for their antiviral activity. Despite some success, cytotoxicity has been an issue in nanomaterial-based antiviral strategies. We previously developed a novel method to fully exfoliate montmorillonite clay to generate the most fundamental units of nanoscale silicate platelet (NSP). We further modified NSP by capping with various surfactants and found that the surfactant-modified NSP (NSQ) was less cytotoxic. In this study, we tested the antiviral potentials of a series of natural-clay-derived nanomaterials. Among the derivatives, NSP modified with anionic sodium dodecyl sulfate (NSQc), but not the pristine clay, unmodified NSP, a silver nanoparticle-NSP hybrid, NSP modified with cationicn-octadecanylamine hydrochloride salt, or NSP modified with nonionic Triton X-100, significantly suppressed the plaque-forming ability of Japanese encephalitis virus (JEV) at noncytotoxic concentrations. NSQc also blocked infection with dengue virus (DEN) and influenza A virus. Regarding the antiviral mechanism, NSQc interfered with viral binding through electrostatic interaction, since its antiviral activity can be neutralized by Polybrene, a cationic polymer. Furthermore, NSQc reduced the lethality of JEV and DEN infection in mouse challenge models. Thus, the surfactant-modified exfoliated nanoclay NSQc may be a novel nanomaterial with broad and potent antiviral activity.IMPORTANCENanomaterials have being investigated as antimicrobial agents, yet their antiviral potential is overshadowed by their cytotoxicity. By using a novel method, we fully exfoliated montmorillonite clay to generate the most fundamental units of nanoscale silicate platelet (NSP). Here, we show that the surfactant-modified NSP (NSQ) is less cytotoxic and that NSQc (NSP modified with sodium dodecyl sulfate) could potently block infection by dengue virus (DEN), Japanese encephalitis virus (JEV), and influenza A virus at noncytotoxic concentrations. For the antiviral mechanism, we find that the electrostatic interaction between the negatively charged NSQc and the positively charged virus particles blocks viral binding. Furthermore, we used mouse challenge models of JEV and DEN to demonstrate thein vivoantiviral potential of NSQc. Thus, NSQc may function as a potent and safe antiviral nanohybrid against several viruses, and our success in synthesizing surfactant-modified NSP with antiviral activity may shed some light on future antiviral development.
Forkhead Box Transcription Factor Regulation and Lipid Accumulation by Hepatitis C Virus
Authors: Bose Sandip K. , Kim Hangeun , Meyer Keith , Wolins Nathan , Davidson Nicholas O. , Ray Ranjit 
Published: January 2014

ABSTRACT
We have previously shown that hepatitis C virus (HCV) infection modulates the expression of forkhead box transcription factors, including FoxO1 and FoxA2, which play key roles in gluconeogenesis and β-oxidation of fatty acid, respectively. The aim of the present study was to determine the role of forkhead box transcription factors in modulating lipid metabolism. HCV infection or core protein expression alone in transfected Huh7.5 cells increased expression of sterol regulatory element binding protein 1c (SREBP-1c) and its downstream target, fatty acid synthase (FASN), which are key proteins involved in lipid synthesis. Knockdown of FoxO1 by small interfering RNA in HCV-infected cells significantly decreased SREBP-1c and FASN expression. Further, HCV infection or core protein expression in Huh7.5 cells significantly decreased the expression of medium-chain acyl coenzyme A dehydrogenase (MCAD) and short-chain acyl coenzyme A dehydrogenase (SCAD), involved in the regulation of β-oxidation of fatty acids. Ectopic expression of FoxA2 in HCV-infected cells rescued the expression of MCAD and SCAD. Oil red O and neutral lipid staining indicated that HCV infection significantly increases lipid accumulation compared to that in the mock-infected control. This was further verified by the increased expression of perilipin-2 and decreased activity of hormone-sensitive lipase (HSL) in HCV-infected hepatocytes, implying increased accumulation of neutral lipids. Knockdown of FoxO1 and ectopic expression of FoxA2 significantly decreased HCV replication. Taken together, these results suggest that HCV modulates forkhead box transcription factors which together increase lipid accumulation and promote viral replication.

IMPORTANCE
Hepatic steatosis is a frequent complication associated with chronic HCV infection. Its presence is a key prognostic indicator associated with the progression to hepatic fibrosis and hepatocellular carcinoma. Several mechanisms have been proposed to account for the development of steatosis and fatty liver during HCV infection. We observed that HCV infection increases expression of both SREBP-1c and FASN. Further investigation suggested that the expression of SREBP-1c and FASN is controlled by the transcription factor FoxO1 during HCV infection. In addition, HCV infection significantly decreased both MCAD and SCAD expression, which is controlled by FoxA2. HCV infection also increased lipid droplet accumulation, increased perilipin-2 expression, and decreased HSL activity. Thus, knockdown of FoxO1 (decreased lipogenesis) and overexpression of FoxA2 (increased β-oxidation) resulted in a significant disruption of the platform and, hence, a decrease in HCV genome replication. Thus, targeting of FoxO1 and FoxA2 might be useful in developing a therapeutic approach against HCV infection.
Reversible and Efficient Activation of HIV-1 Cell Entry by a Tyrosine-Sulfated Peptide Dissects Endocytic Entry and Inhibitor Mechanisms
Authors: Platt Emily J. , Gomes Michelle M. , Kabat David 
Published: January 2014

ABSTRACT

HIV-1 membranes contain gp120-gp41 trimers. Binding of gp120 to CD4 and a coreceptor (CCR5 or CXCR4) reduces the constraint on metastable gp41, enabling a series of conformational changes that cause membrane fusion. An analytic difficulty occurs because these steps occur slowly and asynchronously within cohorts of adsorbed virions. We previously isolated HIV-1
JRCSF
variants that efficiently use CCR5 mutants severely damaged in the tyrosine-sulfated amino terminus or extracellular loop 2. Surprisingly, both independent adaptations included gp120 mutations S298N, F313L, and N403S, supporting other evidence that they function by weakening gp120's grip on gp41 rather than by altering gp120 binding to specific CCR5 sites. Although several natural HIV-1 isolates reportedly use CCR5(Δ18) (CCR5 with a deletion of 18 N-terminal amino acids, including the tyrosine-sulfated region) when the soluble tyrosine-sulfated peptide is present, we show that HIV-1
JRCSF
with the adaptive mutations [HIV-1
JRCSF
(Ad)] functions approximately 100 times more efficiently and that coreceptor activation is reversible, enabling synchronous efficient entry control under physiological conditions. This system revealed that three-stranded gp41 folding intermediates susceptible to the inhibitor enfuvirtide form slowly and asynchronously on cell surface virions but resolve rapidly, with virions generally forming only one target. Adsorbed virions asynchronously and transiently become competent for entry at 37°C but are inactivated if the CCR5 peptide is absent during their window of opportunity. This competency is conferred by endocytosis, which results in inactivation if the peptide is absent. For both wild-type and adapted HIV-1 isolates, early gp41 refolding steps obligatorily occur on cell surfaces, whereas the final step(s) is endosomal. This system powerfully dissects HIV-1 entry and inhibitor mechanisms.

IMPORTANCE
We present a powerful means to reversibly and efficiently activate or terminate HIV-1 entry by adding or removing a tyrosine-sulfated CCR5 peptide from the culture medium. This system uses stable cell clones and a variant of HIV-1
JRCSF
with three adaptive mutations. It enabled us to show that CCR5 coreceptor activation is rapidly reversible and to dissect aspects of entry that had previously been relatively intractable. Our analyses elucidate enfuvirtide (T-20) function and suggest that HIV-1 virions form only one nonredundant membrane fusion complex on cell surfaces. Additionally, we obtained novel and conclusive evidence that HIV-1 entry occurs in an assembly line manner, with some steps obligatorily occurring on cell surfaces and with final membrane fusion occurring in endosomes. Our results were confirmed for wild-type HIV-1. Thus, our paper provides major methodological and mechanistic insights about HIV-1 infection.