bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequential Signaling Crosstalk Regulates Endomesoderm Segregation in Sea Urchin Embryos
Authors: Sethi Aditya J. , Wikramanayake Radhika M. , Angerer Robert C. , Range Ryan C. , Angerer Lynne M.
Published: February 2012

Lineage Identity

Segregation of endoderm and mesoderm lineages is a fundamental event in early embryogenesis. Using sea urchin embryos,

Sethi
et al.

(p.
590
) found that Notch and canonical Wnt pathways crosstalk progressively partitions the endomesoderm to discrete endoderm and mesoderm fates. This three-step signaling exchange demonstrates how the timing of signaling crosstalk is regulated in vivo through temporally and spatially staggered genetic circuits that intersect only at specific developmental stages.
Response to Comment on “Abiotic Pyrite Formation Produces a Large Fe Isotope Fractionation”
Authors: Guilbaud Romain , Butler Ian B. , Ellam Rob M.
Published: February 2012

Czaja
et al
. assert that Guilbaud
et al
. claim that “the geologic record of Fe isotope fractionation can be explained by abiological precipitation of pyrite.” At no point did we suggest this. We reported a previously underestimated Fe isotope fractionation that contributes to the sedimentary Fe isotope signal.
Have We “Met the Enemy”?
American Anthrax
Fear, Crime, and the Investigation of the Nation's Deadliest Bioterror Attack

by Jeanne Guillemin

Times Books, New York, 2011. 336 pp. $27, C$31. ISBN 9780805091045.
Authors: Relman David A.
Published: February 2012

Guillemin describes the aftermath of and investigation into the fall 2001 anthrax letters.
Natural Variation in a Chloride Channel Subunit Confers Avermectin Resistance in
C. elegans
Authors: Ghosh Rajarshi , Andersen Erik C. , Shapiro Joshua A. , Gerke Justin P. , Kruglyak Leonid
Published: February 2012

Natural Resistance

Avermectins are the most widely used class of anthelmintic drugs, both as pesticides and as treatments for nematode-borne diseases, with the evolution of resistance presenting a major global health and agricultural problem.

Ghosh
et al.

(p.
574
; see the Perspective by
Wolstenholme
) observed resistance to avermectin in the model nematode
Caenorhabditis elegans
that varies among isolates. This resistance is caused by a naturally occurring four–amino acid deletion in the ligand-binding domain of a glutamate-gated chloride channel. This variant also conferred resistance to the avermectin-producing ubiquitous soil bacterium,
Streptomyces zitilis
. Many nematodes spend at least part of their life cycle in soil, which may explain avermectin resistance among nematode species.
Growth of Western Australian Corals in the Anthropocene
Authors: Cooper Timothy F. , O’Leary Rebecca A. , Lough Janice M.
Published: February 2012

Heat or Acid?

The question of how tropical coral reefs will respond to increasing atmospheric greenhouse gas concentrations and concomitant climate change is widely debated. Model predictions and laboratory experiments suggest that decreasing carbonate saturation and decreasing pH may reduce calcification in carbonate-depositing organisms, including corals, yet field data are sparse, and recent declines in coral growth rates have been variously attributed to thermal stress or ocean acidification.

Cooper
et al.

(p.
593
) demonstrate that there has been no large-scale decline in calcification rates of massive
Porites
on coral reefs along the Indian Ocean coast of Western Australia. Instead, coral growth has increased significantly in the past 110 years, particularly at high latitudes. Thus, coral calcification appears to increase as ocean waters warm, but—at excessive temperatures—coral bleaching and reduced ocean carbonate saturation may lead to growth declines as observed on the Great Barrier Reef.
Nanoscopy in a Living Mouse Brain
Authors: Berning Sebastian , Willig Katrin I. , Steffens Heinz , Dibaj Payam , Hell Stefan W.
Published: February 2012

Super high-resolution microscopy resolves neuron dynamics in the cerebral cortex of a living mouse.
To Stop or Not to Stop?
Authors: Volkow Nora D. , Baler Ruben D.
Published: February 2012

Does chronic drug abuse cause brain abnormalities, or do they develop before the onset of dependence?
The Global Knowledge Society
Authors: Fedoroff Nina V.
Published: February 2012

Knowledge societies rest on a foundation of educational and research excellence. The Internet, advances in communications technology, and the rapidly expanding global fiber optic network are necessary, but not sufficient. It takes people to train, to educate, to collaborate, and to innovate. Building the global knowledge society is the theme of the 2012 American Association for the Advancement of Science (AAAS) Annual Meeting in Vancouver (16 to 22 February). Bringing together scientists and educators from more than 50 nations, the meeting tackles global issues and new ways of building connections between developed and developing nations.
Technology Is Turning U.S. Oil Around But Not the World's
Authors: Kerr Richard A.
Published: February 2012

The high price of oil is driving technological innovation that has reversed the decline in U.S. oil production, but the world will increasingly depend on OPEC and “non-oil” oil.
Antituberculosis IgG Antibodies as a Marker of Active Mycobacterium tuberculosis Disease
Authors: Welch Ryan J. , Lawless Kathleen M. , Litwin Christine M.
Published: February 2012

Anti-Mycobacterium tuberculosisIgG antibodies may aid in the diagnosis of activeM. tuberculosisdisease. We studied whether anti-M. tuberculosisIgG antibodies are elevated in activeM. tuberculosisdisease and assessed factors contributing to false-positive and -negative results. A retrospective study of 2,150 individuals tested by the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay was conducted at the University of Utah, ARUP Laboratories, November 2008 to December 2010. All samples were tested with the InBios Active TbDetectantituberculosis (anti-TB) IgG antibody assay. Of 1,044 patients with a positive QFT-GIT, 59 (5.7%) were positive forM. tuberculosisantibodies. Fourteen of 1,106 (1.3%) with a negative or indeterminate QFT-GIT were positive forM. tuberculosisantibodies.M. tuberculosisantibody tests were positive in 61.5% with confirmed activeM. tuberculosisdisease and other mycobacterial infections. Over half of the false-negativeM. tuberculosisantibody tests occurred in patients ≥90 years of age. False positives were seen in 12.9% of autoimmune patients. The odds ratio of being positive by the QFT-GIT and the InBios TB IgG assay increased with confirmedM. tuberculosisdisease or highly suspectedM. tuberculosisdisease and was 86.7 (95% confidence interval [CI], 34.4 to 218.5) in these two groups compared to patients negative by both tests. Although anti-M. tuberculosisantibodies can be detected in patients with activeM. tuberculosisdisease, caution should be used with patients where immunoglobulin levels may be decreased or patients with autoantibodies.
First Evaluation of an Improved Assay for Molecular Genetic Detection of Tuberculosis as Well as Rifampin and Isoniazid Resistances
Authors: Crudu Valeriu , Stratan Ecaterina , Romancenco Elena , Allerheiligen Vera , Hillemann Andreas , Moraru Nicolae
Published: February 2012

The commercially available line probe assay MTBDRplus 2.0 (Hain Lifescience, Nehren, Germany) was evaluated for its ability to detect
Mycobacterium tuberculosis
complex (MTBC) and mutations conferring resistance to rifampin (RMP) and isoniazid (INH) directly in smear-negative and smear-positive pulmonary clinical specimens under routine laboratory conditions. A total of 348 samples originating from Moldova, a high-incidence country for tuberculosis (TB), were investigated. Two hundred fifty-seven (73.9%) were smear negative, 12 samples were excluded, and 81 (23.3%) were smear positive. Two DNA extraction methods were applied. Compared to culture and clinical data as the reference standard (adapted from Vadwai V et al., J. Clin. Microbiol.
49:
2540–2545, 2011), overall sensitivity and specificity were 87.6 and 99.2%, respectively. One hundred four of the 257 smear-negative samples turned out to be culture positive, and 20 were MTBC culture negative but were positive based on clinical symptoms. The combined sensitivity and specificity in the subgroup of smear-negative samples were calculated to be 79.8 and 99.2%, respectively. MTBDRplus 2.0 detected RMP and INH resistance with sensitivity and specificity of 94.3 and 96.0%, respectively. In conclusion, the MTBDRplus 2.0 assay is a rapid and highly sensitive test for the detection of
M. tuberculosis
strains from smear-positive and -negative clinical specimens and provides additional information on RMP and INH resistance status, which can easily be included in routine laboratory work flow.
Detection of Galactomannan in Bronchoalveolar Lavage Fluid Samples of Patients at Risk for Invasive Pulmonary Aspergillosis: Analytical and Clinical Validity
Authors: D'Haese Jorien , Theunissen Koen , Vermeulen Edith , Schoemans Hélène , De Vlieger Greet , Lammertijn Liesbet , Meersseman Philippe , Meersseman Wouter , Lagrou Katrien , Maertens Johan
Published: February 2012

Invasive pulmonary aspergillosis (IPA) is frequent and often fatal in immunosuppressed patients. Timely diagnosis of IPA improves survival but is difficult to make. We examined the analytical and clinical validity of galactomannan (GM) testing of bronchoalveolar lavage (BAL) fluid in diagnosing IPA in a mixed population by retrospectively reviewing records of 251 consecutive at-risk patients for whom BAL fluid GM testing was ordered. The performance of the enzyme immunoassay was evaluated by using a range of index cutoffs to define positivity. Three samples were associated with proven IPA, 56 were associated with probable IPA, 63 were associated with possible invasive fungal disease (IFD), and 129 were associated with no IFD. Using a BAL fluid GM index of ≥0.8 (optimal optical density [OD] index cutoff identified by a receiver operating characteristic curve), the sensitivity in diagnosing proven and probable IPA was 86.4%, and the specificity was 90.7%. At this cutoff, positive and negative predictive values were 81% and 93.6%, respectively. However, an OD index value of ≥3.0 corresponded to a 100% specificity, thus ruling the disease in, irrespective of the pretest probability. Conversely, an OD index cutoff of <0.5 corresponded to a high sensitivity, virtually always ruling the disease out. For all values in between, the posttest probability of IPA depends largely on the prevalence of disease in the at-risk population and the likelihood ratio of the OD index value. Detection of GM in BAL fluid samples of patients at risk of IPA has an excellent diagnostic accuracy provided results are interpreted in parallel with clinico-radiological findings and pretest probabilities.
Quantitative Real-Time PCR for Detection of Acinetobacter baumannii Colonization in the Hospital Environment
Authors: McConnell Michael J. , Pérez-Ordóñez Ana , Pérez-Romero Pilar , Valencia Raquel , Lepe José Antonio , Vázquez-Barba Isabel , Pachón Jerónimo
Published: February 2012

A real-time PCR assay was developed for detecting the presence of
Acinetobacter baumannii
on hospital equipment and compared to conventional bacterial culture using 100 hospital environmental samples. The real-time PCR detected contaminated surfaces in 4 h with high sensitivity (100%) compared to conventional culture. Thirty-eight percent of samples were positive by real-time PCR and negative by bacterial culture (false positives), possibly indicating the widespread presence of bacterial DNA that is not associated with viable bacteria.
Human Papillomavirus (HPV) DNA Triage of Women with Atypical Squamous Cells of Undetermined Significance with cobas 4800 HPV and Hybrid Capture 2 Tests for Detection of High-Grade Lesions of the Uterine Cervix
Authors: Lapierre Simon Grandjean , Sauthier Philippe , Mayrand Marie-Hélène , Dufresne Simon , Petignat Patrick , Provencher Diane , Drouin Pierre , Gauthier Philippe , Dupuis Marie-Josée , Michon Bertrand , Ouellet Stéphan , Hadjeres Rachid , Ferenczy Alex , Franco Eduardo L. , Coutlée François
Published: February 2012

The triage of women with high-risk (HR) human papillomavirus (HPV)-positive smears for atypical squamous cells of undetermined significance (ASC-US) to colposcopy is now an integrated option in clinical guidelines. The performance of cobas 4800 HPV and that of Hybrid Capture 2 (HC2) for HR HPV DNA detection in cervical samples in PreservCyt were compared in 396 women referred to colposcopy for ASC-US. Of these, 316 did not have cervical intraepithelial neoplasia (CIN), 47 had CIN1, 29 had CIN2 or CIN3 (CIN2+), and 4 had CIN of unknown grade. HR HPV was detected in 129 (32.6%) and 149 (37.6%) samples with HC2 and cobas 4800 HPV, respectively (
P
= 0.15). The clinical sensitivities and specificities for detecting CIN2+ were 89.7% (95% confidence interval [CI], 72.8 to 97.2%) and 66.7% (95% CI, 61.7 to 71.3%) with cobas 4800 HPV and 93.1% (95% CI, 77.0 to 99.2%) and 72.2% (95% CI 67.4 to 76.5%) with HC2. The performance of cobas 4800 HPV was similar to that of HC2 for identifying women with ASC-US who would benefit the most from colposcopy.
Evaluation of New Biomarker Genes for Differentiating Haemophilus influenzae from Haemophilus haemolyticus
Authors: Theodore M. Jordan , Anderson Raydel D. , Wang Xin , Katz Lee S. , Vuong Jeni T. , Bell Melissa E. , Juni Billie A. , Lowther Sara A. , Lynfield Ruth , MacNeil Jessica R. , Mayer Leonard W.
Published: February 2012

PCR detecting the protein D (
hpd
) and fuculose kinase (
fucK
) genes showed high sensitivity and specificity for identifying
Haemophilus influenzae
and differentiating it from
H. haemolyticus
. Phylogenetic analysis using the 16S rRNA gene demonstrated two distinct groups for
H. influenzae
and
H. haemolyticus
.
A Replication-Incompetent PB2-Knockout Influenza A Virus Vaccine Vector
Authors: Victor Sylvia T. , Watanabe Shinji , Katsura Hiroaki , Ozawa Makoto , Kawaoka Yoshihiro
Published: February 2012

Vaccination is the primary form of protection from influenza virus infection. We recently developed a replication-incompetent PB2-knockout (PB2-KO) influenza virus that possesses a reporter gene (the green fluorescent protein gene) in the coding region of the PB2 segment. This virus replicated to high titers in PB2-expressing, but not unmodified, cells, suggesting its potential safety and feasibility as a vaccine. Here, we tested its efficacy in a murine model. The levels of IgG and IgA antibodies against influenza virus in sera, nasal washes, and bronchoalveolar lavage fluids of mice immunized with the PB2-KO virus were higher than those induced by a conventional inactivated vaccine. All PB2-KO virus-immunized mice survived challenges with lethal doses of influenza virus. Moreover, importantly, mice immunized with the PB2-KO virus produced antibodies against the reporter protein, suggesting that the PB2-KO virus has potential as a multivalent vaccine to combat infection with not only influenza virus but also other pathogens.
Annexin A2 Is Involved in the Formation of Hepatitis C Virus Replication Complex on the Lipid Raft
Authors: Saxena Vikas , Lai Chao-Kuen , Chao Ti-Chun , Jeng King-Song , Lai Michael M. C.
Published: February 2012

The hepatitis C virus (HCV) RNA replicates in hepatic cells by forming a replication complex on the lipid raft (detergent-resistant membrane [DRM]). Replication complex formation requires various viral nonstructural (NS) proteins as well as host cellular proteins. In our previous study (C. K. Lai, K. S. Jeng, K. Machida, and M. M. Lai, J. Virol. 82:8838–8848, 2008), we found that a cellular protein, annexin A2 (Anxa2), interacts with NS3/NS4A. Since NS3/NS4A is a membranous protein and Anxa2 is known as a lipid raft-associated scaffold protein, we postulate that Anxa2 helps in the formation of the HCV replication complex on the lipid raft. Further studies showed that Anxa2 was localized at the HCV-induced membranous web and interacted with NS4B, NS5A, and NS5B and colocalized with them in the perinuclear region. The silencing of Anxa2 decreased the formation of membranous web-like structures and viral RNA replication. Subcellular fractionation and bimolecular fluorescence complementation analysis revealed that Anxa2 was partially associated with HCV at the lipid raft enriched with phosphatidylinositol-4-phosphate (PI4P) and caveolin-2. Further, the overexpression of Anxa2 in HCV-nonsusceptible HEK293 cells caused the enrichment of HCV NS proteins in the DRM fraction and increased the colony-forming ability of the HCV replicon. Since Anxa2 is known to induce the formation of the lipid raft microdomain, we propose that Anxa2 recruits HCV NS proteins and enriches them on the lipid raft to form the HCV replication complex.
Amino Acid Substitutions at Positions 122 and 145 of Hepatitis B Virus Surface Antigen (HBsAg) Determine the Antigenicity and Immunogenicity of HBsAg and InfluenceIn VivoHBsAg Clearance
Authors: Wu Chunchen , Deng Wanyu , Deng Liu , Cao Liang , Qin Bo , Li Songxia , Wang Yun , Pei Rongjuan , Yang Dongliang , Lu Mengji , Chen Xinwen
Published: February 2012

A variety of amino acid substitutions, such as K122I and G145R, have been identified around or within the a determinant of hepatitis B surface antigen (HBsAg), impair HBsAg secretion and antibody binding, and may be responsible for immune escape in patients. In this study, we examined how different substitutions at amino acid positions 122 and 145 of HBsAg influence HBsAg expression, secretion, and recognition by anti-HBs antibodies. The results showed that the hydrophobicity, the presence of the phenyl group, and the charges in the side chain of the amino acid residues at position 145 reduced HBsAg secretion and impaired reactivity with anti-HBs antibodies. Only the substitution K122I at position 122 affected HBsAg secretion and recognition by anti-HBs antibodies. Genetic immunization in mice demonstrated that the priming of anti-HBs antibody response was strongly impaired by the substitutions K122I, G145R, and others, like G145I, G145W, and G145E. Mice preimmunized with wild-type HBsAg (wtHBsAg) or variant HBsAg (vtHBsAg) were challenged by hydrodynamic injection (HI) with a replication-competent hepatitis B virus (HBV) clone. HBsAg persisted in peripheral blood for at least 3 days after HI in mice preimmunized with vtHBsAg but was undetectable in mice preimmunized with wtHBsAg, indicating that vtHBsAgs fail to induce proper immune responses for efficient HBsAg clearance. In conclusion, the biochemical properties of amino acid residues at positions 122 and 145 of HBsAg have a major effect on antigenicity and immunogenicity. In addition, the presence of proper anti-HBs antibodies is indispensable for the neutralization and clearance of HBsAg during HBV infection.
The Cellular Antiviral Protein APOBEC3G Interacts with HIV-1 Reverse Transcriptase and Inhibits Its Function during Viral Replication
Authors: Wang Xiaoxia , Ao Zhujun , Chen Liyu , Kobinger Gary , Peng Jinyu , Yao Xiaojian
Published: February 2012

The cytidine deaminase APOBEC3G (A3G) exerts a multifaceted antiviral effect against HIV-1 infection. First, A3G was shown to be able to terminate HIV infection by deaminating the cytosine residues to uracil in the minus strand of the viral DNA during reverse transcription. Also, a number of studies have indicated that A3G inhibits HIV-1 reverse transcription by a non-editing-mediated mechanism. However, the mechanism by which A3G directly disrupts HIV-1 reverse transcription is not fully understood. In the present study, by using a cell-based coimmunoprecipitation (Co-IP) assay, we detected the direct interaction between A3G and HIV-1 reverse transcriptase (RT) in produced viruses and in the cotransfected cells. The data also suggested that their interaction did not require viral genomic RNA bridging or other viral proteins. Additionally, a deletion analysis showed that the RT-binding region in A3G was located between amino acids 65 and 132. Overexpression of the RT-binding polypeptide A3G
65-132
was able to disrupt the interaction between wild-type A3G and RT, which consequently attenuated the anti-HIV effect of A3G on reverse transcription. Overall, this paper provides evidence for the physical and functional interaction between A3G and HIV-1 RT and demonstrates that this interaction plays an important role in the action of A3G against HIV-1 reverse transcription.
HIV-1 Capsid-Targeting Domain of Cleavage and Polyadenylation Specificity Factor 6
Authors: Lee KyeongEun , Mulky Alok , Yuen Wendy , Martin Thomas D. , Meyerson Nicholas R. , Choi Laura , Yu Hyun , Sawyer Sara L. , KewalRamani Vineet N.
Published: February 2012

The antiviral factor CPSF6-358 restricts human immunodeficiency virus type 1 (HIV-1) infection through an interaction with capsid (CA), preventing virus nuclear entry and integration. HIV-1 acquires resistance to CPSF6-358 through an N74D mutation of CA that impairs binding of the antiviral factor. Here we examined the determinants within CPSF6-358 that are necessary for CA-specific interaction. Residues 314 to 322 include amino acids that are essential for CPSF6-358 restriction of HIV-1. Fusion of CPSF6 residues 301 to 358 to rhesus TRIM5α is also sufficient to restrict wild-type but not N74D HIV-1. Restriction is lost if CPSF6 residues in the amino acid 314 to 322 interaction motif are mutated. Examination of the CA targeting motif in CPSF6-358 did not reveal evidence of positive selection. Given the sensitivity of different primate lentiviruses to CPSF6-358 and apparent conservation of this interaction, our data suggest that CPSF6-358-mediated targeting of HIV-1 could provide a broadly effective antiviral strategy.
Bovine Type III Interferon Significantly Delays and Reduces the Severity of Foot-and-Mouth Disease in Cattle
Authors: Perez-Martin Eva , Weiss Marcelo , Diaz-San Segundo Fayna , Pacheco Juan M. , Arzt Jonathan , Grubman Marvin J. , de los Santos Teresa
Published: February 2012

Interferons (IFNs) are the first line of defense against viral infections. Although type I and II IFNs have proven effective to inhibit foot-and-mouth disease virus (FMDV) replication in swine, a similar approach had only limited efficacy in cattle. Recently, a new family of IFNs, type III IFN or IFN-λ, has been identified in human, mouse, chicken, and swine. We have identified bovine IFN-λ3 (boIFN-λ3), also known as interleukin 28B (IL-28B), and demonstrated that expression of this molecule using a recombinant replication-defective human adenovirus type 5 (Ad5) vector, Ad5-boIFN-λ3, exhibited antiviral activity against FMDV in bovine cell culture. Furthermore, inoculation of cattle with Ad5-boIFN-λ3 induced systemic antiviral activity and upregulation of IFN-stimulated gene expression in the upper respiratory airways and skin. In the present study, we demonstrated that disease could be delayed for at least 6 days when cattle were inoculated with Ad5-boIFN-λ3 and challenged 24 h later by intradermolingual inoculation with FMDV. Furthermore, the delay in the appearance of disease was significantly prolonged when treated cattle were challenged by aerosolization of FMDV, using a method that resembles the natural route of infection. No clinical signs of FMD, viremia, or viral shedding in nasal swabs was found in the Ad5-boIFN-λ3-treated animals for at least 9 days postchallenge. Our results indicate that boIFN-λ3 plays a critical role in the innate immune response of cattle against FMDV. To this end, this work represents the most successful biotherapeutic strategy so far tested to control FMDV in cattle.
Herpes Simplex Virus 1 Tegument Protein US11 Downmodulates the RLR Signaling Pathway via Direct Interaction with RIG-I and MDA-5
Authors: Xing Junji , Wang Shuai , Lin Rongtuan , Mossman Karen L. , Zheng Chunfu
Published: February 2012

The interferon (IFN)-mediated antiviral response is a major defense of the host immune system. In order to complete their life cycle, viruses must modulate host IFN-mediated immune responses. Herpes simplex virus 1 (HSV-1) is a large DNA virus containing more than 80 genes, many of which encode proteins that are involved in virus-host interactions and show immune modulatory capabilities. In this study, we demonstrate that the US11 protein, an RNA binding tegument protein of HSV-1, is a novel antagonist of the beta IFN (IFN-β) pathway. US11 significantly inhibited Sendai virus (SeV)-induced IFN-β production, and its double-stranded RNA (dsRNA) binding domain was indispensable for this inhibition activity. Additionally, wild-type HSV-1 coinfection showed stronger inhibition than US11 mutant HSV-1 in SeV-induced IFN-β production. Coimmunoprecipitation analysis demonstrated that the US11 protein in HSV-1-infected cells interacts with endogenous RIG-I and MDA-5 through its C-terminal RNA-binding domain, which was RNA independent. Expression of US11 in both transfected and HSV-1-infected cells interferes with the interaction between MAVS and RIG-I or MDA-5. Finally, US11 dampens SeV-mediated IRF3 activation. Taken together, the combined data indicate that HSV-1 US11 binds to RIG-I and MDA-5 and inhibits their downstream signaling pathway, preventing the production of IFN-β, which may contribute to the pathogenesis of HSV-1 infection.
Overreliance on the Hexon Gene, Leading to Misclassification of Human Adenoviruses
Authors: Singh Gurdeep , Robinson Christopher M. , Dehghan Shoaleh , Schmidt Timothy , Seto Donald , Jones Morris S. , Dyer David W. , Chodosh James
Published: February 2012

The genome of human adenovirus (HAdV) D30 was sequenced in depth. Sequence assembly and analysis revealed two distinct viral sequences with identical hexon genes, which were the same as the one previously reported for HAdV-D30. However, one of the two viruses was found to be a recombinant of HAdV-D29. Exclusive reliance on serum neutralization can lead to mischaracterization of adenoviruses and miss coinfections. Whole-genome sequencing remains the gold standard for proper classification of HAdVs.
Quantification and Analysis of Thymidine Kinase Expression from Acyclovir-Resistant G-String Insertion and Deletion Mutants in Herpes Simplex Virus-Infected Cells
Authors: Pan Dongli , Coen Donald M.
Published: February 2012

To be clinically relevant, drug-resistant mutants must both evade drug action and retain pathogenicity. Many acyclovir-resistant herpes simplex virus mutants from clinical isolates have one or two base insertions (G8 and G9) or one base deletion (G6) in a homopolymeric run of seven guanines (G string) in the gene encoding thymidine kinase (TK). Nevertheless, G8 and G9 mutants express detectable TK activity and can reactivate from latency in mice, a pathogenicity marker. On the basis of studies using cell-free systems, ribosomal frameshifting can explain this ability to express TK. To investigate frameshifting in infected cells, we constructed viruses that express epitope-tagged versions of wild-type and mutant TKs. We measured TK activity by plaque autoradiography and expression of frameshifted and unframeshifted TK polypeptides using a very sensitive immunoprecipitation-Western blotting method. The G6 mutant expressed ∼0.01% of wild-type levels of TK polypeptide. For the G9 mutant, consistent with previous results, much TK expression could be ascribed to reversion. For the G8 mutant, from these assays and pulse-labeling studies, we determined the ratio of synthesis of frameshifted to unframeshifted polypeptides to be 1:100. The effects of stop codons before or after the G string argue that frameshifting can initiate within the first six guanines. However, frameshifting efficiency was altered by stop codons downstream of the string in the 0 frame. The G8 mutant expressed only 0.1% of the wild-type level of full-length TK, considerably lower than estimated previously. Thus, remarkably low levels of TK are sufficient for reactivation from latency in mice.
The Genome Sequence of the Emerging Common Midwife Toad Virus Identifies an Evolutionary Intermediate within Ranaviruses
Authors: Mavian Carla , López-Bueno Alberto , Balseiro Ana , Casais Rosa , Alcamí Antonio , Alejo Alí
Published: February 2012

Worldwide amphibian population declines have been ascribed to global warming, increasing pollution levels, and other factors directly related to human activities. These factors may additionally be favoring the emergence of novel pathogens. In this report, we have determined the complete genome sequence of the emerging common midwife toad ranavirus (CMTV), which has caused fatal disease in several amphibian species across Europe. Phylogenetic and gene content analyses of the first complete genomic sequence from a ranavirus isolated in Europe show that CMTV is an amphibian-like ranavirus (ALRV). However, the CMTV genome structure is novel and represents an intermediate evolutionary stage between the two previously described ALRV groups. We find that CMTV clusters with several other ranaviruses isolated from different hosts and locations which might also be included in this novel ranavirus group. This work sheds light on the phylogenetic relationships within this complex group of emerging, disease-causing viruses.
Residue Y161 of Influenza Virus Hemagglutinin Is Involved in Viral Recognition of Sialylated Complexes from Different Hosts
Authors: Wang Minxiu , Tscherne Donna M. , McCullough Christopher , Caffrey Michael , García-Sastre Adolfo , Rong Lijun
Published: February 2012

Influenza A virus glycoprotein hemagglutinin (HA) binds to host cell surface sialic acid (SA)-terminated sugars in glycoproteins to initiate viral entry. It is thought that avian influenza viruses preferentially bind to
N
-acetylneuraminic acid α3 (NeuAcα3) sugars, while human influenza viruses exhibit a preference for NeuAcα6-containing sugars. Thus, species-specific SA(s) is one of the determinants in viral host tropism. The SA binding pocket of the HA1 subunit has been extensively studied, and a number of residues important for receptor binding have been identified. In this study, we examined the potential roles of seven highly conserved HA surface-located amino acid residues in receptor binding and viral entry using an H5 subtype. Among them, mutant Y161A showed cell-type-dependent viral entry without obvious defects in HA protein expression or viral incorporation. This mutant also displayed dramatically different ability in agglutinating different animal erythrocytes. Oligosaccharide binding analysis showed that substituting alanine at Y161 of HA changed the SA binding preference from NeuAc to
N
-glycolylneuraminic acid (NeuGc). Rescued mutant Y161A viruses demonstrated a 5- to 10-fold growth defect, but they were robust in viral replication and plaque forming ability. Our results demonstrate that Y161 is a critical residue involved in recognition of different SA species. This residue may play a role in determining influenza virus host tropism.
Recent developments in syntheses of the post-secodine indole alkaloids. Part III: Rearranged alkaloid types
Authors: Hájíček Josef
Published: February 2012

The third part of a planned review on developments in the field of total and formal total synthesis of the post-secodine indole alkaloids focuses on types of rearranged alkaloids, i.e. on the skeletons with altered connectivities next to the indol(e)ine moiety, especially with a new bond to N-1. It reviews the synthesis of melodane, goniomitine, chippiine/dippinine, lirofoline and tronocarpine alkaloids, as well as alkaloids of secoschizozygane/vallesamidine, schizozygane and isoschizozygane type. It covers the literature from approximately 1991 up to May 2011. A review with 115 references.
Diabetes and raised blood glucose as risk factors for future suicide: cohort study of 1 234 927 Korean men and women: Table 1
Authors: David Batty G , Kivimaki Mika , Park Il Su , Jee Sun Ha
Published: February 2012

Background

A diagnosis of diabetes has been shown to be a risk factor for suicide in selected studies. The link between blood glucose and future suicide has yet to be examined.

Aim

To examine if diabetes and blood glucose level are associated with a raised risk of suicide.

Methods

The Korean Cancer Prevention Study is a cohort of 1 329 525 individuals (482 618 women) aged 30–95 years at baseline. A fasting serum specimen was assayed for blood glucose, and diabetes status was categorised into five groups based on existing definitions. Study members were followed for mortality experience over 14 years.

Results

There were 472 suicide deaths (389 in men and 83 in women) during the follow-up. In men, there was a ‘J’-shaped diabetes–suicide death relation. Thus, while the highest suicide rates were apparent in those with type 2 diabetes and there was an incremental fall in suicide risk with decreasing blood glucose level, an inflection was seen in the low-normal group. Similar results were apparent in women, although there was no raised risk in the lowest blood glucose group.

Conclusion

In the present cohort, diabetes (both existing and study detected) but not raised blood glucose was a risk factor for completed suicide.
Hoffmann reflex is increased after 14 days of daily repeated Achilles tendon vibration for the soleus but not for the gastrocnemii muscles
Authors: Lapole Thomas , Pérot Chantal
Published: February 2012

In a previous study, Achilles tendon vibrations were enough to improve the triceps surae (TS) activation capacities and also to slightly increase TS Hoffmann reflex (H-reflex) obtained by summing up soleus (Sol) and gastrocnemii (GM and GL) EMGs. The purpose of the present study was to analyze separately Sol and GM or GL reflexes to account for different effects of the vibrations on the reflex excitability of the slow soleus and of the gastrocnemii muscles. A control group (n = 13) and a vibration group (n = 16) were tested in pre-test and post-test conditions. The Achilles tendon vibration program consisted of 1 h of daily vibration (frequency: 50 Hz) applied during 14 days. Maximal Sol, GM and GL H-reflexes, and M-waves were recorded, and their Hmax/Mmax ratios gave the index of reflex excitability. After the vibration protocol, only Sol Hmax/Mmax was enhanced (p < 0.001). The enhanced Sol reflex excitability after vibration is in favor of a decrease in the pre-synaptic inhibition due to the repeated vibrations and the high solicitation of the reflex pathway. Those results of a short period of vibration applied at rest may be limited to the soleus because of its high density in muscle spindles and slow motor units, both structures being very sensitive to vibrations.
Detraining-induced alterations in metabolic and fitness markers after a multicomponent exercise-training program in older men
Authors: Ratel Sébastien , Gryson Céline , Rance Mélanie , Penando Stéphane , Bonhomme Cécile , Le Ruyet Pascale , Duclos Martine , Boirie Yves , Walrand Stéphane
Published: February 2012

The aim of the present study was to investigate the effects of a 8-week detraining period after a 16-week multicomponent training program including strength and aerobic exercises on the main determinants of aerobic fitness, muscle strength and some metabolic markers in 24 older subjects (60.2 ± 3.0 years). The oxygen uptake at the second ventilatory threshold (VO2VT2) and at the end of exercise (VO2max), maximum voluntary contraction force (MVC) of knee extensors and some metabolic indexes, i.e., insulin sensitivity, blood lipid profile, inflammatory cytokines, and endothelial function, were evaluated at baseline and after the training and detraining periods. The training program induced significant improvements in VO2VT2 (16%, p < 0.05), VO2max (14%, p < 0.05), MVC (6.5%, p < 0.05), insulin sensitivity (16%, p < 0.05), and endothelial function (p < 0.05) but induced no significant change in lipid profile and inflammatory cytokines. Interestingly, VO2VT2 and VO2max (mL·min–1·kg–1) scores remained significantly above pretraining values after the 8-week detraining period. However, the detraining period reversed MVC values, the insulin sensitivity and endothelial function to baseline levels. To conclude, the 8-week detraining partially reversed the major components of aerobic fitness but totally abolished the gains in muscle strength and some metabolic indexes after a 16-week multicomponent training program in older men. Taken as a whole, the results of this study emphasize the importance of exercise prescriptions for older subjects and the need not to interrupt exercise-training over a prolonged period.
Activation of mTOR signalling in young and old human skeletal muscle in response to combined resistance exercise and whey protein ingestion
Authors: Farnfield Michelle M. , Breen Leigh , Carey Kate A. , Garnham Andrew , Cameron-Smith David
Published: February 2012

Purpose: To investigate the impact of whey protein ingestion and resistance exercise training on the phosphorylation of mRNA translational signalling proteins in the skeletal muscle of young and old men. Methods: Sixteen healthy young (aged 18–25 years) and 15 healthy older men (aged 60–75 years) completed 12 weeks of resistance exercise and were randomly assigned to consume a whey protein (WPI) or placebo drink after each session. Muscle biopsies were collected before and 2 h after an acute exercise bout at the beginning and the end of training. Results: All subjects significantly increased strength after following strength training. Phosphorylation of mTOR was significantly greater in the WPI groups compared with placebo for both younger and older subjects. Phosphorylation of p70S6K, eIF4G, and 4EBP1 was greater for older subjects consuming WPI. Phosphorylation of rpS6, eIF4G, and 4EBP1 tended to increase in the younger subjects that had consumed WPI. Post-training, younger subjects demonstrated a similar pattern of mTOR phosphorylation as seen pre-training. In contrast, the initial heightened phosphorylation of mTOR, p70S6K, rpS6, and eIF4G in older muscle to combined resistance exercise and WPI ingestion became less pronounced after repeated training sessions. Conclusions: In the untrained state, resistance exercise coupled with WPI increases the phosphorylation of proteins involved in mRNA translation compared with exercise alone. Post-training, WPI- and exercise-induced protein phosphorylation was reduced in older men, but not in younger men. Thus, strategies to induce hypertrophy should utilize protein and resistance training concurrently. Further investigations should delineate interventions that will maintain sensitivity to anabolic stimuli in older populations.
The effects of acute alcohol consumption and eccentric muscle damage on neuromuscular function
Authors: Barnes Matthew. J. , Mündel Toby , Stannard Stephen R.
Published: February 2012

Voluntary and electrically stimulated muscular performance was examined to identify the effects of acute alcohol consumption on neuromuscular function in the presence and absence of exercise-induced muscle damage (EIMD). After initial neuromuscular performance measures were made, 12 subjects completed a bout of eccentric exercise (EX) using the quadriceps muscles of 1 leg while the remaining 11 subjects did not exercise (NX). Subjects then consumed either an alcoholic beverage containing 1 g·kg–1body weight (ALC) or a nonalcoholic beverage (OJ). On another occasion the contralateral leg of both groups was tested and those in the EX group performed an equivalent bout of eccentric exercise after which the other beverage was consumed. Measurements of neuromuscular function were made pre-exercise and 36 and 60 h post-beverage consumption. Creatine kinase (CK) was measured pre-exercise and at 12, 36, and 60 h. Significantly greater (p < 0.01) decrements in maximal voluntary isometric contraction were observed with EX ALC at 36 and 60 h compared with EX OJ, and no change was seen in the NX group. Significant decreases in voluntary activation were observed at 36 h (p = 0.003) and 60 h (p = 0.01) with EX ALC only. Elevations in CK were observed at all posteccentric exercise time points (all p < 0.05) under both EX OJ and ALC. No change in electromyography or low-frequency fatigue was observed under either treatment in either group. These results suggest that decreased neural drive appears to contribute to alcohol’s effect on the magnitude of EIMD-related decrements in voluntary force generation.
Effects of prior heavy-intensity exercise on oxygen uptake and muscle deoxygenation kinetics of a subsequent heavy-intensity cycling and knee-extension exercise
Authors: Cleland Sarah Margaret , Murias Juan Manuel , Kowalchuk John Michael , Paterson Donald Hugh
Published: February 2012

This study examined the effects of prior heavy-intensity exercise on the adjustment of pulmonary oxygen uptake (VO2p) and muscle deoxygenation Δ[HHb] during the transition to subsequent heavy-intensity cycling (CE) or knee-extension (KE) exercise. Nine young adults (aged 24 ± 5 years) performed 4 repetitions of repeated bouts of heavy-intensity exercise separated by light-intensity CE and KE, which included 6 min of baseline exercise, a 6-min step of heavy-intensity exercise (H1), 6-min recovery, and a 6-min step of heavy-intensity exercise (H2). Exercise was performed at 50 r·min–1 or contractions per minute per leg. Oxygen uptake (VO2) mean response time was ∼20% faster (p < 0.05) during H2 compared with H1 in both modalities. Phase 2 time constants (τ) were not different between heavy bouts of CE (H1, 29.6 ± 6.5 s; H2, 28.0 ± 4.6 s) or KE exercise (H1, 31.6 ± 6.7 s; H2, 29.8 ± 5.6 s). The VO2 slow component amplitude was lower (p < 0.05) in H2 in both modalities (CE, 0.19 ± 0.06 L·min–1; KE, 0.12 ± 0.07 L·min–1) compared with H1 (CE, 0.29 ± 0.09 L·min–1; KE, 0.18 ± 0.07 L·min–1), with the contribution of the slow component to the total VO2 response reduced (p < 0.05) in H2 during both exercise modes. The effective τHHb was similar between bouts for CE (H1, 18.2 ± 3.0 s; H2, 18.0 ± 3.6 s) and KE exercise (H1, 26.0 ± 7.0 s; H2, 24.0 ± 5.8 s). The ΔHHb slow component was reduced during H2 in both CE and KE (p < 0.05). In conclusion, phase 2 VO2p was unchanged with priming exercise; however, a faster mean response time of VO2p during the heavy-intensity exercise preceded by a priming heavy-intensity exercise was attributed to a smaller slow component and reduced muscle deoxygenation indicative of improved muscle O2 delivery during the second bout of exercise.
Combined effects of aerobic exercise and high-carbohydrate meal on plasma acylated ghrelin and levels of hunger
Authors: Becker Geórgia Franco , Macedo Rodrigo Cauduro Oliveira , Cunha Giovani dos Santos , Martins Jocelito Bijoldo , Laitano Orlando , Reischak-Oliveira Alvaro
Published: February 2012

The present study investigated the effect of an aerobic exercise bout associated with a high-carbohydrate (CHO) meal on plasma levels of acylated ghrelin and hunger sensation. Eight healthy males performed an exercise (ET) and a control (CT) trial. In ET, participants performed a 60-min cycling exercise (∼70% of maximal oxygen uptake) after consuming a high-CHO meal. In the CT, participants remained at rest throughout the whole period after consuming the high-CHO meal. Hunger sensation was assessed and blood samples were taken to determine the levels of acylated ghrelin, glucose, insulin, total cholesterol (TC), and triglycerides (TG). There was suppression of hunger after consuming the meal in ET and CT (p = 0.028 and p = 0.011, respectively). Hunger increased in CT in the period correspondent to the exercise session (p = 0.017) and remained suppressed in the ET. The area under the curve for acylated ghrelin showed that its levels were lower in the ET compared with CT in the period of the exercise plus the immediate period (1 h) postexercise (60.7 vs. 96.75 pg·mL–1·2 h–1, respectively; p = 0.04). Inverse correlations between acylated ghrelin levels and insulin, TC, and TG levels at different time points were observed. In conclusion, these findings suggest that 1 bout of aerobic exercise maintains the meal-induced suppression of hunger. The mechanism underlying this effect may involve the exercise-induced suppression of acylated ghrelin. These results implicate that the combination of a high-CHO meal and aerobic exercise may effectively improve appetite control and body weight management.
EFFECTS OF MODEL PARAMETERS IN THERMODYNAMICS OF THE PNJL MODEL
Authors: FRIESEN A. V. , KALINOVSKY YU. L. , TONEEV V. D.
Published: February 2012

The thermodynamic behavior of the two-flavor (Nf = 2) three-color (Nc = 3) Polyakov-loop-extended Nambu–Jona-Lasinio (PNJL) model at the finite chemical potential is investigated. New lattice gluon data for gluon thermodynamics are used defining the effective potential within polynomial and logarithmic forms of its approximation. We study the effects of using different sets of data and different forms of the potential on thermodynamic properties of hot and dense matter. It is found that the PNJL thermodynamics depends stronger on the form of the effective potential than on the used lattice data set. Particular attention is paid to the phase diagram in the (T, μ) plane.
THERMAL AND NON-UNIFORM MAGNETIC QUANTUM DISCORD IN THE TWO-QUBIT HEISENBERG XXZ MODEL
Authors: XIAO RUI-HUA , GUO ZHAN-YING , FANG JIAN-XING
Published: February 2012

The thermal quantum discord (QD) is investigated in the two-qubit anisotropic Heisenberg XXZ model under an external non-uniform magnetic field along the Z-axis. We obtain the analytical expressions of the thermal QD and thermal entanglement measured by concurrence (C). It shows that for any temperature T, QD gradually decreases with the increase of non-uniform magnetic field |b|, in some regions where C increases while QD decreases. It is also found that thermal quantum discord does not vanish at finite temperatures, but concurrence vanishes completely at a critical temperature. It is shown that for a higher value of JZ, the system has a stronger QD. There is a critical magnetic field B c , which increases with the increasing b. QD decay monotonically (for B < B c ) when temperature T increases, or initially increases to some peaks and then decrease (for B > B c ).
DISPERSIVE OPTICAL PARAMETERS OFNi(100) CRYSTAL AND THERMALLY EVAPORATED NICKEL FILMS
Authors: ATUCHIN V. V. , GRIGORIEVA T. I. , POKROVSKY L. D. , KRUCHININ V. N. , LYCHAGIN D. V. , RAMANA C. V.
Published: February 2012

Structure and optical characteristics of nickel ( Ni ) single crystal (100) surface and thin films have been evaluated by the combined use of reflection high-energy electron diffraction (RHEED) and spectroscopic ellipsometry (SE). Nickel films were fabricated by thermal evaporation at 100°C while Ni single crystal was grown by vertical Bridgman method. RHEED analysis indicates that the grown Ni films were polycrystalline. Spectral dependencies of refractive index n(λ) and extinction coefficient k(λ) determined in the spectral range λ ~ 250–1030 nm indicate the typical behavior of metals. The refractive index of Ni films is found to be slightly higher compared to that of Ni (100) crystal.
SYNCHRONIZATION IN BIOCHEMICAL SUBSTANCE EXCHANGE BETWEEN TWO CELLS
Authors: MIHAILOVIĆ DRAGUTIN T. , BALAŽ IGOR
Published: February 2012

In this paper, Mihailović et al. [Mod. Phys. Lett. B25 (2011) 2407–2417] introduce a simplified model of cell communication in a form of coupled difference logistic equations. Then we investigated stability of exchange of signaling molecules under variability of internal and external parameters. However, we have not touched questions about synchronization and effect of noise on biochemical substance exchange between cells. In this paper, we consider synchronization in intercellular exchange in dependence of environmental and cell intrinsic parameters by analyzing the largest Lyapunov exponent, cross sample entropy and bifurcation maps.