bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling Rehydration/Rehydroxylation Mass‐Gain Curves from Davenport Ceramics
Authors: Bowen Patrick K. , Drelich Jaroslaw , Scarlett Timothy J.
Published: January 2013

Rehydroxylation ceramic dating, a new technique that has shown promise as an archeometric breakthrough, was applied to XIX‐century samples of Davenport ceramics from Parowan, Utah in the United States. The samples were dried at 500°C to remove both physically and chemically bonded water and then exposed to a 20% relative humidity air to record the progression of rehydration/rehydroxylation over a period of 40 d. Both time1/4 and time1/n analyses were applied to the experimental mass gain versus time results in an attempt to find the most appropriate treatment for the data. The time1/4 analysis yielded poor reproducibility and nonideal fitting results to the Stage II mass gain, in which water reacts with meta‐clays. Application of the time1/n model, where “n” is the rehydroxylation exponent, improved the apparent linearity of Stage II mass gain in small samples. However, the time1/n treatment still provided a poor fit to data from larger specimens, indicating that some secondary effects related to sample size and water transport may exist. To examine the effects of porosity and macrostructure on rehydration/rehydroxylation processes, a pulverized sample of the same material was analyzed, resulting in improved sample‐to‐sample agreement in time1/n irrespective of mass variations. These findings have implications on the application of rehydroxylation ceramic dating.
Ethical, Legal, and Social Issues in the Translation of Genomics Into Health Care
Authors: Badzek Laurie , Henaghan Mark , Turner Martha , Monsen Rita
Published: January 2013

Purpose: The rapid continuous feed of new information from scientific discoveries related to the human genome makes translation and incorporation of information into the clinical setting difficult and creates ethical, legal, and social challenges for providers. This article overviews some of the legal and ethical foundations that guide our response to current complex issues in health care associated with the impact of scientific discoveries related to the human genome.

Organizing Construct: Overlapping ethical, legal, and social implications impact nurses and other healthcare professionals as they seek to identify and translate into practice important information related to new genomic scientific knowledge.

Methods: Ethical and legal foundations such as professional codes, human dignity, and human rights provide the framework for understanding highly complex genomic issues. Ethical, legal, and social concerns of the health provider in the translation of genomic knowledge into practice including minimizing harms, maximizing benefits, transparency, confidentiality, and informed consent are described. Additionally, nursing professional competencies related to ethical, legal, and social issues in the translation of genomics into health care are discussed.

Conclusions: Ethical, legal, and social considerations in new genomic discovery necessitate that healthcare professionals have knowledge and competence to respond to complex genomic issues and provide appropriate information and care to patients, families, and communities.

Clinical Relevance: Understanding the ethical, legal, and social issues in the translation of genomic information into practice is essential to provide patients, families, and communities with competent, safe, effective health care.
Long‐term tooth loss in periodontally compromised but treated patients according to the type of prosthodontic treatment. A retrospective study
Authors: Müller S. , Eickholz P. , Reitmeir P. , Eger T.
Published: January 2013

If prosthodontic treatment is considered after periodontal therapy, the questions arise i) does prosthodontic treatment affect the treatment outcome of the dentition in general and ii) which type of prosthesis is related to best treatment outcome of abutment teeth? Our goal was to compare long‐term tooth loss after comprehensive periodontal therapy in patients with or without prosthodontic treatment. Ninety patients' charts with a total of 1937 teeth who had received comprehensive periodontal treatment 5–17 years ago by the same periodontist were retrospectively evaluated. Sixty‐five patients received fixed dental prostheses (FDP; n = 29) and/or removable partial dentures anchored with clips (RPDC; n = 25) or double crowns (RPDD; n = 25). Twenty‐five patients were also periodontally compromised but treated without prosthodontic treatment and served as a control group. A total of 317 teeth and 70 abutment teeth were lost during 9·7 ± 4·1 years of observation. Thereof, 273 teeth and 48 abutment teeth were lost due to periodontal reasons. Mean tooth loss amounted to 1·2 ± 1·5 (controls) and 4·4 ± 3·4 (partial dentures). Abutment tooth loss was 0·4 ± 1·1 (FDP), 1·0 ± 1·2 (RPDC) and 1·3 ± 1·0 (RPDD). Poisson regressions identified prosthodontic treatment, age, socio‐economic status, diabetes mellitus, mean initial bone loss and aggressive periodontitis as factors significantly contributing to tooth loss. Age, diabetes and non‐compliance contributed to abutment tooth loss. Not considering biomechanical factors, patients with prosthodontic reconstructions under long‐term supportive periodontal therapy were at higher risk for further tooth loss than patients without prostheses. Not only the type of partial denture but also the patient‐related risk factors were associated with abutment tooth loss.
Influence of resveratrol on oxidative stress resistance and life span in Caenorhabditis elegans
Authors: Chen Wei , Rezaizadehnajafi Leila , Wink Michael
Published: January 2013

Objectives

Resveratrol (3,5,4′-trihydroxy-trans-stilbene), a polyphenol from red wine, has been reported to be beneficial in cases of ageing-related cardiovascular and neurodegenerative diseases owing to its property to reduce oxidative stress. Previous studies on the longevity promoting effect of resveratrol have been partly inconclusive, therefore we set out to investigate whether resveratrol at least promoted longevity in Caenorhabditis elegans under acute oxidative stress conditions.

Methods

C. elegans was cultured under standard conditions with or without resveratrol. After exposure to juglone-induced acute oxidative stress, the survival rate and hsp-16.2::GFP expression were measured. The influence of resveratrol on life span was recorded also under oxidative stress induced by high glucose concentrations in the growth medium.

Key findings

No extension of the normal life span of C. elegans was observed either in liquid or solid growth media containing different concentrations of resveratrol. However, resveratrol alleviated juglone-induced lethal oxidative stress, and significantly prolonged the life span of C. elegans under conditions of acute oxidative damage and oxidative stress caused by high concentrations of glucose.

Conclusions

Resveratrol, as an antioxidant, ameliorated oxidative stress in vivo but did not extend the life span of C. elegans under normal conditions. However, resveratrol did extend life span under conditions of oxidative stress.
Neurological and intellectual disabilities among adolescents within a custodial institution in South‐West Nigeria
Authors: Atilola O. , Omigbodun O. , Bella‐Awusah T. , Lagunju I. , Igbeneghu P.
Published: January 2013

Accessible summary

The findings from this study reveal a significantly higher prevalence of neurological and intellectual disabilities as well as epilepsy among adolescents residing in a social welfare/juvenile justice institution in Nigeria compared with a cohort of school going adolescents. Epilepsy and neurological deficits was particularly prevalent among adolescents admitted into the institution as victims of neglect compared with those brought in as offenders.

Stigmatization of and social prejudices against children with neuro‐psychiatric disabilities and epilepsy as well as lack of support for their caregivers in Nigeria was speculated as the key factor promoting neglect of such children. The speculation was based on the findings from this study and extant literature. Consequently, efforts should be geared towards disengaging childhood epilepsy and neuro‐psychiatric disabilities from myth and prejudices and to provide needed support for caregivers of children with such conditions. Meanwhile curative and restorative neuro‐psychiatric services should be part of the service package for children within social welfare/juvenile justice institutions in Nigeria.

A total of 67 adolescents from a juvenile remand home were matched with 67 other adolescents by age and gender, with a view to determine the prevalence and spectrum of neurological and intellectual disabilities. Intelligence quotient (IQ) was estimated using an adapted version of the Slosson's Intelligence Test and a full neurological evaluation was carried out. The mean IQ score for the remand home participants was significantly lower than the controls (77 ± 11 vs. 99 ± 14; t = 1.6, P = 0.001). Almost half (46.7%) of the participants in the remand home had intellectual disability of varying degrees, including borderline intellectual functioning, compared with only two (3.3%) of the comparison group (P < 0.001). Epilepsy and neurological deficits were significantly more prevalent among the remand home group, particularly those admitted as victims of neglect, compared with the comparison group (P ≤ 0.02). These findings and recent literature were used to speculate the possible underlying factors. Policy implications for child social welfare in Nigeria were suggested.
Masitinib reverses doxorubicin resistance in canine lymphoid cells by inhibiting the function of P‐glycoprotein
Authors: Zandvliet M. , Teske E. , Chapuis T. , Fink‐Gremmels J. , Schrickx J. A.
Published: January 2013

Overexpression of ABC‐transporters including Pgp, MRP1, and BCRP has been associated with multidrug resistance (MDR) in both human and canine oncology. Therapeutic interventions to reverse MDR are limited, but include multidrug protocols and the temporary concomitant use of inhibitors of ABC‐transporters. Recently, the use of tyrosine kinase inhibitors has been proposed to overcome MDR in human oncology. One of the tyrosine kinase inhibitors, masitinib, is licensed for veterinary use in the treatment of canine mast cell tumors. Therefore, this study aimed to assess the potential of masitinib to revert MDR in canine malignant lymphoma using an in vitro model with canine lymphoid cell lines. Masitinib had a mild antiproliferative effect on lymphoid cells, inhibited Pgp function at concentrations equal to or exceeding 1 μm and was able to reverse doxorubicin resistance. The current findings provide the rationale for a combined use of masitinib with doxorubicin in the treatment of dogs with doxorubicin‐resistant malignant lymphoma but await confirmation in clinical trials.
Effects of Hypo‐ and Hyperthyroidism on Proliferation, Angiogenesis, Apoptosis and Expression of COX‐2 in the Corpus Luteum of Female Rats
Authors: Silva JF , Ocarino NM , Vieira ALS , Nascimento EF , Serakides R
Published: January 2013

Contents

Although thyroid dysfunction occurs frequently in humans and some animal species, the mechanisms by which hypo‐ and hyperthyroidism affect the corpus luteum have not been thoroughly elucidated. This study evaluated the levels of proliferative activity, angiogenesis, apoptosis and expression of cyclooxygenase‐2 in the corpus luteum of female rats with thyroid dysfunction. These processes may be important in understanding the reproductive changes caused by thyroid dysfunction. A total of 18 adult female rats were divided into three groups (control, hypothyroid and hyperthyroid) with six animals per group. Three months after treatment to induce thyroid dysfunction, the rats were euthanized in the dioestrus phase. The ovaries were collected and immunohistochemically analysed for expression of the cell proliferation marker CDC‐47, vascular endothelial growth factor (VEGF), VEGF receptor Flk‐1 and cyclooxygenase‐2 (COX‐2). Apoptosis was evaluated using the TUNEL assay. Hypothyroidism reduced the intensity and area of COX‐2 expression in the corpus luteum (p < 0.05), while hyperthyroidism did not alter COX‐2 expression in the dioestrus phase. Hypothyroidism significantly reduced the expression of CDC‐47 in endothelial cells and pericytes in the corpus luteum, whereas hyperthyroidism did not induce a detectable change in CDC‐47 expression (p > 0.05). Hypothyroidism reduced the level of apoptosis in luteal cells (p < 0.05) and increased VEGF expression in the corpus luteum. In contrast, hyperthyroidism increased the level of apoptosis in the corpus luteum (p < 0.05). In conclusion, thyroid dysfunction differentially affects the levels of proliferative activity, angiogenesis and apoptosis and COX‐2 expression in the corpus luteum of female rats.
Effect of Inter-Defect Interaction on Tensile Fatigue Behavior of a Single-Walled Carbon Nanotube With Stone–Wales Defects
Authors: Zhou Z. R. , Liao K.
Published: January 2013

A refined molecular life prediction scheme for single-walled carbon nanotubes (SWCNTs), taking into consideration C–C bond rotation and preexisting strain under mechanical loads, is proposed. The time-dependent fracture behavior of 12 different cases of zigzag (18,0) SWCNT, each embedded with either a single Stone–Wales (SW) defect of different types or two interacting or noninteracting defects, is studied under axially applied tensile load. It is shown that the patterns of atomistic crack propagation and fatigue lives of SWCNTs are influenced by the type and orientation of the SW defect(s), inter-defect distance, as well as the magnitude of externally applied stress. For SWCNTs with two SW defects, if the inter-defect distance is within the so called indifference length, defect-defect interaction does exist, and it has pronounced effects on diminishing the lives of the nanotubes. Also, the defect-defect interaction is stronger at shorter inter-defect distance, resulting in shorter fatigue lives.
Mechanics of Random Discontinuous Long-Fiber Thermoplastics—Part I: Generation and Characterization of Initial Geometry
Authors: Abd El-Rahman Ahmed I. , Tucker Charles L.
Published: January 2013

The deformation mechanics of dry networks of large-aspect-ratio fibers with random orientation controls the processing of long-fiber thermoplastics (LFTs) and greatly affects the mechanical properties of the final composites. Here, we generate initial geometries of fiber networks in a cubic unit cell with a fiber aspect ratio of l/d = 100 and fully periodic boundary conditions for later numerical simulation. The irreversible random sequential adsorption (RSA) process is first used to generate a quasi-random structure due to the excluded-volume requirements. In order to investigate the nonequilibrium character of the RSA, a second method, which is similar to the mechanical contraction method (MCM) (Williams and Philipse, 2003, “Random Packings of Spheres and Spherocylinders Simulated by Mechanical Contraction,” Phys. Rev. E, 67, pp. 1–9) and based on a simplified Metropolis Monte Carlo (MC) simulation is then developed to produce quasi-equilibrium fiber geometries. The RSA packing results (ϕ ≈ 4.423% when using a fiber aspect ratio of 100) are in good agreement with the maximum unforced random packing limits (Evans and Gibson, 1986, “Prediction of the Maximum Packing Fraction Achievable in Randomly Oriented Short-Fibre Composites,” Compos. Sci. Technol., 25, pp. 149–162). The fiber structures were characterized by several distribution functions, including pair-spatial and pair-orientation distributions, based on either the center-to-center distance or the shortest distance between the particles. The results show that the structures generated by the RSA have an easily-detectable long-range spatial correlation but very little orientational correlation. In contrast, the quasi-equilibrium structures have reduced spatial correlation but increased short-range orientational correlation.
Carbon Nanotubes: Present and Future Commercial Applications
Authors: De Volder Michael F. L. , Tawfick Sameh H. , Baughman Ray H. , Hart A. John
Published: January 2013

Exploiting Carbon Nanotubes

Individual defect-free carbon nanotubes can have exceptional mechanical, thermal, and electrical properties, which has led to speculation on a wide range of potential applications. However, challenges in growing large quantities of pure nanotubes, and for some applications tubes of only one type, have limited their widespread use.

De Volder
et al.

(p.
535
) review the efforts that have been made to scale up carbon nanotube production and discuss a number of applications where enhanced materials have made use of carbon nanotubes.
Emergent Sensing of Complex Environments by Mobile Animal Groups
Authors: Berdahl Andrew , Torney Colin J. , Ioannou Christos C. , Faria Jolyon J. , Couzin Iain D.
Published: January 2013

The Power of the Collective

Sensing the environment is generally considered to require significant cognitive sampling and comparison, not to mention time. However, species that do not necessarily have the cognitive ability, or the time, have also proven to be quite adept at sensing and evaluating their environment.

Berdahl
et al.

(p.
574
) show that in shiners, a species of schooling fish, mere attraction to, and movement toward, neighboring individuals allows the group to track preferred darkness in a variable-light environment.
Nanoscale Nuclear Magnetic Resonance with a Nitrogen-Vacancy Spin Sensor
Authors: Mamin H. J. , Kim M. , Sherwood M. H. , Rettner C. T. , Ohno K. , Awschalom D. D. , Rugar D.
Published: January 2013

Nanoscale NMR with Diamond Defects

Although nuclear magnetic resonance (NMR) methods can be used for spatial imaging, the low sensitivity of detectors limits the minimum sample size. Two reports now describe the use of near-surface nitrogen-vacancy (NV) defects in diamond for detecting nanotesla magnetic fields from very small volumes of material (see the Perspective by

Hemmer

). The spin of the defect can be detected by changes in its fluorescence, which allows proton NMR of organic samples only a few nanometers thick on the diamond surface.

Mamin
et al.

(p.
557
) used a combination of electron spin echoes and pulsed NMR manipulation of the proton spins to detect the very weak fields.

Staudacher
et al.

(p.
561
) measured statistical polarization of a population of about 10
4
spins near the NV center with a dynamical decoupling method.
Carbon Cycle Makeover
Authors: Canfield Donald E. , Kump Lee R.
Published: January 2013

Enhanced levels of anaerobic respiration processes may explain oscillations in Earth's carbon cycle.

[Also see Research Article by

Schrag
et al.

]
Measuring Mass in Seconds
Authors: Debs John E. , Robins Nicholas P. , Close John D.
Published: January 2013

An atom interferometer and an optical frequency comb measure the Compton frequency of a cesium atom, creating a "clock" that weighs atoms.

[Also see Report by

Lan
et al.

]
Toward Molecular-Scale MRI
Authors: Hemmer Philip
Published: January 2013

Use of a diamond-based nanomagnetometer reduces the detection volume of MRI to the level of individual protein molecules.

[Also see Reports by

Mamin
et al.

and

Staudacher
et al.

]
Cancer Cell Phenotypes, in Fifty Shades of Grey
Authors: Marusyk Andriy , Polyak Kornelia
Published: January 2013

Intratumor heterogeneity is a major obstacle in successfully eradicating tumors.

[Also see Research Article by

Kreso
et al.

]
Undernutrition—Looking Within for Answers
Authors: Relman David A.
Published: January 2013

A link between the gut microbiota and conditions of undernutrition point to possible therapeutic interventions.

[Also see Research Article by

Smith
et al.

]
Graphene and Brain Projects Win European Jackpot
Authors: Kupferschmidt Kai
Published: January 2013

Winners in Flagship project may get up to €1 billion each, hope to unite neuroscience field and explore graphene applications.
If Budget Woes Continue, Panel Says DOE Should Shut Last U.S. Collider
Authors: Cho Adrian
Published: January 2013

The Relativistic Heavy Ion Collider would be sacrificed for new facility.
Brain Studies Stymied by Statistics
Authors: Underwood Emily
Published: January 2013

Researchers' quest to determine patient awareness leads to vigorous debate.
A Worm Vaccine, Coming at a Snail's Pace
Authors: Kupferschmidt Kai
Published: January 2013

The long struggle to develop a schistosomiasis vaccine badly needs new money.
World's Biggest Health Care System Goes Under the Knife
Authors: Hvistendahl Mara
Published: January 2013

Ambitious reforms of the Chinese medical system aim to expand infrastructure, cover the poor, and combat chronic diseases.
IgG4 Detection of Echinococcus granulosus Paramyosin Is a Useful Diagnostic Test for Human Hydatidosis
Authors: Moghadam Zohreh Kazemi , Ghaffarifar Fatemeh , Khalilpour Akbar , Abdul Aziz Farhanah , Saadatnia Geita , Noordin Rahmah
Published: January 2013

Hydatidosis is a public health problem in many parts of the world, and improvement in diagnosis of the disease is still being pursued. Protoscoleces ofEchinococcus granulosuswere isolated from hydatid cysts collected from naturally infected sheep slaughtered in abattoirs in Iran. Sonicated extract of protoscolex was subjected to two-dimensional gel electrophoresis and Western blot analysis. Primary antibodies were from serum samples from 130 hydatidosis patients, 38 individuals infected with other parasitic infections, and 30 healthy people, whereas peroxidase (HRP)-conjugated anti-human IgG and IgG4 were used as secondary antibodies. The recombinant form of the identified protein was produced and tested for its sensitivity and specificity for the detection of human hydatidosis. An antigenic band of ∼60 kDa was found to be sensitive (82%) and specific (100%) for the detection of hydatidosis when probed with anti-human IgG4-HRP, while the sensitivity and specificity were 33 and 100%, respectively, with anti-human IgG-HRP. By mass spectrometry, the band was identified as protoscolex tegument paramyosin. The sensitivity and specificity of full-length paramyosin-recombinant protein in IgG4 blots were found to be 86 and 98%, respectively. In conclusion, IgG4 detection ofEchinococcus granulosusparamyosin was found to be useful for the diagnosis of human hydatidosis.
Testing for Antireticulin Antibodies in Patients with Celiac Disease Is Obsolete: a Review of Recommendations for Serologic Screening and the Literature
Authors: Nandiwada Sarada L. , Tebo Anne E.
Published: January 2013

Celiac disease (CD) is an autoimmune disorder that occurs in genetically susceptible individuals of all ages and is triggered by immune response to gluten and related proteins. The disease is characterized by the presence of HLA-DQ2 and/or -DQ8 haplotypes, diverse clinical manifestations, gluten-sensitive enteropathy, and production of several autoantibodies of which endomysial, tissue transglutaminase, and deamidated gliadin peptide antibodies are considered specific. Although antireticulin antibodies (ARA) have historically been used in the evaluation of CD, these assays lack optimal sensitivities and specificities for routine diagnostic use. This minireview highlights the advances in CD-specific serologic testing and the rationale for eliminating ARA from CD evaluation consistent with recommendations for diagnosis.
A Single Electroporation Delivery of a DNA Vaccine Containing the Hemagglutinin Gene of Asian H5N1 Avian Influenza Virus Generated a Protective Antibody Response in Chickens against a North American Virus Strain
Authors: Ogunremi Oladele , Pasick John , Kobinger Gary P. , Hannaman Drew , Berhane Yohannes , Clavijo Alfonso , van Drunen Littel-van den Hurk Sylvia
Published: January 2013

Protection against the avian influenza (AI) H5N1 virus is suspected to be mainly conferred by the presence of antibodies directed against the hemagglutinin (HA) protein of the virus. A single electroporation delivery of 100 or 250 μg of a DNA vaccine construct, pCAG-HA, carrying the HA gene of strain A/Hanoi/30408/2005 (H5N1), in chickens led to the development of anti-HA antibody response in 16 of 17 immunized birds, as measured by a hemagglutination inhibition (HI) test, competitive enzyme-linked immunosorbent assay (cELISA), and an indirect ELISA. Birds vaccinated by electroporation (
n
= 11) were protected from experimental AI challenge with strain A/chicken/Pennsylvania/1370/1/1983 (H5N2) as judged by low viral load, absence of clinical symptoms, and absence of mortality (
n
= 11). In contrast, only two out of 10 birds vaccinated with the same vaccine dose (100 or 250 μg) but without electroporation developed antibodies. These birds showed high viral loads and significant morbidity and mortality after the challenge. Seroconversion was reduced in birds electroporated with a low vaccine dose (10 μg), but the antibody-positive birds were protected against virus challenge. Nonelectroporation delivery of a low-dose vaccine did not result in seroconversion, and the birds were as susceptible as those in the control groups that received the control pCAG vector. Electroporation delivery of the DNA vaccine led to enhanced antibody responses and to protection against the AI virus challenge. The HI test, cELISA, or indirect ELISA for anti-H5 antibodies might serve as a good predictor of the potency and efficacy of a DNA immunization strategy against AI in chickens.
Assessment of a Protein Cocktail-Based Skin Test for Bovine Tuberculosis in a Double-Blind Field Test in Cattle
Authors: Xin Ting , Jia Hong , Ding Jiabo , Li Pingjun , Yang Hongjun , Hou Shaohua , Yuan Weifeng , Guo Xiaoyu , Wang Haichun , Liang Qianqian , Li Ming , Wang Bin , Zhu Hongfei
Published: January 2013

Bovine tuberculosis (bTB) is a worldwide zoonosis caused mainly by
Mycobacterium bovis.
The traditional diagnostic method used often is the tuberculin skin test, which uses bovine purified protein derivatives (PPD-B). However, it is difficult to maintain uniformity of PPD-B from batch to batch, and it shares common antigens with nonpathogenic environmental mycobacteria. To overcome these problems,
M. bovis
-specific antigens that showed good T cell stimulation, such as CFP-10, ESAT-6, Rv3615c, etc., have been used in the skin test, but there have been no large-scale clinical studies on these antigens. In this study, two combinations (CFP-10/ESAT-6/TB10.4 protein cocktail and CFP-10/ESAT-6/Rv3872/MPT63 protein cocktail) were developed and used as stimuli in the skin test. Cattle were double-blind tested to assess the efficiency of the protein cocktail-based skin tests. The results showed that the CFP-10/ESAT-6/TB10.4 protein cocktail-based skin test can differentiate TB-infected cattle from
Mycobacterium avium
-infected ones and that it shows a high degree of agreement with the traditional tuberculin skin test (κ = 0.8536) and gamma interferon (IFN-γ) release assay (κ = 0.8154). Compared to the tuberculin skin test, the relative sensitivity and relative specificity of the CFP-10/ESAT-6/TB10.4-based skin test were 87% and 97%, respectively., The relative sensitivity and relative specificity of the CFP-10/ESAT-6/TB10.4-based skin test were 93% and 92%, respectively, on comparison with the IFN-γ release assay. The correlation between the increases in skin thickness observed after the inoculation of stimuli was high (PPD-B versus CFP-10/ESAT-6/TB10.4, Spearman
r
of 0.8435). The correlation between the optical density at 450 nm (OD
450
) obtained after blood stimulation with PPD-B and the increase in skin thickness observed after inoculation of the CFP-10/ESAT-6/TB10.4 protein cocktail was high (Spearman
r
= 0.7335). Therefore, the CFP-10/ESAT-6/TB10.4-based skin test responses correlate to traditional measures of bovine TB evaluation, including skin test and gamma interferon release assay.
Natural Killer Cells and Antifungal Host Response
Authors: Schmidt Stanislaw , Zimmermann Stefanie-Yvonne , Tramsen Lars , Koehl Ulrike , Lehrnbecher Thomas
Published: January 2013

As a result of improved experimental methodologies and a better understanding of the immune system, there is increasing insight into the antifungal activity of natural killer (NK) cells. Murine and human NK cells are able to damage fungi of different genera and speciesin vitro, and they exert both direct and indirect antifungal activity through cytotoxic molecules such as perforin and through cytokines and interferons, respectively. On the other hand, recent data suggest that fungi exhibit immunosuppressive effects on NK cells. Whereas clearin vivodata are lacking in humans, the importance of NK cells in the host response against fungi has been demonstrated in animal models. Further knowledge of the interaction of NK cells with fungi might help to better understand the pathogenesis of invasive fungal infections and to improve treatment strategies.
Long-Term Immunogenicity of the Pandemic Influenza A/H1N1 2009 Vaccine among Health Care Workers: Influence of Prior Seasonal Influenza Vaccination
Authors: Song Joon Young , Cheong Hee Jin , Seo Yu Bin , Kim In Seon , Noh Ji Yun , Choi Won Suk , Lee Jacob , Jeong Hye Won , Kee Sae Yoon , Kim Woo Joo
Published: January 2013

Health care workers (HCWs) are at great risk of influenza infection and transmission. Vaccination for seasonal influenza is routinely recommended, but this strategy should be reconsidered in a pandemic situation. Between October 2009 and September 2010, a multicenter study was conducted to assess the long-term immunogenicity of the A/H1N1 2009 monovalent influenza vaccine among HCWs compared to non-health care workers (NHCWs). The influence of prior seasonal influenza vaccination was also assessed with respect to the immunogenicity of pandemic H1N1 influenza vaccine. Serum hemagglutinin inhibition titers were determined prevaccination and then at 1, 6, and 10 months after vaccination. Of the 360 enrolled HCW subjects, 289 participated in the study up to 10 months after H1N1 monovalent influenza vaccination, while 60 of 65 NHCW subjects were followed up. Seroprotection rates, seroconversion rates, and geometric mean titer (GMT) ratios fulfilled the European Union's licensure criteria for influenza A/California/7/2009 (H1N1) at 1 month after vaccination in both the HCWs and NHCWs, without any significant difference. At 6 months after vaccination, the seroprotection rate was more significantly lowered among the NHCWs than among the HCWs (
P
< 0.01). Overall, postvaccination (1, 6, and 10 months after vaccination) GMTs for A/California/7/2009 (H1N1) were significantly lower among the seasonal influenza vaccine recipients than among the nonrecipients (
P
< 0.05). In conclusion, HCWs should be encouraged to receive an annual influenza vaccination, considering the risk of repeated exposure. However, prior reception of seasonal influenza vaccine showed a negative influence on immunogenicity for the pandemic A/H1N1 2009 influenza vaccine.
Deciphering Genomic Virulence Traits of a Staphylococcus epidermidis Strain Causing Native-Valve Endocarditis
Authors: Fournier Pierre-Edouard , Gouriet Frédérique , Gimenez Grégory , Robert Catherine , Raoult Didier
Published: January 2013

We applied real-time genome sequencing to a
Staphylococcus epidermidis
strain that caused native-aortic-valve endocarditis in a 26-year-old patient. The 2.5-Mb genome from strain CSUR P278 exhibited a unique sequence type among
S. epidermidis
strains and contained 32 genes previously considered virulence genes in this species.
CHROMagar Yersinia, a New Chromogenic Agar for Screening of Potentially Pathogenic Yersinia enterocolitica Isolates in Stools
Authors: Renaud Nicolas , Lecci Laetitia , Courcol René J. , Simonet Michel , Gaillot Olivier
Published: January 2013

CHROMagar Yersinia (CAY) is a new chromogenic medium for the presumptive detection of virulent
Yersinia enterocolitica
in stools. Based on a comparative analysis of 1,494 consecutive stools from hospitalized patients, CAY was found to be just as sensitive as the reference medium (cefsulodin-irgasan-novobiocin agar) but was significantly more specific and had a very low false-positive rate. CAY reduces the workload (and thus costs) for stool analysis and can therefore be recommended for routine laboratory use.
Development of a Novel PCR Restriction Analysis of thehsp65Gene as a Rapid Method To Screen for the Mycobacterium tuberculosis Complex and Nontuberculous Mycobacteria in High-Burden Countries
Authors: Varma-Basil Mandira , Garima Kushal , Pathak Rakesh , Dwivedi Shailendra Kumar Dhar , Narang Anshika , Bhatnagar Anuj , Bose Mridula
Published: January 2013

The limitations of conventional methods of identification ofMycobacterium tuberculosishave led to the development of several nucleic acid amplification techniques which have the advantage of being rapid, sensitive, and specific. However, their expense or the need for technical expertise makes it difficult to use them in regions in which tuberculosis is endemic. A novel PCR restriction analysis (PRA) of thehsp65gene was therefore developed for rapid screening of clinical isolates to identifyMycobacteriumspp. The restriction enzymes NruI and BamHI were selected to obtain a limited number of restriction patterns to further differentiate betweenMycobacterium tuberculosiscomplex (MTBC) and nontuberculous mycobacteria (NTM). Three hundred ten isolates from clinical specimens and 24 reference strains were tested. The assay correctly identified 295 of the 310 culture isolates as MTBC, while the remaining 15 isolates were identified as NTM. Of the isolates tested, 135 MTBC strains and all 15 NTM were also confirmed by PRA using Sau96I and CfoI. Thirty-eight randomly selected MTBC strains and all 15 NTM were further confirmed by sequencing. The NruI/BamHI PRA was simple, as it did not require any elaborate analyses. It was cost-effective, rapid, highly sensitive, and specific and did not require technical expertise. The assay can, therefore, be used as a simple screening test not only to detectMycobacteriumspp. but also to differentiate MTBC from NTM in peripheral laboratories with minimal availability of funds.
Detection and Genetic Diversity of Porcine Group A Rotaviruses in Historic (2004) and Recent (2011 and 2012) Swine Fecal Samples in Ohio: Predominance of the G9P[13] Genotype in Nursing Piglets
Authors: Amimo J. O. , Vlasova A. N. , Saif L. J.
Published: January 2013

Epidemiological surveillance of porcine group A rotavirus (RVA) strains was conducted in five swine herds in Ohio using historical (2004) and recent (2011 to 2012) fecal samples. Of the 371 samples examined, 9.4% (35/371) were positive for RVA. The RVA detection rates increased from 5.9% in 2004 and 8.5% in 2011 to 13.8% in 2012. A total of 23 positive samples were analyzed for RVA G and P genotypes. The dominant G-P combination was G9P[13] found in 60.9% of positive samples. The other combinations were G9P[7] (8.7%), G4P[13] (8.7%), G11P[13] (4.3%), and G11P[7] (4.3%). Sequence analysis of partial VP7 genes of selected strains revealed that the G4 strains were closely related to one another (95%) and, to a lesser extent, to human (82 to 84%) and porcine (84 to 86%) G4 strains. The G11 strains detected shared identical VP7 gene sequences (100%) and were closely related to human (85 to 86%) and other porcine (83%) G11 strains. The G9 strains identified were closely related to one another and to human and other porcine strains (96 to 97%, 89 to 91%, and 89 to 91% nucleotide identities, respectively). The VP4 gene analysis revealed that P[7] strains were closely related to each other and to P[7] strains isolated from porcine, bovine, and panda samples (91 to 99%, 92 to 99% and 92 to 99%, respectively). The P[13] strains showed a higher diversity among themselves and with other porcine P[13] strains, ranging from 83% to 99% and from 82 to 97%, respectively. Our results demonstrate broad genetic heterogeneity of the RVA strains and suggest the possibility of genetic reassortment between different RVA genotypes within these farms.
Epstein-Barr Virus Deubiquitinase Downregulates TRAF6-Mediated NF-κB Signaling during Productive Replication
Authors: Saito Shinichi , Murata Takayuki , Kanda Teru , Isomura Hiroki , Narita Yohei , Sugimoto Atsuko , Kawashima Daisuke , Tsurumi Tatsuya
Published: January 2013

Epstein-Barr virus (EBV), a human oncogenic herpesvirus that establishes a lifelong latent infection in the host, occasionally enters lytic infection to produce progeny viruses. The EBV oncogene latent membrane protein 1 (LMP1), which is expressed in both latent and lytic infection, constitutively activates the canonical NF-κB (p65) pathway. Such LMP1-mediated NF-κB activation is necessary for proliferation of latently infected cells and inhibition of viral lytic cycle progression. Actually, canonical NF-κB target gene expression was suppressed upon the onset of lytic infection. TRAF6, which is activated by conjugation of polyubiquitin chains, associates with LMP1 to mediate NF-κB signal transduction. We have found that EBV-encoded BPLF1 interacts with and deubiquitinates TRAF6 to inhibit NF-κB signaling during lytic infection. HEK293 cells with BPLF1-deficient recombinant EBV exhibited poor viral DNA replication compared with the wild type. Furthermore, exogenous expression of BPLF1 or p65 knockdown in cells restored DNA replication of BPLF1-deficient viruses, indicating that EBV BPLF1 deubiquitinates TRAF6 to inhibit NF-κB signal transduction, leading to promotion of viral lytic DNA replication.
Antigenicity and Immunogenicity of Transmitted/Founder, Consensus, and Chronic Envelope Glycoproteins of Human Immunodeficiency Virus Type 1
Authors: Liao Hua-Xin , Tsao Chun-Yen , Alam S. Munir , Muldoon Mark , Vandergrift Nathan , Ma Ben-Jiang , Lu Xiaozhi , Sutherland Laura L. , Scearce Richard M. , Bowman Cindy , Parks Robert , Chen Haiyan , Blinn Julie H. , Lapedes Alan , Watson Sydeaka , Xia Shi-Mao , Foulger Andrew , Hahn Beatrice H. , Shaw George M. , Swanstrom Ron , Montefiori David C. , Gao Feng , Haynes Barton F. , Korber Bette
Published: January 2013

Human immunodeficiency virus type 1 (HIV-1) vaccine development requires selection of appropriate envelope (Env) immunogens. Twenty HIV-1 Env glycoproteins were examined for their ability to bind human anti-HIV-1 monoclonal antibodies (MAbs) and then used as immunogens in guinea pigs to identify promising immunogens. These included five Envs derived from chronically infected individuals, each representing one of five common clades and eight consensus Envs based on these five clades, as well as the consensus of the entire HIV-1 M group, and seven transmitted/founder (T/F) Envs from clades B and C. Sera from immunized guinea pigs were tested for neutralizing activity using 36 HIV-1 Env-pseudotyped viruses. All Envs bound to CD4 binding site, membrane-proximal, and V1/V2 MAbs with similar apparent affinities, although the T/F Envs bound with higher affinity to the MAb 17b, a CCR5 coreceptor binding site antibody. However, the various Envs differed in their ability to induce neutralizing antibodies. Consensus Envs elicited the most potent responses, but neutralized only a subset of viruses, including mostly easy-to-neutralize tier 1 and some more-difficult-to-neutralize tier 2 viruses. T/F Envs elicited fewer potent neutralizing antibodies but exhibited greater breadth than chronic or consensus Envs. Finally, chronic Envs elicited the lowest level and most limited breadth of neutralizing antibodies overall. Thus, each group of Env immunogens elicited a different antibody response profile. The complementary benefits of consensus and T/F Env immunogens raise the possibility that vaccines utilizing a combination of consensus and T/F Envs may be able to induce neutralizing responses with greater breadth and potency than single Env immunogens.
Emergence in Japan of an HIV-1 Variant Associated with Transmission among Men Who Have Sex with Men (MSM) in China: First Indication of the International Dissemination of the Chinese MSM Lineage
Authors: Kondo Makiko , Lemey Philippe , Sano Takako , Itoda Ichiro , Yoshimura Yukihiro , Sagara Hiroko , Tachikawa Natsuo , Yamanaka Ko , Iwamuro Shinya , Matano Tetsuro , Imai Mitsunobu , Kato Shingo , Takebe Yutaka
Published: January 2013

A survey of HIV-1 strains circulating in the Tokyo-Kanagawa metropolitan area of Japan during 2004 to 2011 (
n
= 477) identified six Japanese males (patients 1 to 6), who harbored viruses with genome segments derived from a distinct CRF01_AE variant uniquely found among men who have sex with men (MSM) in China (designated CN.MSM.01-1). These six HIV infections were diagnosed in 2010 and 2011 among MSM (3 of 75) and men with unknown risk factors (3 of 63) and differed from the vast majority of HIV infections among MSM in Japan, which are overwhelmingly characterized by subtype B (239 of 246 [97.2%]). Approximately one-third (91 of 239 [38.1%]) of subtype B strains from MSM in Japan belong to a large monophyletic cluster (designated JP.MSM.B-1). In addition, we identified a smaller subtype B cluster (
n
= 8) (designated JP.MSM.B-2) that also contains strains from two Chinese MSM living in Japan. Interestingly, patients 5 and 6 were found to be coinfected with CRF01_AE (CN.MSM.01-1) and subtype B (JP.MSM.B-2 or JP.MSM.B-1) variants that are unique to the HIV-1 epidemics among MSM in China and Japan, respectively. Our study demonstrates for the first time the effect of the expanding HIV epidemic among MSM in China on transmission in neighboring countries and shows the ongoing mixing of CRF01_AE and subtype B lineages unique to HIV-1 that cocirculate in MSM populations in East Asia. This finding highlights the importance of strengthening epidemiological surveillance in the region and the need for effective measures to limit transmission among MSM in East Asia.
Release of Severe Acute Respiratory Syndrome Coronavirus Nuclear Import Block Enhances Host Transcription in Human Lung Cells
Authors: Sims Amy C. , Tilton Susan C. , Menachery Vineet D. , Gralinski Lisa E. , Schäfer Alexandra , Matzke Melissa M. , Webb-Robertson Bobbie-Jo M. , Chang Jean , Luna Maria L. , Long Casey E. , Shukla Anil K. , Bankhead Armand R. , Burkett Susan E. , Zornetzer Gregory , Tseng Chien-Te Kent , Metz Thomas O. , Pickles Raymond , McWeeney Shannon , Smith Richard D. , Katze Michael G. , Waters Katrina M. , Baric Ralph S.
Published: January 2013

The severe acute respiratory syndrome coronavirus accessory protein ORF6 antagonizes interferon signaling by blocking karyopherin-mediated nuclear import processes. Viral nuclear import antagonists, expressed by several highly pathogenic RNA viruses, likely mediate pleiotropic effects on host gene expression, presumably interfering with transcription factors, cytokines, hormones, and/or signaling cascades that occur in response to infection. By bioinformatic and systems biology approaches, we evaluated the impact of nuclear import antagonism on host expression networks by using human lung epithelial cells infected with either wild-type virus or a mutant that does not express ORF6 protein. Microarray analysis revealed significant changes in differential gene expression, with approximately twice as many upregulated genes in the mutant virus samples by 48 h postinfection, despite identical viral titers. Our data demonstrated that ORF6 protein expression attenuates the activity of numerous karyopherin-dependent host transcription factors (VDR, CREB1, SMAD4, p53, EpasI, and Oct3/4) that are critical for establishing antiviral responses and regulating key host responses during virus infection. Results were confirmed by proteomic and chromatin immunoprecipitation assay analyses and in parallel microarray studies using infected primary human airway epithelial cell cultures. The data strongly support the hypothesis that viral antagonists of nuclear import actively manipulate host responses in specific hierarchical patterns, contributing to the viral pathogenic potential
in vivo
. Importantly, these studies and modeling approaches not only provide templates for evaluating virus antagonism of nuclear import processes but also can reveal candidate cellular genes and pathways that may significantly influence disease outcomes following severe acute respiratory syndrome coronavirus infection
in vivo
.
An Adjuvanted Herpes Simplex Virus 2 Subunit Vaccine Elicits a T Cell Response in Mice and Is an Effective Therapeutic Vaccine in Guinea Pigs
Authors: Skoberne Mojca , Cardin Rhonda , Lee Alexander , Kazimirova Ana , Zielinski Veronica , Garvie Danielle , Lundberg Amy , Larson Shane , Bravo Fernando J. , Bernstein David I. , Flechtner Jessica B. , Long Deborah
Published: January 2013

Immunotherapeutic herpes simplex virus 2 (HSV-2) vaccine efficacy depends upon the promotion of antigen-specific immune responses that inhibit reactivation or reactivated virus, thus controlling both recurrent lesions and viral shedding. In the present study, a candidate subunit vaccine, GEN-003/MM-2, was evaluated for its ability to induce a broad-spectrum immune response in mice and therapeutic efficacy in HSV-2-infected guinea pigs. GEN-003 is comprised of HSV-2 glycoprotein D2 (gD2ΔTMR
340-363
) and a truncated form of infected cell polypeptide 4 (ICP4
383-766
), formulated with Matrix M-2 (MM-2) adjuvant (GEN-003/MM-2). In addition to eliciting humoral immune responses, CD4
+
and CD8
+
T cells characterized by the secretion of multiple cytokines and cytolytic antigen-specific T cell responses that were able to be recalled at least 44 days after the last immunization were induced in immunized mice. Furthermore, vaccination with either GEN-003 or GEN-003/MM-2 led to significant reductions in both the prevalence and severity of lesions in HSV-2-infected guinea pigs compared to those of phosphate-buffered saline (PBS) control-vaccinated animals. While vaccination with MM-2 adjuvant alone decreased recurrent disease symptoms compared to the PBS control group, the difference was not statistically significant. Importantly, the frequency of recurrent viral shedding was considerably reduced in GEN-003/MM-2-vaccinated animals but not in GEN-003- or MM-2-vaccinated animals. These findings suggest a possible role for immunotherapeutic GEN-003/MM-2 vaccination as a viable alternative to chronic antiviral drugs in the treatment and control of genital herpes disease.
Reassortment Complements Spontaneous Mutation in Influenza A Virus NP and M1 Genes To Accelerate Adaptation to a New Host
Authors: Ince William L. , Gueye-Mbaye Aissatou , Bennink Jack R. , Yewdell Jonathan W.
Published: January 2013

Influenza A virus (IAV) infects a remarkably wide variety of avian and mammalian hosts. Evolution finely hones IAV genes to optimally infect and be transmitted in a particular host species. Sporadically, IAV manages to jump between species, introducing novel antigenic strains into the new host population that wreak havoc until herd immunity develops. IAV adaptation to new hosts typically involves reassortment of IAV gene segments from coinfecting virus strains adapted to different hosts in conjunction with multiple adaptive mutations in the various IAV genes. To better understand host adaptation between mammalian species in real time, we passaged mouse-adapted A/PR8/34 (PR8) in guinea pigs. Guinea pigs, unlike mice, support spontaneous and robust IAV transmission. For some IAV strains, including PR8, adaptation is required for a virus to attain transmissibility, providing an opportunity to understand the evolution of transmissibility in guinea pigs. Multiple guinea pig-adapted PR8 mutants generated by serial nasal wash passaging in independent lines replicated more efficiently and were transmitted by cocaging. All transmissible variants possessed one of two nonsynonymous mutations in M1, either alone or in combination with mutations in PB2, HA, NP, or NA. Rapid reassortment between independently selected variants combined beneficial mutations in NP and M1 to form the fittest virus capable of being transmitted. These findings provide further insight into genetic determinants in NP and M1 involved in PR8 IAV adaptation to be transmitted in a new host and clearly show the benefit of a segmented genome in rapidly generating optimal combinations of mutations in IAV evolution.