bluuebunny/crossref_metadata_2025 huggingface dataset:
Conditional and Unconditional Cash Transfers to Improve Use of Contraception in Low and Middle Income Countries: A Systematic Review
Authors: Khan M. E. , Hazra Avishek , Kant Aastha , Ali Moazzam
Published: November 2016

This systematic review synthesizes evidence on the impact of conditional and unconditional cash transfers (CCT and UCT) on contraception in low‐ and middle‐income countries. Scientific and gray literature databases were searched from 1994 to 2016 and 11 papers from ten studies were included. Most of the studies had low risk of bias. Cash transfers were used for increasing school attendance or improving health and nutrition, but not directly for contraception. Three studies showed positive impact on contraceptive use and four showed a decrease in fertility outcomes. An increase in childbearing was observed in two studies, and three studies demonstrated no impact on fertility indicators. All studies treated contraceptive use or fertility only as unintended and indirect outcomes. The available evidence on impact of CCT and UCT on contraception is inconclusive due to the limited number of studies, varying outcome measures, and lack of intervention specifically for contraception.
A novel allele, HLA‐DRB1*12:60N, detected in a Taiwanese unrelated hematopoietic stem cell donor
Authors: Yang K. L. , Lin P. Y.
Published: November 2016

One nucleotide deletion at residue 157 of HLA‐DRB1*12:02:01 results in a new allele, HLA‐DRB1*12:60N.
Improving phosphorus use efficiency: a complex trait with emerging opportunities
Authors: Heuer Sigrid , Gaxiola Roberto , Schilling Rhiannon , Herrera‐Estrella Luis , López‐Arredondo Damar , Wissuwa Matthias , Delhaize Emmanuel , Rouached Hatem
Published: November 2016

Phosphorus (P) is one of the essential nutrients for plants, and is indispensable for plant growth and development. P deficiency severely limits crop yield, and regular fertilizer applications are required to obtain high yields and to prevent soil degradation. To access P from the soil, plants have evolved high‐ and low‐affinity Pi transporters and the ability to induce root architectural changes to forage P. Also, adjustments of numerous cellular processes are triggered by the P starvation response, a tightly regulated process in plants. With the increasing demand for food as a result of a growing population, the demand for P fertilizer is steadily increasing. Given the high costs of fertilizers and in light of the fact that phosphate rock, the source of P fertilizer, is a finite natural resource, there is a need to enhance P fertilizer use efficiency in agricultural systems and to develop plants with enhanced Pi uptake and internal P‐use efficiency (PUE). In this review we will provide an overview of continuing relevant research and highlight different approaches towards developing crops with enhanced PUE. In this context, we will summarize our current understanding of root responses to low phosphorus conditions and will emphasize the importance of combining PUE with tolerance of other stresses, such as aluminum toxicity. Of the many genes associated with Pi deficiency, this review will focus on those that hold promise or are already at an advanced stage of testing (OsPSTOL1, AVP1, PHO1 and OsPHT1;6). Finally, an update is provided on the progress made exploring alternative technologies, such as phosphite fertilizer.
Copy number variations of CBF genes at the Fr‐A2 locus are essential components of winter hardiness in wheat
Authors: Würschum Tobias , Longin C. Friedrich H. , Hahn Volker , Tucker Matthew R. , Leiser Willmar L.
Published: November 2016

Winter hardiness is important for the adaptation of wheat to the harsh winter conditions in temperate regions and is thus also an important breeding goal. Here, we employed a panel of 407 European winter wheat cultivars to dissect the genetic architecture of winter hardiness. We show that copy number variation (CNV) of CBF (C‐repeat Binding Factor) genes at the Fr‐A2 locus is the essential component for winter survival, with CBF‐A14 CNV being the most likely causal polymorphism, accounting for 24.3% of the genotypic variance. Genome‐wide association mapping identified several markers in the Fr‐A2 chromosomal region, which even after accounting for the effects of CBF‐A14 copy number explained approximately 15% of the genotypic variance. This suggests that additional, as yet undiscovered, polymorphisms are present at the Fr‐A2 locus. Furthermore, CNV of Vrn‐A1 explained an additional 3.0% of the genotypic variance. The allele frequencies of all loci associated with winter hardiness were found to show geographic patterns consistent with their role in adaptation. Collectively, our results from the candidate gene analysis, association mapping and genome‐wide prediction show that winter hardiness in wheat is a quantitative trait, but with a major contribution of the Fr‐A2 locus.
Vicissitudes of Vision: Piety, Pornography, and Shaming the State in Indonesia
Authors: Hoesterey James Bourk
Published: November 2016

When the inaugural Indonesian edition of Playboy magazine was published in 2006, Muslim celebrity televangelist Abdullah Gymnastiar admonished Indonesians that the unbridled sexual gaze could tarnish a pure heart, leaving it blind to the perils of passion. Averting the gaze, he told his followers, would cultivate a sense of shame and thus steer the heart from vice to virtue. Whereas scholars have offered important insights into the study of religion and visual culture, decidedly less attention has been devoted to the faculty of looking as an ethical and political project. In this article, I bring together literatures on affect, subjectivity, and the state to describe how Gymnastiar deploys a moral psychology of vision to discipline state actors and to endow the post‐authoritarian state with a political affect of shame.
Experimental observation of piezoelectric effect in cancellous bone generated by ultrasound irradiation
Authors: Hosokawa A.
Published: November 2016

In this study, piezoelectric cells (PE-cells) of cancellous bone were experimentally produced to receive an ultrasound wave. In the PE-cell, a bovine cancellous bone specimen, in which the pore spaces were saturated with air, was electrically shielded to prevent electromagnetic noise. As a result, the piezoelectric signal generated in the cancellous bone specimen by irradiating an ultrasound burst wave at 1.0 MHz could be clearly observed in water. The experimental results showed that the ultrasound sensitivity per unit area of cancellous bone was estimated to be below 1/100 and 1/100 000 of cortical bone and poly(vinylidene fluoride), respectively.
A Classification of Instructional Programs (CIP) Primer for Kinesiology Leaders
Authors: Knudson Duane
Published: November 2016

Classification of Instructional Programs (CIP) codes were designed to report outcomes in higher education by specific disciplines and professions, however, universities, states, and accreditation bodies also use these codes in other ways. This paper describes CIP-2010 usage in higher education and how these codes are used in funding public universities in Texas, and summarizes the American Kinesiology Association/National Academy of Kinesiology recommendations to the National Center for Education Statistics on updating kinesiology-related CIP codes. Kinesiology leaders should be knowledgeable about how CIP codes are often used behind the scenes in a variety of ways that affect our faculty, programs, and the field. Greater use of the term kinesiology in many future CIP codes would benefit the field and individual departments seeking alignment with institutional priorities.
Internal and External Resource Generation: Creative Strategies for Kinesiology Programs
Authors: Gordon Scott E. , Bartholomew John B. , Kreider Richard B. , Zernicke Ronald F. , Rudisill Mary E.
Published: November 2016

This is an era in which academic units in higher education are expected to do more with less. State- and institutionally-appropriated funding streams are generally decreasing or stagnant. Federal grant funding is at its lowest level in years, and unlikely to rebound anytime soon. Institutions are restricting tuition increases to allow greater accessibility to students of limited means as well as to heed public demand for more accountability in the “educational product”. Enrollment growth adds pressure to academic units but rarely results in immediate resources directed to the affected units. To compound this problem, kinesiology is one of the fastest growing majors nationwide. With such mounting pressures on academic units and their leaders, creative entrepreneurial resourcefulness is not only rewarded, but required. This paper presents a series of successful and practical resource-generating strategies from the unique perspectives of units at several different institutions.
Scientists start to parse a Trump presidency
Authors: Mervis Jeffrey
Published: November 2016

Fears for climate and social science research, hopes for infrastructure boost.
Japan reboots x-ray probe—and mission management
Authors: Normile Dennis
Published: November 2016

After a series of mission failures, Japan's space science agency aims to overhaul lax oversight.
No need to apply, Dutch science academy tells men
Authors: Enserink Martin
Published: November 2016

Two special elections seek to address gender imbalance by admitting only women.
Shaking up the Tree of Life
Authors: Pennisi Elizabeth
Published: November 2016

Species were once thought to keep to themselves. Now, hybrids are turning up everywhere, challenging evolutionary theory.
Crystal clocks
Authors: Rosen Julia
Published: November 2016

How smudged crystals offer windows into a volcano's eruptive past.
Characterization of a dynamic metabolon producing the defense compound dhurrin in sorghum
Authors: Laursen Tomas , Borch Jonas , Knudsen Camilla , Bavishi Krutika , Torta Federico , Martens Helle Juel , Silvestro Daniele , Hatzakis Nikos S. , Wenk Markus R. , Dafforn Timothy R. , Olsen Carl Erik , Motawia Mohammed Saddik , Hamberger Björn , Møller Birger Lindberg , Bassard Jean-Etienne
Published: November 2016

Metabolite channeling by a dynamic metabolon

The specialized metabolite dhurrin breaks down into cyanide when plant cell walls have been chewed, deterring insect pests. Laursen
et al.
found that the enzymes that synthesize dhurrin in sorghum assemble as a metabolon in lipid membranes (see the Perspective by Dsatmaichi and Facchini). The dynamic nature of metabolon assembly and disassembly provides dhurrin on an as-needed basis. Membrane-anchored cytochrome P450s cooperated with a soluble glucosyltransferase to channel intermediates toward efficient dhurrin production.

Science
, this issue p.
890
; see also p.
829
Synthetic lethality and beyond
Authors: Beltran Himisha
Published: November 2016

DNA damage–induced binding of DNA methyltransferases maximizes the efficacy of poly(ADP-ribose) polymerase inhibitors.
Calibration and Evaluation of Quantitative Antibody Titers for Measles Virus by Using the BioPlex 2200
Authors: Hatchette Todd F. , Scholz Heidi , Bolotin Shelly , Crowcroft Natasha S. , Jackson Colleen , McLachlan Elizabeth , Severini Alberto
Published: November 2016

The BioPlex 2200 (Bio-Rad Laboratories, Hercules, CA) is a rapid, automated platform, which can screen large numbers of specimens for antibodies to measles, mumps, rubella, and varicella. Although approved for producing qualitative results, in this study we validated the test (off-label) to allow reporting of quantitative results. To do this, we used the third anti-measles World Health Organization standard to generate a calibration curve that allowed relative fluorescence intensity to be translated into quantitative antibody titer (antibody units [AU]/ml). The results from the BioPlex 2200 and the reference plaque reduction neutralization test (PRNT) exhibited a reasonable correlation following an exponential function, but correlation was poor in low-titer samples. Using a receiver operating characteristics analysis, an equivocal zone for the BioPlex 2200 was established between ≥0.13 and <1.10 AU/ml to achieve 100% specificity (95% confidence interval [CI] = 83.2 to 100%) and 100% sensitivity (95% CI = 93.5 to 100%) versus PRNT. By determining an equivocal range requiring confirmation by PRNT, we can avoid underestimating the levels of immunity through false-negative results and optimize methods for seroepidemiological studies.
Highly Multiplexed Proteomic Analysis of Quantiferon Supernatants To Identify Biomarkers of Latent Tuberculosis Infection
Authors: De Groote Mary Ann , Higgins Michael , Hraha Thomas , Wall Kirsten , Wilson Michael L. , Sterling David G. , Janjic Nebojsa , Reves Randall , Ochsner Urs A. , Belknap Robert
Published: November 2016

The tests for diagnosing latent tuberculosis infection (LTBI) are limited by a poor predictive value for identifying people at the highest risk for progressing to active tuberculosis (TB) and have various sensitivities and specificities in different populations. Identifying a more robust signature for LTBI is important for TB prevention and elimination. A pilot study was conducted with samples from immigrants to the United States that were screened for LTBI by the three commercially approved tests, namely, the tuberculin skin test (TST), the Quantiferon-TB Gold in-tube (QFT-GIT), and the T-SPOT.TB (T-SPOT). QFT-GIT supernatants from 13 people with concordant positive results and 26 people with concordant negative results were analyzed via the highly multiplexed SOMAscan proteomic assay. The proteins in the stimulated supernatants that distinguished LTBI from controls included interleukin-2 (IL-2), monocyte chemotactic protein 2 (MCP-2), interferon gamma inducible protein-10 (IP-10), interferon gamma (IFN-γ), tumor necrosis factor superfamily member 14 (TNFSF14, also known as LIGHT), monokine induced by gamma interferon (MIG), and granzyme B (P<0.00001). In addition, antigen stimulation increased the expression of heparin-binding EGF-like growth factor (HB-EGF) and activin AB in LTBI samples. In nil tubes, LIGHT was the most significant marker (P<0.0001) and was elevated in LTBI subjects. Other prominent markers in nonstimulated QFT-GIT supernatants were the complement-3 components C3b, iC3b, and C3d, which were upregulated in LTBI and markedly decreased upon stimulation. We found known and novel proteins that warrant further studies for developing improved tests for LTBI, for predicting progression to active disease, and for discriminating LTBI from active TB.
Rapid Identification of Measles Virus Vaccine Genotype by Real-Time PCR
Authors: Roy Felicia , Mendoza Lillian , Hiebert Joanne , McNall Rebecca J. , Bankamp Bettina , Connolly Sarah , Lüdde Amy , Friedrich Nicole , Mankertz Annette , Rota Paul A. , Severini Alberto
Published: November 2016

During measles outbreaks, it is important to be able to rapidly distinguish between measles cases and vaccine reactions to avoid unnecessary outbreak response measures such as case isolation and contact investigations. We have developed a real-time reverse transcription-PCR (RT-PCR) method specific for genotype A measles virus (MeV) (MeVA RT-quantitative PCR [RT-qPCR]) that can identify measles vaccine strains rapidly, with high throughput, and without the need for sequencing to determine the genotype. We have evaluated the method independently in three measles reference laboratories using two platforms, the Roche LightCycler 480 system and the Applied Biosystems (ABI) 7500 real-time PCR system. In comparison to the standard real-time RT-PCR method, the MeVA RT-qPCR showed 99.5% specificity for genotype A and 94% sensitivity for both platforms. The new assay was able to detect RNA from five currently used vaccine strains, AIK-C, CAM-70, Edmonston-Zagreb, Moraten, and Shanghai-191. The MeVA RT-qPCR assay has been used successfully for measles surveillance in reference laboratories, and it could be readily deployed to national and subnational laboratories on a wide scale.
A Novel Selective Medium for Isolation of Bacteroides fragilis from Clinical Specimens
Authors: Ho Pak-Leung , Ho Lok-Yan , Yau Chong-Yee , Tong Man-Ki , Chow Kin-Hung
Published: November 2016

A novel
Bacteroides fragilis
selective (BFS) medium, consisting of a brain heart infusion agar base supplemented with yeast extract, cysteine hydrochloride, bile salts, vitamin K, hemin, glucose, esculin, ferric ammonium citrate, bromothymol blue, gentamicin, kanamycin, and novobiocin, was evaluated. When BFS agar was tested with a collection of 303 bacteria of different genera, it allowed the growth of
B. fragilis
as large yellow colonies, with blackening of the medium after 48 h of anaerobic incubation, while the growth of most other anaerobes, facultative anaerobes, and aerobes was inhibited. In a prospective comparison of BFS agar with a routinely used medium (neomycin blood agar) in 1,209 clinical specimens, 60
B. fragilis
bacteria were detected on BFS agar while 46 were detected on the routine agar (McNemar's test,
P
= 0.008). In conclusion, this novel medium may be added to improve the recovery of
B. fragilis
in clinical specimens and to facilitate surveillance of antimicrobial-resistant strains.
Ablation of Programmed −1 Ribosomal Frameshifting in Venezuelan Equine Encephalitis Virus Results in Attenuated Neuropathogenicity
Authors: Kendra Joseph A. , de la Fuente Cynthia , Brahms Ashwini , Woodson Caitlin , Bell Todd M. , Chen Bin , Khan Yousuf A. , Jacobs Jonathan L. , Kehn-Hall Kylene , Dinman Jonathan D.
Published: November 2016

The alphaviruses Venezuelan equine encephalitis virus (VEEV), eastern equine encephalitis virus (EEEV), and western equine encephalitis virus (WEEV) are arthropod-borne positive-strand RNA viruses that are capable of causing acute and fatal encephalitis in many mammals, including humans. VEEV was weaponized during the Cold War and is recognized as a select agent. Currently, there are no FDA-approved vaccines or therapeutics for these viruses. The spread of VEEV and other members of this family due to climate change-mediated vector range expansion underscores the need for research aimed at developing medical countermeasures. These viruses utilize programmed −1 ribosomal frameshifting (−1 PRF) to synthesize the viral
trans
-frame (TF) protein, which has previously been shown to be important for neuropathogenesis in the related Sindbis virus. Here, the alphavirus −1 PRF signals were characterized, revealing novel −1 PRF stimulatory structures. −1 PRF attenuation mildly affected the kinetics of VEEV accumulation in cultured cells but strongly inhibited its pathogenesis in an aerosol infection mouse model. Importantly, the decreased viral titers in the brains of mice infected with the mutant virus suggest that the alphavirus TF protein is important for passage through the blood-brain barrier and/or for neuroinvasiveness. These findings suggest a novel approach to the development of safe and effective live attenuated vaccines directed against VEEV and perhaps other closely related −1 PRF-utilizing viruses.

IMPORTANCE
Venezuelan equine encephalitis virus (VEEV) is a select agent that has been weaponized. This arthropod-borne positive-strand RNA virus causes acute and fatal encephalitis in many mammals, including humans. There is no vaccine or other approved therapeutic. VEEV and related alphaviruses utilize programmed −1 ribosomal frameshifting (−1 PRF) to synthesize the viral
trans
-frame (TF) protein, which is important for neuropathogenesis. −1 PRF attenuation strongly inhibited VEEV pathogenesis in mice, and viral replication analyses suggest that the TF protein is critical for neurological disease. These findings suggest a new approach to the development of safe and effective live attenuated vaccines directed against VEEV and other related viruses.
Mapping of Functional Subdomains in the Terminal Protein Domain of Hepatitis B Virus Polymerase
Authors: Clark Daniel N. , Flanagan John M. , Hu Jianming
Published: November 2016

Hepatitis B virus (HBV) encodes a multifunction reverse transcriptase or polymerase (P), which is composed of several domains. The terminal protein (TP) domain is unique to HBV and related hepadnaviruses and is required for specifically binding to the viral pregenomic RNA (pgRNA). Subsequently, the TP domain is necessary for pgRNA packaging into viral nucleocapsids and the initiation of viral reverse transcription for conversion of the pgRNA to viral DNA. Uniquely, the HBV P protein initiates reverse transcription via a protein priming mechanism using the TP domain as a primer. No structural homologs or high-resolution structure exists for the TP domain. Secondary structure prediction identified three disordered loops in TP with highly conserved sequences. A meta-analysis of mutagenesis studies indicated these predicted loops are almost exclusively where functionally important residues are located. Newly constructed TP mutations revealed a priming loop in TP which plays a specific role in protein-primed DNA synthesis beyond simply harboring the site of priming. Substitutions of potential sites of phosphorylation surrounding the priming site demonstrated that these residues are involved in interactions critical for priming but are unlikely to be phosphorylated during viral replication. Furthermore, the first 13 and 66 TP residues were shown to be dispensable for protein priming and pgRNA binding, respectively. Combining current and previous mutagenesis work with sequence analysis has increased our understanding of TP structure and functions by mapping specific functions to distinct predicted secondary structures and will facilitate antiviral targeting of this unique domain.

IMPORTANCE
HBV is a major cause of viral hepatitis, liver cirrhosis, and hepatocellular carcinoma. One important feature of this virus is its polymerase, the enzyme used to create the DNA genome from a specific viral RNA by reverse transcription. One region of this polymerase, the TP domain, is required for association with the viral RNA and production of the DNA genome. Targeting the TP domain for antiviral development is difficult due to the lack of homology to other proteins and high-resolution structure. This study mapped the TP functions according to predicted secondary structure, where it folds into alpha helices or unstructured loops. Three predicted loops were found to be the most important regions functionally and the most conserved evolutionarily. Identification of these functional subdomains in TP will facilitate its targeting for antiviral development.
A Novel Rabies Vaccine Expressing CXCL13 Enhances Humoral Immunity by Recruiting both T Follicular Helper and Germinal Center B Cells
Authors: Wang Zhao , Li Mingming , Zhou Ming , Zhang Yajing , Yang Jie , Cao Yandi , Wang Kunlun , Cui Min , Chen Huanchun , Fu Zhen F. , Zhao Ling
Published: November 2016

Rabies remains a public health threat in most parts of the world, and approximately 99% of the cases are transmitted by dogs. There is an urgent need to develop an efficacious and affordable vaccine to control canine-transmitted rabies in developing countries. Our previous studies demonstrate that overexpression of chemokines/cytokines such as CCL-3 (MIP-1α) and granulocyte-macrophage colony-stimulating factor (GM-CSF) can enhance the immunogenicity of rabies vaccines. In the present study, the chemokine CXCL13 was inserted into the genome of the recombinant rabies virus (rRABV) strain LBNSE, and the effect of the chemokine CXCL13 on the immunogenicity of RABV was investigated. It was found that LBNSE-CXCL13 recruited follicular helper T (Tfh) and germinal center (GC) B cells, promoted the formation of GCs, and increased the population of plasma cells in immunized mice. Further studies showed that mice immunized with LBNSE-CXCL13 produced more rabies virus-neutralizing antibodies (VNAs) and developed better protection than those immunized with the parent virus LBNSE or the GM-CSF-expressing RABV (LBNSE-GM-CSF). Collectively, these findings provide a better understanding of the role of CXCL13 expression in the immunogenicity of the RABV, which may help in designing more-efficacious rabies vaccines.

IMPORTANCE
Rabies is endemic in most parts of the world, and more effort is needed to develop affordable and effective vaccines to control or eliminate this disease. The chemokine CXCL13 recruits both Tfh and B cells, which is essential for the homing of Tfh cells and the development of B cell follicles. In this study, the effect of the overexpression of CXCL13 on the immunogenicity of the RABV was evaluated in a mouse model. We found that CXCL13 expression promoted humoral immunity by recruiting Tfh and GC B cells, facilitating the formation of GCs, and increasing the number of plasma cells. As expected, the overexpression of CXCL13 resulted in enhanced virus-neutralizing antibody (VNA) production and protection against a virulent RABV challenge. These findings provide a better understanding of the role of CXCL13 in RABV-induced immune responses, which will help in designing more efficacious rabies vaccines.
Palmitoylation of Sindbis Virus TF Protein Regulates Its Plasma Membrane Localization and Subsequent Incorporation into Virions
Authors: Ramsey Jolene , Renzi Emily C. , Arnold Randy J. , Trinidad Jonathan C. , Mukhopadhyay Suchetana
Published: November 2016

Palmitoylation is a reversible, posttranslational modification that helps target proteins to cellular membranes. The alphavirus small membrane proteins 6K and TF have been reported to be palmitoylated and to positively regulate budding. 6K and TF are isoforms that are identical in their N termini but unique in their C termini due to a −1 ribosomal frameshift during translation. In this study, we used cysteine (Cys) mutants to test differential palmitoylation of the Sindbis virus 6K and TF proteins. We modularly mutated the five Cys residues in the identical N termini of 6K and TF, the four additional Cys residues in TF's unique C terminus, or all nine Cys residues in TF. Using these mutants, we determined that TF palmitoylation occurs primarily in the N terminus. In contrast, 6K is not palmitoylated, even on these shared residues. In the C-terminal Cys mutant, TF protein levels increase both in the cell and in the released virion compared to the wild type. In viruses with the N-terminal Cys residues mutated, TF is much less efficiently localized to the plasma membrane, and it is not incorporated into the virion. The three Cys mutants have minor defects in cell culture growth but a high incidence of abnormal particle morphologies compared to the wild-type virus as determined by transmission electron microscopy. We propose a model where the C terminus of TF modulates the palmitoylation of TF at the N terminus, and palmitoylated TF is preferentially trafficked to the plasma membrane for virus budding.

IMPORTANCE
Alphaviruses are a reemerging viral cause of arthritogenic disease. Recently, the small 6K and TF proteins of alphaviruses were shown to contribute to virulence
in vivo
. Nevertheless, a clear understanding of the molecular mechanisms by which either protein acts to promote virus infection is missing. The TF protein is a component of budded virions, and optimal levels of TF correlate positively with wild-type-like particle morphology. In this study, we show that the palmitoylation of TF regulates its localization to the plasma membrane, which is the site of alphavirus budding. Mutants in which TF is not palmitoylated display drastically reduced plasma membrane localization, which effectively prevents TF from participating in budding or being incorporated into virus particles. Investigation of the regulation of TF will aid current efforts in the alphavirus field searching for approaches to mitigate alphaviral disease in humans.
Kaposi's Sarcoma-Associated Herpesvirus MicroRNAs Target GADD45B To Protect Infected Cells from Cell Cycle Arrest and Apoptosis
Authors: Liu Xiaoyan , Happel Christine , Ziegelbauer Joseph M.
Published: November 2016

Kaposi's sarcoma is one of the most common malignancies in HIV-infected individuals. The responsible agent, Kaposi's sarcoma-associated herpesvirus (KSHV; HHV8), expresses multiple microRNAs (miRNAs), but the targets and functions of these miRNAs are not completely understood. After infection in primary endothelial cells with KSHV,
growth arrest DNA damage-inducible gene 45 beta
(
GADD45B
) is one of the most repressed genes using genomic expression profiling.
GADD45B
was also repressed in mRNA expression profiling experiments when KSHV miRNAs were introduced to uninfected cells. We hypothesized that KSHV miRNAs target human
GADD45B
to protect cells from consequences of DNA damage, which can be triggered by viral infection. Expression of GADD45B protein is induced by the p53 activator, Nutlin-3, and KSHV miRNA-K9 inhibits this induction. In addition, Nutlin-3 increased apoptosis and cell cycle arrest based on flow cytometry assays. KSHV miR-K9 protected primary endothelial cells from apoptosis and cell cycle arrest following Nutlin-3 treatment. Similar protective phenotypes were seen for targeting GADD45B with short interfering RNAs (siRNAs), as with miR-K9. KSHV miR-K9 also decreased the protein levels of cleaved caspase-3, cleaved caspase-7, and cleaved poly(ADP-ribose) polymerase (PARP). In B lymphocytes latently infected with KSHV, specific inhibitors of KSHV miR-K9 led to increased GADD45B expression and apoptosis, indicating that miR-K9 is important for reducing apoptosis in infected cells. Furthermore, ectopic expression of GADD45B in KSHV-infected cells promoted apoptosis. Together, these results identify a new miRNA target and demonstrate that KSHV miRNAs are important for protecting infected cells from DNA damage responses.

IMPORTANCE
Kaposi's sarcoma-associated herpesvirus is a leading cause of cancers in individuals with AIDS. Promoting survival of infected cells is essential for maintaining viral infections. A virus needs to combat various cellular defense mechanisms designed to eradicate the viral infection. One such response can include DNA damage response factors, which can promote an arrest in cell growth and trigger cell death. We used a new approach to search for human genes repressed by small nucleic acids (microRNAs) expressed by a gammaherpesvirus (KSHV), which identified a gene called
GADD45B
as a target of microRNAs. Repression of GADD45B, which is expressed in response to DNA damage, benefited survival of infected cells in response to a DNA damage response. This information could be used to design new treatments for herpesvirus infections.
Age-Dependent Differences in Pseudorabies Virus Neuropathogenesis and Associated Cytokine Expression
Authors: Verpoest Sara , Cay Brigitte , Favoreel Herman , De Regge Nick
Published: November 2016

The severity of clinical symptoms induced by pseudorabies virus (PRV) infection of its natural host is inversely related to the age of the pig. During this study, 2- and 15-week-old pigs were inoculated with PRV strain NIA3. This resulted in important clinical disease, although the associated morbidity and mortality were lower in older pigs. Quantitative PCR analysis of viral DNA in different organs confirmed the general knowledge on PRV pathogenesis. Several new findings and potential explanations for the observed age-dependent differences in virulence, however, were determined from the study of viral and cytokine mRNA expression at important sites of neuropathogenesis. First, only limited viral and cytokine mRNA expression was detected in the nasal mucosa, suggesting that other sites may serve as the primary replication site. Second, PRV reached the trigeminal ganglion (TG) and brain stem rapidly upon infection but, compared to 2-week-old pigs, viral replication was less pronounced in 15-week-old pigs, and the decrease in viral mRNA expression was not preceded by or associated with an increased cytokine expression. Third, extensive viral replication associated with a robust expression of cytokine mRNA was detected in the olfactory bulbs of pigs from both age categories and correlated with the observed neurological disease. Our results suggest that age-dependent differences in PRV-induced clinical signs are probably due to enhanced viral replication and associated immunopathology in immature TG and the central nervous system neurons of 2-week-old pigs and that neurological disease is related with extensive viral replication and an associated immune response in the olfactory bulb.

IMPORTANCE
It is well known that alphaherpesvirus infections of humans and animals result in more severe clinical disease in newborns than in older individuals and that this is probably related to differences in neuropathogenesis. The underlying mechanisms, however, remain unclear. Pseudorabies virus infection of its natural host, the pig, provides a suitable infection model to study this more profoundly. We show here that the severe neurological disease observed in 2-week-old pigs does not appear to be related to a hampered innate immune response but is more likely to reflect the immature development state of the trigeminal ganglia (TG) and central nervous system (CNS) neurons, resulting in an inefficient suppression of viral replication. In 15-week-old pigs, viral replication was efficiently suppressed in the TG and CNS without induction of an extensive immune response. Furthermore, our results provide evidence that neurological disease could, at least in part, be related to viral replication and associated immunopathology in the olfactory bulb.
Dual Function of the pUL7-pUL51 Tegument Protein Complex in Herpes Simplex Virus 1 Infection
Authors: Albecka Anna , Owen Danielle J. , Ivanova Lyudmila , Brun Juliane , Liman Rukayya , Davies Laura , Ahmed M. Firoz , Colaco Susanna , Hollinshead Michael , Graham Stephen C. , Crump Colin M.
Published: November 2016

The tegument of herpesviruses is a highly complex structural layer between the nucleocapsid and the envelope of virions. Tegument proteins play both structural and regulatory functions during replication and spread, but the interactions and functions of many of these proteins are poorly understood. Here we focus on two tegument proteins from herpes simplex virus 1 (HSV-1), pUL7 and pUL51, which have homologues in all other herpesviruses. We have now identified that HSV-1 pUL7 and pUL51 form a stable and direct protein-protein interaction, their expression levels rely on the presence of each other, and they function as a complex in infected cells. We demonstrate that expression of the pUL7-pUL51 complex is important for efficient HSV-1 assembly and plaque formation. Furthermore, we also discovered that the pUL7-pUL51 complex localizes to focal adhesions at the plasma membrane in both infected cells and in the absence of other viral proteins. The expression of pUL7-pUL51 is important to stabilize focal adhesions and maintain cell morphology in infected cells and cells infected with viruses lacking pUL7 and/or pUL51 round up more rapidly than cells infected with wild-type HSV-1. Our data suggest that, in addition to the previously reported functions in virus assembly and spread for pUL51, the pUL7-pUL51 complex is important for maintaining the attachment of infected cells to their surroundings through modulating the activity of focal adhesion complexes.

IMPORTANCE
Herpesviridae
is a large family of highly successful human and animal pathogens. Virions of these viruses are composed of many different proteins, most of which are contained within the tegument, a complex structural layer between the nucleocapsid and the envelope within virus particles. Tegument proteins have important roles in assembling virus particles as well as modifying host cells to promote virus replication and spread. However, little is known about the function of many tegument proteins during virus replication. Our study focuses on two tegument proteins from herpes simplex virus 1 that are conserved in all herpesviruses: pUL7 and pUL51. We demonstrate that these proteins directly interact and form a functional complex that is important for both virus assembly and modulation of host cell morphology. Further, we identify for the first time that these conserved herpesvirus tegument proteins localize to focal adhesions in addition to cytoplasmic juxtanuclear membranes within infected cells.
Microbial Community Patterns Associated with Automated Teller Machine Keypads in New York City
Authors: Bik Holly M. , Maritz Julia M. , Luong Albert , Shin Hakdong , Dominguez-Bello Maria Gloria , Carlton Jane M.
Published: November 2016

A
utomated
t
eller
m
achine (ATM) keypads represent a specific and unexplored microhabitat for microbial communities. Although the number of built environment and urban microbial ecology studies has expanded greatly in recent years, the majority of research to date has focused on mass transit systems, city soils, and plumbing and ventilation systems in buildings. ATM surfaces, potentially retaining microbial signatures of human inhabitants, including both commensal taxa and pathogens, are interesting from both a biodiversity perspective and a public health perspective. By focusing on ATM keypads in different geographic areas of New York City with distinct population demographics, we aimed to characterize the diversity and distribution of both prokaryotic and eukaryotic microbes, thus making a unique contribution to the growing body of work focused on the “urban microbiome.” In New York City, the surface area of urban surfaces in Manhattan far exceeds the geographic area of the island itself. We have only just begun to describe the vast array of microbial taxa that are likely to be present across diverse types of urban habitats.
Alcohol consumption among university students: a typology of consumption to aid the tailoring of effective public health policy
Authors: Davoren Martin P , Cronin Mary , Perry Ivan J , O'Connor Karl
Published: November 2016

Objective

Elevated levels of alcohol consumption among university students are well documented. Policymakers have attempted to combat this issue at a university, national and international level. Tailoring public health policy to effectively tackle alcohol use is crucial. Using Q-methodology, the current study aims to develop a typology of alcohol consumption in the Irish university student population.

Setting

A large Irish university.

Participants

Hundreds of possible statements on types of consumption were generated from a systematic review and a set of one-on-one interviews. These were reduced to 36 statements, 6 statements which define each of the 6 previously defined consumption types. Participants were advised to scan through the 36 statements and fill the statements into a ‘forced choice, standardised distribution’. Following this, a 45–90 min interview was conducted with students to illuminate subjectivity surrounding alcohol consumption. Analysis was conducted usingPQ MethodandNVivosoftware. Principal component analysis, followed by varimax rotation, was conducted to uncover the final factor information.

Results

In total, 43 students completed the Q-study: 19 men and 24 women. A typology describing 4 distinct groupings of alcohol consumer was uncovered: the guarded drinker, the calculated hedonist, the peer-influenced drinker and the inevitable binger. Factor loadings of each of the consumer groupings were noted for type description.

Conclusions

This is the first study to propose ideal types of alcohol consumption among a university student population. Further research is required to investigate the degree to which each of these ideal types is subscribed. However, this typology, in addition to informing public policy and strategies, will be a valuable analytic tool in future research.
Long fusion correction of degenerative adult spinal deformity and the selection of the upper or lower thoracic region as the site of proximal instrumentation: a systematic review and meta-analysis
Authors: Fu Xin , Sun Xiao-Lei , Harris Jonathan A , Sheng Sun-Ren , Xu Hua-Zi , Chi Yong-Long , Wu Ai-Min
Published: November 2016

Objective

The aim of this study was to compare outcomes when the upper and lower thoracic regions were used as the site of proximal instrumentation to treat adult spinal deformity.

Methods

MEDLINE, Embase and Cochrane library searches were performed to identify studies that compared outcome measures when the upper and lower thoracic vertebrae (UTV and LTV, respectively) were used as the site of proximal instrumentation. The weighted mean difference (WMD) was calculated for continuous outcomes, and the relative risk (RR) was calculated for dichotomous outcomes.

Results

Seven articles (n=554 patients) met the final inclusion criteria, and we compared the outcome measures of a long fusion extending to the upper and lower thoracic regions. The pooled analysis revealed that extending fixation into the upper thoracic region decreased the risk of proximal junctional kyphosis (PJK) revision surgery (RR: 0.36, 95% CI 0.14 to 0.90, p<0.05). The operation time (WMD: 0.93, 95% CI 0.48 to 1.39, p<0.05) and estimated blood loss (WMD: 0.59, 95% CI 0.33 to 0.85, p<0.05) were significantly greater in the UTV group than in the LTV group. No significant differences were found in the Scoliosis Research Society pain, self-image, function, mental health, subtotal, satisfaction or total scores; the total number of complications or the total number of revision surgeries.

Conclusions

Long posterior fixation extending into the upper thoracic region reduces the incidence of revision surgery related to PJK; however, it increased the operative level resulting in a longer operative time and greater estimated blood loss. This initial analysis indicates that extending fixation to the upper thoracic region is appropriate for patients who are likely to develop PJK following initial scoliosis correction.
Non-alcoholic fatty liver disease and colorectal cancer
Authors: Mikolasevic I , Orlic L , Stimac D , Hrstic I , Jakopcic I , Milic S
Published: November 2016

As a significant cause of cancer death worldwide, colorectal cancer (CRC) is still one of the most common cancers in the world. The most efficient strategies to reduce CRC incidence include identifying risk factors for CRC and performing a preventive colonoscopy in high-risk populations. Some well-established risk factors for CRC development include hereditary syndromes and inflammatory bowel disease. Of note, in recent years, attention has been given to new evidence indicating that more than 75%–95% of CRC occurs in individuals with little or no genetic risk. For these individuals, the risk for CRC is associated with their lifestyle and dietary factors, including central obesity, overweight and physical inactivity. Recently, evidence demonstrated a connection between non-alcoholic fatty liver disease (NAFLD) and CRC. Insulin resistance and metabolic syndrome (MetS) are common risks that NAFLD and colorectal neoplasms share. The incidence of NAFLD is increasing in parallel with an increasing prevalence of MetS and obesity. Consequently, the question arises: will the incidence of CRC increase together with this dramatic increase in obesity, MetS and ultimately NAFLD prevalence? Recent studies of adenomatous polyps, CRC and NAFLD are discussed in this manuscript.
Effectiveness and practicality of control strategies for African swine fever: what do we really know?
Authors: Guinat C. , Vergne T. , Jurado‐Diaz C. , Sánchez‐Vizcaíno J. M. , Dixon L. , Pfeiffer D. U.
Published: November 2016

African swine fever (ASF) is a major pig health problem, and the causative virus is moving closer to Western European regions where pig density is high. Stopping or slowing down the spread of ASF requires mitigation strategies that are both effective and practical. Based on the elicitation of ASF expert opinion, this study identified surveillance and intervention strategies for ASF that are perceived as the most effective by providing the best combination between effectiveness and practicality. Among the 20 surveillance strategies that were identified, passive surveillance of wild boar and syndromic surveillance of pig mortality were considered to be the most effective surveillance strategies for controlling ASF virus spread. Among the 22 intervention strategies that were identified, culling of all infected herds and movement bans for neighbouring herds were regarded as the most effective intervention strategies. Active surveillance and carcase removal in wild boar populations were rated as the most effective surveillance and intervention strategies, but were also considered to be the least practical, suggesting that more research is needed to develop more effective methods for controlling ASF in wild boar populations.
Regularized perturbative series for the ionization potential of atomic ions
Authors: Gil Gabriel , González Augusto
Published: November 2016

We study N-electron atoms with nuclear charge Z. It is well known that, in the cationic (Z > N) large-Z region, the atom behaves as a weakly interacting system. The anionic (Z < N) regime, on the other hand, is characterized by an instability threshold at [Formula: see text], below which the atom spontaneously emits an electron. We construct a regularized perturbative series (RPS) for the ionization potential that is based on the behaviors for large Z and Z near Zc. The large-Z expansion coefficients are analytically computed from perturbation theory, whereas the slope of the energy curve at Z = N − 1 is computed from a kind of zero-range forces theory that uses as input the electron affinity and the covalent radius of the neutral atom with N − 1 electrons. Relativistic effects in the one-particle Hamiltonian are considered at the level of first-order perturbation theory. Our RPS formula is to be used to check the consistency of the ionization potential values for atomic ions contained in the NIST database.
Antimicrobial nanomaterials against biofilms: an alternative strategy
Authors: Liu Chunhua , Guo Jing , Yan Xiaoqing , Tang Yongbing , Mazumder Asit , Wu Shikai , Liang Yan
Published: November 2016

Microbial adhesion to surfaces and the consequent biofilm formation under various environmental conditions is a common ecological phenomenon. Although biofilms play crucial beneficial roles in many processes, they can also cause serious problems for food, biomedical, environmental, and industrial sectors, leading to higher costs of production and equipment maintenance, and negative public health and environmental impacts. Biofilms are difficult to eradicate due to their resistance to conventional antimicrobial applications. Consequently, attention has been devoted to new emerging nanomaterials for their remarkable antimicrobial function. Understanding the inactivation mechanisms is the key to increase the efficiency of nanoparticles (NPs) and enhance the feasibility of their application against various microorganisms under different environments. In this paper, we review the activities of NPs as antimicrobial agents. We also discuss the mechanisms and factors contributing to antimicrobial properties of NPs. In addition, we describe some of the approaches employing NPs as effective antimicrobial agent, and associated challenges and problems in developing NPs as effective antibiofilm agents.