bluuebunny/crossref_metadata_2025 huggingface dataset:
Finite Element Evaluation of Biomechanical Changes of Lumbar Segment Implanted With an Anterior Disc After Subsidance
Authors: Kiapour A. , Goel V. K. , Lee C. K. , Grauer J. N. , Serhan H.
Published: March 2014

Biomechanical studies of artificial discs that quantify parameters like kinematics, the load sharing and stresses have been reported in literature for various artificial disc designs; however literature on the long term biomechanical behavior of the implant in the spine is sparse. Disc subsidence is one of the potential long term issues. In this study finite element method was used to investigate the biomechanics of Charite anterior lumbar disc (DePuy Spine, MA) following potential subsidence of the implant into vertebral endplates.
Analysis of In Vivo Strains in the Tibial Metaphysis of Adult Rats During Voluntary Exercising Protocols
Authors: Bouse S. D. , Swift J. , Bloomfield S. A. , Hogan H. A.
Published: March 2014

In a recent study [1], unexpected results were observed in the bone response of animals undergoing two different exercise protocols. Rats were trained to jump voluntarily, but one group wore weighted backpacks while the other group did not (body weight only). Surprisingly, both of these exercises produced similar osteogenic responses after 5 weeks of training. The purpose of the current study was to compare in vivo bone strain measurements for animals doing these two types of exercises to see if these data could help explain the unexpected results.
High-Throughput Cell Imaging, Counting and Characterization on a Chip
Authors: Su Ting-Wei , Seo Sungkyu , Erlinger Anthony , Ozcan Aydogan
Published: March 2014

We introduce a lensfree on chip imaging platform that enables high-throughput monitoring, counting, and identification of several different microscopic objects such as different cell types within a heterogeneous solution. This imaging platform can in principle be miniaturized to a hand-held device that can be used by minimally trained health care providers at the point-of-care to measure the cell count of e.g., red blood cells from whole blood samples with a counting speed of >100,000 cells/sec. This novel optical imaging platform can also be merged with microfluidic systems to be able to rapidly monitor and count hundreds of thousand of cells within a field-of-view (FOV) of ∼10 cm2 in vitro. The immediate impact of this lensfree on chip cell counting approach is its improved speed, significantly larger field-of-view and simplified design that permits considerable miniaturization of the entire cell counting device.
Modeling and Realistic Simulation of the Carotid Artery Birfurcation Using 3-D Image Segmentation Implemented in a Commercial Software Package for Hemodynamic Simulation (cvSim™)
Authors: Wilson Nathan M. , Migrino Raymond Q. , Harmann Leanne , Prost Robert W. , LaDisa John F.
Published: March 2014

Stroke is the third leading cause of death and a major cause of disability in the United States. Extracranial carotid artery disease is a major risk factor for stroke. Local hemodynamic forces are important in the development and progression of atherogenesis with areas of low and oscillatory wall shear stress (WSS) such as those occurring in the carotid bifurcation being more prone to atheroma development. Despite the importance of WSS in atherosclerosis, there is currently no practical means of measuring this variable clinically. Computational fluid dynamics (CFD) simulations of patient-specific models built from imaging data may provide a clinically relevant solution [1]. For CFD results to be clinically applicable, they need to replicate hemodynamic and imaging measurements to provide physiologic WSS values and the simulation and quantification process must be conducted in a time-frame consistent with the short duration needed for plaque and intima-media thickness assessment. LaDisa, Migrino and colleagues recently reported on a rapid and practical means of generating WSS maps associated with carotid atherosclerosis using patient-specific CFD models derived from 2D and Doppler ultrasound for flow information and MRI for 3D structure before and after 6 months of statin treatment [2]. Although these results were achieved after 17±8 hours/patient instead of days or weeks for prior models, model construction, quantification of results and simulation time were the most time consuming portions of the simulation process with CFD model construction being the most user-intensive portion of the process.
Dynamic Analysis of Soft Tissues Using a State Space Model
Authors: Pelegri Assimina , Shan Baoxiang
Published: March 2014

Research on the biomechanical behavior of soft tissues has drawn a lot of recent attention due to its application in tumor pathology, rehabilitation, surgery and biomaterial implants. In this study a finite element (FE) model is applied to represent soft tissues and phantoms with complex geometry and heterogeneous material properties. A solid 3D mixed u-p element S8P0 (8-node for displacement and 1-node for internal pressure) is implemented to capture the near-incompressibility inherent in soft tissues. A dynamic analysis of soft tissues’ response to excitation is explored in which, the second order differential equation representing the soft tissues in FE necessitates a time-consuming numerical solution procedure. Moreover, the second-order representation is complicated in estimating the tissue mechanical properties by inverse procedure. Thus, a state space (SS) model is used to equivalently represent soft tissues by transforming the second-order differential equation into a system of linear first-order differential equations. The linear and time-invariant SS representation of soft tissues for general dynamic analysis can reduce the computational cost and a provide framework for the “forward” simulation and “inverse” identification of soft tissues.
Addendum to the AAPMˈs TG‐51 protocol for clinical reference dosimetry of high‐energy photon beams
Authors: McEwen Malcolm , DeWerd Larry , Ibbott Geoffrey , Followill David , Rogers David W. O. , Seltzer Stephen , Seuntjens Jan
Published: March 2014

An addendum to the AAPMˈs TG‐51 protocol for the determination of absorbed dose to water in megavoltage photon beams is presented. This addendum continues the procedure laid out in TG‐51 but newkQ data for photon beams, based on Monte Carlo simulations, are presented and recommendations are given to improve the accuracy and consistency of the protocolˈs implementation. The components of the uncertainty budget in determining absorbed dose to water at the reference point are introduced and the magnitude of each component discussed. Finally, the consistency of experimental determination ofND,w coefficients is discussed. It is expected that the implementation of this addendum will be straightforward, assuming that the user is already familiar with TG‐51. The changes introduced by this report are generally minor, although new recommendations could result in procedural changes for individual users. It is expected that the effort on the medical physicistˈs part to implement this addendum will not be significant and could be done as part of the annual linac calibration.
Lethal Interactions Between Parasites and Prey Increase Niche Diversity in a Tropical Community
Authors: Condon Marty A. , Scheffer Sonja J. , Lewis Matthew L. , Wharton Robert , Adams Dean C. , Forbes Andrew A.
Published: March 2014

Hidden Diversity

Why are there so many species in the tropics? Niche partitioning by highly specialized plant species seems to be the main generator of high diversity.

Condon
et al.

(p.
1240
; see the Perspective by

Godfray

) show that niche partitioning can also be generated by interactions between plant resources and parasites, resulting in hyperdiverse communities. The cryptic diversity of 14 neotropical fly pollinators and 18 of their highly specific wasp parasites induced mortality partitions between multiple narrow niches. The extreme specificity of the wasp-fly relationships was initially only revealed by molecular analysis.
Selective Methylation of Histone H3 Variant H3.1 Regulates Heterochromatin Replication
Authors: Jacob Yannick , Bergamin Elisa , Donoghue Mark T. A. , Mongeon Vanessa , LeBlanc Chantal , Voigt Philipp , Underwood Charles J. , Brunzelle Joseph S. , Michaels Scott D. , Reinberg Danny , Couture Jean-François , Martienssen Robert A.
Published: March 2014

Making a Histone Mark

The covalent marks on histones (the principal components of chromatin) play a critical role in the regulation of gene expression. Somehow these marks are preserved when a cell in a tissue divides so that the daughter cells maintain the gene expression program and tissue identity of the parent cell.

Jacob
et al.

(p.
1249
) show that the
Arabidopsis
histone methylase ATXR5 is specific for the replication-dependent histone variant H3.1 and maintains the repressive histone H3 lysine-27 methyl mark on the H3.1 variant during genome replication, thus, preserving cell-type–specific regions of heterochromatin and gene repression through cell division and beyond.
Main-Group Compounds Selectively Oxidize Mixtures of Methane, Ethane, and Propane to Alcohol Esters
Authors: Hashiguchi Brian G. , Konnick Michael M. , Bischof Steven M. , Gustafson Samantha J. , Devarajan Deepa , Gunsalus Niles , Ess Daniel H. , Periana Roy A.
Published: March 2014

Light Alkanes, Heavy Metals

Hydraulic fracturing, or fracking, has rapidly increased the supply of natural gas and has motivated methods to convert its constituents into commodity chemicals.

Hashiguchi
et al.

(p.
1232
) have found that lead and thallium salts are both efficient and selective oxidants, not only for methane, but for ethane and propane as well. In trifluoroacetic acid solvent, the alkanes are cleanly oxidized to the trifluoroacetate esters of their respective alcohols and 1,2-diols. Building on earlier discoveries, this work paves the way to developing methods that reduce our dependence on petroleum for industrial feedstocks.
Reading Clues in the Sky
Celestial Sleuth
Using Astronomy to Solve Mysteries in Art, History and Literature

by Donald W. Olson

Springer, New York, 2014. 373 pp. Paper, 39.99. ISBN 9781461484028. Springer-Praxis Books in Popular Astronomy.
Authors: Altschuler Eric L.
Published: March 2014

Astronomical clues provide the foundation for Olson's engaging detective work.
Time for New Schizophrenia Rx
Authors: Hyman Steven E.
Published: March 2014

Last month, the battle against four major diseases received some good news. The U.S. National Institutes of Health (NIH) and 10 of the world's largest pharmaceutical companies decided that instead of working ineffectively in silos, they would work together to discover therapies for Alzheimer's disease, type 2 diabetes, rheumatoid arthritis, and lupus. This initiative—the Accelerating Medicines Partnership (AMP)—recognizes that progress toward new therapies for common chronic diseases increasingly requires large-scale collaborative efforts that range from the need to grapple with heterogeneous polygenic disease phenotypes to the validation of biomarkers in large populations. What is disappointing is that, at least for the time being, the consortium dropped schizophrenia from its list, despite vast unmet medical need and substantial, albeit still recent, scientific advances. Was schizophrenia deemed too risky to pursue? If innovative partnerships such as the AMP are not willing to take on common and serious but otherwise neglected disorders such as schizophrenia, then the scientific community will have to find new ways of pooling intellectual and financial resources to address them.
Serum Bactericidal Assays To Evaluate Typhoidal and Nontyphoidal Salmonella Vaccines
Authors: Boyd Mary Adetinuke , Tennant Sharon M. , Saague Venant A. , Simon Raphael , Muhsen Khitam , Ramachandran Girish , Cross Alan S. , Galen James E. , Pasetti Marcela F. , Levine Myron M.
Published: March 2014

InvasiveSalmonellainfections for which improved or new vaccines are being developed include enteric fever caused bySalmonella entericaserovars Typhi, Paratyphi A, and Paratyphi B and sepsis and meningitis in young children in sub-Saharan Africa caused by nontyphoidalSalmonella(NTS) serovars, particularlyS. entericaserovars Typhimurium and Enteritidis. Assays are needed to measure functional antibodies elicited by the new vaccines to assess their immunogenicities and potential protective capacities. We developedin vitroassays to quantify serum bactericidal antibody (SBA) activity induced byS. Typhi,S. Paratyphi A,S. Typhimurium, andS. Enteritidis vaccines in preclinical studies. Complement from various sources was tested in assays designed to measure antibody-dependent complement-mediated killing. Serum from rabbits 3 to 4 weeks of age provided the best complement source compared to serum from pigs, goats, horses, bovine calves, or rabbits 8 to 12 weeks of age. ForS. Enteritidis,S. Typhimurium, andS. Typhi SBA assays to be effective, bacteria had to be harvested at log phase. In contrast,S. Paratyphi A was equally susceptible to killing whether it was grown to the stationary or log phase. The typhoidal serovars were more susceptible to complement-mediated killing than were the nontyphoidal serovars. Lastly, the SBA endpoint titers correlated with serum IgG anti-lipopolysaccharide (LPS) titers in mice immunized with mucosally administeredS. Typhimurium,S. Enteritidis, andS. Paratyphi A but notS. Typhi live attenuated vaccines. The SBA assay described here is a useful tool for measuring functional antibodies elicited bySalmonellavaccine candidates.
Posttraumatic Brain Abscess Caused by Aeromonas hydrophila
Authors: Mahabeer Yesholata , Khumalo Amanda , Kiratu Erastus , Mlisana Koleka
Published: March 2014

Posttraumatic brain abscesses are usually caused by Gram-negative bacilli, notably
Enterobacteriaceae
and
Staphylococcus aureus
. Although
Aeromonas hydrophila
is a recognized cause of trauma-related sepsis, it has not been previously isolated from posttraumatic brain abscesses. We describe the first case of
Aeromonas hydrophila
brain abscess.
High Rates of Infection with Novel Enterovirus Variants in Wild Populations of Mandrills and Other Old World Monkey Species
Authors: Nguyen Dung Van , Harvala Heli , Ngole Eitel Mpoudi , Delaporte Eric , Woolhouse Mark E. J. , Peeters Martine , Simmonds Peter
Published: March 2014

Enteroviruses (EVs) are a genetically and antigenically diverse group of viruses infecting humans. A mostly distinct set of EV variants have additionally been documented to infect wild apes and several, primarily captive, Old World monkey (OWM) species. To investigate the prevalence and genetic characteristics of EVs infecting OWMs in the wild, fecal samples from mandrills (
Mandrillus sphinx
) and other species collected in remote regions of southern Cameroon were screened for EV RNA. Remarkably high rates of EV positivity were detected in
M. sphinx
(100 of 102 screened),
Cercocebus torquatus
(7/7), and
Cercopithecus cephus
(2/4), with high viral loads indicative of active infection. Genetic characterization in VP4/VP2 and VP1 regions allowed EV variants to be assigned to simian species H (
EV-H
) and
EV-J
(including one or more new types), while seven matched simian
EV-B
variants, SA5 and EV110 (chimpanzee). Sequences from the remaining 70 formed a new genetic group distinct in VP4/2 and VP1 region from all currently recognized human or simian EV species. Complete genome sequences were obtained from three to determine their species assignment. In common with
EV-J
and the
EV-A
A13 isolate, new group sequences were chimeric, being most closely related to
EV-A
in capsid genes and to
EV-B
in the nonstructural gene region. Further recombination events created different groupings in 5′ and 3′ untranslated regions. While clearly a distinct EV group, the hybrid nature of new variants prevented their unambiguous classification as either members of a new species or as divergent members of
EV-A
using current International Committee on Taxonomy of Viruses (ICTV) assignment criteria.

IMPORTANCE
This study is the first large-scale investigation of the frequency of infection and diversity of enteroviruses (EVs) infecting monkeys (primarily mandrills) in the wild. Our findings demonstrate extremely high frequencies of active infection (95%) among mandrills and other Old World monkey species inhabiting remote regions of Cameroon without human contact. EV variants detected were distinct from those infecting human populations, comprising members of enterovirus species B, J, and H and a large novel group of viruses most closely related to species A in the P1 region. The viral sequences obtained contribute substantially to our growing understanding of the genetic diversity of EVs and the existence of interspecies chimerism that characterizes the novel variants in the current study, as well as in previously characterized species A and J viruses infecting monkeys. The latter findings will contribute to future development of consensus criteria for species assignments in enteroviruses and other picornavirus genera.
Emergence and Evolution of Avian H5N2 Influenza Viruses in Chickens in Taiwan
Authors: Lee Chang-Chun David , Zhu Huachen , Huang Pei-Yu , Peng Liuxia , Chang Yun-Cheng , Yip Chun-Hung , Li Yao-Tsun , Cheung Chung-Lam , Compans Richard , Yang Chinglai , Smith David K. , Lam Tommy Tsan-Yuk , King Chwan-Chuen , Guan Yi
Published: March 2014

Sporadic activity by H5N2 influenza viruses has been observed in chickens in Taiwan from 2003 to 2012. The available information suggests that these viruses were generated by reassortment between a Mexican-like H5N2 virus and a local enzootic H6N1 virus. Yet the origin, prevalence, and pathogenicity of these H5N2 viruses have not been fully defined. Following the 2012 highly pathogenic avian influenza (HPAI) outbreaks, surveillance was conducted from December 2012 to July 2013 at a live-poultry wholesale market in Taipei. Our findings showed that H5N2 and H6N1 viruses cocirculated at low levels in chickens in Taiwan. Phylogenetic analyses revealed that all H5N2 viruses had hemagglutinin (HA) and neuraminidase (NA) genes derived from a 1994 Mexican-like virus, while their internal gene complexes were incorporated from the enzootic H6N1 virus lineage by multiple reassortment events. Pathogenicity studies demonstrated heterogeneous results even though all tested viruses had motifs (R-X-K/R-R) supportive of high pathogenicity. Serological surveys for common subtypes of avian viruses confirmed the prevalence of the H5N2 and H6N1 viruses in chickens and revealed an extraordinarily high seroconversion rate to an H9N2 virus, a subtype that is not found in Taiwan but is prevalent in mainland China. These findings suggest that reassortant H5N2 viruses, together with H6N1 viruses, have become established and enzootic in chickens throughout Taiwan and that a large-scale vaccination program might have been conducted locally that likely led to the introduction of the 1994 Mexican-like virus to Taiwan in 2003.

IMPORTANCE
H5N2 avian influenza viruses first appeared in chickens in Taiwan in 2003 and caused a series of outbreaks afterwards. Phylogenetic analyses show that the chicken H5N2 viruses have H5 and N2 genes that are closely related to those of a vaccine strain originating from Mexico in 1994, while the contemporary duck H5N2 viruses in Taiwan belong to the Eurasian gene pool. The unusually high similarity of the chicken H5N2 viruses to the Mexican vaccine strain suggests that these viruses might have been introduced to Taiwan by using inadequately inactivated or attenuated vaccines. These chicken H5N2 viruses are developing varying levels of pathogenicity that could lead to significant consequences for the local poultry industry. These findings emphasize the need for strict quality control and competent oversight in the manufacture and usage of avian influenza virus vaccines and indicate that alternatives to widespread vaccination may be desirable.
Envelope Proteins Derived from Naturally Integrated Hepatitis B Virus DNA Support Assembly and Release of Infectious Hepatitis Delta Virus Particles
Authors: Freitas Natalia , Cunha Celso , Menne Stephan , Gudima Severin O.
Published: March 2014

A natural subviral agent of human hepatitis B virus (HBV), hepatitis delta virus (HDV), requires only the envelope proteins from HBV in order to maintain persistent infection. HBV surface antigens (HBsAgs) can be produced either by HBV replication or from integrated HBV DNA regardless of replication. The functional properties of the integrant-generated HBsAgs were examined using two human hepatocellular carcinoma-derived cell lines, Hep3B and PLC/PRF/5, that contain HBV integrants but do not produce HBV virions and have no signs of HBV replication. Both cell lines were able to support HDV replication and assembly/egress of HDV virions. Neither of the cell lines was able to produce substantial amounts of the pre-S1-containing HDV particles. HDV virions assembled in PLC/PRF/5 cells were able to infect primary human hepatocytes, while Hep3B-derived HDV appeared to be noninfectious. These results correlate with the findings that the entire open reading frame (ORF) for the large (L) envelope protein that is essential for infectivity is present on HBV RNAs from PLC/PRF/5 cells, while an L protein ORF that was truncated and fused to inverted precore sequences was found using RNAs from Hep3B cells. This study demonstrates for the first time that at least some of the HBV DNA sequence naturally integrated during infection can produce functional small and large envelope proteins capable of the formation of infectious HDV virions. Our data indicate that
in vivo
chronic HDV infection can persist in the absence of HBV replication (or when HBV replication is profoundly suppressed) if functional envelope proteins are supplied from HBV integrants.

IMPORTANCE
The study addresses the unique mechanism of HDV persistence in the absence of ongoing HBV replication, advances our understanding of HDV-HBV interactions, and supports the implementation of treatments directly targeting HDV for HDV/HBV-infected individuals.
An Epistatic Relationship between the Viral Protein Kinase UL97 and the
UL133-UL138
Latency Locus during the Human Cytomegalovirus Lytic Cycle
Authors: Li Gang , Rak Michael , Nguyen Christopher C. , Umashankar Mahadevaiah , Goodrum Felicia D. , Kamil Jeremy P.
Published: March 2014

We report that
UL133-UL138
(
UL133/8
), a transcriptional unit within the UL
b
′ region (UL
b
′) of the human cytomegalovirus (HCMV) genome, and UL97, a viral protein kinase encoded by HCMV, play epistatic roles in facilitating progression of the viral lytic cycle. In studies with HCMV strain TB40/E, pharmacological blockade or genetic ablation of UL97 significantly reduced the levels of mRNA and protein for IE2 and viral early and early-late genes during a second wave of viral gene expression that commenced at between 24 and 48 h postinfection. These effects were accompanied by significant defects in viral DNA synthesis and viral replication. Interestingly, deletion of
UL133/8
likewise caused significant defects in viral DNA synthesis, viral gene expression, and viral replication, which were not exacerbated upon UL97 inhibition. When
UL133/8
was restored to HCMV laboratory strain AD169, which otherwise lacks the locus, the resulting recombinant virus replicated similarly to the parental virus. However, during UL97 inhibitor treatment, the virus in which
UL133/8
was restored showed significantly exacerbated defects in viral DNA synthesis, viral gene expression, and production of infectious progeny virus, thus recapitulating the differences between wild-type TB40/E and its
UL133/8
-null derivative. Phenotypic evaluation of mutants null for specific open reading frames within
UL133/8
revealed a role for UL135 in promoting viral gene expression, viral DNA synthesis, and viral replication, which depended on UL97. Taken together, our findings suggest that UL97 and UL135 play interdependent roles in promoting the progression of a second phase of the viral lytic cycle and that these roles are crucial for efficient viral replication.

IMPORTANCE
A unique feature of the herpesviruses, such as human cytomegalovirus (HCMV), is that they can undergo latency, a state during which the virus silences its gene expression, which allows lifelong viral persistence in immunocompetent hosts. We have uncovered an unexpected link between a cluster of HCMV genes involved in latency,
UL133-UL138
, and a virally encoded protein kinase, UL97, which plays crucial roles in manipulating the cell cycle during HCMV lytic replication. Although viral immediate early (IE) gene expression is essential for HCMV lytic replication, the activation of IE gene expression in latently infected cells is not sufficient to result in production of infectious virus. Our findings here and in an accompanying study (
M. Umashankar, M. Rak, F. Bughio, P. Zagallo, K. Caviness, and F. D. Goodrum
, J. Virol. 88:5987–6002, 2014) show that proteins expressed from the
UL133-UL138
latency locus and UL97 play interdependent roles in overcoming checkpoints that restrict the viral lytic replication cycle, findings which suggest intriguing implications for establishment of and reactivation from HCMV latency.
Sp100 Isoform-Specific Regulation of Human Adenovirus 5 Gene Expression
Authors: Berscheminski Julia , Wimmer Peter , Brun Juliane , Ip Wing Hang , Groitl Peter , Horlacher Tim , Jaffray Ellis , Hay Ron T. , Dobner Thomas , Schreiner Sabrina
Published: March 2014

Promyelocytic leukemia nuclear bodies (PML-NBs) are nuclear structures that accumulate intrinsic host factors to restrict viral infections. To ensure viral replication, these must be limited by expression of viral early regulatory proteins that functionally inhibit PML-NB-associated antiviral effects. To benefit from the activating capabilities of Sp100A and simultaneously limit repression by Sp100B, -C, and -HMG, adenoviruses (Ads) employ several features to selectively and individually target these isoforms. Ads induce relocalization of Sp100B, -C, and -HMG from PML-NBs prior to association with viral replication centers. In contrast, Sp100A is kept at the PML tracks that surround the newly formed viral replication centers as designated sites of active transcription. We concluded that the host restriction factors Sp100B, -C, and -HMG are potentially inactivated by active displacement from these sites, whereas Sp100A is retained to amplify Ad gene expression. Ad-dependent loss of Sp100 SUMOylation is another crucial part of the virus repertoire to counteract intrinsic immunity by circumventing Sp100 association with HP1, therefore limiting chromatin condensation. We provide evidence that Ad selectively counteracts antiviral responses and, at the same time, benefits from PML-NB-associated components which support viral gene expression by actively recruiting them to PML track-like structures. Our findings provide insights into novel strategies for manipulating transcriptional regulation to either inactivate or amplify viral gene expression.

IMPORTANCEWe describe an adenoviral evasion strategy that involves isoform-specific and active manipulation of the PML-associated restriction factor Sp100. Recently, we reported that the adenoviral transactivator E1A targets PML-II to efficiently activate viral transcription. In contrast, the PML-associated proteins Daxx and ATRX are inhibited by early viral factors. We show that this concept is more intricate and significant than originally believed, since adenoviruses apparently take advantage of specific PML-NB-associated proteins and simultaneously inhibit antiviral measures to maintain the viral infectious program. Specifically, we observed Ad-induced relocalization of the Sp100 isoforms B, C, and HMG from PML-NBs juxtaposed with viral replication centers. In contrast, Sp100A is retained at Ad-induced PML tracks that surround the newly formed viral replication centers, acting as designated sites of active transcription. The host restriction factors Sp100B, -C, and -HMG are potentially inactivated by active displacement from these sites, whereas Sp100A is retained to amplify Ad gene expression.
Cocirculation of Three Hemagglutinin and Two Neuraminidase Subtypes of Avian Influenza Viruses in Huzhou, China, April 2013: Implication for the Origin of the Novel H7N9 Virus
Authors: Han Jiankang , Wang Lili , Liu Jia , Jin Meihua , Hao Fangyuan , Zhang Peng , Zhang Zhao , Wen Dong , Wu Xiaofang , Liu Guangtao , Ji Lei , Xu Deshun , Zhou Dongming , Leng Qibin , Lan Ke , Zhang Chiyu
Published: March 2014

We detected three avian influenza hemagglutinin (HA) subtypes (H7, H9, and H5) and two neuraminidase (NA) subtypes (N9 and N2), as well as H7N9-related H9N9 reassortant intermediates, cocirculating among poultry in Huzhou, China, during April 2013. The results of our study reveal not only that Huzhou is one of the geographic origins of the novel H7N9 virus but also that cocirculation poses a potential threat to humans in the future.
Mechanisms of RIG-I-Like Receptor Activation and Manipulation by Viral Pathogens
Authors: Gack Michaela U.
Published: March 2014

RIG-I-like receptors (RLRs) play important roles in the host defense to numerous viral pathogens. Since they were discovered, much light has been shed on the molecular details of how these cytoplasmic viral RNA receptors sense viral infection and orchestrate antiviral innate immunity. Intriguingly, in addition to viral RNA binding, a series of posttranslational modifications (PTMs) is required for the rapid activation of RLRs and, inversely, for the prevention of aberrant innate immune signaling. Recent discoveries have shown that viruses manipulate the PTMs of RLRs to escape innate immune detection. This article highlights some of these recent findings in this fast-evolving field.
Antagonistic Determinants Controlling Replicative and Latent States of Human Cytomegalovirus Infection
Authors: Umashankar Mahadevaiah , Rak Michael , Bughio Farah , Zagallo Patricia , Caviness Katie , Goodrum Felicia D.
Published: March 2014

The mechanisms by which viruses persist and particularly those by which viruses actively contribute to their own latency have been elusive. Here we report the existence of opposing functions encoded by genes within a polycistronic locus of the human cytomegalovirus (HCMV) genome that regulate cell type-dependent viral fates: replication and latency. The locus, referred to as the
UL133-UL138
(
UL133/8
) locus, encodes four proteins, pUL133, pUL135, pUL136, and pUL138. As part of the UL
b
′ region of the genome, the
UL133/8
locus is lost upon serial passage of clinical strains of HCMV in cultured fibroblasts and is therefore considered dispensable for replication in this context. Strikingly, we could not reconstitute infection in permissive fibroblasts from bacterial artificial chromosome clones of the HCMV genome where
UL135
alone was disrupted. The loss of
UL135
resulted in complex phenotypes and could ultimately be overcome by infection at high multiplicities. The requirement for
UL135
but not the entire locus led us to hypothesize that another gene in this locus suppressed virus replication in the absence of
UL135
. The defect associated with the loss of
UL135
was largely rescued by the additional disruption of the
UL138
latency determinant, indicating a requirement for
UL135
for virus replication when
UL138
is expressed. In the CD34
+
hematopoietic progenitor model of latency, viruses lacking only
UL135
were defective for viral genome amplification and reactivation. Taken together, these data indicate that
UL135
and
UL138
comprise a molecular switch whereby
UL135
is required to overcome
UL138
-mediated suppression of virus replication to balance states of latency and reactivation.

IMPORTANCE
Mechanisms by which viruses persist in their host remain one of the most poorly understood phenomena in virology. Herpesviruses, including HCMV, persist in an incurable, latent state that has profound implications for immunocompromised individuals, including transplant patients. Further, the latent coexistence of HCMV may increase the risk of age-related pathologies, including vascular disease. The key to controlling or eradicating HCMV lies in understanding the molecular basis for latency. In this work, we describe the complex interplay between two viral proteins, pUL135 and pUL138, which antagonize one another in infection to promote viral replication or latency, respectively. We previously described the role of pUL138 in suppressing virus replication for latency. Here we demonstrate a role of pUL135 in overcoming pUL138-mediated suppression for viral reactivation. From this work, we propose that pUL135 and pUL138 constitute a molecular switch balancing states of latency and reactivation.
A rare association of extragonadal seminoma with synchronous papillary carcinoma of the thyroid
Authors: Barrington Craig , Bertelli Gianfilippo , Evans Rhodri
Published: March 2014

A 45-year-old man presented with a large para-aortic retroperitoneal tumour, a smaller second mediastinal tumour and elevated lactate dehydrogenase (LDH). Biopsy established a diagnosis of extragonadal seminoma. Treatment with cisplatin and etoposide resulted in complete resolution of the mediastinal mass, reduction of the size of the retroperitoneal mass and normalisation of LDH. Postchemotherapy positron emission tomography (PET) scan showed a small residual focus of uptake in the retroperitoneal mass and an unexpected focus in the left side of the neck. This was initially thought to represent residual active disease, but an ultrasound (US) scan and US-guided core biopsy of a cervical lymph node demonstrated metastatic papillary thyroid cancer rather than seminoma. A small (1 cm) primary papillary tumour in the thyroid was identified subsequently. The patient received consolidation radiotherapy to the retroperitoneum and underwent total thyroidectomy and neck dissection followed by radio-iodine treatment. He is currently in complete remission from both cancers.
Successful gefitinib treatment administration via gastrostomy tube in a patient with non-small cell lung cancer with dysphagia
Authors: Suzumura Tomohiro , Yonesaka Kimio , Tsukuda Hiroshi , Fukuoka Masahiro
Published: March 2014

A 72-year-old woman with dysphagia was diagnosed with lung adenocarcinoma and metastatic meningeal tumour that impaired the medulla. Owing to a bulky tumour beside the medulla, radiosurgical control of the meningeal tumour was achieved before systemic therapy. Genomic examination of the tumour revealed an existing epidermal growth factor receptor (EGFR) exon 19 deletion, for which an EGFR tyrosine kinase inhibitor such as gefitinib was the standard therapy. However, because of dysphagia, the patient was unable to orally ingest gefitinib. Gefitinib was delivered via gastrostomy tube as a suspension after spontaneous dissolution in hot water. One month later, the patient's symptoms, including dysphagia, were drastically improved and she had recovered sufficiently to orally ingest gefitinib. Gefitinib-associated toxicity comprises only mild liver dysfunction and skin rash. CT scanning and MRI detected drastic shrinkage of the primary lung and meningeal tumours. The patient continued to take gefitinib and has remained symptom-free for 9 months.
Midlife and late-life handgrip strength and risk of cause-specific death in a general Japanese population: the Hisayama Study
Authors: Kishimoto Hiro , Hata Jun , Ninomiya Toshiharu , Nemeth Hajnalka , Hirakawa Yoichiro , Yoshida Daigo , Kumagai Shuzo , Kitazono Takanari , Kiyohara Yutaka
Published: March 2014

Background

Decreased handgrip strength has been reported to be a risk factor for all-cause death among the elderly. However, it is unclear whether handgrip strength measured in midlife is associated with risk of all-cause and cause-specific death in the general population.

Methods

We followed, prospectively, a total of 2527 community-dwelling Japanese (1064 men and 1463 women) aged ≥40 years for 19 years. Participants were divided into three groups according to the age-specific and sex-specific tertiles of handgrip strength (T1, lowest; T3, highest).

Results

During the follow-up period, 783 participants died, of whom 235 died of cardiovascular disease, 249 of cancer, 154 of respiratory disease and 145 of other causes. In the middle-aged group (40–64 years), multivariable-adjusted HRs (95% CIs) for all-cause death were 0.75 (0.56 to 0.99) in T2 and 0.49 (0.35 to 0.68) in T3 compared with T1 as a reference. Corresponding HRs (95% CI) in the elderly group (≥65 years) were 0.50 (0.40 to 0.62) and 0.41 (0.32 to 0.51), respectively. As regards the cause of death, higher levels of handgrip strength were significantly associated with decreased risks of cardiovascular death, respiratory death and death from other causes, but not of cancer, in the middle-aged and the elderly.

Conclusions

Our findings suggest that handgrip strength levels in midlife and late life are inversely associated with the risks of all-cause and non-cancer death in the general Japanese population.
Acute psychological and physical stress transiently enhances brachial artery flow-mediated dilation stimulated by exercise-induced increases in shear stress
Authors: Szijgyarto Ingrid C. , Poitras Veronica J. , Gurd Brendon J. , Pyke Kyra E.
Published: March 2014

Exercise elevates conduit artery shear stress and stimulates flow-mediated dilation (FMD). However, little is known regarding the impact of acute psychological and physical stress on this response. The purpose of this study was to examine the impact of the Trier Social Stress Test (TSST (speech and arithmetic tasks)) and a cold pressor test (CPT) with and without social evaluation (SE) on exercise-induced brachial artery FMD (EX-FMD). A total of 59 healthy male subjects were randomly assigned to 1 of 3 conditions: TSST, CPT, or CPT with SE. During 6 min of handgrip exercise, brachial artery EX-FMD was assessed before and 15 and 35 min poststress with echo and Doppler ultrasound. Shear stress was estimated as shear rate, calculated as brachial artery mean blood velocity/brachial artery diameter. Results are means ± SD. All conditions elicited significant physiological stress responses. Salivary cortisol increased from 4.6 ± 2.4 nmol/L to 10.0 ± 5.0 nmol/L (p < 0.001; condition effect: p = 0.292). Mean arterial pressure increased from 98.6 ± 12.1 mm Hg to 131.9 ± 18.7 mm Hg (p < 0.001; condition effect: p = 0.664). Exercise shear rate did not differ between conditions (p = 0.592), although it was modestly lower poststress (prestress: 72.3 ± 4.5 s−1; 15 min poststress: 70.8 ± 5.4 s−1; 35 min poststress: 70.6 ± 6.1 s−1; trial effect: p = 0.011). EX-FMD increased from prestress to 15 min poststress in all conditions (prestress: 6.2% ± 2.8%; 15 min poststress: 7.9% ± 3.2%; 35 min poststress: 6.6% ± 2.9%; trial effect: p < 0.001; condition effect: p = 0.611). In conclusion, all conditions elicited similar stress responses that transiently enhanced EX-FMD. This response may help to support muscle perfusion during stress.
Material and growth mechanism studies of microcrystalline silicon deposited from SiF4/H2/Ar gas mixtures
Authors: Dornstetter Jean-Christophe , Wang Junkang , Bruneau Bastien , Johnson Erik V. , Roca i Cabarrocas Pere
Published: March 2014

Hydrogenated microcrystalline silicon is of great interest as the intrinsic layer in thin film solar cells. It is generally accepted that optimized cells use an I-layer with a crystalline fraction ranging from 50% to 70%. We report here on the use of fully crystallized layers deposited from SiF4/H2/Ar gas mixtures. A VOC of 536 mV and a JSC of 25.4 mA/cm2 have been obtained in PIN solar cells using a fully crystallized intrinsic material. Fourier transform photocurrent spectroscopy measurements show that the films have a very low defect density down to 5.1 × 1014 cm−3. The role of H2 during deposition has been investigated: it is demonstrated that H2 is needed to remove F by forming HF molecules. When all atomic F has been removed from the plasma, the remaining atomic H can then contribute to μc-Si:H growth.
Path integral of a relativistic spinning particle in (1+1) dimension with vector and scalar linear potentials in the presence of a minimal length
Authors: Benzair H. , Merad M. , Boudjedaa T.
Published: March 2014

Using the path integral formalism in (1+1) dimension of the energy–momentum space representation, we calculate the Green function of relativistic spinning particle subjected to the action of combined vector and scalar linear potentials in the framework of deformed Heisenberg algebra which distinguish to the appearance of nonzero minimum position uncertainty given by [Formula: see text] where β is the deformation parameter of the modified Heisenberg uncertainty relation [Formula: see text]. We adapt the space–time transformation method to evaluate quantum corrections and this latter are dependent on the α-point discretization interval. The exact bound states spectrum and the corresponding momentum space wave function are obtained.
Gravitating dyons in Vaidya geometry
Authors: Tripathi Buddhi Vallabh , Nandan Hemwati , Dehnen Heinz , Purohit K. D.
Published: March 2014

Gravitating monopoles and dyons in Einstein–Yang–Mills (EYM) or Einstein–Yang–Mills–Higgs (EYMH) systems have been extensively studied for various curved space–times, including those of black holes. We construct dyonic solutions of the EYMH theory in Vaidya space–time using a set of generalized Julia–Zee ansatz for the fields. It is found that the dyonic charge is static in nature and it does not contribute to the energy of the null dust.
Prokinetic effects of mirtazapine on gastrointestinal transit
Authors: Yin Jieyun , Song Jun , Lei Yong , Xu Xiaohong , Chen Jiande D. Z.
Published: March 2014

Mirtazapine is a noradrenergic and specific serotonergic antidepressant. The aim of this study was to investigate the effects of mirtazapine on gastrointestinal motility in dogs, including solid gastric emptying, antral and small intestinal contractions, and small intestinal and colonic transit. Six dogs were implanted with two cannulas located at the duodenum and the ascending colon; another six dogs were implanted with gastric cannula 6 cm proximal to the pylorus. Mirtazapine 45 mg was administered orally 90 min before the study. We found that 1) Mirtazapine accelerated gastric emptying during the entire 3 h in normal dogs ( P < 0.04) and accelerated delayed gastric emptying induced by rectal distention ( P < 0.04). 2) Mirtazapine restored impaired gastric tone and accommodation induced by rectal distention ( P < 0.05). 3) No significant changes were noted in small intestinal contractions or transit with mirtazapine ( P > 0.1). 4) Mirtazapine accelerated colonic transit at 2 and 4 h but not 6 h. The geometric center was increased from 1.9 ± 0.6 to 3.0 ± 0.5 and 3.9 ± 0.5 to 4.7 ± 0.1 at 2 and 4 h respectively ( P = 0.04 vs. corresponding control). In conclusion, mirtazapine improves gastric emptying in healthy dogs and normalizes rectal distention-induced delay in gastric emptying and accelerates colon but not small intestinal transit in healthy dogs. Clinical studies are warranted to assess the effects of mirtazapine on gastrointestinal motility and sensory functions in patients with functional gastrointestinal diseases.
Hydrogen sulfide alleviates cardiac contractile dysfunction in an Akt2-knockout murine model of insulin resistance: role of mitochondrial injury and apoptosis
Authors: Hu Nan , Dong Maolong , Ren Jun
Published: March 2014

Hydrogen sulfide (H2S) is a toxic gas now being recognized as an endogenous signaling molecule in multiple organ systems, in particular, the cardiovascular system. H2S is known to regulate cardiac function and protect against ischemic injury. However, little information is available regarding the effect of H2S on cardiac function in insulin resistance. This study was designed to examine the impact of H2S supplementation on cardiac function using an Akt2 knockout model of insulin resistance. Wild-type and Akt2 knockout mice were treated with NaHS (50 μM·kg−1·day−1 ip for 10 days) prior to evaluation of echocardiographic, cardiomyocyte contractile, and intracellular Ca2+ properties, apoptosis, and mitochondrial damage. Our results revealed that Akt2 ablation led to overtly enlarged ventricular end-systolic diameter, reduced myocardial and cardiomyocyte contractile function, and disrupted intracellular Ca2+ homeostasis and apoptosis, the effects of which were ameliorated by H2S. Furthermore, Akt2 knockout displayed upregulated apoptotic protein markers (Bax, caspase-3, caspase-9, and caspace-12) and mitochondrial damage (reduced aconitase activity and NAD+, elevated cytochrome- c release from mitochondria) along with reduced phosphorylation of PTEN, Akt, and GSK3β in the absence of changes in pan protein expression, the effects of which were abolished or significantly ameliorated by H2S treatment. In vitro data revealed that H2S-induced beneficial effect against Akt2 ablation was obliterated by mitochondrial uncoupling. Taken together, our findings suggest the H2S may reconcile Akt2 knockout-induced myocardial contractile defect and intracellular Ca2+ mishandling, possibly via attenuation of mitochondrial injury and apoptosis.
High glucose and diabetes enhanced store-operated Ca2+entry and increased expression of its signaling proteins in mesangial cells
Authors: Chaudhari Sarika , Wu Peiwen , Wang Yanxia , Ding Yanfeng , Yuan Joseph , Begg Malcolm , Ma Rong
Published: March 2014

The present study was conducted to determine whether and how store-operated Ca2+entry (SOCE) in glomerular mesangial cells (MCs) was altered by high glucose (HG) and diabetes. Human MCs were treated with either normal glucose or HG for different time periods. Cyclopiazonic acid-induced SOCE was significantly greater in the MCs with 7-day HG treatment and the response was completely abolished by GSK-7975A, a selective inhibitor of store-operated Ca2+channels. Similarly, the inositol 1,4,5-trisphosphate-induced store-operated Ca2+currents were significantly enhanced in the MCs treated with HG for 7 days, and the enhanced response was abolished by both GSK-7975A and La3+. In contrast, receptor-operated Ca2+entry in MCs was significantly reduced by HG treatment. Western blotting showed that HG increased the expression levels of STIM1 and Orai1 in cultured MCs. A significant HG effect occurred at a concentration as low as 10 mM, but required a minimum of 7 days. The HG effect in cultured MCs was recapitulated in renal glomeruli/cortex of both type I and II diabetic rats. Furthermore, quantitative real-time RT-PCR revealed that a 6-day HG treatment significantly increased the mRNA expression level of STIM1. However, the expressions of STIM2 and Orai1 transcripts were not affected by HG. Taken together, these results suggest that HG/diabetes enhanced SOCE in MCs by increasing STIM1/Orai1 protein expressions. HG upregulates STIM1 by promoting its transcription but increases Orai1 protein through a posttranscriptional mechanism.
Decoupling motor plans from perceptual decisions to investigate whether and when decisions are embodied
Authors: Sandrone Stefano
Published: March 2014

Decision making is a crucial part of our life: we sense information from the environment and perform our motor response. However, “whether” and “when” decisions are embodied still needs to be fully elucidated. Neuroimaging data obtained by the disentanglement of perceptual decision from motor preparation revealed an increase in connectivity between inferior frontal cortex and sensory regions, and the important role played by intraparietal sulcus in motor decisions. The results obtained as well as the new research questions prompted by this work are carefully discussed herein.