bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Muscle Hypertrophy on the Moment Arm of the Triceps Brachii Muscle
Authors: Sugisaki Norihide , Wakahara Taku , Murata Koichiro , Miyamoto Naokazu , Kawakami Yasuo , Kanehisa Hiroaki , Fukunaga Tetsuo
Published: November 2014

Although the moment arm of the triceps brachii muscle has been shown to be associated with the muscle’s anatomical crosssectional area, whether training-induced muscle hypertrophy alters the moment arm of the muscle remains unexplored. Therefore, the current study aimed to examine this. Eleven men underwent a 12-week resistance training program for the triceps brachii muscle. The maximum muscle anatomical cross-sectional area (ACSAmax), the moment arm of the triceps brachii muscle, and the anterior-posterior dimension of the olecranon were measured using a magnetic resonance imaging system before and after intervention. The ACSAmax (33.6 ± 11.9%, P < .001) and moment arm (5.5 ± 4.0%, P = .001) significantly increased after training, whereas the anterior-posterior dimension of the olecranon did not change (P > .05). The change in moment arm was smaller than that expected from the relationship between the ACSAmax and the moment arm before the intervention. The present results indicate that training-induced triceps brachii muscle hypertrophy could increase the muscle moment arm, but its impact can be small or negligible.
Low-Cost and Scalable Classroom Equipment to Promote Physical Activity and Improve Education
Authors: McCrady-Spitzer Shelly K. , Manohar Chinmay U. , Koepp Gabriel A. , Levine James A.
Published: November 2014

Background:

We tested a low-cost and scalable set of classroom equipment, called Active Classroom Equipment, which was designed to promote physical activity while children learn. We hypothesized the Active Classroom Equipment would be associated with increased physical activity without impairing learning.

Methods:

Fourteen first-grade students in a public elementary school (7 females, 7 males, aged 6.9 ± (SD) 0.4 years, 24 ± 5.4 kg, BMI 15.8 ± 2.6 kg/m2) used the Active Classroom Equipment for 30 minutes each day throughout the school year. Five-day physical activity was measured using validated triaxial accelerometers at baseline (before the intervention began) and on 4 sequential occasions during the 9-month intervention.

Results:

For the baseline period, 5-day physical activity averaged 157 ± 65 AU/min. When the 14 children accessed the Active Classroom Equipment, their mean 5-day physical activity was 229 ± 103 Acceleration Units (AU)/min (P < .0001). There were sequential increases in physical activity over the 9-month intervention (Quarter 1: 163 ± 94 AU/min, Quarter 2: 227 ± 108 AU/min, Quarter 3: 278 ± 61 AU/min, Quarter 4: 305 ± 65 AU/min). Students’ Dynamic Indicators of Basic Early Literacy Skills (DIBELS) scores improved.

Conclusion:

Active Classroom Equipment may be one approach to increase physical activity.
Participation in a Social-Support Physical Activity Intervention Modestly Improves Lipoprotein Cholesterol Distribution Among Postpartum Sedentary Hispanic Women
Authors: Vega-López Sonia , Pignotti Giselle A.P. , Keller Colleen , Todd Michael , Ainsworth Barbara , Williams Allison Nagle , Records Kathie , Coonrod Dean , Permana Paska
Published: November 2014

Background:

The effects of moderate intensity walking on lipoprotein remodeling in postpartum Hispanic women are unknown.

Methods:

Sedentary postpartum Hispanic women (28.2 ± 5.6 y; BMI = 29.3 ± 3.3 kg/m2) participating in a social support physical activity (PA) intervention, were randomly assigned to a 12-month walking program (walkers; n = 22; target 150 min/wk, moderate intensity) or a control group (nonwalkers; n = 22). Fasting lipids and cholesterol distribution within low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles were measured at baseline (BL), 6 months, and 12 months.

Results:

Walkers had an 11% increase and nonwalkers a 7% decrease in HDL cholesterol from 6 to 12 months (P = .0367) without an effect on LDL cholesterol. Whereas nonwalkers had virtually no change in mean LDL particle size, walkers had a borderline reduction in LDL size from BL (268.7 ± 4.1 Å) to 6 months (266.9 ± 4.9 Å), followed by a significant increase in size by 12 months (269.7 ± 4.1 Å; P = .011). The proportion of cholesterol in large LDL particles decreased by 15% from BL to 6 months, but subsequently increased 25% by 12 months among walkers; changes among nonwalkers were smaller and in opposite direction (4% and –3%, respectively; P = .0004).

Conclusions:

Participation in the social-support PA intervention resulted in slightly increased HDL cholesterol concentrations and a modest and beneficial shift toward larger, less atherogenic LDL particles.
Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution
Authors: Vierstra Jeff , Rynes Eric , Sandstrom Richard , Zhang Miaohua , Canfield Theresa , Hansen R. Scott , Stehling-Sun Sandra , Sabo Peter J. , Byron Rachel , Humbert Richard , Thurman Robert E. , Johnson Audra K. , Vong Shinny , Lee Kristen , Bates Daniel , Neri Fidencio , Diegel Morgan , Giste Erika , Haugen Eric , Dunn Douglas , Wilken Matthew S. , Josefowicz Steven , Samstein Robert , Chang Kai-Hsin , Eichler Evan E. , De Bruijn Marella , Reh Thomas A. , Skoultchi Arthur , Rudensky Alexander , Orkin Stuart H. , Papayannopoulou Thalia , Treuting Piper M. , Selleri Licia , Kaul Rajinder , Groudine Mark , Bender M. A. , Stamatoyannopoulos John A.
Published: November 2014

To study the evolutionary dynamics of regulatory DNA, we mapped >1.3 million deoxyribonuclease I–hypersensitive sites (DHSs) in 45 mouse cell and tissue types, and systematically compared these with human DHS maps from orthologous compartments. We found that the mouse and human genomes have undergone extensive cis-regulatory rewiring that combines branch-specific evolutionary innovation and loss with widespread repurposing of conserved DHSs to alternative cell fates, and that this process is mediated by turnover of transcription factor (TF) recognition elements. Despite pervasive evolutionary remodeling of the location and content of individual cis-regulatory regions, within orthologous mouse and human cell types the global fraction of regulatory DNA bases encoding recognition sites for each TF has been strictly conserved. Our findings provide new insights into the evolutionary forces shaping mammalian regulatory DNA landscapes.
The gentle touch receptors of mammalian skin
Authors: Zimmerman Amanda , Bai Ling , Ginty David D.
Published: November 2014

The skin is our largest sensory organ, transmitting pain, temperature, itch, and touch information to the central nervous system. Touch sensations are conveyed by distinct combinations of mechanosensory end organs and the low-threshold mechanoreceptors (LTMRs) that innervate them. Here we explore the various structures underlying the diverse functions of cutaneous LTMR end organs. Beyond anchoring of LTMRs to the surrounding dermis and epidermis, recent evidence suggests that the non-neuronal components of end organs play an active role in signaling to LTMRs and may physically gate force-sensitive channels in these receptors. Combined with LTMR intrinsic properties, the balance of these factors comprises the response properties of mechanosensory neurons and, thus, the neural encoding of touch.
Convergent evolution of complex regulatory landscapes and pleiotropy at
Hox
loci
Authors: Lonfat Nicolas , Montavon Thomas , Darbellay Fabrice , Gitto Sandra , Duboule Denis
Published: November 2014

Hox
genes are required during the morphogenesis of both vertebrate digits and external genitals. We investigated whether transcription in such distinct contexts involves a shared enhancer-containing landscape. We show that the same regulatory topology is used, yet with some tissue-specific enhancer-promoter interactions, suggesting the hijacking of a regulatory backbone from one context to the other. In addition, comparable organizations are observed at both
HoxA
and
HoxD
clusters, which separated through genome duplication in an ancestral invertebrate animal. We propose that this convergent regulatory evolution was triggered by the preexistence of some chromatin architecture, thus facilitating the subsequent recruitment of the appropriate transcription factors. Such regulatory topologies may have both favored and constrained the evolution of pleiotropic developmental loci in vertebrates.
Philae probe makes bumpy touchdown on a comet
Authors: Hand Eric
Published: November 2014

Elation and disappointment as lander goes into early hibernation, curtailing experiments.
Taking the measure of molten uranium oxide
Authors: Navrotsky Alexandra
Published: November 2014

Levitated droplets of uranium oxide reveal a complex structure below and above the melting point

[Also see Report by

Skinner
et al.

]
Can erosion drive tectonics?
Authors: Whipple Kelin X.
Published: November 2014

Data from the eastern Himalaya challenge the idea that climate-driven erosion can control tectonics

[Also see Report by

Wang
et al.

]
The gut microbiota influences blood-brain barrier permeability in mice
Authors: Braniste Viorica , Al-Asmakh Maha , Kowal Czeslawa , Anuar Farhana , Abbaspour Afrouz , Tóth Miklós , Korecka Agata , Bakocevic Nadja , Ng Lai Guan , Kundu Parag , Gulyás Balázs , Halldin Christer , Hultenby Kjell , Nilsson Harriet , Hebert Hans , Volpe Bruce T. , Diamond Betty , Pettersson Sven
Published: November 2014

The intestinal microbiota helps to maintain the integrity of the blood-brain barrier in fetal and adult mice.
Inhaling H(
2
)ope
Authors: Kolandaivelu Kumaran
Published: November 2014

Inhaled hydrogen may improve survival and neurological outcomes following cardiac arrest.
Protective Immunity against Infection with Mycoplasma haemofelis
Authors: Hicks Chelsea A. E. , Willi Barbara , Riond Barbara , Novacco Marilisa , Meli Marina L. , Stokes Christopher R. , Helps Christopher R. , Hofmann-Lehmann Regina , Tasker Séverine
Published: November 2014

Hemoplasmas are potentially zoonotic mycoplasmal pathogens, which are not consistently cleared by antibiotic therapy.Mycoplasma haemofelisis the most pathogenic feline hemoplasma species. The aim of this study was to determine how cats previously infected withM. haemofelisthat had recovered reacted when rechallenged withM. haemofelisand to characterize the immune response followingde novoM. haemofelisinfection and rechallenge. Five specific-pathogen-free (SPF)-derived naive cats (group A) and five cats that had recovered fromM. haemofelisinfection (group B) were inoculated subcutaneously withM. haemofelis. BloodM. haemofelisloads were measured by quantitative PCR (qPCR), antibody response to heat shock protein 70 (DnaK) by enzyme-linked immunosorbent assay (ELISA), blood lymphocyte cell subtypes by flow cytometry, and cytokine mRNA levels by quantitative reverse transcriptase PCR. Group A cats all became infected with high bacterial loads and seroconverted, while group B cats were protected from reinfection, thus providing the unique opportunity to study the immunological parameters associated with this protective immune response againstM. haemofelis. First, a strong humoral response to DnaK was only observed in group A, demonstrating that an antibody response to DnaK is not important for protective immunity. Second, proinflammatory cytokine interleukin-6 (IL-6) mRNA levels appeared to increase rapidly postinoculation in group B, indicating a possible role in protective immunity. Third, an increase in IL-12p35 and -p40 mRNA and decrease in the Th2/Th1 ratio observed in group A suggest that a Th1-type response is important in primary infection. This is the first study to demonstrate protective immunity againstM. haemofelisreinfection, and it provides important information for potential future hemoplasma vaccine design.
Comparison of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry and Molecular Biology Techniques for Identification of Culicoides (Diptera: Ceratopogonidae) Biting Midges in Senegal
Authors: Sambou Masse , Aubadie-Ladrix Maxence , Fenollar Florence , Fall Becaye , Bassene Hubert , Almeras Lionel , Sambe-Ba Bissoume , Perrot Nadine , Chatellier Sonia , Faye Ngor , Parola Philippe , Wade Boubacar , Raoult Didier , Mediannikov Oleg
Published: November 2014

Biting midges of the genus
Culicoides
are implicated as vectors for a wide variety of pathogens. The morphological identification of these arthropods may be difficult because of a lack of detailed investigation of taxonomy for this species in Africa. However, matrix-assisted laser desorption ionization−time of flight mass spectrometry (MALDI-TOF MS) profiling is efficient for arthropod identification at the species level. This study established a spectrum database of
Culicoides
spp. from Senegal using MALDI-TOF. Identification of
Culicoides
insects to the species level before mass spectrometry was performed on the basis of morphological characters. MALDI-TOF MS reference spectra were determined for 437 field-caught
Culicoides
of 10 species. The protein profiles of all tested
Culicoides
revealed several peaks with mass ranges of 2 to 20 kDa. In a validation study, 72
Culicoides
specimens in the target species were correctly identified at the species level with a similarity of 95 to 99.9%. Four
Culicoides
protein profiles were misidentified. Nevertheless, six SuperSpectra (
C. imicola
,
C. enderleini
,
C. oxystoma
,
C. kingi
,
C. magnus
, and
C. fulvithorax
) were created. Abdomens of midges were used to amplify and sequence a portion of the mitochondrial cytochrome oxidase I gene (COI). The results obtained using the MALDI-TOF MS method were consistent with the morphological identification and similar to the genetic identification. Protein profiling using MALDI-TOF is an efficient approach for the identification of
Culicoides
spp., and it is economically advantageous for approaches that require detailed and quantitative information of vector species that are collected in field. The database of African
Culicoides
MS spectra created is the first database in Africa. The COI sequences of five
Culicoides
species that were previously noncharacterized using molecular methods were deposited in GenBank.
Identification of Clinical Aeromonas Species by
rpoB
and
gyrB
Sequencing and Development of a Multiplex PCR Method for Detection of Aeromonas hydrophila, A. caviae, A. veronii, and A. media
Authors: Persson Søren , Al-Shuweli Suzan , Yapici Seval , Jensen Joan N. , Olsen Katharina E. P.
Published: November 2014

Conventional identification of
Aeromonas
species based on biochemical methods is challenged by the heterogeneous nature of the species. Here, we present a new multiplex PCR method directed toward the
gyrB
and
rpoB
genes that identifies four
Aeromonas
species,
A. hydrophila
,
A. media
,
A. veronii
, and
A. caviae
, and we describe the application of this method on a Danish strain collection.
Development of a Multiple-Locus Variable-Number Tandem-Repeat Typing Scheme for Genetic Fingerprinting of Burkholderia cenocepacia and Application to Nationwide Epidemiological Analysis
Authors: Segonds Christine , Thouverez Michelle , Barthe Antoine , Bossuet-Greif Nadège , Tisseyre Lenka , Plésiat Patrick , Vergnaud Gilles , Chabanon Gérard , Pourcel Christine
Published: November 2014

Organisms of the
Burkholderia cepacia
complex are especially important pathogens in cystic fibrosis (CF), with a propensity for patient-to-patient spread and long-term respiratory colonization.
B. cenocepacia
and
Burkholderia multivorans
account for the majority of infections in CF, and major epidemic clones have been recognized throughout the world. The aim of the present study was to develop and evaluate a multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) scheme for
B. cenocepacia
. Potential VNTR loci were identified upon analysis of the annotated genome sequences of
B. cenocepacia
strains AU1054, J2315, and MCO-3, and 10 of them were selected on the basis of polymorphisms and size. A collection of 100
B. cenocepacia
strains, including epidemiologically related and unrelated strains, as well as representatives of the major epidemic lineages, was used to evaluate typeability, epidemiological concordance, and the discriminatory power of MLVA-10 compared with those of pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Longitudinal stability was assessed by testing 39 successive isolates from 14 patients. Typeability ranged from 0.91 to 1, except for that of one marker, which was not amplified in 53% of the
B. cenocepacia
IIIA strains. The MLVA types were shown to be stable in chronically colonized patients and within outbreak-related strains, with excellent epidemiological concordance. Epidemic and/or globally distributed lineages (epidemic Edinburgh-Toronto electrophoretic type 12 [ET-12], sequence type 32 [ST-32], ST-122, ST-234, and ST-241) were successfully identified. Conversely, the discriminatory power of MLVA was lower than that of PFGE or MLST, although PFGE variations within the epidemic lineages sometimes masked their genetic relatedness. In conclusion, MLVA represents a promising cost-effective first-line tool in
B. cenocepacia
surveillance.
Dual Proinflammatory and Antiviral Properties of Pulmonary Eosinophils in Respiratory Syncytial Virus Vaccine-Enhanced Disease
Authors: Su Yung-Chang , Townsend Dijana , Herrero Lara J. , Zaid Ali , Rolph Michael S. , Gahan Michelle E. , Nelson Michelle A. , Rudd Penny A. , Matthaei Klaus I. , Foster Paul S. , Dent Lindsay , Tripp Ralph A. , Lee James , Simson Ljubov , Mahalingam Suresh
Published: November 2014

Human respiratory syncytial virus (RSV) is a major cause of morbidity and severe lower respiratory tract disease in the elderly and very young, with some infants developing bronchiolitis, recurrent wheezing, and asthma following infection. Previous studies in humans and animal models have shown that vaccination with formalin-inactivated RSV (FI-RSV) leads to prominent airway eosinophilic inflammation following RSV challenge; however, the roles of pulmonary eosinophilia in the antiviral response and in disease pathogenesis are inadequately understood.In vivostudies in mice with eotaxin and/or interleukin 5 (IL-5) deficiency showed that FI-RSV vaccination did not lead to enhanced pulmonary disease, where following challenge there were reduced pulmonary eosinophilia, inflammation, Th2-type cytokine responses, and altered chemokine (TARC and CCL17) responses. In contrast to wild-type mice, RSV was recovered at high titers from the lungs of eotaxin- and/or IL-5-deficient mice. Adoptive transfer of eosinophils to FI-RSV-immunized eotaxin- and IL-5-deficient (double-deficient) mice challenged with RSV was associated with potent viral clearance that was mediated at least partly through nitric oxide. These studies show that pulmonary eosinophilia has dual outcomes: one linked to RSV-induced airway inflammation and pulmonary pathology and one with innate features that contribute to a reduction in the viral load.

IMPORTANCEThis study is critical to understanding the mechanisms attributable to RSV vaccine-enhanced disease. This study addresses the hypothesis that IL-5 and eotaxin are critical in pulmonary eosinophil response related to FI-RSV vaccine-enhanced disease. The findings suggest that in addition to mediating tissue pathology, eosinophils within a Th2 environment also have antiviral activity.
Cancer-Causing Human Papillomavirus E6 Proteins Display Major Differences in the Phospho-Regulation of Their PDZ Interactions
Authors: Boon Siaw Shi , Tomaić Vjekoslav , Thomas Miranda , Roberts Sally , Banks Lawrence
Published: November 2014

Previous studies have shown that the cancer-causing high-risk human papillomavirus (HPV) E6 oncoproteins have PDZ binding potential, an activity which is important for their ability to support the viral life cycle and to cooperate in the induction of malignancy. However, PDZ interactions are not constitutive, and they can be negatively regulated by phosphorylation within the E6 PDZ binding motif (PBM). In this study, we have investigated the differential regulation of the HPV E6 PBMs from diverse high-risk HPV types. We show that, depending on the HPV type, PDZ binding activity can be regulated by phosphorylation with protein kinase A (PKA) or AKT, which, in turn, inhibits PDZ recognition. Such regulation is highly conserved between E6 proteins derived from HPV-16, HPV-18, and HPV-58 while being somewhat weaker or absent from other types such as HPV-31, HPV-33, and HPV-51. In the case of HPV31, PKA phosphorylation occurs within the core of the E6 protein and has no effect on PDZ interactions, and this demonstrates a surprising degree of heterogeneity among the different high-risk HPV E6 oncoproteins in how they are regulated by different cellular signaling pathways.

IMPORTANCE
This study demonstrated that the cancer-causing HPV E6 oncoproteins are all subject to posttranslational modification of their extreme C-terminal PDZ binding motifs through phosphorylation. However, the identities of the kinase are not the same for all HPV types. This demonstrates a very important divergence between these HPVs, and it suggests that changes in cell signaling pathways have different consequences for different high-risk virus infections and their associated malignancies.
Focal Adhesion Kinase Is Involved in Rabies Virus Infection through Its Interaction with Viral Phosphoprotein P
Authors: Fouquet Baptiste , Nikolic Jovan , Larrous Florence , Bourhy Hervé , Wirblich Christoph , Lagaudrière-Gesbert Cécile , Blondel Danielle
Published: November 2014

The rabies virus (RABV) phosphoprotein P is a multifunctional protein: it plays an essential role in viral transcription and replication, and in addition, RABV P has been identified as an interferon antagonist. Here, a yeast two-hybrid screen revealed that RABV P interacts with the focal adhesion kinase (FAK). The binding involved the 106-to-131 domain, corresponding to the dimerization domain of P and the C-terminal domain of FAK containing the proline-rich domains PRR2 and PRR3. The P-FAK interaction was confirmed in infected cells by coimmunoprecipitation and colocalization of FAK with P in Negri bodies. By alanine scanning, we identified a single mutation in the P protein that abolishes this interaction. The mutant virus containing a substitution of Ala for Arg in position 109 in P (P.R109A), which did not interact with FAK, is affected at a posttranscriptional step involving protein synthesis and viral RNA replication. Furthermore, FAK depletion inhibited viral protein expression in infected cells. This provides the first evidence of an interaction of RABV with FAK that positively regulates infection.

IMPORTANCE
Rabies virus exhibits a small genome that encodes a limited number of viral proteins. To maintain efficient virus replication, some of them are multifunctional, such as the phosphoprotein P. We and others have shown that P establishes complex networks of interactions with host cell components. These interactions have revealed much about the role of P and about host-pathogen interactions in infected cells. Here, we identified another cellular partner of P, the focal adhesion kinase (FAK). Our data shed light on the implication of FAK in RABV infection and provide evidence that P-FAK interaction has a proviral function.
Deletion Mutants of Schmallenberg Virus Are Avirulent and Protect from Virus Challenge
Authors: Kraatz Franziska , Wernike Kerstin , Hechinger Silke , König Patricia , Granzow Harald , Reimann Ilona , Beer Martin
Published: November 2014

Since its emergence, Schmallenberg virus (SBV), a novel insect-transmitted orthobunyavirus which predominantly infects ruminants, has caused a large epidemic in European livestock. Newly developed inactivated vaccines are available, but highly efficacious and safe live vaccines are still not available. Here, the properties of novel recombinant SBV mutants lacking the nonstructural protein NSs (rSBVΔNSs) or NSm (rSBVΔNSm) or both of these proteins (rSBVΔNSs/ΔNSm) were tested
in vitro
and
in vivo
in type I interferon receptor knockout mice (IFNAR
−/−
) and in a vaccination/challenge trial in cattle. As for other bunyaviruses, both nonstructural proteins of SBV are not essential for viral growth
in vitro
. In interferon-defective BHK-21 cells, rSBVΔNSs and rSBVΔNSm replicated to levels comparable to that of the parental rSBV; the double mutant virus, however, showed a mild growth defect, resulting in lower final virus titers. Additionally, both mutants with an NSs deletion induced high levels of interferon and showed a marked growth defect in interferon-competent sheep SFT-R cells. Nevertheless, in IFNAR
−/−
mice, all mutants were virulent, with the highest mortality rate for rSBVΔNSs and a reduced virulence for the NSm-deleted virus. In cattle, SBV lacking NSm caused viremia and seroconversion comparable to those caused by the wild-type virus, while the NSs and the combined NSs/NSm deletion mutant induced no detectable virus replication or clinical disease after immunization. Furthermore, three out of four cattle immunized once with the NSs deletion mutant and all animals vaccinated with the virus lacking both nonstructural proteins were fully protected against a challenge infection. Therefore, the double deletion mutant will provide the basis for further developments of safe and efficacious modified live SBV vaccines which could be also a model for other viruses of the Simbu serogroup and related orthobunyaviruses.

IMPORTANCE
SBV induces only mild clinical signs in adult ruminants but causes severe fetal malformation and, thereby, can have an important impact on animal welfare and production. As SBV is an insect-transmitted pathogen, vaccination will be one of the most important aspects of disease control. Here, mutant viruses lacking one or two proteins that essentially contribute to viral pathogenicity were tested as modified live vaccines in cattle. It could be demonstrated that a novel recombinant double deletion mutant is a safe and efficacious vaccine candidate. This is the first description of a putative modified live vaccine for the complete genus
Orthobunyavirus
, and in addition, such a vaccine type has never been tested in cattle for any virus of the entire family
Bunyaviridae
. Therefore, the described vaccine also represents the first model for a broad range of related viruses and is of high importance to the field.
BGLF4 Kinase Modulates the Structure and Transport Preference of the Nuclear Pore Complex To Facilitate Nuclear Import of Epstein-Barr Virus Lytic Proteins
Authors: Chang Chou-Wei , Lee Chung-Pei , Su Mei-Tzu , Tsai Ching-Hwa , Chen Mei-Ru
Published: November 2014

BGLF4 kinase, the only Ser/Thr protein kinase encoded by the Epstein-Barr virus (EBV) genome, phosphorylates multiple viral and cellular substrates to optimize the cellular environment for viral DNA replication and the nuclear egress of nucleocapsids. Previously, we found that nuclear targeting of BGLF4 is through direct interaction with the FG repeat-containing nucleoporins (FG-Nups) Nup62 and Nup153 independently of cytosolic transport factors. Here, we investigated the regulatory effects of BGLF4 on the structure and biological functions of the nuclear pore complex (NPC). In EBV-positive NA cells, the distribution of FG-Nups was modified during EBV reactivation. In transfected cells, BGLF4 changed the staining pattern of Nup62 and Nup153 in a kinase activity-dependent manner. Detection with anti-phospho-Ser/Thr-Pro MPM-2 antibody demonstrated that BGLF4 induced the phosphorylation of Nup62 and Nup153. The nuclear targeting of importin β was attenuated in the presence of BGLF4, leading to inhibition of canonical nuclear localization signal (NLS)-mediated nuclear import. An
in vitro
nuclear import assay revealed that BGLF4 induced the nuclear import of larger molecules. Notably, we found that BGLF4 promoted the nuclear import of several non-NLS-containing EBV proteins, including the viral DNA-replicating enzymes BSLF1, BBLF2/3, and BBLF4 and the major capsid protein (VCA), in cotransfected cells. The data presented here suggest that BGLF4 interferes with the normal functions of Nup62 and Nup153 and preferentially helps the nuclear import of viral proteins for viral DNA replication and assembly. In addition, the nuclear import-promoting activity was found in cells expressing the BGLF4 homologs of another two gammaherpesviruses but not those from alpha- and betaherpesviruses.

IMPORTANCE
During lytic replication, many EBV genome-encoded proteins need to be transported into the nucleus, not only for viral DNA replication but also for the assembly of nucleocapsids. Because nuclear pore complexes are effective gateways that control nucleocytoplasmic traffic, most EBV proteins without canonical NLSs are retained in the cytoplasm until they form complexes with their NLS-containing partners for nuclear targeting. In this study, we found that EBV BGLF4 protein kinase interacts with the Nup62 and Nup153 and induces the redistribution of FG-Nups. BGLF4 modulates the function of the NPC to inhibit the nuclear import of host NLS-containing proteins. Simultaneously, the nuclear import of non-NLS-containing EBV lytic proteins was enhanced, possibly through phosphorylation of Nup62 and Nup153, nuclear pore dilation, or microtubule reorganization. Overall, our data suggest that BGLF4-induced modification of nuclear pore transport may block nuclear targeting of cellular proteins and increase the import of viral proteins to promote viral lytic replication.
The HIV-1 Nucleocapsid Protein Recruits Negatively Charged Lipids To Ensure Its Optimal Binding to Lipid Membranes
Authors: Kempf Noémie , Postupalenko Viktoriia , Bora Saurabh , Didier Pascal , Arntz Youri , de Rocquigny Hugues , Mély Yves
Published: November 2014

The HIV-1 Gag polyprotein precursor composed of the matrix (MA), capsid (CA), nucleocapsid (NC), and p6 domains orchestrates virus assembly via interactions between MA and the cell plasma membrane (PM) on one hand and NC and the genomic RNA on the other hand. As the Gag precursor can adopt a bent conformation, a potential interaction of the NC domain with the PM cannot be excluded during Gag assembly at the PM. To investigate the possible interaction of NC with lipid membranes in the absence of any interference from the other domains of Gag, we quantitatively characterized by fluorescence spectroscopy the binding of the mature NC protein to large unilamellar vesicles (LUVs) used as membrane models. We found that NC, either in its free form or bound to an oligonucleotide, was binding with high affinity (∼10
7
M
−1
) to negatively charged LUVs. The number of NC binding sites, but not the binding constant, was observed to decrease with the percentage of negatively charged lipids in the LUV composition, suggesting that NC and NC/oligonucleotide complexes were able to recruit negatively charged lipids to ensure optimal binding. However, in contrast to MA, NC did not exhibit a preference for phosphatidylinositol-(4,5)-bisphosphate. These results lead us to propose a modified Gag assembly model where the NC domain contributes to the initial binding of the bent form of Gag to the PM.

IMPORTANCE
The NC protein is a highly conserved nucleic acid binding protein that plays numerous key roles in HIV-1 replication. While accumulating evidence shows that NC either as a mature protein or as a domain of the Gag precursor also interacts with host proteins, only a few data are available on the possible interaction of NC with lipid membranes. Interestingly, during HIV-1 assembly, the Gag precursor is thought to adopt a bent conformation where the NC domain may interact with the plasma membrane. In this context, we quantitatively characterized the binding of NC, as a free protein or as a complex with nucleic acids, to lipid membranes and showed that the latter constitute a binding platform for NC. Taken together, our data suggest that the NC domain may play a role in the initial binding events of Gag to the plasma membrane during HIV-1 assembly.
Islet autoantibody status in a multi-ethnic UK clinic cohort of children presenting with diabetes
Authors: Perchard R , MacDonald D , Say J , Pitts J , Pye S , Allgrove J , Banerjee K , Amin R
Published: November 2014

Objective

We prospectively determined islet autoantibody status in children presenting with diabetes to a single UK region in relation to ethnicity.

Design

316 (68.0% non-white) children presenting with diabetes between 2006 and 2013 were tested centrally for islet cell autoantibodies (ICA) and glutamic acid decarboxylase autoantibodies (GAD-65) at diagnosis, and if negative for both, tested for insulin autoantibodies (IAA). The assay used to measure GAD-65 autoantibodies changed from an in-house to a standardised ELISA method during the study.

Results

Even with use of the standardised ELISA method, 25.8% of children assigned a diagnosis of type 1 diabetes still tested negative for all three autoantibodies. 30% of children assigned a diagnosis of type 2 diabetes were autoantibody positive, and these had the highest glycated haemoglobin (HbA1c) levels at 12 months follow-up compared with other groups (p value for analysis of variance <0.001), although the sample size was small. Autoantibody positivity was similar between non-white and white children regardless of assay used (60.0% (n=129) vs 56.4% (n=57), χ2=0.9, p=0.35), as was mean GAD-65 autoantibody levels, but fewer non-white children had two or more autoantibodies detectable (13% (n=28) vs 27.7% (n=28), χ2=12.1, p=0.001).

Conclusions

Islet autoantibody positivity was associated with a more severe phenotype, as demonstrated by poorer glycaemic control, regardless of assigned diabetes subtype. Positivity did not differ by ethnic group.
Gossypiboma as a rare cause of abdominal mass
Authors: Yildirim Afra , İmamoğlu Hakan , Erzurumdağ Aslı , Doğan Serap
Published: November 2014

Gossypiboma is a reaction to a foreign body/object left accidentally inside a patient as a consequence of surgery. This phenomenon may be overlooked due to its rarity or under-reported due to possible repercussions. We report an intra-abdominal gossypiboma that was misdiagnosed on ultrasound, and discuss its radiological findings.
Acquired haemophilia A: the importance of early recognition in cases of spontaneous bleeding in the elderly
Authors: Patel Neeral , Wyrko Zoe , Naqvi Syeda , Croft Adam P
Published: November 2014

We describe the case of a 79-year-old man who presented ‘off legs’ with acute right leg pain. He was initially treated for suspected cellulitis but subsequently found to have spontaneous soft tissue bleeding into the right thigh. He was eventually diagnosed with idiopathic acquired haemophilia A and treated with activated prothrombin complex concentrates to control acute bleeding followed by immunosuppressant therapy. Acquired haemophilia A is a potentially life-threatening and under-recognised bleeding disorder that results from the immune-mediated development of autoantibodies directed against coagulation factor VIII. The disease is more common in elderly individuals where early recognition and treatment is compounded by the presence of other comorbid conditions, including other potential causes of bleeding. These confounding factors and lack of awareness among non-specialists accounts for the delay in diagnosis that is common in this disease and contributes to the persistently high mortality in this age group.
Multifocal necrotising fasciitis: a rarer presentation of a rare disease
Authors: Herrod Philip James Joseph , Boghossian Shahe , Vasas Peter
Published: November 2014

Necrotising fasciitis is a rare life-threatening surgical emergency in which timely diagnosis and treatment are key. We present a case in which a patient rapidly succumbed to synchronous multifocal necrotising fasciitis from a likely intra-abdominal source. The ability for the disease to present in the unusual fashion described in this case must be highlighted to all clinicians.
Unusual bilateral traumatic maculopathy following whiplash injury
Authors: Chronopoulos Argyrios , Lipski Andreas , Jonescu-Cuypers Christian-Paul , Thumann Gabriele
Published: November 2014

An unusual extensive bilateral macular oedema (MO) with spontaneous resolution occurred following a car crash accident. Qualitative and quantitative analysis of the macular region using spectral domain optical coherence tomography (SD-OCT) and multifocal electroretinogram (mfERG) was performed daily during the first 7 days, as well as at 3 and 6 months following the accident. SD-OCT examination demonstrated extensive MO accompanied by neurosensory detachment and subretinal fluid. During the 7 days following the accident there was gradual resolution of the oedema accompanied by visual recovery. One year later no anatomical changes were observed, the mfERG showed complete recovery and visual acuity returned to normal level. Although whiplash is a common injury in motor vehicle accidents, whiplash maculopathy (WMP) is rarely reported, most likely due to underdiagnosis. Here we describe the spontaneous resolution of a severe MO after whiplash injury in a car crash accident.
Patient safety is not elective: a debate at the NPSF Patient Safety Congress
Authors: McTiernan Patricia , Wachter Robert M , Meyer Gregg S , Gandhi Tejal K
Published: November 2014

The opening keynote session of the 16th Annual National Patient Safety Foundation Patient Safety Congress, held 14–16 May 2014, featured a debate addressing the merits and challenges of accountability with respect to key issues in patient safety. The specific resolution debated was: Certain safety practices should be inviolable, and transgressions should result in penalties, potentially including fines, suspensions, and firing. The themes discussed in the debate are issues that healthcare professionals and leaders commonly struggle with in their day-to-day work. How do we draw a line between systems problems and personal failings? When should clinicians and staff be penalised for failing to follow a known safety protocol? The majority of those who listened to the live debate agreed that it is time to begin holding health professionals accountable when they wilfully or repeatedly violate policies or protocols put in place by their institutions to protect the safety of patients. This article summarises the debate as well as the questions and discussion generated by each side. A video of the original debate can be found athttp://bit.ly/Npsf_debate.
TheACTN3R577X genotype is associated with muscle function in a Japanese population
Authors: Kikuchi Naoki , Yoshida Shou , Min Seok-ki , Lee Kihyuk , Sakamaki-Sunaga Mikako , Okamoto Takanobu , Nakazato Koichi
Published: November 2014

Homozygosity for the common nonsense polymorphism R577X in the α-actinin-3 gene (ACTN3) causes complete α-actinin-3 deficiency in fast-twitch skeletal muscle fibers. This study investigated whether the ACTN3 R577X polymorphism affects fitness status using a battery of tests in a large Japanese cohort. In the present study, 1227 subjects (age: 25–85 years) were genotyped for the ACTN3 R577X polymorphism (rs1815739) using a TaqMan SNP genotyping assay (Applied Biosystems). All subjects were divided into 2 groups based on their age (<55 years and ≥55 years). All subjects completed a questionnaire about exercise habits and were subjected to a battery of tests to assess their fitness status (including grip strength test, chair stand test, and 8-foot walking test). A significant association between the ACTN3 R577X genotype and chair stand test performance was observed in the group of men ≥55 using ANCOVA adjusted for age and exercise habits (p = 0.036). The ACTN3 R577X genotype accounted for 2.5% of the variability in the results of the chair stand test among men in the ≥55 age group. Moreover, for the ≥55 age group, performance in the chair stand test was lower among those with the XX genotype than among those with the RR genotype (p = 0.024) or RX genotype (p = 0.005), unlike results for the <55 age group. No significant difference was noted for hand grip strength or 8-foot walking time. Thus, our results suggest that the ACTN3 R577X genotype is associated with lower-extremity muscle function in the Japanese population.
Road weather information system stations — where and how many to install: a cost benefit analysis approach
Authors: Kwon Tae Jung , Fu Liping , Jiang Chaozhe
Published: November 2014

This paper presents a cost–benefit based approach to the problem of finding the optimal location and density of road weather information system (RWIS) stations over a regional road network. The novelty of the proposed method lies in the models that can be used to estimate the benefits of RWIS information, including reduced maintenance costs and collisions, thus determining the optimal number and location of a RWIS network. A case study based on the existing RWIS network in Northern Minnesota in the US is used to show the application of the proposed approach. Linear regression models are developed for the annual maintenance costs and the expected number of collisions that could occur on two types of highways delineated by the existence of a RWIS station nearby. The calibrated models are then applied to individual highway segments defined on the basis of a uniform grid system to determine the expected benefit of having a RWIS station installed. These benefits along with RWIS installation and maintenance costs are converted into net benefits and then the net present value, which are then used in determining the optimal number of RWIS stations and prioritizing the candidate locations. It was found from the case study that a total of 45 stations would provide the best return of investment with a 25 year net benefit of approximately $6.5 million and a life-cycle benefit-to-cost ratio of 3.5.
Lie and generalized Tanaka–Webster derivatives on real hypersurfaces in complex projective spaces
Authors: Pérez Juan de Dios
Published: November 2014

On a real hypersurface M in complex projective space we can consider the Levi-Civita connection and for any nonnull constant k the kth g-Tanaka–Webster connection. We classify real hypersurfaces such that both the Lie derivative associated to the Levi-Civita connection and the kth g-Tanaka–Webster derivative in the direction of the structure vector field ξ coincide when we apply them to either the shape operator or the structure Jacobi operator of M.
Sensitivity Enhancement for Structural Condition Assessment with Noisy Excitation or with Only Output
Authors: Liu Kun , Law Siu-Seong , Zhu Xin-Qun
Published: November 2014

Revisited herein is the response sensitivity method for structural condition assessment. The performance of a sensitivity enhancement technique for structural damage identification is discussed with reference to cases with noisy excitation or with only output. An extended study on the structural condition assessment is conducted based on a newly developed force identification technique and the response sensitivity enhancement method. Numerical simulations with a planar truss structure show that the adverse effect of noise in excitation cannot be ignored in damage detection. A two-step method including the sensitivity enhancement technique for damage detection could improve the identification accuracy with less influence from the identified excitations. The improved structural condition assessment with sensitivity enhancement technique out-performs the conventional sensitivity approach with more accurate results from the truss structure studied even with a 10% noise in the measured responses.
Thermal Buckling Analysis of Axially Loaded Columns of Thin-Walled Open Section with Nonuniform Sectional Properties
Authors: Cheng Shanshan , Yan Qi-Wu , Li Long-Yuan , Kim Boksun
Published: November 2014

This paper presents an analytical study on the thermal buckling analysis of axially loaded columns of thin-walled open section with nonuniform sectional properties. Obtained herein are critical loads related to flexural, torsional and flexural-torsional buckling of an I-section column subjected to an axial compressive load applied at the geometric centroid, and under linearly varied non-uniform temperature distribution scenarios. The analysis is accomplished using traditional energy methods. The influences of thermal strain, nonuniform distribution of pre-buckling stresses, and variation of pre-buckling stresses along the longitudinal axis of the column on critical buckling loads are examined. The present results highlight the importance of nonuniform sectional properties in the buckling analysis of columns of doubly symmetric section.
Quantum codes from cyclic codes over F3 + vF3
Authors: Ashraf Mohammad , Mohammad Ghulam
Published: November 2014

Let R = F3 + vF3 be a finite commutative ring, where v2 = 1. It is a finite semi-local ring, not a chain ring. In this paper, we give a construction for quantum codes from cyclic codes over R. We derive self-orthogonal codes over F3 as Gray images of linear and cyclic codes over R. In particular, we use two codes associated with a cyclic code over R of arbitrary length to determine the parameters of the corresponding quantum code.
Variable Correlation Digital Noise Source on FPGA — A Versatile Tool for Debugging Radio Telescope Backends
Authors: Buch Kaushal D. , Gupta Yashwant , Ajith Kumar B.
Published: November 2014

Contemporary wideband radio telescope backends are generally developed on Field Programmable Gate Arrays (FPGA) or hybrid (FPGA+GPU) platforms. One of the challenges faced while developing such instruments is the functional verification of the signal processing backend at various stages of development. In the case of an interferometer or pulsar backend, the typical requirement is for one independent noise source per input, with provision for a common, correlated signal component across all the inputs, with controllable level of correlation. This paper describes the design of a FPGA-based variable correlation Digital Noise Source (DNS), and its applications to built-in testing and debugging of correlators and beamformers. This DNS uses the Central Limit Theorem-based approach for generation of Gaussian noise, and the architecture is optimized for resource requirements and ease of integration with existing signal processing blocks on FPGA.
Exchange-Traded Funds: An Overview of Institutions, Trading, and Impacts
Authors: Madhavan Ananth
Published: November 2014

Exchange-traded funds (ETFs) have grown substantially in diversity and size in recent years, reflecting a broader shift toward passive, index investing. As a consequence, there is increased attention by investors, regulators, and academics seeking to assess and understand the implications of this rapid growth. This article provides a unified framework to examine these issues and review the research to date, demonstrating that ETFs have extended significant benefits to investors and to the functioning of markets that meaningfully outweigh any perceived or actual weaknesses.