bluuebunny/crossref_metadata_2025 huggingface dataset:
Tracking motor units longitudinally across experimental sessions with high‐density surface electromyography
Authors: Martinez‐Valdes E. , Negro F. , Laine C. M. , Falla D. , Mayer F. , Farina D.
Published: December 2016

Key points

Classic motor unit (MU) recording and analysis methods do not allow the same MUs to be tracked across different experimental sessions, and therefore, there is limited experimental evidence on the adjustments in MU properties following training or during the progression of neuromuscular disorders.

We propose a new processing method to track the same MUs across experimental sessions (separated by weeks) by using high‐density surface electromyography.

The application of the proposed method in two experiments showed that individual MUs can be identified reliably in measurements separated by weeks and that changes in properties of the tracked MUs across experimental sessions can be identified with high sensitivity.

These results indicate that the behaviour and properties of the same MUs can be monitored across multiple testing sessions.

The proposed method opens new possibilities in the understanding of adjustments in motor unit properties due to training interventions or the progression of pathologies.

A new method is proposed for tracking individual motor units (MUs) across multiple experimental sessions on different days. The technique is based on a novel decomposition approach for high‐density surface electromyography and was tested with two experimental studies for reliability and sensitivity. Experiment I (reliability): ten participants performed isometric knee extensions at 10, 30, 50 and 70% of their maximum voluntary contraction (MVC) force in three sessions, each separated by 1 week. Experiment II (sensitivity): seven participants performed 2 weeks of endurance training (cycling) and were tested pre–post intervention during isometric knee extensions at 10 and 30% MVC. The reliability (Experiment I) and sensitivity (Experiment II) of the measured MU properties were compared for the MUs tracked across sessions, with respect to all MUs identified in each session. In Experiment I, on average 38.3% and 40.1% of the identified MUs could be tracked across two sessions (1 and 2 weeks apart), for the vastus medialis and vastus lateralis, respectively. Moreover, the properties of the tracked MUs were more reliable across sessions than those of the full set of identified MUs (intra‐class correlation coefficients ranged between 0.63—0.99 and 0.39–0.95, respectively). In Experiment II, ∼40% of the MUs could be tracked before and after the training intervention and training‐induced changes in MU conduction velocity had an effect size of 2.1 (tracked MUs) and 1.5 (group of all identified motor units). These results show the possibility of monitoring MU properties longitudinally to document the effect of interventions or the progression of neuromuscular disorders.
Contrast enhanced ultrasound of a rare case of Peliosis hepatis
Authors: Loizides Alexander , Glodny Bernhard , Zoller Heinz , Zelger Bettina Gudrun , Junker Daniel , Henninger Benjamin , Putzer Daniel , Gruber Hannes
Published: December 2016

Peliosis hepatis is a rare benign disorder of the liver, histologically characterized by blood-filled cystic cavities of various sizes and irregular shapes, communicating with the hepatic sinusoids. Only a few cases of peliosis hepatis have been described using contrast enhanced ultrasound showing admittedly various dynamic enhancement patterns. We present a case of peliosis hepatis with a typical target-sign enhancement depicted by means of contrast enhanced ultrasound.
Enhanced process and composition control for atomic layer deposition with lithium trimethylsilanolate
Authors: Ruud Amund , Miikkulainen Ville , Mizohata Kenichiro , Fjellvåg Helmer , Nilsen Ola
Published: December 2016

The authors report on the application of the novel lithium precursor lithium trimethylsilanolate (LiTMSO) for use in atomic layer deposition (ALD) processes. Through different reaction paths, LiTMSO have been used for the deposition of Li2CO3, LixSiyOz, and LixAlyOz in the temperature range 200–300 °C. LiTMSO can provide enhanced process and composition control for the deposition of lithium containing materials by ALD, as compared to the commonly used precursors. It was possible to vary the Li:Al ratio in the deposition of LixAlyOz in a larger range than previously shown, as confirmed by time-of-flight elastic recoil detection analysis. The authors also report on the applicability of lithium benzoate, lithium acetate, and lithium trifluoroacetate as precursors for ALD, proving inferior to LiTMSO.
Effect of illumination and electric field intensity on the efficiency improvement of amorphous silicon tandem solar cells
Authors: Scuto Andrea , Gerardi Cosimo , Battaglia Anna , Lombardo Salvatore
Published: December 2016

The improvement of tandem hydrogenated amorphous/microcrystalline Si solar cells under prolonged exposure to reverse bias direct current electric fields and illumination has been investigated. In this work, the authors show that the application of reverse bias stress in the presence of illumination slows down the solar cell ageing kinetics (caused mainly by the Staebler–Wronski effect and by the increase in the series resistance) and, in suitable conditions, it produces an improvement of the solar cell characteristic parameters as a function of stress time. The authors discuss the effect of temperature, electric field intensity, and illumination level.
Room temperature TiO2 atomic layer deposition on collagen membrane from a titanium alkylamide precursor
Authors: Bishal Arghya K. , Sukotjo Cortino , Takoudis Christos G.
Published: December 2016

Low temperature atomic layer deposition (ALD) is an increasingly important technique to functionalize and modify heat-sensitive biomaterials. Collagen is a heat-sensitive biomaterial used in several biomedical applications. In this study, commercially available collagen membrane was selected as a substrate for the ALD of titanium dioxide (TiO2); a thin film of TiO2 on collagen could potentially change the mechanical and chemical properties of collagen. The ALD process was carried out at room temperature using tetrakis(dimethylamido)titanium, a novel titanium precursor for such applications, and ozone as the oxidizer. Four different sample groups were studied: control (native collagen), and collagen-150 cycles, collagen-300 cycles, and collagen-600 cycles, that is, collagen with 150, 300, and 600 TiO2 ALD cycles, respectively. Chemical analysis of the substrate surface showed the presence of titanium oxide on as-deposited samples. Electron microscopy results showed a significant increase in collagen fiber thickness among control and collagen samples with as-deposited TiO2. The collagen fiber diameter was found to increase more than linearly with increasing number of TiO2 ALD cycles. This titanium dioxide-infiltrated dense collagen could be used for the tuning of its properties in several biomedical applications, including bone grafting and wound healing.
In-gap states in titanium dioxide and oxynitride atomic layer deposited films
Authors: Henkel Karsten , Das Chittaranjan , Kot Małgorzata , Schmeißer Dieter , Naumann Franziska , Kärkkänen Irina , Gargouri Hassan
Published: December 2016

Valence band (VB) spectra of titanium dioxide (TiO2) and oxynitride (TiOxNy) films prepared by different atomic layer deposition (ALD) processes are compared and related to electrical characterization [current–voltage (JV) and capacitance–voltage (CV)] results. By increasing the nitrogen amount in the TiO2 film, band-gap narrowing is observed. The band-gap decrease is related to the contribution of the nitrogen density of states, which induces defects within the band-gap and thus reduces its optical band-gap. In-gap states are found in the VB spectra at 1 eV below the Fermi energy in all investigated ALD samples, i.e., in TiO2 as well as in TiOxNy films. An exponential correlation between leakage current density and in-gap state intensity is derived by the combination of JV measurements and VB spectra, whereas the in-gap states seem to have no influence on hysteresis and fixed oxide charges found in the CV data. It is argued that the in-gap states in TiO2 and TiOxNy have an excitonic or polaronic origin. Both, band-gap narrowing and in-gap state intensity can be tuned by the ALD process selection and the variation of its parameters.
Atomic layer etching in close-to-conventional plasma etch tools
Authors: Goodyear Andy , Cooke Mike
Published: December 2016

Atomic layer etching using plasma is a cyclical etching process of gas dosing and surface bombardment that removes material layer by layer, and has the potential to remove single atomic layers. The authors consider how a conventional plasma etcher can be modified to perform this style of recipe and give results for silicon etching using a chlorine/argon plasma. The need for precise control of ion bombardment energy and gas dose is highlighted.
Objectively Measured Sedentary Behavior, Obesity, and Psychological Well-Being: A Cross-Sectional Study of Japanese Schoolchildren
Authors: Ishii Kaori , Shibata Ai , Adachi Minoru , Mano Yoshiyuki , Oka Koichiro
Published: December 2016

Background:

Sedentary behaviors (SB) are associated with health indicators; however, there are currently very few studies that have examined these associations, especially in conjunction with psychological factors, in children. The current study examined the independent relationship between objectively assessed SB, and indicators of obesity and psychological well-being, among Japanese children.

Methods:

A total of 967 elementary-school children completed a cross-sectional survey. SB was measured with accelerometers for 7 consecutive days. Psychological well-being data (eg, anxiety and behavior problems) were collected via a self-report questionnaire. To determine the relationship of SB with degree of obesity and psychological well-being, linear regression analyses were conducted to relate the indicators of obesity and psychological well-being on SB, adjusted by gender, grade, percentage of moderate-to-vigorous physical activity per day, duration spent wearing the accelerometer, and degree of obesity.

Results:

SB was significantly related to behavioral/emotional problems (β = .280, P = .010, R2 = .015). There was a statistically significant relationship between SB and anxiety (β = .206, P = .059, R2 = .007). No significant association with degree of obesity was found.

Conclusions:

Excess SB relates higher levels of behavioral/emotional problems and anxiety. These results can inspire the development of interventions that promote well-being and enhance psychological health, by focusing on SB in Japanese children.
Understanding the Consequences of Newcomer Integration Processes: The Sport Team Socialization Tactics Questionnaire
Authors: Benson Alex J. , Eys Mark
Published: December 2016

The ways in which newcomers are integrated into sport teams may have broad consequences for the athletes entering the group, as well as for the existing team members. Drawing from organizational socialization theory, the current research developed a questionnaire to assess athletes’ perceptions of how newcomers are socialized into their group. Across four studies, think-aloud interviews (N = 8), an expert panel review (N = 6), cross-sectional tests of the factor structure (NStudy 2 = 197; NStudy 3 = 460), and a two-wave correlational design (NStudy 4 = 194) were used to evaluate the construct validity and the internal consistency of the Sport Team Socialization Tactics Questionnaire (STSTQ). Collectively, these efforts identified a three-factor structure underlying the STSTQ and provided preliminary evidence for its validity. The STSTQ enables researchers to systematically examine the individual- and group-level consequences associated with the socialization tactics implemented in sport teams.
Nonverbal Communication of Confidence in Soccer Referees: An Experimental Test of Darwin’s Leakage Hypothesis
Authors: Furley Philip , Schweizer Geoffrey
Published: December 2016

The goal of the present paper was to investigate whether soccer referees’ nonverbal behavior (NVB) differed based on the difficulty of their decisions and whether perceivers could detect these systematic variations. On the one hand, communicating confidence via NVB is emphasized in referee training. On the other hand, it seems feasible from a theoretical point of view that particularly following relatively difficult decisions referees have problems controlling their NVB. We conducted three experiments to investigate this question. Experiment 1 (N = 40) and Experiment 2 (N = 60) provided evidence that perceivers regard referees’ NVB as less confident following ambiguous decisions as compared with following unambiguous decisions. Experiment 3 (N = 58) suggested that perceivers were more likely to debate with the referee when referees nonverbally communicated less confidence. We discuss consequences for referee training.
A Phage-Like IncY Plasmid Carrying the
mcr-1
Gene in Escherichia coli from a Pig Farm in China
Authors: Zhang Chunping , Feng Yuqing , Liu Fei , Jiang Hui , Qu Zhina , Lei Meng , Wang Jianfeng , Zhang Bing , Hu Yongfei , Ding Jiabo , Zhu Baoli
Published: December 2016

We report here a new type of plasmid that carries the
mcr-1
gene, the pMCR-1-P3 plasmid, harbored in an
Escherichia coli
strain isolated from a pig farm in China. pMCR-1-P3 belongs to the IncY incompatibility group and is a phage-like plasmid that contains a large portion of phage-related sequences. The backbone of this plasmid is different from that of other
mcr-1
-carrying plasmids reported previously.
Chronic Plasmodium chabaudi Infection Generates CD4 Memory T Cells with Increased T Cell Receptor Sensitivity but Poor Secondary Expansion and Increased Apoptosis
Authors: Opata Michael M. , Stephens Robin
Published: December 2016

Exposure to blood-stage malaria infection is often persistent, leading to generation of CD4 effector and effector memory T cells that contribute to protection. We showed previously that chronic exposure to blood-stagePlasmodium chabaudioffers the best protection from parasitemia and pathology in reinfection cases, correlating with an increase in Th1 cells. Although much is known about the features of resting or exhausted memory T cells (Tmem), little is known about the functional capacities of chronically stimulated but protective T cells. To determine the functional capacity of CD4 T cells generated by chronic infection upon reexposure to parasite, we compared their responses to known features of classical Tmem. The numbers of cytokine-producing T cells increased following infection in the polyclonal populations, suggesting an increase in pathogen-specific T cells. Malaria antigen-specific B5 T cell receptor (TCR) transgenic (Tg) T cells from chronic infection proliferated on reinfection and were highly sensitive to TCR stimulation without costimulation, as shown for Tmem in acute stimulations. However, B5 Tmem did not accumulate more than naive B5 T cellsin vivoorin vitroand became apoptotic. Failure to accumulate was partly the result of chronic stimulation, since eliminating persistent parasites before reinfection slightly increased the accumulation of B5 Tg T cells upon reinfection. The levels of specific gamma interferon-positive, interleukin-10-positive T cells, which protect animals from pathology, increased after malaria infection. These data demonstrate that although chronic infection generates a protective T cell population with increased TCR sensitivity and cytokine production, they do not reexpand upon reexposure due to increased apoptosis.
Immunization with Pneumocystis Cross-Reactive Antigen 1 (Pca1) Protects Mice against Pneumocystis Pneumonia and Generates Antibody to Pneumocystis jirovecii
Authors: Tesini Brenda L. , Wright Terry W. , Malone Jane E. , Haidaris Constantine G. , Harber Martha , Sant Andrea J. , Nayak Jennifer L. , Gigliotti Francis
Published: December 2016

Pneumocystis
pneumonia (PcP) is a life-threatening infection that affects immunocompromised individuals. Nearly half of all PcP cases occur in those prescribed effective chemoprophylaxis, suggesting that additional preventive methods are needed. To this end, we have identified a unique mouse
Pneumocystis
surface protein, designated
Pneumocystis
cross-reactive antigen 1 (Pca1), as a potential vaccine candidate. Mice were immunized with a recombinant fusion protein containing Pca1. Subsequently, CD4
+
T cells were depleted, and the mice were exposed to
Pneumocystis murina
. Pca1 immunization completely protected nearly all mice, similar to immunization with whole
Pneumocystis
organisms. In contrast, all immunized negative-control mice developed PcP. Unexpectedly, Pca1 immunization generated cross-reactive antibody that recognized
Pneumocystis jirovecii
and
Pneumocystis carinii
. Potential orthologs of Pca1 have been identified in
P. jirovecii
. Such cross-reactivity is rare, and our findings suggest that Pca1 is a conserved antigen and potential vaccine target. The evaluation of Pca1-elicited antibodies in the prevention of PcP in humans deserves further investigation.
Pseudomonas aeruginosa GroEL Stimulates Production of PTX3 by Activating the NF-κB Pathway and Simultaneously Downregulating MicroRNA-9
Authors: Shin Heesung , Jeon Jisu , Lee Jung-Hoon , Jin Shouguang , Ha Un-Hwan
Published: December 2016

As one of the first lines of host defense, monocytes play important roles in clearing infected microbes. The defensive response is triggered by recognition of diverse microbial moieties, including released factors, which modulate host immune responses to establish a harsh environment for clinically important bacterial pathogens. In this study, we found that the expression of PTX3, a soluble form of pattern recognition receptor, was induced by infection with livePseudomonas aeruginosaor treatment of cells with its supernatant.P. aeruginosaGroEL, a homolog of heat shock protein 60, was identified as one of the factors responsible for inducing the expression ofPTX3in host cells. GroEL inducedPTX3expression by activating the Toll-like receptor 4 (TLR4)-dependent pathway via nuclear factor-kappa B (NF-κB), while simultaneously inhibiting expression of microRNA-9, which targets thePTX3transcript. Finally, by acting as an opsonin, GroEL-induced PTX3 promoted the association and phagocytosis ofStaphylococcus aureusinto macrophages. These data suggest that the host defensive environment is supported by the production of PTX3 in response to GroEL, which thus has therapeutic potential for clearance of bacterial infections.
TonB-Dependent Heme/Hemoglobin Utilization by Caulobacter crescentus HutA
Authors: Balhesteros Heloise , Shipelskiy Yan , Long Noah J. , Majumdar Aritri , Katz Benjamin B. , Santos Naara M. , Leaden Laura , Newton Salete M. , Marques Marilis V. , Klebba Phillip E.
Published: December 2016

Siderophore nutrition tests with
Caulobacter crescentus
strain NA1000 revealed that it utilized a variety of ferric hydroxamate siderophores, including asperchromes, ferrichromes, ferrichrome A, malonichrome, and ferric aerobactin, as well as hemin and hemoglobin.
C. crescentus
did not transport ferrioxamine B or ferric catecholates. Because it did not use ferric enterobactin, the catecholate aposiderophore was an effective agent for iron deprivation. We determined the kinetics and thermodynamics of [
59
Fe]apoferrichrome and
59
Fe-citrate binding and transport by NA1000. Its affinity and uptake rate for ferrichrome (equilibrium dissociation constant [

K
d

], 1 nM; Michaelis-Menten constant [

K
M

], 0.1 nM;
V
max
, 19 pMol/10
9
cells/min) were similar to those of
Escherichia coli
FhuA. Transport properties for
59
Fe-citrate were similar to those of
E. coli
FecA (

K
M

, 5.3 nM;
V
max
, 29 pMol/10
9
cells/min). Bioinformatic analyses implicated Fur-regulated loci
00028
,
00138
,
02277
, and
03023
as TonB-dependent transporters (TBDT) that participate in iron acquisition. We resolved TBDT with elevated expression under high- or low-iron conditions by SDS-PAGE of sodium sarcosinate cell envelope extracts, excised bands of interest, and analyzed them by mass spectrometry. These data identified five TBDT: three were overexpressed during iron deficiency (00028, 02277, and 03023), and 2 were overexpressed during iron repletion (00210 and 01196). CLUSTALW analyses revealed homology of putative TBDT 02277 to
Escherichia coli
FepA and BtuB. A Δ
02277
mutant did not transport hemin or hemoglobin in nutrition tests, leading us to designate the
02277
structural gene as
hutA
(for
h
eme/hemoglobin
u
tilization).

IMPORTANCE
The physiological roles of the 62 putative TBDT of
C. crescentus
are mostly unknown, as are their evolutionary relationships to TBDT of other bacteria. We biochemically studied the iron uptake systems of
C. crescentus
, identified potential iron transporters, and clarified the phylogenetic relationships among its numerous TBDT. Our findings identified the first outer membrane protein involved in iron acquisition by
C. crescentus
, its heme/hemoglobin transporter (HutA).
An Optimized Hepatitis C Virus E2 Glycoprotein Core Adopts a Functional Homodimer That Efficiently Blocks Virus Entry
Authors: McCaffrey Kathleen , Boo Irene , Owczarek Catherine M. , Hardy Matthew P. , Perugini Matthew A. , Fabri Louis , Scotney Pierre , Poumbourios Pantelis , Drummer Heidi E.
Published: December 2016

The hepatitis C virus (HCV) envelope glycoprotein E2 is the major target of broadly neutralizing antibodies
in vivo
and is the focus of efforts in the rational design of a universal B cell vaccine against HCV. The E2 glycoprotein exhibits a high degree of amino acid variability which localizes to three discrete regions: hypervariable region 1 (HVR1), hypervariable region 2 (HVR2), and the intergenotypic variable region (igVR). All three variable regions contribute to immune evasion and/or isolate-specific structural variations, both important considerations for vaccine design. A high-resolution structural definition of the intact HCV envelope glycoprotein complex containing E1 and E2 remains to be elucidated, while crystallographic structures of a recombinant E2 ectodomain failed to resolve HVR1, HVR2, and a major neutralization determinant adjacent to HVR1. To obtain further information on E2, we characterized the role of all three variable regions in E2 ectodomain folding and function in the context of a recombinant ectodomain fragment (rE2). We report that removal of the variable regions accelerates binding to the major host cell receptor CD81 and that simultaneous deletion of HVR2 and the igVR is required to maintain wild-type CD81-binding characteristics. The removal of the variable regions also rescued the ability of rE2 to form a functional homodimer. We propose that the rE2 core provides novel insights into the role of the variable motifs in the higher-order assembly of the E2 ectodomain and may have implications for E1E2 structure on the virion surface.

IMPORTANCE
Hepatitis C virus (HCV) infection affects ∼2% of the population globally, and no vaccine is available. HCV is a highly variable virus, and understanding the presentation of key antigenic sites at the virion surface is important for the design of a universal vaccine. This study investigates the role of three surface-exposed variable regions in E2 glycoprotein folding and function in the context of a recombinant soluble ectodomain. Our data demonstrate the variable motifs modulate binding of the E2 ectodomain to the major host cell receptor CD81 and have an impact on the formation of an E2 homodimer with high-affinity binding to CD81.
Interaction of the Small GTPase Cdc42 with Arginine Kinase Restricts White Spot Syndrome Virus in Shrimp
Authors: Xu Ji-Dong , Jiang Hai-Shan , Wei Tian-Di , Zhang Ke-Yi , Wang Xian-Wei , Zhao Xiao-Fan , Wang Jin-Xing
Published: December 2016

Many types of small GTPases are widely expressed in eukaryotes and have different functions. As a crucial member of the Rho GTPase family, Cdc42 serves a number of functions, such as regulating cell growth, migration, and cell movement. Several RNA viruses employ Cdc42-hijacking tactics in their target cell entry processes. However, the function of Cdc42 in shrimp antiviral immunity is not clear. In this study, we identified a Cdc42 protein in the kuruma shrimp (
Marsupenaeus japonicus
) and named it
Mj
Cdc42.
Mj
Cdc42 was upregulated in shrimp challenged by white spot syndrome virus (WSSV). The knockdown of
Mj
Cdc42 and injection of Cdc42 inhibitors increased the proliferation of WSSV. Further experiments determined that
Mj
Cdc42 interacted with an arginine kinase (
Mj
AK). By analyzing the binding activity and enzyme activity of
Mj
AK and its mutant, Δ
Mj
AK, we found that
Mj
AK could enhance the replication of WSSV in shrimp.
Mj
AK interacted with the envelope protein VP26 of WSSV. An inhibitor of AK activity, quercetin, could impair the function of
Mj
AK in WSSV replication. Further study demonstrated that the binding of
Mj
Cdc42 and
Mj
AK depends on Cys
271
of
Mj
AK and suppresses the WSSV replication-promoting effect of
Mj
AK. By interacting with the active site of
Mj
AK and suppressing its enzyme activity,
Mj
Cdc42 inhibits WSSV replication in shrimp. Our results demonstrate a new function of Cdc42 in the cellular defense against viral infection in addition to the regulation of actin and phagocytosis, which has been reported in previous studies.

IMPORTANCE
The interaction of Cdc42 with arginine kinase plays a crucial role in the host defense against WSSV infection. This study identifies a new mechanism of Cdc42 in innate immunity and enriches the knowledge of the antiviral innate immunity of invertebrates.
Zika Virus Methyltransferase: Structure and Functions for Drug Design Perspectives
Authors: Coutard Bruno , Barral Karine , Lichière Julie , Selisko Barbara , Martin Baptiste , Aouadi Wahiba , Lombardia Miguel Ortiz , Debart Françoise , Vasseur Jean-Jacques , Guillemot Jean Claude , Canard Bruno , Decroly Etienne
Published: December 2016

The
Flavivirus
Zika virus (ZIKV) is the causal agent of neurological disorders like microcephaly in newborns or Guillain-Barre syndrome. Its NS5 protein embeds a methyltransferase (MTase) domain involved in the formation of the viral mRNA cap. We investigated the structural and functional properties of the ZIKV MTase. We show that the ZIKV MTase can methylate RNA cap structures at the N-7 position of the cap, and at the 2′-O position on the ribose of the first nucleotide, yielding a cap-1 structure. In addition, the ZIKV MTase methylates the ribose 2′-O position of internal adenosines of RNA substrates. The crystal structure of the ZIKV MTase determined at a 2.01-Å resolution reveals a crystallographic homodimer. One chain is bound to the methyl donor (
S
-adenosyl-
l
-methionine [SAM]) and shows a high structural similarity to the dengue virus (DENV) MTase. The second chain lacks SAM and displays conformational changes in the αX α-helix contributing to the SAM and RNA binding. These conformational modifications reveal a possible molecular mechanism of the enzymatic turnover involving a conserved Ser/Arg motif. In the second chain, the SAM binding site accommodates a sulfate close to a glycerol that could serve as a basis for structure-based drug design. In addition, compounds known to inhibit the DENV MTase show similar inhibition potency on the ZIKV MTase. Altogether these results contribute to a better understanding of the ZIKV MTase, a central player in viral replication and host innate immune response, and lay the basis for the development of potential antiviral drugs.

IMPORTANCE
The Zika virus (ZIKV) is associated with microcephaly in newborns, and other neurological disorders such as Guillain-Barre syndrome. It is urgent to develop antiviral strategies inhibiting the viral replication. The ZIKV NS5 embeds a methyltransferase involved in the viral mRNA capping process, which is essential for viral replication and control of virus detection by innate immune mechanisms. We demonstrate that the ZIKV methyltransferase methylates the mRNA cap and adenosines located in RNA sequences. The structure of ZIKV methyltransferase shows high structural similarities to the dengue virus methyltransferase, but conformational specificities highlight the role of a conserved Ser/Arg motif, which participates in RNA and SAM recognition during the reaction turnover. In addition, the SAM binding site accommodates a sulfate and a glycerol, offering structural information to initiate structure-based drug design. Altogether, these results contribute to a better understanding of the
Flavivirus
methyltransferases, which are central players in the virus replication.
The Structural Interface between HIV-1 Vif and Human APOBEC3H
Authors: Ooms Marcel , Letko Michael , Simon Viviana
Published: December 2016

Human APOBEC3H (A3H) is a cytidine deaminase that inhibits HIV-1 replication. To evade this restriction, the HIV-1 Vif protein binds A3H and mediates its proteasomal degradation. To date, little information on the Vif-A3H interface has been available. To decipher how both proteins interact, we first mapped the Vif-binding site on A3H by functionally testing a large set of A3H mutants in single-cycle infectivity and replication assays. Our data show that the two A3H α-helixes α3 and α4 represent the Vif-binding site of A3H. We next used viral adaptation and a set of Vif mutants to identify novel, reciprocal Vif variants that rescued viral infectivity in the presence of two Vif-resistant A3H mutants. These A3H-Vif interaction points were used to generate the first A3H-Vif structure model, which revealed that the A3H helixes α3 and α4 interact with the Vif β-sheet (β2-β5). This model is in good agreement with previously reported Vif and A3H amino acids important for interaction. Based on the predicted A3H-Vif interface, we tested additional points of contact, which validated our model. Moreover, these experiments showed that the A3H and A3G binding sites on HIV-1 Vif are largely distinct, with both host proteins interacting with Vif β-strand 2. Taken together, this virus-host interface model explains previously reported data and will help to identify novel drug targets to combat HIV-1 infection.

IMPORTANCE
HIV-1 needs to overcome several intracellular restriction factors in order to replicate efficiently. The human APOBEC3 locus encodes seven proteins, of which A3D, A3F, A3G, and A3H restrict HIV-1. HIV encodes the Vif protein, which binds to the APOBEC3 proteins and leads to their proteasomal degradation. No HIV-1 Vif-APOBEC3 costructure exists to date despite extensive research. We and others previously generated HIV-1 Vif costructure models with A3G and A3F by mapping specific contact points between both proteins. Here, we applied a similar approach to HIV-1 Vif and A3H and successfully generated a Vif-A3H interaction model. Importantly, we find that the HIV-1 Vif-A3H interface is distinct from the Vif-A3G and Vif-A3F interfaces, with a small Vif region being important for recognition of both A3G and A3H. Our Vif-A3H structure model informs on how both proteins interact and could guide toward approaches to block the Vif-A3H interface to target HIV replication.
Herpes Simplex Virus 1 Ubiquitin-Specific Protease UL36 Abrogates NF-κB Activation in DNA Sensing Signal Pathway
Authors: Ye Ruijie , Su Chenhe , Xu Haiyan , Zheng Chunfu
Published: December 2016

The DNA sensing pathway triggers innate immune responses against DNA virus infection, and NF-κB signaling plays a critical role in establishing innate immunity. We report here that the herpes simplex virus 1 (HSV-1) ubiquitin-specific protease (UL36USP), which is a deubiquitinase (DUB), antagonizes NF-κB activation, depending on its DUB activity. In this study, ectopically expressed UL36USP blocked promoter activation of beta interferon (IFN-β) and NF-κB induced by cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). UL36USP restricted NF-κB activation mediated by overexpression of STING, TANK-binding kinase 1, IκB kinase α (IKKα), and IKKβ, but not p65. UL36USP was also shown to inhibit IFN-stimulatory DNA-induced IFN-β and NF-κB activation under conditions of HSV-1 infection. Furthermore, UL36USP was demonstrated to deubiquitinate IκBα and restrict its degradation and, finally, abrogate NF-κB activation. More importantly, the recombinant HSV-1 lacking UL36USP DUB activity, denoted as C40A mutant HSV-1, failed to cleave polyubiquitin chains on IκBα. For the first time, UL36USP was shown to dampen NF-κB activation in the DNA sensing signal pathway to evade host antiviral innate immunity.

IMPORTANCE
It has been reported that double-stranded-DNA-mediated NF-κB activation is critical for host antiviral responses. Viruses have established various strategies to evade the innate immune system. The N terminus of the HSV-1 UL36 gene-encoded protein contains the DUB domain and is conserved across all herpesviruses. This study demonstrates that UL36USP abrogates NF-κB activation by cleaving polyubiquitin chains from IκBα and therefore restricts proteasome-dependent degradation of IκBα and that DUB activity is indispensable for this process. This study expands our understanding of the mechanisms utilized by HSV-1 to evade the host antiviral innate immune defense induced by NF-κB signaling.
MRI appearance does not change in the first 7 days after acute hamstring injury—a prospective study
Authors: Wangensteen Arnlaug , Bahr Roald , Van Linschoten Robbart , Almusa Emad , Whiteley Rodney , Witvrouw Erik , Tol Johannes L
Published: December 2016

Background

The optimal timing of MRI following acute hamstring injury is not known and is mainly based on expert opinions.

Aims

To describe the day-to-day changes in the extent of oedema and investigate the optimal timing for detection of fibre disruption on MRI following acute hamstring injuries.

Study design

Prospective, descriptive study.

Methods

We performed standardised MRI (1.5T) ≤1 day after injury in male athletes with acute hamstring injury. If initial MRI revealed positive signs of injury (increased signal intensity on fluid sensitive sequences), consecutive MRIs were obtained daily throughout the subsequent week (ie, 7 times). The MRI parameters (day 1–7) were scored by a single radiologist using a standardised scoring form. The day-to-day changes in the extent of oedema (distance from tuber, craniocaudal length, mediolateral width and anteroposterior depth) and the presence and extent of fibre disruption (tear) were assessed with descriptive statistics and repeated measures using analysis of variance of log-transformed data. The overall main effect for time was reported with a significance level set at p<0.05.

Results

13 out of 132 male athletes assessed for eligibility between January 2014 and December 2015 were included. 1 dropped out, while 12 (31 years, range 20–49) completed the study; 11 had 7 MRI scans each and one had 5 MRI scans performed. There were no significant day-to-day changes for any of the extent of oedema measures (p values ranging from 0.12 to 0.81). Fibre disruption (tear), present in 5 of the athletes, was detectable from day 1, with small and insignificant day-to-day changes (p values ranging from 0.45 to 0.95).

Conclusions

We observed insignificant day-to-day changes in the extent of oedema throughout the first week following acute hamstring injury. Fibre disruption (tear) was detectable from the first day after injury. These findings indicate that MRI can be performed on any day during the first week following an acute (hamstring) muscle injury.
Undiagnosed diabetes and impaired fasting glucose inHFEC282Y homozygotes andHFEwild-type controls in the HEIRS Study
Authors: Barton James C , Barton J Clayborn , Adams Paul C , Acton Ronald T
Published: December 2016

Objective

To determine prevalences and predictors of undiagnosed diabetes mellitus (UDM) and impaired fasting glucose (IFG) in non-Hispanic whites withHFEp.C282Y homozygosity and controls without commonHFEmutations identified in population screening.

Research design and methods

We analyzed these observations in a postscreening examination: age; sex; body mass index; systolic/diastolic blood pressure; metacarpophalangeal joint hypertrophy; hepatomegaly; blood neutrophils; alanine and aspartate aminotransferase; elevated C reactive protein; transferrin saturation; serum ferritin; and Field Center.

Results

There were 223 p.C282Y homozygotes and 449 controls without diagnosed diabetes (43.9% men). Mean age of p.C282Y homozygotes was 52±13 years (controls 57±14 years; p<0.0001). Mean transferrin saturation in p.C282Y homozygotes was 67±26% (controls 34±14%; p<0.0001). Mean serum ferritin in p.C282Y homozygotes was 607 pmol/L (95% CI 497 to 517; controls 274 pmol/L (247 to 301); p<0.0001). Overall prevalences of UDM (4.0% vs 4.2%) and IFG (23.8% vs 25.6%) did not differ significantly between p.C282Y homozygotes and wt/wt controls, respectively. In logistic regressions, male sex, body mass index, and alanine aminotransferase were significantly associated with UDM. ORs were 2.7 (1.2 to 2.8); 1.0 (1.0 to 1.1); and 1.0 (1.0 to 1.0), respectively. Age, male sex, and body mass index were significantly associated with IFG. ORs were 1.0 (1.0 to 1.1); 2.8 (1.9 to 4.2); and 1.0 (1.0 to 1.1), respectively.

Conclusions

Prevalences of UDM and IFG were similar in p.C282Y homozygotes and controls in a postpopulation screening examination. Male sex was the strongest predictor of UDM and IFG.
Perception of first respiratory infection withPseudomonas aeruginosaby people with cystic fibrosis and those close to them: an online qualitative study
Authors: Palser Sally C , Rayner Oliver C , Leighton Paul A , Smyth Alan R
Published: December 2016

Background

People with cystic fibrosis (CF) are susceptible to respiratory infection withPseudomonas aeruginosa(PA), which may become chronic if initial eradication fails. Environmental acquisition and person-to-person transmission can occur. Respiratory PA infection is associated with increased mortality and more hospitalisations. This may cause patients and families anxiety and lead them to adopt preventive measures which may be ineffectual and intrusive. It is not possible to hold a conventional focus group to explore these issues because people with CF cannot meet together due to the risk of cross-infection.

Objective

To explore the perceptions of first respiratory infection with PA in people with CF and those close to them.

Design

We designed an online survey, to maximise accessibility and avoid the risk of cross-infection. This established the respondent's relationship with CF, asked 3 open questions about perceptions of PA and a final question about the prioritisation of research. Responses were analysed using a structured, iterative process. We identified keywords, analysed these incontext and derived key themes.

Setting

Promotion through social media allowed respondents from any country to participate.

Participants

People with CF and those close to them.

Results

Responses were received from 393 people, including 266 parents and 97 people with CF. The key themes were the emotional burden of PA (fear in particular); the burden of treatment PA entails and the need for accurate knowledge about PA.

Conclusions

Lack of knowledge and the health beliefs of individuals may promote fear of infection and inappropriate avoidance measures. Uncertainty about the implications of PA infection and the treatment required may cause anxiety. Healthcare professionals should provide clear information about how PA might be acquired and the treatment necessary, making clear the limitations of current understanding and acknowledging health beliefs.
Model-based cost-effectiveness analysis of B-type natriuretic peptide-guided care in patients with heart failure
Authors: Mohiuddin Syed , Reeves Barnaby , Pufulete Maria , Maishman Rachel , Dayer Mark , Macleod John , McDonagh Theresa , Purdy Sarah , Rogers Chris , Hollingworth William
Published: December 2016

Objective

Monitoring B-type natriuretic peptide (BNP) to guide pharmacotherapy might improve survival in patients with heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). However, the cost-effectiveness of BNP-guided care is uncertain and guidelines do not uniformly recommend it. We assessed the cost-effectiveness of BNP-guided care in patient subgroups defined by age and ejection fraction.

Methods

We used a Markov model with a 3-month cycle length to estimate the lifetime health service costs, quality-adjusted life years (QALYs) and incremental net monetary benefits (iNMBs) of BNP-guided versus clinically guided care in 3 patient subgroups: (1) HFrEF patients <75 years; (2) HFpEF patients <75 years; and (3) HFrEF patients ≥75 years. There is no evidence of benefit in patients with HFpEF aged ≥75 years. We used individual patient data meta-analyses and linked primary care, hospital and mortality data to inform the key model parameters. We performed probabilistic analysis to assess the uncertainty in model results.

Results

In younger patients (<75 years) with HFrEF, the mean QALYs (5.57 vs 5.02) and costs (£63 527 vs £58 139) were higher with BNP-guided care. At the willingness-to-pay threshold of £20 000 per QALY, the positive iNMB (£5424 (95% CI £987 to £9469)) indicates that BNP-guided care is cost-effective in this subgroup. The evidence of cost-effectiveness of BNP-guided care is less strong for younger patients with HFpEF (£3155 (−£10 307 to £11 613)) and older patients (≥75 years) with HFrEF (£2267 (−£1524 to £6074)). BNP-guided care remained cost-effective in the sensitivity analyses, albeit the results were sensitive to assumptions on its sustained effect.

Conclusions

We found strong evidence that BNP-guided care is a cost-effective alternative to clinically guided care in younger patients with HFrEF. It is potentially cost-effective in younger patients with HFpEF and older patients with HFrEF, but more evidence is required, particularly with respect to the frequency, duration and BNP target for monitoring. Cost-effectiveness results from trials in specialist settings cannot be generalised to primary care.
Inflammatory lung disease a potential risk factor for onset of idiopathic inflammatory myopathies: results from a pilot study
Authors: Helmers Sevim Barbasso , Jiang Xia , Pettersson David , Wikman Anna-Lis , Axelman Pia , Lundberg Åsa , Lundberg Ingrid E , Alfredsson Lars
Published: December 2016

Objectives

To assess the association between inflammatory lung disease and the risk of developing idiopathic inflammatory myopathies.

Methods

A population-based case–control study was conducted. Adult myositis cases, identified from the Swedish inpatient registry (diagnosed between 1995 and 1997), and randomly selected controls matched to cases on the date of birth, gender and residency, were asked to fill out a questionnaire with questions on lifestyle, environmental exposures and health. Eventually, 100 cases and 402 controls responded to the questionnaire and were included in the analyses. Exposure was defined as self-reported preceding inflammatory lung diseases (pneumonia, tuberculosis or sarcoidosis). The association between the exposure and risk of developing myositis was evaluated by calculating OR together with 95% CIs in logistic regressions.

Results

42 (42%) cases and 112 (28%) controls reported preceding inflammatory lung disease. Median duration between inflammatory lung disease and first symptom of myositis was 30 years. We observed a significant association between self-reported history of lung disease at study inclusion and diagnosis of myositis (crude OR=1.8 (1.1 to 2.9); smoking adjusted OR=1.9 (1.2 to 3.1)). We further identified a modestly increased, yet non-significant, association between preceding inflammatory lung disease (prior to index year) and diagnosis of myositis (smoking adjusted OR=1.6 (0.9 to 2.8)). The association was more pronounced among the cases of myositis with concurrent interstitial lung disease (OR=3.8 (1.0 to 14.5)).

Conclusions

Patients with preceding inflammatory lung disease tend to have an increased risk of developing myositis compared to those without. The effect was more pronounced among patients with myositis with concurrent interstitial lung disease. Thus inflammatory lung disease may constitute a risk factor for myositis.
Resonance Induced Rhythmogenesis in Chua’s Circuits Using Conjugate Variables
Authors: Kumar Pawan , Avasthi Anshul , Jain Shreyans , Singla Tanu , Parmananda P.
Published: December 2016

Interactions involving conjugate coupling and feedback have been known to induce rhythmogenesis in Chua’s circuits exhibiting fixed point behavior [Singla et al., 2011; Mandal et al., 2013]. It was reported, in these works, that beyond a threshold value of coupling/feedback strength, interaction term involving difference of conjugate variables can induce oscillations in Chua’s circuit. Furthermore, it has been observed that the parametric thresholds, in nonlinear oscillators, can be regulated by suitable forcing techniques [Parmananda et al., 2001; Mahara et al., 2005]. In the present work, a conjunction of these two ideas has been entertained i.e. we study the rhythmogenesis in Chua’s circuit when the conjugate coupling/feedback terms are modulated sinusoidally. It was noted that, when the forcing frequency lies in the vicinity of the natural frequency of Chua’s circuit, maximum lowering of the threshold coupling/feedback constant occurred. Appearance of Arnold’s tongue was also observed as a result of these perturbations. Numerical results have been complimented with the experimental observations.
Complex Networks Unveiling Spatial Patterns in Turbulence
Authors: Scarsoglio Stefania , Iacobello Giovanni , Ridolfi Luca
Published: December 2016

Numerical and experimental turbulence simulations are nowadays reaching the size of the so-called big data, thus requiring refined investigative tools for appropriate statistical analyses and data mining. We present a new approach based on the complex network theory, offering a powerful framework to explore complex systems with a huge number of interacting elements. Although interest in complex networks has been increasing in the past years, few recent studies have been applied to turbulence. We propose an investigation starting from a two-point correlation for the kinetic energy of a forced isotropic field numerically solved. Among all the metrics analyzed, the degree centrality is the most significant, suggesting the formation of spatial patterns which coherently move with similar vorticity over the large eddy turnover time scale. Pattern size can be quantified through a newly-introduced parameter (i.e. average physical distance) and varies from small to intermediate scales. The network analysis allows a systematic identification of different spatial regions, providing new insights into the spatial characterization of turbulent flows. Based on present findings, the application to highly inhomogeneous flows seems promising and deserves additional future investigation.
THE CANTOR SET’S MULTI-FRACTAL SPECTRUM FORMED BY DIFFERENT PROBABILITY FACTORS IN MATHEMATICAL EXPERIMENT
Authors: PAN XUEZAI , SHANG XUDONG , WANG MINGGANG , ZUO-FEI
Published: December 2016

With the purpose of researching the changing regularities of the Cantor set’s multi-fractal spectrums and generalized fractal dimensions under different probability factors, from statistical physics, the Cantor set is given a mass distribution, when the mass is given with different probability ratios, the different multi-fractal spectrums and the generalized fractal dimensions will be acquired by computer calculation. The following conclusions can be acquired. On one hand, the maximal width of the multi-fractal spectrum and the maximal vertical height of the generalized fractal dimension will become more and more narrow with getting two probability factors closer and closer. On the other hand, when two probability factors are equal to 1/2, both the multi-fractal spectrum and the generalized fractal dimension focus on the value 0.6309, which is not the value of the physical multi-fractal spectrum and the generalized fractal dimension but the mathematical Hausdorff dimension.