bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validity of spectral analysis based on heart rate variability from 1‐minute or less ECG recordings
Authors: Takahashi Naomi , Kuriyama Akira , Kanazawa Hoshinori , Takahashi Yoshimitsu , Nakayama Takeo 
Published: June 2017

AbstractBackgroundTo broaden the utility of heart rate variability (HRV) in clinical medicine and mass screening, results based on shorter electrocardiogram (ECG) recordings require validation with those based on standard 5‐minute recordings. We investigated the association between HRV variables obtained from 5‐minute ECGs with those obtained from ECGs shorter than 5 minutes.MethodsTwenty‐two participants aged 20–69 years underwent 5‐minute resting ECG recordings in the supine position with natural breathing. Spectral analysis using MemCalc method was performed to calculate high‐frequency (HF, which required at least 10 seconds) and low‐frequency (LF, which required at least 30 seconds) components. Participants were not strictly preconditioned as in previous experimental studies in order to simulate a setting similar to that of a general health checkup. Associations of each variable between the 5‐minute ECG recordings and those for shorter recordings were examined by Pearson's correlation coefficients and Bland‐Altman plots.ResultsHF and LF components were log‐transformed based on their distributions. Correlation coefficients between 5‐minute data and shorter recordings in the supine position with natural breathing ranged from 0.80 to 0.91 (HF by 10‐second recording, 0.80; LF by 30‐second recording, 0.83, respectively). Bland‐Altman plots showed that gaps between the values from both methods slightly increased as the HF and LF component values increased.ConclusionsAlthough slight proportional errors were possible, values from standard 5‐minute and shorter recordings in the supine position were strongly correlated. Our findings suggest that shorter ECG data without strict preconditioning can be reliably used for spectral analysis.
Development of a Web Tool for Escherichia coli Subtyping Based on
fimH
Alleles
Authors: Roer Louise , Tchesnokova Veronika , Allesøe Rosa , Muradova Mariya , Chattopadhyay Sujay , Ahrenfeldt Johanne , Thomsen Martin C. F. , Lund Ole , Hansen Frank , Hammerum Anette M. , Sokurenko Evgeni , Hasman Henrik 
Published: June 2017

ABSTRACT

The aim of this study was to construct a valid publicly available method for
in silico fimH
subtyping of
Escherichia coli
particularly suitable for differentiation of fine-resolution subgroups within clonal groups defined by standard multilocus sequence typing (MLST). FimTyper was constructed as a FASTA database containing all currently known
fimH
alleles. The software source code is publicly available at
https://bitbucket.org/genomicepidemiology/fimtyper
, the database is freely available at
https://bitbucket.org/genomicepidemiology/fimtyper_db
, and a service implementing the software is available at
https://cge.cbs.dtu.dk/services/FimTyper
. FimTyper was validated on three data sets: one containing Sanger sequences of
fimH
alleles of 42
E. coli
isolates generated prior to the current study (data set 1), one containing whole-genome sequence (WGS) data of 243 third-generation-cephalosporin-resistant
E. coli
isolates (data set 2), and one containing a randomly chosen subset of 40
E. coli
isolates from data set 2 that were subjected to conventional
fimH
subtyping (data set 3). The combination of the three data sets enabled an evaluation and comparison of FimTyper on both Sanger sequences and WGS data. FimTyper correctly predicted all 42
fimH
subtypes from the Sanger sequences from data set 1 and successfully analyzed all 243 draft genomes from data set 2. FimTyper subtyping of the Sanger sequences and WGS data from data set 3 were in complete agreement. Additionally,
fimH
subtyping was evaluated on a phylogenetic network of 122 sequence type 131 (ST131)
E. coli
isolates. There was perfect concordance between the typology and
fimH
-based subclones within ST131, with accurate identification of the pandemic multidrug-resistant clonal subgroup ST131-
H
30. FimTyper provides a standardized tool, as a rapid alternative to conventional
fimH
subtyping, highly suitable for surveillance and outbreak detection.
HDM2 Promotes NEDDylation of Hepatitis B Virus HBx To Enhance Its Stability and Function
Authors: Liu Ningning , Zhang Jinfang , Yang Xiaohai , Jiao Tong , Zhao Xin , Li Wenxia , Zhu Jianhua , Yang Pu , Jin Jianping , Peng Jirun , Li Zhiwei , Ye Xin 
Published: June 2017

ABSTRACT
Hepatitis B virus (HBV)-encoded X protein (HBx) plays a critical role in HBV-related hepatocarcinoma development. In this study, we demonstrate that HBx is specifically modified by NEDD8. We found that E3 ligase HDM2 promotes NEDDylation of HBx to enhance HBx stability by preventing its ubiquitination-mediated degradation. Consistently, analysis of 160 hepatocellular carcinoma patient specimens indicated that the amount of HDM2 protein correlates with HBx protein level. We identified that HBx K91 and K95 as the key HBx NEDDylation sites and observed that the NEDDylation-deficient HBx has shorter half-life. We generated Huh7 cell lines which ectopically express wild-type and NEDDylation-deficient HBx and found that NEDDylation-deficient HBx showed less chromatin localization and less DDB1 binding. Consistently, the expression of HBx-regulated genes (IL-8, MMP9, and YAP) and HBV transcription (the activity of HBV enhancer and the amount of pgRNA transcribed from cccDNA) were significantly higher in cells expressing wild-type (WT) HBx than that in cells expressing mutant HBx. In addition, HBx-expressing cells proliferated faster than control and mutant HBx-expressing cells. We also showed that the ability of WT HBx-expressing cells to form tumors in nude mice was significantly higher than that of mutant HBx-expressing cells. In conclusion, we revealed that E3 ligase HDM2 promotes NEDDylation of HBx to enhance HBx stability and chromatin localization, which in turn favors HBx-dependent transcriptional regulation, cell proliferation, and HBV-driven tumor growth.

IMPORTANCE
Hepatitis B virus (HBV) HBx protein plays a critical role in viral replication and hepatocarcinogenesis. However, the regulation of HBx stability is not well understood. We found that HBx is modified by NEDD8 and that the HDM2 E3 ligase promotes HBx NEDDylation to enhance HBx stability by inhibiting its ubiquitination. We provide a new evidence to show the positive correlation between HDM2 and HBx in clinical hepatocellular carcinoma (HCC) samples. We also identified the major NEDDylation sites on HBx. Our studies indicate that the defective NEDDylation of HBx negatively affects its ability to activate the transcription of downstream genes and promote cell proliferation and tumor growth
in vivo
. Taken together, our findings reveal a novel posttranslational modification of HBx by HDM2 which regulates its stability, subcellular localization, and functions. These findings indicate that HDM2 is an important regulator on HBx and a potential diagnosis/therapeutic marker for HBV-associated HCC.
Evasion of the STING DNA-Sensing Pathway by VP11/12 of Herpes Simplex Virus 1
Authors: Deschamps Thibaut , Kalamvoki Maria 
Published: June 2017

ABSTRACT

The
st
imulator of
in
terferon (IFN)
g
enes (STING) is a broad antimicrobial factor that restricts herpes simplex virus (HSV) by activating type I interferon and proinflammatory responses upon sensing of foreign DNA. UL46 is one of the most abundant tegument proteins of HSV-1, but a well-established function has yet to be found. We found that the HSV-1 UL46 protein interacts with and colocalizes with STING. A ΔUL46 virus displayed growth defects and activated innate immunity, but both effects were alleviated in STING knockdown cells. UL46 was also required for the inhibition of the 2′,3′-cyclic GMP-AMP (cGAMP)-dependent immune responses during infection. In cells expressing UL46, out of the context of the infection, innate immunity to a ΔICP0 virus was largely compromised, and that permitted ICP0-deficient mutants to replicate. The UL46-expressing cell lines also rescued the defects of the ΔUL46 virus and enhanced wild-type virus infection. The UL46-expressing cell lines did not activate interferon-stimulated gene (ISG) transcription following treatment with the noncanonical cyclic dinucleotide 2′,3′-cGAMP, suggesting that the STING pathway may be compromised. Indeed, we found that both proteins STING and IFI16 were eliminated in cells constitutively expressing UL46 and that the accumulation of their transcripts was blocked. Finally, we demonstrated that UL46 via its N terminus binds to STING and, via its C terminus, to TBK1. These interactions appear to modulate the functions of STING during HSV-1 infection. Taken together, our studies describe a novel function for one of the least-studied proteins of HSV, the tegument protein UL46, and that function involves the evasion of foreign DNA-sensing pathways.

IMPORTANCE
Herpes simplex virus 1 (HSV-1) afflicts 80% of the population worldwide, causing various diseases. After initial infection, the virus establishes latent reservoirs in sensory neurons and persists for life. Here we describe novel interactions between HSV-1 and the DNA sensor STING. We found that (i) HSV-1 tegument protein UL46 interacts with and colocalizes with STING; (ii) UL46 expressed out of the context of the infection blocks type I interferon triggered by STING stimuli, through the elimination of STING and of interferon-inducible protein 16 (IFI16); (iii) a ΔUL46 virus displayed growth defects, which were rescued in STING knockdown cells; (iv) the ΔUL46 virus failed to block innate immunity triggered by ligands of STING such as 2′,3′-cGAMP and also activated IFN-β and ISG expression; and (v) UL46 binds to both STING and TBK1 through different domains. We conclude that UL46 counteracts the actions of STING during HSV-1 infection.
Guanylate-Binding Protein 1 Inhibits Nuclear Delivery of Kaposi's Sarcoma-Associated Herpesvirus Virions by Disrupting Formation of Actin Filament
Authors: Zou Zhe , Meng Zhihua , Ma Chao , Liang Deguang , Sun Rui , Lan Ke 
Published: June 2017

ABSTRACT
Kaposi's sarcoma-associated herpesvirus (KSHV) is a typical gammaherpesvirus that establishes persistent lifelong infection in host cells. In order to establish successful infection, KSHV has evolved numerous immune evasion strategies to bypass or hijack the host immune system. However, host cells still produce immune cytokines abundantly during primary KSHV infection. Whether the immune effectors produced are able to inhibit viral infection and how KSHV successfully conquers these immune effectors remain largely unknown. The guanylate-binding protein 1 (GBP1) gene is an interferon-stimulated gene and exerts antiviral functions on several RNA viruses; however, its function in DNA virus infection is less well understood. In this study, we found that KSHV infection increases both the transcriptional and protein levels of GBP1 at the early stage of primary infection by activating the NF-κB pathway. The overexpression of GBP1 significantly inhibited KSHV infection, while the knockdown of GBP1 promoted KSHV infection. The GTPase activity and dimerization of GBP1 were demonstrated to be responsible for its anti-KSHV activity. Furthermore, we found that GBP1 inhibited the nuclear delivery of KSHV virions by disrupting the formation of actin filaments. Finally, we demonstrated that replication and transcription activator (RTA) promotes the degradation of GBP1 through a proteasome pathway. Taken together, these results provide a new understanding of the antiviral mechanism of GBP1, which possesses potent anti-KSHV activity, and suggest the critical role of RTA in the evasion of the innate immune response during primary infection by KSHV.

IMPORTANCE
GBP1 can be induced by various cytokines and exerts antiviral activities against several RNA viruses. Our study demonstrated that GBP1 can exert anti-KSHV function by inhibiting the nuclear delivery of KSHV virions via the disruption of actin filaments. Moreover, we found that KSHV RTA can promote the degradation of GBP1 through a proteasome-mediated pathway. Taken together, our results elucidate a novel mechanism of GBP1 anti-KSHV activity and emphasize the critical role of RTA in KSHV evasion of the host immune system during primary infection.
Gender Parity Trends for Invited Speakers at Four Prominent Virology Conference Series
Authors: Kalejta Robert F. , Palmenberg Ann C. 
Published: June 2017

ABSTRACT
Scientific conferences are most beneficial to participants when they showcase significant new experimental developments, accurately summarize the current state of the field, and provide strong opportunities for collaborative networking. A top-notch slate of invited speakers, assembled by conference organizers or committees, is key to achieving these goals. The perceived underrepresentation of female speakers at prominent scientific meetings is currently a popular topic for discussion, but one that often lacks supportive data. We compiled the full rosters of invited speakers over the last 35 years for four prominent international virology conferences, the American Society for Virology Annual Meeting (ASV), the International Herpesvirus Workshop (IHW), the Positive-Strand RNA Virus Symposium (PSR), and the Gordon Research Conference on Viruses & Cells (GRC). The rosters were cross-indexed by unique names, gender, year, and repeat invitations. When plotted as gender-dependent trends over time, all four conferences showed a clear proclivity for male-dominated invited speaker lists. Encouragingly, shifts toward parity are emerging within all units, but at different rates. Not surprisingly, both selection of a larger percentage of first-time participants and the presence of a woman on the speaker selection committee correlated with improved parity. Session chair information was also collected for the IHW and GRC. These visible positions also displayed a strong male dominance over time that is eroding slowly. We offer our personal interpretation of these data to aid future organizers achieve improved equity among the limited number of available positions for session moderators and invited speakers.

IMPORTANCE
Politicians and media members have a tendency to cite anecdotes as conclusions without any supporting data. This happens so frequently now, that a name for it has emerged: fake news. Good science proceeds otherwise. The underrepresentation of women as invited speakers at international scientific conferences exemplifies a present-day discussion topic usually occurring without facts to support or refute the arguments. We now provide records profiling four prominent virology conferences over the years 1982 to 2017 with the intention that the trends and accompanying analyses of the gender parity of invited speakers may allow the ongoing discussions to be informed.
Newcastle Disease Virus Establishes Persistent Infection in Tumor Cells
In Vitro
: Contribution of the Cleavage Site of Fusion Protein and Second Sialic Acid Binding Site of Hemagglutinin-Neuraminidase
Authors: Rangaswamy Udaya S. , Wang Weijia , Cheng Xing , McTamney Patrick , Carroll Danielle , Jin Hong 
Published: June 2017

ABSTRACT

Newcastle disease virus (NDV) is an oncolytic virus being developed for the treatment of cancer. Following infection of a human ovarian cancer cell line (OVCAR3) with a recombinant low-pathogenic NDV, persistent infection was established in a subset of tumor cells. Persistently infected (PI) cells exhibited resistance to superinfection with NDV and established an antiviral state, as demonstrated by upregulation of interferon and interferon-induced genes such as myxoma resistance gene 1 (Mx1) and retinoic acid-inducing gene-I (RIG-I). Viruses released from PI cells induced higher cell-to-cell fusion than the parental virus following infection in two tumor cell lines tested, HT1080 and HeLa, and remained attenuated in chickens. Two mutations, one in the fusion (F) protein cleavage site, F117S (F
117S
), and another in hemagglutinin-neuraminidase (HN), G169R (HN
169R
), located in the second sialic acid binding region, were responsible for the hyperfusogenic phenotype. F
117S
improves F protein cleavage efficiency, facilitating cell-to-cell fusion, while HN
169R
possesses a multifaceted role in contributing to higher fusion, reduced receptor binding, and lower neuraminidase activity, which together result in increased fusion and reduced viral replication. Thus, establishment of persistent infection
in vitro
involves viral genetic changes that facilitate efficient viral spread from cell to cell as a potential mechanism to escape host antiviral responses. The results of our study also demonstrate a critical role in the viral life cycle for the second receptor binding region of the HN protein, which is conserved in several paramyxoviruses.

IMPORTANCE
Oncolytic Newcastle disease virus (NDV) could establish persistent infection in a tumor cell line, resulting in a steady antiviral state reflected by constitutively expressed interferon. Viruses isolated from persistently infected cells are highly fusogenic, and this phenotype has been mapped to two mutations, one each in the fusion (F) and hemagglutinin-neuraminidase (HN) proteins. The F
117S
mutation in the F protein cleavage site improved F protein cleavage efficiency while the HN
169R
mutation located at the second receptor binding site of the HN protein contributed to a complex phenotype consisting of a modest increase in fusion and cell killing, lower neuraminidase activity, and reduced viral growth. This study highlights the intricate nature of these two mutations in the glycoproteins of NDV in the establishment of persistent infection. The data also shed light on the critical balance between the F and HN proteins required for efficient NDV infection and their role in avian pathogenicity.
Growth of meibomian gland tissue after intraductal meibomian gland probing in patients with obstructive meibomian gland dysfunction
Authors: Maskin Steven L , Testa Whitney R 
Published: June 2017

PurposeTo investigate the impact of meibomian gland probing (MGP) on meibomian gland (MG) area from the upper lids of patients with obstructive meibomian gland dysfunction (o-MGD).MethodsRetrospective study comparing pre-MGP/post-MGP non-contact infrared meibography results in patients with o-MGD, viewing signs of MG growth within total measurement field.ResultsPost-MGP meibography of 34 lids (19 patients, ≥4.5 to ≤12 months’ follow-up) showed 41.2% with MG growth. Ten lids had meibographies suitable for analysis, showing significant collective (116 glands) increase in mean individual glandular area (MIGA) of 4.87% (p=0.0145). Four of 10 lids independently showed significant increase in MIGA, ranging from 10.70% to 21.13% (p<0.0001, p=0.0277, p=0.0292, p=0.0345), while six did not.At >12 and <25 months’ follow-up, 16 lids (9 additional patients) had follow-up showing 25% with signs of MG growth. Analysis of three lids showed a significant collective (33 glands) increase in MIGA of 11.19% (p=0.0004). Two of three lids independently showed significant increase in MIGA of 13.73% and 20.00% (p=0.0097, p=0.0001). Collectively, for all 13 analysed lids (149 glands), there was a significant increase of 6.38% in total glandular area (p=0.0447) and a significant increase of 6.23% in MIGA (p=0.0003).ConclusionMGP was associated with increased MG tissue area and growth of atrophied MGs as viewed on meibography. MGP provides unequivocal physical proof of a patent meibum outflow tract through the natural orifice, and may promote glandular growth in part by direct mechanical establishment of a patent duct/orifice system.
Resisting the urge to prescribe vancomycin
Authors: Magalhães‐Sant'Ana Manuel 
Published: June 2017

THIS series gives readers the opportunity to consider and contribute to discussion of some of the ethical dilemmas that can arise in veterinary practice. Each month, a case scenario is presented, followed by discussion of some of the issues involved.In addition, a possible way forward is suggested; however, there is rarely a cut‐and‐dried answer in such cases, and readers may wish to suggest an alternative approach. This month's dilemma, ‘Resisting the urge to prescribe vancomycin’, was submitted and is discussed by Manuel Magalhães‐Sant'Ana. Readers with comments to contribute are invited to send them as soon as possible, so that they can be considered for publication in the next issue.The series is being coordinated by Steven McCulloch, a practising vet with a PhD in the ethics of veterinary policy. It aims to provide a framework that will help practitioners find solutions when facing similar dilemmas.
Analysis of neointima development in flow diverters using optical coherence tomography imaging
Authors: Matsuda Yoshikazu , Chung Joonho , Lopes Demetrius K 
Published: June 2017

BackgroundFlow diverters are used for the treatment of intracranial aneurysms. Surface modification may decrease the thrombogenicity of flow diverters but the details are unknown. Optical coherence tomography (OCT) is an intravascular imaging test with high resolution which identifies neointimal growth over stents. We compared the development of neointima in a flow diverter and stents with and without surface modification in a swine model.MethodsIn this study we implanted four devices (two in each carotid artery) in four pigs. The devices used were the Pipeline Flex embolization device (PED Flex, n=6), PED with Shield technology (PED Shield, n=6), and Solitaire AB (n=4). Serial carotid angiographic and OCT images were obtained on days 0, 7, 14, and 21. The data analyzed included: neointimal area (lumen area − stent area), neointimal ratio ([lumen area − stent area]/stent area), and the neointimal thickness ratio (minimum neointimal thickness/maximum neointimal thickness).ResultsThere was no significant difference in where neointima formation was initiated in relation to the implanted device (distal vs middle vs proximal). The PED Shield had a trend towards earlier endothelial formation at day 7. By day 21 the neointimal ratio was significantly higher for the PED Flex and PED Shield devices than for Solitaire (p<0.05 and p<0.01, respectively). The neointimal thickness ratio was significantly higher with PED Shield than with PED Flex and Solitaire (p<0.05 and p<0.01, respectively).ConclusionsOCT enabled us to follow and compare in vivo the development of neointima over implants. PED Shield showed a similar neointimal volume to PED Flex and more concentric neointima.
Thermodynamic properties of spin-polarized 3He gas in the temperature range 1 mK–4 K from the quantum second virial coefficient
Authors: Al-Maaitah A. F. , Sandouqa A. S. , Joudeh B. R. , Ghassib H. B. 
Published: June 2017

The quantum second virial coefficient B[Formula: see text] of 3He[Formula: see text] gas is determined in the temperature range 0.001–4 K from the Beth–Uhlenbeck formula. The corresponding phase shifts are calculated from the Lippmann–Schwinger equation using a highly-accurate matrix-inversion technique. A positive B[Formula: see text] corresponds to an overall repulsive interaction; whereas a negative B[Formula: see text] represents an overall attractive interaction. It is found that in the low-energy limit, B[Formula: see text] tends to increase with increasing spin polarization. The compressibility Z is evaluated as another measure of nonideality of the system. Z becomes most significant at low temperatures and increases with polarization. From the pressure–temperature (P–T) behavior of 3He[Formula: see text] at low T, it is deduced that P decreases with increasing T below 8 mK.