bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-dimensional Ca
2+
imaging advances understanding of astrocyte biology
Authors: Bindocci Erika , Savtchouk Iaroslav , Liaudet Nicolas , Becker Denise , Carriero Giovanni , Volterra Andrea
Published: May 2017

Glial calcium dynamics in space and time

Astrocytes use calcium signals to process information received from neighboring brain cells and thus generate modulatory responses at the local or network level. Previous studies have relied on calcium imaging in line scans or in a single focal plane mostly focusing on the cell bodies of astrocytes. Bindocci
et al.
used more powerful scanners that can rapidly scan many focal planes. They combined this technique with advanced genetic tools for monitoring calcium gradients with high sensitivity, which allowed three-dimensional calcium imaging of a whole astrocyte. Most of the basal calcium activity occurred in the astrocyte processes, some in the endfeet, and only a small fraction actually in the cell bodies of astrocytes.

Science
, this issue p.
eaai8185
Higher predation risk for insect prey at low latitudes and elevations
Authors: Roslin Tomas , Hardwick Bess , Novotny Vojtech , Petry William K. , Andrew Nigel R. , Asmus Ashley , Barrio Isabel C. , Basset Yves , Boesing Andrea Larissa , Bonebrake Timothy C. , Cameron Erin K. , Dáttilo Wesley , Donoso David A. , Drozd Pavel , Gray Claudia L. , Hik David S. , Hill Sarah J. , Hopkins Tapani , Huang Shuyin , Koane Bonny , Laird-Hopkins Benita , Laukkanen Liisa , Lewis Owen T. , Milne Sol , Mwesige Isaiah , Nakamura Akihiro , Nell Colleen S. , Nichols Elizabeth , Prokurat Alena , Sam Katerina , Schmidt Niels M. , Slade Alison , Slade Victor , Suchanková Alžběta , Teder Tiit , van Nouhuys Saskya , Vandvik Vigdis , Weissflog Anita , Zhukovich Vital , Slade Eleanor M.
Published: May 2017

Risky in the tropics

It is well known that diversity increases toward the tropics. Whether this increase translates into differences in interaction rates among species, however, remains unclear. To simplify the problem, Roslin
et al.
tested for predation rates by using a single approach involving model caterpillars across six continents. Predator attack rates were higher toward the equator, but only for arthropod predators.

Science
, this issue p.
742
A dedicated network for social interaction processing in the primate brain
Authors: Sliwa J. , Freiwald W. A.
Published: May 2017

A brain region for social cognition

Monkeys recognize social interactions and their meanings quickly and effortlessly. Little is known about the neural circuitry that underlies this understanding. Sliwa and Freiwald scanned monkey brains as the monkeys watched static or moving stimuli. A subset of brain areas was exclusively active during monkey-monkey interactions, as opposed to physical interactions between two objects. This network shares some of its components with the monkey mirror neuron system mapped previously by others and with a possible homolog of the human network involved in the theory of mind.

Science, this issue p.745
ATP controls the crowd
Authors: Rice Allyson M. , Rosen Michael K.
Published: May 2017

A major energy carrier of the cell also promotes protein solubility
Culture-Based Methods and Molecular Tools for Azole-Resistant Aspergillus fumigatus Detection in a Belgian University Hospital
Authors: Montesinos I. , Argudín M. A. , Hites M. , Ahajjam F. , Dodémont M. , Dagyaran C. , Bakkali M. , Etienne I. , Jacobs F. , Knoop C. , Patteet S. , Lagrou K.
Published: May 2017

Azole-resistant
Aspergillus fumigatus
is an increasing worldwide problem with major clinical implications. Surveillance is warranted to guide clinicians to provide optimal treatment to patients. To investigate azole resistance in clinical
Aspergillus
isolates in our institution, a Belgian university hospital, we conducted a laboratory-based surveillance between June 2015 and October 2016. Two different approaches were used: a prospective culture-based surveillance using VIPcheck on unselected
A. fumigatus
(
n
= 109 patients, including 19 patients with proven or probable invasive aspergillosis [IA]), followed by molecular detection of mutations conferring azole resistance, and a retrospective detection of azole-resistant
A. fumigatus
in bronchoalveolar lavage fluid using the commercially available AsperGenius PCR (
n
= 100 patients, including 29 patients with proven or probable IA). By VIPcheck, 25 azole-resistant
A. fumigatus
specimens were isolated from 14 patients (12.8%). Of these 14 patients, only 2 had proven or probable IA (10.5%). Mutations at the
cyp51A
gene were observed in 23 of the 25
A. fumigatus
isolates; TR
34
/L98H was the most prevalent mutation (46.7%), followed by TR
46
/Y121F/T289A (26.7%). Twenty-seven (27%) patients were positive for the presence of
Aspergillus
species by AsperGenius PCR.
A. fumigatus
was detected by AsperGenius in 20 patients, and 3 of these patients carried
cyp51A
mutations. Two patients had proven or probable IA and
cyp51A
mutation (11.7%). Our study has shown that the detection of azole-resistant
A. fumigatus
in clinical isolates was a frequent finding in our institution. Hence, a rapid method for resistance detection may be useful to improve patient management. Centers that care for immunocompromised patients should perform routine surveillance to determine their local epidemiology.
Attenuation of Foot-and-Mouth Disease Virus by Engineered Viral Polymerase Fidelity
Authors: Rai Devendra K. , Diaz-San Segundo Fayna , Campagnola Grace , Keith Anna , Schafer Elizabeth A. , Kloc Anna , de los Santos Teresa , Peersen Olve , Rieder Elizabeth
Published: May 2017

Foot-and-mouth disease virus (FMDV) RNA-dependent RNA polymerase (RdRp) (3D
pol
) catalyzes viral RNA synthesis. Its characteristic low fidelity and absence of proofreading activity allow FMDV to rapidly mutate and adapt to dynamic environments. In this study, we used the structure of FMDV 3D
pol
in combination with previously reported results from similar picornaviral polymerases to design point mutations that would alter replication fidelity. In particular, we targeted Trp237 within conserved polymerase motif A because of the low reversion potential inherent in the single UGG codon. Using biochemical and genetic tools, we show that the replacement of tryptophan 237 with phenylalanine imparts higher fidelity, but replacements with isoleucine and leucine resulted in lower-fidelity phenotypes. Viruses containing these W237 substitutions show
in vitro
growth kinetics and plaque morphologies similar to those of the wild-type (WT) A
24
Cruzeiro strain in BHK cells, and both high- and low-fidelity variants retained fitness during coinfection with the wild-type virus. The higher-fidelity W237F (W237F
HF
) mutant virus was more resistant to the mutagenic nucleoside analogs ribavirin and 5-fluorouracil than the WT virus, whereas the lower-fidelity W237I (W237I
LF
) and W237L
LF
mutant viruses exhibited lower ribavirin resistance. Interestingly, the variant viruses showed heterogeneous and slightly delayed growth kinetics in primary porcine kidney cells, and they were significantly attenuated in mouse infection experiments. These data demonstrate, for a single virus, that either increased or decreased RdRp fidelity attenuates virus growth in animals, which is a desirable feature for the development of safer and genetically more stable vaccine candidates.

IMPORTANCE
Foot-and-mouth disease (FMD) is the most devastating disease affecting livestock worldwide. Here, using structural and biochemical analyses, we have identified FMDV 3D
pol
mutations that affect polymerase fidelity. Recombinant FMDVs containing substitutions at 3D
pol
tryptophan residue 237 were genetically stable and displayed plaque phenotypes and growth kinetics similar to those of the wild-type virus in cell culture. We further demonstrate that viruses harboring either a W237F
HF
substitution or W237I
LF
and W237L
LF
mutations were highly attenuated in animals. Our study shows that obtaining 3D
pol
fidelity variants by protein engineering based on polymerase structure and function could be exploited for the development of attenuated FMDV vaccine candidates that are safer and more stable than strains obtained by selective pressure via mutagenic nucleotides or adaptation approaches.
Molluscum Contagiosum Virus MC159 Abrogates cIAP1-NEMO Interactions and Inhibits NEMO Polyubiquitination
Authors: Biswas Sunetra , Shisler Joanna L.
Published: May 2017

Molluscum contagiosum virus (MCV) is a dermatotropic poxvirus that causes benign skin lesions. MCV lesions persist because of virally encoded immune evasion molecules that inhibit antiviral responses. The MCV MC159 protein suppresses NF-κB activation, a powerful antiviral response, via interactions with the NF-κB essential modulator (NEMO) subunit of the IκB kinase (IKK) complex. Binding of MC159 to NEMO does not disrupt the IKK complex, implying that MC159 prevents IKK activation via an as-yet-unidentified strategy. Here, we demonstrated that MC159 inhibited NEMO polyubiquitination, a posttranslational modification required for IKK and downstream NF-κB activation. Because MCV cannot be propagated in cell culture, MC159 was expressed independent of infection or during a surrogate vaccinia virus infection to identify how MC159 prevented polyubiquitination. Cellular inhibitor of apoptosis protein 1 (cIAP1) is a cellular E3 ligase that ubiquitinates NEMO. Mutational analyses revealed that MC159 and cIAP1 each bind to the same NEMO region, suggesting that MC159 may competitively inhibit cIAP1-NEMO interactions. Indeed, MC159 prevented cIAP1-NEMO interactions. MC159 also diminished cIAP1-mediated NEMO polyubiquitination and cIAP1-induced NF-κB activation. These data suggest that MC159 competitively binds to NEMO to prevent cIAP1-induced NEMO polyubiquitination. To our knowledge, this is the first report of a viral protein disrupting NEMO-cIAP1 interactions to strategically suppress IKK activation. All viruses must antagonize antiviral signaling events for survival. We hypothesize that MC159 inhibits NEMO polyubiquitination as a clever strategy to manipulate the host cell environment to the benefit of the virus.

IMPORTANCE
Molluscum contagiosum virus (MCV) is a human-specific poxvirus that causes persistent skin neoplasms. The persistence of MCV has been attributed to viral downregulation of host cell immune responses such as NF-κB activation. We show here that the MCV MC159 protein interacts with the NEMO subunit of the IKK complex to prevent NEMO interactions with the cIAP1 E3 ubiquitin ligase. This interaction correlates with a dampening of cIAP1 to polyubiquitinate NEMO and to activate NF-κB. This inhibition of cIAP1-NEMO interactions is a new viral strategy to minimize IKK activation and to control NEMO polyubiquitination. This research provides new insights into mechanisms that persistent viruses may use to cause long-term infection of host cells.
Natural Variation of Epstein-Barr Virus Genes, Proteins, and Primary MicroRNA
Authors: Correia Samantha , Palser Anne , Elgueta Karstegl Claudio , Middeldorp Jaap M. , Ramayanti Octavia , Cohen Jeffrey I. , Hildesheim Allan , Fellner Maria Dolores , Wiels Joelle , White Robert E. , Kellam Paul , Farrell Paul J.
Published: May 2017

Viral gene sequences from an enlarged set of about 200 Epstein-Barr virus (EBV) strains, including many primary isolates, have been used to investigate variation in key viral genetic regions, particularly LMP1, Zp, gp350, EBNA1, and the BART microRNA (miRNA) cluster 2. Determination of type 1 and type 2 EBV in saliva samples from people from a wide range of geographic and ethnic backgrounds demonstrates a small percentage of healthy white Caucasian British people carrying predominantly type 2 EBV. Linkage of Zp and gp350 variants to type 2 EBV is likely to be due to their genes being adjacent to the EBNA3 locus, which is one of the major determinants of the type 1/type 2 distinction. A novel classification of EBNA1 DNA binding domains, named QCIGP, results from phylogeny analysis of their protein sequences but is not linked to the type 1/type 2 classification. The BART cluster 2 miRNA region is classified into three major variants through single-nucleotide polymorphisms (SNPs) in the primary miRNA outside the mature miRNA sequences. These SNPs can result in altered levels of expression of some miRNAs from the BART variant frequently present in Chinese and Indonesian nasopharyngeal carcinoma (NPC) samples. The EBV genetic variants identified here provide a basis for future, more directed analysis of association of specific EBV variations with EBV biology and EBV-associated diseases.

IMPORTANCE
Incidence of diseases associated with EBV varies greatly in different parts of the world. Thus, relationships between EBV genome sequence variation and health, disease, geography, and ethnicity of the host may be important for understanding the role of EBV in diseases and for development of an effective EBV vaccine. This paper provides the most comprehensive analysis so far of variation in specific EBV genes relevant to these diseases and proposed EBV vaccines. By focusing on variation in LMP1, Zp, gp350, EBNA1, and the BART miRNA cluster 2, new relationships with the known type 1/type 2 strains are demonstrated, and a novel classification of EBNA1 and the BART miRNAs is proposed.
A Point Mutation in the Rhesus Rotavirus VP4 Protein Generated through a Rotavirus Reverse Genetics System Attenuates Biliary Atresia in the Murine Model
Authors: Mohanty Sujit K. , Donnelly Bryan , Dupree Phylicia , Lobeck Inna , Mowery Sarah , Meller Jaroslaw , McNeal Monica , Tiao Greg
Published: May 2017

Rotavirus infection is one of the most common causes of diarrheal illness in humans. In neonatal mice, rhesus rotavirus (RRV) can induce biliary atresia (BA), a disease resulting in inflammatory obstruction of the extrahepatic biliary tract and intrahepatic bile ducts. We previously showed that the amino acid arginine (R) within the sequence SRL (amino acids 445 to 447) in the RRV VP4 protein is required for viral binding and entry into biliary epithelial cells. To determine if this single amino acid (R) influences the pathogenicity of the virus, we generated a recombinant virus with a single amino acid mutation at this site through a reverse genetics system. We demonstrated that the RRV mutant (RRV
VP4-R446G
) produced less symptomatology and replicated to lower titers both
in vivo
and
in vitro
than those seen with wild-type RRV, with reduced binding in cholangiocytes. Our results demonstrate that a single amino acid change in the RRV VP4 gene influences cholangiocyte tropism and reduces pathogenicity in mice.

IMPORTANCE
Rotavirus is the leading cause of diarrhea in humans. Rhesus rotavirus (RRV) can also lead to biliary atresia (a neonatal human disease) in mice. We developed a reverse genetics system to create a mutant of RRV (RRV
VP4-R446G
) with a single amino acid change in the VP4 protein compared to that of wild-type RRV.
In vitro
, the mutant virus had reduced binding and infectivity in cholangiocytes.
In vivo
, it produced fewer symptoms and lower mortality in neonatal mice, resulting in an attenuated form of biliary atresia.
Deletion of the Vaccinia Virus B1 Kinase Reveals Essential Functions of This Enzyme Complemented Partly by the Homologous Cellular Kinase VRK2
Authors: Olson Annabel T. , Rico Amber B. , Wang Zhigang , Delhon Gustavo , Wiebe Matthew S.
Published: May 2017

The vaccinia virus B1 kinase is highly conserved among poxviruses and is essential for the viral life cycle. B1 exhibits a remarkable degree of similarity to vaccinia virus-related kinases (VRKs), a family of cellular kinases, suggesting that the viral enzyme has evolved to mimic VRK activity. Indeed, B1 and VRKs have been demonstrated to target a shared substrate, the DNA binding protein BAF, elucidating a signaling pathway important for both mitosis and the antiviral response. In this study, we further characterize the role of B1 during vaccinia infection to gain novel insights into its regulation and integration with cellular signaling pathways. We begin by describing the construction and characterization of the first B1 deletion virus (vvΔB1) produced using a complementing cell line expressing the viral kinase. Examination of vvΔB1 revealed that B1 is critical for the production of infectious virions in various cell types and is sufficient for BAF phosphorylation. Interestingly, the severity of the defect in DNA replication following the loss of B1 varied between cell types, leading us to posit that cellular VRKs partly complement for the absence of B1 in some cell lines. Using cell lines devoid of either VRK1 or VRK2, we tested this hypothesis and discovered that VRK2 expression facilitates DNA replication and allows later stages of the viral life cycle to proceed in the absence of B1. Finally, we present evidence that the impact of VRK2 on vaccinia virus is largely independent of BAF phosphorylation. These data support a model in which B1 and VRK2 share additional substrates important for the replication of cytoplasmic poxviruses.

IMPORTANCEViral mimicry of cellular signaling modulators provides clear evidence that the pathogen targets an important host pathway during infection. Poxviruses employ numerous viral homologs of cellular proteins, the study of which have yielded insights into signaling pathways used by both virus and cells alike. The vaccinia virus B1 protein is a homolog of cellular vaccinia virus-related kinases (VRKs) and is needed for viral DNA replication and likely other stages of the viral life cycle. However, much remains to be learned about how B1 and VRKs overlap functionally. This study utilizes new tools, including a B1 deletion virus and VRK knockout cells, to further characterize the functional links between the viral and cellular enzymes. As a result, we have discovered that B1 and VRK2 target a common set of substrates vital to productive infection of this large cytoplasmic DNA virus.
A Novel A(H7N2) Influenza Virus Isolated from a Veterinarian Caring for Cats in a New York City Animal Shelter Causes Mild Disease and Transmits Poorly in the Ferret Model
Authors: Belser Jessica A. , Pulit-Penaloza Joanna A. , Sun Xiangjie , Brock Nicole , Pappas Claudia , Creager Hannah M. , Zeng Hui , Tumpey Terrence M. , Maines Taronna R.
Published: May 2017

In December 2016, a low-pathogenic avian influenza (LPAI) A(H7N2) virus was identified to be the causative source of an outbreak in a cat shelter in New York City, which subsequently spread to multiple shelters in the states of New York and Pennsylvania. One person with occupational exposure to infected cats became infected with the virus, representing the first LPAI H7N2 virus infection in a human in North America since 2003. Considering the close contact that frequently occurs between companion animals and humans, it was critical to assess the relative risk of this novel virus to public health. The virus isolated from the human case, A/New York/108/2016 (NY/108), caused mild and transient illness in ferrets and mice but did not transmit to naive cohoused ferrets following traditional or aerosol-based inoculation methods. The environmental persistence of NY/108 virus was generally comparable to that of other LPAI H7N2 viruses. However, NY/108 virus replicated in human bronchial epithelial cells with an increased efficiency compared with that of previously isolated H7N2 viruses. Furthermore, the novel H7N2 virus was found to utilize a relatively lower pH for hemagglutinin activation, similar to human influenza viruses. Our data suggest that the LPAI H7N2 virus requires further adaptation before representing a substantial threat to public health. However, the reemergence of an LPAI H7N2 virus in the northeastern United States underscores the need for continuous surveillance of emerging zoonotic influenza viruses inclusive of mammalian species, such as domestic felines, that are not commonly considered intermediate hosts for avian influenza viruses.

IMPORTANCE
Avian influenza viruses are capable of crossing the species barrier to infect mammals, an event of public health concern due to the potential acquisition of a pandemic phenotype. In December 2016, an H7N2 virus caused an outbreak in cats in multiple animal shelters in New York State. This was the first detection of this virus in the northeastern United States in over a decade and the first documented infection of a felid with an H7N2 virus. A veterinarian became infected following occupational exposure to H7N2 virus-infected cats, necessitating the evaluation of this virus for its capacity to cause disease in mammals. While the H7N2 virus was associated with mild illness in mice and ferrets and did not spread well between ferrets, it nonetheless possessed several markers of virulence for mammals. These data highlight the promiscuity of influenza viruses and the need for diligent surveillance across multiple species to quickly identify an emerging strain with pandemic potential.
Reducing musculoskeletal injury and concussion risk in schoolboy rugby players with a pre-activity movement control exercise programme: a cluster randomised controlled trial
Authors: Hislop Michael D , Stokes Keith A , Williams Sean , McKay Carly D , England Mike E , Kemp Simon P T , Trewartha Grant
Published: May 2017

Background

Injury risk in youth rugby has received much attention, highlighting the importance of establishing evidence-based injury reduction strategies.

Aim

To determine the efficacy of a movement control exercise programme in reducing injuries in youth rugby players and to investigate the effect of programme dose on injury measures.

Methods

In a cluster-randomised controlled trial, 40 independent schools (118 teams, 3188 players aged 14–18 years) were allocated to receive either the intervention or a reference programme, both of which were to be delivered by school coaches. The intervention comprised balance training, whole-body resistance training, plyometric training, and controlled rehearsal of landing and cutting manoeuvres. Time-loss (>24 hours) injuries arising from school rugby matches were recorded by coaches and medical staff.

Results

441 time-loss match injuries (intervention, 233; control, 208) were reported across 15 938 match exposure-hours (intervention, 9083; control, 6855). Intention-to-treat results indicated unclear effects of trial arm on overall match injury incidence (rate ratio (RR)=0.85, 90% confidence limits 0.61 to 1.17), although clear reductions were evident in the intervention arm for concussion incidence (RR=0.71, 0.48 to 1.05). When trial arm comparisons were limited to teams who had completed three or more weekly programme sessions on average, clear reductions in overall match injury incidence (RR=0.28, 0.14 to 0.51) and concussion incidence (RR=0.41, 0.17 to 0.99) were noted in the intervention group.

Conclusion

A preventive movement control exercise programme can reduce match injury outcomes, including concussion, in schoolboy rugby players when compared with a standardised control exercise programme, although to realise the greatest effects players should complete the programme at least three times per week.
Pictorial prescribing reduces fentanyl drug administration errors: a simulated controlled study
Authors: Booth Stephen W , Gloag Maria , Kinna Sara , Bell Andrew , Wheble Joanna L C , Wheeler Daniel W
Published: May 2017

Objectives

Transmucosal fentanyl is used to treat transient exacerbations of cancer pain. Several immediate release products are available, presented as intranasal sprays, sublingual and buccal tablets, or lozenges. These are not interchangeable, creating potential for medication errors. We compared the incidence of medication errors in a simulated scenario using handwritten drug charts and charts labelled with preprinted self-adhesive stickers with full pictorial fentanyl prescriptions.

Methods

54 nurses were shown 5 handwritten drug charts and 5 with self-adhesive pictorial labels. Nurses indicated which preparation and dose they would administer from boxes of Instanyl, Abstral, Effentora and Actiq (Nycomed, ProStrakan, Cephalon and Teva, respectively). We measured the frequency of drug administration errors and asked them to rate the prescriptions for clarity on four-point Likert items.

Results

The use of pictorial self-adhesive prescriptions significantly reduced errors in choice of preparation, from 20 with traditional handwritten charts to 6 with self-adhesive labels (OR 3.52, 95% CI 1.39 to 8.90, p=0.006), but the incidence of dose error was not significantly different (OR 1.47, 95% CI 0.80 to 2.70, p=0.281). Analysis of Likert items showed using pictorial printed labels significantly improved nurses’ understanding of choice of preparation, dose and maximum four hourly dose (p<0.0001, p=0.006 and p=0.028, respectively).

Conclusions

The use of pictorial prescribing appears to be a promising strategy that could reduce medication errors in choice of fentanyl preparations. There may be a wider use for pictorial prescribing where non-interchangeable preparations of the same drug exist.
Impact of perceived control on all-cause and cardiovascular disease mortality in three urban populations of Central and Eastern Europe: the HAPIEE study
Authors: Kozela Magdalena , Pająk Andrzej , Micek Agnieszka , Besala Agnieszka , Kubinova Ruzena , Malyutina Sofia , Tamosiunas Abdonas , Pikhart Hynek , Peasey Anne , Nikitin Yuri , Marmot Michael , Bobak Martin
Published: May 2017

Background

Inverse associations between perceived control and cardiovascular disease (CVD) have been reported in studies from Western Europe and the USA. To assess this relationship across different populations, we investigated the association between perceived control and all-cause and CVD mortality in three population-based cohorts of Eastern European countries.

Methods

We analysed data from a prospective cohort study in random population samples in Krakow (Poland), Novosibirsk (Russia) and six Czech towns. Baseline survey included structured questionnaire and objective examination in a clinic. Perceived control was assessed using an 11-item scale developed by the MacArthur Foundation Programme on Successful Midlife. Information on vital status was obtained from death registers. Effect of perceived control on mortality was assessed using Cox proportional hazards models.

Results

A total of 2377 deaths (1003 from CVD) occurred among 27 249 participants over a median 7-year follow-up. In the Czech and Polish cohorts, perceived control was inversely associated with mortality; the adjusted HRs for the lowest versus highest control quintiles were 1.71 (1.34 to 2.19) in men and 1.63 (1.14 to 2.35) in women for all-cause mortality and 2.31 (1.48 to 3.59) and 5.50 (2.14 to 14.13) for CVD deaths. There was no association between perceived control and mortality in Russia; the adjusted HRs for all-cause mortality were 1.03 (0.79 to 1.34) in men and 1.29 (0.82 to 2.02) in women.

Conclusions

Low perceived control was associated with increased risk of all-cause and CVD mortality in Czech and Polish cohorts but not in Russia. It is possible that this inconsistency may partly reflect a different sociocultural understanding of the concept of control in Russia.
MiR-301b promotes the proliferation, mobility, and epithelial-to-mesenchymal transition of bladder cancer cells by targeting EGR1
Authors: Yan Lei , Wang Yan , Liang Jun , Liu Zhixin , Sun Xiaodong , Cai Kerui
Published: May 2017

We investigated the role of miR-301b in the modulation of the proliferation, migration, and invasion of bladder cancer (BLCA) cells. The expression of miR-301b and EGR1 (early growth response gene 1) mRNA were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). A dual-luciferase reporter gene system was used to identify the target relationship between miR-301b and EGR1. Cell proliferation, cell cycle, and apoptosis were analyzed by MTT assay, colony-forming assay, and flow cytometry, respectively. Cell motility and invasiveness were assessed by wound healing and Transwell assays. The expression of proteins involved in epithelial-to-mesenchymal transition (EMT) and EGR1 were determined by Western blot. Our results showed that miR-301b was up-regulated while EGR1 was down-regulated in BLCA tissues compared with adjacent normal tissues. The proliferation, migration, and invasiveness of T24 cells (a kind of human BLCA cell) were suppressed by decreasing miR-301b expression or increasing EGR1 expression. In addition, miR-301b promoted EMT signaling by influencing the expression of related proteins. In conclusion, miR-301b promotes the proliferation, migration, and aggressiveness of human BLCA cells by inhibiting the expression of EGR1.
Rainbow trout movement behavior and habitat occupancy are influenced by sex and Pacific salmon presence in an Alaska river system
Authors: Fraley Kevin M. , Falke Jeffrey A. , McPhee Megan V. , Prakash Anupma
Published: May 2017

We used spatially continuous field-measured and remotely sensed aquatic habitat characteristics paired with weekly ground-based telemetry tracking and snorkel surveys to describe movements and habitat occupancy of adult rainbow trout (Oncorhynchus mykiss) (N = 82) in a runoff-fed, salmon-influenced southcentral Alaska river system. We found that during the ice-free feeding season (June through September) rainbow trout occurrence was associated more with fine-scale (channel unit) characteristics relative to coarse-scale (stream reach) variables. The presence of Pacific salmon (Oncorhynchus spp., which provide an important seasonal food subsidy) and habitat size were particularly useful predictors. Weekly movement distance differed between pre- and postspawning salmon arrival, but did not vary by sex. Habitat quality, season, and the arrival of spawning salmon influenced the likelihood of rainbow trout movement, and fish moved farther to seek out higher-quality habitats. Because rainbow trout respond to habitat factors at multiple scales and seek out salmon-derived subsidies, it will be important to take a multiscale approach in protecting trout and salmon populations and managing the associated fisheries.
Ethanol-induced stress response of Staphylococcus aureus
Authors: Pando Jasmine M. , Pfeltz Richard F. , Cuaron Jesus A. , Nagarajan Vijayaraj , Mishra Mukti N. , Torres Nathanial J. , Elasri Mohamed O. , Wilkinson Brian J. , Gustafson John E.
Published: May 2017

Transcriptional profiles of 2 unrelated clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates were analyzed following 10% (v/v) ethanol challenge (15 min), which arrested growth but did not reduce viability. Ethanol-induced stress (EIS) resulted in differential gene expression of 1091 genes, 600 common to both strains, of which 291 were upregulated. With the exception of the downregulation of genes involved with osmotic stress functions, EIS resulted in the upregulation of genes that contribute to stress response networks, notably those altered by oxidative stress, protein quality control in general, and heat shock in particular. In addition, genes involved with transcription, translation, and nucleotide biosynthesis were downregulated. relP, which encodes a small alarmone synthetase (RelP), was highly upregulated in both MRSA strains following ethanol challenge, and relP inactivation experiments indicated that this gene contributed to EIS growth arrest. A number of persistence-associated genes were also upregulated during EIS, including those that encode toxin–antitoxin systems. Overall, transcriptional profiling indicated that the MRSA investigated responded to EIS by entering a state of dormancy and by altering the expression of elements from cross protective stress response systems in an effort to protect preexisting proteins.
AFFINE MODELS WITH STOCHASTIC MARKET PRICE OF RISK
Authors: REBONATO RICCARDO
Published: May 2017

In this paper we discuss the common shortcomings of a large class of essentially-affine models in the current monetary environment of repressed rates, and we present a class of reduced-form stochastic-market-risk affine models that can overcome these problems. In particular, we look at the extension of a popular doubly-mean-reverting Vasicek model, but the idea can be applied to all essentially-affine models. The model straddles the [Formula: see text]- and [Formula: see text]-measures. By allowing for a market price of risk whose stochasticity is not fully spanned by the yield-curve state variables that enter the model specification, we break the deterministic link between the yield-curve-based return-predicting factors and the market price of risk, but we retain, on average, the observed statistical regularities reported in the literature. We discuss in detail how this approach relates to the recent work by Joslin et al. (2014) [S. Joslin, M. Priebsch & K. J. Singleton (2014) Risk premiums in dynamic term structure models with unspanned macro risk, Journal of Finance LXIX (3), 1197–1233]. We show that the parameters of the model can be estimated in a simple and robust manner using survey-like information; and that the model we propose affords a more plausible decomposition of observed market yields into expectations and risk premia during an important recent market event than the one produced by mainstream essentially-affine models.
Developing an Understanding of Organisational Knowledge Creation: A Review Framework
Authors: Izunwanne Pamela Chidiogo
Published: May 2017

The purpose of this paper is to develop an understanding of the dimensions of organisational knowledge creation. To this end, the literature from numerous bodies of research is reviewed. Over the past 20 years, the literature on organisational knowledge creation has significantly grown and advanced. Many new and conflicting terminologies have evolved to shed more light on the subject. As a result, there are overlaps and conflicts in the literature. The framework suggested in this paper is therefore considered to be a useful means to structure further research on the subject. This paper presents an extensive review of the organisational knowledge creation literature as well as an overview of existing empirical studies. The framework that is presented in this paper emerged from the review and maps out two dimensions of organisational knowledge creation. Although there are many other possible dimensions that could potentially be included in the framework, this study focuses on the dimensions that are believed to reflect more obvious distinctions made in the extant literature on organisational knowledge creation. Furthermore, limiting the review to only two dimensions is believed to provide more coherence.
Cybersecurity skeptics now embracing formal methods
Authors: Lewis Ted G.
Published: May 2017

There is new hope for those who despair securing computer systems from external hackers. The recent DARPA HACMS project demonstrated conclusively that "certain pathways for attackers have all been shut down in a way that's mathematically proven to be unhackable for those pathways." Continuing research at DARPA and IARPA will eventually shut down all the pathways, and the external hackers will be out of business permanently.
Enhancing the extended hensel construction by using Gröbner basis
Authors: Sasaki Tateaki , Inaba Daiju
Published: May 2017

Contrary to that the general Hensel construction (GHC: [3]) uses univariate initial Hensel factors, the extended Hensel construction (EHC: [8]) uses multivariate initial Hensel factors determined by the Newton polygon (see below) of the given multivariate polynomial

F (x,
u
)

∈ K[
x
,

u

], where (

u

) = (
u
1
,...,
u

ℓ

), with
ℓ
≥ 2, and K is a number field. The
F
(

x,
u

) may be such that its leading coefficient may vanish at (

u

) = (
0
) = (0,...,0), and even may be
F
(
x
,
0
) = 0. The EHC was used so far for computing series expansion of multivariate algebraic function determined by
F
(

x,
u

) = 0, at critical points [8, 5] and for factorization [4, 1] and GCD computation [7] of
F
(
x
,

u

), without shifting the origin of

u

. It allows us to construct efficient algorithms for sparse multivariate polynomials [1, 7]. The EHC is another and promising approach than Zippel's sparse Hensel lifting [9, 10].
Finding maximum rank moment matrices by facial reduction on primal form and Douglas-Rachford iteration
Authors: Wang Fei , Reid Greg , Wolkowicz Henry
Published: May 2017

Recent breakthroughs have been made in the use of semi-definite programming and its application to real polynomial solving. For example, the real radical of a zero dimensional ideal, can be determined by such approaches. Some progress has been made on the determination of the real radical in positive dimension by Ma, Wang and Zhi[5, 4]. Such work involves the determination of maximal rank semidefinite matrices. Existing methods are computationally expensive and have poorer accuracy on larger examples.

In previous work we showed that regularity in the form of the Slater constraint qualification (strict feasibility) fails for the moment matrix in the SDP feasibility problem[6]. We used facial reduction to obtain a smaller regularized problem for which strict feasibility holds. However we did not have a theoretical guarantee that our methods, based on facial reduction and Douglas-Rachford iteration ensured the satisfaction of the maximum rank condition.

Our work is motivated by the problems above. We discuss how to compute the moment matrix and its kernel using facial reduction techniques where the maximum rank property can be guaranteed by solving the dual problem. The facial reduction algorithms on the primal form is presented. We give examples that exhibit for the first time additional facial reductions beyond the first which are effective in practice with much better accuracy than SeDuMi(CVX).
Loss of NHERF-1 expression prevents dopamine-mediated Na-K-ATPase regulation in renal proximal tubule cells from rat models of hypertension: aged F344 rats and spontaneously hypertensive rats
Authors: Barati Michelle T. , Ketchem Corey J. , Merchant Michael L. , Kusiak Walter B. , Jose Pedro A. , Weinman Edward J. , LeBlanc Amanda J. , Lederer Eleanor D. , Khundmiri Syed J.
Published: May 2017

Dopamine decreases Na-K-ATPase (NKA) activity by PKC-dependent phosphorylation and endocytosis of the NKA α1. Dopamine-mediated regulation of NKA is impaired in aging and some forms of hypertension. Using opossum (OK) proximal tubule cells (PTCs), we demonstrated that sodium-hydrogen exchanger regulatory factor-1 (NHERF-1) associates with NKA α1 and dopamine-1 receptor (D1R). This association is required for the dopamine-mediated regulation of NKA. In OK cells, dopamine decreases NHERF-1 association with NKA α1 but increases its association with D1R. However, it is not known whether NHERF-1 plays a role in dopamine-mediated NKA regulation in animal models of hypertension. We hypothesized that defective dopamine-mediated regulation of NKA results from the decrease in NHERF-1 expression in rat renal PTCs isolated from animal models of hypertension [spontaneously hypertensive rats (SHRs) and aged F344 rats]. To test this hypothesis, we isolated and cultured renal PTCs from 22-mo-old F344 rats and their controls, normotensive 4-mo-old F344 rats, and SHRs and their controls, normotensive Wistar-Kyoto (WKY) rats. The results demonstrate that in both hypertensive models (SHR and aged F344), NHERF-1 expression, dopamine-mediated phosphorylation of NKA, and ouabain-inhibitable K+ transport are reduced. Transfection of NHERF-1 into PTCs from aged F344 and SHRs restored dopamine-mediated inhibition of NKA. These results suggest that decreased renal NHERF-1 expression contributes to the impaired dopamine-mediated inhibition of NKA in PTCs from animal models of hypertension.
Brain-derived neurotrophic factor and airway fibrosis in asthma
Authors: Freeman Michelle R. , Sathish Venkatachalem , Manlove Logan , Wang Shengyu , Britt Rodney D. , Thompson Michael A. , Pabelick Christina M. , Prakash Y. S.
Published: May 2017

Airway remodeling in asthma driven by inflammation involves proliferation of epithelial cells and airway smooth muscle (ASM), as well as enhanced extracellular matrix (ECM) generation and deposition, i.e., fibrosis. Accordingly, understanding profibrotic mechanisms is important for developing novel therapeutic strategies in asthma. Recent studies, including our own, have suggested a role for locally produced growth factors such as brain-derived neurotrophic factor (BDNF) in mediating and modulating inflammation effects. In this study, we explored the profibrotic influence of BDNF in the context of asthma by examining expression, activity, and deposition of ECM proteins in primary ASM cells isolated from asthmatic vs. nonasthmatic patients. Basal BDNF expression and secretion, and levels of the high-affinity BDNF receptor TrkB, were higher in asthmatic ASM. Exogenous BDNF significantly increased ECM production and deposition, especially of collagen-1 and collagen-3 (less so fibronectin) and the activity of matrix metalloproteinases (MMP-2, MMP-9). Exposure to the proinflammatory cytokine TNFα significantly increased BDNF secretion, particularly in asthmatic ASM, whereas no significant changes were observed with IL-13. Chelation of BDNF using TrkB-Fc reversed TNFα-induced increase in ECM deposition. Conditioned media from asthmatic ASM enhanced ECM generation in nonasthmatic ASM, which was blunted by BDNF chelation. Inflammation-induced changes in MMP-2, MMP-9, and tissue inhibitor metalloproteinases (TIMP-1, TIMP-2) were reversed in the presence of TrkB-Fc. These novel data suggest ASM as an inflammation-sensitive source of BDNF within human airways, with autocrine effects on fibrosis relevant to asthma.
Exercise training in Tgαq*44 mice during the progression of chronic heart failure: cardiac vs. peripheral (soleus muscle) impairments to oxidative metabolism
Authors: Grassi Bruno , Majerczak Joanna , Bardi Eleonora , Buso Alessia , Comelli Marina , Chlopicki Stefan , Guzik Magdalena , Mavelli Irene , Nieckarz Zenon , Salvadego Desy , Tyrankiewicz Urszula , Skórka Tomasz , Bottinelli Roberto , Zoladz Jerzy A. , Pellegrino Maria Antonietta
Published: May 2017

Cardiac function, skeletal (soleus) muscle oxidative metabolism, and the effects of exercise training were evaluated in a transgenic murine model (Tgαq*44) of chronic heart failure during the critical period between the occurrence of an impairment of cardiac function and the stage at which overt cardiac failure ensues (i.e., from 10 to 12 mo of age). Forty-eight Tgαq*44 mice and 43 wild-type FVB controls were randomly assigned to control groups and to groups undergoing 2 mo of intense exercise training (spontaneous running on an instrumented wheel). In mice evaluated at the beginning and at the end of training we determined: exercise performance (mean distance covered daily on the wheel); cardiac function in vivo (by magnetic resonance imaging); soleus mitochondrial respiration ex vivo (by high-resolution respirometry); muscle phenotype [myosin heavy chain (MHC) isoform content; citrate synthase (CS) activity]; and variables related to the energy status of muscle fibers [ratio of phosphorylated 5′-AMP-activated protein kinase (AMPK) to unphosphorylated AMPK] and mitochondrial biogenesis and function [peroxisome proliferative-activated receptor-γ coactivator-α (PGC-1α)]. In the untrained Tgαq*44 mice functional impairments of exercise performance, cardiac function, and soleus muscle mitochondrial respiration were observed. The impairment of mitochondrial respiration was related to the function of complex I of the respiratory chain, and it was not associated with differences in CS activity, MHC isoforms, p-AMPK/AMPK, and PGC-1α levels. Exercise training improved exercise performance and cardiac function, but it did not affect mitochondrial respiration, even in the presence of an increased percentage of type 1 MHC isoforms. Factors “upstream” of mitochondria were likely mainly responsible for the improved exercise performance.

NEW & NOTEWORTHY Functional impairments in exercise performance, cardiac function, and soleus muscle mitochondrial respiration were observed in transgenic chronic heart failure mice, evaluated in the critical period between the occurrence of an impairment of cardiac function and the terminal stage of the disease. Exercise training improved exercise performance and cardiac function, but it did not affect the impaired mitochondrial respiration. Factors “upstream” of mitochondria, including an enhanced cardiovascular O2 delivery, were mainly responsible for the functional improvement.
Clinical Significance and Prognostic Value of the Expression of LAMP3 in Oral Squamous Cell Carcinoma
Authors: Lu Jun , Ma Hengcheng , Lian Shuijin , Huang Dan , Lian Min , Zhang Ye , Huang Jianfei , Feng Xingmei
Published: May 2017

Recent studies demonstrated high expression of lysosome-associated membrane protein 3 (LAMP3) in a variety of malignancies including esophageal squamous cell carcinoma, gastrointestinal cancer, breast cancer, and cervical cancer and its involvement in several biological activities of tumor cells. However, the expression of LAMP3 and its value in oral squamous cell carcinoma (OSCC) remain unclear. In this study, we examined the expression of LAMP3 in OSCC tissue samples and investigated the relationship between LAMP3 and clinical characteristics of patients with OSCC. We examined mRNA and protein levels of LAMP3 in OSCC tissues and neighboring normal tissues using quantitative real-time polymerase chain reaction and immunohistochemistry analyses, respectively. Both the mRNA and protein levels of LAMP3 were significantly higher in OSCC tissues than in adjacent normal tissues. Chi-square analysis showed that the high LAMP3 expression was notably linked to the degree of tumor differentiation and advanced TNM stage. Univariate and multivariate analyses showed that the high LAMP3 expression was an independent prognostic marker in OSCC. Our results suggest that LAMP3 might act as a potential anticancer target and a prognostic marker in patients with OSCC.
Association of Platelet Membrane Glycoprotein HPA-2a/b, GP VI T13254C, and GP IbαVNTR Polymorphisms with Risk of Coronary Artery Disease: A Meta-Analysis
Authors: Ni Wei , He Jidong , Wang Haoyu , Liu Tao
Published: May 2017

Background and Aims. Recently, controversial results have been reported regarding the association of the polymorphisms of platelet membrane glycoproteins (HPA-2a/b, GP VI T13254C, and GP IbαVNTR) with coronary artery disease (CAD). We performed this meta-analysis to further assess the polymorphisms of platelet membrane glycoproteins with a risk of CAD.Methods. A systematic electronic literature search was conducted in Embase, Cochrane Library, PubMed, and the Chinese Biomedical Literature Database (CBM). Analyses were performed using the Cochrane software package Review Manager 5.2 and Stata 12.0 software package.Results. Twenty-nine full-text articles were included in the meta-analysis. Based on random-effects meta-analysis, a significant association between the HPA-2a/b polymorphism and CAD was identified (allele model: odds ratio = 1.43, 95% confidence interval = 1.07–1.91; dominant genetic model: odds ratio = 1.57, 95% confidence interval = 1.08–2.28). Our study showed no association between the GP VI T13254C polymorphism and CAD in either a random-effects model or a fixed-effects model. Furthermore, there was no evidence to suggest that the GP IbαVNTR polymorphism was associated with CAD in any of the genetic analysis models.Conclusions. The HPA-2a/b polymorphism correlated significantly with a risk of CAD, and the HPA-2b allele and the HPA-2ab + HPA-2bb genotype may increase the risk of CAD. There was no evidence to suggest that polymorphisms of GP VI T13254C and GP IbαVNTR were associated with CAD.