bluuebunny/crossref_metadata_2025 huggingface dataset:
SUMO Ligase Protein Inhibitor of Activated STAT1 (PIAS1) Is a Constituent Promyelocytic Leukemia Nuclear Body Protein That Contributes to the Intrinsic Antiviral Immune Response to Herpes Simplex Virus 1
Authors: Brown James R. , Conn Kristen L. , Wasson Peter , Charman Matthew , Tong Lily , Grant Kyle , McFarlane Steven , Boutell Chris
Published: April 2016

Aspects of intrinsic antiviral immunity are mediated by
p
ro
m
yelocytic
l
eukemia
n
uclear
b
ody (PML-NB) constituent proteins. During herpesvirus infection, these antiviral proteins are independently recruited to nuclear domains that contain infecting viral genomes to cooperatively promote viral genome silencing. Central to the execution of this particular antiviral response is the
s
mall
u
biquitin-like
mo
difier (SUMO) signaling pathway. However, the participating SUMOylation enzymes are not fully characterized. We identify the SUMO ligase
p
rotein
i
nhibitor of
a
ctivated
S
TAT1 (PIAS1) as a constituent PML-NB protein. We show that PIAS1 localizes at PML-NBs in a
S
UMO
i
nteraction
m
otif (SIM)-dependent manner that requires SUMOylated or SUMOylation-competent PML. Following infection with herpes simplex virus 1 (HSV-1), PIAS1 is recruited to nuclear sites associated with viral genome entry in a SIM-dependent manner, consistent with the SIM-dependent recruitment mechanisms of other well-characterized PML-NB proteins. In contrast to that of Daxx and Sp100, however, the recruitment of PIAS1 is enhanced by PML. PIAS1 promotes the stable accumulation of SUMO1 at nuclear sites associated with HSV-1 genome entry, whereas the accumulation of other evaluated PML-NB proteins occurs independently of PIAS1. We show that PIAS1 cooperatively contributes to HSV-1 restriction through mechanisms that are additive to those of PML and cooperative with those of PIAS4. The antiviral mechanisms of PIAS1 are counteracted by ICP0, the HSV-1 SUMO-targeted ubiquitin ligase, which disrupts the recruitment of PIAS1 to nuclear domains that contain infecting HSV-1 genomes through mechanisms that do not directly result in PIAS1 degradation.

IMPORTANCE
Adaptive, innate, and intrinsic immunity cooperatively and efficiently restrict the propagation of viral pathogens. Intrinsic immunity mediated by constitutively expressed cellular proteins represents the first line of intracellular defense against infection. PML-NB constituent proteins mediate aspects of intrinsic immunity to restrict herpes simplex virus 1 (HSV-1) as well as other viruses. These proteins repress viral replication through mechanisms that rely on SUMO signaling. However, the participating SUMOylation enzymes are not known. We identify the SUMO ligase PIAS1 as a constituent PML-NB antiviral protein. This finding distinguishes a SUMO ligase that may mediate signaling events important in PML-NB-mediated intrinsic immunity. Moreover, this research complements the recent identification of PIAS4 as an intrinsic antiviral factor, supporting a role for PIAS proteins as both positive and negative regulators of host immunity to virus infection.
The Autophagosomal SNARE Protein Syntaxin 17 Is an Essential Factor for the Hepatitis C Virus Life Cycle
Authors: Ren Huimei , Elgner Fabian , Jiang Bingfu , Himmelsbach Kiyoshi , Medvedev Regina , Ploen Daniela , Hildt Eberhard
Published: April 2016

Syntaxin 17 is an autophagosomal SNARE (soluble
N
-ethylmaleimide-sensitive factor attachment protein receptor) protein required for the fusion of autophagosomes with lysosomes to form autolysosomes and thereby to deliver the enclosed contents for degradation. Hepatitis C virus (HCV) induces autophagy. In light of the observation that the number of viral particles formed by HCV-infected cells is much greater than the number of infectious viral particles finally released by HCV-infected cells, the regulation of fusion between autophagosomes and lysosomes might fulfill a key function controlling the number of released virions. HCV-replicating cells possess a decreased amount of syntaxin 17 due to impaired expression and increased turnover of syntaxin 17. Overexpression of syntaxin 17 in HCV-replicating cells diminishes the number of released infectious viral particles and decreases the amount of intracellular retained viral particles by favoring the formation of autolysosomes, in which HCV particles are degraded. Inhibition of lysosomal acidification by bafilomycin rescues the decreased release of virions from syntaxin 17-overexpressing cells, while induction of autophagy by rapamycin enforces the impairment of release under these conditions. Vice versa, inhibition of syntaxin 17 expression by specific small interfering RNAs results in an elevated amount of intracellular retained viral particles and facilitates the release of HCV virions by impairment of autophagosome-lysosome fusion. HCV genome replication, however, is not affected by modulation of syntaxin 17 expression. These data identify syntaxin 17 to be a novel factor controlling the release of HCV. This is achieved by regulation of autophagosome-lysosome fusion, which affects the equilibrium between the release of infectious viral particles and lysosomal degradation of intracellular retained viral particles.

IMPORTANCE
Hepatitis C virus (HCV) induces autophagy. Syntaxin 17 is an autophagosomal SNARE protein required for the fusion of autophagosomes with lysosomes. In HCV-infected cells, a major fraction of the
de novo
-synthesized viral particles is not released but is intracellularly degraded. In this context, the effect of HCV on the amount and distribution of syntaxin 17 and the relevance of syntaxin 17 for the viral life cycle were investigated. This study demonstrates that the amount of syntaxin 17 decreased in HCV-replicating cells. In addition, syntaxin 17 is identified to be a novel factor controlling the release of HCV, and the relevance of autophagosome-lysosome fusion as a regulator of the amount of released viral particles is revealed. Taken together, these findings indicate that syntaxin 17 is involved in the regulation of autophagosome-lysosome fusion and thereby affects the equilibrium between the release of infectious viral particles and the lysosomal degradation of intracellularly retained viral particles.
NOD1 Participates in the Innate Immune Response Triggered by Hepatitis C Virus Polymerase
Authors: Vegna Serena , Gregoire Damien , Moreau Marie , Lassus Patrice , Durantel David , Assenat Eric , Hibner Urszula , Simonin Yannick
Published: April 2016

Hepatitis C virus (HCV) triggers innate immunity signaling in the infected cell. Replication of the viral genome is dispensable for this phenotype, and we along with others have recently shown that NS5B, the viral RNA-dependent RNA polymerase, synthesizes double-stranded RNA (dsRNA) from cellular templates, thus eliciting an inflammatory response, notably via activation of type I interferon and lymphotoxin β. Here, we investigated intracellular signal transduction pathways involved in this process. Using HepaRG cells, a model that largely recapitulates the
in vivo
complexities of the innate immunity receptor signaling, we have confirmed that NS5B triggered increased expression of the canonical pattern recognition receptors (PRRs) specific for dsRNA, namely, RIG-I, MDA5, and Toll-like receptor 3 (TLR3). Unexpectedly, intracellular dsRNA also led to accumulation of NOD1, a receptor classically involved in recognition of bacterial peptidoglycans. NOD1 activation, confirmed by analysis of its downstream targets, was likely due to its interaction with dsRNA and was independent of RIG-I and mitochondrial antiviral signaling protein (MAVS/IPS-1/Cardif/VISA) signaling. It is likely to have a functional significance in the cellular response in the context of HCV infection since interference with the NOD1 pathway severely reduced the inflammatory response elicited by NS5B.

IMPORTANCE
In this study, we show that NOD1, a PRR that normally senses bacterial peptidoglycans, is activated by HCV viral polymerase, probably through an interaction with dsRNA, suggesting that NOD1 acts as an RNA ligand recognition receptor. In consequence, interference with NOD1-mediated signaling significantly weakens the inflammatory response to dsRNA. These results add a new level of complexity to the understanding of the cross talk between different classes of pattern recognition receptors and may be related to certain complications of chronic hepatitis C virus infection.
Utilisation of the falciform ligament pedicle flap as an alternative approach for the repair of a perforated gastric ulcer
Authors: Boshnaq Mohamed , Thakrar Amit , Martini Iana , Doughan Samer
Published: April 2016

An 83-year-old woman presented to the emergency department with sudden onset of severe abdominal pain. She had a background of ulcerative colitis managed surgically at the age of 18 years with panproctocolectomy and permanent ileostomy. On admission, clinical assessment suggested a visceral perforation and an urgent CT scan demonstrated a perforated prepyloric ulcer. Emergency laparotomy was performed and confirmed a 3 cm perforated pre-pyloric ulcer. Repair of the defect was challenging due to the absence of omental fat to patch the perforation. A modification to the standard technique was therefore performed: the falciform ligament was mobilised and its free end used as a patch to repair the defect. The patient made a good postoperative recovery. This case report highlights an alternative operative technique for the treatment of perforated gastric/duodenal ulcers in patients who lack omentum, or when omentum cannot be used to cover perforated gastroduodenal ulcers.
Multifactorial intervention to prevent cardiovascular disease in patients with early rheumatoid arthritis: protocol for a multicentre randomised controlled trial
Authors: Svensson Annemarie Lyng , Christensen Robin , Persson Frederik , Løgstrup Brian Bridal , Giraldi Annamaria , Graugaard Christian , Fredberg Ulrich , Blegvad Jesper , Thygesen Tina , Hansen Inger Marie Jensen , Colic Ada , Bagdat Döne , Ahlquist Palle , Jensen Hanne Slott , Hørslev-Petersen Kim , Sheetal Ekta , Christensen Torben Grube , Svendsen Lone , Emmertsen Henrik , Ellingsen Torkell
Published: April 2016

Introduction

Cardiovascular morbidity is a major burden in patients with rheumatoid arthritis (RA). In this study, we compare the effect of a targeted, intensified, multifactorial intervention with that of conventional treatment of modifiable risk factors for cardiovascular disease (CVD) in patients with early RA fulfilling the 2010 American College of Rheumatology European League Against Rheumatism (ACR/EULAR) criteria.

Methods and analysis

The study is a prospective, randomised, open label trial with blinded end point assessment and balanced randomisation (1:1) conducted in 10 outpatient clinics in Denmark. The primary end point after 5 years of follow-up is a composite of death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke and cardiac revascularisation. Secondary outcomes are: the proportion of patients achieving low-density lipoprotein cholesterol <2.5 mmol/L, glycated haemoglobin <48 mmol/mol, blood pressure <140/90 mm  Hg for patients without diabetes and <130/80 mm Hg for patients with diabetes and normoalbuminuria (urinary albumin creatinine ratio <30 mg/g) after 1 year of follow-up and the proportion of patients in each treatment group achieving low RA disease activity after 1 year, defined as a disease activity score C-reactive protein (DAS28-CRP) <3.2 and a DAS28-CRP score <2.6 after 12, 24 and 60 months. Furthermore, all hospitalisations for acute and elective reasons will be adjudicated by the event committee after 12, 24 and 60 months. Three hundred treatment-naive patients with early RA will be randomly assigned (1:1) to receive either conventional treatment administered and monitored by their general practitioner according to national guidelines (control group) or a stepwise implementation administered and monitored in a quarterly rheumatological nurse-administered set-up of behaviour modification and pharmacological therapy targeting (1) hyperlipidaemia, (2) hypertension, (3) hyperglycaemia and (4) microalbuminuria (intervention group).

Ethics and dissemination

This protocol is approved by the local ethics committee (DK-S-2014007) and The Danish Health and Medicines Authority. Dissemination will occur through presentations at National and International conferences and publications in international peer-reviewed journals.

Trial registration number

NCT02246257
Multicentre open-label randomised controlled trial to compare colistin alone with colistin plus meropenem for the treatment of severe infections caused by carbapenem-resistant Gram-negative infections (AIDA): a study protocol
Authors: Dickstein Yaakov , Leibovici Leonard , Yahav Dafna , Eliakim-Raz Noa , Daikos George L , Skiada Anna , Antoniadou Anastasia , Carmeli Yehuda , Nutman Amir , Levi Inbar , Adler Amos , Durante-Mangoni Emanuele , Andini Roberto , Cavezza Giusi , Mouton Johan W , Wijma Rixt A , Theuretzbacher Ursula , Friberg Lena E , Kristoffersson Anders N , Zusman Oren , Koppel Fidi , Dishon Benattar Yael , Altunin Sergey , Paul Mical
Published: April 2016

Introduction

The emergence of antibiotic-resistant bacteria has driven renewed interest in older antibacterials, including colistin. Previous studies have shown that colistin is less effective and more toxic than modern antibiotics. In vitro synergy studies and clinical observational studies suggest a benefit of combining colistin with a carbapenem. A randomised controlled study is necessary for clarification.

Methods and analysis

This is a multicentre, investigator-initiated, open-label, randomised controlled superiority 1:1 study comparing colistin monotherapy with colistin–meropenem combination therapy for infections caused by carbapenem-resistant Gram-negative bacteria. The study is being conducted in 6 centres in 3 countries (Italy, Greece and Israel). We include patients with hospital-associated and ventilator-associated pneumonia, bloodstream infections and urosepsis. The primary outcome is treatment success at day 14, defined as survival, haemodynamic stability, stable or improved respiratory status for patients with pneumonia, microbiological cure for patients with bacteraemia and stability or improvement of the Sequential Organ Failure Assessment (SOFA) score. Secondary outcomes include 14-day and 28-day mortality as well as other clinical end points and safety outcomes. A sample size of 360 patients was calculated on the basis of an absolute improvement in clinical success of 15% with combination therapy. Outcomes will be assessed by intention to treat. Serum colistin samples are obtained from all patients to obtain population pharmacokinetic models. Microbiological sampling includes weekly surveillance samples with analysis of resistance mechanisms and synergy. An observational trial is evaluating patients who met eligibility requirements but were not randomised in order to assess generalisability of findings.

Ethics and dissemination

The study was approved by ethics committees at each centre and informed consent will be obtained for all patients. The trial is being performed under the auspices of an independent data and safety monitoring committee and is included in a broad dissemination strategy regarding revival of old antibiotics.

Trial registration number

NCT01732250 and 2012-004819-31; Pre-results.
Varicella zoster virus-associated morbidity and mortality in Africa: a systematic review protocol
Authors: Hussey Hannah S , Abdullahi Leila H , Collins Jamie E , Muloiwa Rudzani , Hussey Gregory D , Kagina Benjamin M
Published: April 2016

Introduction

Varicella zoster virus (VZV) causes varicella (chicken pox) and herpes zoster (shingles). Worldwide, these diseases are associated with significant morbidity. Most of the epidemiological data on VZV come from high income countries. There are few data on VZV in Africa, where tropical climates and high HIV/AIDS prevalence rates are expected to impact the epidemiology of VZV. Safe and effective vaccinations for both varicella and herpes zoster exist, but are not routinely used in Africa. There are very few data available on VZV disease burden in Africa to guide the introduction of these vaccines on the continent. Our aim is to conduct a systematic review of the VZV-associated morbidity and mortality in Africa, which will provide critical information that could be used to develop vaccination policies against these diseases in Africa.

Methods and analysis

Electronic databases will be searched and all studies published after 1974 that meet predefined criteria will be assessed. The primary outcomes for the study are VZV incidence/prevalence, hospitalisation rates and total death rates. The secondary outcome for this study is the proportion of VZV hospitalisations and/or deaths associated with HIV/AIDS. Two reviewers will screen the titles and abstracts, and then independently review the full texts, to determine if studies are eligible for inclusion. A risk of bias and quality assessment tool will be used to score all included studies. Following standardised data extraction, a trend analysis using R-programming software will be conducted to investigate the trend of VZV. Depending on the characteristics of included studies, subgroup analyses will be performed. This review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.

Ethics and dissemination

As this is a protocol for a systematic review, which will use already published data, no ethics approval is required. Findings will be disseminated in peer-reviewed journals.

Trial registration number

CRD42015026144.
Factors influencing women's attitudes towards antenatal vaccines, group BStreptococcusand clinical trial participation in pregnancy: an online survey
Authors: McQuaid Fiona , Jones Christine , Stevens Zoe , Plumb Jane , Hughes Rhona , Bedford Helen , Voysey Merryn , Heath Paul T , Snape Matthew D
Published: April 2016

Objectives

To explore factors influencing the likelihood of antenatal vaccine acceptance of both routine UK antenatal vaccines (influenza and pertussis) and a hypothetical group BStreptococcus(GBS) vaccine in order to improve understanding of how to optimise antenatal immunisation acceptance, both in routine use and clinical trials.

Setting

An online survey distributed to women of childbearing age in the UK.

Participants

1013 women aged 18–44 years in England, Scotland and Wales.

Methods

Data from an online survey conducted to gauge the attitudes of 1013 women of childbearing age in England, Scotland and Wales to antenatal vaccination against GBS were further analysed to determine the influence of socioeconomic status, parity and age on attitudes to GBS immunisation, using attitudes to influenza and pertussis vaccines as reference immunisations. Factors influencing likelihood of participation in a hypothetical GBS vaccine trial were also assessed.

Results

Women with children were more likely to know about each of the 3 conditions surveyed (GBS: 45% vs 26%, pertussis: 79% vs 63%, influenza: 66% vs 54%), to accept vaccination (GBS: 77% vs 65%, pertussis: 79% vs 70%, influenza: 78% vs 68%) and to consider taking part in vaccine trials (37% vs 27% for a hypothetical GBS vaccine tested in 500 pregnant women). For GBS, giving information about the condition significantly increased the number of respondents who reported that they would be likely to receive the vaccine. Health professionals were the most important reported source of information.

Conclusions

Increasing awareness about GBS, along with other key strategies, would be required to optimise the uptake of a routine vaccine, with a specific focus on informing women without previous children. More research specifically focusing on acceptability in pregnant women is required and, given the value attached to input from healthcare professionals, this group should be included in future studies.
Portrait of trauma care in Quebec's rural emergency departments and identification of priority intervention needs to improve the quality of care: a study protocol
Authors: Fleet Richard , Tounkara Fatoumata Korika , Ouimet Mathieu , Dupuis Gilles , Poitras Julien , Tanguay Alain , Fortin Jean Paul , Trottier Jean-Guy , Ouellet Jean , Lortie Gilles , Plant Jeff , Morris Judy , Chauny Jean Marc , Lauzier François , Légaré France
Published: April 2016

Introduction

Trauma remains the primary cause of death in individuals under 40 years of age in Canada. In Quebec, the Trauma Care Continuum (TCC) has been demonstrated to be effective in decreasing the mortality rate among trauma victims. Although rural citizens are at greater risk for trauma and trauma death, no empirical data concerning the effectiveness of the TCC for the rural population in Quebec are available. The emergency departments (EDs) are important safety nets for rural citizens. However, our data indicate that access to diagnostic support services, such as intensive care units and CT is limited in rural areas. The objectives are to (1) draw a portrait of trauma services in rural EDs; (2) explore geographical variations in trauma care in Quebec; (3) identify adaptable factors that could reduce variation; and (4) establish consensus solutions for improving the quality of care.

Methods and analysis

The study will take place from November 2015 to November 2018. A mixed methodology (qualitative and quantitative) will be used. We will include data (2009–2013) from all trauma victims treated in the 26 rural EDs and tertiary/secondary care centres in Quebec. To meet objectives 1 and 2, data will be gathered from the Ministry's Database of the Quebec Trauma Registry Information System. For objectives 3 and 4, the project will use the Delphi method to develop consensus solutions for improving the quality of trauma care in rural areas. Data will be analysed using a Poisson regression to compare mortality rate during hospital stay or death on ED arrival (objectives 1 and 2). Average scores and 95% CI will be calculated for the Delphi questionnaire (objectives 3 and 4).

Ethics and dissemination

This protocol has been approved by CSSS Alphonse-Desjardins research ethics committee (Project MP-HDL-2016-003). The results will be published in peer-reviewed journals.
Royal College of General Practitioners Research and Surveillance Centre (RCGP RSC) sentinel network: a cohort profile
Authors: Correa Ana , Hinton William , McGovern Andrew , van Vlymen Jeremy , Yonova Ivelina , Jones Simon , de Lusignan Simon
Published: April 2016

Purpose

The Royal College of General Practitioners Research and Surveillance Centre (RCGP RSC) is one of the longest established primary care sentinel networks. In 2015, it established a new data and analysis hub at the University of Surrey. This paper evaluates the representativeness of the RCGP RSC network against the English population.

Participants and method

The cohort includes 1 042 063 patients registered in 107 participating general practitioner (GP) practices. We compared the RCGP RSC data with English national data in the following areas: demographics; geographical distribution; chronic disease prevalence, management and completeness of data recording; and prescribing and vaccine uptake. We also assessed practices within the network participating in a national swabbing programme.

Findings to date

We found a small over-representation of people in the 25–44 age band, under-representation of white ethnicity, and of less deprived people. Geographical focus is in London, with less practices in the southwest and east of England. We found differences in the prevalence of diabetes (national: 6.4%, RCPG RSC: 5.8%), learning disabilities (national: 0.44%, RCPG RSC: 0.40%), obesity (national: 9.2%, RCPG RSC: 8.0%), pulmonary disease (national: 1.8%, RCPG RSC: 1.6%), and cardiovascular diseases (national: 1.1%, RCPG RSC: 1.2%). Data completeness in risk factors for diabetic population is high (77–99%). We found differences in prescribing rates and costs for infections (national: 5.58%, RCPG RSC: 7.12%), and for nutrition and blood conditions (national: 6.26%, RCPG RSC: 4.50%). Differences in vaccine uptake were seen in patients aged 2 years (national: 38.5%, RCPG RSC: 32.8%). Owing to large numbers, most differences were significant (p<0.00015).

Future plans

The RCGP RSC is a representative network, having only small differences with the national population, which have now been quantified and can be assessed for clinical relevance for specific studies. This network is a rich source for research into routine practice.
Prescribing patterns of combined hormonal products containing cyproterone acetate, levonorgestrel and drospirenone in the UK
Authors: Cea-Soriano Lucía , Wallander Mari-Ann , García Rodríguez Luis Alberto
Published: April 2016

Background

There are limited data to show the levels of prescribing of combined oral contraceptives (COCs) and other hormonal products containing estrogen/progestogen combinations that may be outside the product licence.

Aims

To determine the diagnosis/indication recorded at the time of prescription of cyproterone acetate/ethinylestradiol (CPA/EE) and two COCs, levonorgestrel/EE (LNG/EE) and drospirenone/EE (DRSP/EE).

Design and setting

Retrospective study using a primary care database, The Health Improvement Network (THIN).

Methods

Women in THIN aged 12–49 years prescribed CPA/EE, LNG/EE or DRSP/EE in 2002–2010 were identified. Overall use of each product and proportion of new users each year were determined. Among new users, database codes were analysed to infer the reason for prescription.

Results

The proportion of new users of each product in 2002 and 2010, respectively, were: LNG/EE, 2.03% and 2.40%; CPA/EE, 0.45% and 0.27%; and DRSP/EE, 0.27% and 0.56%. Most new users prescribed CPA/EE had a record of acne (51.0% and 79.2% in 2002 and 2010, respectively) or hirsutism (3.0% and 5.0% in 2002 and 2010, respectively); the proportion of new users with a record only for contraception decreased from 32.9% in 2002 to 8.6% in 2010. Among new users prescribed DRSP/EE or LNG/EE in 2010, 43.2% and 30.8% of women, respectively, did not have a record indicating use for contraception.

Conclusions

Adherence to prescribing guidelines for CPA/EE has improved over time. A substantial proportion of women using DRSP/EE or LNG/EE had records for hormone-responsive conditions only, suggesting that many women were prescribed these therapies for non-contraceptive use.
Work with animals or children? Career choices for Scotland's CVO
Authors: Voas Sheila
Published: April 2016

Working with pre‐school age children while her own sons were growing up almost led Sheila Voas to retrain as a teacher, but she found she missed veterinary work
Long-term effects of channelization on a cold-water stream community
Authors: Lennox Preston A. , Rasmussen Joseph B.
Published: April 2016

Stream channelization is a common form of anthropogenic disturbance, whose impacts on cold-water biological communities have received little attention in comparison with the body of work demonstrating its negative effects on lowland, warm-water systems. Furthermore, it has been suggested that physical stream processes, given sufficient temporal scale, are capable of restoring channelized reaches to their natural state; however, empirical evidence of this is lacking. Here, we examine the effects of stream channelization on fish and invertebrate communities and their habitats in disturbed and undisturbed cold-water mountain streams in southern Alberta, 80 years postchannelization. Our results show that negative impacts associated with channelization, such as a significant reduction of deep pools and loss of flow refugia, remain prevalent along impacted reaches, inhibiting the reestablishment of native species across multiple trophic levels. While these findings are applicable for a range of cold-water salmonid populations, we suggest that they may be of special importance to the management of mountain whitefish (Prosopium williamsoni) populations, which may be more sensitive to channelization than other cold-water species.
Effect of land management practices and environmental parameters on growing season denitrification rates under dairy crop rotations in Atlantic Canada
Authors: Fuller Keith D. , Burton David L. , Grimmett Mark G. , Franklin Jeff , Drury Craig F. , Zebarth Bernie J. , Rodd A. Vernon , St. George Eddie
Published: April 2016

Denitrification losses from agricultural land have been identified as a significant nitrogen (N) loss pathway that contributes to poor utilization of applied N. Higher losses have been reported when inorganic fertilizer N is substituted with an organic N source such as livestock manure. This research examines the relationships between denitrification rates, land management practices and soil processes when using spring applied liquid dairy manure (LDM) as principal N source. Mean daily denitrification rates (DDRs) in a perennial hayfield (PH) rotation and a corn–soybean–wheat (CSW) rotation with or without tillage (T and NT respectively) ranged between 0.9 and 27.0 g N ha−1 day−1. Mean, seasonal DDRs in the PH rotation were significantly lower in three out of six seasons when compared with the CSW-T and (or) CSW-NT rotation. When averaged across the six season study period, the mean DDR in PH of 4.4 g N ha−1 day−1was also significantly lower than CSW-T and NT (7.6 and 8.1 g N ha−1 day−1, respectively). There were no significant effects of tillage in the CSW rotations in any of the six growing seasons. When treatment and growing season data were combined, a positive relationship between water-filled pore space (WFPS) and DDR indicated a threshold of approximately 40% WFPS for onset of significant denitrification. Similarly, the relationship between soil nitrate levels and denitrification rates in the population data set demonstrated that NO3−began to limit DDR below 2–5 mg N kg−1. This 6-year study of denitrification losses suggests a primary effect of WFPS, a secondary effect of O2consumption as reflected by soil respiration, and nitrate limiting only at relatively low concentrations. Environmental variables were more consistent drivers of denitrification in three manure-fed crop rotations typical of Atlantic Canada dairy operations than were land management decisions and practices.
Scale invariant density perturbations from cyclic cosmology
Authors: Frampton Paul Howard
Published: April 2016

It is shown how quantum fluctuations of the radiation during the contraction era of a comes back empty (CBE) cyclic cosmology can provide density fluctuations which re-enter the horizon during the subsequent expansion era and at lowest order are scale invariant, in a Harrison–Zel’dovich–Peebles sense. It is necessary to be consistent with observations of large scale structure.
Hot-electron relaxation in metals within the Götze–Wölfle memory function formalism
Authors: Das Nabyendu , Singh Navinder
Published: April 2016

We consider nonequilibrium relaxation of electrons due to their coupling with phonons in a simple metal. In our model, electrons are living at a higher temperature than that of the phonon bath, mimicking a nonequilibrium steady-state situation. We study the relaxation of such hot electrons proposing a suitable generalization of the memory function formalism formulated by Götze and Wölfle (GW) [W. Götze and P. Wölfle, Phys. Rev. B 6, 1226 (1972)]. We derive analytical expressions for both the DC or zero frequency scattering rates and the optical scattering rates in various temperature and frequency regimes. Limiting cases are in accord with the previous studies. An interesting feature that the DC scattering rate at high temperatures and optical scattering rate at high frequencies are independent of the temperature difference between the electrons and the phonons is found in this study. The present formalism forms a basis which can also be extended to study hot-electron relaxation in variety of complex materials.
Waves and null congruences in a draining bathtub
Authors: Dempsey David , Dolan Sam R.
Published: April 2016

We study wave propagation in a draining bathtub: a black hole analogue in fluid mechanics whose perturbations are governed by a Klein–Gordon equation on an effective Lorentzian geometry. Like the Kerr spacetime, the draining bathtub geometry possesses an (effective) horizon, an ergosphere and null circular orbits. We propose here that a ‘pulse’ disturbance may be used to map out the light-cone of the effective geometry. First, we apply the eikonal approximation to elucidate the link between wavefronts, null geodesic congruences and the Raychaudhuri equation. Next, we solve the wave equation numerically in the time domain using the method of lines. Starting with Gaussian initial data, we demonstrate that a pulse will propagate along a null congruence and thus trace out the light-cone of the effective geometry. Our new results reveal features, such as wavefront intersections, frame-dragging, winding and interference effects, that are closely associated with the presence of null circular orbits and the ergosphere.
A PRELIMINARY IN VITRO BIOMECHANICAL EVALUATION OF PROPHYLACTIC CEMENT AUGMENTATION OF THE THORACOLUMBAR VERTEBRAE
Authors: CRISTOFOLINI LUCA , BRANDOLINI NICOLA , DANESI VALENTINA , ERANI PAOLO , VICECONTI MARCO , FERGUSON STEPHEN J.
Published: April 2016

In this paper, the biomechanical effectiveness of prophylactic augmentation in preventing fracture was investigated. In vitro biomechanical tests were performed to assess which factors make prophylactic augmentation effective/ineffective in reducing fracture risk. Nondestructive and destructive in vitro tests were performed on isolated osteoporotic vertebrae. Five sets of three-adjacent-vertebrae were tested. The central vertebra of each triplet was tested in the natural condition (control) non-destructively (axial-compression, torsion) and destructively (axial-compression). The two adjacent vertebrae were first tested nondestructively (axial-compression, torsion) pre-augmentation; prophylactic augmentation (uni- or bi-pedicular access) was then performed delivering 5.04[Formula: see text]mL to 8.44[Formula: see text]mL of acrylic cement by means of a customized device; quality of augmentation was CT-assessed; the augmented vertebrae were re-tested nondestructively (axial-compression, torsion), and eventually loaded to failure (axial-compression). Vertebral stiffness was correlated with the first-failure, but not with ultimate failure. The force and work to ultimate failure in prophylactic-augmented vertebrae was consistently larger than in the controls. However, in some cases the first-failure force and work in the augmented vertebrae were lower than for the controls. To investigate the reasons for such unpredictable results, the correlation with augmentation quality was analyzed. Some augmentation parameters seemed more correlated with mechanical outcome (statistically not-significant due to the limited sample size): uni-pedicular access resulted in a single cement mass, which tended to increase the force and work to first- and ultimate failure. The specimens with the highest strength and toughness also had: at least 25% cement filling, cement mass shifted anteriorly, and cement-endplate contact. These findings seem to confirm that prophylactic augmentation may aid reducing the risk of fracture. However, inadequate augmentation may have detrimental consequences. This study suggests that, to improve the strength of the augmented vertebrae, more attention should be dedicated to the quality of augmentation in terms of amount and position of the injected cement.
On operator norms for hyperbolic groups
Authors: Nica Bogdan
Published: April 2016

We estimate the operator norm of radial non-negative functions on hyperbolic groups. As a consequence, we show that several forms of Haagerup’s inequality are optimal.
Introduction to the Special Issue on Sounding Rockets and Instrumentation
Authors: Christe Steven , Zeiger Ben , Pfaff Rob , Garcia Michael
Published: April 2016

Rocket technology, originally developed for military applications, has provided a low-cost observing platform to carry critical and rapid-response scientific investigations for over 70 years. Even with the development of launch vehicles that could put satellites into orbit, high altitude sounding rockets have remained relevant. In addition to science observations, sounding rockets provide a unique technology test platform and a valuable training ground for scientists and engineers. Most importantly, sounding rockets remain the only way to explore the tenuous regions of the Earth’s atmosphere (the upper stratosphere, mesosphere, and lower ionosphere/thermosphere) above balloon altitudes ([Formula: see text]40[Formula: see text]km) and below satellite orbits ([Formula: see text]160[Formula: see text]km). They can lift remote sensing telescope payloads with masses up to 400[Formula: see text]kg to altitudes of 350[Formula: see text]km providing observing times of up to 6[Formula: see text]min above the blocking influence of Earth’s atmosphere. Though a number of sounding rocket research programs exist around the world, this article focuses on the NASA Sounding Rocket Program, and particularly on the astrophysical and solar sounding rocket payloads.
An introduction to the Mesozoic biotas of Scandinavia and its Arctic territories
Authors: Kear Benjamin P. , Lindgren Johan , Hurum Jørn H. , Milàn Jesper , Vajda Vivi
Published: April 2016

The Mesozoic biotas of Scandinavia have been studied for nearly two centuries. However, the last 15 years have witnessed an explosive advance in research, most notably on the richly fossiliferous Triassic (Olenekian–Carnian) and Jurassic (Tithonian)
Lagerstätten
of the Norwegian Arctic Svalbard archipelago, Late Cretaceous (Campanian) Kristianstad Basin and Vomb Trough of Skåne in southern Sweden, and the UNESCO heritage site at Stevns Klint in Denmark – the latter constituting one of the most complete Cretaceous–Palaeogene (Maastrichtian–Danian) boundary sections known globally. Other internationally significant deposits include earliest (Induan) and latest Triassic (Norian–Rhaetian) strata from the Danish autonomous territory of Greenland, and the Early Jurassic (Sinemurian–Pliensbachian) to Early Cretaceous (Berriasian) rocks of southern Sweden and the Danish Baltic island of Bornholm, respectively. Marine palaeocommunities are especially well documented, and comprise prolific benthic macroinvertebrates, together with pelagic cephalopods, chondrichthyans, actinopterygians and aquatic amniotes (ichthyopterygians, sauropterygians and mosasauroids). Terrestrial plant remains (lycophytes, sphenophytes, ferns, pteridosperms, cycadophytes, bennettitaleans and ginkgoes), including exceptionally well-preserved carbonized flowers, are also world famous, and are occasionally associated with faunal traces such as temnospondyl amphibian bones and dinosaurian footprints. While this collective documented record is substantial, much still awaits discovery. Thus, Scandinavia and its Arctic territories represent some of the most exciting prospects for future insights into the spectacular history of Mesozoic life and environments.
Postnatal development of the myenteric glial network and its modulation by butyrate
Authors: Cossais François , Durand Tony , Chevalier Julien , Boudaud Marie , Kermarrec Laetitia , Aubert Philippe , Neveu Isabelle , Naveilhan Philippe , Neunlist Michel
Published: April 2016

The postnatal period is crucial for the development of gastrointestinal (GI) functions. The enteric nervous system is a key regulator of GI functions, and increasing evidences indicate that 1) postnatal maturation of enteric neurons affect the development of GI functions, and 2) microbiota-derived short-chain fatty acids can be involved in this maturation. Although enteric glial cells (EGC) are central regulators of GI functions, the postnatal evolution of their phenotype remains poorly defined. We thus characterized the postnatal evolution of EGC phenotype in the colon of rat pups and studied the effect of short-chain fatty acids on their maturation. We showed an increased expression of the glial markers GFAP and S100β during the first postnatal week. As demonstrated by immunohistochemistry, a structured myenteric glial network was observed at 36 days in the rat colons. Butyrate inhibited EGC proliferation in vivo and in vitro but had no effect on glial marker expression. These results indicate that the EGC myenteric network continues to develop after birth, and luminal factors such as butyrate endogenously produced in the colon may affect this development.
microRNA-192 suppresses the expression of the farnesoid X receptor
Authors: Krattinger Regina , Boström Adrian , Schiöth Helgi B. , Thasler Wolfgang E. , Mwinyi Jessica , Kullak-Ublick Gerd A.
Published: April 2016

Farnesoid X receptor (FXR, NR1H4) plays an important role in the regulation of bile acid homeostasis in liver and intestine and may exert protective effects against certain forms of cancer such as colon carcinoma. However, the role of FXR in cell growth regulation, apoptosis, and carcinogenesis is still controversial. Similar to FXR, microRNA-192 (miR-192) is mainly expressed in the liver and colon and plays an important role in the pathogenesis of colon carcinoma. In this study, we investigated the extent to which FXR is regulated by miR-192. Two in silico-predicted binding sites for miR-192-3p within the NR1H4-3′ untranslated region (UTR) were examined in vitro by luciferase reporter assays. Wild-type and mutated forms of the NR1H4-3′UTR were subcloned into a pmirGLO vector and cotransfected into Huh-7 cells with miR-192-3p. To study the effects of miR-192 on the expression of FXR, FXR target genes and cell proliferation, Huh-7 and Caco-2 cells were transfected with miR-192-5p and -3p mimics or antagomirs. In addition, the correlation between FXR and miR-192 expression was studied by linear regression analyses in colonic adenocarcinoma tissue from 27 patients. MiR-192-3p bound specifically to the NR1H4-3′UTR and significantly decreased luciferase activity. Transfection with miR-192 led to significant decreases in NR1H4 mRNA and protein levels as well as the mRNA levels of the FXR-inducible bile acid transporters OSTα-OSTβ and OATP1B3. Significant inverse correlations were detected in colonic adenocarcinoma between NR1H4 mRNA and miR-192-3p expression. In summary, microRNA-192 suppresses the expression of FXR and FXR target genes in vitro and in vivo.
Inhibition of cyclooxygenase-2 alleviates liver cirrhosis via improvement of the dysfunctional gut-liver axis in rats
Authors: Gao Jin-Hang , Wen Shi-Lei , Tong Huan , Wang Chun-Hui , Yang Wen-Juan , Tang Shi-Hang , Yan Zhao-Ping , Tai Yang , Ye Cheng , Liu Rui , Huang Zhi-Yin , Tang Ying-Mei , Yang Jin-Hui , Tang Cheng-Wei
Published: April 2016

Inflammatory transport through the gut-liver axis may facilitate liver cirrhosis. Cyclooxygenase-2 (COX-2) has been considered as one of the important molecules that regulates intestinal epithelial barrier function. This study was aimed to test the hypothesis that inhibition of COX-2 by celecoxib might alleviate liver cirrhosis via reduction of intestinal inflammatory transport in thiacetamide (TAA) rat model. COX-2/prostaglandin E2 (PGE2)/EP-2/p-ERK integrated signal pathways regulated the expressions of intestinal zonula occludens-1 (ZO-1) and E-cadherin, which maintain the function of intestinal epithelial barrier. Celecoxib not only decreased the intestinal permeability to a 4-kDa FITC-dextran but also significantly increased expressions of ZO-1 and E-cadherin. When celecoxib greatly decreased intestinal levels of LPS, TNF-α, and IL-6, it significantly enhanced T cell subsets reduced by TAA. As a result, liver fibrosis induced by TAA was significantly alleviated in the celecoxib group. These data indicated that celecoxib improved the integrity of intestinal epithelial barrier, blocked inflammatory transport through the dysfunctional gut-liver axis, and ameliorated the progress of liver cirrhosis.
Plasma syndecan-1 and heparan sulfate correlate with microvascular glycocalyx degradation in hemorrhaged rats after different resuscitation fluids
Authors: Torres Filho Ivo P. , Torres Luciana N. , Salgado Christi , Dubick Michael A.
Published: April 2016

The endothelial glycocalyx plays an essential role in many physiological functions and is damaged after hemorrhage. Fluid resuscitation may further change the glycocalyx after an initial hemorrhage-induced degradation. Plasma levels of syndecan-1 and heparan sulfate have been used as indirect markers for glycocalyx degradation, but the extent to which these measures are representative of the events in the microcirculation is unknown. Using hemorrhage and a wide range of resuscitation fluids, we studied quantitatively the relationship between plasma biomarkers and changes in microvascular parameters, including glycocalyx thickness. Rats were bled 40% of total blood volume and resuscitated with seven different fluids (fresh whole blood, blood products, and crystalloids). Intravital microscopy was used to estimate glycocalyx thickness in >270 postcapillary venules from 58 cremaster preparations in 9 animal groups; other microvascular parameters were measured using noninvasive techniques. Systemic physiological parameters and blood chemistry were simultaneously collected. Changes in glycocalyx thickness were negatively correlated with changes in plasma levels of syndecan-1 ( r = −0.937) and heparan sulfate ( r = −0.864). Changes in microvascular permeability were positively correlated with changes in both plasma biomarkers ( r = 0.8, P < 0.05). Syndecan-1 and heparan sulfate were also positively correlated ( r = 0.7, P < 0.05). Except for diameter and permeability, changes in local microcirculatory parameters (red blood cell velocity, blood flow, and wall shear rate) did not correlate with plasma biomarkers or glycocalyx thickness changes. This work provides a quantitative framework supporting plasma syndecan-1 and heparan sulfate as valuable clinical biomarkers of glycocalyx shedding that may be useful in guiding resuscitation strategies following hemorrhage.
IK1-enhanced human-induced pluripotent stem cell-derived cardiomyocytes: an improved cardiomyocyte model to investigate inherited arrhythmia syndromes
Authors: Vaidyanathan Ravi , Markandeya Yogananda S. , Kamp Timothy J. , Makielski Jonathan C. , January Craig T. , Eckhardt Lee L.
Published: April 2016

Currently available induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) do not ideally model cellular mechanisms of human arrhythmic disease due to lack of a mature action potential (AP) phenotype. In this study, we create and characterize iPS-CMs with an electrically mature AP induced by potassium inward rectifier ( IK1) enhancement. The advantages of IK1-enhanced iPS-CMs include the absence of spontaneous beating, stable resting membrane potentials at approximately −80 mV and capability for electrical pacing. Compared with unenhanced, IK1-enhanced iPS-CMs calcium transient amplitudes were larger ( P < 0.05) with a typical staircase pattern. IK1-enhanced iPS-CMs demonstrated a twofold increase in cell size and membrane capacitance and increased DNA synthesis compared with control iPS-CMs ( P < 0.05). Furthermore, IK1-enhanced iPS-CMs expressing the F97C-CAV3 long QT9 mutation compared with wild-type CAV3 demonstrated an increase in AP duration and late sodium current. IK1-enhanced iPS-CMs represent a more mature cardiomyocyte model to study arrhythmia mechanisms.