bluuebunny/crossref_metadata_2025 huggingface dataset:
GABA receptors as oxytocin targets
Authors: Gough Nancy R.
Published: March 2015

Oxytocin limits the ataxia and sedation effects of ethanol by reducing its potentiation of the GABA
A
family of Cl
–
channels.
Innate immune receptor signaling, united
Authors: Mueller Kristen L.
Published: March 2015

Diverse innate immune receptors use a common signaling mechanism to activate type I interferons.
The N-end rule finds a physiological function
Authors: Hurtley Stella M.
Published: March 2015

A G protein signaling regulator and its hypertension-associated mutants are short-lived physiological substrates of the Teb4 ubiquitin ligase.
A sensitive regulator of cellular potassium
Authors: Vinson Valda
Published: March 2015

Crystal structures clarify how a two-pore potassium channel is regulated by diverse stimuli.
A new therapeutic target for sepsis
Authors: Mueller Kristen L.
Published: March 2015

The cytokine interleukin-3 drives sepsis in mice and is associated with worse prognosis in septic patients.
Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells
Authors: Watanabe Rei , Gehad Ahmed , Yang Chao , Scott Laura L. , Teague Jessica E. , Schlapbach Christoph , Elco Christopher P. , Huang Victor , Matos Tiago R. , Kupper Thomas S. , Clark Rachael A.
Published: March 2015

Four different T cell populations with different functions and migration patterns protect human skin.
A microRNA-Hippo pathway that promotes cardiomyocyte proliferation and cardiac regeneration in mice
Authors: Tian Ying , Liu Ying , Wang Tao , Zhou Ning , Kong Jun , Chen Li , Snitow Melinda , Morley Michael , Li Deqiang , Petrenko Nataliya , Zhou Su , Lu Minmin , Gao Erhe , Koch Walter J. , Stewart Kathleen M. , Morrisey Edward E.
Published: March 2015

A microRNA-based therapeutic approach could be used to promote cardiac regeneration through the transient activation of cardiomyocyte proliferation.
Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy
Authors: Leverson Joel D. , Phillips Darren C. , Mitten Michael J. , Boghaert Erwin R. , Diaz Dolores , Tahir Stephen K. , Belmont Lisa D. , Nimmer Paul , Xiao Yu , Ma Xiaoju Max , Lowes Kym N. , Kovar Peter , Chen Jun , Jin Sha , Smith Morey , Xue John , Zhang Haichao , Oleksijew Anatol , Magoc Terrance J. , Vaidya Kedar S. , Albert Daniel H. , Tarrant Jacqueline M. , La Nghi , Wang Le , Tao Zhi-Fu , Wendt Michael D. , Sampath Deepak , Rosenberg Saul H. , Tse Chris , S. Huang David C. , Fairbrother Wayne J. , Elmore Steven W. , Souers Andrew J.
Published: March 2015

Selective inhibition of BCL-X
L
synergizes with docetaxel to inhibit the growth of solid tumors but does not inhibit granulopoiesis.
Fine-tuning inflammasome activity with a small molecule or ketogenic diet
Authors: Erbay Ebru
Published: March 2015

Selective and potent inhibition of NLRP3 inflammasome is a promising therapeutic approach for many complex, metabolic, and inflammatory diseases.
You can’t unring a bell
Authors: Stecker Eric C.
Published: March 2015

Genetic mouse models of hypertrophic cardiomyopathy suggest that the timing of therapies may be critical for inducing disease regression.
Nonribosomal Peptides, Key Biocontrol Components for Pseudomonas fluorescens In5, Isolated from a Greenlandic Suppressive Soil
Authors: Michelsen Charlotte F. , Watrous Jeramie , Glaring Mikkel A. , Kersten Roland , Koyama Nobuhiro , Dorrestein Pieter C. , Stougaard Peter
Published: March 2015

Potatoes are cultivated in southwest Greenland without the use of pesticides and with limited crop rotation. Despite the fact that plant-pathogenic fungi are present, no severe-disease outbreaks have yet been observed. In this report, we document that a potato soil at Inneruulalik in southern Greenland is suppressive against
Rhizoctonia solani
Ag3 and uncover the suppressive antifungal mechanism of a highly potent biocontrol bacterium,
Pseudomonas fluorescens
In5, isolated from the suppressive potato soil. A combination of molecular genetics, genomics, and matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) imaging mass spectrometry (IMS) revealed an antifungal genomic island in P. fluorescens In5 encoding two nonribosomal peptides, nunamycin and nunapeptin, which are key components for the biocontrol activity by strain In5
in vitro
and in soil microcosm experiments. Furthermore, complex microbial behaviors were highlighted. Whereas nunamycin was demonstrated to inhibit the mycelial growth of R. solani Ag3, but not that of
Pythium aphanidermatum
, nunapeptin instead inhibited P. aphanidermatum but not R. solani Ag3. Moreover, the synthesis of nunamycin by P. fluorescens In5 was inhibited in the presence of P. aphanidermatum. Further characterization of the two peptides revealed nunamycin to be a monochlorinated 9-amino-acid cyclic lipopeptide with similarity to members of the syringomycin group, whereas nunapeptin was a 22-amino-acid cyclic lipopeptide with similarity to corpeptin and syringopeptin.

IMPORTANCE
Crop rotation and systematic pest management are used to only a limited extent in Greenlandic potato farming. Nonetheless, although plant-pathogenic fungi are present in the soil, the farmers do not experience major plant disease outbreaks. Here, we show that a Greenlandic potato soil is suppressive against
Rhizoctonia solani
, and we unravel the key biocontrol components for
Pseudomonas fluorescens
In5, one of the potent biocontrol bacteria isolated from this Greenlandic suppressive soil. Using a combination of molecular genetics, genomics, and microbial imaging mass spectrometry, we show that two cyclic lipopeptides, nunamycin and nunapeptin, are important for the biocontrol activity of P. fluorescens In5 both
in vitro
and in microcosm assays. Furthermore, we demonstrate that the synthesis of nunamycin is repressed by the oomycete
Pythium aphanidermatum
. Overall, our report provides important insight into interkingdom interference between bacteria and fungi/oomycetes.
Deficiency of the Novel Exopolyphosphatase Rv1026/PPX2 Leads to Metabolic Downshift and Altered Cell Wall Permeability in Mycobacterium tuberculosis
Authors: Chuang Yu-Min , Bandyopadhyay Nirmalya , Rifat Dalin , Rubin Harvey , Bader Joel S. , Karakousis Petros C.
Published: March 2015

Mycobacterium tuberculosis
can persist for decades in the human host. Stringent response pathways involving inorganic polyphosphate [poly(P)], which is synthesized and hydrolyzed by polyphosphate kinase (PPK) and exopolyphosphatase (PPX), respectively, are believed to play a key regulatory role in bacterial persistence. We show here that
M. tuberculosis
poly(P) accumulation is temporally linked to bacillary growth restriction. We also identify
M. tuberculosis
Rv1026 as a novel exopolyphosphatase with hydrolytic activity against long-chain poly(P). Using a tetracycline-inducible expression system to knock down expression of
Rv1026
(
ppx2
), we found that
M. tuberculosis
poly(P) accumulation leads to slowed growth and reduced susceptibility to isoniazid, increased resistance to heat and acid pH, and enhanced intracellular survival during macrophage infection. By transmission electron microscopy, the
ppx2
knockdown strain exhibited increased cell wall thickness, which was associated with reduced cell wall permeability to hydrophilic drugs rather than induction of drug efflux pumps or altered biofilm formation relative to the empty vector control. Transcriptomic and metabolomic analysis revealed a metabolic downshift of the
ppx2
knockdown characterized by reduced transcription and translation and a downshift of glycerol-3-phosphate levels. In summary, poly(P) plays an important role in
M. tuberculosis
growth restriction and metabolic downshift and contributes to antibiotic tolerance through altered cell wall permeability.

IMPORTANCE
The stringent response, involving the regulatory molecules inorganic polyphosphate [poly(P)] and (p)ppGpp, is believed to mediate
Mycobacterium tuberculosis
persistence. In this study, we identified a novel enzyme (Rv1026, PPX2) responsible for hydrolyzing long-chain poly(P). A genetically engineered M. tuberculosis strain deficient in the
ppx2
gene showed increased poly(P) levels, which were associated with early bacterial growth arrest and reduced susceptibility to the first-line drug isoniazid, as well as increased bacterial survival during exposure to stress conditions and within macrophages. Relative to the control strain, the mutant showed increased thickness of the cell wall and reduced drug permeability. Global gene expression and metabolite analysis revealed reduced expression of the transcriptional and translational machinery and a shift in carbon source utilization. In summary, regulation of the poly(P) balance is critical for persister formation in M. tuberculosis.
Ralstonia solanacearum Uses Inorganic Nitrogen Metabolism for Virulence, ATP Production, and Detoxification in the Oxygen-Limited Host Xylem Environment
Authors: Dalsing Beth L. , Truchon Alicia N. , Gonzalez-Orta Enid T. , Milling Annett S. , Allen Caitilyn
Published: March 2015

Genomic data predict that, in addition to oxygen, the bacterial plant pathogen
Ralstonia solanacearum
can use nitrate (NO
3
−
), nitrite (NO
2
−
), nitric oxide (NO), and nitrous oxide (N
2
O) as terminal electron acceptors (TEAs). Genes encoding inorganic nitrogen reduction were highly expressed during tomato bacterial wilt disease, when the pathogen grows in xylem vessels. Direct measurements found that tomato xylem fluid was low in oxygen, especially in plants infected by R. solanacearum. Xylem fluid contained ~25 mM NO
3
−
, corresponding to R. solanacearum's optimal NO
3
−
concentration for anaerobic growth
in vitro
. We tested the hypothesis that R. solanacearum uses inorganic nitrogen species to respire and grow during pathogenesis by making deletion mutants that each lacked a step in nitrate respiration (Δ
narG
), denitrification (Δ
aniA
, Δ
norB
, and Δ
nosZ
), or NO detoxification (Δ
hmpX
). The
ΔnarG
,
ΔaniA
, and
ΔnorB
mutants grew poorly on NO
3
−
compared to the wild type, and they had reduced adenylate energy charge levels under anaerobiosis. While NarG-dependent NO
3
−
respiration directly enhanced growth, AniA-dependent NO
2
−
reduction did not. NO
2
−
and NO inhibited growth in culture, and their removal depended on denitrification and NO detoxification. Thus, NO
3
−
acts as a TEA, but the resulting NO
2
−
and NO likely do not. None of the mutants grew as well as the wild type
in planta
, and strains lacking AniA (NO
2
−
reductase) or HmpX (NO detoxification) had reduced virulence on tomato. Thus, R. solanacearum exploits host NO
3
−
to respire, grow, and cause disease. Degradation of NO
2
−
and NO is also important for successful infection and depends on denitrification and NO detoxification systems.

IMPORTANCE
The plant-pathogenic bacterium
Ralstonia solanacearum
causes bacterial wilt, one of the world's most destructive crop diseases. This pathogen's explosive growth in plant vascular xylem is poorly understood. We used biochemical and genetic approaches to show that R. solanacearum rapidly depletes oxygen in host xylem but can then respire using host nitrate as a terminal electron acceptor. The microbe uses its denitrification pathway to detoxify the reactive nitrogen species nitrite (a product of nitrate respiration) and nitric oxide (a plant defense signal). Detoxification may play synergistic roles in bacterial wilt virulence by converting the host's chemical weapon into an energy source. Mutant bacterial strains lacking elements of the denitrification pathway could not grow as well as the wild type in tomato plants, and some mutants were also reduced in virulence. Our results show how a pathogen's metabolic activity can alter the host environment in ways that increase pathogen success.
Stress Granules Regulate Double-Stranded RNA-Dependent Protein Kinase Activation through a Complex Containing G3BP1 and Caprin1
Authors: Reineke Lucas C. , Kedersha Nancy , Langereis Martijn A. , van Kuppeveld Frank J. M. , Lloyd Richard E.
Published: March 2015

Stress granules (SGs) are dynamic cytoplasmic repositories containing translationally silenced mRNAs that assemble upon cellular stress. We recently reported that the SG nucleating protein G3BP1 promotes antiviral activity and is essential in double-stranded RNA-dependent protein kinase (PKR) recruitment to stress granules, thereby driving phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α). Here, we delineate the mechanism for SG-dependent PKR activation. We show that G3BP1 and inactive PKR directly interact with each other, dependent on both the NTF2-like and PXXP domains of G3BP1. The G3BP1-interacting protein Caprin1 also directly interacts with PKR, regulates efficient PKR activation at the stress granule, and is also integral for the release of active PKR into the cytoplasm to engage in substrate recognition. The G3BP1-Caprin1-PKR complex represents a new mode of PKR activation and is important for antiviral activity of G3BP1 and PKR during infection with mengovirus. Our data links stress responses and their resultant SGs with innate immune activation through PKR without a requirement for foreign double-stranded RNA (dsRNA) pattern recognition.

IMPORTANCE
Our previous work indicates that stress granules have antiviral activity and mediate innate immunity through functions of G3BP1; however, the mechanistic details of these functions were not resolved. We show that much of the antiviral activity of stress granules is contingent on the function of PKR in a complex with G3BP1 and Caprin1. The PKR-G3BP1-Caprin1 complex undergoes dynamic transitioning within and outside stress granules to accomplish PKR activation and translational repression. This mechanism appears to function distinctly from canonical pattern recognition of double-stranded RNA by PKR. Therefore, this mechanism bridges the stress response with innate immunity, allowing the cell to respond to many cellular stressors and amplify the pathogen pattern recognition systems of innate immunity.
Defining normal ranges and centiles for heart and respiratory rates in infants and children: a cross-sectional study of patients attending an Australian tertiary hospital paediatric emergency department
Authors: O'Leary Fenton , Hayen Andrew , Lockie Francis , Peat Jennifer
Published: March 2015

Objective

Key components in the assessment of a child in the emergency department (ED) are their heart and respiratory rates. In order to interpret these signs, practitioners must know what is normal for a particular age. The aim of this paper is to develop age-specific centiles for these parameters and to compare centiles with the previously published work of Fleming and Bonafide, and the Advanced Paediatric Life Support (APLS) reference ranges.

Design

A retrospective cross-sectional study.

Setting

The ED of the Children's Hospital at Westmead, Australia.

Patients

Afebrile, Triage Category 5 (low priority) patients aged 0–15 years attending the ED.

Interventions

Centiles were developed using quantile regression analysis, with cubic B-splines to model the centiles.

Main outcome measures

Centile charts were compared with previous studies by concurrently plotting the estimates.

Results

668 616 records were retrieved for ED attendances from 1995 to 2011, and 111 696 heart and respiratory rates were extracted for inclusion in the analysis. Graphical comparison demonstrates that with heart rate, our 50th centile agrees with the results of Bonafide, is considerably higher than the Fleming centiles and fits well between the APLS reference ranges. With respiratory rate, our 50th centile was considerably lower than the comparison centiles in infants, becomes higher with increasing age and crosses the lower APLS range in infants and upper range in teenagers.

Conclusions

Clinicians should consider adopting these centiles when assessing acutely unwell children. APLS should review their normal values for respiratory rate in infants and teenagers.
Predicting severe motor impairment in preterm children at age 5 years
Authors: Synnes Anne , Anderson Peter J , Grunau Ruth E , Dewey Deborah , Moddemann Diane , Tin Win , Davis Peter G , Doyle Lex W , Foster Gary , Khairy May , Nwaesei Chukwuma , Schmidt Barbara
Published: March 2015

Objective

To determine whether the ability to predict severe motor impairment at age 5 years improves between birth and 18 months.

Design

Ancillary study of the Caffeine for Apnea of Prematurity Trial.

Setting and Patients

International cohort of very low birth weight children who were assessed sequentially from birth to 5 years.

Outcome Measures

Severe motor impairment was defined as a score <5th percentile on the Movement Assessment Battery of Children (MABC), or inability to complete the MABC because of cerebral palsy. Multivariable logistic regression cumulative risk models used four sets of predictor variables: early neonatal risk factors, risk factors at 36 weeks’ postmenstrual age, risk factors at a corrected age of 18 months, and sociodemographic variables. A receiver operating characteristic curve (ROC) was generated for each model, and the four ROC curves were compared to determine if the addition of the new set of predictors significantly increased the area under the curve (AUC).

Results

Of 1469 children, 291 (19.8%) had a severe motor impairment at 5 years. The AUC increased from 0.650 soon after birth, to 0.718 (p<0.001) at 36 weeks’ postmenstrual age, and to 0.797 at 18 months (p<0.001). Sociodemographic variables did not significantly improve the AUC (AUC=0.806; p=0.07).

Conclusions

Prediction of severe motor impairment at 5 years of age using a cumulative risk model improves significantly from birth to 18 months of age in children with birth weights between 500 g and 1250 g.

Trial registration number

ClinicalTrials.gov numberNCT00182312.
Estimation of perinatal mortality rate for institutional births in Rajasthan state, India, using capture–recapture technique
Authors: Mony Prem K , Varghese Beena , Thomas Tinku
Published: March 2015

Objective

The objective of our investigation was to estimate the perinatal mortality rate among institutional births and to compare the sensitivities of different data collection methods.

Setting

A hospital-based prospective cohort study was undertaken during late-2012 in 21 public sector health facilities of 10 districts of the northern state of Rajasthan, India.

Participants

A total of 6872 births were included in this epidemiological study.

Primary and secondary outcome measures

Perinatal mortality rate of institutional births was the primary outcome. Sensitivities of ‘active’ and passive’ data collection methods were the secondary outcome measures.

Methods

All stillbirth data were from routine government records (‘passive system’); early neonatal outcome data from government records (‘passive’) were compared against the method of ‘phone-tracking’ of outcomes through the community health worker (‘active system’). The Lincoln-Petersen formula for capture-recapture method was used to calculate the probable missing number of early neonatal deaths and thereby estimate the institutional perinatal mortality rate.

Results

Ratio of births in district:subdistrict facilities was 55:45. The estimated perinatal mortality rate (95% CI) by capture–recapture method was 35.8 (34 to 37) per 1000 births. The sensitivity of the passive system was 87–89% while the sensitivity of the active system was 91%. Three-fourths of perinatal deaths were documented as stillbirths. However, for these reported intrauterine deaths or stillbirths, clinical classification by typologies (term vs preterm; intrapartum vs antepartum; macerated vs fresh; with or without congenital anomalies) was absent in the recording system.

Conclusions

Capture–recapture technique can be used to estimate the institutional perinatal mortality rate and also to assess the level of under-reporting by the ‘passive’ government reporting system. This can subsequently be used for monitoring of trends and studying the impact of health interventions. Accurate clinical categorisation of perinatal deaths is also recommended for improving quality of care.
Socioeconomic status in relation to cardiovascular disease and cause-specific mortality: a comparison of Asian and Australasian populations in a pooled analysis
Authors: Woodward Mark , Peters Sanne A E , Batty G David , Ueshima Hirotsugu , Woo Jean , Giles Graham G , Barzi Federica , Ho Suzanne C , Huxley Rachel R , Arima Hisatomi , Fang Xianghua , Dobson Annette , Lam Tai Hing , Vathesatogkit Prin
Published: March 2015

Objectives

In Western countries, lower socioeconomic status is associated with a higher risk of cardiovascular disease (CVD) and premature mortality. These associations may plausibly differ in Asian populations, but data are scarce and direct comparisons between the two regions are lacking. We, thus, aimed to compare such associations between Asian and Western populations in a large collaborative study, using the highest level of education attained as our measure of social status.

Setting

Cohort studies in general populations conducted in Asia or Australasia.

Participants

303 036 people (71% from Asia) from 24 studies in the Asia Pacific Cohort Studies Collaboration. Studies had to have a prospective cohort study design, have accumulated at least 5000 person-years of follow-up, recorded date of birth (or age), sex and blood pressure at baseline and date of, or age at, death during follow-up.

Outcome measures

We used Cox regression models to estimate relationships between educational attainment and CVD (fatal or non-fatal), as well as all-cause, cardiovascular and cancer mortality.

Results

During more than two million person-years of follow-up, 11 065 deaths (3655 from CVD and 4313 from cancer) and 1809 CVD non-fatal events were recorded. Adjusting for classical CVD risk factors and alcohol drinking, hazard ratios (95% CIs) for primary relative to tertiary education in Asia (Australasia) were 1.81 (1.38, 2.36) (1.10 (0.99, 1.22)) for all-cause mortality, 2.47(1.47, 4.17) (1.24 (1.02, 1.51)) for CVD mortality, 1.66 (1.00, 2.78) (1.01 (0.87, 1.17)) for cancer mortality and 2.09 (1.34, 3.26) (1.23 (1.04, 1.46)) for all CVD.

Conclusions

Lower educational attainment is associated with a higher risk of CVD or premature mortality in Asia, to a degree exceeding that in the Western populations of Australasia.
Lifelong bound feet in China: a quantitative ultrasound and lifestyle questionnaire study in postmenopausal women
Authors: Qin Ling , Pan Yi , Zhang Ming , Xu Mian , Lao Hanchang , O'Laughlin Michael C , Tong Shan , Zhao Yanling , Hung VWY , Cheng JCY , Guo Xia
Published: March 2015

Objective

The phenomenon of foot binding, also known as ‘lotus feet’, has an enduring and influential history in China. To achieve a man-made smaller foot size, lifelong foot binding may have had adverse effects on the skeleton. We investigated bone properties in postmenopausal women with bound feet, which may provide new information for developing countermeasures for prevention of fragility fractures.

Design

Population-based cohort study.

Participants

This study involved 254 postmenopausal women aged 65–80, including 172 with bound feet and 82 age- and gender-matched control subjects, living in a remote region of China.

Outcomes

Anthropometric, SF-36 Lifestyle Questionnaire and heel quantitative ultrasound (QUS) data were collected for the whole study population. A small subset of two cases was also invited for assessment of bone mineral density and microarchitecture at the distal tibia using high-resolution peripheral quantitative CT (HR-pQCT) and gait and balance tests.

Results

Women with bound feet had significantly lower QUS values than age-matched women with normal feet; this was supported by HR-pQCT data. However, SF-36 Questionnaire results did not reveal any statistically significant differences in any categorical responses, including physical functioning, general health vitality and physical component summary score, and number of previous fractures. No impairment of body balance was found in the small subset.

Conclusions

The man-made changes caused by foot binding led to reduced physical activity, making the subjects prone to osteoporosis. Women with bound feet and osteoporosis did not have a higher incidence of fragility fractures than controls. This might be explained by compensation in physical activity to improve body balance, implying the importance of improving or maintaining body balance in overall prevention strategies against fragility fractures.
Lung cancer in South Africa: a forecast to 2025 based on smoking prevalence data
Authors: Winkler Volker , Mangolo Nosimanana J , Becher Heiko
Published: March 2015

Objective

This study aims to forecast lung cancer mortality with respect to recent changes in smoking prevalence and compares the results to estimates from GLOBOCAN and the Global Burden of Disease study.

Setting

An established epidemiological model is applied to detailed smoking prevalence data from South Africa to estimate lung cancer mortality from 2010 to 2025.

Participants

Data from the South Africa Demographic and Health Survey conducted in 2003 was analysed by sex and ethnic group, and combined with longitudinal estimates on smoking prevalence from 1980 to 2010.

Primary and secondary outcome measures

Results provide detailed data on tobacco smoking behaviour by age, sex and ethnic group as well as modelled age-adjusted lung cancer mortality and number of yearly lung cancer deaths.

Results

From 2010 to 2025, a decrease in age-adjusted lung cancer mortality is shown from 17.1 to 14.1 among men; whereas rates were stable around 7.2 among women. As a consequence, the estimated number of yearly lung cancer deaths is expected to increase slightly for men and more for women. With respect to ethnic groups, male mortality is expected to be highest for Asians and lowest for blacks. Female rates were lowest for Asians and highest for whites and for coloured.

Conclusions

Mortality estimates of this study are close to the WHO mortality database and to Global Burden of Disease estimates for 2010, but significantly lower compared with GLOBOCAN estimates. In conclusion, our study demonstrates the impact of demographic changes and the positive effects of antismoking policy on lung cancer mortality in South Africa. Results may help decision makers to further improve smoking control.
Prevalence and incidence of dyslipidaemia among adults in Africa: a systematic review and meta-analysis protocol
Authors: Noubiap Jean Jacques N , Nansseu Jobert Richie N , Bigna Jean Joel R , Jingi Ahmadou M , Kengne André Pascal
Published: March 2015

Introduction

Cardiovascular disease (CVD) is the leading cause of death globally and disproportionately affects low-income and middle-income countries. Dyslipidaemia is an important modifiable risk factor for CVD. There are important knowledge gaps regarding the population levels of lipid variables and frequency of non-optimal levels in populations within Africa. We propose to conduct a systematic review to determine the prevalence and occurrence of dyslipidaemia in adult populations within countries in Africa.

Methods and analysis

We will perform a comprehensive search to identify all possible published and unpublished studies on the prevalence or incidence of dyslipidaemia in Africa reported from 1 January 1980, without language restriction. The scientific databases PubMed MEDLINE, EMBASE and ISI Web of Science will be searched, as well as Grey literature. Following study selection, full-text papers acquisition, and data extraction and synthesis, we will appraise the quality of studies and risk of bias, and assess heterogeneity. Prevalence/incidence data will be summarised by country and geographic regions and a meta-analysis will be conducted for variables defined identically across studies. Variance stabilising transformations will be applied as appropriate to the row data before meta-analysis. This systematic review will be reported according to the MOOSE Guidelines for Meta-Analyses and Systematic Reviews of Observational Studies.

Ethics and dissemination

The current study is based on published data and as such ethics consideration is not a requirement. This review is expected to provide relevant data to help in quantifying the magnitude of dyslipidaemia in African populations, to emphasise the need for appropriate prevention and control strategies, and to identify research gaps and remaining challenges. The final report of the systematic review in the form of a scientific paper will be published in peer-reviewed journals. Findings will further be presented at conferences and submitted to relevant health authorities.

Trial registration number

PROSPERO CRD42014015376.
Mortality meetings in geriatric medicine: strategies for improvement
Authors: Dunbar Joanne , George James
Published: March 2015

A large proportion of patients who die in hospital will be under the care of geriatric medicine. Mortality reviews have traditionally used trigger tools to try and identify preventable deaths, but the majority of hospital deaths are not preventable and lapses in care are often very complex. Over a period of 14 months we performed four PDSA cycles to change the focus of mortality meetings within care of the elderly and stroke medicine at Cumberland Infirmary to look beyond preventable deaths. The aim was to maximise learning from mortality meetings to improve patient care.

We used collaborative working at a trust and departmental level, moving from trigger tool preparation to a narrative approach, and we set up strategies to focus and disseminate our learning. The mean number of cases discussed per meeting and the mean number of lessons identified per case discussed increased, as did the learning levels (trust, department, individual). Maintaining multidisciplinary input and consolidating lessons learnt was difficult because of clinical commitments and natural staff turnover.
Coronary artery stenosis risk and time course in Kawasaki disease patients: experience at a US tertiary pediatric centre
Authors: Patel Alok Sunil , Bruce Margaret , Harrington Whitney , Portman Michael A
Published: March 2015

Objective

Despite treatment with intravenous immunoglobulin (IVIG), the natural progression to coronary artery stenosis in Kawasaki disease is not well defined and remains a potential cause of long-term morbidity. We present a novel study, at a US tertiary paediatric care centre, identifying risk factors for stenosis.

Methods

We reviewed charts of all children who underwent cardiac catheterisation for coronary artery abnormalities, from 1998 to January 2014, at a tertiary paediatric care centre. Demographic and diagnostic data included time intervals to echocardiographic changes and confirmed catheterisation cases of stenosis. Multivariate survival analysis was used to evaluate risk factors with stenosis formation as the main outcome measure.

Results

53 children met the inclusion criteria and 18 (34.6%) developed stenosis. Only those with giant coronary aneurysms (GCA) developed stenosis, with the highest risk group overall being children under the age of 6 months (hazard ratio (HR) 2.82 3.79, p=0.004). In a subset of only cases of GCA (33), a majority went on to develop stenosis (18/33). Median time to diagnosis was 190 days. In this group, children under the age of 6 months were again at highest risk (HR 2.62, p=0.04). IVIG administration, sex and ethnicity were not statistically significant predictors.

Conclusions

This retrospective study demonstrates a relatively high incidence of stenosis in children with Kawasaki disease and coronary vascular abnormalities. Overall, a majority of cases with GCA progressed into stenosis, with children under the age of 6 months being at highest risk.
Prescription of perioperative analgesics by UK small animal veterinary surgeons in 2013
Authors: Hunt J. R. , Knowles T. G. , Lascelles B. D. X. , Murrell J. C.
Published: March 2015

Data from a survey conducted in 1996–1997 suggested a low level of perioperative analgesic administration to cats and dogs in the UK. In order to evaluate current practice and attitudes with regards to perioperative analgesic prescription, a cross‐sectional survey of UK practising small animal veterinary surgeons was undertaken in spring 2013. Four thousand one hundred paper questionnaires were distributed and the survey was made available online. Seven hundred and twenty valid responses were received and analysed. All respondents had access to at least one non‐steroidal anti‐inflammatory drug (NSAID) and one opioid within their practice. Respondents considered analgesic efficacy, and degree of intraoperative pain, the most important factors governing their selection of NSAID and opioid analgesics. Perioperative NSAIDs were administered by approximately 98 per cent of respondents to dogs and cats undergoing neutering. Multimodal (opioid+NSAID) analgesia was prescribed by the majority of respondents. Neutering was considered more painful in dogs than in cats, and lower rates of opioid and postdischarge NSAID prescription were reported for cats. Orthopaedic, abdominal and dental surgeries were considered equally painful in dogs and cats. Local analgesic techniques were not commonly used. Analgesic prescription has increased since previous surveys, which should translate to improved animal welfare.
51V magic angle spinning NMR spectroscopy and quantum chemical calculations in vanadium bio-inorganic systems: current perspective
Authors: Gupta Rupal , Yehl Jenna , Li Mingyue , Polenova Tatyana
Published: March 2015

In recent years, 51V magic angle spinning (MAS) NMR spectroscopy has been widely used to characterize vanadium centers in biology, biomimetic complexes, and inorganic compounds of medicinal and industrial relevance. It has been demonstrated that 51V NMR parameters are sensitive probes of the coordination geometry and chemical environment of the metal center, beyond the first coordination sphere. To establish the relationships between NMR parameters and structure of the vanadium centers, over the past decade a large series of coordination complexes have been analyzed by MAS NMR spectroscopy. It has been demonstrated that the interpretation of the NMR parameters requires the use of theoretical methods, such as density functional (DFT) theory, whereby the experimental NMR observables are linked to the electronic and structural properties of a molecule. DFT calculations have been successfully employed to not only predict NMR parameters but to also yield valuable information regarding the structure and function of various vanadium compounds. In this report, we review the current state of the field, and present a survey of bioinorganic vanadium complexes as well as vanadium-dependent haloperoxidases analyzed using 51V MAS NMR spectroscopy and DFT calculations, to illustrate the rich information content available from such a combined approach.
Response of lodgepole pine health to soil disturbance treatments in British Columbia, Canada
Authors: Reid Anya M. , Chapman William K. , Kranabetter John Marty , Prescott Cindy E.
Published: March 2015

Soil disturbance from organic matter loss and soil compaction can impair site productivity, but less is known about whether these disturbances also affect forest health (defined here as the presence and severity of damaging pests and diseases, mortality, and overall vigour). We used six long-term soil productivity (LTSP) sites in the interior of British Columbia, Canada to test the effects of organic-matter removal and soil compaction on forest health, and to explore the relationship between forest health response and potential indicators of site sensitivity: mineral soil pH, base saturation, carbon to nitrogen ratio (C:N), carbon to phosphorus ratio (C:P), and calcium to aluminum ratio (Ca:Al). Visual forest health surveys were conducted on 5400 15 and 20 year old lodgepole pine (Pinus contorta Dougl. ex Loud.) trees. Soil disturbance treatments significantly affected forest health metrics, but this response typically differed among sites. Principle component analyses indicated the response of healthy trees was negatively related to soil base saturation, the response of dead or dying trees related to soil C:P, and the response of tree disease related to soil Ca:Al, pH, base saturation, and C:N. We found forest health response to soil disturbance varied among sites with relationships between response and soil chemical properties, suggesting a greater vulnerability of pine stands to disease with increasing soil acidity.
Mitochondrial miRNA (MitomiR): a new player in cardiovascular health
Authors: Srinivasan Hemalatha , Das Samarjit
Published: March 2015

Cardiovascular disease is one of the major causes of human morbidity and mortality in the world. MicroRNAs (miRNAs) are small RNAs that regulate gene expression and are known to be involved in the pathogenesis of heart diseases, but the translocation phenomenon and the mode of action in mitochondria are largely unknown. Recent mitochondrial proteome analysis unveiled at least 2000 proteins, of which only 13 are made by the mitochondrial genome. There are numerous studies demonstrating the translocation of proteins into the mitochondria and also translocation of ribosomal RNA (viz., 5S rRNA) into mitochondria. Recent studies have suggested that miRNAs contain sequence elements that affect their subcellular localization, particularly nuclear localization. If there are sequence elements that direct miRNAs to the nucleus, it is also possible that similar sequence elements exist to direct miRNAs to the mitochondria. In this review we have summarized most of the miRNAs that have been shown to play an important role in mitochondrial function, either by regulating mitochondrial genes or by regulating nuclear genes that are known to influence mitochondrial function. While the focus of this review is cardiovascular diseases, we also illustrate the role of mitochondrial miRNA (MitomiR) in the initiation and progression of various diseases, including cardiovascular diseases, metabolic diseases, and cancer. Our goal here is to summarize the miRNAs that are localized to the mitochondrial fraction of cells, and how these miRNAs modulate cardiovascular health.
Serum serotonin reduced the expression of hepatic transporter Mrp2 and P-gp via regulating nuclear receptor CAR in PI-IBS rats
Authors: Shao Yun-yun , Huang Jing , Ma Yan-rong , Han Miao , Ma Kang , Qin Hong-yan , Rao Zhi , Wu Xin-an
Published: March 2015

Hepatic transporters and drug metabolizing enzymes (DMEs) play important roles in the pharmacological effects and (or) side-effects of many drugs, and are regulated by several mediators, including neurotransmitters. This work aimed to investigate whether serum levels of 5-hydroxytryptamine (5-HT) affected the expression of hepatic transporters or DMEs. The expression of hepatic transporters was assessed using the Western-blot technique in a 2,4,6-trinitrobenzenesulfonic-acid-induced rat model of post-infectious irritable bowel syndrome (PI-IBS), in which serum levels of 5-HT were significantly elevated. To further clarify the underlying mechanism, the 5-HT precursor 5-hydroxytryptophan (5-HTP) and the 5-HT depleting agent parachlorophenylalanine (pCPA) were applied to adjust serum levels of 5-HT. Serum levels of 5-HT were measured using LC-MS/MS; the expression of hepatic transporters, DMEs, and nuclear receptors were examined by Western-blot technique. Our results showed that in PI-IBS rats the expression of multidrug resistance protein 2 (Mrp2) was significantly decreased, while colonic enterochromaffin cell density and serum levels of 5-HT were all significantly increased. Moreover, 5-HTP treatment significantly increased serum levels of 5-HT and decreased the expression of Mrp2 and glycoprotein P (P-gp), whereas treatment with pCPA markedly decreased serum levels of 5-HT and increased the expression of Mrp2 and P-gp. Our results indicated that serum 5-HT regulates the expression of Mrp2 and P-gp, and the underlying mechanism may be related to the altered expression of the nuclear receptor constitutive androstane receptor (CAR).
Contaminant intrusion in water distribution networks: review and proposal of an integrated model for decision making
Authors: Islam Nilufar , Farahat Ashraf , Al-Zahrani Mohammad Abdullah M. , Rodriguez Manuel J. , Sadiq Rehan
Published: March 2015

Contaminant intrusion in a distribution network (DN) refers to the entry of harmful chemicals and pathogens in the presence of three conditions: (i) the availability of a contaminant source near water mains; (ii) a pathway: leakage or breakage; and (iii) a driving force: low or negative pressure in the water main. The occurrence of contamination in a DN can take place frequently as there is no specific treatment at this stage except secondary disinfection. Contaminant intrusion requires as much attention as source water protection or treatment plants, particularly given that at this point, water is near the final stage prior to human consumption. Failure to detect and treat at this time could have potential negative impacts on consumers’ health. Following the September 11, 2001 attack, strict regulations are now enforced by the municipalities to monitor water quality within DNs. This review article focuses on various aspects of contaminant intrusion in DNs based on more than 90 journal articles, peer-reviewed conference proceedings, and research reports. Here we present details on the conditions of contaminant intrusion, water quality regulations, sampling, protection and mitigation strategies, and various modelling approaches for decision making. Based on this review, we propose an integrated model that will help guide effective decision making for contaminant detection and mitigation.
On geodesics with negative energies in the ergoregions of dirty black holes
Authors: Zaslavskii O. B.
Published: March 2015

We consider behavior of equatorial geodesics with the negative energy in the ergoregion of a generic rotating "dirty" (surrounded by matter) black hole. It is shown that under very simple and generic conditions on the metric coefficients, there are no such circular orbits. This entails that such geodesic must originate and terminate under the event horizon. These results generalize the observation made for the Kerr metric in A. A. Grib, Yu. V. Pavlov and V. D. Vertogradov, Mod. Phys. Lett.29, 1450110 (2014), arXiv:1304.7360.
Complex potential and bottomonium suppression at LHC energy
Authors: Kakade Uttam , Patra Binoy Krishna , Thakur Lata
Published: March 2015

We have studied the thermal suppression of the bottomonium states in relativistic heavy-ion collision at LHC energies as function of centrality, rapidity, transverse momentum. First, we address the effects of the nonperturbative confining force and the momentum anisotropy together on heavy quark potential at finite temperature, which are resolved by correcting both the perturbative and nonperturbative terms of the potential at T = 0 in a weakly-anisotropic medium, not its perturbative term alone as usually done in the literature. Second, we model the expansion of medium by the Bjorken hydrodynamics in the presence of both shear and bulk viscosity, followed by an additional pre-equilibrium anisotropic evolution. Finally, we couple them together to quantify the yields of bottomonium production in nucleus–nucleus collisions at LHC energies and found a better agreement with the CMS data. Our estimate of the inclusive ϒ(1S) production indirectly constrains both the uncertainties in isotropization time and the shear-to-entropy density ratio and favors the values as 0.3 fm/c and 0.3 (perturbative result), respectively.
Maximum Drawdown and Risk Tolerances
Authors: Baghdadabad Mohammad Reza Tavakoli
Published: March 2015

Due to the numerous studies of asymmetric portfolio returns, asymmetric risk measures have widely been used in risk management with extensive uses on the methodology of n-degree lower partial moment (LPM). Unlike the initial studies, we use the risk measure of n-degree maximum drawdown, which is a special case of n-degree LPM, to investigate the reduction impacts of n-degree maximum drawdown risk on risk tolerances generated by management styles from US equity-based mutual funds. We found that skewness does not impose any significant problems on the model of n-degree maximum drawdown. Thus, the tolerance effect of maximum drawdown risk in the n-degree M-DRM models is a decrease in fund returns. The n-degree CM-DRM optimization model decreased investors' risk more than two conventional models. Thus, the M-DRM can be accommodated with risk-averse investors' approach. The efficient set of mean-variance choices from the investment opportunity set, as described by Markowitz, shows that the n-degree CM-DRM algorithms create this set with lower risk than other algorithms. It implies that the mean-variance opportunity set generated by the n-degree CM-DRM creates lower risk for a given return than covariance and CLPM.
The Biology of Proteostasis in Aging and Disease
Authors: Labbadia Johnathan , Morimoto Richard I
Published: March 2015

Loss of protein homeostasis (proteostasis) is a common feature of aging and disease that is characterized by the appearance of nonnative protein aggregates in various tissues. Protein aggregation is routinely suppressed by the proteostasis network (PN), a collection of macromolecular machines that operate in diverse ways to maintain proteome integrity across subcellular compartments and between tissues to ensure a healthy life span. Here, we review the composition, function, and organizational properties of the PN in the context of individual cells and entire organisms and discuss the mechanisms by which disruption of the PN, and related stress response pathways, contributes to the initiation and progression of disease. We explore emerging evidence that disease susceptibility arises from early changes in the composition and activity of the PN and propose that a more complete understanding of the temporal and spatial properties of the PN will enhance our ability to develop effective treatments for protein conformational diseases.
Cellulose Degradation by Polysaccharide Monooxygenases
Authors: Beeson William T. , Vu Van V. , Span Elise A. , Phillips Christopher M. , Marletta Michael A.
Published: March 2015

Polysaccharide monooxygenases (PMOs), also known as lytic PMOs (LPMOs), enhance the depolymerization of recalcitrant polysaccharides by hydrolytic enzymes and are found in the majority of cellulolytic fungi and actinomycete bacteria. For more than a decade, PMOs were incorrectly annotated as family 61 glycoside hydrolases (GH61s) or family 33 carbohydrate-binding modules (CBM33s). PMOs have an unusual surface-exposed active site with a tightly bound Cu(II) ion that catalyzes the regioselective hydroxylation of crystalline cellulose, leading to glycosidic bond cleavage. The genomes of some cellulolytic fungi contain more than 20 genes encoding cellulose-active PMOs, suggesting a diversity of biological activities. PMOs show great promise in reducing the cost of conversion of lignocellulosic biomass to fermentable sugars; however, many questions remain about their reaction mechanism and biological function. This review addresses, in depth, the structural and mechanistic aspects of oxidative depolymerization of cellulose by PMOs and considers their biological function and phylogenetic diversity.