10 research outputs found
Understanding the role of the cytoskeleton inthe complex regulation of the endothelial repair
Actin microfilaments and microtubules are
important cytoskeletal proteins that regulate endothelial
repair through alterations in cell shape and through
regulation of cell migration following wounding of the
endothelium. Upstream pathways have been identified in
the regulation of actin and microtubule organization,
especially small GTPases. Recently, there have been
numerous proteins suggested to be capable of regulating
interaction between microtubules and microfilaments to
mediate microtubule regulation of endothelial repair, an
important process in limiting injury to the artery wall
and in reducing the extent of arterial disease. If
disrupted, a rapid repair mechanism is important in
reestablishing the integrity of the endothelium in order to
reestablish its function as a macromolecular barrier, a
thromboresistant surface, and a biologically active
tissue. Strategies to improve repair should alter the
pathobiology of the atherosclerotic plaque and thus
improve the prognosis of patients with atherosclerosis
Microtubules regulate aortic endothelial cell actin microfilament reorganization in intact and repairing monolayers
To understand the role of microtubules and
microfilaments in regulating endothelial monolayer
integrity and repair, and since microtubules and
microfilaments show some co-alignment in endothelial
cells, we tested the hypothesis that microtubules
organize microfilament distribution. Disruption of
microtubules with colchicine in resting confluent aortic
endothelial monolayers resulted in disruption of
microfilament distribution with a loss of dense
peripheral bands, an increase in actin microfilament
bundles, and an associated increase of focal adhesion
proteins at the periphery of the cells. However, when
microfilaments were disrupted with cytochalasin B,
microtubule distribution did not change. During the early
stages of wound repair of aortic endothelial monolayers,
microtubules and microfilaments undergo a sequential
series of changes in distribution prior to cell migration.
They are initially distributed randomly relative to the
wound edge, then align parallel to the wound edge and
then elongate perpendicular to the wound edge. When
microtubules in wounded cultures were disrupted, dense
peripheral bands and lamellipodia formation were lost with increases in central stress fibers. However,
following microfilament disruption, microtubule
redistribution was not disrupted and the microtubules
elongated perpendicular to the wound edge similar to
non-treated cultures. Microtubules may organize
independently of microfilaments while microfilaments
require microtubules to maintain normal organization in
confluent and repairing aortic endothelial monolayers
Voluntary community service in medical school: A qualitative study on obstacles faced by student leaders and potential solutions
10.3402/gha.v8.27562Global Health Action812756
Differences in the compliance with hospital infection control practices during the 2009 influenza H1N1 pandemic in three countries
Background
In December 2009, the World Health Organization (WHO) issued updated guidelines on the prevention of H1N1 influenza virus in healthcare settings. In 2010, the WHO pandemic influenza alert level was still at phase 6.
Aim
To study the practice of infection control measures during the 2009 influenza H1N1 pandemic among healthcare workers (HCWs) in three countries.
Methods
A standardized, self-administered anonymous questionnaire survey was conducted in 2010 among doctors, nurses and allied HCWs in 120 hospital-based clinical departments in Hong Kong, Singapore and the UK. Questions were asked on demographics; previous experience and perceived severity of influenza; infection control practices; uptake of seasonal influenza vaccination and H1N1 vaccination. Multiple logistic regression was used to test the independent association with different factors.
Findings
A total of 2100 HCWs in the three countries participated. They reported high compliance (>80%) with infection control procedures regarded as standard for droplet-transmitted infections including wearing and changing gloves, and washing hands before and after patient contact. However, the reported use of masks with indirect or direct patient contact (surgical or N95 as required by their hospital) varied considerably (96.4% and 70.4% for Hong Kong; 82.3% and 87.7% for Singapore; 25.3% and 62.0% for the UK). Reported compliance was associated with job title, number of patient contacts and perceived severity of pandemics. There was no association between the uptake for seasonal or 2009 H1N1 vaccines and compliance.
Conclusions
Compliance with infection control measures for pandemic influenza appears to vary widely depending on the setting
Ratio of Klebsiella/Bifidobacterium in early life correlates with later development of paediatric allergy
10.3920/BM2017.0020Beneficial Microbes85681-695GUSTO (Growing up towards Healthy Outcomes
Ratio of Klebsiella/Biffidobacterium in early life correlates with later development of paediatric allergy
Several studies have reported that intestinal microbial colonisation patterns differ between non-allergic and allergic infants. However, the microbial signature underlying the pathogenesis of allergies remains unclear. We aim to gain insight into the development of the intestinal microbiota of healthy infants and infants who develop allergy in early life, and identify potential microbiota biomarkers of later allergic disease. Using a case-control design in a Chinese sub-cohort of a Singaporean birth cohort (GUSTO), we utilised 16S rRNA gene sequencing to assess intestinal microbial composition and diversity of 21 allergic and 18 healthy infants at 3 weeks, 3 months and 6 months of age, and correlated the microbiota with allergy at ages 18 and 36 months. Pronounced differences in intestinal microbiota composition between allergic and healthy infants were observed at 3 months of age. The intestine of healthy infants was colonised with higher abundance of commensal Bifidobacterium. Conversely, Klebsiella, an opportunistic pathogen, was significantly enriched in the allergic infants. Interestingly, infants with a high Klebsiella/Bifidobacterium (K/B) ratio (above the population median K/B ratio) at age 3 months had an odds ratio of developing allergy by 3 years of age of 9.00 (95% confidence interval 1.46-55.50) compared to those with low K/B ratio. This study demonstrated a relationship between the ratio of genera Klebsiella and Bifidobacterium during early infancy and development of paediatric allergy in childhood. Our study postulates that an elevated K/B ratio in early infancy could be a potential indicator of an increased risk of allergy development. This line of research might enable future intervention strategies in early life to prevent or treat allergy. Our study provides new insights into microbial signatures associated with childhood allergy, in particular, suggests that an elevated K/B ratio could be a potential early-life microbiota biomarker of allergic disease
Potential Embolic Sources in Embolic Stroke of Undetermined Source Patients with Patent Foramen Ovale
10.1159/000527791Cerebrovascular Disease
METTL6 is a tRNA m<sup>3</sup>C methyltransferase that regulates pluripotency and tumor cell growth.
Recently, covalent modifications of RNA, such as methylation, have emerged as key regulators of all aspects of RNA biology and have been implicated in numerous diseases, for instance, cancer. Here, we undertook a combination of in vitro and in vivo screens to test 78 potential methyltransferases for their roles in hepatocellular carcinoma (HCC) cell proliferation. We identified methyltransferase-like protein 6 (METTL6) as a crucial regulator of tumor cell growth. We show that METTL6 is a bona fide transfer RNA (tRNA) methyltransferase, catalyzing the formation of 3-methylcytidine at C32 of specific serine tRNA isoacceptors. Deletion of Mettl6 in mouse stem cells results in changes in ribosome occupancy and RNA levels, as well as impaired pluripotency. In mice, Mettl6 knockout results in reduced energy expenditure. We reveal a previously unknown pathway in the maintenance of translation efficiency with a role in maintaining stem cell self-renewal, as well as impacting tumor cell growth profoundly