The influence of OLR1 and PCSK9 gene polymorphisms on ischemic stroke: Evidence from a meta-analysis

It has been reported that both OLR1 and PCSK9 genes are related to various vascular diseases such as atherosclerosis, cardiovascular disease, peripheral artery disease and stroke, in particular ischemic stroke. The prevalence of PCSK9 rs505151 and OLR1 rs11053646 variants in ischemic stroke were 0.005 and 0.116, respectively. However, to date, association between OLR1 rs11053646 and PCSK9 rs505151 polymorphisms and the risk of ischemic stroke remains unclear and inconclusive. Therefore, this first meta-analysis was carried out to clarify the presumed influence of genetic polymorphisms on ischemic stroke, by analyzing the complete coverage of all relevant studies. All eligible case-control and cohort studies that met the search term were retrieved in multiple scientific databases. Data of interest such as demographic data and genotyping methods were extracted from each study, and the meta-analysis was performed using RevMan 5.3 and Metafor R 3.2.1. The pooled odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed- and random-effect models. A total of seven case-control studies encompassing 1897 ischemic stroke cases and 2119 healthy controls were critically evaluated. Pooled results from the genetic models indicated that OLR1 rs11053646 dominant (OR=1.33. 95%CI:1.11-1.58) and co-dominant models (OR=1.24, 95%CI:1.02-1.51) were significantly associated with ischemic stroke. For PCSK9 rs505151 polymorphism, the OR of co-dominant model (OR=1.36, 95%CI:1.01-1.58) was found to be higher among ischemic stroke patients. In conclusion, the current meta-analysis highlighted that variant allele of OLR1 rs11053646 G>C and PCSK9 rs505151 A>G may contribute to the susceptibility risk of ischemic stroke.

Next generation sequencing identifies novel CACNA1A gene mutations in Episodic Ataxia type 2

Episodic Ataxia type 2 (EA2) is a rare autosomal dominantly inherited neurological disorder characterized by recurrent disabling imbalance, vertigo and episodes of ataxia lasting minutes to hours. EA2 is caused most often by loss of function mutations of the calcium channel gene CACNA1A. In addition to EA2, mutations in CACNA1A are responsible for two other allelic disorders: familial hemiplegic migraine type1 (FHM1) and spinocerebellar ataxia type 6 (SCA6). Herein, we have utilised Next Generation Sequencing (NGS) to screen the coding sequence, exon-intron boundaries and UTRs of five genes where mutation is known to produce symptoms related to EA2, including CACNA1A. We performed this screening in a group of 31 unrelated patients with EA2 symptoms. Both novel and known mutations were detected through NGS technology, and confirmed through Sanger sequencing. Genetic testing showed in total 15 mutation bearing patients (48%), of which 9 were novel mutations (6 missense and 3 small frameshift deletion mutations) and six known mutations (4 missense and 2 nonsense).These results demonstrate the efficiency of our NGS-panel for detecting known and novel mutations for EA2 in the CACNA1A gene, also identifying a novel missense mutation in ATP1A2 which is not a normal target for EA2 screening.

Clinical relevance of MTHFR, eNOS, ACE, and ApoE gene polymorphisms and serum vitamin profile among Malay patients with ischemic stroke

Background The purpose of this study was threefold. First, it was to determine the relationship between serum vitamin profiles and ischemic stroke. The second purpose was to investigate the association of methylenetetrahydrofolate reductase (MTHFR), endothelial nitric oxide synthase (eNOS), angiotensin converting enzyme (ACE), and apolipoprotein-E (ApoE) gene polymorphisms with ischemic stroke and further correlate with serum vitamin profiles among ischemic stroke patients. The third purpose of the study was to highlight the interaction of MTHFR and eNOS haplotypes with serum vitamin profiles and ischemic stroke risks. Methods Polymorphisms of these genes were analyzed in age-, sex-, and ethnicity-matched case–controls (n = 594); serum vitamin profiles were determined using immunoassays. Results The MTHFR 677C>T, 1298A>C, eNOS intron 4a/b, and ApoE polymorphisms were significantly associated with the increased risk of ischemic stroke. Elevated serum homocysteine and vitamin B12 levels were associated with MTHFR 677C>T and eNOS intron 4a/b polymorphisms. The ApoE and eNOS −786T>C polymorphisms were associated with increased serum vitamin B12 levels. However, none of the polymorphisms influenced serum folate levels except for the MTHFR 1298A>C. Different patterns of MTHFR and eNOS haplotypes tend to affect serum vitamin profiles to different degrees, which contribute to either different susceptibility risk or protective effect on ischemic stroke. Overall, increased levels of serum homocysteine and vitamin B12 levels were associated with higher risk of ischemic stroke in the investigated population. Conclusions The present study suggests that the genotypes and haplotypes of MTHFR 677C>T and eNOS intron 4a/b polymorphisms are potential serum biomarkers in the pathophysiological processes of ischemic stroke, by modulating homocysteine and vitamin B12 levels.

HDAC inhibitor valproic acid enhances tumor cell kill in adenovirus-HSVtk mediated suicide gene therapy in HNSCC xenograft mouse model

Safety, efficacy and enhanced transgene expression are the primary concerns while using any vector for gene therapy. One of the widely used vectors in clinical. trials is adenovirus which provides a safe way to deliver the therapeutic gene. However, adenovirus has poor transduction efficiency in vivo since most tumor cells express low coxsackie and adenovirus receptors. Similarly transgene expression remains low, possibly because of the chromatization of adenoviral genome upon infection in eukaryotic cells, an effect mediated by histone deacetylases (HDACs). Using a recombinant adenovirus (Ad-HSVtk) carrying the herpes simplex thymidine kinase (HSVtk) and GFP genes we demonstrate that HDAC inhibitor valproic acid can bring about an increase in CAR expression on host cells and thereby enhanced Ad-HSVtk infectivity. It also resulted in an increase in transgene (HSVtk and GFP) expression. This, in turn, resulted in increased cell kill of HNSCC cells, following ganciclovir treatment in vitro as well as in vivo in a xenograft nude mouse model.

Introduction: Sustainability reconsidered

Indeed this is still a common interpretation of sustainability and sustainable development. in actual fact the report highlighted three fundamental components to sustainable development: environmental protection, economic growth, and social equity. It stated that the environment should be conserved and our resource base enhanced, by gradually changing the ways in which we develop and use technologies. Moreover it was clear that developing nations must be allowed to meet their basic needs of employment, food, water, energy, ...

Distress call-induced gene expression in the brain of the Indian short-nosed fruit bat, Cynopterus sphinx

Individuals in distress emit audible vocalizations to either warn or inform conspecifics. The Indian short-nosed fruit bat, Cynopterus sphinx, emits distress calls soon after becoming entangled in mist nets, which appear to attract conspecifics. Phase I of these distress calls is longer and louder, and includes a secondary peak, compared to phase II. Activity-dependent expression of egr-1 was examined in free-ranging C. sphinx following the emissions and responses to a distress call. We found that the level of expression of egr-1 was higher in bats that emitted a distress call, in adults that responded, and in pups than in silent bats. Up-regulated cDNA was amplified to identify the target gene (TOE1) of the protein Egr-1. The observed expression pattern Toe1 was similar to that of egr-1. These findings suggest that the neuronal activity related to recognition of a distress call and an auditory feedback mechanism induces the expression of Egr-1. Co-expression of egr-1 with Toe1 may play a role in initial triggering of the genetic mechanism that could be involved in the consolidation or stabilization of distress call memories.

Cucumber chloroplast trnL(CAA) gene: nucleotide sequence and in vivo expression analysis in etiolated cucumber seedlings treated with benzyladenine and light.

The nucleotide sequence of a 714 bp BamHI-EcoRI fragment of cucumber chloroplast DNA was determined. The fragment contained a gene for tRNA(Leu) together with its flanking regions. The trnL(CAA) gene sequence is about 99% in similarity to broad bean, cauliflower, maize, spinach and tobacco corresponding genes. The relative expression level of the gene was determined by Northern (tRNA) gel blot and Northern (total cellular RNA) slot-blot analyses using the trnL gene probe in 6-day old etiolated cucumber seedlings and the seedlings that had been kept in the dark (dark-grown), treated with benzyladenine (BA) and kept in the dark (BA-treated dark-grown), illuminated (light-grown), and treated with BA and illuminated (BA-treated light-grown), for additional 4, 8 or 12 hr. The trnL transcripts and tRNA(Leu) levels in BA-treated dark-grown seedlings were 5 and 3 times higher, respectively after 4 hr BA treatment, while in the BA treated light-grown seedlings the level of trnL transcripts was only 3 times higher and had no detectable effect on mature tRNA(Leu) when compared to the time-4 hr dark-grown seedlings. However, the level of mature tRNA(Leu) did not show marked changes in the light-grown seedlings, whereas the level of trnL transcripts increases 3 times after 8 hr illumination of dark-grown seedlings. These data indicate that both light and cytokinin can signal changes in plastid tRNA gene expression. The possible regulatory mechanisms for such changes are discussed.

Cucumber chloroplast trnL(CAA) gene: nucleotide sequence and in vivo expression analysis in etiolated cucumber seedlings treated with benzyladenine and light

The nucleotide sequence of a 714 bp BamHI-EcoRI fragment of cucumber chloroplast DNA was determined. The fragment contained a gene for tRNA(Leu) together with its flanking regions. The trnL(CAA) gene sequence is about 99% in similarity to broad bean, cauliflower, maize, spinach and tobacco corresponding genes. The relative expression level of the gene was determined by Northern (tRNA) gel blot and Northern (total cellular RNA) slot-blot analyses using the trnL gene probe in 6-day old etiolated cucumber seedlings and the seedlings that had been kept in the dark (dark-grown), treated with benzyladenine (BA) and kept in the dark (BA-treated dark-grown), illuminated (light-grown), and treated with BA and illuminated (BA- treated light-grown), for additional 4, 8 or 12 hr. The trnL transcripts and tRNA(Leu) levels in BA-treated dark-grown seedlings were 5 and 3 times higher, respectively after 4 hr BA treatment, while in the BA treated light-grown seedlings the level of trnL transcripts was only 3 times higher and had not detectable effect on mature tRNA(Leu) when compared to the time-4 hr dark-grown seedlings. However, the level of mature tRNA(Leu) did not show marked changes in the light-grown seedlings, whereas the level of trnL transcripts increases 3 times after 8 hr illumination of dark-grown seedlings. These date indicate that both light and cytokinin can signal changes in plastid tRNA gene expression. The possible regulatory mechanisms for such changes are discussed.

An introduction to ophthalmic biomaterials and their role in tissue engineering and regenerative medicine

This chapter presents a brief history of the development of ophthalmic biomaterials. Particularities in the development of ophthalmic biomaterials are discussed and some of their historic priorities within the general field of biomaterials are revealed or emphasized. The chapter then discusses the role and integration of ophthalmic biomaterials in tissue engineering and regenerative medicine applications.

An elementary introduction to solar dynamo theory

The cyclically varying magnetic field of the Sun is believed to be produced by the hydromagnetic dynamo process. We first summarize the relevant observational data pertaining to sunspots and solar cycle. Then we review the basic principles of MHD needed to develop the dynamo theory. This is followed by a discussion how bipolar sunspots form due to magnetic buoyancy of flux tubes formed at the base of the solar convection zone. Following this, we come to the heart of dynamo theory. After summarizing the basic ideas of a turbulent dynamo and the basic principles of its mean field formulation, we present the famous dynamo wave solution, which was supposed to provide a model for the solar cycle. Finally we point out how a flux transport dynamo can circumvent some of the difficulties associated with the older dynamo models.

Introduction to Public Health [3rd Ed.]

Why is public health important? An Introduction to Public Health is about the discipline of public health, the nature and scope of public health activity, and the challenges that face public health in the twenty-first century. The book is designed as an introductory text to the principles and practice of public health. This is a complex and multifaceted area. What we have tried to do in this book is make public health easy to understand without making it simplistic. As many authors have stated, public health is essentially about the organised efforts of society to promote, protect and restore the public’s health (Brownson 2011, Last 2001, Schneider 2011, Turnock 2012, Winslow 1920). It is multidisciplinary in nature, and it is influenced by genetic, physical, social, cultural, economic and political determinants of health. How do we define public health, and what are the disciplines that contribute to public health? How has the area changed over time? Are there health issues in the twenty-first century that change the focus and activity of public health? Yes, there are! There are many challenges facing public health now and in the future, just as there have been over the course of the history of organised public health efforts, dating from around 1850 in the Western world. Of what relevance is public health to the many health disciplines that contribute to it? How might an understanding of public health contribute to a range of health professionals who use the principles and practices of public health in their professional activities? These are the questions that this book addresses. Introduction to Public Health leads the reader on a journey of discovery that concludes with an understanding of the nature and scope of public health and the challenges facing the field into the future. In this edition we have included one new chapter, ‘Public health and social policy’, in order to broaden our understanding of the policy influences on public health. The book is designed for a range of students undertaking health courses where there is a focus on advancing the health of the population. While it is imperative that people wanting to be public health professionals understand the theory and practice of public health, many other health workers contribute to effective public health practice. The book would also be relevant to a range of undergraduate students who want an introductory understanding of public health and its practice.

Introduction: Reviewing Australian screen history

This special issue of Studies in Australasian Cinema features a selection of papers presented at the 17th Film and History Association of Australia and New Zealand (FHAANZ) conference, held at Queensland University of Technology between 1 and 3 July 2015. This was the first FHAANZ conference to be hosted in Queensland since 1998. Informed by historical and archival research, the articles examine overlooked or underdeveloped aspects of screen history, offer new historical perspectives, or consider key contemporary issues regarding the preservation of Australian screen history.