72 research outputs found
Rare coding SNP in DZIP1 gene associated with late-onset sporadic Parkinson's disease
We present the first application of the hypothesis-rich mathematical theory
to genome-wide association data. The Hamza et al. late-onset sporadic
Parkinson's disease genome-wide association study dataset was analyzed. We
found a rare, coding, non-synonymous SNP variant in the gene DZIP1 that confers
increased susceptibility to Parkinson's disease. The association of DZIP1 with
Parkinson's disease is consistent with a Parkinson's disease stem-cell ageing
theory.Comment: 14 page
Suppression of Osteosarcoma Cell Invasion by Chemotherapy Is Mediated by Urokinase Plasminogen Activator Activity via Up-Regulation of EGR1
Background: The cellular and molecular mechanisms of tumour response following chemotherapy are largely unknown. We
found that low dose anti-tumour agents up-regulate early growth response 1 (EGR1) expression. EGR1 is a member of the
immediate-early gene group of transcription factors which modulate transcription of multiple genes involved in cell
proliferation, differentiation, and development. It has been reported that EGR1 act as either tumour promoting factor or
suppressor. We therefore examined the expression and function of EGR1 in osteosarcoma.
Methods: We investigated the expression of EGR1 in human osteosarcoma cell lines and biopsy specimens. We next
examined the expression of EGR1 following anti-tumour agents treatment. To examine the function of EGR1 in
osteosarcoma, we assessed the tumour growth and invasion in vitro and in vivo.
Results: Real-time PCR revealed that EGR1 was down-regulated both in osteosarcoma cell lines and osteosarcoma patients’
biopsy specimens. In addition, EGR1 was up-regulated both in osteosarcoma patient’ specimens and osteosarcoma cell lines
following anti-tumour agent treatment. Although forced expression of EGR1 did not prevent osteosarcoma growth, forced
expression of EGR1 prevented osteosarcoma cell invasion in vitro. In addition, forced expression of EGR1 promoted downregulation
of urokinase plasminogen activator, urokinase receptor, and urokinase plasminogen activity. Xenograft mice
models showed that forced expression of EGR1 prevents osteosarcoma cell migration into blood vessels.
Conclusions: These findings suggest that although chemotherapy could not prevent osteosarcoma growth in
chemotherapy-resistant patients, it did prevent osteosarcoma cell invasion by down-regulation of urokinase plasminogen
activity via up-regulation of EGR1 during chemotherapy periods
T1 mapping in cardiac MRI
Quantitative myocardial and blood T1 have recently achieved clinical utility in numerous pathologies, as they provide non-invasive tissue characterization with the potential to replace invasive biopsy. Native T1 time (no contrast agent), changes with myocardial extracellular water (edema, focal or diffuse fibrosis), fat, iron, and amyloid protein content. After contrast, the extracellular volume fraction (ECV) estimates the size of the extracellular space and identifies interstitial disease. Spatially resolved quantification of these biomarkers (so-called T1 mapping and ECV mapping) are steadily becoming diagnostic and prognostically useful tests for several heart muscle diseases, influencing clinical decision-making with a pending second consensus statement due mid-2017. This review outlines the physics involved in estimating T1 times and summarizes the disease-specific clinical and research impacts of T1 and ECV to date. We conclude by highlighting some of the remaining challenges such as their community-wide delivery, quality control, and standardization for clinical practice
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Northern Eurasia Future Initiative (NEFI): facing the challenges and pathways of global change in the 21st century
During the past several decades, the Earth system has changed significantly, especially across Northern Eurasia. Changes in the socio-economic conditions of the larger countries in the region have also resulted in a variety of regional environmental changes that can
have global consequences. The Northern Eurasia Future Initiative (NEFI) has been designed as an essential continuation of the Northern Eurasia Earth Science
Partnership Initiative (NEESPI), which was launched in 2004. NEESPI sought to elucidate all aspects of ongoing environmental change, to inform societies and, thus, to
better prepare societies for future developments. A key principle of NEFI is that these developments must now be secured through science-based strategies co-designed
with regional decision makers to lead their societies to prosperity in the face of environmental and institutional challenges. NEESPI scientific research, data, and
models have created a solid knowledge base to support the NEFI program. This paper presents the NEFI research vision consensus based on that knowledge. It provides the reader with samples of recent accomplishments in regional studies and formulates new NEFI science questions. To address these questions, nine research foci are identified and their selections are briefly justified. These foci include: warming of the Arctic; changing frequency, pattern, and intensity of extreme and inclement environmental conditions; retreat of the cryosphere; changes in terrestrial water cycles; changes in the biosphere; pressures on land-use; changes in infrastructure; societal actions in response to environmental change; and quantification of Northern Eurasia's role in the global Earth system. Powerful feedbacks between the Earth and human systems in Northern Eurasia (e.g., mega-fires, droughts, depletion of the cryosphere essential for water supply, retreat of sea ice) result from past and current human activities (e.g., large scale water withdrawals, land use and governance change) and
potentially restrict or provide new opportunities for future human activities. Therefore, we propose that Integrated Assessment Models are needed as the final stage of global
change assessment. The overarching goal of this NEFI modeling effort will enable evaluation of economic decisions in response to changing environmental conditions and justification of mitigation and adaptation efforts
Correction to: Clinical recommendations for cardiovascular magnetic resonance mapping of T1, T2, T2* and extracellular volume: A consensus statement by the Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imaging (EACVI).
CORRECTION TO: J CARDIOVASC MAGN RESON (2017) 19: 75. DOI: 10.1186/S12968-017-0389-8: In the original publication of this article [1] the "Competing interests" section was incorrect. The original publication stated the following competing interests
Dz13: c-Jun downregulation and tumour cell death
DNAzymes (DNA enzymes and deoxyribozymes)
are synthetic, single-stranded DNA-based catalysts
engineered to bind to their complementary
sequence in a target messenger RNA (mRNA)
through Watson–Crick rules for base-pairing and
cleave the mRNA at predetermined phosphodiester
linkages. Dz13, a DNAzyme that cleaves c-Jun
mRNA, has been found to have efficacious effects
against tumours directly, activity against tumourinduced
angiogenesis, inhibition of neointima
formation after arterial injury and control of
inflammatory responses. Recent studies in endothelial
cells demonstrate that the off-target
effects of Dz13 may in fact be driving some of
these potentially therapeutic effects, although no
mechanisms have been clearly defined in tumour
cells. Recent data show that Dz13 is capable of
inhibiting more types of tumours and potently
induces apoptosis in a panel of tumour cell lines.
Hand-in-hand with in vivo testing, Dz13 has been
formulated into a biocompatible nanoparticle,
enabling its full potential to be realized. Its chemistry is partly responsible for its activity
against tumour cells, but it is safe to use in vivo
and surprisingly shows little harmful effects
against normal cells. These findings provide hope
that Dz13 may be useful clinically for the treatment
of a variety of cancers
Injectable chitosan hydrogels for localised cancer therapy
The pace of development of delivery systems that could target drugs to specific body sites and control the release of drugs for prolonged
periods of time have been steady though slow. Till a decade ago, mostly microspheres or nanoparticles were widely studied and applied in cancer
treatment. However, due to shortcomings of these systems, there has been a surge in interest for in situ hydrogels. This review focuses on the
current use of injectable in situ chitosan hydrogels in cancer treatment. Formulation protocols for in situ hydrogel systems, their cytotoxic
properties, loading and in vitro release of drugs, their effect on cell growth in vitro and inhibition of tumor growth in vivo using mouse models,
and future directions to enhance this technology are discussed
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