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Cellular stage specific functional analysis of REX1: In human embryonic stem cells. - Proteomics
As transcription and translation are dynamic and can vary among the cell types and conditions, proteomics may reveal the tissue-specific functions of a protein, more relevant to its genuine functions on cellular mechanisms. The new proteome analysis by Son et al. [Proteomics 2015, 15, 2220-2229] identified the functions of the pluripotency marker protein, REX1 in hESCs, and unraveling its regulatory network orchestrating pluripotency. Compared to the previous transcriptome analysis that showed mechanisms irrelevant to pluripotency, Son et al. employed a proteome analysis determined convincing and meaningful mechanisms of REX. In addition to demonstrating the biological importance of REX1, this research by Son et al. is also a compelling example of the conceptual significance of connecting proteomics with stem cell biology.Â© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Characterization of wastes from construction and demolition sector. - Environmental monitoring and assessment
In Republic of Korea, construction and demolition (C&D) waste accounts for 49.9% of the total waste. In the present work, the mineralogical composition, the concentrations of 11 heavy metals, 19 PAH, and 7 polychlorinated biphenyl (PCB) congeners present in the 6 broad category (9 subcategories) of C&D hazardous waste were discussed along with their leaching characteristics. In concrete/mixed cement waste, the concentrations of As, Cr(6+), Hg, and Zn were in the range of 1.76-7.86, ND-1.63, 0.026-0.047, and 110.90-280.17 mg/kg, respectively. The asphalt waste sample A1 possessed relatively high concentrations of phenanthrene, fluoranthene, pyrene, benz(a)anthracene, benzo(a)pyrene, and indeno(1,2,3-cd)pyrene comparing to the other samples and it contains 0.08-0.1% of coal tar. Hazardous nature of the C&D wastes greatly depends on the source of the collection. Zn concentration was above 1000 mg/kg for road asphalt waste samples A4 and A5. Total PCB concentration were high in the soil waste sample S1 (130 Î¼g/kg) as it was the excavated soil obtained from the premises of an oil station. Leaching of As, Ba, CN(-), and F(-) were observed in most of the C&D waste samples.
Generation of multipotent induced neural crest by direct reprogramming of human postnatal fibroblasts with a single transcription factor. - Cell stem cell
Neural crest (NC) generates diverse lineages including peripheral neurons, glia, melanocytes, and mesenchymal derivatives. Isolating multipotent human NC has proven challenging, limiting our ability to understand NC development and model NC-associated disorders. Here, we report direct reprogramming of human fibroblasts into induced neural crest (iNC) cells by overexpression of a single transcription factor, SOX10, in combination with environmental cues including WNT activation. iNC cells possess extensive capacity for migration inÂ vivo, and single iNC clones can differentiate into the four main NC lineages. We further identified a cell surface marker for prospective isolation of iNCs, which was used to generate and purify iNCs from familial dysautonomia (FD) patient fibroblasts. FD-iNC cells displayed defects in cellular migration and alternative mRNA splicing, providing insights into FD pathogenesis. Thus, this study provides an accessible platform for studying NC biology and disease through rapid and efficient reprogramming of human postnatal fibroblasts.Copyright Â© 2014 Elsevier Inc. All rights reserved.
IGF-I improves mitochondrial membrane potential during hypothermic storage of canine spermatozoa. - The Journal of veterinary medical science / the Japanese Society of Veterinary Science
The aim of study was to evaluate the effects of insulin-like growth factor I (IGF-I) on canine sperm function during cooled and freeze-thaw storage. Extenders supplemented with different IGF-I concentrations (0, 100 and 200 ng/ml) were added to canine spermatozoa, and the sperm samples were stored at 4Â°C for 48 hr or freeze-thawed. Sperm motility, morphology, plasma-membrane integrity (PMI) and mitochondrial membrane potential (MMP) were evaluated. IGF-I had no effect on PMI or morphology during cooling and freeze-thawing. However, IGF-I alleviated the reduction in progressive motility and MMP caused by cooled storage and led to an improvement in MMP after freeze-thawing. In conclusion, IGF-I can be helpful to maintain progressive motility of canine spermatozoa during hypothermic storage via increased MMP.
Candidate ALS therapeutics motor toward "in vitro clinical trials". - Cell stem cell
Conducting drug discovery efforts in patient- and disease-specific cells can maximize their likelihood of success. In this issue of Cell Stem Cell, Yang et al. (2013) demonstrate the power of lineage-specific cell-based drug screens by identifying a compound that promotes survival of stem-cell-derived ALS mutant motor neurons.Copyright Â© 2013 Elsevier Inc. All rights reserved.
Large-scale screening using familial dysautonomia induced pluripotent stem cells identifies compounds that rescue IKBKAP expression. - Nature biotechnology
Patient-specific induced pluripotent stem cells (iPSCs) represent a novel system for modeling human genetic disease and could provide a source of cells for large-scale drug-discovery screens. Here we demonstrate the feasibility of performing a primary screen in neural crest precursors derived from iPSCs that were generated from individuals with familial dysautonomia (FD), a rare, fatal genetic disorder affecting neural crest lineages. We tested 6,912 small-molecule compounds and characterized eight that rescued expression of IKBKAP, the gene responsible for FD. One of the hits, SKF-86466, was found to induce IKBKAP transcription through modulation of intracellular cAMP levels and PKA-dependent CREB phosphorylation. SKF-86466 also rescued IKAP protein expression and the disease-specific loss of autonomic neuronal marker expression. Our data implicate alpha-2 adrenergic receptor activity in regulating IKBKAP expression and demonstrate that small-molecule discovery using an iPSC-based disease model can identify candidate drugs for potential therapeutic intervention.
Improvement of wireless power transmission efficiency of implantable subcutaneous devices by closed magnetic circuit mechanism. - Medical & biological engineering & computing
Induction coils were fabricated based on flexible printed circuit board for inductive transcutaneous power transmission. The coil had closed magnetic circuit (CMC) structure consisting of inner and outer magnetic core. The power transmission efficiency of the fabricated device was measured in the air and in vivo condition. It was confirmed that the CMC coil had higher transmission efficiency than typical air-core coil. The power transmission efficiency during a misalignment between primary coil and implanted secondary coil was also evaluated. The decrease of mutual inductance between the two coils caused by the misalignment led to a low efficiency of the inductive link. Therefore, it is important to properly align the primary coil and implanted secondary coil for effective power transmission. To align the coils, a feedback coil was proposed. This was integrated on the backside of the primary coil and enabled the detection of a misalignment of the primary and secondary coils. As a result of using the feedback coil, the primary and secondary coils could be aligned without knowledge of the position of the implanted secondary coil.
Residents' expectation of family medicine-specific training program and its current state. - Korean journal of family medicine
The family medicine residency program consists mainly of clinical rotations in other specialties and the family medicine-specific training. We conducted this study to investigate how family medicine residents evaluated their training program that include family-oriented medicine, clinical preventive medicine, behavioral science and research in primary care.In 2009, third-year residents of 129 training hospitals in Korea were surveyed to investigate the current state and their expectation of the residency program. The contents of questionnaires included training periods, conferences, procedures, interview techniques, outpatient and inpatient consultations, and written thesis.Total 133 out of 142 residents (93.7%) responded that 3 years of training is ideal or pertinent. Residents responded that the types of conference that they need most are journal review (81%), staff lecture (73.2%), and clinical topic review (73.2%), in that order. Procedures and interview techniques that the residents want to learn most were gastroscopy (72.5%), abdominal ultrasonography (65.2%), and pain management (46.4%). Hospitals where family medicine residents do not see hospitalized patients or patients in the outpatient clinic were 7.9% and 6.5%, respectively, whereas hospitals that maintain continuous family medicine outpatient clinics were only 40.8%. Education in outpatient clinic and articlewriting seminars was done less frequently in the secondary hospitals than in the tertiary hospitals.Evaluation and quality improvement of family medicine training program as well as specialty rotations should be considered in order to foster better family physicians. The efforts have to be made to minimize the difference in quality of each family medicine residency program.
Spontaneous synchronized burst firing of subthalamic nucleus neurons in rat brain slices measured on multi-electrode arrays. - Neuroscience research
The current study presents an organotypic rat midbrain slice culture that served as a consistent and informative framework, where the STN neurons and their interconnectivity were closely examined with respect to electrophysiological and pharmacological properties. From multi-electrode array recordings, it was found that the majority of STN neurons spontaneously fired in bursts rather than tonically under control conditions, and the neural activity between pairs of burst-firing STN neurons was tightly correlated. This spontaneous synchronized burst firing was also affected by a glutamate receptor antagonist, yet unaffected by a GABA receptor antagonist. Moreover, even when the STN was isolated from all its known external inputs, spontaneous synchronized burst firing was still observed under control conditions and consistently switched to tonic firing following the application of a glutamate receptor antagonist. Therefore, the results indicated the existence of glutamatergic projections to the STN in the slice preparation, and these excitatory synaptic connections appeared to originate from axon collaterals within the STN rather than other basal ganglia nuclei. It could be concluded that the STN neurons and their interconnectivity are essential requirements in the rat brain slice preparation to produce spontaneous synchronized burst firing.Copyright Ã‚Â© 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
Rapid freezing without cooling equilibration in canine sperm. - Animal reproduction science
The aim of this study was to develop a rapid method of canine semen freezing without cooling equilibration using treatment with different cryoprotectant agents (CPAs) and freezing in liquid nitrogen (LN(2)) vapor in a 0.5-mL straw via modifying vitrification. Ejaculates from eight beagle dogs were frozen with different CPAs (CPA-free, 5% glycerol, 5% ethylene glycol, and 10% ethylene glycol) and freezing times (direct plunging into LN(2) or freezing for 1, 2, 3, or 10 min in LN(2) vapor before plunging into LN(2)). Frozen-thawed sperm were evaluated for motility, viability, normal morphology, and plasma- and acrosome-membrane integrities. The 5% glycerol treatment resulted in improved sperm motility, plasma-membrane integrity and acrosome-membrane integrity (P<0.05). Freezing in LN(2) vapor showed improved sperm motility, viability, and plasma membrane integrity (P<0.05), and freezing for more than 2 min in LN(2) vapor increased acrosome-membrane integrity compared with direct plunging into LN(2) (P<0.05). The direct plunging into LN(2) showed no motile sperm. However, freezing for more than 2 min in LN(2) vapor increased the total abnormalities compared to direct plunging into LN(2) (P<0.05). In conclusion, use of 5% glycerol and freezing in LN(2) vapor were essential for the rapid freezing of canine sperm without cooling equilibration. In particular, holding for 2 min in LN(2) vapor was sufficient to yield successful rapid freezing. This rapid freezing method is simple and effective in canine sperm and would be helpful to offer information for trial of vitrification in large volumes of canine sperm.Copyright Ã‚Â© 2012 Elsevier B.V. All rights reserved.
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