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  • 1
    Publication Date: 2015-04-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rais, Yoach -- Zviran, Asaf -- Geula, Shay -- Gafni, Ohad -- Chomsky, Elad -- Viukov, Sergey -- Mansour, Abed AlFatah -- Caspi, Inbal -- Krupalnik, Vladislav -- Zerbib, Mirie -- Maza, Itay -- Mor, Nofar -- Baran, Dror -- Weinberger, Leehee -- Jaitin, Diego A -- Lara-Astiaso, David -- Blecher-Gonen, Ronnie -- Shipony, Zohar -- Mukamel, Zohar -- Hagai, Tzachi -- Gilad, Shlomit -- Amann-Zalcenstein, Daniela -- Tanay, Amos -- Amit, Ido -- Novershtern, Noa -- Hanna, Jacob H -- England -- Nature. 2015 Apr 30;520(7549):710. doi: 10.1038/nature14369. Epub 2015 Apr 1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25830885" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2013-09-21
    Description: Somatic cells can be inefficiently and stochastically reprogrammed into induced pluripotent stem (iPS) cells by exogenous expression of Oct4 (also called Pou5f1), Sox2, Klf4 and Myc (hereafter referred to as OSKM). The nature of the predominant rate-limiting barrier(s) preventing the majority of cells to successfully and synchronously reprogram remains to be defined. Here we show that depleting Mbd3, a core member of the Mbd3/NuRD (nucleosome remodelling and deacetylation) repressor complex, together with OSKM transduction and reprogramming in naive pluripotency promoting conditions, result in deterministic and synchronized iPS cell reprogramming (near 100% efficiency within seven days from mouse and human cells). Our findings uncover a dichotomous molecular function for the reprogramming factors, serving to reactivate endogenous pluripotency networks while simultaneously directly recruiting the Mbd3/NuRD repressor complex that potently restrains the reactivation of OSKM downstream target genes. Subsequently, the latter interactions, which are largely depleted during early pre-implantation development in vivo, lead to a stochastic and protracted reprogramming trajectory towards pluripotency in vitro. The deterministic reprogramming approach devised here offers a novel platform for the dissection of molecular dynamics leading to establishing pluripotency at unprecedented flexibility and resolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rais, Yoach -- Zviran, Asaf -- Geula, Shay -- Gafni, Ohad -- Chomsky, Elad -- Viukov, Sergey -- Mansour, Abed AlFatah -- Caspi, Inbal -- Krupalnik, Vladislav -- Zerbib, Mirie -- Maza, Itay -- Mor, Nofar -- Baran, Dror -- Weinberger, Leehee -- Jaitin, Diego A -- Lara-Astiaso, David -- Blecher-Gonen, Ronnie -- Shipony, Zohar -- Mukamel, Zohar -- Hagai, Tzachi -- Gilad, Shlomit -- Amann-Zalcenstein, Daniela -- Tanay, Amos -- Amit, Ido -- Novershtern, Noa -- Hanna, Jacob H -- England -- Nature. 2013 Oct 3;502(7469):65-70. doi: 10.1038/nature12587. Epub 2013 Sep 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24048479" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cells, Cultured ; Cellular Reprogramming/genetics/*physiology ; DNA-Binding Proteins/genetics ; Embryonic Stem Cells ; Female ; Gene Expression Regulation ; HEK293 Cells ; Humans ; Induced Pluripotent Stem Cells/*physiology ; Male ; Mice ; *Models, Biological ; Transcription Factors/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2018-09-21
    Description: Phosphorothioate nucleotides have emerged as powerful pharmacological substitutes of their native phosphodiester analogs with important translational applications in antisense oligonucleotide (ASO) therapeutics and cyclic dinucleotide (CDN) synthesis. Stereocontrolled installation of this chiral motif has long been hampered by the systemic use of phosphorus(III) [P(III)]–based reagent systems as the sole practical means of oligonucleotide assembly. A fundamentally different approach is described herein: the invention of a P(V)-based reagent platform for programmable, traceless, diastereoselective phosphorus-sulfur incorporation. The power of this reagent system is demonstrated through the robust and stereocontrolled synthesis of various nucleotidic architectures, including ASOs and CDNs, via an efficient, inexpensive, and operationally simple protocol.
    Keywords: Chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    ISSN: 1432-0827
    Keywords: Single energy x-ray absorptiometry ; Dual energy x-ray absorptiometry ; Bone mineral density ; Bone mineral content
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract The performance of a single X-ray absorptiometry (SXA) device incorporating an X-ray tube as a photon source was evaluated with respect to precision in vivo and in vitro, scan time, image quality, and correlation with an existing dual energy X-ray absorptiometry (DXA) device. SXA precision in vivo, expressed as a coefficient of variation (CV), was 0.66% for bone mineral content (BMC) and 1.05% for bone mineral density (BMD). Precision in vitro, based on 78 BMC measurements of a forearm phantom over 195 days, was 0.53%. Correlation with DXA at the 8 mm distal forearm site was high (r=0.97 for BMC and r=0.96 for BMD). A preliminary SXA reference database composed of 151 healthy Caucasian American women was developed to facilitate the interpretation of patient measurements. SXA scan time was 4 minutes and delivered a radiation exposure of 1.68 mrem. SXA image quality and spatial resolution were superior to SPA and comparable to DXA.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0827
    Keywords: Diabetes mellitus ; Osteocalcin ; Osteoblast number ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract The accumulated data indicate that bone mineral density (BMD) is decreased in humans with insulin-dependent diabetes mellitus. The purpose of this study was to prospectively determine sequential lumbar and femoral BMD utilizing dual energy X-ray absorptiometry in rats that spontaneously become diabetic to determine if weight and blood glucose control would prevent the diabetes-related bone mass changes. BMD of the lumbar spine and femur was measured prior to the onset of diabetes and at 3-week intervals after the diagnosis of diabetes for 12 weeks in 14 diabetes-prone BB/Wor rats (DP) and eight diabetes-resistant BB/Wor control rats (DR). At 12 weeks, the lumbar (0.238±0.013 vs 0.262±0.007 g/cm2, P〈0.001) and femoral (0.313±0.013 vs 0.343±0.013 g/cm2, P〈0.001) BMD were significantly lower in the DP rats despite significantly greater body weights (387±26 vs 329±46 g, P〈0.001) and plasma glucose levels of only 178 mg/dl. There was no difference in plasma values of calcium, phosphorus, osteocalcin, or tartrate-resistant acid phosphatase between groups or differences in osteoblast numbers in histologic sections. There was a significant (P〈0.001) decrease in plasma creatinine in the diabetic animals. The results indicate that in this animal model of type I diabetes, spine and femoral BMD do not increase comparable to control despite weight and blood glucose control. This would suggest that the diabetic condition itself affects bone mass in the absence of weight loss and poor blood glucose control.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0827
    Keywords: Collagen ; Osteocalcin ; Bone mineral density ; Skeletal heterogeneity ; TRAP ; Cell proliferation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract We have previously shown that calcitonin (CT), an inhibitor of bone resorption, increases vertebral, but not femoral bone density in the rat [3]. To address the physiologic responses associated with these effects on bone mineral density (BMD), we assessed mRNA transcripts reflecting activities of osteoblasts (type I collagen, osteocalcin, osteopontin, and alkaline phosphatase), osteoclasts [tartrate-resistant acid phosphatase (TRAP)], and cell proliferation (histone H4) in the spine and femur of these rats. CT increased spine BMD while increasing type I collagen and decreasing TRAP and histone mRNAs. In the femur, where CT had no effect on BMD, it decreased type I collagen and histone H4 mRNA but did not affect TRAP. CT had no effect on the gene expression of osteocalcin, osteopontin, or alkaline phosphatase at either site. The results indicate that selective alterations in gene expression, as reflected by steady state mRNA levels, are consistent with the changes observed by BMD measurement, and can more clearly define the specific contribution from osteoblast and osteoclast activity. This study demonstrates a heterogeneity in response of the axial and appendicular skeleton to CT, reflected by alterations in gene expression that provide a basis for understanding the observed BMD responses to various pharmacologic interventions.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0827
    Keywords: Osteoporosis ; Calcaneus ; Ultrasonic measurement ; Density
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Broadband ultrasound attenuation (BUA) of the calcaneus predicts axial density in women and is decreased in women who sustain hip fractures. To determine the relationship between ultrasonic and densitometric assessments of bone mass at the same site, BUA and velocity of sound (VOS) were correlated with bone density as measured by dual energy x-ray absorptiometry (DXA) at the calcaneus in 64 Caucasian women aged 35–83 years. BUA, VOS, and bone density in these women decreased annually as a function of age by 1.0%, 0.3%, and 0.9%, respectively. Holding age, years since menopause, height and weight constant, BUA correlated with VOS (r=0.74, P〈0.001), and calcaneal density correlated with BUA (r=0.73, P〈0.001) and with VOS (r=0.66, P〈0.01). The results indicate that both BUA and VOS measurements reflect density at the calcaneus, but suggest that they measure properties of bone other than density and different from each other. The assessment of these additional properties may be useful in the prediction of fracture risk.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A sample of 107 Belgian cystic fibrosis patients has been tested for the presence of the ΔF508 deletion. We have shown that 166 (78%) of the CF chromosomes presented the deletion, and that 97% of the deleted chromosomes and 50% of the non-deleted chromosomes presented the haplotype B (KM19-2/XV2c-1).
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 0730-2312
    Keywords: nuclear calcium ; inositol triphosphate ; osteosarcoma cells ; osteoblast nuclei ; vitamin D ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: 1α,25-Dihydroxyvitamin D3 (1α, 25-(OH)2D3) has been shown to increase cytosolic calcium and inositol trophosphate levels in rat osteosarcoma cells (ROS 17/2.8) and to increase nuclear calcium in these cells. To determine the mechanism(s) of 1α, (OH)2D3-induced changes in the calcium, the effect of the hormone on phospholipid metabolism in isolated osteoblast nuclei wa assessed. 1α,25 (OH)2D3, 20 nM, increased inositol triphosphate levels in the nuclei after 5 min of treatment. The biologically inactive epimer, 1β,25-(OH)2D3, had no significant effect on inositol triphosphate levels. ATP, 1 mM, also increased inositol triphosphate levels in the isolated nuclei after 5 min. 1α,25-(OH)2D3, 20 nM, increased calcium in the isolated nuclei in the presence but not in the absence of extranuclear calcium with 5 min. Nuclear calcium was also increased within 5 min by ATP, 1 mM, and inositol triphosphate, 1 mM. The effects of ATP on nuclear calcium was not additive with 1α, 25-(OH)2D3, suggesting that these two agents increase nuclear calcium in these osteoblast-like cells by similar mechanisms. In summary, 1α,25-(OH)2D3 amd ATP rapidly increase inositol triphosphate levels in isolated from ROS 17/2.8 cells. The hormone, the nucleotide, and the inositol phospholipid nuclear calcium. Thus, the 1α,25-(OH)2D3 and ATP effects of nuclear calcium may be mediated by changes in phospholipid metabolism in the nuclei of these osteoblastlike cells. © Wiley-Liss, Inc.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 52 (1993), S. 330-336 
    ISSN: 0730-2312
    Keywords: gallium nitrate ; bone mineral density ; osteocalcin ; collagen ; tartrate-resistant acid phosphatase ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Gallium nitrate (GN) is an inhibitor of bone resorption and thereby may result in a change in coupled bone formation. In the present investigation the effects of GN on bone formation were studied in the rat osteosarcoma (ROS) 17/2.8 cell line and normal diploid rat osteoblasts (ROB) in vitro and the femur of rats treated in vivo, measuring mRNA levels for two osteoblast parameters, type I collagen, a marker of matrix formation, and osteocalcin, a bone specific protein and also histone H4, a marker of cell proliferation. GN, at 50 μM for 3 h, increased type I collagen mRNA levels by 132% in ROS 17/2.8 cells and by 122% in proliferating ROB cells. Osteocalcin (OC) mRNA levels were decreased by 61% in ROS 17/2.8 cells and by 97% in differentiated ROB cells. These changes occurred in the absence of any effects on cell proliferation. Seventy-day-old female rats were then treated with GN, 0.5 mg/kg/day, for 3 weeks. As previously reported, GN decreased serum calcium levels, but had no effect on lumbar or femoral bone density. In contrast to the in vitro effects, GN had no effect on type I collagen steady-state mRNA levels in the femur; however, it decreased OC steady-state mRNA levels in the femur by 58%. These results suggest that GN has similar in vitro effects in transformed and normal osteoblasts, while the collagen-stimulatory effects observed in vitro cannot be extrapolated to in vivo models. The consistent inhibition of osteocalcin in vitro and in vivo suggests a more specific target for GN that may relate to its effects in inhibiting bone resorption in normal rats.
    Additional Material: 7 Tab.
    Type of Medium: Electronic Resource
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