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Mordechai S Gradstein L Pasanen A Ofir R El Amour K Levy J Belfair N Lifshitz T Joshua S Narkis G Elbedour K Myllyharju J Birk OS 《American journal of human genetics》2011,(3):438-445
Autosomal-recessive high-grade axial myopia was diagnosed in Bedouin Israeli consanguineous kindred. Some affected individuals also had variable expressivity of early-onset cataracts, peripheral vitreo-retinal degeneration, and secondary sight loss due to severe retinal detachments. Through genome-wide linkage analysis, the disease-associated gene was mapped to ~1.7 Mb on chromosome 3q28 (the maximum LOD score was 11.5 at θ = 0 for marker D3S1314). Sequencing of the entire coding regions and intron-exon boundaries of the six genes within the defined locus identified a single mutation (c.1523G>T) in exon 10 of LEPREL1, encoding prolyl 3-hydroxylase 2 (P3H2), a 2-oxoglutarate-dependent dioxygenase that hydroxylates collagens. The mutation affects a glycine that is conserved within P3H isozymes. Analysis of wild-type and p.Gly508Val (c.1523G>T) mutant recombinant P3H2 polypeptides expressed in insect cells showed that the mutation led to complete inactivation of P3H2. 相似文献
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Recognition and killing of human and murine pancreatic beta cells by the NK receptor NKp46 总被引:1,自引:0,他引:1
Gur C Enk J Kassem SA Suissa Y Magenheim J Stolovich-Rain M Nir T Achdout H Glaser B Shapiro J Naparstek Y Porgador A Dor Y Mandelboim O 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(6):3096-3103
Type 1 diabetes is an incurable disease that is currently treated by insulin injections or in rare cases by islet transplantation. We have recently shown that NKp46, a major killer receptor expressed by NK cells, recognizes an unknown ligand expressed by β cells and that in the absence of NKp46, or when its activity is blocked, diabetes development is inhibited. In this study, we investigate whether NKp46 is involved in the killing of human β cells that are intended to be used for transplantation, and we also thoroughly characterize the interaction between NKp46 and its human and mouse β cell ligands. We show that human β cells express an unknown ligand for NKp46 and are killed in an NKp46-dependent manner. We further demonstrate that the expression of the NKp46 ligand is detected on human β cells already at the embryonic stage and that it appears on murine β cells only following birth. Because the NKp46 ligand is detected on healthy β cells, we wondered why type 1 diabetes does not develop in all individuals and show that NK cells are absent from the vicinity of islets of healthy mice and are detected in situ in proximity with β cells in NOD mice. We also investigate the molecular mechanisms controlling NKp46 interactions with its β cell ligand and demonstrate that the recognition is confined to the membrane proximal domain and stalk region of NKp46 and that two glycosylated residues of NKp46, Thr(125) and Asn(216), are critical for this recognition. 相似文献
136.
Mordechai E. Kislev Orit Simchoni Yoel Melamed Lior Maroz 《Vegetation History and Archaeobotany》2011,20(6):579-584
For thousands of years, flax was a winter crop of major importance in the ancient Levant, second only to wheat and barley. It was cultivated from the beginning of the early Neolithic period through to Roman times and it is still grown there today. Flax seeds (linseed) contain high concentrations of two essential polyunsaturated fatty acids—linoleic acid (ω-6) and α-linolenic acid (ω-3), which cannot be produced by the human body. Their oxidation occurs rapidly in the air. So, long term storage of linseed needed airtight containers, and tightly stoppered bottles could be used to keep its oil as a remedy. However, were flax seeds consumed as a food, oil or medicament in ancient periods? How commonly were flax seeds eaten? From archaeobotanical finds of flax seed, it is difficult to determine whether the flax was cultivated for fibres alone or for its seeds that can be cold-pressed to release the valuable oil. We have therefore studied ancient written documents describing various uses of flax seeds, including their consumption as a food supplement and uses in medical applications. We conclude that until recently flax was grown primarily for textile fibres, and only smaller quantities of flax seeds were consumed. So, the flax seed finds from the early Iron Age site of Tel Beth-Shean also represent seed consumption or oil extraction. 相似文献
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Cancellous and cortical morselized allograft in revision total hip replacement: A biomechanical study of implant stability 总被引:3,自引:0,他引:3
To restore femoral intramedullary bone stock loss in revision surgery of failed total hip arthroplasties, impacted morselized cancellous allograft is recommended. This study investigated the mechanical properties of both impacted cortical (group A) and cancellous (group B) morselized bone graft for reconstruction of femoral bones. Ten matched pairs of fresh frozen human femora were prepared by over-reaming to create a smooth-walled cortical shell. Each pair had one cortical and one cancellous impacted morselized allograft and cement. Stem subsidence was evaluated by a cyclic axial load, which was applied by a servohydraulic test. The stem subsidence was measured for initial subsidence (subsidence at the first 1000 cycles), the total axial subsidence (subsidence at the end of cycles under load) and the final axial subsidence (subsidence after the unloading phase). Torque test was measured by torsional loads through the prosthetic femoral heads. Total axial subsidence was significantly higher in group B (mean: 1.32+/-0.32 mm) compared to group A (mean: 0.94+/-0.26 mm) (P<0.01).There was no significant difference between the two groups in terms of initial subsidence (P=0.09) and final axial subsidence.The mean maximum torque before failure was 39.5+/-22.2 N-m for the cortical morselized allograft and 32.5+/-18.1N-m for cancellous.We concluded that impacted morselized cortical bone graft used for reconstruction of contained femoral bone loss in revision hip arthroplasty, may reduce the stem subsidence. Further animal experimentation for mechanical and histological evaluation of in vivo application is warranted. 相似文献
139.
Yonath H Marek-Yagel D Resnik-Wolf H Abu-Horvitz A Baris HN Shohat M Frydman M Pras E 《Journal of applied genetics》2011,52(4):437-441
The purpose of this study was to identify a gene causing non-syndromic X-linked mental retardation in an extended family, taking advantage of the X chromosome inactivation status of the females in order to determine their carrier state. X inactivation in the females was determined with the androgen receptor methylation assay; thereafter, the X chromosome was screened with evenly spaced polymorphic markers. Once initial linkage was identified, the region of interest was saturated with additional markers and the males were added to the analysis. Candidate genes were sequenced. Ten females showed skewed inactivation, while six revealed a normal inactivation pattern. A maximal lod score of 5.54 at θ?=?0.00 was obtained with the marker DXS10151. Recombination events mapped the disease gene to a 17.4-Mb interval between the markers DXS10153 and DXS10157. Three candidate genes in the region were sequenced and a previously described missense mutation (P375L) was identified in the ACSL4/FACL4 gene. On the basis of the female X inactivation status, we have mapped and identified the causative mutation in a gene causing non-syndromic X-linked mental retardation. 相似文献
140.