Local structural variations near twins in YBa2Cu3O7- delta.
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K36.16 is an AKR H-2k thymoma which expresses an aberrant H-2Dd-like allospecificity, does not have a detectable amount of the H-2Kk syngeneic antigen and grows very easily in syngeneic mice. By DNA-mediated gene transfer experiments, we were able to obtain transformed clones which do express the H-2Kk molecules and are rejected by AKR mice. Southern hybridization was performed to assess whether any gross changes had occurred in the K36.16 H-2K locus or elsewhere in the MHC, which might explain the lack of H-2K expression and/or the presence of the aberrant H-2Dd-like allospecificity. Specific H-2 class I DNA probes were used to compare the K36.16 genomic DNA with normal AKR thymus DNA after digestion with a variety of restriction enzymes. After hybridization with the pH-2IIa probe a 2.8 kb 'Hind III' fragment was identified in the K36.16 genomic DNA which is absent from AKR DNA. The pH-2IIa probe detects the third, transmembrane and cytoplasmic domains of class I genes. Although these changes are indicative of MHC genome modifications it is not yet possible to link these specific Southern blot pattern variations with the phenotypic changes mentioned above.
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This study examined 3-dimensional (3D) distribution of sectors with contrasting density in the equine third metacarpal (McIII) and third metatarsal (MtIII) bones with a view to explaining the aetiology of distal condylar fractures. Macroradiography and computed tomographic (CT) imaging were used in the nondestructive study of bones obtained from horses, most of which were Thoroughbreds in race training. Distal condylar regions of McIII and MtIII were also studied in microradiographs of 100 microm thick mediolateral sections cut perpendicular to the dorsal and palmar/plantar articular surfaces. Qualitative and quantitative results from all methods used (radiography, CT and microradiographic stereology) demonstrated a densification (sclerosis) of subchondral bone located in the palmar/plantar regions of the medial and lateral condyles of both McIII and MtIII. Substantial density gradients between the denser condyles and the subchondral bone of the sagittal groove were shown to equate with anatomical differences in loading intensity during locomotion. It is hypothesised that such differences in bone density results in stress concentration at the palmar/plantar aspect of the condylar grooves, which may predispose to fracture.
Studies on erucyl alcohol ethoxylated with 40 and 47 units, and on behenyl alcohol ethoxylated with 33 and 43 units, gave values of 106, 101, 271, and 304 (all X 10(3)) for the micellar weight, 51,42,152, and 137 for the aggregation numbers, and 257,362,209, and 311 moles water mol-1 surfactant for the micellar hydration, respectively. Measurements of the solubilization of azobenzene, cortisone acetate, griseofulvin, sulphadiazine, phenylbutazone, betamethasone, tolbutamide, and menaphthone showed that the erucyl derivatives were better solubilizers than the behenyl compounds, and that solubilization increased as the polyoxyethylene chain was shortened; this change was more pronounced with the erucyl compounds.
Novel non-ionic surfactants have been synthesized in which a polar group (either an ether or a keto group) has been introduced into the hydrocarbon chain of an octadecylpolyoxyethylene glycol monoether (C18En) with an oxyethylene chain length, n, of 17-18 units. Light scattering studies have indicated aggregation numbers for these semi-polar surfactants in aqueous solution of between 55-65% of that of an unsubstituted octadecylpolyoxyethylene glycol monoether, C18E22. The solubilizing capacities of the semi-polar surfactant micelles for test compounds which were mainly solubilized at the polyoxyethylene/core interface were lower than those of C18E22 whilst solubilizates which exhibited a reasonable degree of solubility in both the interface and the micellar core showed an increased solubilization.
The surface properties of a series of non-ionic surfactants in which a polar group (either an ether or a keto group) has been introduced into a hydrocarbon chain of octadecylpolyoxyethylene glycol monoether (C18E17-19) have been investigated. Surface tension measurements indicated that the critical micelle concentrations for these semi-polar surfactants in aqueous solution were all significantly higher than those of C18E22, the corresponding unsubstituted octadecylpolyoxyethylene glycol monoether. The minimum areas per molecule of the semi-polar surfactants in the surface monolayer were all larger than the area obtained for C18E22, from which it was concluded that the hydrophobe, and not the polyoxyethylene chain was the main determinant of surface area.
Charcot-Marie-Tooth (CMT) neuropathy is a clinically and genetically heterogeneous group of diseases characterized by the length-dependent axonal degeneration of peripheral nerves. We previously mapped a rare form of X-linked CMT, CMTX3, to a 5.7-Mb interval on chromosome Xq26.3-q27.1 and excluded the coding region of all known genes in the linkage interval for mutations. Whole genome sequencing subsequently identified a 78-kb region of chromosome 8q24.3 that had been duplicated and inserted into the CMTX3 locus between the genes HAPSTR2 and SOX3. The 78-kb insertion, which contains a partial transcript of ARHGAP39, fully segregated in families with CMTX3 and was absent in neurologically normal controls. To retain the CMTX3 insertion and investigate its consequences in appropriate neuronal tissue, we generated induced pluripotent stem cells (iPSCs) from CMTX3 fibroblasts. Using bulk RNA sequencing of patient-derived spinal motor neurons, ARHGAP39 was deemed nonpathogenic by excluding both the formation of novel fusion transcripts and dosage effects from the partial duplication. Subsequent NanoString expression analyses of candidate genes within the CMTX3 locus, across different stages of neuronal differentiation, identified spatiotemporal dysregulation of SOX3. NanoString showed reduced SOX3 expression in patient iPSCs. RNA sequencing detected SOX3 downregulation in CMTX3 neuroepithelial progenitor cells, which was further confirmed by quantitative proteomics. Given the early onset and relatively rapid progression of CMTX3, these data prioritise SOX3 as a leading candidate gene, consistent with its role as one of the earliest transcription factors expressed in the developing nervous system and a key regulator of neuronal fate.
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Measurement of human chorionic gonadotrophin (hCG) is used in many areas of clinical medicine. Recent interest has focused on the stability of this molecule and its fragments during sample storage. In the body hCG is degraded and removed by specific metabolic processes which begin while the molecule is in the bloodstream. In particular, the receptor binding loop of the beta subunit is cut or 'nicked', initiating a catabolic cascade. Furthermore, the extent and nature of glycosylation is believed to have a significant influence on this process. In these studies we incubated seven glycoforms of hCG, each with different degrees of 'nicking', in phosphate-buffered saline, serum, defibrinated blood and urine from healthy non-pregnant women, under varying conditions. Degradation was expressed as the molar increase in free beta subunit. Under all conditions there was a steady dissociation of hCG over time, the process being more rapid at higher temperatures. 'Nicked' hCG dissociated more rapidly than did non-'nicked' hCG. Glycosylation reduced the rate of dissociation. Dissociation was most rapid in urine and buffer solutions, and slowest in serum and defibrinated blood.
alpha 2-Macroglobulin (alpha 2M) is a major plasma protease inhibitor that has been studied because of its suggested role in the pathology of cystic fibrosis (CF). A panel of monoclonal antibodies specific for human alpha 2M were produced and screened for their ability to bind to a number of human alpha 2M samples. We have used these antibodies to characterize individual antigenic sites in this protein. alpha 2M was purified from plasma by polyethylene glycol precipitation followed by zinc chelate chromatography. A total of 23 alpha 2M samples in the native configuration, as well as the nucleophile-treated configuration, were screened by the panel of 18 monoclonal antibodies in an enzyme-linked immunosorbent assay procedure. Five of the samples tested were from individuals with cystic fibrosis. alpha 2M from family members of two of these patients was subsequently tested for reactivity with the monoclonal antibodies. One antibody, SAM94, exhibited a significant difference in binding to alpha 2M obtained from CF patients as compared with control individuals. This difference was particularly apparent in the binding of SAM94 to the nucleophile-treated CF alpha 2M; SAM94 showed significantly reduced binding to four of five unrelated CF individuals (p less than 0.005) and three of four cystic fibrosis obligate heterozygotes (p less than 0.005).
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The modulus of elasticity of cubes of cancellous bone, tested in three orthogonal directions, was measured along with apparent density, fabric (measured using image analysis techniques), connectivity and mineral volume fraction. Multiple regression was used to relate Young's modulus and the explanatory variables. The most important explanatory variable was apparent density; fabric was also important. Connectivity was highly correlated with apparent density, and so it is difficult to assign relative weights to these two variables. However, both have a significant, and separate, effect on Young's modulus. The total variance in Young's modulus explained by these three variables was about 85 per cent. This implies that other explanatory variables are either unimportant or highly correlated with the variables listed above. Mineral volume fraction is shown to be an unimportant variable, and arguments are produced why this is to be expected, even though it is highly important in explaining the variation in Young's modulus of compact bone.
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The jugular foramen was examined in 300 Anatolian skulls from the 17th and 18th centuries. In 61.6% the foramen was larger on the right and in 26% on the left, with the remainder being of almost equal size. An obvious dome caused by a superior jugular bulb was present bilaterally in 49%, on the right only in 36%, on the left only in 6%; it was absent bilaterally in 10.3%. Complete bony septation occurred in 5.6% on the right and in 4.3% on the left, partial septation was observed in 2.6% on the right and in 19.6% on the left. Another foramen which is completely separated by a spicule of bone and which transmits the inferior petrosal sinus was present in 5.6% of skulls on the right and in 4.6% on the left.