Frequency-dependent conductivity of insulating Si:P and Si:As near the metal-insulator transition.
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Squashing brings circumferentially separated areas of a carbon nanotube into close proximity, drastically altering the low-energy electronic properties and (in some cases) reversing standard rules for metallic versus semiconducting behavior. Such a deformation mode, not requiring motion of tube ends, may be useful for devices. Uniaxial stress of a few kbar can reversibly collapse a small-radius tube, inducing a 0.1 eV gap with a very strong pressure dependence, while the collapsed state of a larger tube is stable. The low-energy electronic properties of chiral tubes are surprisingly insensitive to collapse.
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The objectives of the present study were to evaluate the effects of scrotal insulation on sperm production, semen quality, and testicular echotexture in Bos indicus and Bos indicus x Bos taurus crossbred bulls. In one experiment, B. indicus bulls (n=12) were allocated to control and whole-scrotum insulation groups, while in a second experiment, crossbred bulls (n=21) were allocated into control, whole-scrotum, and scrotal-neck insulation groups. Insulation was applied for 4 days (start of insulation = Day 0) and semen collection and testicular ultrasonographic examinations were performed twice weekly until Day 35. Sperm concentration and total sperm output during the post-insulation period were greater in control groups, but significant differences were observed only in B. indicus bulls. Overall, sperm motility in scrotal-insulated B. indicus bulls was lower (P<0.05) than in the control group. After whole-scrotum insulation in crossbred bulls, sperm motility was lower (P<0.05) than pre-insulation levels between Days 21 and 31, and lower than control levels on Day 24. The proportion of normal sperm after whole-scrotum insulation was lower than pre-insulation and control values from Day 11 to the end of the experiment in B. indicus bulls (P<0.05 from Days 14 to 21 and on Day 27), and from Days 14 to 25 in crossbred bulls (P<0.05 on Days 14 and 18). Insulation of the scrotal neck in crossbred bulls did not significantly affect semen quality. Loose sperm heads (Day 11), midpiece defects (Days 11 and 14), and acrosome defects (Days 27 and 31) increased (P<0.05) in insulated B. indicus bulls, while proximal cytoplasmic droplets (Days 14, 18 and 27 in B. indicus; Days 24 and 27 in crossbred bulls) and sperm vacuoles (Days 18 and 21 in B. indicus; Day 18 in crossbred bulls) increased (P<0.05) in whole-scrotum insulation groups in both experiments. There was considerable variation among bulls in the incidence of specific sperm defects. The timing of appearance of sperm defects after insulation provided insights into the pathogenesis of specific abnormalities. Neither whole-scrotum nor scrotal-neck insulation affected testicular echotexture in either experiment. In conclusion, whole-scrotum insulation resulted in decreased sperm production and semen quality in B. indicus and B. indicus x B. taurus bulls, but those changes were not associated with changes in testicular echotexture.
Insulators are a class of elements that define independent domains of gene function. The Drosophila gypsy insulator is proposed to establish regulatory isolation by forming loop domains that constrain interactions between transcriptional control elements. This supposition is based upon the observation that insertion of a single gypsy insulator between an enhancer and promoter blocks enhancer function, while insertion of two gypsy insulators promotes enhancer bypass and activation of transcription. To investigate this model, we determined whether non-gypsy insulators interacted with each other and with the gypsy insulator. Pairs of scs or scs' insulators blocked enhancer function. Further, an intervening scs insulator did not block gypsy insulator interactions. Taken together, these data suggest that not all Drosophila insulators interact, with this property restricted to some insulators, such as gypsy. Three gypsy insulators inserted between an enhancer and promoter blocked enhancer function, indicating that gypsy insulator interactions may be restricted to pairs. Our studies imply that formation of loop domains may represent one of many mechanisms used by insulators to impart regulatory isolation.
Chromatin boundaries or insulators modulate enhancer-promoter interactions in complex genetic loci. However, the mechanism underlying insulator activity is not known. Previous studies showed that the activity of the Drosophila suHw insulator is abolished by the tandem arrangement (pairing) of the insulator elements, suggesting that interactions between insulators or like elements may be involved in their enhancer-blocking mechanism. To test whether such phenomenon reflects a general property of chromatin insulators, we tested the effect of pairing on enhancer-blocking activity of 11 homologous and heterologous insulator combinations using suHw, scs, or SF1 insulators. We found that, unlike the homologous pairing of suHw, the heterologous combinations of suHw with other insulators do not reduce their enhancer-blocking activity. Rather, paired insulators exhibit a higher level of enhancer-blocking activity than either single insulator alone, suggesting that they can function independently or additively. Furthermore, the analyses of two additional chromatin boundaries, scs and SF1, in homologous or heterologous pairing with other boundary elements, also showed no reduction but rather enhancement of insulator activity. We propose that diverse mechanisms may underlie insulator activity, and selective interactions among insulators could influence their function as well as the formations of independent chromatin domains.
Multiple injections of low-dose streptozotocin induce lymphocytic insulitis and autoimmune diabetes in male CD-1 mice. Prior to the onset of insulitis, macrophages infiltrate the islets (single cell insulitis) and presumably help initiate the lymphocytic response directed at streptozotocin-induced neoantigens on islet beta cells. Essential fatty acid deficiency ameliorates the lymphocytic insulitis and prevents diabetes in this model. We hypothesize that essential fatty acid deficiency, which perturbs eicosanoid pathways and blocks the production of inflammatory mediators such as leukotriene B4, might prevent or diminish the single cell insulitis and, thus, abrogate the lymphocytic response. The purpose of the study was to determine whether essential fatty acid deficiency causes any differences in the immunophenotype or the time course of single cell insulitis or insulitis after low-dose streptozotocin. Three to five essential fatty acid deficient and 3-5 control mice were treated with low-dose streptozotocin and killed on days 0, 3, 5, 8, 10, 12 and 15. Frozen sections of the pancreata were stained using an immunoperoxidase method with antibodies against mouse macrophages, CD4T-lymphocytes and CD8 T-lymphocytes. Sections were assessed for the presence and severity of single cell insulitis and insulitis. Based on cell counts in the most severely involved islet from each pancreas, there was no difference in the single cell insulitis in control and essential fatty acid deficient mice. Islets from control pancreata had a higher mean grade of lymphocytic insulitis. These findings suggest that autoimmune diabetes following low-dose streptozotocin in control mice is the result of both lymphocytic and histiocytic infiltrates with subsequent beta-cell destruction. Our results do not support the hypothesis that the protective effect of essential fatty acid deficiency is due to diminished influx of macrophages into the islets. It is, however, possible that essential fatty acid deficiency deleteriously affects macrophage function and, thus, blunts the lymphocytic response.
Tissue, external and whole animal insulation values were determined for 12 newborn male Holstein calves continuously housed for two weeks in hutches within environmental chambers in which temperature was maintained at a constant 17 degrees C (three calves) or cycled on a daily basis either between -20 degrees and -8 degrees C (three calves) or between -30 degrees and -18 degrees C (six calves). Three of the six calves at the coldest temperature were outfitted with an insulated coat. The insulated coat provided calves a 52% increase in total insulation. Tissue insulation of cold-housed calves increased 37.2% over the first two weeks of life. It was concluded that the capacity for vasoconstriction improved with age. External insulation did not change significantly except during the first week in cold-housed calves without insulated coats. External insulation values were five to eight times those of tissue insulation values for all treatment groups. This indicated that insulation of structures external to the skin (hair, bedding, ground, etc.) provided most of the insulation for calves.
Chromatin insulators are gene regulatory elements implicated in the establishment of independent chromatin domains. The gypsy insulator of D. melanogaster confers its activity through a protein complex that consists of three known components, Su(Hw), Mod(mdg4)2.2, and CP190. We have identified a factor, Drosophila Topoisomerase I-interacting RS protein (dTopors) that interacts with the insulator protein complex and is required for gypsy insulator function. In the absence of Mod(mdg4)2.2, nuclear clustering of insulator complexes is disrupted and insulator activity is compromised. Overexpression of dTopors in the mod(mdg4)2.2 null mutant rescues insulator activity and restores the formation of nuclear insulator bodies. dTopors associates with the nuclear lamina, and mutations in lamin disrupt dTopors localization as well as nuclear organization and activity of the gypsy insulator. Thus, dTopors appears to be involved in the establishment of chromatin organization through its ability to mediate the association of insulator complexes with a fixed nuclear substrate.
Chromatin insulators or boundaries are proposed to structure the chromatin fiber into functionally independent domains by promoting the formation of chromatin loops. These elements can block the communication between an enhancer and a gene when placed between them. Interestingly, it has been previously observed that two tandem copies of the Drosophila Su(Hw) insulator abolish this enhancer-blocking activity, presumably through pairing. This bypass effect has not been described with other insulators, however. In this report, we show that the insertion of binding sites for the GAGA factor (GAF) between an enhancer and the Su(Hw) insulator allows bypassing of the insulator. This bypass relies on the activity of both the GAF protein and the Mod(mdg4)-67.2 protein, a factor required for Su(Hw) insulator activity. We show that these two proteins interact in vitro and in vivo, providing molecular evidence of pairing between the GAF sites and the Su(Hw) insulator. Finally, we show that placing the Mcp boundary together with the Su(Hw) insulator between an enhancer and a promoter leads to bypass, again in a GAF- and Mod(mdg4)-dependent manner. Our data provide direct evidence that heterologous insulators can be bypassed by distal enhancers and identify the interaction between GAF and Mod(mdg4) as a possible means to regulate insulator activity.