Deinococcus radiodurans is extremely resistant to ionizing radiation. How this bacterium can grow under chronic γ radiation 50 grays (Gy) per hour or recover from acute doses greater than 10 kGy is ...unknown. We show that D. radiodurans accumulates very high intracellular manganese and low iron levels compared with radiation-sensitive bacteria and that resistance exhibits a concentration-dependent response to manganous chloride Mn(II). Among the most radiation-resistant bacterial groups reported, Deinococcus, Enterococcus, Lactobacillus, and cyanobacteria accumulate Mn(II). In contrast, Shewanella oneidensis and Pseudomonas putida have high iron but low intracellular manganese concentrations and are very sensitive. We propose that Mn(II) accumulation facilitates recovery from radiation injury.
The human ABCG1 gene encodes a member of the ATP-binding cassette (ABC) superfamily of transporter proteins and is highly induced when macrophages are incubated with oxysterols. Using mRNA from ...oxysterol-treated human THP-1 cells together with 5'-rapid amplification of cDNA ends and polymerase chain reaction, we identified a novel ABCG1 transcript that encodes a putative protein of 786 residues containing a new amino terminus of 203 amino acids. Characterization of the genomic organization and structure of the human ABCG1 gene demonstrates that: (i) the gene consists of 23 exons spanning 98 kilobase pairs (kb) on chromosome 21q22.3, (ii) the 203 amino acids are encoded on three previously unidentified exons, 8-10, and (iii) a promoter, containing a TATA box and two liver X receptor (LXR) alpha response elements (LXREs), is located upstream of exon 8. Northern analysis using exon-specific probes confirms that oxysterol treatment results in >10-fold induction of ABCG1 transcripts that are derived from either exons 8-23 or exons 5, 7, and 11-23. Electromobility shift assays demonstrate that LXRalpha and retinoid X receptor alpha bind to the two LXREs in intron 7. Cells were transiently transfected with reporter luciferase constructs under the control of either (i) 9 kb of genomic DNA corresponding to intron 7 and part of exon 8 and containing either wild-type or mutant LXREs or (ii) two copies of the wild-type or mutant LXRE. In all cases, the wild-type construct was regulated in an LXR- and oxysterol-dependent manner, and this regulation was attenuated when the LXREs were mutated. In conclusion, the human ABCG1 gene contains multiple promoters, spans more than 98 kb and comprises 23 exons that give rise to alternative transcripts encoding proteins with different amino-terminal sequences. Elucidation of the various roles of different ABCG1 isoforms will be important for our understanding of mammalian cholesterol homeostasis.
According to local legend, towards the end of his life people noticed that a mere touch of his hand cured many ailments, especially mental illnesses, and stories spread about his healing powers. ...According to the legend of the temple, and an idea widely held among the people who come for help, it is the experience of residing in the temple for a period of time, rather than therapy provided by a healer, that brings relief from mental illnesses.
Groove pancreatitis is a rare type of segmental pancreatitis characterized by fibrous scars of the anatomic space between the dorsocranial part of the head of the pancreas, the duodenum, and the ...common bile duct.
A 40-year-old man, with a past history of chronic alcohol consumption presented with epigastric pain radiating to the back and intermittent vomiting and a weight loss of 9 kg. A CT of the abdomen revealed swelling of the pancreatic head, a hypodense mass and duodenal wall thickening with luminal narrowing. Peripancreatic fluid and dense strands were also seen. Upper gastrointestinal endoscopy revealed an edematous, shiny, reddish raised mucosa having a polypoid appearance with narrowing of the second portion of the duodenum. Histological examination of the duodenal biopsy specimens showed preservation of the crypt-villus ratio, and the submucosa showed Brunner gland hyperplasia. These findings appeared consistent with the diagnosis of groove pancreatitis. Presently, the patient is on conservative medical management with analgesics, proton pump inhibitors and a pancreatic enzyme supplement.
Groove pancreatitis often masquerades as pancreatic head carcinoma. This condition should be kept in mind when making the differential diagnosis between pancreatic masses and duodenal stenosis. In all cases of focal pancreatitis involving the head or uncinate process of the pancreas with involvement of the adjacent duodenum, the possibility of groove pancreatitis should be considered.
LXRα is a nuclear receptor that has previously been shown to regulate the metabolic conversion of cholesterol to bile acids. Here we define a role for this transcription factor in the control of ...cellular cholesterol efflux. We demonstrate that retroviral expression of LXRα in NIH 3T3 fibroblasts or RAW264.7 macrophages and/or treatment of these cells with oxysterol ligands of LXR results in 7- to 30-fold induction of the mRNA encoding the putative cholesterol/phospholipid transporter ATP-binding cassette (ABC)A1. In contrast, induction of ABCA1 mRNA in response to oxysterols is attenuated in cells that constitutively express dominant-negative forms of LXRα or LXRβ that lack the AF2 transcriptional activation domain. We further demonstrate that expression of LXRα in NIH 3T3 fibroblasts and/or treatment of these cells with oxysterols is sufficient to stimulate cholesterol efflux to extracellular apolipoprotein AI. The ability of oxysterol ligands of LXR to stimulate efflux is dramatically reduced in Tangier fibroblasts, which carry a loss of function mutation in the ABCA1 gene. Taken together, these results indicate that cellular cholesterol efflux is controlled, at least in part, at the level of transcription by a nuclear receptor-signaling pathway. They suggest a model in which activation of LXRs by oxysterols in response to cellular sterol loading leads to induction of the ABCA1 transporter and the stimulation of lipid efflux to extracellular acceptors. These findings have important implications for our understanding of mammalian cholesterol homeostasis and suggest new opportunities for pharmacological regulation of cellular lipid metabolism.
Linear predictive techniques perform poorly when used with color-mapped images where pixel values represent indices that point to color values in a look-up table. Reordering the color table, however, ...can lead to a lower entropy of prediction errors. In this paper, we investigate the problem of ordering the color table such that the absolute sum of prediction errors is minimized. The problem turns out to be intractable, even for the simple case of one-dimensional (1-D) prediction schemes. We give two heuristic solutions for the problem and use them for ordering the color table prior to encoding the image by lossless predictive techniques. We demonstrate that significant improvements in actual bit rates can be achieved over dictionary-based coding schemes that are commonly employed for color-mapped images.
Molecular statics and molecular dynamics, and constant temperature, constant volume (NVT) simulations, were performed to determine the core structure and critical stress for motion of a/3〈112¯0〉 ...screw dislocations in α-Ti at temperatures ranging from 0 to 50K using a modified embedded atom method (MEAM) potential. Five different core structures were obtained for the a/3〈112¯0〉 screw dislocations in α-Ti, one completely spread on the prism plane, three others partially spread on the prism plane and partially spread on the pyramidal and basal planes, and one with predominantly Shockley partial splitting on the basal plane. The core completely spread on the prism plane is found to be the lowest energy structure. The Peierls stress for the minimum energy structure completely spread on the prism plane at 0K is found to be a high value of 6.875×10−3μ, where μ is the shear modulus and is independent of the orientation of the applied stress. It is shown that this high Peierls stress at 0K is a consequence of the angular interactions in the MEAM potential. The kink-pair formation energy at zero applied stress is found to be low and equal to 0.16eV. NVT molecular dynamics simulations show that the minimum stress required to move the screw dislocations by kink-pair formation at temperatures ranging from 5 to 50K is significantly lower than the 0K Peierls stress value. A classical phenomenological kink-pair model is fitted to the molecular dynamics data and used to correct for the significantly lower strain rate of deformation present in experiments as compared to molecular dynamics simulations. The corrected simulation data are in reasonable agreement with low-temperature experimental observations of yield stress in single-crystal α-Ti oriented for a/3〈112¯0〉 prism slip. The developed kink-pair model for prism slip in α-Ti will be useful in higher length scale crystal plasticity models for the deformation behavior of α-Ti.
Deinococcus radiodurans R1 (DEIRA) is a bacterium best known for its extreme resistance to the lethal effects of ionizing radiation, but the molecular mechanisms underlying this phenotype remain ...poorly understood. To define the repertoire of DEIRA genes responding to acute irradiation (15 kGy), transcriptome dynamics were examined in cells representing early, middle, and late phases of recovery by using DNA microarrays covering ≈94% of its predicted genes. At least at one time point during DEIRA recovery, 832 genes (28% of the genome) were induced and 451 genes (15%) were repressed 2-fold or more. The expression patterns of the majority of the induced genes resemble the previously characterized expression profile of recA after irradiation. DEIRA recA, which is central to genomic restoration after irradiation, is substantially up-regulated on DNA damage (early phase) and down-regulated before the onset of exponential growth (late phase). Many other genes were expressed later in recovery, displaying a growth-related pattern of induction. Genes induced in the early phase of recovery included those involved in DNA replication, repair, and recombination, cell wall metabolism, cellular transport, and many encoding uncharacterized proteins. Collectively, the microarray data suggest that DEIRA cells efficiently coordinate their recovery by a complex network, within which both DNA repair and metabolic functions play critical roles. Components of this network include a predicted distinct ATP-dependent DNA ligase and metabolic pathway switching that could prevent additional genomic damage elicited by metabolism-induced free radicals.
PDF
