铁代谢与铁调素hepcidin

2005-2006 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Significance of somatic mutations and content alteration of mitochondrial DNA in esophageal cancer

BACKGROUND: The roles of mitochondria in energy metabolism, the generation of ROS, aging, and the initiation of apoptosis have implicated their importance in tumorigenesis. In this study we aim to establish the mutation spectrum and to understand the role of somatic mtDNA mutations in esophageal cancer. METHODS: The entire mitochondrial genome was screened for somatic mutations in 20 pairs (18 esophageal squamous cell carcinomas, one adenosquamous carcinoma and one adenocarcinoma) of tumor/surrounding normal tissue of esophageal cancers, using temporal temperature gradient gel electrophoresis (TTGE), followed by direct DNA sequencing to identify the mutations. RESULTS: Fourteen somatic mtDNA mutations were identified in 55% (11/20) of tumors analyzed, including 2 novel missense mutations and a frameshift mutation in ND4L, ATP6 subunit, and ND4 genes respectively. Nine mutations (64%) were in the D-loop region. Numerous germline variations were found, at least 10 of them were novel and five were missense mutations, some of them occurred in evolutionarily conserved domains. Using real-time quantitative PCR analysis, the mtDNA content was found to increase in some tumors and decrease in others. Analysis of molecular and other clinicopathological findings does not reveal significant correlation between somatic mtDNA mutations and mtDNA content, or between mtDNA content and metastatic status. CONCLUSION: Our results demonstrate that somatic mtDNA mutations in esophageal cancers are frequent. Some missense and frameshift mutations may play an important role in the tumorigenesis of esophageal carcinoma. More extensive biochemical and molecular studies will be necessary to determine the pathological significance of these somatic mutations

Controlling Cherenkov angles with resonance transition radiation

Cherenkov radiation provides a valuable way to identify high energy particles in a wide momentum range, through the relation between the particle velocity and the Cherenkov angle. However, since the Cherenkov angle depends only on material's permittivity, the material unavoidably sets a fundamental limit to the momentum coverage and sensitivity of Cherenkov detectors. For example, Ring Imaging Cherenkov detectors must employ materials transparent to the frequency of interest as well as possessing permittivities close to unity to identify particles in the multi GeV range, and thus are often limited to large gas chambers. It would be extremely important albeit challenging to lift this fundamental limit and control Cherenkov angles as preferred. Here we propose a new mechanism that uses constructive interference of resonance transition radiation from photonic crystals to generate both forward and backward Cherenkov radiation. This mechanism can control Cherenkov angles in a flexible way with high sensitivity to any desired range of velocities. Photonic crystals thus overcome the severe material limit for Cherenkov detectors, enabling the use of transparent materials with arbitrary values of permittivity, and provide a promising option suited for identification of particles at high energy with enhanced sensitivity.Comment: There are 16 pages and 4 figures for the manuscript. Supplementary information with 18 pages and 5 figures, appended at the end of the file with the manuscript. Source files in Word format converted to PDF. Submitted to Nature Physic

Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium

Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored. © 2013 Mishra et al

The addition of a pH-sensitive gel improves microemulsion stability for the targeted removal of colonic ammonia

<p>Abstract</p> <p>Background</p> <p>We prepared an oral W/O microemulsion for the removal of colonic ammonia (ME-RCA). The effect of this microemulsion was influenced by the digestion process in the gastrointestinal tract. In this paper, we aim to show that stability was improved by using a microemulsion-based gel for the removal of colonic ammonia (MBG-RCA).</p> <p>Methods</p> <p>MBG-RCA was prepared by adding sodium alginate to the ME-RCA. MBG-RCA and ME-RCA were passed through a simulated gastrointestinal environment, and the amount of colonic ammonia present was then determined by titration with a standard solution of hydrochloric acid. The pH of the gastrointestinal fluid was measured using a pH test paper and the size and form of the microemulsions were examined under the microscope. 18 healthy rats were randomly divided into three groups, fasted for 24 hours and allowed to drink normally. Three-way pipes were placed at the gastroduodenal junction in Group I, and at the terminal ileum in Group II. After the intragastric administration of ME-RCA, the stomach contents in Group I, the effluent from the terminal ileum in Group II and discharge from the anus in Group III were collected. The pH values of the gastrointestinal juice were measured by the pH test paper and those of the colon were determined by a universal indicator. These animal experiments were also used to test the effect of MBG-RCA.</p> <p>Results</p> <p>MBG-RCA showed a better removal rate of artificial colonic ammonia than ME-RCA (P < 0.05). The decrease in pH value of the artificial small intestinal fluid due to ME-RCA did not occur when MBG-RCA was used. In the simulated gastrointestinal process, MBG-RCA maintained greater stability and released the emulsion (ME-RCA) in the colonic fluid. In the gastrointestinal tract of normal SD rats, ME-RCA decreased in size and lost its stable form after entering the small intestine, while MBG-RCA remained stable and intact emulsion-drops were observed from the anus. Neither substance had any effect on the pH of the stomach or colon of normal rats (partly because normal rats were fasted for 24 hours and allowed to drink normally, which resulted in a low level of ammonia production in the colon). Unlike ME-RCA, MBG-RCA did not reduce the pH of the small intestine.</p> <p>Conclusions</p> <p>MBG-RCA was more stable in the gastrointestinal tract and more effective at removing colonic ammonia when a higher concentration of ammonia was present. This made it possible to achieve the targeted removal of colonic ammonia and is a promising method to prevent hepatic encephalopathy (HE) in future studies.</p

Narrowband Biphotons: Generation, Manipulation, and Applications

In this chapter, we review recent advances in generating narrowband biphotons with long coherence time using spontaneous parametric interaction in monolithic cavity with cluster effect as well as in cold atoms with electromagnetically induced transparency. Engineering and manipulating the temporal waveforms of these long biphotons provide efficient means for controlling light-matter quantum interaction at the single-photon level. We also review recent experiments using temporally long biphotons and single photons.Comment: to appear as a book chapter in a compilation "Engineering the Atom-Photon Interaction" published by Springer in 2015, edited by A. Predojevic and M. W. Mitchel

Temporal Trends in Vertebral Size and Shape from Medieval to Modern-Day

Human lumbar vertebrae support the weight of the upper body. Loads lifted and carried by the upper extremities cause significant loading stress to the vertebral bodies. It is well established that trauma-induced vertebral fractures are common especially among elderly people. The aim of this study was to investigate the morphological factors that could have affected the prevalence of trauma-related vertebral fractures from medieval times to the present day. To determine if morphological differences existed in the size and shape of the vertebral body between medieval times and the present day, the vertebral body size and shape was measured from the 4th lumbar vertebra using magnetic resonance imaging (MRI) and standard osteometric calipers. The modern samples consisted of modern Finns and the medieval samples were from archaeological collections in Sweden and Britain. The results show that the shape and size of the 4th lumbar vertebra has changed significantly from medieval times in a way that markedly affects the biomechanical characteristics of the lumbar vertebral column. These changes may have influenced the incidence of trauma- induced spinal fractures in modern populations

The contribution of PA-X to the virulence of pandemic 2009 H1N1 and highly pathogenic H5N1 avian influenza viruses

PA-X is a novel protein encoded by PA mRNA and is found to decrease the pathogenicity of pandemic 1918 H1N1 virus in mice. However, the importance of PA-X proteins in current epidemiologically important influenza A virus strains is not known. In this study, we report on the pathogenicity and pathological effects of PA-X deficient 2009 pandemic H1N1 (pH1N1) and highly pathogenic avian influenza H5N1 viruses. We found that loss of PA-X expression in pH1N1 and H5N1 viruses increased viral replication and apoptosis in A549 cells and increased virulence and host inflammatory response in mice. In addition, PA-X deficient pH1N1 and H5N1 viruses up-regulated PA mRNA and protein synthesis and increased viral polymerase activity. Loss of PA-X was also accompanied by accelerated nuclear accumulation of PA protein and reduced suppression of PA on non-viral protein expression. Our study highlights the effects of PA-X on the moderation of viral pathogenesis and pathogenicity

Factor XII mutations, estrogen-dependent inherited angioedema, and related conditions

The clinical, biochemical and genetic features of the conditions known as estrogen-dependent inherited angioedema, estrogen-associated angioedema, hereditary angioedema with normal C-1 inhibitor, type III angioedema, or factor XII angioedema are reviewed. Discussion emphasizes pathogenesis, diagnosis, and management

The Spider Effect: Morphological and Orienting Classification of Microglia in Response to Stimuli in Vivo

The different morphological stages of microglial activation have not yet been described in detail. We transected the olfactory bulb of rats and examined the activation of the microglial system histologically. Six stages of bidirectional microglial activation (A) and deactivation (R) were observed: from stage 1A to 6A, the cell body size increased, the cell process number decreased, and the cell processes retracted and thickened, orienting toward the direction of the injury site; until stage 6A, when all processes disappeared. In contrast, in deactivation stages 6R to 1R, the microglia returned to the original site exhibiting a stepwise retransformation to the original morphology. Thin highly branched processes re-formed in stage 1R, similar to those in stage 1A. This reverse transformation mirrored the forward transformation except in stages 6R to 1R: cells showed multiple nuclei which were slowly absorbed. Our findings support a morphologically defined stepwise activation and deactivation of microglia cells