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51.
The mammalian genome is compacted to fit within the confines of the cell nucleus. DNA is wrapped around nucleosomes, forming the classic ‘beads‐on‐a‐string’ 10‐nm chromatin fibre. Ten‐nanometre chromatin fibres are thought to condense into 30‐nm fibres. This structural reorganization is widely assumed to correspond to transitions between active and repressed chromatin, thereby representing a chief regulatory event. Here, by combining electron spectroscopic imaging with tomography, three‐dimensional images are generated, revealing that both open and closed chromatin domains in mouse somatic cells comprise 10‐nm fibres. These findings indicate that the 30‐nm chromatin model does not reflect the true regulatory structure in vivo.  相似文献   
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A 69-year-old man underwent an emergency laparoscopic procedure after the acute appendicitis diagnosis has been established. Laparoscopic exploration showed inflamed appendix and perforation of terminal ileum with a swallowed part of the wooden toothpick. The treatment consisted of typical laparoscopic appendectomy and laparoscopic removal of the foreign body, followed by laparoscopic closure of the perforation site and lavage of the abdominal cavity. The postoperative course was uneventful and the patient was discharged from the hospital on day 3 after the operation.  相似文献   
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Barrier-to-autointegration factor (BAF or BANF1) is highly conserved in multicellular eukaryotes and was first identified for its role in retroviral DNA integration. Homozygous BAF mutants are lethal and depletion of BAF results in defects in chromatin segregation during mitosis and subsequent nuclear envelope assembly. BAF exists both in phosphorylated and unphosphorylated forms with phosphorylation sites Thr-2, Thr-3, and Ser-4, near the N terminus. Vaccinia-related kinase 1 is the major kinase responsible for phosphorylation of BAF. We have identified the major phosphatase responsible for dephosphorylation of Ser-4 to be protein phosphatase 4 catalytic subunit. By examining the cellular distribution of phosphorylated BAF (pBAF) and total BAF (tBAF) through the cell cycle, we found that pBAF is associated with the core region of telophase chromosomes. Depletion of BAF or perturbing its phosphorylation state results not only in nuclear envelope defects, including mislocalization of LEM domain proteins and extensive invaginations into the nuclear interior, but also impaired cell cycle progression. This phenotype is strikingly similar to that seen in cells from patients with progeroid syndrome resulting from a point mutation in BAF.  相似文献   
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Psoriasis is a disease state characterized by epidermal proliferation, neutrophil infiltration, along with release of the proinflammatory mediators leukotriene-B4(LTB4) and 12(R)-hydroxyeicosatetraenoic acid [12(R)-HETE]. LTB4 and 12(R)-HETE are chemoattractant to the neutrophil, the latter approximately 1000x less potent. LTB4 and 12(R)-HETE are present in psoriatic scale, the latter in quantities so much greater than LTB4 that it is proposed as a primary mediator of neutrophil infiltration in psoriasis. 12(R)-HETE, synthesized in optically pure form by a new, shorter route, was injected into the dermis of the cavine, lapine, canine, mouse and rat. At doses up to 50 mu gm per intradermal site, 12(R)-HETE was chemoattractant to the neutrophil (as assessed by dermal myeloperoxidase levels) with response in the cavine greater than canine greater than lapine greater than mouse greater than rat.  相似文献   
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Accumulating evidence indicates that microRNAs are implicated in tumor initiation and progression through negatively regulating oncogenes or tumor suppressor genes. In the present study, we report that the expression of miR-200a was significantly lower in renal cell carcinoma (RCC) specimens and RCC cell lines. Restoration of miR-200a suppressed cell growth, arrested cell cycle progression, and promoted cell apoptosis in RCC cell lines. We next used qRT-PCR array technology to identify Sirtuin 1 (SIRT1) as one of the downregulated proteins during miR-200a overexpression in 786-O cells. Following a further assay by luciferase reporter system, SIRT1 was validated as a direct target of miR-200a. Moreover, siRNA-mediated knockdown of SIRT1 could partially phenocopy the effects of miR-200a overexpression. In contrast, overexpression of truncated SIRT1 (without an endogenous 3′-UTR) could rescue the effect of miR-200a overexpression on 786-O cells, which suggested that SIRT1 3′-UTR is targeted by miR-200a specifically. These observations provide further evidence for a critical tumor-suppressive role of the miR-200a in RCC in addition to identifying a novel regulatory mechanism, which may contribute to SIRT1 upregulation in RCC.  相似文献   
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Background

Low back pain (LBP) is the symptom of a group of syndromes with heterogeneous underlying mechanisms and molecular pathologies, making treatment selection and patient prognosis very challenging. Moreover, symptoms and prognosis of LBP are influenced by age, gender, occupation, habits, and psychological factors. LBP may be characterized by an underlying inflammatory process. Previous studies indicated a connection between inflammatory response and total plasma N-glycosylation. We wanted to identify potential changes in total plasma N-glycosylation pattern connected with chronic low back pain (CLBP), which could give an insight into the pathogenic mechanisms of the disease.

Methods

Plasma samples of 1128 CLBP patients and 760 healthy controls were collected in clinical centers in Italy, Belgium and Croatia and used for N-glycosylation profiling by hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC) after N-glycans release, fluorescent labeling and clean-up. Observed N-glycosylation profiles have been compared with a cohort of 126 patients with acute inflammation that underwent abdominal surgery.

Results

We have found a statistically significant increase in the relative amount of high-branched (tri-antennary and tetra-antennary) N-glycan structures on CLBP patients' plasma glycoproteins compared to healthy controls. Furthermore, relative amounts of disialylated and trisialylated glycan structures were increased, while high-mannose and glycans containing bisecting N-acetylglucosamine decreased in CLBP.

Conclusions

Observed changes in CLBP on the plasma N-glycome level are consistent with N-glycosylation changes usually seen in chronic inflammation.

General significance

To our knowledge, this is a first large clinical study on CLBP patients and plasma N-glycome providing a new glycomics perspective on potential disease pathology.  相似文献   
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The mutagenic effects of low doses of radiation on occupationally exposed subjects were studied on lymphocyte culture using two methods: analysis of structural chromosome aberrations and micronucleus assay. The results obtained in subjects exposed to ionising radiation alone were compared to those exposed to both ionising radiation and ultrasound. A correlation between the total number of chromosome aberrations and distribution of micronuclei in the genome of somatic cells show higher deviation in the group exposed to X-ray and ultrasound than in the group exposed to X-rays alone. The degree of genome damage in occupational exposure to X-rays and ultrasound were discussed.  相似文献   
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