Loss of heterozygosity in multistage carcinogenesis of esophageal carcinoma at high-incidence area in Henan Province, China

Aim: Microsatellites are the repeated DNA sequences scattered widely within the genomes and closely linked with many important genes. This study was designed to characterize the changes of microsatellite DNA loss of heterozygosity (LOH) in esophageal carcinogenesis. Methods: Allelic deletions in 32 cases of matched precancerous, cancerous and normal tissues were examined by syringe microdissection under an anatomic microscope and microsatellite polymorphism analysis using 15 polymorphic markers on chromosomes 3p, 5q, 6p, 9p, 13q, 17p, 17q and 18q. Results: Microsatellite DNA LOH was observed in precancerous and cancerous tissues, except D9S1752. The rate of LOH increased remarkably with the lesions progressed from basal cell hyperplasia (BCH) to squamous cell carcinoma (SCC) (P60%). LOH loci were different in precancerous and cancerous tissues. LOH in D3S1234 and TP53 was the common event in different lesions from the same patients. Conclusion: Microsatellite DNA LOH occurs in early stage of human esophageal carcinogenesis, even in BCH. With the lesion progressed, gene instability increases, the accumulation of this change may be one of the important mechanisms driving precancerous lesions to cancer. © 2005 The WJG Press and Elsevier Inc. All rights reserved.published_or_final_versio

Solar influenced late Holocene temperature changes on the northern Tibetan Plateau

Considerable efforts have been made to extend temperature records beyond the instrumental period through proxy reconstructions, in order to further understand the mechanisms of past climate variability. Yet, the global coverage of existing temperature records is still limited, especially for some key regions like the Tibetan Plateau and for earlier times including the Medieval Warm Period (MWP). Here we present decadally-resolved, alkenone-based, temperature records from two lakes on the northern Tibetan Plateau. Characterized by marked temperature variability, our records provide evidence that temperatures during the MWP were slightly higher than the modern period in this region. Further, our temperature reconstructions, within age uncertainty, can be well correlated with solar irradiance changes, suggesting a possible link between solar forcing and natural climate variability, at least on the northern Tibetan Plateau. © 2013 The Author(s).published_or_final_versio

食管癌原發灶與淋巴結轉移灶細胞染色體變化特征的比較

BACKGROUND & OBJECTIVE: Local lymph node and blood metastasis could occur at early stage of esophageal squamous cell carcinoma (ESCC), which may be the key factors of its recurrence and poor prognosis. However, the mechanism of ESCC metastasis is unclear. This study was to analyze the genetic changes in primary lesion and lymph node metastases of ESCC, to screen for and locate ESCC metastasis-related genes. METHODS: Genomic alterations in 15 pairs of primary lesions and matched metastatic lymph nodes of ESCC were analyzed by comparative genomic hybridization (CGH). RESULTS: In the 15 pairs of tissues, the most common chromosomal alterations were the gains of 3q, 8q, 6p, 20p, 5p, 18p, 2p, 2q and 1q, and the losses of 10p, 10q, 17p, 18q, 4p and 13q. Of these changes, the most significant finding was the gain of 6p with a frequency of 47% in metastatic lymph nodes and 13% in primary lesions, and the gain of 20p with a frequency of 73% in metastatic lymph nodes and 33% in primary lesions. The second interesting finding was the loss of 10p with a frequency of 53% in metastatic lymph nodes and 13% in primary lesions, and the loss of 10q with a frequency of 47% in metastatic lymph nodes and 13% in primary lesions. CONCLUSION: The gains of 6p and 20p and the losses of 10p and 10q are common genomic alterations in primary lesion and lymph node metastases of ESCC, which may code ESCC metastasis-related genes.背景與目的:食管癌早期可發生局部淋巴或血行轉移,這是導致復發和預后差的主要原因。但是,食管癌轉移發生的分子機制尚不清楚。本研究旨在分析食管癌原發灶和淋巴結轉移灶腫瘤細胞染色體變化的特征,尋找或定位與食管癌轉移相關基因,加深對其轉移機制的了解。方法:應用比較基因組雜交技術(comparativegenomichybridization,CGH)分析15例食管癌患者原發灶和其對應的淋巴結轉移灶的染色體基因組改變。結果:最常見染色體DNA拷貝數增加的部位是3q,8q,6p,20p,5p,18p,2p,2q,1q;常見的染色體DNA拷貝數丟失的部位是10p,10q,17p,18q,4p,13q。其中,最有意義的發現是6p增加(原發灶:2/15,13%,轉移灶:7/15,47%),20p增加(原發灶:5/15,33.3%,轉移灶:11/15,73.3%)。第二個發現是10p丟失(原發灶:2/15,13.3%,轉移灶:8/15,53%),10q丟失(原發灶:2/15,13.3%,轉移灶:7/15,46.6%)。結論:食管癌原發灶和淋巴結轉移灶細胞染色體基因組改變最顯著的部位是6p,20p的增加和10p,10q的丟失;這些部位可能存在與食管癌細胞淋巴結轉移相關的基因。link_to_subscribed_fulltex

Fabrication of Densely Packed AlN Nanowires by a Chemical Conversion of Al2O3Nanowires Based on Porous Anodic Alumina Film

Porous alumina film on aluminum with gel-like pore wall was prepared by a two-step anodization of aluminum, and the corresponding gel-like porous film was etched in diluted NaOH solution to produce alumina nanowires in the form of densely packed alignment. The resultant alumina nanowires were reacted with NH3and evaporated aluminum at an elevated temperature to be converted into densely packed aluminum nitride (AlN) nanowires. The AlN nanowires have a diameter of 15–20 nm larger than that of the alumina nanowires due to the supplement of the additional evaporated aluminum. The results suggest that it might be possible to prepare other aluminum compound nanowires through similar process

Heterogeneity of Paucigranulocytic Asthma: A Prospective Cohort Study with Hierarchical Cluster Analysis.

BACKGROUND: Asthma, a heterogeneous disease, can be divided into 4 inflammatory phenotypes using induced sputum cell counts-eosinophilic asthma (EA), neutrophilic asthma (NA), mixed granulocytic asthma, and paucigranulocytic asthma (PGA). Although research has focused on EA and NA, there is little known about PGA. OBJECTIVE: To study the heterogeneity of PGA and identify possible PGA clusters to guide clinical treatment. METHODS: Patients with PGA were grouped by hierarchical cluster analysis and enrolled into a prospective cohort study to validate the clusters, relative to future risk of asthma exacerbations in a real-world setting. Clusters were validated by tree analysis in a separate population. Finally, we explored PGA stability. RESULTS: Cluster analysis of 145 patients with PGA identified 3 clusters: cluster 1 (n = 110, 75.9%) was "mild PGA," cluster 2 (n = 20, 13.8%) was "PGA with psychological dysfunction and rhinoconjunctivitis and other allergic diseases," and cluster 3 (n = 15, 10.3%) was "smoking-associated PGA." Cluster 3 had significantly increased risk of severe exacerbation (relative risk [RR] = 6.43, P = .01), emergency visit (RR = 8.61, P = .03), and hospitalization (RR = 12.94, P < .01). Results of the cluster analysis were successfully validated in an independent PGA population classified using decision tree analysis. Although PGA can transform into or develop from other phenotypes, 70% were stable over time. CONCLUSIONS: Among 3 identified PGA clusters, cluster 3 had a higher risk of severe exacerbation. PGA heterogeneity indicates the requirement of novel targeted interventions

Treatable Traits in Elderly Asthmatics from the Australasian Severe Asthma Network: A Prospective Cohort Study.

BACKGROUND: Data on treatable traits (TTs) in different populations are limited. OBJECTIVE: To assess TTs in elderly patients with asthma and compare them to younger patients, to evaluate the association of TTs with future exacerbations, and to develop an exacerbation prediction model. METHODS: We consecutively recruited 521 participants at West China Hospital, Sichuan University based on the Australasian Severe Asthma Network, classified as elderly (n = 62) and nonelderly (n = 459). Participants underwent a multidimensional assessment to characterize the TTs and were then followed up for 12 months. TTs and their relationship with future exacerbations were described. Based on the TTs and asthma control levels, an exacerbation prediction model was developed, and the overall performance was externally validated in an independent cohort. RESULTS: A total of 38 TTs were assessed. Elderly patients with asthma had more chronic metabolic diseases, fixed airflow limitation, emphysema, and neutrophilic inflammation, whereas nonelderly patients with asthma exhibited more allergic characteristics and psychiatric diseases. Nine traits were associated with increased future exacerbations, of which exacerbation prone, upper respiratory infection-induced asthma attack, cardiovascular disease, diabetes, and depression were the strongest. A model including exacerbation prone, psychiatric disease, cardiovascular disease, upper respiratory infection-induced asthma attack, noneosinophilic inflammation, cachexia, food allergy, and asthma control was developed to predict exacerbation risk and showed good performance. CONCLUSIONS: TTs can be systematically assessed in elderly patients with asthma, some of which are associated with future exacerbations, proving their clinical utility of evaluating them. A model based on TTs can be used to predict exacerbation risk in people with asthma

Cloning, expression and characterization of alcohol dehydrogenases in the silkworm Bombyx mori

Alcohol dehydrogenases (ADH) are a class of enzymes that catalyze the reversible oxidation of alcohols to corresponding aldehydes or ketones, by using either nicotinamide adenine dinucleotide (NAD) or nicotinamide adenine dinucleotide phosphate (NADP), as coenzymes. In this study, a short-chain ADH gene was identified in Bombyx mori by 5′-RACE PCR. This is the first time the coding region of BmADH has been cloned, expressed, purified and then characterized. The cDNA fragment encoding the BmADH protein was amplified from a pool of silkworm cDNAs by PCR, and then cloned into E. coli expression vector pET-30a(+). The recombinant His-tagged BmADH protein was expressed in E. coli BL21 (DE3), and then purified by metal chelating affinity chromatography. The soluble recombinant BmADH, produced at low-growth temperature, was instrumental in catalyzing the ethanol-dependent reduction of NAD+, thereby indicating ethanol as one of the substrates of BmADH

Display of Bombyx mori Alcohol Dehydrogenases on the Bacillus subtilis Spore Surface to Enhance Enzymatic Activity under Adverse Conditions

Alcohol dehydrogenases (ADHs) are oxidoreductases catalyzing the reversible oxidation of alcohols to corresponding aldehydes or ketones accompanied by nicotinamide adenine dinucleotide (NAD) or nicotinamide adenine dinucleotide phosphate (NADP) as coenzyme. ADHs attract major scientific and industrial interest for the evolutionary perspectives, afforded by their wide occurrence in nature, and for their use in industrial synthesis. However, the low activity of ADHs under extremes of pH and temperature often limits their application. To obtain ADH with high activity, in this study, we used Bombyx mori alcohol dehydrogenases (BmADH) as foreign gene and constructed a recombinant integrative plasmid pJS700-BmADH. This pJS700-BmADH was transformed into Bacillus subtilis by double cross-over and produced an amylase inactivated mutant. The fusion protein containing BmADH was expressed on the spore surface and recognized by BmADH-specific antibody. We also assayed the alcohol dehydrogenase activity of the fusion protein together with the native BmADH at different pH and temperature levels, which indicated the recombinant enzyme exhibits activity over wider ranges of temperature and pH than its native form, perhaps due to the resistance properties of B. subtilis spores against adverse conditions