Gastric cancers of Western European and African patients show different patterns of genomic instability

Background

Infection with H. pylori is important in the etiology of gastric cancer. Gastric cancer is infrequent in Africa, despite high frequencies of H. pylori infection, referred to as the African enigma. Variation in environmental and host factors influencing gastric cancer risk between different populations have been reported but little is known about the biological differences between gastric cancers from different geographic locations. We aim to study genomic instability patterns of gastric cancers obtained from patients from United Kingdom (UK) and South Africa (SA), in an attempt to support the African enigma hypothesis at the biological level.

Methods

DNA was isolated from 67 gastric adenocarcinomas, 33 UK patients, 9 Caucasian SA patients and 25 native SA patients. Microsatellite instability and chromosomal instability were analyzed by PCR and microarray comparative genomic hybridization, respectively. Data was analyzed by supervised univariate and multivariate analyses as well as unsupervised hierarchical cluster analysis.

Results

Tumors from Caucasian and native SA patients showed significantly more microsatellite instable tumors (p < 0.05). For the microsatellite stable tumors, geographical origin of the patients correlated with cluster membership, derived from unsupervised hierarchical cluster analysis (p = 0.001). Several chromosomal alterations showed significantly different frequencies in tumors from UK patients and native SA patients, but not between UK and Caucasian SA patients and between native and Caucasian SA patients.

Conclusions

Gastric cancers from SA and UK patients show differences in genetic instability patterns, indicating possible different biological mechanisms in patients from different geographical origin. This is of future clinical relevance for stratification of gastric cancer therapy.

     

Molecular Ecological Analysis of Fecal Bacterial Populations from Term Infants Fed Formula Supplemented with Selected Blends of Prebiotics

Supplementation of infant formulas with prebiotic ingredients continues the effort to mimic functional properties of human milk. In this double-blind, controlled, 28-day study, healthy term infants received control formula (control group; n = 25) or control formula supplemented with polydextrose (PDX) and galactooligosaccharide (GOS) (4 g/liter) (PG4 group; n = 27) or with PDX, GOS, and lactulose (LOS) (either 4 g/liter [PGL4 group; n = 27] or 8 g/liter [PGL8 group; n = 25]). A parallel breast-fed group (BF group) (n = 30) was included. Stool characteristics, formula tolerance, and adverse events were monitored. Fecal bacterial subpopulations were evaluated by culture-based selective enumeration (Enterobacteriaceae), quantitative real-time PCR (Clostridium clusters I, XI, and XIV, Lactobacillus, and Bifidobacterium), and fluorescence in situ hybridization (FISH) (Bifidobacterium). Fecal bacterial community profiles were examined by using 16S rRNA gene PCR-denaturing gradient gel electrophoresis. The daily stool consistency was significantly softer or looser in the BF group than in all of the groups that received formula. The formulas were well tolerated, and the incidences of adverse events did not differ among feeding groups. Few significant changes in bacterial subpopulations were observed at any time point. The bacterial communities were stable; individual profiles tended to cluster by subject rather than by group. Post hoc analysis, however, demonstrated that the bacterial community profiles for subjects in the BF, PG4, PGL4, and PGL8 groups that first received formula at a younger age were less stable than the profiles for subjects in the same groups that received formula at an older age, but there was no difference for the control group. These data indicate that formulas containing PDX, GOS, and LOS blends are more likely to influence gut microbes when administration is begun in early infancy and justify further investigation of the age-related effects of these blends on fecal microbiota.     

Floc Formation by Azospirillum lipoferum Grown on Poly-beta-Hydroxybutyrate

Azospirillum lipoferum RG6xx was grown under conditions similar to those resulting in encystment of Azotobacter spp. A. lipoferum produced cells of uniform shape when grown on nitrogen-free beta-hydroxybutyrate agar. Cells accumulated poly-beta-hydroxybutyrate and often grew as chains or filaments that eventually lost motility and formed capsules. Within 1 week, vegetative A. lipoferum inocula were converted into microflocs arising from filaments or chains. Cells within microflocs were pleomorphic, contained much poly-beta-hydroxybutyrate, and were encapsulated. Some cells had a cystlike morphology. Up to 57% of the dry weight of encapsulated flocs was poly-beta-hydroxybutyrate, whereas vegetative cells grown in broth with combined nitrogen had only 3% of their dry weight as poly-beta-hydroxybutyrate. Neither encapsulated cells in flocs nor nonencapsulated vegetative cells were significantly desiccation resistant. Under starvation conditions (9 days) only 25% of encapsulated cells remained viable, whereas vegetative cells multiplied severalfold. In short-term germination experiments with encapsulated flocs, nitrate, ammonium, and soil extract promoted formation of motile vegetative cells. Most cells in treatments lacking combined nitrogen eventually depleted their visible poly-beta-hydroxybutyrate reserves without germinating. The remaining cells retained the reserve polymer and underwent size reduction.     

Effect of genetic background on the developmental expression of c-fos and c-myc in chicken

The developmental expression of the protooncogenes, c-fos and c-myc, in muscle and liver of 14-and 19-day embryos and 1-, 6-, 8-and 28-day-old chicks of Athens Canadian Random Bred (ACRB) Single Comb White Leghorn (SCWL) and Peterson X Arbor Acres commercial broiler (PXAA) was determined. For the three stocks of chicken, significant differences were found in c-fos and c-myc expression. For both muscle and liver, averaged across ages, abundance of c-fos RNA was highest in PXAA and lowest in ACRB with differences significant at the P<0.01 level. c-myc RNA levels were significantly higher (P<0.01) in PXAA than in ACRB or SCWL liver. Taken over the developmental period, expression of c-fos RNA in muscle increased at different rates between breeds from 14-day embryo levels to peak levels in 6- to 8-day-old chicks and declined in 28-day-old chicks. Levels of c-fos were much lower in liver and showed no consistent differences related to developmental stage. A steady decline in c-myc from 14-day embryo levels to 28-day-old chicks was found in both muscle and liver. This decline in c-myc levels generally parallels the decline in relative growth rates which occurs in all breeds over the developmental period. In liver, the fast growing PXAA had the highest levels of c-myc. c-fos, on the other hand, showed elevated levels in PXAA for both muscle and liver and distinctly different patterns between these two tissues over the developmental period, suggesting tissue-specific involvement in growth.     

Positive selection driving the evolution of a gene of male reproduction, Acp26Aa, of Drosophila: II. Divergence versus polymorphism

The evolution of the gene for a male ejaculatory protein, Acp26Aa, has been shown to be driven by positive selection when nonsibling species in the Drosophila melanogaster subgroup are compared. To know if selection has been operating in the recent past and to understand the details of its dynamics, we obtained DNA sequences of Acp26Aa and the nearby Acp26Ab gene from 39 D. melanogaster chromosomes. Together with the 10 published sequences, we analyzed 49 sequences from five populations in four continents. The southern African population is somewhat differentiated from all other populations, but its nucleotide diversity is lower at these two loci. We find the following results for Acp26Aa: (1) The R: S (replacement : silent changes) ratio is significantly higher in the between-species comparisons than in the within-species data by the McDonald and Kreitman test. Positive selection is probably responsible for the excess of amino acid replacements between species. (2) However, within-species nucleotide diversity is high. Neither the Tajima test nor the Fu and Li test indicates a reduction in nucleotide diversity due to positive selection in the recent past. (3) The newly derived nucleotides in D. melanogaster are at high frequency significantly more often than predicted by the neutral equilibrium. Since the nearby Acp26Ab gene does not show these patterns, these observations cannot be attributed to the characteristics of this chromosomal region. We suggest that positive selection is active, but may be weak, for each amino acid change in the Acp26Aa gene.      

Population structure of the Japanese eel, Anguilla japonica

Mitochondrial DNA (mtDNA) sequences that include (a) a part of the cytochrome b gene, (b) two tRNA genes, and (c) a part of the noncoding D-loop region of 31 Anguilla japonica (Japanese eel) and 1 A. marmorata collected from Taiwan, Japan, and mainland China were determined to evaluate the population structure of Japanese eel. Among 30 genotypes identified from the 31 Japanese eel mtDNAs sequenced, there are 58 variable sites, predominantly clustered at the D-loop region. The phylogenetic tree constructed by the unweighted pair-group method with arithmetic mean shows neither significant genealogical branches nor geographic clusters. Furthermore, the sequence-statistics test reveals little, if any, significant genetic differentiation. These results indicate that the 31 Japanese eels might come from a single population. Analysis of sequence variation in mtDNA by using the relationship between the number of segregating sites and the average number of nucleotide differences under the neutral mutation hypothesis reveals that neutral mutation acts as a major factor influencing the evolutionary divergence of the Japanese eel mitochondrial genome sequenced, especially in the noncoding region.      

膝关节挫伤的磁共振影像表现

目的 :探讨磁共振短时的反转恢复序列 (STIR)在膝关节骨挫伤中的临床应用。方法 :通过 32例膝关节外伤病例在常规SE序列、FSE序列和STIR序列中的影像表现 ,分析STIR序列的优越性。结果 :32例共 45个骨挫伤病灶 ,T1W发现 38个 (占 84% ) ,T2W发现 37个 (占 82 % ) ,STIR序列病灶全部显示( 1 0 0 % )。结论 :STIR序列对骨挫伤的敏感性较高 ,能显示微小的骨髓水肿 ,充血及骨小梁的微骨折及其周围的骨软骨、关节囊的细微变化 ,对膝关节外伤具有较高价值。