Mechanisms of increased risk of tumorigenesis in Atm and Brca1 double heterozygosity

<p>Abstract</p> <p>Background</p> <p>Both epidemiological and experimental studies suggest that heterozygosity for a single gene is linked with tumorigenesis and heterozygosity for two genes increases the risk of tumor incidence. Our previous work has demonstrated that <it>Atm/Brca1 </it>double heterozygosity leads to higher cell transformation rate than single heterozygosity. However, the underlying mechanisms have not been fully understood yet. In the present study, a series of pathways were investigated to clarify the possible mechanisms of increased risk of tumorigenesis in <it>Atm </it>and <it>Brca1 </it>heterozygosity.</p> <p>Methods</p> <p>Wild type cells, <it>Atm </it>or <it>Brca1 </it>single heterozygous cells, and <it>Atm</it>/<it>Brca1 </it>double heterozygous cells were used to investigate DNA damage and repair, cell cycle, micronuclei, and cell transformation after photon irradiation.</p> <p>Results</p> <p>Remarkable high transformation frequency was confirmed in <it>Atm</it>/<it>Brca1 </it>double heterozygous cells compared to wild type cells. It was observed that delayed DNA damage recognition, disturbed cell cycle checkpoint, incomplete DNA repair, and increased genomic instability were involved in the biological networks. Haploinsufficiency of either ATM or BRCA1 negatively impacts these pathways.</p> <p>Conclusions</p> <p>The quantity of critical proteins such as ATM and BRCA1 plays an important role in determination of the fate of cells exposed to ionizing radiation and double heterozygosity increases the risk of tumorigenesis. These findings also benefit understanding of the individual susceptibility to tumor initiation.</p

The comprehensive effect of natural food quality and quantity on growth rate of herbivore consumers

The performance of herbivore consumers in freshwater ecosystems is influenced by food quality and quantity, which are crucial factors in understanding energy flow. However, the comprehensive effects of these factors on consumer growth based on natural food research remain unclear. To address this gap, we conducted a growth experiment culturing the Cladocera Daphnia similis in natural lake water collected from 30 subtropical lakes. Our results showed that the seston concentration (SC), seston phosphorus (seston P), and seston carbon: phosphorus ratio (seston C:P, in moles) were the most important factors in influencing the growth rate of D. similis according to the Random Forest model. Specifically, the growth rate of D. similis was significantly positive correlated with SC and seston P, and significantly negative correlated with seston C:P. D. similis exhibited the optimal growth performance within the seston C:P range of 32.8 to 69.8, with a sharp decline in growth rate observed at a break point of seston C:P of 70. The combined effect of food quality and quantity on growth rate was that higher SC (≥0.26 mg C/L), lower seston C:P (≤69.80), and higher P (≥0.11 mmol/g) were associated with significantly higher growth rates. Additionally, the growth rate increased significantly with the biomass of cryptophyte, indicating the importance of food composition. Our study shows that the growth rate of D. similis is co-affected by the quality and quantity of natural food. SC, seston C:P, seston P and algae composition are reliable indicators for assessing the growth rate of consumer in freshwater ecosystems. The inhibitory effect of low C:P on consumer growth should be applied with caution when assessing the development of herbivore consumers in natural lakes

Comprehensive analysis of clinical significance of stem-cell related factors in renal cell cancer

<p>Abstract</p> <p>Background</p> <p>C-MYC, LIN28, OCT4, KLF4, NANOG and SOX2 are stem cell related factors. We detected whether these factors express in renal cell carcinoma (RCC) tissues to study their correlations with the clinical and pathological characteristics.</p> <p>Methods</p> <p>The expressions of c-MYC, LIN28, SOX2, KLF4, OCT4 and NANOG in 30 RCC patients and 5 non-RCC patients were detected with quantitative real-time reverse transcription-PCR (qRT-PCR). The data were analyzed with Wilcoxon signed rank sum test and x²test.</p> <p>Results</p> <p>In RCC group, c-MYC expression was significantly higher in RCC tissues compared with normal tissues (P < 0.05). The expression levels of OCT4, KLF4, NANOG and SOX2 were significantly lower in RCC tissues compared with normal tissues (P < 0.05). LIN28 expression level was not significant. No difference was observed when it comes to clinical and pathological characteristics such as gender, age, tumor size, cTNM classification and differentiation status (P > 0.05). Also the expression levels of all above factors were not significantly changed in non-RCC group (P > 0.05).</p> <p>Conclusions</p> <p>The present analysis strongly suggests that altered expression of several stem cell related factors may play different roles in RCC. C-MYC may function as an oncogene and OCT4, KLF4, NANOG and SOX2 as tumor suppressors.</p

Thermal stability of Mg_2Si_(0.4)Sn_(0.6) in inert gases and atomic-layer-deposited Al_2O_3 thin film as a protective coating

Mg_2Si_(1−x)Sn_x solid solutions are promising thermoelectric materials to be applied in vehicle waste-heat recovery. Their thermal stability issue, however, needs to be addressed before the materials can be applied in practical thermoelectric devices. In this work, we studied the crystal structure and chemical composition of Mg_2Si_(1−x)Sn_x in inert gas atmosphere up to 823 K. We found that the sample was oxidized even in high-purity inert gases. Although no obvious structural change has been found in the slightly oxidized sample, carrier concentration decreased significantly since oxidation creates Mg vacancies in the lattice. We demonstrated that an atomic-layer deposited Al_2O_3 coating can effectively protect Mg_2Si_(1−x)Sn_x from oxidation in inert gases and even in air. In addition, this Al_2O_3 thin film also provides in situ protection to the Sb-doped Mg_2Si_(1−x)Sn_x samples during the laser-flash measurement and therefore eliminates the measurement error that occurs in uncoated samples as a result of sample oxidation and graphite exfoliation issues

Dynamic Development of Fecal Microbiome During the Progression of Diabetes Mellitus in Zucker Diabetic Fatty Rats

Background: Although substantial efforts have been made to link the gut microbiota to type 2 diabetes, dynamic changes in the fecal microbiome under the pathological conditions of diabetes have not been investigated.Methods: Four male Zucker diabetic fatty (ZDF) rats received Purina 5008 chow [protein = 23.6%, Nitrogen-Free Extract (by difference) = 50.3%, fiber (crude) = 3.3%, ash = 6.1%, fat (ether extract) = 6.7%, and fat (acid hydrolysis) = 8.1%] for 8 weeks. A total of 32 stool samples were collected from weeks 8 to 15 in four rats. To decipher the microbial populations in these samples, we used a 16S rRNA gene sequencing approach.Results: Microbiome analysis showed that the changes in the fecal microbiome were associated with age and disease progression. In all the stages from 8 to 15 weeks, phyla Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria primarily dominated the fecal microbiome of the rats. Although Lactobacillus and Turicibacter were the predominant genera in 8- to 10-week-old rats, Bifidobacterium, Lactobacillus, Ruminococcus, and Allobaculum were the most abundant genera in 15-week-old rats. Of interest, compared to the earlier weeks, relatively greater diversity (at the genus level) was observed at 10 weeks of age. Although the microbiome of 12-week-old rats had the highest diversity, the diversity in 13–15-week-old rats was reduced. Spearman’s correlation analysis showed that F/B was negatively correlated with age. Random blood glucose was negatively correlated with Lactobacillus and Turicibacter but positively correlated with Ruminococcus and Allobaculum and Simpson’s diversity index.Conclusion: We demonstrated the time-dependent alterations of the abundance and diversity of the fecal microbiome during the progression of diabetes in ZDF rats. At the genus level, dynamic changes were observed. We believe that this work will enhance our understanding of fecal microbiome development in ZDF rats and help to further analyze the role of the microbiome in metabolic diseases. Furthermore, our work may also provide an effective strategy for the clinical treatment of diabetes through microbial intervention