Purpose: Gut microbiota have been implicated in the development of colorectal cancer. We evaluated the utility of fecal bacterial marker candidates identified by our metagenome sequencing analysis for colorectal cancer diagnosis.Experimental Design: Subjects (total 439; 203 colorectal cancer and 236 healthy subjects) from two independent Asian cohorts were included. Probe-based duplex quantitative PCR (qPCR) assays were established for the quantification of bacterial marker candidates.Results: Candidates identified by metagenome sequencing, including Fusobacterium nucleatum (Fn), Bacteroides clarus (Bc), Roseburia intestinalis (Ri), Clostridium hathewayi (Ch), and one undefined species (labeled as m7), were examined in fecal samples of 203 colorectal cancer patients and 236 healthy controls by duplex-qPCR. Strong positive correlations were demonstrated between the quantification of each candidate by our qPCR assays and metagenomics approach (r ¼ 0.801-0.934, all P < 0.0001). Fn was significantly more abundant in colorectal cancer than controls (P < 0.0001), with AUROC of 0.868 (P < 0.0001). At the best cut-off value maximizing sum of sensitivity and specificity, Fn discriminated colorectal cancer from controls with a sensitivity of 77.7%, and specificity of 79.5% in cohort I. A simple linear combination of four bacteria (Fn þ Ch þ m7-Bc) showed an improved diagnostic ability compared with Fn alone (AUROC ¼ 0.886, P < 0.0001) in cohort I. These findings were further confirmed in an independent cohort II. In particular, improved diagnostic performances of Fn alone (sensitivity 92.8%, specificity 79.8%) and four bacteria (sensitivity 92.8%, specificity 81.5%) were achieved in combination with fecal immunochemical testing for the detection of colorectal cancer.Conclusions: Stool-based colorectal cancer-associated bacteria can serve as novel noninvasive diagnostic biomarkers for colorectal cancer.

We have recently shown that Deinococcus radiodurans and other radiation resistant bacteria accumulate exceptionally high intracellular manganese and low iron levels. In comparison, the dissimilatory metal-reducing bacterium Shewanella oneidensis accumulates Fe but not Mn and is extremely sensitive to radiation. We have proposed that for Fe-rich, Mn-poor cells killed at radiation doses which cause very little DNA damage, cell death might be induced by the release of Fe(II) from proteins during irradiation, leading to additional cellular damage by Fe(II)-dependent oxidative stress. In contrast, Mn(II) ions concentrated in D. radiodurans might serve as antioxidants that reinforce enzymic systems which defend against oxidative stress during recovery. We extend our hypothesis here to include consideration of respiration, tricarboxylic acid cycle activity, peptide transport and metal reduction, which together with Mn(II) transport represent potential new targets to control recovery from radiation injury.

We have developed a radiation resistant bacterium for the treatment of mixed radioactive wastes containing ionic mercury. The high cost of remediating radioactive waste sites from nuclear weapons production has stimulated the development of bioremediation strategies using Deinococcus radiodurans, the most radiation resistant organism known. As a frequent constituent of these sites is the highly toxic ionic mercury (Hg) (II), we have generated several D. radiodurans strains expressing the cloned Hg (II) resistance gene (merA) from Escherichia coli strain BL308. We designed four different expression vectors for this purpose, and compared the relative advantages of each. The strains were shown to grow in the presence of both radiation and ionic mercury at concentrations well above those found in radioactive waste sites, and to effectively reduce Hg (II) to the less toxic volatile elemental mercury. We also demonstrated that different gene clusters could be used to engineer D. radiodurans for treatment of mixed radioactive wastes by developing a strain to detoxify both mercury and toluene. These expression systems could provide models to guide future D. radiodurans engineering efforts aimed at integrating several remediation functions into a single host.

Cancer from the gastrointestinal tract and its associated excretory organs will occur in over 300,000 Americans in 2017, with colorectal cancer responsible for over forty percent of that burden; there will be over 150,000 deaths from this group of cancers in the same time period. Disparities among subgroups related to these cancers’ incidence and mortality exist. The epidemiology and risk factors associated with each cancer bear out differences for racial groups in the United States. Esophageal adenocarcinoma is more frequent in Non-Hispanic Whites, whereas esophageal squamous cell carcinoma with risk factors of tobacco and alcohol is more frequent among Blacks. Liver cancer has been most frequent among Asian/Pacific Islanders chiefly due to hepatitis B vertical transmission, but other racial groups show increasing rates due to hepatitis C and emergence of cirrhosis from non-alcoholic fatty liver disease. Gastric cancer incidence remains highest among Asian/Pacific Islanders likely due to gene-environment interaction. In addition to esophageal squamous cell carcinoma, cancers of the small bowel, pancreas and colorectum show the highest rates among Blacks, where the explanations for the disparity are not as obvious and are likely multifactorial, including socio-economic and health care access, treatment and prevention (vaccination and screening) differences, dietary and composition of the gut microbiome, as well as biological and genetic influences. Cognizance of these disparities in gastrointestinal cancer risk, as well as approaches that apply precision medicine methods to populations with the increased risk, may reduce the observed disparities for digestive cancers.

Classification of metal-resistant bacteria from industrial biotopes as), respectively. Six isolates were allocated to Ralstonia basilensis, which presently contains only the type strain ; an emendation of the latter species description is therefore proposed.

Non-alcoholic fatty liver disease (NAFLD), a clinical syndrome that is predicted to affect millions of people worldwide, will become the next global epidemic. The natural course of this disease, including its subtype, non-alcoholic steatohepatitis (NASH), is not clearly defined, especially in the US minority populations. The aim of this review is to report the global epidemiology of NAFLD, with emphasis on US minority populations on the basis of database searches using using Pubmed and other online databases. The US Hispanic population is the most disproportionately affected ethnic group with hepatic steatosis whereas African-Americans are the least affected. Genetic disparities involved in lipid metabolism seem to be the leading explanation for the lowest incidence and prevalence of both NAFLD and NASH in African-Americans.

BackgroundMutations and promoters' methylation of a set of candidate cancer genes (CAN genes) are associated with progression of colorectal cancer (CRC). We hypothesized that these genes' promoters are inactivated through epigenetic silencing and may show a different profile in high-risk populations. We investigated the status of CAN gene methylation and CHD5 protein expression in African American CRC tissue microarrays (TMA) using immunohistochemical staining.Methodology/Principal FindingsThe promoter methylation status of the CAN genes was studied by methylation-specific PCR (MSP) in 51 Iranians (a white population) and 51 African Americans (AA). Microsatellite instability (MSI) was analyzed as well. The differential frequency of methylation for each gene was tested by chi-square analysis between the two groups based on matched age and sex. CHD5 protein expression was evaluated in moderate to well differentiated and poorly differentiated carcinomas compared to matched normal tissue using TMA. In addition, the correlation between these epigenetic biomarkers and various clinicopathological factors, including, age, location, and stage of the disease were analyzed.Seventy-seven and 34% of tumors were distal in Iranian and African American patients, respectively. In both populations, the percentage of methylation was >65% for SYNE1, MMP2, APC2, GPNMB, EVL, PTPRD, and STARD8, whereas methylation was <50% for LGR6, RET, CD109, and RNF. The difference in methylation between the two populations was statistically significant for CHD5, ICAM5 and GPNMB. Thirty-one percent AA tumors showed MSI-H, compared to 28% in Iranians.Conclusions/SignificanceA significantly higher methylation rate was found for GPNMB, ICAM5, and CHD5 genes in AA patients compared to Iranians. These genes might play a role in the high incidence and aggressiveness of CRC in the AA population. The hypermethylation of the CAN genes can be considered as a marker of colon carcinogenesis.

Deinococcus geothermalis is an extremely radiation-resistant thermophilic bacterium closely related to the mesophile Deinococcus radiodurans, which is being engineered for in situ bioremediation of radioactive wastes. We report that D. geothermalis is transformable with plasmids designed for D. radiodurans and have generated a Hg(II)-resistant D. geothermalis strain capable of reducing Hg(II) at elevated temperatures and in the presence of 50 Gy/h. Additionally, D. geothermalis is capable of reducing Fe(III)-nitrilotriacetic acid, U(VI), and Cr(VI). These characteristics support the prospective development of this thermophilic radiophile for bioremediation of radioactive mixed waste environments with temperatures as high as 55°C.The bacterium Deinococcus geothermalis (13) is remarkable not only for its extreme resistance to ionizing radiation but also for its ability to grow at temperatures as high as 55°C (13) and in the presence of chronic irradiation (8). The organism was isolated by Ferreira et al. (13) from hot springs together with Deinococcus murrayi. Both bacteria are moderately thermophilic and belong to the bacterial family Deinococcaceae (4, 7, 22), currently comprised of seven distinct nonpathogenic radiation-resistant species, of which Deinococcus radiodurans strain R1 is the best characterized (4). Advances in genetic engineering for D. radiodurans (9-12, 29) were a stimulus for its genome sequencing (17, 33), annotation (22), and proteomic (18) and transcriptome (19) analyses. The other deinococcal species have been reported as nontransformable or have not yet been tested for transformability by chromosomal or plasmid DNA and have been left unexplored by recombinant DNA technologies. Other genetic approaches including conjugation and protoplast fusion have not been successful in the Deinococcaceae (16).A present genetic engineering goal for D. radiodurans is its development for bioremediation of U.S. Department of Energy (DOE) mixed radioactive environmental waste sites left over from nuclear weapons production during the Cold War (21,25,27,28). These sites contain immense volumes of waste (3 ϫ 10 6 m 3 ) that include radionuclides, heavy metals, and toxic organic compounds and have contaminated 40 million cubic meters of soil and 4 trillion liters of groundwater since 1946 (1,21,25,27,28). While there has been significant progress in engineering D. radiodurans for remediation of radioactive DOE waste environments (5,8,15), prospective treatment of contaminated sites with engineered D. radiodurans will be limited to temperatures below 39°C, its maximum growth temperature. However, there is a need to develop bioremediating bacteria that are resistant to both radiation and high temperatures because of the existence of thermally insulated contaminated environments where temperatures are elevated by the decay of long-lived radionuclides (e.g., 137 Cs and 90 Sr) (1). For example, soil columns beneath at least 67 radioactive leaking tanks at DOE's Hanford Site in south-central Washington State have bee...