Towards standards for human fecal sample processing in metagenomic studies

Technical variation in metagenomic analysis must be minimized to confidently assess the contributions of microbiota to human health. Here we tested 21 representative DNA extraction protocols on the same fecal samples and quantified differences in observed microbial community composition. We compared them with differences due to library preparation and sample storage, which we contrasted with observed biological variation within the same specimen or within an individual over time. We found that DNA extraction had the largest effect on the outcome of metagenomic analysis. To rank DNA extraction protocols, we considered resulting DNA quantity and quality, and we ascertained biases in estimates of community diversity and the ratio between Gram-positive and Gram-negative bacteria. We recommend a standardized DNA extraction method for human fecal samples, for which transferability across labs was established and which was further benchmarked using a mock community of known composition. Its adoption will improve comparability of human gut microbiome studies and facilitate meta-analyses

Redox Modulation at Work: Natural Phytoprotective Polysulfanes From Alliums Based on Redox-Active Sulfur

Purpose of review: This article provides a brief overview of natural phytoprotective products of allium with a special focus on the therapeutic potential of diallyl polysulfanes from garlic, their molecular targets and their fate in the living organisms. A comprehensive overview of antimicrobial and anticancer properties of published literature is presented for the reader to understand the effective concentrations of polysulfanes and their sensitivity towards different human pathogenic microbes, fungi, and cancer cell lines. Recent findings: The article finds polysulfanes potentials as new generation novel antibiotics and chemo preventive agent. The effective dose rates of polysulfanes for antimicrobial properties are in the range of 0.5–40 mg/L and for anticancer 20–100 μM. The molecular targets for these redox modulators are mainly cellular thiols as well as inhibition and/or activation of certain cellular proteins in cancer cell lines. Summary: Antimicrobial and anticancer activities of polysulfanes published in the literature indicate that with further development, they could be promising candidates for cancer prevention due to their selectivity towards abnormal cells

Epigenetics Offer New Horizons for Colorectal Cancer Prevention

In recent years, colorectal cancer (CRC) incidence has been increasing to become a major cause of morbidity and mortality worldwide from cancers, with high rates in westernized societies and increasing rates in developing countries. Epigenetic modifications including changes in DNA methylation, histone modifications, and non-coding RNAs play a critical role in carcinogenesis. Epidemiological data suggest that, in comparison to other cancers, these alterations are particularly common within the gastrointestinal tract. To explain these observations, environmental factors and especially diet were suggested to both prevent and induce CRC. Epigenetic alterations are, in contrast to genetic modifications, potentially reversible, making the use of dietary agents a promising approach in CRC for the development of chemopreventive strategies targeting epigenetic mechanisms. This review focuses on CRC-related epigenetic alterations as a rationale for various levels of prevention strategies and their potential modulation by natural dietary compounds

Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells

Genomic instability is a common feature of cancer etiology. This provides an avenue for therapeutic intervention, since cancer cells are more susceptible than normal cells to DNA damaging agents. However, there is growing evidence that the epigenetic mechanisms that impact DNA methylation and histone status also contribute to genomic instability. The DNA damage response, for example, is modulated by the acetylation status of histone and non-histone proteins, and by the opposing activities of histone acetyltransferase and histone deacetylase (HDAC) enzymes. Many HDACs overexpressed in cancer cells have been implicated in protecting such cells from genotoxic insults. Thus, HDAC inhibitors, in addition to unsilencing tumor suppressor genes, also can silence DNA repair pathways, inactivate non-histone proteins that are required for DNA stability, and induce reactive oxygen species and DNA double-strand breaks. This review summarizes how dietary phytochemicals that affect the epigenome also can trigger DNA damage and repair mechanisms. Where such data is available, examples are cited from studies in vitro and in vivo of polyphenols, organosulfur/organoselenium compounds, indoles, sesquiterpene lactones, and miscellaneous agents such as anacardic acid. Finally, by virtue of their genetic and epigenetic mechanisms, cancer chemopreventive agents are being redefined as chemo- or radio-sensitizers. A sustained DNA damage response coupled with insufficient repair may be a pivotal mechanism for apoptosis induction in cancer cells exposed to dietary phytochemicals. Future research, including appropriate clinical investigation, should clarify these emerging concepts in the context of both genetic and epigenetic mechanisms dysregulated in cancer, and the pros and cons of specific dietary intervention strategies

Metastasis-associated in colon cancer-1 and aldehyde dehydrogenase 1 are metastatic and prognostic biomarker for non-small cell lung cancer

BACKGROUND: Tumor recurrence and metastasis are the most common reason for treatment failure. Metastasis-associate in colon cancer-1 (MACC1) has been identified as a metastatic and prognostic biomarker for colorectal cancer and other solid tumors. Aldehyde dehydrogenase 1 (ALDH1), a marker of cancer stem cells, is also associated with metastasis and poor prognosis in many tumors. However, the prognostic value of either MACC1 or ALDH1 in non-small cell lung cancer (NSCLC) is unclear. In this study, we explored the relationship between MACC1 and ALDH1 expression, as well as their respective associations with clinicopathological features, to determine if either could be useful for improvement of survival prognosis in NSCLC. METHODS: The expression levels of both MACC1 and ALDH1 in 240 whole tissue sections of NSCLC were examined by immunohistochemistry. Clinical data were also collected. RESULTS: MACC1 and ALDH1 were significantly overexpressed in NSCLC tissues when compared to levels in normal lung tissues. Investigation of associations between MACC1 or ALDH1 protein levels with clinicopathological parameters of NSCLC revealed correlations between the expression of each with tumor grade, lymph node metastasis, and tumor node metastasis. The overall survival of patients with MACC1- or ALDH1-positive NSCLC tumors was significantly lower than that of those who were negative. Importantly, multivariate analysis suggested that positive expression of either MACC1 or ALDH1, as well as TNM stage, could be independent prognostic factors for overall survival in patients with NSCLC. CONCLUSIONS: MACC1 and ALDH1 may represent promising metastatic and prognostic biomarkers, as well as potential therapeutic targets, for NSCLC

Variability analysis of frequency dependent visco-elastic three-layered beams

International audienceThe modal stability procedure is combined with Monte-Carlo simulations to estimate the variability of natural frequencies and damping ratios of frequency dependent visco-elastic sandwich structures. In the pre-processing phase, the Diamant approach is used, at nominal, to compute complex eigenvalues and eigenmodes. Then, in the on-line phase i.e within the Monte-Carlo simulation loop, a non-linear equation is solved with Newton-Raphson algorithm to obtain perturbed complex eigenvalues. The low computational times of the method enable the use of large scale Monte-Carlo simulations yielding accurate estimates of means and coefficients of variation of frequencies and damping ratios. The method is illustrated on a three-layered sandwich rectangular beam with visco-elastic core. A frequency dependent visco-elastic material 3M ISD112 is used and two different set of boundary conditions are considered. The stochastic variables are the Young modulus of the elastic faces and the delayed elasticity shear modulus. In particular, it is shown that the mechanism of uncertainty propagation affects mostly damping ratios that experience higher coefficients of variation than natural frequencies

Harmonic pressure optimization on numerical electric motor model

International audienceAudible noise of electric machines has become an important criterion in their design. In this paper we used a multi-physics numerical model (electromagnetic-dynamic) in order to predict mechanical vibration caused by magnetic pressure in a wound rotor synchronous machine. The final objective is to reduce this vibration. The novelty of this paper is to use an optimization method applied to this multi-physics numerical model in order to reduce important vibration peaks thanks to magnetic pressure harmonics

Oropharyngeal Dysphagia in Community-Dwelling Older Patients with Dementia: Prevalence and Relationship with Geriatric Parameters.

To define the prevalence of oropharyngeal dysphagia (OD) in community-dwelling older persons with dementia, using V-VST (Volume-Viscosity Swallow Test), the reference clinical screening test for swallowing disorders, to assess the feasibility of the V-VST in an ambulatory care setting, to search for associations between geriatric parameters and OD, and to identify a relationship between severities of cognitive impairment and OD. Prospective, monocentric study. Population from a geriatric outpatients clinic. Patients older than 70 with a diagnosis of dementia (NINCDS-ADRDA criteria), effective cough, and ability of voluntary swallowing for testing. OD screening was realized using V-VST during consultation. Severity of cognitive impairment was estimated by the MMSE and severity of OD by the Dysphagia Outcome Severity Scale (DOSS). Six geriatric domains were evaluated (comorbidities, functional abilities, cognition, nutrition, mood disorders, frailty). 117 patients participated in the study (77 women, mean age = 84.5 ± 5.1 years). Prevalence of OD was 86.6%. Among the 97 patients with OD, 3 (3.1%) had only safety impairment, 52 (53.6%) had only efficacy impairment and 42 (43.3%) had both. The mean time necessary to realize V-VST was 8.7 ± 2.7 minutes with a rate of success of 96%. Dependency was independently associated with OD [odds ratio (OR) 4.8; 95% confidence interval (CI) 1.5-15.9; P < .05], and age and grip strength were associated with safety impairment (OR 1.1; 95% CI 1.0-1.2 and OR 1.9; 95% CI 1.2-3.2 respectively; both P < .05). No significant relationship was found between severity of OD and severity of cognitive impairment. OD is very frequent in community-dwelling older persons with dementia and is associated with dependency and frailty. The V-VST is an easy-to-perform and well tolerated screening test in this population and therefore should be systematically included in the geriatric assessment of older persons with dementia. The role of V-VST in therapeutic strategies of OD remains to be evaluated