Many intestinal pathogens, including Clostridioides difficile, use mucus-derived sugars as crucial nutrients in the gut. Commensals that compete with pathogens for such nutrients are therefore ecological gatekeepers in healthy guts, and are attractive candidates for therapeutic interventions. Nevertheless, there is a poor understanding of which commensals use mucin-derived sugars in situ as well as their potential to impede pathogen colonization. Here, we identify mouse gut commensals that utilize mucus-derived monosaccharides within complex communities using single-cell stable isotope probing, Raman-activated cell sorting and mini-metagenomics. Sequencing of cell-sorted fractions reveals members of the underexplored family Muribaculaceae as major mucin monosaccharide foragers, followed by members of Lachnospiraceae, Rikenellaceae, and Bacteroidaceae families. Using this information, we assembled a five-member consortium of sialic acid and N-acetylglucosamine utilizers that impedes C. difficile’s access to these mucosal sugars and impairs pathogen colonization in antibiotic-treated mice. Our findings underscore the value of targeted approaches to identify organisms utilizing key nutrients and to rationally design effective probiotic mixtures.

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R 2019, 'An automated Raman-based platform for the sorting of live cells by functional properties', Nature Microbiology.

BackgroundWe examined the longitudinal association between participation in individual or combinations of physical, social, and religious activity and risk of depression in the elderly.MethodsElderly subjects aged ≥60 years who completed the Living Profiles of Older People Survey in Korea (n = 6,647) were included. The baseline assessment, Wave 1, was conducted in 2008, and a follow-up assessment, Wave 2, was conducted in 2011. We defined participation in frequent physical activity as ≥3 times weekly (at least 30 minutes per activity). Frequent participation in social and religious activity was defined as ≥1 activity weekly. The primary outcome was depression at 3-year follow up.ResultsMultivariable logistic regression analysis showed that subjects who participated in frequent physical, social, and religious activity had an adjusted odds ratio of 0.81 (95% confidence interval [CI], 0.69–0.96), 0.87 (95% CI, 0.75–1.00), and 0.78 (95% CI, 0.67–0.90), respectively, compared with participants who did not participate in each activity. Participants who participated in only one type of activity frequently and participants who participated in two or three types of activities frequently had an adjusted odds ratio of 0.86 (95% CI, 0.75–0.98) and 0.64 (95% CI, 0.52–0.79), respectively, compared with participants who did not participate in any type of physical, social, and religious activity frequently.ConclusionParticipation in physical, social, and religious activity was associated with decreased risk of depression in the elderly. In addition, risk of depression was much lower in the elderly people who participated in two or three of the above-mentioned types of activity than that in the elderly who did not.

A chronic inflammatory process has been implicated in the neuropathology of Alzheimer’s disease (AD). The present review focuses on the current knowledge of circulating serum and plasma biomarkers of AD that are linked to inflammatory reactions. There is abundant evidence that inflammatory mechanisms within the central nervous system contribute to cognitive impairment via cytokine-mediated interactions between neurons and glial cells. Interleukins 1, 4, 6, 10, 12, 16, and 18, tumour necrosis factor, and several chemokines have been suggested as biomarkers of AD. Nonetheless, data on circulating cytokine levels are somewhat inconsistent with regard to peripheral cytokine dysregulation in AD. In summary, definite statements concerning differences in inflammatory biomarkers between controls and AD patients will require the use of sensitive multiplex assays in large patient groups in conjunction with measures of disease severity.

Background/Aims: The purposes of this study were to describe restrictions in instrumental activities of daily living (IADL) in mild cognitive impairment (MCI) and to assess different patterns of IADL in each MCI subtype. Methods: A total of 566 participants, those not cognitively impaired (NCI; n = 311) and MCI patients (n = 255), 60–94 years old (71.25 ± 6.00), were examined. Neuropsychological tests were administered to participants, and each MCI patient was classified into one of four subtypes. They completed the Barthel ADL and Seoul-IADL (S-IADL) for ADL measures. Results: There was a significant difference between NCI and MCI in terms of total S-IADL scores. ANOVA and a post hoc Dunnett analysis revealed that MCI patients performed significantly worse on four out of a total 15 items (i.e. telephone, transportation, finances and household appliances). ANCOVA showed a significant difference in S-IADL-MCI (4 of 15 items) between NCI and amnestic MCI-multiple domains after adjusting for age, gender, education and Geriatric Depression Scale (F = 4.257, d.f. = 1,556, p = 0.002). Conclusion: These findings suggest that scorings of specific IADL items are different in MCI subjects, and these items can possibly help in the identification of MCI subtypes, especially amnestic MCI-multiple domains.

We report an observation of rapid (exceeding 2,000 K/s) heating of polydimethylsiloxane (PDMS), one of the most popular microchannel materials, under cyclic loadings at high (~MHz) frequencies. A microheater was developed based on the finding. The heating mechanism utilized vibration damping in PDMS induced by sound waves that were generated and precisely controlled using a conventional surface acoustic wave (SAW) microfluidic system. The refraction of SAW into the PDMS microchip, called the leaky SAW, takes a form of bulk wave and rapidly heats the microchannels in a volumetric manner. The penetration depths were measured to range from 210 μm to 1290 μm, enough to cover most sizes of microchannels. The energy conversion efficiency was SAW frequency-dependent and measured to be the highest at around 30 MHz. Independent actuation of each interdigital transducer (IDT) enabled independent manipulation of SAWs, permitting spatiotemporal control of temperature on the microchip. All the advantages of this microheater facilitated a two-step continuous flow polymerase chain reaction (CFPCR) to achieve the billion-fold amplification of a 134 bp DNA amplicon in less than 3 min.

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