Patterns of Oral Microbiota Diversity in Adults and Children: A Crowdsourced Population Study.

Oral microbiome dysbiosis has been associated with various local and systemic human diseases such as dental caries, periodontal disease, obesity, and cardiovascular disease. Bacterial composition may be affected by age, oral health, diet, and geography, although information about the natural variation found in the general public is still lacking. In this study, citizen-scientists used a crowdsourcing model to obtain oral bacterial composition data from guests at the Denver Museum of Nature & Science to determine if previously suspected oral microbiome associations with an individual's demographics, lifestyle, and/or genetics are robust and generalizable enough to be detected within a general population. Consistent with past research, we found bacterial composition to be more diverse in youth microbiomes when compared to adults. Adult oral microbiomes were predominantly impacted by oral health habits, while youth microbiomes were impacted by biological sex and weight status. The oral pathogen Treponema was detected more commonly in adults without recent dentist visits and in obese youth. Additionally, oral microbiomes from participants of the same family were more similar to each other than to oral microbiomes from non-related individuals. These results suggest that previously reported oral microbiome associations are observable in a human population containing the natural variation commonly found in the general public. Furthermore, these results support the use of crowdsourced data as a valid methodology to obtain community-based microbiome data

The Future of Aminoglycosides: The End or Renaissance?

Although aminoglycosides have been used as antibacterials for decades, their use has been hindered by their inherent toxicity and the resistance that has emerged to these compounds. It seems that such issues have relegated a formerly front-line class of antimicrobials to the proverbial back shelf. However, recent advances have demonstrated that novel aminoglycosides have a potential to overcome resistance as well as to be used to treat HIV-1 and even human genetic disorders, with abrogated toxicity. It is not the end for aminoglycosides, but rather, the challenges faced by researchers have led to ingenuity and a change in how we view this class of compounds, a renaissance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71366/1/880_ftp.pd

Chemical and Structural Insights into the Regioversatility of the Aminoglycoside Acetyltransferase Eis

A recently discovered cause of tuberculosis resistance to a drug of last resort, the aminoglycoside kanamycin, results from modification of this drug by the enhanced intracellular survival (Eis) protein. Eis is a structurally and functionally unique acetyltransferase with an unusual capability of acetylating aminoglycosides at multiple positions. The extent of this regioversatility and its defining protein features are unclear. Herein, we determined the positions and order of acetylation of five aminoglycosides by NMR spectroscopy. This analysis revealed unprecedented acetylation of the 3′′‐amine of kanamycin, amikacin, and tobramycin, and the γ‐amine of the 4‐amino‐2‐hydroxybutyryl group of amikacin. A crystal structure of Eis in complex with coenzyme A and tobramycin revealed how tobramycin can be accommodated in the Eis active site in two binding modes, consistent with its diacetylation. These studies, describing chemical and structural details of acetylation, will guide future efforts towards designing aminoglycosides and Eis inhibitors to overcome resistance in tuberculosis. Novel modifications of aminoglycosides: The enhanced intracellular survival (Eis) protein of Mycobacterium tuberculosis can acetylate amines at two unprecedented positions on aminoglycoside antibiotics: the 3′′‐amine of kanamycin, amikacin, and tobramycin, and the γ‐amine of the 4‐amino‐2‐hydroxybutyryl group in amikacin.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100269/1/cbic_201300359_sm_miscellaneous_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/100269/2/2127_ftp.pd

Interaction of eddies and mean zonal flow on Jupiter as inferred from Voyager 1 and 2 images

Voyager 1 and 2 narrow-angle frames were used to obtain displacements of features at resolutions of 130 km over time intervals of 1 Jovian rotation. The zonal velocity ū was constant to 1.5% during the 4 months between the Voyager 1 and 2 encounters. The latitudes of the zonal jet maxima (extrema of ū) are the same as inferred from earth-based observations extending over the past 80 years. The curvature of the velocity profile d²ū/dy² varies with latitudinal coordinate y in the range from −3β to +2β, where β is the planetary vorticity gradient. The barotropic stability criterion is violated at about 10 latitudes between ±60°. The eddy momentum flux variation with latitude (u'ν')(overbar) is positively correlated with dū/dy for both Voyager 1 and 2 data. The rate of conversion {K'K(overbar)} of eddy kinetic energy into zonal mean kinetic energy is in the range 1.5–3.0 Wm^(−2), for a layer 2.5 bar deep. The time constant for resupply of zonal mean kinetic energy by eddies is in the range 2–4 months, less than the interval between Voyager encounters. The rate of energy conversion is more than 10% of the total infrared heat flux for Jupiter, in contrast with earth where it is only 0.1% of the infrared heat flux. This hundred-fold difference suggests that the thermomechanical energy cycles are very different on the two planets

Designing multiplayer games to facilitate emergent social behaviours online

This paper discusses an exploratory case study of the design of games that facilitate spontaneous social interaction and group behaviours among distributed individuals, based largely on symbolic presence 'state' changes. We present the principles guiding the design of our game environment: presence as a symbolic phenomenon, the importance of good visualization and the potential for spontaneous self-organization among groups of people. Our game environment, comprising a family of multiplayer 'bumper-car' style games, is described, followed by a discussion of lessons learned from observing users of the environment. Finally, we reconsider and extend our design principles in light of our observations

Flow fields within Jupiter's great red spot and white oval BC

Using sequences of Voyager 1 high-resolution images of Jupiter's Great Red Spot (GRS) and White Oval BC we map the flow fields within the GRS and Oval BC. We compute relative vorticity within these features as a function of semi-major axis length and position angle in a coordinate system consisting of concentric ellipses of equal eccentricity. Both the velocity and the relative vorticity profiles are nearly identical for Oval BC and the outer portion of the GRS. Wind speeds of 110–120 m/s are observed near the outer edges of both features. Along their minor axes relative vorticity profiles reach a maximum of ∼6 × 10^(−5) s^(−1). This is several times greater than the ambient 1.5 × 10^(−5) s^(−1) meridional shear of zonal winds at the latitudes of the GRS and Oval BC. Maximum Rossby numbers of 0.36 are computed for flows within both the GRS and the Oval BC. Generally, the Rossby numbers within these features are much lower, indicating strongly geostrophic constraints on the flow. The difference in streamline curvature within the GRS and the Oval BC is found to compensate for the difference in planetary vorticity at the respective latitudes of the features. Motions within the central region of the GRS are much slower and more random than around the spot’s outer portion

Ornithine Decarboxylase mRNA is Stabilized in an mTORC1-dependent Manner in Ras-transformed Cells

Upon Ras activation, ODC (ornithine decarboxylase) is markedly induced, and numerous studies suggest that ODC expression is controlled by Ras effector pathways. ODC is therefore a potential target in the treatment and prevention of Ras-driven tumours. In the present study we compared ODC mRNA translation profiles and stability in normal and Ras12V-transformed RIE-1 (rat intestinal epithelial) cells. While translation initiation of ODC increased modestly in Ras12V cells, ODC mRNA was stabilized 8-fold. Treatment with the specific mTORC1 [mTOR (mammalian target of rapamycin) complex 1] inhibitor rapamycin or siRNA (small interfering RNA) knockdown of mTOR destabilized the ODC mRNA, but rapamycin had only a minor effect on ODC translation initiation. Inhibition of mTORC1 also reduced the association of the mRNA-binding protein HuR with the ODC transcript. We have shown previously that HuR binding to the ODC 3′UTR (untranslated region) results in significant stabilization of the ODC mRNA, which contains several AU-rich regions within its 3′UTR that may act as regulatory sequences. Analysis of ODC 3′UTR deletion constructs suggests that cis-acting elements between base 1969 and base 2141 of the ODC mRNA act to stabilize the ODC transcript. These experiments thus define a novel mechanism of ODC synthesis control. Regulation of ODC mRNA decay could be an important means of limiting polyamine accumulation and subsequent tumour development

The long-term fate of permafrost peatlands under rapid climate warming

Permafrost peatlands contain globally important amounts of soil organic carbon, owing to cold conditions which suppress anaerobic decomposition. However, climate warming and permafrost thaw threaten the stability of this carbon store. The ultimate fate of permafrost peatlands and their carbon stores is unclear because of complex feedbacks between peat accumulation, hydrology and vegetation. Field monitoring campaigns only span the last few decades and therefore provide an incomplete picture of permafrost peatland response to recent rapid warming. Here we use a high-resolution palaeoecological approach to understand the longer-term response of peatlands in contrasting states of permafrost degradation to recent rapid warming. At all sites we identify a drying trend until the late-twentieth century; however, two sites subsequently experienced a rapid shift to wetter conditions as permafrost thawed in response to climatic warming, culminating in collapse of the peat domes. Commonalities between study sites lead us to propose a five-phase model for permafrost peatland response to climatic warming. This model suggests a shared ecohydrological trajectory towards a common end point: inundated Arctic fen. Although carbon accumulation is rapid in such sites, saturated soil conditions are likely to cause elevated methane emissions that have implications for climate-feedback mechanisms

Structural basis for CRISPR RNA-guided DNA recognition by Cascade

The CRISPR (clustered regularly interspaced short palindromic repeats) immune system in prokaryotes uses small guide RNAs to neutralize invading viruses and plasmids. In Escherichia coli, immunity depends on a ribonucleoprotein complex called Cascade. Here we present the composition and low-resolution structure of Cascade and show how it recognizes double-stranded DNA (dsDNA) targets in a sequence-specific manner. Cascade is a 405-kDa complex comprising five functionally essential CRISPR-associated (Cas) proteins (CasA1B2C6D1E1) and a 61-nucleotide CRISPR RNA (crRNA) with 5′-hydroxyl and 2′,3′-cyclic phosphate termini. The crRNA guides Cascade to dsDNA target sequences by forming base pairs with the complementary DNA strand while displacing the noncomplementary strand to form an R-loop. Cascade recognizes target DNA without consuming ATP, which suggests that continuous invader DNA surveillance takes place without energy investment. The structure of Cascade shows an unusual seahorse shape that undergoes conformational changes when it binds target DNA.