Community assembly of the native C. elegans microbiome is influenced by time, substrate and individual bacterial taxa

Summary Microbiome communities are complex assemblages of bacteria. The dissection of their assembly dynamics is challenging because it requires repeated sampling of both host and source communities. We used the nematode Caenorhabditis elegans as a model to study these dynamics. We characterized microbiome variation from natural worm populations and their substrates for two consecutive years using 16S rDNA amplicon sequencing. We found conservation in microbiome composition across time at the genus, but not amplicon sequencing variant (ASV) level. Only three ASVs were consistently present across worm samples (Comamonas ASV10859, Pseudomonas ASV7162 and Cellvibrio ASV9073). ASVs were more diverse in worms from different rather than the same substrates, indicating an influence of the source community on microbiome assembly. Surprisingly, almost 50% of worm-associated ASVs were absent in corresponding substrates, potentially due to environmental filtering. Ecological network analysis revealed strong effects of bacteria–bacteria interactions on community composition: While a dominant Erwinia strain correlated with decreased alpha-diversity, predatory bacteria of the Bdellovibrio and like organisms associated with increased alpha-diversity. High alpha-diversity was further linked to high worm population growth, especially on species-poor substrates. Our results highlight that microbiomes are individually shaped and sensitive to dramatic community shifts in response to particular competitive species

Nuclear spin coherence in a quantum wire

We have observed millisecond-long coherent evolution of nuclear spins in a quantum wire at 1.2 K. Local, all-electrical manipulation of nuclear spins is achieved by dynamic nuclear polarization in the breakdown regime of the Integer Quantum Hall Effect combined with pulsed Nuclear Magnetic Resonance. The excitation thresholds for the breakdown are significantly smaller than what would be expected for our sample and the direction of the nuclear polarization can be controlled by the voltage bias. As a four-level spin system, the device is equivalent to two qubits.Comment: 5 pages, 5 figure

Cellular hysteresis as a principle to maximize the efficacy of antibiotic therapy

Rapid evolution is central to the current antibiotic crisis. Sustainable treatments must thus take account of the bacteria’s potential for adaptation. We identified cellular hysteresis as a principle to constrain bacterial evolution. Cellular hysteresis is a persistent change in bacterial physiology, reminiscent of cellular memory, which is induced by one antibiotic and enhances susceptibility toward another antibiotic. Cellular hysteresis increases bacterial extinction in fast sequential treatments and reduces selection of resistance by favoring responses specific to the induced physiological effects. Fast changes between antibiotics are key, because they create the continuously high selection conditions that are difficult to counter by bacteria. Our study highlights how an understanding of evolutionary processes can help to outsmart human pathogens.Antibiotic resistance has become one of the most dramatic threats to global health. While novel treatment options are urgently required, most attempts focus on finding new antibiotic substances. However, their development is costly, and their efficacy is often compromised within short time periods due to the enormous potential of microorganisms for rapid adaptation. Here, we developed a strategy that uses the currently available antibiotics. Our strategy exploits cellular hysteresis, which is the long-lasting, transgenerational change in cellular physiology that is induced by one antibiotic and sensitizes bacteria to another subsequently administered antibiotic. Using evolution experiments, mathematical modeling, genomics, and functional genetic analysis, we demonstrate that sequential treatment protocols with high levels of cellular hysteresis constrain the evolving bacteria by (i) increasing extinction frequencies, (ii) reducing adaptation rates, and (iii) limiting emergence of multidrug resistance. Cellular hysteresis is most effective in fast sequential protocols, in which antibiotics are changed within 12 h or 24 h, in contrast to the less frequent changes in cycling protocols commonly implemented in hospitals. We found that cellular hysteresis imposes specific selective pressure on the bacteria that disfavors resistance mutations. Instead, if bacterial populations survive, hysteresis is countered in two distinct ways, either through a process related to antibiotic tolerance or a mechanism controlled by the previously uncharacterized two-component regulator CpxS. We conclude that cellular hysteresis can be harnessed to optimize antibiotic therapy, to achieve both enhanced bacterial elimination and reduced resistance evolution

Validation of Urban NO2NO_2 Concentrations and Their Diurnal and Seasonal Variations Observed from the SCIAMACHY and OMI Sensors Using In Situ Surface Measurements in Israeli Cities

We compare a full-year (2006) record of surface air $NO_2$ concentrations measured in Israeli cities to coinciding retrievals of tropospheric $NO_2$ columns from satellite sensors (SCIAMACHY aboard ENVISAT and OMI aboard Aura). This provides a large statistical data set for validation of $NO_2$ satellite measurements in urban air, where validation is difficult yet crucial for using these measurements to infer $NO_x$ emissions by inverse modeling. Assuming that $NO_2$ is well-mixed throughout the boundary layer (BL), and using observed average seasonal boundary layer heights, near-surface $NO_2$ concentrations are converted into BL $NO_2$ columns. The agreement between OMI and (13:45) BL $NO_2$ columns (slope=0.93, n=542), and the comparable results at 10:00 h for SCIAMACHY, allow a validation of the seasonal, weekly, and diurnal cycles in satellite-derived $NO_2$. OMI and BL $NO_2$ columns show consistent seasonal cycles (winter $NO_2$ 1.6–2.7× higher than summer). BL and coinciding OMI columns both show a strong weekly cycle with 45–50% smaller $NO_2$ columns on Saturday relative to the weekday mean, reflecting the reduced weekend activity, and validating the weekly cycle observed from space. The diurnal difference between SCIAMACHY (10:00) and OMI (13:45) $NO_2$ is maximum in summer when SCIAMACHY is up to 40% higher than OMI, and minimum in winter when OMI slightly exceeds SCIAMACHY. A similar seasonal variation in the diurnal difference is found in the source region of Cairo. The surface measurements in Israel cities confirm this seasonal variation in the diurnal cycle. Using simulations from a global 3-D chemical transport model (GEOS-Chem), we show that this seasonal cycle can be explained by a much stronger photochemical loss of $NO_2$ in summer than in winter.Engineering and Applied Science

Tree-space statistics and approximations for large-scale analysis of anatomical trees

Statistical analysis of anatomical trees is hard to perform due to differences in the topological structure of the trees. In this paper we define statistical properties of leaf-labeled anatomical trees with geometric edge attributes by considering the anatomical trees as points in the geometric space of leaf-labeled trees. This tree-space is a geodesic metric space where any two trees are connected by a unique shortest path, which corresponds to a tree deformation. However, tree-space is not a manifold, and the usual strategy of performing statistical analysis in a tangent space and projecting onto tree-space is not available. Using tree-space and its shortest paths, a variety of statistical properties, such as mean, principal component, hypothesis testing and linear discriminant analysis can be defined. For some of these properties it is still an open problem how to compute them; others (like the mean) can be computed, but efficient alternatives are helpful in speeding up algorithms that use means iteratively, like hypothesis testing. In this paper, we take advantage of a very large dataset (N = 8016) to obtain computable approximations, under the assumption that the data trees parametrize the relevant parts of tree-space well. Using the developed approximate statistics, we illustrate how the structure and geometry of airway trees vary across a population and show that airway trees with Chronic Obstructive Pulmonary Disease come from a different distribution in tree-space than healthy ones. Software is available from http://image.diku.dk/aasa/software.php

Holocene environment of Central Kamchatka, Russia: Implications from a multi-proxy record of Two-Yurts Lake

© 2015 Elsevier B.V. Within the scope of Russian-German palaeoenvironmental research, Two-Yurts Lake (TYL, Dvuh-Yurtochnoe in Russian) was chosen as the main scientific target area to decipher Holocene climate variability on Kamchatka. The 5. ×. 2 km large and 26 m deep lake is of proglacial origin and situated on the eastern flank of Sredinny Ridge at the northwestern end of the Central Kamchatka Valley, outside the direct influence of active volcanism. Here, we present results of a multi-proxy study on sediment cores, spanning about the last 7000 years. The general tenor of the TYL record is an increase in continentality and winter snow cover in conjunction with a decrease in temperature, humidity, and biological productivity after 5000-4500. cal. yrs. BP, inferred from pollen and diatom data and the isotopic composition of organic carbon. The TYL proxy data also show that the late Holocene was punctuated by two colder spells, roughly between 4500 and 3500 cal. yrs. BP and between 1000 and 200 cal. yrs. BP, as local expressions of the Neoglacial and Little Ice Age, respectively. These environmental changes can be regarded as direct and indirect responses to climate change, as also demonstrated by other records in the regional terrestrial and marine realm. Long-term climate deterioration was driven by decreasing insolation, while the short-term climate excursions are best explained by local climatic processes. The latter affect the configuration of atmospheric pressure systems that control the sources as well as the temperature and moisture of air masses reaching Kamchatka

Use of Serum MicroRNAs as Biomarker for Hepatobiliary Diseases in Dogs

Copyrigh

A multi-parent recombinant inbred line population of C. elegans allows identification of novel QTLs for complex life history traits

Background The nematode Caenorhabditis elegans has been extensively used to explore the relationships between complex traits, genotypes, and environments. Complex traits can vary across different genotypes of a species, and the genetic regulators of trait variation can be mapped on the genome using quantitative trait locus (QTL) analysis of recombinant inbred lines (RILs) derived from genetically and phenotypically divergent parents. Most RILs have been derived from crossing two parents from globally distant locations. However, the genetic diversity between local C. elegans populations can be as diverse as between global populations and could thus provide means of identifying genetic variation associated with complex traits relevant on a broader scale. Results To investigate the effect of local genetic variation on heritable traits, we developed a new RIL population derived from 4 parental wild isolates collected from 2 closely located sites in France: Orsay and Santeuil. We crossed these 4 genetically diverse parental isolates to generate a population of 200 multi-parental RILs and used RNA-seq to obtain sequence polymorphisms identifying almost 9000 SNPs variable between the 4 genotypes with an average spacing of 11 kb, doubling the mapping resolution relative to currently available RIL panels for many loci. The SNPs were used to construct a genetic map to facilitate QTL analysis. We measured life history traits such as lifespan, stress resistance, developmental speed, and population growth in different environments, and found substantial variation for most traits. We detected multiple QTLs for most traits, including novel QTLs not found in previous QTL analysis, including those for lifespan and pathogen responses. This shows that recombining genetic variation across C. elegans populations that are in geographical close proximity provides ample variation for QTL mapping. Conclusion Taken together, we show that using more parents than the classical two parental genotypes to construct a RIL population facilitates the detection of QTLs and that the use of wild isolates facilitates the detection of QTLs. The use of multi-parent RIL populations can further enhance our understanding of local adaptation and life history trade-offs

Murine Fig4 is dispensable for muscle development but required for muscle function

Abstract Background Phosphatidylinositol phosphates (PIPs) are low-abundance phospholipids that participate in a range of cellular processes, including cell migration and membrane traffic. PIP levels and subcellular distribution are regulated by a series of lipid kinases and phosphatases. In skeletal muscle, PIPs and their enzymatic regulators serve critically important functions exemplified by mutations of the PIP phosphatase MTM1 in myotubular myopathy (MTM), a severe muscle disease characterized by impaired muscle structure and abnormal excitation–contraction coupling. FIG4 functions as a PIP phosphatase that participates in both the synthesis and breakdown of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2). Mutation of FIG4 results in a severe neurodegenerative disorder in mice and a progressive peripheral polyneuropathy in humans. The effect of FIG4 mutation on skeletal muscle has yet to be examined. Methods Herein we characterize the impact of FIG4 on skeletal muscle development and function using the spontaneously occurring mouse mutant pale tremor (plt), a mouse line with a loss of function mutation in Fig4. Results In plt mice, we characterized abnormalities in skeletal muscle, including reduced muscle size and specific force generation. We also uncovered ultrastructural abnormalities and increased programmed cell death. Conversely, we detected no structural or functional abnormalities to suggest impairment of excitation–contraction coupling, a process previously shown to be influenced by PI(3,5)P2 levels. Conditional rescue of Fig4 mutation in neurons prevented overt muscle weakness and the development of obvious muscle abnormalities, suggesting that the changes observed in the plt mice were primarily related to denervation of skeletal muscle. On the basis of the ability of reduced FIG4 levels to rescue aspects of Mtmr2-dependent neuropathy, we evaluated the effect of Fig4 haploinsufficiency on the myopathy of Mtm1-knockout mice. Male mice with a compound Fig4 +/−/Mtm1 –/Y genotype displayed no improvements in muscle histology, muscle size or overall survival, indicating that FIG4 reduction does not ameliorate the Mtm1-knockout phenotype. Conclusions Overall, these data indicate that loss of Fig4 impairs skeletal muscle function but does not significantly affect its structural development.http://deepblue.lib.umich.edu/bitstream/2027.42/112676/1/13395_2013_Article_83.pd