Association of Borrelia garinii and B. valaisiana with Songbirds in Slovakia

In Europe, 6 of the 11 genospecies of Borrelia burgdorferi sensu lato are prevalent in questing Ixodes ricinus ticks. In most parts of Central Europe, B. afzelii, B. garinii, and B. valaisiana are the most frequent species, whereas B. burgdorferi sensu stricto, B. bissettii, and B. lusitaniae are rare. Previously, it has been shown that B. afzelii is associated with European rodents. Therefore, the aim of this study was to identify reservoir hosts of B. garinii and B. valaisiana in Slovakia. Songbirds were captured in a woodland near Bratislava and investigated for engorged ticks. Questing I. ricinus ticks were collected in the same region. Both tick pools were analyzed for spirochete infections by PCR, followed by DNA-DNA hybridization and, for a subsample, by nucleotide sequencing. Three of the 17 captured songbird species were infested with spirochete-infected ticks. Spirochetes in ticks that had fed on birds were genotyped as B. garinii and B. valaisiana, whereas questing ticks were infected with B. afzelii, B. garinii, and B. valaisiana. Furthermore, identical ospA alleles of B. garinii were found in ticks that had fed on the birds and in questing ticks. The data show that songbirds are reservoir hosts of B. garinii and B. valaisiana but not of B. afzelii. This and previous studies confirm that B. burgdorferi sensu lato is host associated and that this bacterial species complex contains different ecotypes.     

Discovery and validation of a colorectal cancer classifier in a new blood test with improved performance for high-risk subjects

Background

The aim was to improve upon an existing blood-based colorectal cancer (CRC) test directed to high-risk symptomatic patients, by developing a new CRC classifier to be used with a new test embodiment. The new test uses a robust assay format—electrochemiluminescence immunoassays—to quantify protein concentrations. The aim was achieved by building and validating a CRC classifier using concentration measures from a large sample set representing a true intent-to-test (ITT) symptomatic population.

Methods

4435 patient samples were drawn from the Endoscopy II sample set. Samples were collected at seven hospitals across Denmark between 2010 and 2012 from subjects with symptoms of colorectal neoplasia. Colonoscopies revealed the presence or absence of CRC. 27 blood plasma proteins were selected as candidate biomarkers based on previous studies. Multiplexed electrochemiluminescence assays were used to measure the concentrations of these 27 proteins in all 4435 samples. 3066 patients were randomly assigned to the Discovery set, in which machine learning was used to build candidate classifiers. Some classifiers were refined by allowing up to a 25% indeterminate score range. The classifier with the best Discovery set performance was successfully validated in the separate Validation set, consisting of 1336 samples.

Results

The final classifier was a logistic regression using ten predictors: eight proteins (A1AG, CEA, CO9, DPPIV, MIF, PKM2, SAA, TFRC), age, and gender. In validation, the indeterminate rate of the new panel was 23.2%, sensitivity/specificity was 0.80/0.83, PPV was 36.5%, and NPV was 97.1%.

Conclusions

The validated classifier serves as the basis of a new blood-based CRC test for symptomatic patients. The improved performance, resulting from robust concentration measures across a large sample set mirroring the ITT population, renders the new test the best available for this population. Results from a test using this classifier can help assess symptomatic patients’ CRC risk, increase their colonoscopy compliance, and manage next steps in their care.

     

Life Cycle Impacts and Benefits of Wood along the Value Chain: The Case of Switzerland

Sustainable use of wood may contribute to coping with energy and material resource challenges. The goal of this study is to increase knowledge of the environmental effects of wood use by analyzing the complete value chain of all wooden goods produced or consumed in Switzerland. We start from a material flow analysis of current wood use in Switzerland. Environmental impacts related to the material flows are evaluated using life cycle assessment–based environmental indicators. Regarding climate change, we find an overall average benefit of 0.5 tonnes carbon dioxide equivalent per cubic meter of wood used. High environmental benefits are often achieved when replacing conventional heat production and energy‐consuming materials in construction and furniture. The environmental performance of wood is, however, highly dependent on its use and environmental indicators. To exploit the mitigation potential of wood, we recommend to (1) apply its use where there are high substitution benefits like the replacement of fossil fuels for energy or energy‐intensive building materials, (2) take appropriate measures to minimize negative effects like particulate matter emissions, and (3) keep a systems perspective to weigh effects like substitution and cascading against each other in a comprehensive manner. The results can provide guidance for further in‐depth studies and prospective analyses of wood‐use scenarios.     

Increase of methane formation by ethanol addition during continuous fermentation of biogas sludge

Very recently, it was shown that the addition of acetate or ethanol led to enhanced biogas formation rates during an observation period of 24 h. To determine if increased methane production rates due to ethanol addition can be maintained over longer time periods, continuous reactors filled with biogas sludge were developed which were fed with the same substrates as the full-scale reactor from which the sludge was derived. These reactors are well reflected conditions of a full-scale biogas plant during a period of 14 days. When the fermenters were pulsed with 50–100 mM ethanol, biomethanation increased by 50–150 %, depending on the composition of the biogas sludge. It was also possible to increase methane formation significantly when 10–20 mM pure ethanol or ethanolic solutions (e.g. beer) were added daily. In summary, the experiments revealed that “normal” methane production continued to take place, but ethanol led to production of additional methane.     

State-of-the art data normalization methods improve NMR-based metabolomic analysis

Extracting biomedical information from large metabolomic datasets by multivariate data analysis is of considerable complexity. Common challenges include among others screening for differentially produced metabolites, estimation of fold changes, and sample classification. Prior to these analysis steps, it is important to minimize contributions from unwanted biases and experimental variance. This is the goal of data preprocessing. In this work, different data normalization methods were compared systematically employing two different datasets generated by means of nuclear magnetic resonance (NMR) spectroscopy. To this end, two different types of normalization methods were used, one aiming to remove unwanted sample-to-sample variation while the other adjusts the variance of the different metabolites by variable scaling and variance stabilization methods. The impact of all methods tested on sample classification was evaluated on urinary NMR fingerprints obtained from healthy volunteers and patients suffering from autosomal polycystic kidney disease (ADPKD). Performance in terms of screening for differentially produced metabolites was investigated on a dataset following a Latin-square design, where varied amounts of 8 different metabolites were spiked into a human urine matrix while keeping the total spike-in amount constant. In addition, specific tests were conducted to systematically investigate the influence of the different preprocessing methods on the structure of the analyzed data. In conclusion, preprocessing methods originally developed for DNA microarray analysis, in particular, Quantile and Cubic-Spline Normalization, performed best in reducing bias, accurately detecting fold changes, and classifying samples.

     

Evolution under pH stress and high population densities leads to increased density-dependent fitness in the protist Tetrahymena thermophila

Abiotic stress is a major force of selection that organisms are constantly facing. While the evolutionary effects of various stressors have been broadly studied, it is only more recently that the relevance of interactions between evolution and underlying ecological conditions, that is, eco-evolutionary feedbacks, have been highlighted. Here, we experimentally investigated how populations adapt to pH-stress under high population densities. Using the protist species Tetrahymena thermophila, we studied how four different genotypes evolved in response to stressfully low pH conditions and high population densities. We found that genotypes underwent evolutionary changes, some shifting up and others shifting down their intrinsic rates of increase (r₀). Overall, evolution at low pH led to the convergence of r₀ and intraspecific competitive ability (α) across the four genotypes. Given the strong correlation between r₀ and α, we argue that this convergence was a consequence of selection for increased density-dependent fitness at low pH under the experienced high density conditions. Increased density-dependent fitness was either attained through increase in r₀, or decrease of α, depending on the genetic background. In conclusion, we show that demography can influence the direction of evolution under abiotic stress.     

Genome duplication and the origin of angiosperms

Despite intensive research, little is known about the origin of the angiosperms and their rise to ecological dominance during the Early Cretaceous. Based on whole-genome analyses of Arabidopsis thaliana, there is compelling evidence that angiosperms underwent two whole-genome duplication events early during their evolutionary history. Recent studies have shown that these events were crucial for the creation of many important developmental and regulatory genes found in extant angiosperm genomes. Here, we argue that these ancient polyploidy events might have also had an important role in the origin and diversification of the angiosperms.     

M line-deficient titin causes cardiac lethality through impaired maturation of the sarcomere

Titin, the largest protein known to date, has been linked to sarcomere assembly and function through its elastic adaptor and signaling domains. Titin's M-line region contains a unique kinase domain that has been proposed to regulate sarcomere assembly via its substrate titin cap (T-cap). In this study, we use a titin M line-deficient mouse to show that the initial assembly of the sarcomere does not depend on titin's M-line region or the phosphorylation of T-cap by the titin kinase. Rather, titin's M-line region is required to form a continuous titin filament and to provide mechanical stability of the embryonic sarcomere. Even without titin integrating into the M band, sarcomeres show proper spacing and alignment of Z discs and M bands but fail to grow laterally and ultimately disassemble. The comparison of disassembly in the developing and mature knockout sarcomere suggests diverse functions for titin's M line in embryonic development and the adult heart that not only involve the differential expression of titin isoforms but also of titin-binding proteins.