ALBERT

Description: : We introduce PHOXTRACK (PHOsphosite-X-TRacing Analysis of Causal Kinases), a user-friendly freely available software tool for analyzing large datasets of post-translational modifications of proteins, such as phosphorylation, which are commonly gained by mass spectrometry detection. In contrast to other currently applied data analysis approaches, PHOXTRACK uses full sets of quantitative proteomics data and applies non-parametric statistics to calculate whether defined kinase-specific sets of phosphosite sequences indicate statistically significant concordant differences between various biological conditions. PHOXTRACK is an efficient tool for extracting post-translational information of comprehensive proteomics datasets to decipher key regulatory proteins and to infer biologically relevant molecular pathways. Availability: PHOXTRACK will be maintained over the next years and is freely available as an online tool for non-commercial use at http://phoxtrack.molgen.mpg.de . Users will also find a tutorial at this Web site and can additionally give feedback at https://groups.google.com/d/forum/phoxtrack-discuss . Contact: sauer@molgen.mpg.de . Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Since its 2001 debut, the University of California, Santa Cruz (UCSC) Genome Browser ( http://genome.ucsc.edu/ ) team has provided continuous support to the international genomics and biomedical communities through a web-based, open source platform designed for the fast, scalable display of sequence alignments and annotations landscaped against a vast collection of quality reference genome assemblies. The browser's publicly accessible databases are the backbone of a rich, integrated bioinformatics tool suite that includes a graphical interface for data queries and downloads, alignment programs, command-line utilities and more. This year's highlights include newly designed home and gateway pages; a new ‘multi-region’ track display configuration for exon-only, gene-only and custom regions visualization; new genome browsers for three species (brown kiwi, crab-eating macaque and Malayan flying lemur); eight updated genome assemblies; extended support for new data types such as CRAM, RNA-seq expression data and long-range chromatin interaction pairs; and the unveiling of a new supported mirror site in Japan.

Description: The Lower Rhine Embayment in Central Europe hosts a rift system that has very low deformation rates. The faults in this area have slip rates of less than 0.1 mm yr –1 , which does not allow to investigate ongoing tectonic deformation with geodetic techniques, unless they cover very long time spans. Instrumental seismicity does only cover a small fraction of the very long earthquake recurrence intervals of several thousands of years. Palaeoseismological studies are needed to constrain slip rates and the earthquake history of such faults. Destructive earthquakes are rare in the study area, but did occur in historic times. In 1755/1756, a series of strong earthquakes caused significant destruction in the city of Düren (Germany) and the surrounding areas. In this study we document palaeoseismological data from the nearby Rurrand Fault. In contrast to earlier studies on the same fault, we found evidence for a surface rupturing earthquake in the Holocene, and we identified at least one more surface rupturing event. Our study shows that the Rurrand Fault currently accommodates deformation in earthquakes rather than by creeping. The coseismic offsets were determined to be between less than 0.5 m per event. We assign maximum possible magnitudes of M w 5.9–6.8 for the Rurrand Fault and a slip rate of at least 0.02–0.03 mm yr –1 for the last ~130–50 kyr. The surface ruptures did not occur at the main fault trace that has a clear morphological expression due to older tectonic motions, but on a younger fault strand in the hanging wall of the main fault. Terrain analyses based on 1 m resolution airborne LiDAR data have been used to image the subtle morphological expression of this young fault zone. Georadar and electric resistivity tomography were applied to image the fault zone at depth and to test if these shallow geophysical methods can be used to identify and trace the fault zone. Georadar failed to produce reliable results, but geoelectrics were successfully applied and allowed us to retrieve slip rate estimates. Our results indicate that the Düren 1755/1756 earthquakes did not produce surface ruptures at the Rurrand Fault, either because they did not rupture the surface at all, or because they occurred at another, neighbouring fault.

Description: Yeast species represent an ideal model system for population genomic studies but large-scale polymorphism surveys have only been reported for species of the Saccharomyces genus so far. Hence, little is known about intraspecific diversity and evolution in yeast. To obtain a new insight into the evolutionary forces shaping natural populations, we sequenced the genomes of an expansive worldwide collection of isolates from a species distantly related to Saccharomyces cerevisiae : Lachancea kluyveri (formerly S. kluyveri ). We identified 6.5 million single nucleotide polymorphisms and showed that a large introgression event of 1 Mb of GC-rich sequence in the chromosomal arm probably occurred in the last common ancestor of all L. kluyveri strains. Our population genomic data clearly revealed that this 1-Mb region underwent a molecular evolution pattern very different from the rest of the genome. It is characterized by a higher recombination rate, with a dramatically elevated A:T -〉 G:C substitution rate, which is the signature of an increased GC-biased gene conversion. In addition, the predicted base composition at equilibrium demonstrates that the chromosome-scale compositional heterogeneity will persist after the genome has reached mutational equilibrium. Altogether, the data presented herein clearly show that distinct recombination and substitution regimes can coexist and lead to different evolutionary patterns within a single genome.

Description: Nature Physics 13, 276 (2017). doi:10.1038/nphys3942 Authors: A. Caratti o Garatti, B. Stecklum, R. Garcia Lopez, J. Eislöffel, T. P. Ray, A. Sanna, R. Cesaroni, C. M. Walmsley, R. D. Oudmaijer, W. J. de Wit, L. Moscadelli, J. Greiner, A. Krabbe, C. Fischer, R. Klein & J. M. Ibañez Solar-mass stars form via disk-mediated accretion. Recent findings indicate that this process is probably episodic in the form of accretion bursts, possibly caused by disk fragmentation. Although it cannot be ruled out that high-mass young stellar objects arise from the coalescence of their low-mass brethren, the latest results suggest that they more likely form via disks. It follows that disk-mediated accretion bursts should occur. Here we report on the discovery of the first disk-mediated accretion burst from a roughly twenty-solar-mass high-mass young stellar object. Our near-infrared images show the brightening of the central source and its outflow cavities. Near-infrared spectroscopy reveals emission lines typical for accretion bursts in low-mass protostars, but orders of magnitude more luminous. Moreover, the released energy and the inferred mass-accretion rate are also orders of magnitude larger. Our results identify disk-accretion as the common mechanism of star formation across the entire stellar mass spectrum.

Description: Polyglutamine diseases, including spinocerebellar ataxia type 3 (SCA3), are caused by CAG repeat expansions that encode abnormally long glutamine repeats in the respective disease proteins. While the mechanisms underlying neurodegeneration remain uncertain, evidence supports a proteotoxic role for the mutant protein dictated in part by the specific genetic and protein context. To further define pathogenic mechanisms in SCA3, we generated a mouse model in which a CAG expansion of 82 repeats was inserted into the murine locus by homologous recombination. SCA3 knockin mice exhibit region-specific aggregate pathology marked by intranuclear accumulation of the mutant Atxn3 protein, abundant nuclear inclusions and, in select brain regions, extranuclear aggregates localized to neuritic processes. Knockin mice also display altered splicing of the disease gene, promoting expression of an alternative isoform in which the intron immediately downstream of the CAG repeat is retained. In an independent mouse model expressing the full human ATXN3 disease gene, expression of this alternatively spliced transcript is also enhanced. These results, together with recent findings in other polyglutamine diseases, suggest that CAG repeat expansions can promote aberrant splicing to produce potentially more aggregate-prone isoforms of the disease proteins. This report of a SCA3 knockin mouse expands the repertoire of existing models of SCA3, and underscores the potential contribution of alternative splicing to disease pathogenesis in SCA3 and other polyglutamine disorders.

Description: Increased physiological levels of oxysterols are major risk factors for developing atherosclerosis and cardiovascular disease. Lipid-loaded macrophages, termed foam cells, are important during the early development of atherosclerotic plaques. To pursue the hypothesis that ligand-based modulation of the nuclear receptor LXRα is crucial for cell homeostasis during atherosclerotic processes, we analysed genome-wide the action of LXRα in foam cells and macrophages. By integrating chromatin immunoprecipitation-sequencing (ChIP-seq) and gene expression profile analyses, we generated a highly stringent set of 186 LXRα target genes. Treatment with the nanomolar-binding ligand T0901317 and subsequent auto-regulatory LXRα activation resulted in sequence-dependent sharpening of the genome-binding patterns of LXRα. LXRα-binding loci that correlated with differential gene expression revealed 32 novel target genes with potential beneficial effects, which in part explained the implications of disease-associated genetic variation data. These observations identified highly integrated LXRα ligand-dependent transcriptional networks, including the APOE/C1/C4/C2 -gene cluster, which contribute to the reversal of cholesterol efflux and the dampening of inflammation processes in foam cells to prevent atherogenesis.

Description: Profile hidden Markov models (profile HMMs) are known to efficiently predict whether an amino acid (AA) sequence belongs to a specific protein family. Profile HMMs can also be used to search for protein domains in genome sequences. In this case, HMMs are typically learned from AA sequences and then used to search on the six-frame translation of nucleotide (NT) sequences. However, this approach demands additional processing of the original data and search results. Here, we propose an alternative and more direct method which converts an AA alignment into an NT one, after which an NT-based HMM is trained to be applied directly on a genome. Contact : carlos@rc.unesp.br Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Milk is a major food of global economic importance, and its consumption is regarded as a classic example of gene-culture evolution. Humans have exploited animal milk as a food resource for at least 8500 years, but the origins, spread, and scale of dairying remain poorly understood. Indirect lines of evidence, such as lipid isotopic ratios of pottery residues, faunal mortality profiles, and lactase persistence allele frequencies, provide a partial picture of this process; however, in order to understand how, where, and when humans consumed milk products, it is necessary to link evidence of consumption directly to individuals and their dairy livestock. Here we report the first direct evidence of milk consumption, the whey protein β-lactoglobulin (BLG), preserved in human dental calculus from the Bronze Age (ca. 3000 BCE) to the present day. Using protein tandem mass spectrometry, we demonstrate that BLG is a species-specific biomarker of dairy consumption, and we identify individuals consuming cattle, sheep, and goat milk products in the archaeological record. We then apply this method to human dental calculus from Greenland's medieval Norse colonies, and report a decline of this biomarker leading up to the abandonment of the Norse Greenland colonies in the 15th century CE. Scientific Reports 4 doi: 10.1038/srep07104

Description: A Unified Framework for Reservoir Computing and Extreme Learning Machines based on a Single Time-delayed Neuron Scientific Reports, Published online: 8 October 2015; doi:10.1038/srep14945