Conserved substitution patterns around nucleosome footprints in eukaryotes and Archaea derive from frequent nucleosome repositioning through evolution.

Nucleosomes, the basic repeat units of eukaryotic chromatin, have been suggested to influence the evolution of eukaryotic genomes, both by altering the propensity of DNA to mutate and by selection acting to maintain or exclude nucleosomes in particular locations. Contrary to the popular idea that nucleosomes are unique to eukaryotes, histone proteins have also been discovered in some archaeal genomes. Archaeal nucleosomes, however, are quite unlike their eukaryotic counterparts in many respects, including their assembly into tetramers (rather than octamers) from histone proteins that lack N- and C-terminal tails. Here, we show that despite these fundamental differences the association between nucleosome footprints and sequence evolution is strikingly conserved between humans and the model archaeon Haloferax volcanii. In light of this finding we examine whether selection or mutation can explain concordant substitution patterns in the two kingdoms. Unexpectedly, we find that neither the mutation nor the selection model are sufficient to explain the observed association between nucleosomes and sequence divergence. Instead, we demonstrate that nucleosome-associated substitution patterns are more consistent with a third model where sequence divergence results in frequent repositioning of nucleosomes during evolution. Indeed, we show that nucleosome repositioning is both necessary and largely sufficient to explain the association between current nucleosome positions and biased substitution patterns. This finding highlights the importance of considering the direction of causality between genetic and epigenetic change

Finding exonic islands in a sea of non-coding sequence: splicing related constraints on protein composition and evolution are common in intron-rich genomes

Biased usage of amino acids near exon-intron boundaries is phylogenetically widespread and characteristic of species for which there are expected to be problems defining exons

The Impact of the Nucleosome Code on Protein-Coding Sequence Evolution in Yeast

Coding sequence evolution was once thought to be the result of selection on optimal protein function alone. Selection can, however, also act at the RNA level, for example, to facilitate rapid translation or ensure correct splicing. Here, we ask whether the way DNA works also imposes constraints on coding sequence evolution. We identify nucleosome positioning as a likely candidate to set up such a DNA-level selective regime and use high-resolution microarray data in yeast to compare the evolution of coding sequence bound to or free from nucleosomes. Controlling for gene expression and intra-gene location, we find a nucleosome-free “linker” sequence to evolve on average 5–6% slower at synonymous sites. A reduced rate of evolution in linker is especially evident at the 5′ end of genes, where the effect extends to non-synonymous substitution rates. This is consistent with regular nucleosome architecture in this region being important in the context of gene expression control. As predicted, codons likely to generate a sequence unfavourable to nucleosome formation are enriched in linker sequence. Amino acid content is likewise skewed as a function of nucleosome occupancy. We conclude that selection operating on DNA to maintain correct positioning of nucleosomes impacts codon choice, amino acid choice, and synonymous and non-synonymous rates of evolution in coding sequence. The results support the exclusion model for nucleosome positioning and provide an alternative interpretation for runs of rare codons. As the intimate association of histones and DNA is a universal characteristic of genic sequence in eukaryotes, selection on coding sequence composition imposed by nucleosome positioning should be phylogenetically widespread

Рациональная организация работы при проведении горноразведочных выработок в Карамкенской геологоразведочной экспедиции СВГУ

Описаны условия проведения выработок в Северной экспедиции, КГУ и Карамкенской экспедиции СВТГУ. На основании хронометражных наблюдений за продолжительностью операций цикла при проведении выработок по общеизвестной формуле Н. М. Покровского l=f(Тц ) произведен расчет продолжительности цикла. Расчет произведен по трем схемам. За основу взято количество проходчиков, занятых на операции, порядок выполнения операций во времени (последовательно, параллельно) и длина откатки составов. Приведены наиболее рациональные, по мнению авторов, циклограммы работ при проведении выработок двумя и более забоями в условиях Карамкенской ГРЭ, СВТГУ

GroEL dependency affects codon usage—support for a critical role of misfolding in gene evolution

Integrating genome-scale sequence, expression, structural and protein interaction data from E. coli we establish an interaction between chaperone (GroEL) dependency and optimal codon usage.Highly expressed sporadic substrates of GroEL employ more optimal codons than expected, show enrichment for optimal codons at structurally sensitive sites and greater conservation of codon optimality under conditions of relaxed purifying selection.We suggest that highly expressed genes cannot routinely utilize GroEL for error control so that codon usage has evolved to provide complementary error limitation, whereas obligate GroEL substrates experience relaxed selection on codon usage.Our results support a critical role of misfolding prevention in gene evolution

Strategies for weed control in maize in water sensitive areas

Dargestellt werden seit 2014 vom Pflanzenschutzdienst Niedersachsen durchgeführten Gemeinschaftsversuche zur Unkrautbekämpfung unter besonderer Berücksichtigung von Wasserschutzaspekten. Herbizid-Wirkstoffe, deren Metabolite vermehrt in Grundwasser-Gütemessnetzen in Niedersachsen gefunden wurden (Chloracetamide, v.a. S-Metolachlor) standen dabei im Mittelpunkt der Untersuchungen. Es zeigte sich, dass bezüglich S-Metolachlor gleichwertige bodenwirksame Alternativwirkstoffe zur Verfügung stehen. Gleichwohl wird die Frage diskutiert, ob durch ein gezieltes Wirkstoffmanagement (Rotation) die Austragsgefahr für die o.a. Wirkstoffgruppe minimiert werden kann. Ziel dabei ist, eine möglichst breite Wirkstoffpalette mit Bodenherbiziden im Maisanbau zu erhalten, um dadurch zum einen einer Resistenzbildung vorzubeugen und zum anderen einer `Übernutzung` verbleibender Wirkstoffe entgegen zu wirken. Letzteres könnte dann ebenfalls zu einer stärkeren Grundwassergefährdung führen. In einem ergänzenden Versuchsprojekt in 2017 konnten Erkenntnisse zur Wirksamkeit und Umsetzbarkeit mechanischer und kombinierter Verfahren der Unkrautbekämpfung gesammelt werden. Dabei zeigte sich, dass rein mechanische Maßnahmen mit einem hohen Risiko von Ertragsverlusten verbunden sind, hauptsächlich dann, wenn die Unkrautkonkurrenz in der Maisreihe nicht ausreichend ausgeschaltet werden kann. Höhere Wirkungssicherheit bei geringeren Kosten wurde durch die Kombination aus breitflächiger Vorlage eines blattaktiven Herbizids und anschließendem Hackeinsatz erzielt. Mögliche Strategien der Unkrautbekämpfung insbesondere in Wasserschutzgebeiten werden diskutiert.Since 2014, the Crop Protection Service Niedersachsen has carried out joint experiments on weed control with special consideration of water protection aspects. The focus of the investigations was the handling of herbicidal active substances whose metabolites were increasingly found in groundwater quality measurement networks in Lower Saxony (chloroacetamides, especially S-metolachlor). It was found that s-metolachlor has equivalent soil active ingredients. Nonetheless, the question is being discussed whether a targeted active ingredient management (rotation) can reduce the risk of discharge for the active ingredient. The aim ist o obtain the widest possible range of active ingredients with soil herbicides in maize cultivation, thereby preventing the formation of resistance on the one hand, and counteracting an overuse of remaining active ingredients on the other hand. The latter could then also lead to a stronger groundwater hazard. An additional experimental project in 2017 provided insights into the effectiveness and practicability of mechanical and combined weed control methods. It showed that purely mechanical measures are associated with a high risk of yield losses, especially if the weed competition in the corn line cannot be sufficiently eliminated. Greater efficacy at lower cost was achieved through the combination of broad leafy herbicide presentation and subsequent hacking. Possible strategies for weed control, especially in water conservation areas, are discussed

Recommendations for Standards of Network Care for Patients with Parkinson’s Disease in Germany

Although our understanding of Parkinson’s disease (PD) has improved and effective treatments are available, caring for people with PD remains a challenge. The large heterogeneity in terms of motor symptoms, nonmotor symptoms, and disease progression makes tailored individual therapy and individual timing of treatment necessary. On the other hand, only limited resources are available for a growing number of patients, and the high quality of treatment cannot be guaranteed across the board. At this point, networks can help to make better use of resources and improve care. The working group PD Networks and Integrated Care, part of the German Parkinson Society, is entrusted to convene clinicians, therapists, nurses, researchers, and patients to promote the development of PD networks. This article summarizes the work carried out by the working group PD Networks and Integrated Care in the development of standards of network care for patients with PD in Germany

Immune Cell Activation in the Cerebrospinal Fluid of Patients With Parkinson's Disease

Background: Parkinson's disease (PD) is a common neurodegenerative disorder. The contribution of the immune system to its pathogenesis remains incompletely understood.Methods: In this study, we performed comprehensive immune cell profiling in the cerebrospinal fluid (CSF) and peripheral blood (PB) of PD patients. Ten PD patients were diagnosed according to brain bank criteria and underwent detailed clinical examination, magnetic resonance imaging, PB and CSF immune cell profiling by multiparameter flow cytometry, and cytokine and chemokine measurements by bead-based arrays. Thirteen healthy elderly volunteers served as control population.Results: The proportions of activated T-lymphocytes and non-classical monocytes in the CSF were increased in patients with PD compared to the control group. In accordance, we found increased levels of the pro-inflammatory cytokines IL-2, IL-6 and TNFα and of the monocyte chemoattractant protein 1 (MCP-1) in the CSF of the included PD patients.Conclusions: Our data provide novel evidence for a response of the innate and adaptive immune system in the central nervous system of patients with PD

KDM2A integrates DNA and histone modification signals through a CXXC/PHD module and direct interaction with HP1.

Functional genomic elements are marked by characteristic DNA and histone modification signatures. How combinatorial chromatin modification states are recognized by epigenetic reader proteins and how this is linked to their biological function is largely unknown. Here we provide a detailed molecular analysis of chromatin recognition by the lysine demethylase KDM2A. Using biochemical approaches we identify a nucleosome interaction module within KDM2A consisting of a CXXC type zinc finger, a PHD domain and a newly identified Heterochromatin Protein 1 (HP1) interaction motif that mediates direct binding between KDM2A and HP1. This nucleosome interaction module enables KDM2A to decode nucleosomal H3K9me3 modification in addition to CpG methylation signals. The multivalent engagement with DNA and HP1 results in a nucleosome binding circuit in which KDM2A can be recruited to H3K9me3-modified chromatin through HP1, and HP1 can be recruited to unmodified chromatin by KDM2A. A KDM2A mutant deficient in HP1-binding is inactive in an in vivo overexpression assay in zebrafish embryos demonstrating that the HP1 interaction is essential for KDM2A function. Our results reveal a complex regulation of chromatin binding for both KDM2A and HP1 that is modulated by DNA- and H3K9-methylation, and suggest a direct role for KDM2A in chromatin silencing

A Smart Device System to Identify New Phenotypical Characteristics in Movement Disorders

Parkinson's disease and Essential Tremor are two of the most common movement disorders and are still associated with high rates of misdiagnosis. Collected data by technology-based objective measures (TOMs) has the potential to provide new promising and highly accurate movement data for a better understanding of phenotypical characteristics and diagnostic support. A technology-based system called Smart Device System (SDS) is going to be implemented for multi-modal high-resolution acceleration measurement of patients with PD or ET within a clinical setting. The 2-year prospective observational study is conducted to identify new phenotypical biomarkers and train an Artificial Intelligence System. The SDS is going to be integrated and tested within a 20-min assessment including smartphone-based questionnaires, two smartwatches at both wrists and tablet-based Archimedean spirals drawing for deeper tremor-analyses. The electronic questionnaires will cover data on medication, family history and non-motor symptoms. In this paper, we describe the steps for this novel technology-utilizing examination, the principal steps for data analyses and the targeted performances of the system. Future work considers integration with Deep Brain Stimulation, dissemination into further sites and patient's home setting as well as integration with further data sources as neuroimaging and biobanks. Study Registration ID on ClinicalTrials.gov: NCT03638479