Epigenetic clocks provide powerful tools to evaluate nutritional, hormonal, and genetic effects on aging. What can we learn from differences between species in how these clocks tick?Please see ...related Research articles: http://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1203-5 , http://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1186-2 , http://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1187-1 and http://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1185-3.
Replicative senescence of cells
is often considered as counterpart for aging of the organism
. In fact, both processes are associated with functional decay and similar molecular modifications. On ...epigenetic level, replicative senescence and aging evoke characteristic modifications in the DNA methylation (DNAm) pattern, but at different sites in the genome. Various epigenetic signatures, which are often referred to as epigenetic clocks, provide useful biomarkers: Senescence-associated epigenetic modifications can be used for quality control of cell preparations or to elucidate effects of culture conditions on the state of cellular aging. Age-associated epigenetic modifications hold high expectations to determine chronological age in forensics or to identify parameters that impact on biological aging. Despite these differences, there are some striking similarities between senescence- and age-associated DNAm, such as complete rejuvenation during reprogramming into induced pluripotent stem cells (iPSCs). It is yet unclear what makes epigenetic clocks tick, but there is evidence that the underlying mechanisms of both processes are related to similar modifications in the histone code or higher order chromatin. Replicative senescence therefore appears to be a suitable model system to gain better insight into how organismal aging might be governed epigenetically.
Recent advances in sequencing technologies provide unprecedented opportunities for epigenetic biomarker development. Particularly the DNA methylation pattern-which is modified at specific sites in ...the genome during cellular differentiation, aging, and disease-holds high hopes for a wide variety of diagnostic applications. While many epigenetic biomarkers have been described, only very few of them have so far been successfully translated into clinical practice and almost exclusively in the field of oncology. This discrepancy might be attributed to the different demands of either publishing a new finding or establishing a standardized and approved diagnostic procedure. This is exemplified for epigenetic leukocyte counts and epigenetic age-predictions. To ease later clinical translation, the following hallmarks should already be taken into consideration when designing epigenetic biomarkers: 1) Identification of best genomic regions, 2) pre-analytical processing, 3) accuracy of DNA methylation measurements, 4) identification of confounding parameters, 5) accreditation as diagnostic procedure, 6) standardized data analysis, 7) turnaround time, and 8) costs and customer requirements. While the initial selection of relevant genomic regions is usually performed on genome wide DNA methylation profiles, it might be advantageous to subsequently establish targeted assays that focus on specific genomic regions. Development of an epigenetic biomarker for clinical application is a long and cumbersome process that is only initiated with the identification of an epigenetic signature.
We propose a method for merging soil moisture retrievals from spaceborne active and passive microwave instruments based on weighted averaging taking into account the error characteristics of the ...individual data sets. The merging scheme is parameterized using error variance estimates obtained from using triple collocation analysis (TCA). In regions where TCA is deemed unreliable, we use correlation significance levels (<inline-formula> <tex-math notation="LaTeX">p </tex-math></inline-formula>-values) as indicator for retrieval quality to decide whether to use active data only, passive data only, or an unweighted average. We apply the proposed merging scheme to active retrievals from advanced scatterometer and passive retrievals from the Advanced Microwave Scanning Radiometer-Earth Observing System using Global Land Data Assimilation System-Noah to complement the triplet required for TCA. The merged time series is evaluated against soil moisture estimates from ERA-Interim/Land and in situ measurements from the International Soil Moisture Network using the European Space Agency's (ESA's) current Climate Change Initiative-Soil Moisture (ESA CCI SM) product version v02.3 as benchmark merging scheme. Results show that the <inline-formula> <tex-math notation="LaTeX">p </tex-math></inline-formula>-value classification provides a robust basis for decisions regarding using either active or passive data alone, or an unweighted average in cases where relative weights cannot be estimated reliably, and that the weights estimated from TCA in almost all cases outperform the ternary decision upon which the ESA CCI SM v02.3 is based. The proposed method forms the basis for the new ESA CCI SM product version v03.x and higher.
Aging is associated with highly reproducible DNA methylation (DNAm) changes, which may contribute to higher prevalence of malignant diseases in the elderly. In this study, we analyzed epigenetic ...aging signatures in 5,621 DNAm profiles of 25 cancer types from The Cancer Genome Atlas (TCGA). Overall, age-associated DNAm patterns hardly reflect chronological age of cancer patients, but they are coherently modified in a non-stochastic manner, particularly at CpGs that become hypermethylated upon aging in non-malignant tissues. This coordinated regulation in epigenetic aging signatures can therefore be used for aberrant epigenetic age-predictions, which facilitate disease stratification. For example, in acute myeloid leukemia (AML) higher epigenetic age-predictions are associated with increased incidence of mutations in RUNX1, WT1, and IDH2, whereas mutations in TET2, TP53, and PML-PARA translocation are more frequent in younger age-predictions. Furthermore, epigenetic aging signatures correlate with overall survival in several types of cancer (such as lower grade glioma, glioblastoma multiforme, esophageal carcinoma, chromophobe renal cell carcinoma, cutaneous melanoma, lung squamous cell carcinoma, and neuroendocrine neoplasms). In conclusion, age-associated DNAm patterns in cancer are not related to chronological age of the patient, but they are coordinately regulated, particularly at CpGs that become hypermethylated in normal aging. Furthermore, the apparent epigenetic age-predictions correlate with clinical parameters and overall survival in several types of cancer, indicating that regulation of DNAm patterns in age-associated CpGs is relevant for cancer development.
Living covalent polymerization has been a subject of intense research for many decades and has culminated in the synthesis of a large variety of block copolymers (BCPs) with structural and functional ...diversity. In contrast, the research on supramolecular BCPs is still in its infancy and their generation by living processes remains a challenge. Here we report the formation of supramolecular block copolymers by two-component seeded living polymerization of properly designed perylene bisimides (PBIs) under precise kinetic control. Our detailed studies on thermodynamically and kinetically controlled supramolecular polymerization of three investigated PBIs, which contain hydrogen-bonding amide side groups in imide position and chlorine, methoxy, or methylthio substituents in 1,7 bay-positions, revealed that these PBIs form kinetically metastable H-aggregates, which can be transformed into the thermodynamically favored J-aggregates by seed-induced living polymerization. We show here that copolymerization of kinetically trapped states of one PBI with seeds of another PBI leads to the formation of supramolecular block copolymers by chain-growth process from the seed termini as confirmed by UV/vis spectroscopy and atomic force microscopy (AFM). This work demonstrates for the first time the formation of triblock supramolecular polymer architectures with A-B-A and B-A-B block pattern by alternate two-component seeded polymerization in a living manner.
Abstract Culture media for therapeutic cell preparations—such as mesenchymal stromal cells (MSCs)—usually comprise serum additives. Traditionally, fetal bovine serum is supplemented in basic research ...and in most clinical trials. Within the past years, many laboratories adapted their culture conditions to human platelet lysate (hPL), which further stimulates proliferation and expansion of MSCs. Particularly with regard to clinical application, human alternatives for fetal bovine serum are clearly to be preferred. hPL is generated from human platelet units by disruption of the platelet membrane, which is commonly performed by repeated freeze and thaw cycles. Such culture supplements are notoriously ill-defined, and many parameters contribute to batch-to-batch variation in hPL such as different amounts of plasma, a broad range of growth factors and donor-specific effects. The plasma components of hPL necessitate addition of anticoagulants such as heparins to prevent gelatinization of hPL medium, and their concentration must be standardized. Labels for description of hPL—such as “xenogen-free,” “animal-free” and “serum free”—are not used consistently in the literature and may be misleading if not critically assessed. Further analysis of the precise composition of relevant growth factors, attachment factors, microRNAs and exosomes will pave the way for optimized and defined culture conditions. The use of hPL has several advantages and disadvantages: they must be taken into account because the choice of cell culture additive has major impact on cell preparations.
Due to its relation to the Earth’s climate and weather and phenomena like drought, flooding, or landslides, knowledge of the soil moisture content is valuable to many scientific and professional ...users. Remote-sensing offers the unique possibility for continuous measurements of this variable. Especially for agriculture, there is a strong demand for high spatial resolution mapping. However, operationally available soil moisture products exist with medium to coarse spatial resolution only (≥1 km). This study introduces a machine learning (ML)—based approach for the high spatial resolution (50 m) mapping of soil moisture based on the integration of Landsat-8 optical and thermal images, Copernicus Sentinel-1 C-Band SAR images, and modelled data, executable in the Google Earth Engine. The novelty of this approach lies in applying an entirely data-driven ML concept for global estimation of the surface soil moisture content. Globally distributed in situ data from the International Soil Moisture Network acted as an input for model training. Based on the independent validation dataset, the resulting overall estimation accuracy, in terms of Root-Mean-Squared-Error and R², was 0.04 m3·m−3 and 0.81, respectively. Beyond the retrieval model itself, this article introduces a framework for collecting training data and a stand-alone Python package for soil moisture mapping. The Google Earth Engine Python API facilitates the execution of data collection and retrieval which is entirely cloud-based. For soil moisture retrieval, it eliminates the requirement to download or preprocess any input datasets.
Crop monitoring is of great importance for e.g., yield prediction and increasing water use efficiency. The Copernicus Sentinel-1 mission operated by the European Space Agency provides the opportunity ...to monitor Earth’s surface using radar at high spatial and temporal resolution. Sentinel-1’s Synthetic Aperture Radar provides co- and cross-polarized backscatter, enabling the calculation of microwave indices. In this study, we assess the potential of Sentinel-1 VV and VH backscatter and their ratio VH/VV, the cross ratio (CR), to monitor crop conditions. A quantitative assessment is provided based on in situ reference data of vegetation variables for different crops under varying meteorological conditions. Vegetation Water Content (VWC), biomass, Leaf Area Index (LAI) and height are measured in situ for oilseed-rape, corn and winter cereals at different fields during two growing seasons. To quantify the sensitivity of backscatter and microwave indices to vegetation dynamics, linear and exponential models and machine learning methods have been applied to the Sentinel-1 data and in situ measurements. Using an exponential model, the CR can account for 87% and 63% of the variability in VWC for corn and winter cereals. In oilseed-rape, the coefficient of determination ( R 2 ) is lower ( R 2 = 0.34) due to the large difference in VWC between the two growing seasons and changes in vegetation structure that affect backscatter. Findings from the Random Forest analysis, which uses backscatter, microwave indices and soil moisture as input variables, show that CR is by and large the most important variable to estimate VWC. This study demonstrates, based on a quantitative analysis, the large potential of microwave indices for vegetation monitoring of VWC and phenology.
A new amphiphilic BF2‐azadipyrromethene (aza‐BODIPY) dye 1 has been synthesized using a CuI‐catalyzed “click” reaction. For this dye, two self‐assembly pathways that lead to different type of ...J‐aggregates with distinct near‐infrared optical properties have been discovered. The metastable off‐pathway product displays a broad, structureless absorption band while the thermodynamically stable on‐pathway aggregate exhibits the characteristic spectral features of a J‐aggregate, that is, red‐shifted intense absorption band with significantly narrowed linewidth. The morphology and structure of the aggregates were studied by atomic force microscopy, transmission and scanning electron microscopy. The aggregation processes of 1 were investigated by temperature‐ and concentration‐dependent UV/Vis spectroscopy and evaluated by models for cooperative self‐assembly.
Chlorophyll analog: An amphiphilic BF2‐azadipyrromethene (aza‐BODIPY) dye 1 forms two types of aggregates with distinct optical properties and nanoscale morphologies through competing cooperative self‐assembly pathways. The observed rod‐like morphology and exciton characteristics for the aza‐BODIPY‐based J‐aggregates are comparable to those of natural chlorophyll dye assemblies.
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