Circulating tumor DNA dynamics and clinical outcome in metastatic colorectal cancer patients undergoing front-line chemotherapy.

Purpose: we tested whether ctDNA changes may be used to assess early response and clinical outcome in metastatic colorectal cancer (mCRC) patients undergoing front-line systemic anti-cancer therapy (SACT).

Experimental Design: 862 plasma samples were collected 4-weekly from baseline (BL) until disease progression in mCRC patients receiving front line SACT. ctDNA normalization was defined as ≥99% clearance after 1 month of therapy (Mo1) in the 3 variants with the highest allele frequency in BL ctDNA.

Birds influence vegetation coverage and structure on sandy biogeomorphic islands in the Dutch Wadden Sea.

Small uninhabited islands form important roosting and breeding habitats for many coastal birds. Previous studies have demonstrated that guano can promote ecosystem productivity and functionality on island ecosystems. Here, we assess the role of external nutrient input by coastal birds on the vegetation structure and coverage on sandy biogeomorphic islands, where island-forming processes depend on vegetation-sedimentation feedbacks.

Tumor evolution metrics predict recurrence beyond 10 years in locally advanced prostate cancer.

Cancer evolution lays the groundwork for predictive oncology. Testing evolutionary metrics requires quantitative measurements in controlled clinical trials. We mapped genomic intratumor heterogeneity in locally advanced prostate cancer using 642 samples from 114 individuals enrolled in clinical trials with a 12-year median follow-up.

Harnessing ecological theory to enhance ecosystem restoration.

Ecosystem restoration can increase the health and resilience of nature and humanity. As a result, the international community is championing habitat restoration as a primary solution to address the dual climate and biodiversity crises. Yet most ecosystem restoration efforts to date have underperformed, failed, or been burdened by high costs that prevent upscaling.

Long-term Multimodal Recording Reveals Epigenetic Adaptation Routes in Dormant Breast Cancer Cells.

Unlabelled: Patients with estrogen receptor-positive breast cancer receive adjuvant endocrine therapies (ET) that delay relapse by targeting clinically undetectable micrometastatic deposits. Yet, up to 50% of patients relapse even decades after surgery through unknown mechanisms likely involving dormancy. To investigate genetic and transcriptional changes underlying tumor awakening, we analyzed late relapse patients and longitudinally profiled a rare cohort treated with long-term neoadjuvant ETs until progression.

Habitat modification by marram grass negatively affects recruitment of conspecifics.

Ecosystem engineers alter their environment often benefiting their own survival and growth yielding self-reinforcing feedbacks. Moreover, these habitat modifications have been found to facilitate recruitment of conspecifics for some species, while for others engineering inhibits recruitment. Whether dune grasses facilitate or inhibit recruitment of conspecifics is yet unknown.

Epigenome and early selection determine the tumour-immune evolutionary trajectory of colorectal cancer.

Immune system control is a major hurdle that cancer evolution must circumvent. The relative timing and evolutionary dynamics of subclones that have escaped immune control remain incompletely characterized, and how immune-mediated selection shapes the epigenome has received little attention. Here, we infer the genome- and epigenome-driven evolutionary dynamics of tumour-immune coevolution within primary colorectal cancers (CRCs).

Contribution of pks E. coli mutations to colorectal carcinogenesis.

The dominant mutational signature in colorectal cancer genomes is C > T deamination (COSMIC Signature 1) and, in a small subgroup, mismatch repair signature (COSMIC signatures 6 and 44). Mutations in common colorectal cancer driver genes are often not consistent with those signatures. Here we perform whole-genome sequencing of normal colon crypts from cancer patients, matched to a previous multi-omic tumour dataset.

The seafloor from a trait perspective. A comprehensive life history dataset of soft sediment macrozoobenthos.

Biological trait analysis (BTA) is a valuable tool for evaluating changes in community diversity and its link to ecosystem processes as well as environmental and anthropogenic perturbations. Trait-based analytical techniques like BTA rely on standardised datasets of species traits. However, there are currently only a limited number of datasets available for marine macrobenthos that contain trait data across multiple taxonomic groups.

Benchmark Data Set of Crystalline Organic Semiconductors.

This work reports a Benchmark Data set of Crystalline Organic Semiconductors to test calculations of the structural and electronic properties of these materials in the solid state. The data set contains 67 crystals consisting of mostly rigid molecules with a single dominant conformer, covering the majority of known structural types. The experimental crystal structure is available for the entire data set, whereas zero-temperature unit cell volume can be reliably estimated for a subset of 28 crystals.

Restoration ecology meets design-engineering: Mimicking emergent traits to restore feedback-driven ecosystems.

Ecosystems shaped by habitat-modifying organisms such as reefs, vegetated coastal systems and peatlands, provide valuable ecosystem services, such as carbon storage and coastal protection. However, they are declining worldwide. Ecosystem restoration is a key tool for mitigating these losses but has proven failure-prone, because ecosystem stability often hinges on self-facilitation generated by emergent traits from habitat modifiers.

Machine Learning Enhanced DFTB Method for Periodic Systems: Learning from Electronic Density of States.

Density functional tight binding (DFTB) is an approximate density functional based quantum chemical simulation method with low computational cost. In order to increase its accuracy, we have introduced a machine learning algorithm to optimize several parameters of the DFTB method, concentrating on solids with defects. The backpropagation algorithm was used to reduce the error between DFTB and DFT results with respect to the training data set and to obtain adjusted DFTB Hamiltonian and overlap matrix elements.

Molecular dynamics study of plasmon-mediated chemical transformations.

Heterogeneous catalysis of adsorbates on metallic surfaces mediated by plasmons has potential high photoelectric conversion efficiency and controllable reaction selectivity. Theoretical modeling of dynamical reaction processes enables in-depth analyses complementing experimental investigations. Especially for plasmon-mediated chemical transformations, light absorption, photoelectric conversion, electron-electron scattering, and electron-phonon coupling occur simultaneously on different timescales, making it very challenging to delineate the complex interplay of different factors.

Early indicators of tidal ecosystem shifts in estuaries.

Forecasting transitions between tidal ecosystem states, such as between bare tidal flats and vegetated marshes, is crucial because it may imply the irreversible loss of valuable ecosystem services. In this study, we combine geospatial analyses of three European estuaries with a simple numerical model to demonstrate that the development of micro-topographic patterning on tidal flats is an early indicator of marsh establishment. We first show that the development of micro-topographic patterns precedes vegetation establishment, and that patterns tend to form only on tidal flats with a slope of <0.

Phase-separation physics underlies new theory for the resilience of patchy ecosystems.

Spatial self-organization of ecosystems into large-scale (from micron to meters) patterns is an important phenomenon in ecology, enabling organisms to cope with harsh environmental conditions and buffering ecosystem degradation. Scale-dependent feedbacks provide the predominant conceptual framework for self-organized spatial patterns, explaining regular patterns observed in, e.g.

Phenotypic plasticity and genetic control in colorectal cancer evolution.

Genetic and epigenetic variation, together with transcriptional plasticity, contribute to intratumour heterogeneity. The interplay of these biological processes and their respective contributions to tumour evolution remain unknown. Here we show that intratumour genetic ancestry only infrequently affects gene expression traits and subclonal evolution in colorectal cancer (CRC).

The co-evolution of the genome and epigenome in colorectal cancer.

Colorectal malignancies are a leading cause of cancer-related deathand have undergone extensive genomic study. However, DNA mutations alone do not fully explain malignant transformation. Here we investigate the co-evolution of the genome and epigenome of colorectal tumours at single-clone resolution using spatial multi-omic profiling of individual glands.

Recovering wetland biogeomorphic feedbacks to restore the world's biotic carbon hotspots.

Biogeomorphic wetlands cover 1% of Earth's surface but store 20% of ecosystem organic carbon. This disproportional share is fueled by high carbon sequestration rates and effective storage in peatlands, mangroves, salt marshes, and seagrass meadows, which greatly exceed those of oceanic and forest ecosystems. Here, we review how feedbacks between geomorphology and landscape-building vegetation underlie these qualities and how feedback disruption can switch wetlands from carbon sinks into sources.

Adaptive intertidal seed-based seagrass restoration in the Dutch Wadden Sea.

Seagrasses form the foundation of many coastal ecosystems but are rapidly declining on a global scale. The Dutch Wadden Sea once supported extensive subtidal seagrass meadows that have all disappeared. Here, we report on the setbacks and successes of intertidal seed-based restoration experiments in the Dutch Wadden Sea between 2014-2017.

Circulating tumour DNA sequencing to determine therapeutic response and identify tumour heterogeneity in patients with paediatric solid tumours.

Objective: Clinical diagnostic sequencing of circulating tumour DNA (ctDNA) is well advanced for adult patients, but application to paediatric cancer patients lags behind.

Methods: To address this, we have developed a clinically relevant (67 gene) NGS capture panel and accompanying workflow that enables sensitive and reliable detection of low-frequency genetic variants in cell-free DNA (cfDNA) from children with solid tumours. We combined gene panel sequencing with low pass whole-genome sequencing of the same library to inform on genome-wide copy number changes in the blood.

Overcoming establishment thresholds for peat mosses in human-made bog pools.

Globally, peatlands have been affected by drainage and peat extraction, with adverse effects on their functioning and services. To restore peat-forming vegetation, drained bogs are being rewetted on a large scale. Although this practice results in higher groundwater levels, unfortunately it often creates deep lakes in parts where peat was extracted to greater depths than the surroundings.

Restoration of biogeomorphic systems by creating windows of opportunity to support natural establishment processes.

In degraded landscapes, recolonization by pioneer vegetation is often halted by the presence of persistent environmental stress. When natural expansion does occur, it is commonly due to the momentary alleviation of a key environmental variable previously limiting new growth. Thus, studying the circumstances in which expansion occurs can inspire new restoration techniques, wherein vegetation establishment is provoked by emulating natural events through artificial means.

Saltmarsh resilience controlled by patch size and plant density of habitat-forming species that trap shells.

Habitat fragmentaion into small patches is regarded as a vital cause of biodiversity loss. Fragmentationof habitat-forming species is especially harmful, as patchiness of such species often controls ecosystem stability and resilience by density and patch size-dependent self-reinforcing feedbacks. Although fragmentation are expected to weaken or even break such feedbacks, it remains unclear how the resulting patchiness of habitat-forming species affect ecosystem resilience to environmental stresses.