Comparative Grain-Size Measurements for Validating Sampling and Pretreatment Techniques in Terms of Solifluction Landforms, Southern Carpathians, Romania

Grain-size distribution has become in the last years an important indicator in the analysis of periglacial processes and landforms. However, as they exhibit a complex sedimentology, careful sampling is required to draw meaningful conclusions. The aim of the present study was therefore to validate the sampling procedure carried out on solifluction forms and to evaluate the effect of sampling pretreatment during grain size analysis. A comparison between multiple measurements of grain size distribution using the laser diffraction method (LDM) was performed on 54 sediment samples collected from different solifluction landforms at different depths in the alpine area of the Southern Carpathians. The results of parallel measurements were compared using textural and statistical indicators. The received distributions reinforced the properness of field sampling procedure in most of the cases. The results of textural classification and fractional composition showed a high consistency between the two parallel measurements made on untreated and pretreated samples. An overall fining as a matter of etching was identified. Relative deviation increased and correlation decreased as pretreatment advanced. HCl etching resulted a greater deviation and variability in case of the sand fraction, H2O2 rather affected the silt fraction. The greatest deviations were experienced in case of landforms developed on crystalline limestone. Pretreatment of samples introduced a major uncertainty to further comparison and interpretation. Thus, multiple LD measurements on a representative group of samples from the entire sample set were suggested before the geomorphological or environmental interpretation of results to decrease the uncertainties and to validate the processes

Stroma AReactive Invasion Front Areas (SARIFA) proves prognostic relevance in gastric carcinoma and is based on a tumor–adipocyte interaction indicating an altered immune response

Background Recently, we presented Stroma AReactive Invasion Front Areas (SARIFA) as a new histomorphologic negative prognostic biomarker in gastric cancer. It is defined as direct contact between tumor cells and fat cells. The aim of this study was to further elucidate the underlying genomic, transcriptional, and immunological mechanisms of the SARIFA phenomenon. Methods To address these questions, SARIFA was classified on H&E-stained tissue sections of three cohorts: an external cohort (n = 489, prognostic validation), the TCGA-STAD cohort (n = 194, genomic and transcriptomic analysis), and a local cohort (n = 60, digital spatial profiling (whole transcriptome) and double RNA in situ hybridization/immunostaining of cytokines). Results SARIFA status proved to be an independent negative prognostic factor for overall survival in an external cohort of gastric carcinomas. In TCGA-STAD cohort, SARIFA is not driven by distinct genomic alterations, whereas the gene expression analyses showed an upregulation of FABP4 in SARIFA-positive tumors. In addition, the transcriptional regulations of white adipocyte differentiation, triglyceride metabolism, and catabolism were upregulated in pathway analyses. In the DSP analysis of SARIFA-positive tumors, FABP4 and the transcriptional regulation of white adipocyte differentiation were upregulated in macrophages. Additionally, a significantly lower expression of the cytokines IL6 and TNFα was observed at the invasion front. Conclusions SARIFA proves to be a strong negative prognostic biomarker in advanced gastric cancer, implicating an interaction of tumor cells with tumor-promoting adipocytes with crucial changes in tumor cell metabolism. SARIFA is not driven by tumor genetics but is very likely driven by an altered immune response as a causative mechanism

Next-Generation Global Biomonitoring: Large-scale, Automated Reconstruction of Ecological Networks

We foresee a new global-scale, ecological approach to biomonitoring emerging within the next decade that can detect ecosystem change accurately, cheaply, and generically. Next-generation sequencing of DNA sampled from the Earth's environments would provide data for the relative abundance of operational taxonomic units or ecological functions. Machine-learning methods would then be used to reconstruct the ecological networks of interactions implicit in the raw NGS data. Ultimately, we envision the development of autonomous samplers that would sample nucleic acids and upload NGS sequence data to the cloud for network reconstruction. Large numbers of these samplers, in a global array, would allow sensitive automated biomonitoring of the Earth's major ecosystems at high spatial and temporal resolution, revolutionising our understanding of ecosystem change

Targeting of Aberrant αvβ6 Integrin Expression in Solid Tumors Using Chimeric Antigen Receptor-Engineered T Cells.

Expression of the αvβ6 integrin is upregulated in several solid tumors. In contrast, physiologic expression of this epithelial-specific integrin is restricted to development and epithelial re-modeling. Here, we describe, for the first time, the development of a chimeric antigen receptor (CAR) that couples the recognition of this integrin to the delivery of potent therapeutic activity in a diverse repertoire of solid tumor models. Highly selective targeting αvβ6 was achieved using a foot and mouth disease virus-derived A20 peptide, coupled to a fused CD28+CD3 endodomain. To achieve selective expansion of CAR T cells ex vivo, an IL-4-responsive fusion gene (4αβ) was co-expressed, which delivers a selective mitogenic signal to engineered T cells only. In vivo efficacy was demonstrated in mice with established ovarian, breast, and pancreatic tumor xenografts, all of which express αvβ6 at intermediate to high levels. SCID beige mice were used for these studies because they are susceptible to cytokine release syndrome, unlike more immune-compromised strains. Nonetheless, although the CAR also engages mouse αvβ6, mild and reversible toxicity was only observed when supra-therapeutic doses of CAR T cells were administered parenterally. These data support the clinical evaluation of αvβ6 re-targeted CAR T cell immunotherapy in solid tumors that express this integrin

Channel forms recovery in an ephemeral river after gravel mining (Palancia River, Eastern Spain)

During the 1970s, the Palancia River was intensively affected by gravel mining instream. This activity completely destroyed the fluvial forms, devastating the original wandering pattern. At the end of the 1980s, gravel mining ceased and the river started a process of recovery, only altered by several clearing operations. The aim of this work is to describe these processes of change, analyzing the river's morphosedimentary conditions through a GIS analysis of aerial photographs previous to, simultaneous with, and subsequent to the intense gravel mining activity. Results explain the current difficulties of some ephemeral rivers to recover their original forms, because of the sediment and water deficit conditions, the critical role of channel incision and inappropriate actions of river clearing and channelization for flood prevention

Evolutionary timeline and genomic plasticity underlying the lifestyle diversity in rhizobiales

Members of the order include those capable of nitrogen fixation in nodules as well as pathogens of animals and plants. This lifestyle diversity has important implications for agricultural and medical research. Leveraging large-scale genomic data, we infer that originated as a free-living ancestor ∼1,500 million years ago (Mya) and that the later emergence of host-associated lifestyles broadly coincided with the rise of their eukaryotic hosts. In particular, the first nodulating lineage arose from either or 150 to 80 Mya, a time range in general concurrent with the emergence of legumes. The rates of lifestyle transitions are highly variable; nodule association is more likely to be lost than gained, whereas animal association likely represents an evolutionary dead end. We searched for statistical correlations between gene presence and lifestyle and identified genes likely contributing to the transition and adaptation to the same lifestyle in divergent lineages. Among the genes potentially promoting successful transitions to major nodulation lineages, the and clusters for nodulation and nitrogen fixation, respectively, were repeatedly acquired during each transition; the , , and clusters involved in energy conservation under micro-oxic conditions were present in the nonnodulating ancestors; and the secretion systems were acquired in lineage-specific patterns. Our study data suggest that increased eukaryote diversity drives lifestyle diversification of bacteria and highlight both acquired and preexisting traits facilitating the origin of host association. Bacteria form diverse interactions with eukaryotic hosts. This is well represented by the , a clade of strategically important for their large diversity of lifestyles with implications for agricultural and medical research. To investigate their lifestyle evolution, we compiled a comprehensive data set of genomes and lifestyle information for over 1,000 genomes. We show that the origins of major host-associated lineages in broadly coincided with the emergences of their host plants/animals, suggesting bacterium-host interactions as a driving force in the evolution of We further found that, in addition to gene gains, preexisting traits and recurrent losses of specific genomic traits may have played underrecognized roles in the origin of host-associated lineages, providing clues to genetic engineering of microbial agricultural inoculants and prevention of the emergence of potential plant/animal pathogens

Long-baseline neutrino oscillation physics potential of the DUNE experiment

The sensitivity of the Deep Underground Neutrino Experiment (DUNE) to neutrino oscillation is determined, based on a full simulation, reconstruction, and event selection of the far detector and a full simulation and parameterized analysis of the near detector. Detailed uncertainties due to the flux prediction, neutrino interaction model, and detector effects are included. DUNE will resolve the neutrino mass ordering to a precision of 5σ, for all ΑCP values, after 2 years of running with the nominal detector design and beam configuration. It has the potential to observe charge-parity violation in the neutrino sector to a precision of 3σ (5σ) after an exposure of 5 (10) years, for 50% of all ΑCP values. It will also make precise measurements of other parameters governing long-baseline neutrino oscillation, and after an exposure of 15 years will achieve a similar sensitivity to sin22θ13 to current reactor experiments