Eco-Efficiency of Forage Production in Northern Germany

A 2-year field experiment was conducted at two sites in Schleswig-Holstein, northern Germany, to quantify and evaluate the carbon footprint of arable forage cropping systems (continuous silage maize, maize-wheat-grass rotation, perennial ryegrass ley) as affected by N fertilizer type and N amount. Total greenhouse gas emission showed a linear increase with N application, with mineral N supply resulting in a higher slope. Product carbon footprint ranged between -66 and 119 kg CO2eq/(GJ NEL) and revealed a quadratic or linear response to fertilizer N input, depending on the cropping system. At N input required for achieving maximum energy yield, perennial ryegrass caused lower emission per product unit than continuous maize or the maize-wheat-grass rotation. The data indicate potential for sustainable intensification when crop management options are adopted to increase resource use efficiency

Cancer-associated fibroblast classification in single-cell and spatial proteomics data

Cancer-associated fibroblasts (CAFs) are a diverse cell population within the tumour microenvironment, where they have critical effects on tumour evolution and patient prognosis. To define CAF phenotypes, we analyse a single-cell RNA sequencing (scRNA-seq) dataset of over 16,000 stromal cells from tumours of 14 breast cancer patients, based on which we define and functionally annotate nine CAF phenotypes and one class of pericytes. We validate this classification system in four additional cancer types and use highly multiplexed imaging mass cytometry on matched breast cancer samples to confirm our defined CAF phenotypes at the protein level and to analyse their spatial distribution within tumours. This general CAF classification scheme will allow comparison of CAF phenotypes across studies, facilitate analysis of their functional roles, and potentially guide development of new treatment strategies in the future

Identification of factors influencing the Puumala virus seroprevalence within its reservoir in aMontane Forest Environment.

Puumala virus (PUUV) is a major cause of mild to moderate haemorrhagic fever with renal syndrome and is transmitted by the bank vole (Myodes glareolus). There has been a high cumulative incidence of recorded human cases in South-eastern Germany since 2004 when the region was first recognized as being endemic for PUUV. As the area is well known for outdoor recreation and the Bavarian Forest National Park (BFNP) is located in the region, the increasing numbers of recorded cases are of concern. To understand the population and environmental effects on the seroprevalence of PUUV in bank voles we trapped small mammals at 23 sites along an elevation gradient from 317 to 1420m above sea level. Generalized linear mixed effects models(GLMEM) were used to explore associations between the seroprevalence of PUUV in bank voles and climate and biotic factors. We found that the seroprevalence of PUUV was low (6%-7%) in 2008 and 2009, and reached 29% in 2010. PUUV seroprevalence was positively associated with the local species diversity and deadwood layer, and negatively associated with mean annual temperature, mean annual solar radiation, and herb layer. Based on these findings, an illustrative risk map for PUUV seroprevalence prediction in bank voles was created for an area of the national park. The map will help when planning infrastructure in the national park (e.g., huts, shelters, and trails)

Molecular adsorbent recirculating system and hemostasis in patients at high risk of bleeding: an observational study

INTRODUCTION: Liver failure is associated with reduced synthesis of clotting factors, consumptive coagulopathy, and platelet dysfunction. The aim of the study was to evaluate the effects of liver support using a molecular adsorbent recirculating system (MARS) on the coagulation system in patients at high risk of bleeding. METHODS: We studied 61 MARS treatments in 33 patients with acute liver failure (n = 15), acute-on-chronic liver failure (n = 8), sepsis (n = 5), liver graft dysfunction (n = 3), and cholestasis (n = 2). Standard coagulation tests, standard thromboelastography (TEG), and heparinase-modified and abciximab-fab-modified TEG were performed immediately before and 30 minutes after commencement of MARS, and after the end of MARS treatment. Prostaglandin I(2 )was administered extracorporeally to all patients; 17 patients additionally received unfractioned heparin. RESULTS: Three moderate bleeding complications in three patients, requiring three to four units of packed red blood cells, were observed. All were sufficiently managed without interrupting MARS treatment. Although there was a significant decrease in platelet counts (median, 9 G/l; range, -40 to 145 G/l) and fibrinogen concentration (median, 15 mg/dl; range, -119 to 185 mg/dl) with a consecutive increase in thrombin time, the platelet function, as assessed by abciximab-fab-modified TEG, remained stable. MARS did not enhance fibrinolysis. CONCLUSION: MARS treatment appears to be well tolerated during marked coagulopathy due to liver failure. Although MARS leads to a further decrease in platelet count and fibrinogen concentration, platelet function, measured as the contribution of the platelets to the clot firmness in TEG, remains stable. According to TEG-based results, MARS does not enhance fibrinolysis

A comprehensive single-cell map of T cell exhaustion-associated immune environments in human breast cancer

Immune checkpoint therapy in breast cancer remains restricted to triple negative patients, and long-term clinical benefit is rare. The primary aim of immune checkpoint blockade is to prevent or reverse exhausted T cell states, but T cell exhaustion in breast tumors is not well understood. Here, we use single-cell transcriptomics combined with imaging mass cytometry to systematically study immune environments of human breast tumors that either do or do not contain exhausted T cells, with a focus on luminal subtypes. We find that the presence of a PD-1high exhaustion-like T cell phenotype is associated with an inflammatory immune environment with a characteristic cytotoxic profile, increased myeloid cell activation, evidence for elevated immunomodulatory, chemotactic, and cytokine signaling, and accumulation of natural killer T cells. Tumors harboring exhausted-like T cells show increased expression of MHC-I on tumor cells and of CXCL13 on T cells, as well as altered spatial organization with more immature rather than mature tertiary lymphoid structures. Our data reveal fundamental differences between immune environments with and without exhausted T cells within luminal breast cancer, and show that expression of PD-1 and CXCL13 on T cells, and MHC-I - but not PD-L1 - on tumor cells are strong distinguishing features between these environments

Presence and Diversity of Different Enteric Viruses in Wild Norway Rats (Rattus norvegicus)

Abstract: Rodents are common reservoirs for numerous zoonotic pathogens, but knowledge about diversity of pathogens in rodents is still limited. Here, we investigated the occurrence and genetic diversity of enteric viruses in 51 Norway rats collected in three different countries in Europe. RNA of at least one virus was detected in the intestine of 49 of 51 animals. Astrovirus RNA was detected in 46 animals, mostly of rat astroviruses. Human astrovirus (HAstV-8) RNA was detected in one, rotavirus group A (RVA) RNA was identified in eleven animals. One RVA RNA could be typed as rat G3 type. Rat hepatitis E virus (HEV) RNA was detected in five animals. Two entire genome sequences of ratHEV were determined. Human norovirus RNA was detected in four animals with the genotypes GI.P4-GI.4, GII.P33-GII.1, and GII.P21. In one animal, a replication competent coxsackievirus A20 strain was detected. Additionally, RNA of an enterovirus species A strain was detected in the same animal, albeit in a different tissue. The results show a high detection rate and diversity of enteric viruses in Norway rats in Europe and indicate their significance as vectors for zoonotic transmission of enteric viruses. The detailed role of Norway rats and transmission pathways of enteric viruses needs to be investigated in further studies.Peer Reviewe

The radiosensitizing effect of platinum nanoparticles in proton irradiations is not caused by an enhanced proton energy deposition at the macroscopic scale

Objective. Due to the radiosensitizing effect of biocompatible noble metal nanoparticles (NPs), their administration is considered to potentially increase tumor control in radiotherapy. The underlying physical, chemical and biological mechanisms of the NPs' radiosensitivity especially when interacting with proton radiation is not conclusive. In the following work, the energy deposition of protons in matter containing platinum nanoparticles (PtNPs) is experimentally investigated. Approach. Surfactant-free monomodal PtNPs with a mean diameter of (40 ± 10) nm and a concentration of 300 μg ml−1, demonstrably leading to a substantial production of reactive oxygen species (ROS), were homogeneously dispersed into cubic gelatin samples serving as tissue-like phantoms. Gelatin samples without PtNPs were used as control. The samples' dimensions and contrast of the PtNPs were verified in a clinical computed tomography scanner. Fields from a clinical proton machine were used for depth dose and stopping power measurements downstream of both samples types. These experiments were performed with a variety of detectors at a pencil beam scanning beam line as well as a passive beam line with proton energies from about 56–200 MeV. Main results. The samples' water equivalent ratios in terms of proton stopping as well as the mean proton energy deposition downstream of the samples with ROS-producing PtNPs compared to the samples without PtNPs showed no differences within the experimental uncertainties of about 2%. Significance. This study serves as experimental proof that the radiosensitizing effect of biocompatible PtNPs is not due to a macroscopically increased proton energy deposition, but is more likely caused by a catalytic effect of the PtNPs. Thus, these experiments provide a contribution to the highly discussed radiobiological question of the proton therapy efficiency with noble metal NPs and facilitate initial evidence that the dose calculation in treatment planning is straightforward and not affected by the presence of sensitizing PtNPs

Endothelial LRP1 transports amyloid-β1-42 across the blood-brain barrier

According to the neurovascular hypothesis, impairment of low-density lipoprotein receptor-related protein-1 (LRP1) in brain capillaries of the blood-brain barrier (BBB) contributes to neurotoxic amyloid-beta (A beta) brain accumulation and drives Alzheimer's disease (AD) pathology. However, due to conflicting reports on the involvement of LRP1 in A beta transport and the expression of LRP1 in brain endothelium, the role of LRP1 at the BBB is uncertain. As global Lrp1 deletion in mice is lethal, appropriate models to study the function of LRP1 are lacking. Moreover, the relevance of systemic A beta clearance to AD pathology remains unclear, as no BBB-specific knockout models have been available. Here, we developed transgenic mouse strains that allow for tamoxifen-inducible deletion of Lrp1 specifically within brain endothelial cells (Slo1c1-CreER(Tz) Lrp1(fl/fl) mice) and used these mice to accurately evaluate LRP1-mediated A beta BBB clearance in vivo. Selective deletion of Lrp1 in the brain endothelium of C57BL/6 mice strongly reduced brain efflux of injected [I-125] A beta(1-42). Additionally, in the 5xFAD mouse model of AD, brain endothelial-specific Lrp1 deletion reduced plasma A beta levels and elevated soluble brain A beta, leading to aggravated spatial learning and memory deficits, thus emphasizing the importance of systemic AD elimination via the BBB. Together, our results suggest that receptor-mediated A beta BBB clearance may be a potential target for treatment and prevention of A beta brain accumulation in AD