Biomonitoring der weiträumigen Verdriftung von Pestiziden mittels Baumrinde, Vegetation und Passivsammler

Anlass für ein Biomonitoring zur weiträumigen Verfrachtung von Pestiziden über die Luft war die wiederholte und erhebliche Kontamination von Bio-Körnerfenchel mit zugelassenen, häufig applizierten Pflanzenschutzmitteln, die kilometerweit von den Fenchelflächen angewendet wurden. Zudem wurde für Glyphosat eine breite Belastung der Bevölkerung gemessen: 99,6% von über 2000 Probanden der bundesweiten Studie „Urinale 2015“. Das Luftgüte-Rindenmonitoring mit Analysen von über 500 Pestiziden wurde von 2014 bis 2017 an 24 Standorten in Brandenburg und Bayern durchgeführt. Weitere Vegetationsproben wie Körnerfenchel und Grünkohl wurden an 11 Standorten und technische Passivsammler (PUF-SIP) an 2 Standorten zur Kalibrierung analysiert. Insgesamt wurden 55 Pestiziden gefunden, im Durchschnitt 27 (4 - 36) pro Standort. Insbesondere zeigten 15 Pestizide eine über einzelne Standorte hinausgehende, weiträumige Verbreitung auf. Diese Drift verursacht eine ubiquitäre Kontamination bishin zu weit entfernt liegenden Naturschutzgebieten. So wurde Pendimethalin an 22 von 24 Standorten (93%), Prosulfocarb bei 75% und sogar Glyphosat bei 33% aller Standorte gemessen. Für derartige hochproblematischen Pestizide sind angemessene Änderungen im Zulassungsverfahren erforderlich, um  Umweltbelastungen wirksam zu reduzieren und die Koexistenz alternativer Anbaumethoden, wie zum Beispiel des ökologischen Landbaus, zu gewährleisten

Neurotensin and Xenin Show Positive Correlations With Perceived Stress, Anxiety, Depressiveness and Eating Disorder Symptoms in Female Obese Patients

Objective Neurotensin and xenin are two closely related anorexigenic neuropeptides synthesized in the small intestine that exert diverse peripheral and central functions. Both act via the neurotensin-1-receptor. In animal models of obesity reduced central concentrations of these peptides have been found. Dysregulations of the acute and chronic stress response are associated with development and maintenance of obesity. Until now, associations of both peptides with stress, anxiety, depressiveness, and eating disorder symptoms have not been investigated. The aim of the present study was to examine associations of neurotensin and xenin with these psychological characteristics under conditions of obesity. Materials and Methods From 2010 to 2016 we consecutively enrolled 160 inpatients (63 men and 97 women), admitted due to obesity and its mental and somatic comorbidities. Blood withdrawal und psychometric tests (PSQ-20, GAD-7, PHQ-9, and EDI-2) occurred within one week after admission. We measured levels of neurotensin and xenin in plasma by ELISA. Results Mean body mass index was 47.2 +/- 9.5 kg/m(2). Concentrations of neurotensin and xenin positively correlated with each other (women: r = 0.788, p 0.05). Women generally displayed higher psychometric values than men (PSQ-20: 58.2 +/- 21.7 vs. 47.0 +/- 20.8, p = 0.002; GAD-7: 9.7 +/- 5.8 vs. 7.1 +/- 5.3, p = 0.004; PHQ-9: 11.6 +/- 6.6 vs. 8.8 +/- 5.9, p = 0.008; EDI-2: 50.5 +/- 12.8 vs. 39.7 +/- 11.9, p 0.05). Conclusion Neurotensin and xenin plasma levels of female obese patients are positively correlated with perceived stress, anxiety, depressiveness, and eating disorder symptoms. These associations could be influenced by higher prevalence of mental disorders in women and by sex hormones. In men, no correlations were observed, which points toward a sex-dependent regulation

Shotgun ion mobility mass spectrometry sequencing of heparan sulfate saccharides

Despite evident regulatory roles of heparan sulfate (HS) saccharides in numerous biological processes, definitive information on the bioactive sequences of these polymers is lacking, with only a handful of natural structures sequenced to date. Here, we develop a “Shotgun” Ion Mobility Mass Spectrometry Sequencing (SIMMS2) method in which intact HS saccharides are dissociated in an ion mobility mass spectrometer and collision cross section values of fragments measured. Matching of data for intact and fragment ions against known values for 36 fully defined HS saccharide structures (from di- to decasaccharides) permits unambiguous sequence determination of validated standards and unknown natural saccharides, notably including variants with 3O-sulfate groups. SIMMS2 analysis of two fibroblast growth factor-inhibiting hexasaccharides identified from a HS oligosaccharide library screen demonstrates that the approach allows elucidation of structure-activity relationships. SIMMS2 thus overcomes the bottleneck for decoding the informational content of functional HS motifs which is crucial for their future biomedical exploitation

A case study of epistemic order in mathematics classroom dialogue

This paper defines epistemic order as the way in which the exchange and development of knowledge takes place in the classroom, breaking this down into a system of three components: epistemic initiative relating to who sets the agenda in classroom dialogue, and how; epistemic appraisal relating to who judges contributions to classroom dialogue, and how; and epistemic framing relating to the terms in which development and exchange of knowledge are represented, particularly in reflexive talk. These components are operationalised in terms of various types of structural and semantic analysis of dialogue which are then applied in conducting a case study of a lesson segment. This study demonstrates how the triangulation of various types of analysis can provide a more nuanced model of epistemic order. It shows that the lesson segment displays a multi-layered epistemic order differing from that of conventional classroom recitation, particularly in passages where the teacher scaffolds indirect exchanges between pupils or manoeuvres exchanges so that pupils take more of a lead in developing knowledge. In passages of the former type, the teacher also introduces a register which acknowledges participants as sense-making subjects exchanging and forming knowledge.Thanks are due to the Economic and Social Research Council which funded collection of the video data analysed here as part of the epiSTEMe project (grant reference RES-179-25-0003)

Osteogenic differentiation driven by osteoclasts and macrophages

Introduction Osteoclasts are bone-resorbing cells closely related to bone turnover, whereas different macrophage subtypes contribute to bone fracture healing. As osteoclasts and macrophages share the same hematopoietic origin, the difference between both cell types on osteoblast coupling, crosstalk extent and consequent bone formation remains poorly understood. This study compares the potential of primary cells that are routinely considered as osteoclast and macrophage cultures on their ability to support osteogenic differentiation of human mesenchymal stromal cells (hMSCs). Methods Human Peripheral Blood Mononuclear Cells (hPBMCs) were used to obtain macrophage or osteoclast cultures using appropriate stimulatory factors. With different seeding densities of hPBMCs, conditioned media from macrophage or osteoclast cultures were harvested for comparative evaluation of effects thereof on the osteogenic differentiation of hMSCs. Specific cytological staining was used to qualitatively evaluate macrophage and osteoclast cultures. Additionally, quantitative data on hMSC proliferation, osteogenic differentiation and mineralization were obtained via biochemical assays. Results Conditioned medium from osteoclast cultures obtained via low hPBMCs seeding densities, but not from high hPBMCs seeding densities or macrophages, stimulated hMSC osteogenic differentiation and mineralization. Upon cellular crosstalk, both pre-differentiated osteoclasts and non-polarized macrophages equally supported early hMSC osteogenic differentiation and mineralization, as confirmed by increased alkaline phosphatase levels within 7 days and increased calcium content within 14 days in comparison with undifferentiated controls. Initial hPBMCs seeding density strongly influences osteoclastogenesis and the paracrine effect of the resultant osteoclast population on the osteogenic differentiation of hMSCs. In addition, only in indirect coculture, macrophages provide similar stimulatory effects as pre-differentiated osteoclasts on the osteogenic differentiation of MSCs and mineralization. Conclusion Our results demonstrate stimulatory effects of osteoclast conditioned medium on hMSC osteogenic differentiation, depending on initial hPBMC seeding density. In addition, we show that osteoclast and macrophage cultures contain pools of polarized macrophages, which may be involved in the osteogenic effects. Our data provide insight into bone tissue engineering approaches by using multicellular interactions related to bone remodeling and healing for the in vitro modulation of osteogenic differentiation

Pancreatic Polypeptide but Not Other Members of the Neuropeptide Y Family Shows a Moderate Association With Perceived Anxiety in Obese Men

Neuropeptide Y (NPY), peptide tyrosine tyrosine (PYY), and pancreatic polypeptide (PP) are important mediators in the bidirectional communication along the gut-brain-axis. Best known for their role in the regulation of appetite and food intake they are considered to play a crucial role in the development of obesity. Additionally, mounting evidence indicates a regulatory function in anxiety, mood and stress resilience with potential sex differences. In the present study, we examined the associations of NPY, PYY, and PP plasma levels with anxiety, depressiveness and perceived stress in obese patients. We analyzed 144 inpatients (90 female, 54 male, BMI mean: 49.4 kg/m(2)) in a naturalistic treatment setting for obesity and its somatic and mental comorbidities. Fasting blood samples were taken, and patients completed psychometric self-assessment questionnaires (GAD-7, PHQ-9, PSQ-20) within the first week after admission and before discharge. Plasma concentrations of the peptides were measured by ELISA. Women showed significant higher anxiety (GAD-7: 8.13 +/- 5.67 vs. 5.93 +/- 5.42, p = 0.04) and stress scores (PSQ-20: 52.62 +/- 23.5 vs. 41.23 +/- 22.53, p = 0.01) than men. In the longitudinal analysis women with a clinically relevant improvement of anxiety ( \u3e /= 5 points on GAD-7, p \u3c 0.001) also showed significant improvements in depression (PHQ-9: 38%, p = 0.002) and PSQ-20 scores (23%, p = 0.005) while anxiety-improved male patients only improved in the subscale tension of the PSQ-20 (34%, p = 0.02). In men we observed a positive correlation of PP with anxiety scores (GAD-7: r = 0.41, p = 0.007) and with age (r = 0.49, p = 0.001) on admission while NPY negatively correlated with age (r = -0.38, p = 0.01). In contrast, there were no significant associations (p \u3e 0.05) in female subjects in the cross-sectional as well as in the longitudinal analysis. In conclusion, women suffering from morbid obesity showed greater psychological comorbidity and considerable interactions among them. Despite that we solely observed associations of PP with anxiety and age with NPY and PP in men, suggesting a possible influence of sex hormones on the NPY system. However, improvement of anxiety scores did not lead to significant changes in NPY

A Combination of the Immunotherapeutic Drug Anti-Programmed Death 1 with Lenalidomide Enhances Specific T Cell Immune Responses against Acute Myeloid Leukemia Cells

Immune checkpoint inhibitors can block inhibitory molecules on the surface of T cells, switching them from an exhausted to an active state. One of these inhibitory immune checkpoints, programmed cell death protein 1 (PD-1) is expressed on T cell subpopulations in acute myeloid leukemia (AML). PD-1 expression has been shown to increase with AML progression following allo-haematopoeitic stem cell transplantation, and therapy with hypomethylating agents. We have previously shown that anti-PD-1 can enhance the response of leukemia-associated antigen (LAA)-specific T cells against AML cells as well as leukemic stem and leukemic progenitor cells (LSC/LPCs) ex vivo. In concurrence, blocking of PD-1 with antibodies such as nivolumab has been shown to enhance response rates post-chemotherapy and stem cell transplant. The immune modulating drug lenalidomide has been shown to promote anti-tumour immunity including anti-inflammatory, anti-proliferative, pro-apoptotic and anti-angiogenicity. The effects of lenalidomide are distinct from chemotherapy, hypomethylating agents or kinase inhibitors, making lenalidomide an attractive agent for use in AML and in combination with existing active agents. To determine whether anti-PD-1 (nivolumab) and lenalidomide alone or in combination could enhance LAA-specific T cell immune responses, we used colony-forming immune and ELISpot assays. Combinations of immunother-apeutic approaches are believed to increase antigen-specific immune responses against leukemic cells including LPC/LSCs. In this study we used a combination of LAA-peptides with the immune checkpoint inhibitor anti-PD-1 and lenalidomide to enhance the killing of LSC/LPCs ex vivo. Our data offer a novel insight into how we could improve AML patient responses to treatment in future clinical studies