[Thrombotic microangiopathy as a rare complication after lung transplantation].

Thrombotic microangiopathy (TMA) is defined by the typical triad of severe thrombocytopenia, hemolytic anemia and endorgan dysfunction and can be characterized by the pathophysiology of ischemia-inducing microthrombi in arterioles and capillaries possibly leading to severe organ dysfunction up to acutely life-threatening endorgan damage. In terms of etiology, management, therapy and prognosis, the following manifestations are distinguished: thrombotic thrombocytopenic purpura (TTP), shigatoxin-induced hemolytic-uremic syndrome (STEC-HUS), secondary comorbidity-related TMA and atypical hemolytic-uremic syndrome (aHUS). We present the case of a 49 year old lung transplant recipient developing aHUS.

Association of Polymorphic Cytochrome P450 Enzyme Pathways with Falls in Multimedicated Older Adults.

Objectives: Dose exposure is considered relevant for drug-associated falls in older adults, pointing to an importance of drug metabolism. Aim was to analyze individual factors altering drug metabolism such as enzyme saturation by drug exposure and pharmacogenetics in the context of drug-associated falls.

Design: Prospective population-based study (ActiFE-Ulm study).

Striking parallels between dorsoventral patterning in and reveal a complex evolutionary history behind a model gene regulatory network.

Dorsoventral pattering relies on Toll and BMP signalling in all insects studied so far, with variations in the relative contributions of both pathways. and the beetle share extensive dependence on Toll, while representatives of more distantly related lineages like the wasp and bug rely more strongly on BMP signalling. Here, we show that in the cricket , an evolutionarily distant outgroup, Toll has, like in , a direct patterning role for the ventral half of the embryo.

Effect of hairy vetch cover crop on maize nitrogen supply and productivity at varying yield environments in Southern Brazil.

Cover crops play a critical role on conservation and sustainable agriculture due to their well-documented benefits on both soil and crop productivity. Inclusion of legumes (e.g.

Fluorescent Biosensors for Multiplexed Imaging of Phosphoinositide Dynamics.

Phosphoinositides constitute a critical family of lipids that regulate numerous cellular processes. Phosphatidylinositol 4,5-bisphosphate (PIP) is arguably the most important plasma membrane phosphoinositide and is involved in regulating diverse processes. It is also the precursor of phosphatidylinositol 3,4,5-trisphosphate (PIP), which is critical for growth factor signaling, as well as membrane polarization and dynamics.

Pre-planting weed detection based on ground field spectral data.

Background: Site-specific weed management (SSWM) demands higher resolution data for mapping weeds in fields, but the success of this tool relies on the efficiency of optical sensors to discriminate weeds relative to other targets (soils and residues) before cash crop establishment. The objectives of this study were to (i) evaluate the accuracy of spectral bands to differentiate weeds (target) and other non-targets, (ii) access vegetation indices (VIs) to assist in the discrimination process, and (iii) evaluate the accuracy of the thresholds to distinguish weeds relative to non-targets for each VI using training and validation data sets.

Results: The main outcomes of this study for effectively distinguishing weeds from other non-targets are (i) training and validation data exhibited similar spectral curves, (ii) red and near-infrared spectral bands presented greater accuracy relative to the other bands, and (iii) the tested VIs increased the discrimination accuracy related to single bands, with an overall accuracy above 95% and a kappa above 0.

Immune Exclusion Is Frequent in Small-Cell Carcinoma of the Bladder.

Small-cell cancer of the urinary bladder is a rare but highly aggressive disease. It is currently unclear whether immune checkpoint therapies that have been approved for urothelial carcinomas will also be efficient in small-cell carcinomas. In this study, we analyzed potential predictors of response including PD-L1 expression and the quantity and location of tumor-infiltrating lymphocytes (TILs) in 12 small-cell and 69 "classical" urothelial cancers by immunohistochemistry.

Biased signaling of Ca-sensing receptors in cardiac myocytes regulates GIRK channel activity.

Ca-sensing receptors (CaSRs) belong to the class C of G protein-coupled receptors and are activated by extracellular Ca. CaSRs display biased G protein signaling by coupling to different classes of heterotrimeric G proteins depending on agonist and cell type. In this study we used fluorescent biosensors to directly analyze G protein coupling to CaSRs and downstream signaling in living cells.

Familial Sinus Node Disease Caused by a Gain of GIRK (G-Protein Activated Inwardly Rectifying K Channel) Channel Function.

Background: Inherited forms of sinus node dysfunction (SND) clinically include bradycardia, sinus arrest, and chronotropic incompetence and may serve as disease models to understand sinus node physiology and impulse generation. Recently, a gain-of-function mutation in the G-protein gene GNB2 led to enhanced activation of the GIRK (G-protein activated inwardly rectifying K channel). Thus, human cardiac GIRK channels are important for heart rate regulation and subsequently, genes encoding their subunits Kir3.

Expression of the immune checkpoint receptor TIGIT in Hodgkin's lymphoma.

Hodgkin's lymphoma (HL) is characterized by a high background of inflammatory cells which play an important role for the pathogenesis of the disease. T cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory immune checkpoint receptor and a putative target for novel immunotherapies. To study patterns of TIGIT expression in the T cell background surrounding malignant cells including Hodgkin cells, Reed-Sternberg cells and histiocytic cells, a microenvironment (ME) tissue microarray (TMA) was constructed from tissue punches measuring 2 mm in diameter obtained from formalin-fixed tissue samples of Hodgkin's lymphoma lymph nodes (n = 40) and normal human tonsil (n = 2).

NHS-based Tandem Mass Tagging of Proteins at the Level of Whole Cells: A Critical Evaluation in Comparison to Conventional TMT-Labeling Approaches for Quantitative Proteome Analysis.

Tandem mass tags (TMT) are usually introduced at the levels of isolated proteins or peptides. Here, for the first time, we report the labeling of whole cells and a critical evaluation of its performance in comparison to conventional labeling approaches. The obtained results indicated that TMT protein labeling using intact cells is generally possible, if it is coupled to a subsequent enrichment using anti-TMT antibody.

Annexin A10 optimally differentiates between intrahepatic cholangiocarcinoma and hepatic metastases of pancreatic ductal adenocarcinoma: a comparative study of immunohistochemical markers and panels.

Discriminating intrahepatic cholangiocarcinoma (ICC) from hepatic metastases of pancreatic ductal adenocarcinoma (mPDAC) can be challenging. While pathologists might depend on clinical information regarding a primary tumor, their diagnosis will lead the patient either to potentially curative surgery (for ICC) or to palliation (for mPDAC). Beyond the validation of recently published potential biomarkers for PDAC (primary or metastatic) in a large cohort, we assessed diagnostic performance of the most promising candidates in the challenging task of discriminating metastatic PDAC (mPDAC) from ICC.

Eukaryotic elongation factor 2 is a prognostic marker and its kinase a potential therapeutic target in HCC.

Unlabelled: Hepatocellular carcinoma is a cancer with increasing incidence and largely refractory to current anticancer drugs. Since Sorafenib, a multikinase inhibitor has shown modest efficacy in advanced hepatocellular carcinoma additional treatments are highly needed. Protein phosphorylation via kinases is an important post-translational modification to regulate cell homeostasis including proliferation and apoptosis.

Liver steatosis in pre-transplant liver biopsies can be quantified rapidly and accurately by nuclear magnetic resonance analysis.

Donor livers marginally acceptable or acceptable according to extended criteria are more frequently transplanted due to the growing discrepancy between demand and availability of donor organs. One type of marginally acceptable graft is a steatotic donor liver, because it is more sensitive to ischemia-reperfusion injury. Thus, quantitative assessment of steatosis is crucial prior to liver transplantation.

Receptor Species-dependent Desensitization Controls KCNQ1/KCNE1 K+ Channels as Downstream Effectors of Gq Protein-coupled Receptors.

Activation of G protein-coupled receptors (GPCRs) might induce divergent cellular responses, related to receptor-specific activation of different branches of the G signaling pathway. Receptor-specific desensitization provides a mechanism of effector modulation by restricting the spatiotemporal activation of signaling components downstream of G We quantified signaling events downstream of GPCR activation with FRET-based biosensors in CHO and HEK 293 cells. KCNQ1/KCNE1 channels (I) were measured as a functional readout of receptor-specific activation.

KCNE1 induces fenestration in the Kv7.1/KCNE1 channel complex that allows for highly specific pharmacological targeting.

Most small-molecule inhibitors of voltage-gated ion channels display poor subtype specificity because they bind to highly conserved residues located in the channel's central cavity. Using a combined approach of scanning mutagenesis, electrophysiology, chemical ligand modification, chemical cross-linking, MS/MS-analyses and molecular modelling, we provide evidence for the binding site for adamantane derivatives and their putative access pathway in Kv7.1/KCNE1 channels.

Bathing in carbon dioxide-enriched water alters protein expression in keratinocytes of skin tissue in rats.

Beneficial effects of balneotherapy using naturally occurring carbonated water (CO enriched) have been known since the Middle Ages. Although this therapy is clinically applied for peripheral artery disease and skin disorder, the underlying mechanisms are not fully elucidated.Under controlled conditions, rats were bathed in either CO-enriched water (CO content 1200 mg/L) or tap water, both at 37 °C, for 10 min daily over 4 weeks.

Markers of Hippo-Pathway Activity in Tumor Forming Liver Lesions.

Hepatocellular Carcinoma (HCC) is a lethal cancer worldwide. Recently, the hippo signaling pathway has been implicated in tumorigenesis of HCC and other malignant tumors. Aim of the study was therefore to evaluate the hippo signaling pathway activity and its clinico-pathological associations and crosstalk in different tumor forming hepatocellular lesions (HCC, hepatocellular adenoma (HCA), focal nodular hyperplasia (FNH) and cirrhosis).

Novel immunohistochemical markers differentiate intrahepatic cholangiocarcinoma from benign bile duct lesions.

Aims: The distinction between intrahepatic cholangiocarcinoma (ICC) and benign bile duct lesions can be challenging. Using our previously identified potential biomarkers for ICC, we examined whether these are useful for the differential diagnosis of ICC, bile duct adenoma and reactive bile duct proliferations in an immunohistochemical approach and identified a diagnostic marker panel including known biomarkers.

Methods: Subjects included samples from 77 patients with ICC, 33 patients with bile duct adenoma and 47 patients with ductular reactions in liver cirrhosis.

Differential proteomic and tissue expression analyses identify valuable diagnostic biomarkers of hepatocellular differentiation and hepatoid adenocarcinomas.

The exact discrimination of lesions with true hepatocellular differentiation from secondary tumours and neoplasms with hepatocellular histomorphology like hepatoid adenocarcinomas (HAC) is crucial. Therefore, we aimed to identify ancillary protein biomarkers by using complementary proteomic techniques (2D-DIGE, label-free MS). The identified candidates were immunohistochemically validated in 14 paired samples of hepatocellular carcinoma (HCC) and non-tumourous liver tissue (NT).

NCI-H295R cell line as in vitro model of hyperaldosteronism lacks functional KCNJ5 (GIRK4; Kir3.4) channels.

As a major cause of aldosterone producing adenomas, numerous gain-of-function mutations in the KCNJ5 gene (encoding the K(+) channel subunit GIRK4) have been identified. The human adrenocortical carcinoma cell line NCI-H295R is the most frequently used cellular model for in vitro studies related to regulation of aldosterone-synthesis. Because of the undefined role of KCNJ5 (GIRK4) in regulating synthesis of aldosterone, we aimed at identifying basal and G protein-activated GIRK4 currents in this paradigmatic cell line.

Novel Kv7.1-phosphatidylinositol 4,5-bisphosphate interaction sites uncovered by charge neutralization scanning.

Kv7.1 to Kv7.5 α-subunits belong to the family of voltage-gated potassium channels (Kv).

Differential effects of genetically-encoded Gβγ scavengers on receptor-activated and basal Kir3.1/Kir3.4 channel current in rat atrial myocytes.

Opening of G-protein-activated inward-rectifying K(+) (GIRK, Kir3) channels is regulated by interaction with βγ-subunits of Pertussis-toxin-sensitive G proteins upon activation of appropriate GPCRs. In atrial and neuronal cells agonist-independent activity (I(basal)) contributes to the background K(+) conductance, important for stabilizing resting potential. Data obtained from the Kir3 signaling pathway reconstituted in Xenopus oocytes suggest that I(basal) requires free G(βγ).

Structural basis of PI(4,5)P2-dependent regulation of GluA1 by phosphatidylinositol-5-phosphate 4-kinase, type II, alpha (PIP5K2A).

Ionotropic glutamate receptors are the most important excitatory receptors in the central nervous system, and their impairment can lead to multiple neuronal diseases. Here, we show that glutamate-induced currents in oocytes expressing GluA1 are increased by coexpression of the schizophrenia-associated phosphoinositide kinase PIP5K2A. This effect was due to enhanced membrane abundance and was blunted by a point mutation (N251S) in PIP5K2A.