Tenascin-C affects invasiveness of EGFR-mutated lung adenocarcinoma through a putative paracrine loop.

Tenascin C (TNC) is an extracellular matrix (ECM) protein and a potential biomarker affecting progression of different tumor types, such as pancreatic and lung cancer. Alternative splicing variants of TNC are known to have an impact on interaction partners like other ECM proteins or cell surface receptors, including epidermal growth factor receptor (EGFR), leading to numerous and sometimes opposite roles of TNC in tumor cell dissemination and proliferation. Only little is known about the impact of TNC on biologic characteristics of lung cancer, such as invasion and metastatic potential.

Molecular heterogeneity and commonalities in pancreatic cancer precursors with gastric and intestinal phenotype.

Objective: Due to the limited number of modifiable risk factors, secondary prevention strategies based on early diagnosis represent the preferred route to improve the prognosis of pancreatic ductal adenocarcinoma (PDAC). Here, we provide a comparative morphogenetic analysis of PDAC precursors aiming at dissecting the process of carcinogenesis and tackling the heterogeneity of preinvasive lesions.

Design: Targeted and whole-genome low-coverage sequencing, genome-wide methylation and transcriptome analyses were applied on a final collective of 122 morphologically well-characterised low-grade and high-grade PDAC precursors, including intestinal and gastric intraductal papillary mucinous neoplasms (IPMN) and pancreatic intraepithelial neoplasias (PanIN).

Tumor Microenvironment in Pancreatic Intraepithelial Neoplasia.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors with a poor prognosis. A characteristic of PDAC is the formation of an immunosuppressive tumor microenvironment (TME) that facilitates bypassing of the immune surveillance. The TME consists of a desmoplastic stroma, largely composed of cancer-associated fibroblasts (CAFs), immunosuppressive immune cells, immunoregulatory soluble factors, neural network cells, and endothelial cells with complex interactions.

Keratinocytes Counteract UVB-Induced Immunosuppression in Mice through HIF-1a Signaling.

The transcription factor HIF-1a regulates cellular metabolism under hypoxia but also immune responses and UVB-induced skin reactions. In keratinocytes (KCs), HIF-1a is an environmental sensor orchestrating the adaptation to environmental changes. In this study, we investigated the role of HIF-1a in KCs for skin reactions to acute and chronic UVB exposure in mice.

Use of anthropogenic-related nest material and nest parasite prevalence have increased over the past two centuries in Australian birds.

Global plastic production has increased exponentially since the 1940s, resulting in the increased presence of anthropogenic debris in the environment. Recent studies have shown that birds incorporate anthropogenic debris into their nests, which can reduce nest ectoparasite loads. However, we know little about the long-term history of interactions among birds, anthropogenic debris, and ectoparasites.

Bile-Based Cell-Free DNA Analysis Is a Reliable Diagnostic Tool in Pancreatobiliary Cancer.

Currently available serum biomarkers for pancreatobiliary cancers lack sensitivity and specificity and ultimate diagnosis still requires invasive procedures for histological confirmation. The detection of tumor-specific genetic aberrations with utilization of cell free DNA (cfDNA) is a less invasive approach than traditional tissue biopsies; however, it has not been implemented into clinical routine. In this study, we investigated bile as a liquid biopsy source in pancreatobiliary cancers and compared its potential as cell-free DNA source to plasma.

Monetary policy and US housing expansions: The case of time-varying supply elasticities.

We challenge the assumption in the literature of constant housing supply elasticities across housing expansions. Using a time-varying parameter (TVP)-VAR model on monthly US data since the early 1990s, we find that the response of housing supply to an expansionary monetary policy shock to the response of house prices has declined substantially since the Great Financial Crisis (GFC). Our findings are consistent with research suggesting that land-use regulation has tightened.

Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID.

The prerequisite to prevent childhood B-cell acute lymphoblastic leukemia (B-ALL) is to decipher its etiology. The current model suggests that infection triggers B-ALL development through induction of activation-induced cytidine deaminase (AID; also known as AICDA) in precursor B-cells. This evidence has been largely acquired through the use of ex vivo functional studies.

Targeting HSP90 dimerization via the C terminus is effective in imatinib-resistant CML and lacks the heat shock response.

Heat shock protein 90 (HSP90) stabilizes many client proteins, including the BCR-ABL1 oncoprotein. BCR-ABL1 is the hallmark of chronic myeloid leukemia (CML) in which treatment-free remission (TFR) is limited, with clinical and economic consequences. Thus, there is an urgent need for novel therapeutics that synergize with current treatment approaches.

RNA Aptamers Recognizing Murine CCL17 Inhibit T Cell Chemotaxis and Reduce Contact Hypersensitivity In Vivo.

The chemokine CCL17, mainly produced by dendritic cells (DCs) in the immune system, is involved in the pathogenesis of various inflammatory diseases. As a ligand of CCR4, CCL17 induces chemotaxis and facilitates T cell-DC interactions. We report the identification of two novel RNA aptamers, which were validated in vitro and in vivo for their capability to neutralize CCL17.

Requirement of MyD88 signaling in keratinocytes for Langerhans cell migration and initiation of atopic dermatitis-like symptoms in mice.

Atopic dermatitis (AD) is a chronic inflammatory disease controlled by the innate and adaptive immune system. To elucidate the impact of innate immune signaling in AD, we analyzed MyD88-deficient mice in a murine model of AD-like dermatitis by epicutaneous sensitization with ovalbumin (OVA). Global MyD88 deficiency led to reduced epidermal thickening and diminished accumulation of macrophages within the inflamed skin.

hypD as a marker for [NiFe]-hydrogenases in microbial communities of surface waters.

Hydrogen is an important trace gas in the atmosphere. Soil microorganisms are known to be an important part of the biogeochemical H2 cycle, contributing 80 to 90% of the annual hydrogen uptake. Different aquatic ecosystems act as either sources or sinks of hydrogen, but the contribution of their microbial communities is unknown.

Distribution analysis of hydrogenases in surface waters of marine and freshwater environments.

Background: Surface waters of aquatic environments have been shown to both evolve and consume hydrogen and the ocean is estimated to be the principal natural source. In some marine habitats, H(2) evolution and uptake are clearly due to biological activity, while contributions of abiotic sources must be considered in others. Until now the only known biological process involved in H(2) metabolism in marine environments is nitrogen fixation.

Phenotypical plasticity of vascular smooth muscle cells-effect of in vitro and in vivo shear stress for tissue engineering of blood vessels.

Vascular smooth muscle cells (vSMCs) can switch between a contractile (differentiated) and a synthetic (dedifferentiated) phenotype. Synthetic, proliferative vSMCs are observed during embryogenesis, wound repair, and tissue engineering. The potential of isolated vSMCs to reverse this phenotypic modulation depends strictly on culture conditions.

Annexin A4 binding to anionic phospholipid vesicles modulated by pH and calcium.

Annexin A4 belongs to a class of Ca(2+)-binding proteins for which different functions in the cell have proposed, e.g. involvement in exocytosis and in the coagulation process.

Tissue engineering of aortic tissue: dire consequence of suboptimal elastic fiber synthesis in vivo.

Objective: To study autologous tissue engineered blood vessels (TEBV) in the descending aorta of juvenile sheep.

Methods: Autologous vascular smooth muscle cells (vSMC) and endothelial cells were obtained from ovine carotid arteries. vSMC were seeded on bioresorbable scaffolds and dynamically cultured for 14 days.

Comparative study of cellular and extracellular matrix composition of native and tissue engineered heart valves.

Tissue engineering of heart valves utilizes biodegradable or metabolizable scaffolds for remodeling by seeded autologous cells. The aim of this study was to determine and compare extracellular matrix (ECM) formations, cellular phenotypes and cell location of native and tissue engineered (TE) valve leaflets. Ovine carotid arteries, ovine and porcine hearts were obtained from slaughterhouses.

ProteinChip system technology: a powerful tool to analyze expression differences in tissue-engineered blood vessels.

At the time of implantation, tissue-engineered constructs should resemble native tissues as closely as possible. At present, histology and biochemical methods are commonly used to compare tissue-engineered constructs with native tissue. A ProteinChip system based on surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI) has been developed that allows visualization of complex protein profiles from biological samples.

Tissue engineering of ovine aortic blood vessel substitutes using applied shear stress and enzymatically derived vascular smooth muscle cells.

Compared to native blood vessels, all clinically available blood vessel substitutes perform suboptimally. Numerous approaches to tissue engineer (TE) blood vessels have been pursued using different scaffold materials, cell types, and culture conditions. Several limitations however remain to be overcome prior to the potential application in the arterial system.

Complete dynamic repopulation of decellularized heart valves by application of defined physical signals-an in vitro study.

Objective: Cardiovascular tissue engineering is a novel concept to develop ideal heart valve substitutes. The objective of this study was to use decellularized porcine pulmonary valves, ovine cells and dynamic tissue culture to obtain viable and biomechanically stable constructs, resembling native aortic heart valves.

Methods: Endothelial cells and myofibroblasts were obtained from ovine carotid arteries.

Impact of decellularization of xenogeneic tissue on extracellular matrix integrity for tissue engineering of heart valves.

The multidisciplinary research of tissue engineering utilizes biodegradable or decellularized scaffolds with autologous cell seeding. Objective of this study was to investigate the impact of different decellularization protocols on extracellular matrix integrity of xenogeneic tissue by means of multiphoton femtosecond laser scanning microscopy, biochemical and histological analysis. Pulmonary valves were dissected from porcine hearts and placed in a solution of trypsin-EDTA and incubated at 37 degrees C for either 5, 8, or 24 h, followed by a 24 h PBS washing.

Fission yeast Prp4p kinase regulates pre-mRNA splicing by phosphorylating a non-SR-splicing factor.

We provide evidence that Prp4p kinase activity is required for pre-mRNA splicing in vivo and show that loss of activity impairs G1-S and G2-M progression in the cell cycle. Prp4p interacts genetically with the non-SR (serine/arginine) splicing factors Prp1p and Prp5p. Bacterially produced Prp1p is phosphorylated by Prp4p in vitro.