Salt-inducible kinase 3 protects tumor cells from cytotoxic T-cell attack by promoting TNF-induced NF-κB activation.

Background: Cancer immunotherapeutic strategies showed unprecedented results in the clinic. However, many patients do not respond to immuno-oncological treatments due to the occurrence of a plethora of immunological obstacles, including tumor intrinsic mechanisms of resistance to cytotoxic T-cell (TC) attack. Thus, a deeper understanding of these mechanisms is needed to develop successful immunotherapies.

M1 Macrophages Induce Protumor Inflammation in Melanoma Cells through TNFR-NF-κB Signaling.

The tumor microenvironment, with distinctive cell types and a complex extracellular matrix has a tremendous impact on cancer progression. In this study, we investigated the effects of proinflammatory (M1) and immunosuppressive (M2) macrophages on hyaluronan (HA) matrix formation and inflammatory response in melanoma cells. Proinflammatory factors secreted from M1 macrophages stimulated the formation of a thick pericellular HA matrix in melanoma cells due to upregulation of HA synthase 2 (HAS2).

Calpain-2 regulates hypoxia/HIF-induced plasticity toward amoeboid cancer cell migration and metastasis.

Hypoxia, through hypoxia inducible factor (HIF), drives cancer cell invasion and metastatic progression in various cancer types. In epithelial cancer, hypoxia induces the transition to amoeboid cancer cell dissemination, yet the molecular mechanisms, relevance for metastasis, and effective intervention to combat hypoxia-induced amoeboid reprogramming remain unclear. Here, we identify calpain-2 as a key regulator and anti-metastasis target of hypoxia-induced transition from collective to amoeboid dissemination of breast and head and neck (HN) carcinoma cells.

Targeted transcript quantification in single disseminated cancer cells after whole transcriptome amplification.

Gene expression analysis of rare or heterogeneous cell populations such as disseminated cancer cells (DCCs) requires a sensitive method allowing reliable analysis of single cells. Therefore, we developed and explored the feasibility of a quantitative PCR (qPCR) assay to analyze single-cell cDNA pre-amplified using a previously established whole transcriptome amplification (WTA) protocol. We carefully selected and optimized multiple steps of the protocol, e.

[Management and prognosis of patients with squamous cell carcinomas of the nasal cavity and the paranasal sinuses].

Squamous cell carcinomas (SCC) of the nasal cavity and the paranasal sinuses are a very rare and poorly understood tumor entity. To date, no consistent management strategy exists. The purpose of our study was to demonstrate our therapeutic strategy and to correlate clinicopathological features with clinical follow-up data.

[Grisel's syndrome after otoplasty].

Grisel's syndrome is known as a very rare complication of ENT surgery. It is described as non-traumatic atlantoaxial rotatory subluxation, often seen after tonsillectomy or adenoidectomy in children. Therapy is staged according to the Fielding classification.

DNA damage in oocytes induces a switch of the quality control factor TAp63α from dimer to tetramer.

TAp63α, a homolog of the p53 tumor suppressor, is a quality control factor in the female germline. Remarkably, already undamaged oocytes express high levels of the protein, suggesting that TAp63α's activity is under tight control of an inhibitory mechanism. Biochemical studies have proposed that inhibition requires the C-terminal transactivation inhibitory domain.

Strategies for the cell-free expression of membrane proteins.

Cell-free expression offers an interesting alternative method to produce membrane proteins in high amounts. Elimination of toxicity problems, reduced proteolytic degradation and a nearly unrestricted option to supply potentially beneficial compounds like cofactors, ligands or chaperones into the reaction are general advantages of cell-free expression systems. Furthermore, the membrane proteins may be translated directly into appropriate hydrophobic and membrane-mimetic surrogates, which might offer significant benefits for the functional folding of the synthesized proteins.

Membrane protein expression in cell-free systems.

Cell-free expression has emerged as a promising tool for the fast and efficient production of membrane proteins. The rapidly growing number of successfully produced targets in combination with the continuous development of new applications significantly promotes the distribution of this technology. Membrane protein synthesis by cell-free expression does not appear to be restricted by origin, size or topology of the target, and its global application is therefore a highly valuable characteristic.

The C-terminus of p63 contains multiple regulatory elements with different functions.

The transcription factor p63 is expressed as at least six different isoforms, of which two have been assigned critical biological roles within ectodermal development and skin stem cell biology on the one hand and supervision of the genetic stability of oocytes on the other hand. These two isoforms contain a C-terminal inhibitory domain that negatively regulates their transcriptional activity. This inhibitory domain contains two individual components: one that uses an internal binding mechanism to interact with and mask the transactivation domain and one that is based on sumoylation.

Role of molecular phonons and interfacial-temperature discontinuities in water evaporation.

During steady-state water evaporation, when the vapor phase is heated electrically, the temperature on the vapor side of the interface has been reported to be as much as 27.83 degrees C greater than that on the liquid side. The reported interfacial temperatures were measured with thermocouple beads that were less than 50 microm in diameter and centered 35 microm from the interface in each phase.

The better tag remains unseen.

One of the most crucial steps in protein structure determination by nuclear magnetic resonance (NMR) spectroscopy is the preparation of highly concentrated and well behaving protein samples. Here we present a system of modular tags which allows for high level expression, sophisticated purification of full-length protein, and solubility enhancement while keeping the amount of additional resonances low. This system consists of two different expression constructs and utilizes the tight binding of human calmodulin (hCaM) to the calmodulin binding peptide (CBP), which has already been used as a purification tag.

Transmembrane segment enhanced labeling as a tool for the backbone assignment of alpha-helical membrane proteins.

Recent advances in cell-free expression protocols have opened a new avenue toward high-resolution structural investigations of membrane proteins by x-ray crystallography and NMR spectroscopy. One of the biggest challenges for liquid-state NMR-based structural investigations of membrane proteins is the significant peak overlap in the spectra caused by large line widths and limited chemical shift dispersion of alpha-helical proteins. Contributing to the limited chemical shift dispersion is the fact that approximately 60% of the amino acids in transmembrane regions consist of only six different amino acid types.

E-cadherin but not beta-catenin expression is decreased in laryngeal biopsies from patients with laryngopharyngeal reflux.

Abnormal exposure of acid refluxate on the esophageal mucosa has been shown to decrease the epithelial barrier function through an alteration in the intercellular junctional complex. However, only few studies have examined the molecular effects caused by abnormal exposure of gastric refluxate on the laryngeal epithelium. E-cadherin and beta-catenin are cell membrane-associated proteins playing a major role in the maintenance of cell-cell adhesion in epithelial tissues.

Preparative scale expression of membrane proteins in Escherichia coli-based continuous exchange cell-free systems.

Cell-free expression is emerging as a prime method for the rapid production of preparative quantities of high-quality membrane protein samples. The technology facilitates easy access to large numbers of proteins that have been extremely difficult to obtain. Most frequently used are cell-free systems based on extracts of Escherichia coli cells, and the reaction procedures are reliable and efficient.

[Repeated dual-probe pH monitoring as a diagnostic tool to control therapy for laryngopharyngeal reflux].

Objectives: The most effective current treatment option for patients suffering from laryngopharyngeal reflux (LPR) is the use of proton pump inhibitors (PPIs). Compared to other PPIs, esomeprazole seems to provide best 24-h control of intragastric acid. However, some patients remain resistant to medical acid suppression with PPIs.

[Numerical simulations of pulsating flow in intracranial blood vessels with aneurysms using Lattice Boltzmann methods].

A major prerequisite for successful planning and control of the medical treatment of blood vessels with stenoses or aneurysms is the detailed knowledge of the individual situation in the damaged vessels. Modern tomography methods provide good spatial resolution, so that vessel walls as well as prostheses can be easily and rapidly identified. However, the mechanical loads of the walls remain largely unknown.

Thermocapillary transport of energy during water evaporation.

When evaporation occurs at a spherical water-vapor interface maintained at the circular mouth of a small funnel, studies of the energy transport have indicated that thermal conduction alone does not provide enough energy to evaporate the liquid at the observed rate. If the Gibbs model of the interface is adopted and the "surface-thermal capacity" is assigned a value of 30.6+/-0.

Analysis of the flow field and pressure drop in fixed-bed reactors with the help of lattice Boltzmann simulations.

The pressure drop of technical devices is a crucial property for their design and operation. In this paper, we show how the results of lattice Boltzmann simulations can be used in science and engineering to improve the physical understanding of the pressure drop and the flow inhomogeneities in porous media, especially in sphere-packed fixed-bed reactors with low aspect ratios. Commonly used pressure drop correlations are based on simplified assumptions such as the capillary or tortuosity model, which do not reflect all hydrodynamic effects.

CYP94A1, a plant cytochrome P450-catalyzing fatty acid omega-hydroxylase, is selectively induced by chemical stress in Vicia sativa seedlings.

CYP94A1 is a cytochrome P450 (P450) catalyzing fatty acid (FA) omega-hydroxylation in Vicia sativa seedlings. To study the physiological role of this FA monooxygenase, we report here on its regulation at the transcriptional level (Northern blot). Transcripts of CYP94A1, as those of two other P450-dependent FA hydroxylases (CYP94A2 and CYP94A3) from V.

In-cell NMR spectroscopy.

The role of a protein inside a cell is determined by both its location and its conformational state. Although fluorescence techniques are widely used to determine the cellular localization of proteins in vivo, these approaches cannot provide detailed information about a protein's three-dimensional state. This gap, however, can be filled by NMR spectroscopy, which can be used to investigate both the conformation as well as the dynamics of proteins inside living cells.

Bi-directional flow sensor with a wide dynamic range for medical applications.

This paper describes a novel three-wire thermal flow sensor for medical applications. The present innovation for low-frequency measurements involves the use of a pulsed-wire anemometer with a comparatively large wire diameter (12.5 microm and larger) together with a novel signal processing approach.