Genetic screening for anticancer genes highlights FBLN5 as a synthetic lethal partner of MYC.

Background: When ectopically overexpressed, anticancer genes, such as TRAIL, PAR4 and ORCTL3, specifically destroy tumour cells without harming untransformed cells. Anticancer genes can not only serve as powerful tumour specific therapy tools but studying their mode of action can reveal mechanisms underlying the neoplastic transformation, sustenance and spread.

Methods: Anticancer gene discovery is normally accidental.

The IMPACT of the COVID-19 Pandemic on Prescription Drug Use in Patients with Psoriasis Vulgaris in Germany.

Introduction: Real-world evidence (RWE) data is increasingly important to generate rapid insights to effectively manage patient populations. Disruptions like the coronavirus disease 2019 (COVID-19) pandemic may negatively impact the choice of medications used for managing chronic diseases such as psoriasis (PSO). Here, we explored the effect of the COVID-19 pandemic on the sales volumes of treatment guideline-based PSO medication in Germany.

TMEFF2: A Transmembrane Proteoglycan with Multifaceted Actions in Cancer and Disease.

Transmembrane protein with an EGF-like and two Follistatin-like domains 2 (TMEFF2) is a 374-residue long type-I transmembrane proteoglycan which is proteolytically shed from the cell surface. The protein is involved in a range of functions including metabolism, neuroprotection, apoptosis, embryonic development, onco-suppression and endocrine function. is methylated in numerous cancers, and an inverse correlation with the stage, response to therapy and survival outcome has been observed.

Glucocorticoid receptor antagonism reverts docetaxel resistance in human prostate cancer.

Resistance to docetaxel is a major clinical problem in advanced prostate cancer (PCa). Although glucocorticoids (GCs) are frequently used in combination with docetaxel, it is unclear to what extent GCs and their receptor, the glucocorticoid receptor (GR), contribute to the chemotherapy resistance. In this study, we aim to elucidate the role of the GR in docetaxel-resistant PCa in order to improve the current PCa therapies.

Photoluminescence enhancement of aligned arrays of single-walled carbon nanotubes by polymer transfer.

The photoluminescence of as-grown, aligned single-walled carbon nanotubes (SWNTs) on quartz is strongly quenched and barely detectable. Here we show that transferring these SWNTs to another substrate such as clean quartz or glass increases their emission efficiency by up to two orders of magnitude. By statistical analysis of large nanotube arrays we show at what point of the transfer process the emission enhancement occurs and how it depends on the receiving substrate and the employed transfer polymer.

Optomotor-blind negatively regulates Drosophila eye development by blocking Jak/STAT signaling.

Organ formation requires a delicate balance of positive and negative regulators. In Drosophila eye development, wingless (wg) is expressed at the lateral margins of the eye disc and serves to block retinal development. The T-box gene optomotor-blind (omb) is expressed in a similar pattern and is regulated by Wg.

IκΒα inhibits apoptosis at the outer mitochondrial membrane independently of NF-κB retention.

IκBα resides in the cytosol where it retains the inducible transcription factor NF-κB. We show that IκBα also localises to the outer mitochondrial membrane (OMM) to inhibit apoptosis. This effect is especially pronounced in tumour cells with constitutively active NF-κB that accumulate high amounts of mitochondrial IκBα as a NF-κB target gene.

Mapping charge-carrier density across the p-n junction in ambipolar carbon-nanotube networks by Raman microscopy.

In situ confocal Raman microscopy is used to map the recombination zone (induced p-n junction) in an ambipolar carbon-nanotube-network transistor with high spatial resolution. The shift of the 2D mode (G' mode) depending on hole and electron accumulation serves as a measure for the local charge-carrier density and provides complementary information about charge transport and recombination in ambipolar transistors.

Trion electroluminescence from semiconducting carbon nanotubes.

Near-infrared emission from semiconducting single-walled carbon nanotubes (SWNTs) usually results from radiative relaxation of excitons. By binding an additional electron or hole through chemical or electrochemical doping, charged three-body excitons, so-called trions, are created that emit light at lower energies. The energy difference is large enough to observe weak trion photoluminescence from doped SWNTs even at room temperature.

Isolation and characterization of the anticancer gene organic cation transporter like-3 (ORCTL3).

ORCTL3, an organic cation/anion transporter expressed in various tissue types, was isolated in a genome-wide cDNA screen as a gene with a tumor-specific apoptosis activity. When overexpressed it elicits an apoptosis response in many transformed cells, while normal cells remain unaffected. It can be activated for apoptosis induction by individual tumorigenic mutations in renal cells.

Powerhouse down: Complex II dissociation in the respiratory chain.

Complex II of the respiratory chain (RC) recently emerged as a prominent regulator of cell death. In both cancer cells as well as neurodegenerative diseases, mutations in subunits have been found along with other genetic alterations indirectly affecting this complex. Anticancer compounds were developed that target complex II and cause cell death in a tumor-specific way.

Optomotor-blind in the development of the Drosophila HS and VS lobula plate tangential cells.

The horizontal system and vertical system cells of the dipteran optic lobes are well understood regarding their physiology and role in visually guided behavior. Little is known, however, about their development. Drosophila optomotor-blind (omb) is required for the development of the HS/VS cells which are lacking in the adult brain of the In(1)omb[H31] regulatory mutant.

CKMT1 regulates the mitochondrial permeability transition pore in a process that provides evidence for alternative forms of the complex.

The permeability transition pore (PT-pore) mediates cell death through the dissipation of the mitochondrial membrane potential (ΔΨm). Because the exact composition of the PT-pore is controversial, it is crucial to investigate the actual molecular constituents and regulators of this complex. We found that mitochondrial creatine kinase-1 (CKMT1) is a universal and functionally necessary gatekeeper of the PT-pore, as its depletion induces mitochondrial depolarization and apoptotic cell death.

Investigation of the thermal stability of the carbon framework of graphene oxide.

In this study, we use our recently prepared graphene oxide (GO) with an almost intact σ-framework of carbon atoms (ai-GO) to probe the thermal stability of the carbon framework for the first time. Ai-GO exhibits few defects because CO2 formation is prevented during synthesis. Ai-GO was thermally treated before chemical reduction and the resulting defect density in graphene was subsequently determined by statistical Raman microscopy.

Reconstitution of CKMT1 expression fails to rescue cells from mitochondrial membrane potential dissipation: implications for controlling RNAi experiments.

RNA interference (RNAi) is an essential method in molecular biology to reduce the expression of target genes and thereby determine their function. Since this tool is known to also have unspecific effects, control experiments are needed, chiefly among them the exclusion of off-target effects and the reconstitution of the genes' expression for the rescue of the cellular RNAi effects. We show here that the knock-down of the mitochondrial creatine kinase-1 (CKMT1) by RNA interference causes the dissipation of the mitochondrial membrane potential ΔΨm.

Graphene oxide: efficiency of reducing agents.

The efficiency of reducing agents for the reduction of graphene oxide (GO) could be probed by scanning Raman spectroscopy. A film of graphene flakes derived from GO was probed to be graphene like. We also focus on the surface quality of reduced GO (rGO).

Wet chemical synthesis of graphene.

A suitable technology for the preparation of graphene based on versatile wet chemistry is presented for the first time. The protocol allows the wet chemical synthesis of graphene from a new form of graphene oxide that consists of an intact hexagonal σ-framework of C-atoms. Thus, it can be easily reduced to graphene that is no longer dominated by defects.

Respiratory chain complex II as general sensor for apoptosis.

I review here the evidence that complex II of the respiratory chain (RC) constitutes a general sensor for apoptosis induction. This concept emerged from work on neurodegenerative diseases and from recent data on metabolic alterations in cancer cells affecting the RC and in particular on mutations of complex II subunits. It is also supported by experiments with many anticancer compounds that compared the apoptosis sensitivities of complex II-deficient versus WT cells.

Dissecting mitochondrial apoptosis pathways by gain-of-function cell culture screens.

While more primitive organism such as Caenorhabditis elegans and Drosophila melanogaster feature a limited, and by now probably mostly known, array of basic cell death factors, the mammalian cell is replete with additional regulators of the cell's demise. This abundance of apoptosis mediators has made it imperative to set up a systematic inventory of mammalian cell death genes. Genetic screens in this biological system have recently uncovered the rich diversity of cell death signalling and have in particular highlighted mitochondria as an organelle loaded with apoptosis regulators.

De-ubiquitinating proteases USP2a and USP2c cause apoptosis by stabilising RIP1.

Dynamic ubiquitination impacts on the degradation of proteins by the proteasome as well as on their effects as signalling factors. Of the many cellular responses that are regulated by changes in ubiquitination, apoptosis has garnered special attention. We have found that USP2a and USP2c, two isoforms of the ubiquitin-specific protease USP2, cause cell death upon ectopic expression.

The ER-mitochondria interface: the social network of cell death.

When cellular organelles communicate bad things can happen. Recent findings uncovered that the junction between the endoplasmic reticulum (ER) and the mitochondria holds a crucial role for cell death regulation. Not only does this locale connect the two best-known organelles in apoptosis, numerous regulators of cell death are concentrated at this spot, providing a terrain for intense signal transfers.

Fis1 and Bap31 bridge the mitochondria-ER interface to establish a platform for apoptosis induction.

The mitochondria and the endoplasmic reticulum (ER) are two organelles that critically contribute to apoptosis induction. While it is established that they communicate, how cell death signals are transmitted from the mitochondria to the ER is unknown. Here, we show that the mitochondrial fission protein Fission 1 homologue (Fis1) conveys an apoptosis signal from the mitochondria to the ER by interacting with Bap31 at the ER and facilitating its cleavage into the pro-apoptotic p20Bap31.

Anticancer genes: inducers of tumour-specific cell death signalling.

Recent studies have revealed a new class of genes encoding proteins with specific anticancer activity. Upon ectopic expression, these factors cause cell death specifically in tumour cells by apoptosis, autophagy or mitotic catastrophe, yet normal cells are spared. Some of these genes or their encoded proteins are in clinical development and show promising results, and their signalling pathways are currently under intense investigation.