Dynamic microvilli sculpt bristles at nanometric scale.

Organisms generate shapes across size scales. Whereas patterning and morphogenesis of macroscopic tissues has been extensively studied, the principles underlying the formation of micrometric and submicrometric structures remain largely enigmatic. Individual cells of polychaete annelids, so-called chaetoblasts, are associated with the generation of chitinous bristles of highly stereotypic geometry.

A Cryptochrome adopts distinct moon- and sunlight states and functions as sun- versus moonlight interpreter in monthly oscillator entrainment.

The moon's monthly cycle synchronizes reproduction in countless marine organisms. The mass-spawning bristle worm Platynereis dumerilii uses an endogenous monthly oscillator set by full moon to phase reproduction to specific days. But how do organisms recognize specific moon phases? We uncover that the light receptor L-Cryptochrome (L-Cry) discriminates between different moonlight durations, as well as between sun- and moonlight.

The cation exchanger Letm1, circadian rhythms, and NAD(H) levels interconnect in diurnal zebrafish.

Mitochondria are fundamental for life and require balanced ion exchange to maintain proper functioning. The mitochondrial cation exchanger LETM1 sparks interest because of its pathophysiological role in seizures in the Wolf Hirschhorn Syndrome (WHS). Despite observation of sleep disorganization in epileptic WHS patients, and growing studies linking mitochondria and epilepsy to circadian rhythms, LETM1 has not been studied from the chronobiological perspective.

Two light sensors decode moonlight versus sunlight to adjust a plastic circadian/circalunidian clock to moon phase.

Many species synchronize their physiology and behavior to specific hours. It is commonly assumed that sunlight acts as the main entrainment signal for ∼24-h clocks. However, the moon provides similarly regular time information.

Comparative Assessment of the Shaping Ability of Reciproc Blue, WaveOne Gold, and ProTaper Gold in Simulated Root Canals.

Maintaining the original trajectory of the root canal is a major challenge in endodontic therapy, especially in narrow and curved root canals. The present study aims to assess the shaping capacity of three endodontic systems made of different nickel−titanium alloys on simulated curved root canals. Thirty-six endodontic resin blocks (Ref.

Evaluation of the Shaping Ability of Three Thermally Treated Nickel-Titanium Endodontic Instruments on Standardized 3D-printed Dental Replicas Using Cone-Beam Computed Tomography.

The aim of the present study is to compare the efficacy of three root canal preparation systems in the shaping of 3D-printed root canal replicas of single rooted teeth. : Sixty 3D-printed root canal replicas were produced and divided into three groups, each consisting of twenty samples. Each group was shaped with a different instrument: Reciproc Blue R25/08 (VDW GmbH, Munich, Gemany), WaveOne Gold Primary 25/07 (Dentsply Sirona, Ballaigues, Switzerland), and ProTaper Gold F2 25/08 (Denstply Sirona).

Characterization of cephalic and non-cephalic sensory cell types provides insight into joint photo- and mechanoreceptor evolution.

Rhabdomeric opsins (r-opsins) are light sensors in cephalic eye photoreceptors, but also function in additional sensory organs. This has prompted questions on the evolutionary relationship of these cell types, and if ancient r-opsins were non-photosensory. A molecular profiling approach in the marine bristleworm revealed shared and distinct features of cephalic and non-cephalic -expressing cells.

α-Catulin downregulates E-cadherin and promotes melanoma progression and invasion.

Metastasis is associated with poor prognosis for melanoma responsible for about 90% of skin cancer-related mortality. To metastasize, melanoma cells must escape keratinocyte control, invade across the basement membrane and survive in the dermis by resisting apoptosis before they can intravasate into the circulation. α-Catulin (CTNNAL1) is a cytoplasmic molecule that integrates the crosstalk between nuclear factor-kappa B and Rho signaling pathways, binds to β-catenin and increases the level of both α-catenin and β-catenin and therefore has potential effects on inflammation, apoptosis and cytoskeletal reorganization.

COP9 signalosome interacts ATP-dependently with p97/valosin-containing protein (VCP) and controls the ubiquitination status of proteins bound to p97/VCP.

Ubiquitinated proteins can alternatively be delivered directly to the proteasome or via p97/VCP (valosin-containing protein). Whereas the proteasome degrades ubiquitinated proteins, the homohexameric ATPase p97/VCP seems to control the ubiquitination status of recruited substrates. The COP9 signalosome (CSN) is also involved in the ubiquitin/proteasome system (UPS) as exemplified by regulating the neddylation of ubiquitin E3 ligases.

Crosstalk between the NF-kappaB activating IKK-complex and the CSN signalosome.

A great variety of signalling pathways regulating inflammation, cell development and cell survival require NF-kappaB transcription factors, which are normally inactive due to binding to inhibitors, such as IkappaBalpha. The canonical activation pathway of NF-kappaB is initiated by phosphorylation of the inhibitor by an IkappaB kinase (IKK) complex triggering ubiquitination of IkappaB molecules by SCF-type E3-ligase complexes and rapid degradation by 26S-proteasomes. The ubiquitination machinery is regulated by the COP9 signalosome (CSN).

Role of the erythropoietin receptor in ETV6/RUNX1-positive acute lymphoblastic leukemia.

Purpose: We explored the mechanisms leading to the distinct overexpression of EPOR as well as the effects of EPO signaling on ETV6/RUNX1-positive acute lymphoblastic leukemias.

Experimental Design: ETV6/RUNX1-expressing model cell lines and leukemic cells were used for real-time PCR of EPOR expression. Proliferation, viability, and apoptosis were analyzed on cells exposed to EPO, prednisone, or inhibitors of EPOR pathways by [3H]thymidine incorporation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and Annexin V/propidium iodide staining.

Genes proximal and distal to MYCN are highly expressed in human neuroblastoma as visualized by comparative expressed sequence hybridization.

MYCN amplification is associated with poor prognosis in neuroblastoma disease. To improve our understanding of the influence of the MYCN amplicon and its corresponding expression, we investigated the 2p expression pattern of MYCN amplified (n = 13) and nonamplified (n = 4) cell lines and corresponding primary tumors (n = 3) using the comparative expressed sequence hybridization technique. All but one MYCN amplified cell line displayed overexpression at 2p.

A highly conserved proapoptotic gene, IKIP, located next to the APAF1 gene locus, is regulated by p53.

We describe here the identification and initial characterization of a novel human gene termed IKIP (I kappa B kinase interacting protein) that is located on chromosome 12 in close proximity to APAF1 (apoptotic protease-activating factor-1). IKIP and APAF1 share a common 488 bp promoter from which the two genes are transcribed in opposite directions. Three IKIP transcripts are generated by differential splicing and alternative exon usage that do not show significant homology to other genes in the databases.

Oligodeoxynucleotides containing CpG motifs induce low levels of TNF-alpha in human B lymphocytes: possible adjuvants for Th1 responses.

Oligodeoxynucleotides containing CpG motifs (CpG-ODN) represent potential adjuvants for specific immunotherapy of type I allergies because they foster Th1-like immune responses. However, previous work has shown that CpG-ODN induce systemically active levels of TNF-alpha in murine macrophages. The goal of the present study was to evaluate the release of TNF-alpha in human cells by a CpG-ODN proven to induce Th1 immune responses in cells from atopic individuals and in mice.

Characterisation of genotoxic properties of 2',2'-difluorodeoxycytidine.

The genotoxic properties of 2',2'-difluorodeoxycytidine (dFdC) were characterised using diploid, mortal low-passage fibroblasts (LPF cells) and the spontaneously transformed fibroblast cell line V79. In both cell types, incorporation of dFdC into the DNA led to an increase of DNA single-strand breaks evaluated by an in situ nick translation assay and to an accumulation of cells in the S-phase of the cell cycle. At concentrations below those leading to cell cycle arrest, dFdC neither induced sister chromatid exchange (SCE) nor structural chromosome aberrations in LPF cells, whereas V79 cells accumulated SCEs as well as chromosome breaks over a broad dose range.

alpha-Melanocyte stimulating hormone downregulates differentiation-driven heat shock protein 70 expression in keratinocytes.

Heat shock proteins are versatile tools engaged in several cellular functions. In particular, the stress-inducible 70-kDa heat shock protein (hsp70) not only confers protection on cells but also is involved in the regulation of the production of cellular stress response mediators including cytokines. In addition to cytokines, neurohormones such as alpha-melanocyte stimulating hormone (alphaMSH) were recently found to be potent mediators of inflammatory and immune responses.

Drug resistance against gemcitabine and topotecan mediated by constitutive hsp70 overexpression in vitro: implication of quercetin as sensitiser in chemotherapy.

Heat shock proteins have been reported to confer resistance to certain antineoplastic drugs. We investigated the impact of hsp70 overexpression on the efficacy of two new anti-cancer drugs, topotecan and gemcitabine. We used the fibrosarcoma WEHI-S cells stably transfected to overexpress the hsp70 cDNA from the constitutive SV40 promoter and appropriate control cells.

HSP70 overexpression mediates the escape of a doxorubicin-induced G2 cell cycle arrest.

The stress inducible heat shock protein 70 (hsp70) confers resistance to a variety of adverse environmental conditions including certain anticancer drugs. In the present study we explored cellular consequences of hsp70 overexpression with respect to genotoxic stress. Employing an isogenic set of stable transfectant cells, one overexpressing hsp70 and the other serving as control, we found that a high hsp70 expression level is sufficient to provide protection against the cytotoxicity of doxorubicin.