Synthesis, Cytotoxicity and Antiproliferative Effect of New Pyrrole Hydrazones.

Novel pyrrole-based carbohydrazide () and hydrazones (-) were synthesized, characterized, and subjected to spectroscopic studies. The hydrazones were obtained by reacting a pyrrole hydrazide with substituted pyrrole aldehydes. The initial carbohydrazide was prepared by selective hydrazinolysis of the obtained -pyrrolylcarboxylic acid ethyl ester.

Effect of Co-Sputtered Copper and Titanium Oxide Coatings on Bacterial Resistance and Cytocompatibility of Osteoblast Cells.

One of the primary risk factors for implant failure is thought to be implant-related infections during the early healing phase. Developing coatings with cell stimulatory behaviour and bacterial adhesion control is still difficult for bone implants. This study proposes an approach for one-step deposition of biocompatible and antimicrobial Cu-doped TiO coatings via glow-discharge sputtering of a mosaic target.

A template wizard for the cocreation of machine-readable data-reporting to harmonize the evaluation of (nano)materials.

Making research data findable, accessible, interoperable and reusable (FAIR) is typically hampered by a lack of skills in technical aspects of data management by data generators and a lack of resources. We developed a Template Wizard for researchers to easily create templates suitable for consistently capturing data and metadata from their experiments. The templates are easy to use and enable the compilation of machine-readable metadata to accompany data generation and align them to existing community standards and databases, such as eNanoMapper, streamlining the adoption of the FAIR principles.

Development of a mouse embryonic stem cell model for investigating the functions of the linker histone H1-4.

The linker histone H1 C-terminal domain (CTD) plays a pivotal role in chromatin condensation. De novo frameshift mutations within the CTD coding region of H1.4 have recently been reported to be associated with Rahman syndrome, a neurological disease that causes intellectual disability and overgrowth.

Deglycation activity of the Escherichia coli glycolytic enzyme phosphoglucose isomerase.

Glycation is a spontaneous chemical reaction, which affects the structure and function of proteins under normal physiological conditions. Therefore, organisms have evolved diverse mechanisms to combat glycation. In this study, we show that the Escherichia coli glycolytic enzyme phosphoglucose isomerase (Pgi) exhibits deglycation activity.

The CENP-A nucleosome: where and when it happens during the inner kinetochore's assembly.

CENP-A is an essential histone variant that replaces the canonical H3 at the centromeres and marks these regions epigenetically. The CENP-A nucleosome is the specific building block of centromeric chromatin, and it is recognized by CENP-C and CENP-N, two components of the constitutive centromere-associated network (CCAN), the first protein layer of the kinetochore. Recent proposals of the yeast and human (h)CCAN structures position the assembly on exposed DNA, suggesting an elusive spatiotemporal recognition.

Molecular Mechanism of Nucleosome Recognition by the Pioneer Transcription Factor Sox.

Pioneer transcription factors (PTFs) have the remarkable ability to directly bind to chromatin to stimulate vital cellular processes. In this work, we dissect the universal binding mode of Sox PTF by combining extensive molecular simulations and physiochemistry approaches, along with DNA footprinting techniques. As a result, we show that when Sox consensus DNA is located at the solvent-facing DNA strand, Sox binds to the compact nucleosome without imposing any significant conformational changes.

Chromatin regulators in DNA replication and genome stability maintenance during S-phase.

The duplication of genetic information is central to life. The replication of genetic information is strictly controlled to ensure that each piece of genomic DNA is copied only once during a cell cycle. Factors that slow or stop replication forks cause replication stress.

Advances in Multifunctional Bioactive Coatings for Metallic Bone Implants.

To fix the bone in orthopedics, it is almost always necessary to use implants. Metals provide the needed physical and mechanical properties for load-bearing applications. Although widely used as biomedical materials for the replacement of hard tissue, metallic implants still confront challenges, among which the foremost is their low biocompatibility.

Surface Modification of Additively Fabricated Titanium-Based Implants by Means of Bioactive Micro-Arc Oxidation Coatings for Bone Replacement.

In this work, the micro-arc oxidation method is used to fabricate surface-modified complex-structured titanium implant coatings to improve biocompatibility. Depending on the utilized electrolyte solution and micro-arc oxidation process parameters, three different types of coatings (one of them-oxide, another two-calcium phosphates) were obtained, differing in their coating thickness, crystallite phase composition and, thus, with a significantly different biocompatibility. An analytical approach based on X-ray computed tomography utilizing software-aided coating recognition is employed in this work to reveal their structural uniformity.

Safe(r) by design guidelines for the nanotechnology industry.

Expectations for safer and sustainable chemicals and products are growing to comply with the United Nations and European strategies for sustainability. The application of Safe(r) by Design (SbD) in nanotechnology implies an iterative process where functionality, human health and safety, environmental and economic impact and cost are assessed and balanced as early as possible in the innovation process and updated at each step. The EU H2020 NanoReg2 project was the first European project to implement SbD in six companies handling and/or manufacturing nanomaterials (NMs) and nano-enabled products (NEP).

New Heterocyclic Combretastatin A-4 Analogs: Synthesis and Biological Activity of Styryl-2(3)-benzothiazolones.

Here, we describe the synthesis, characterization, and biological activities of a series of 26 new styryl-2(3H)-benzothiazolone analogs of combretastatin-A4 (CA-4). The cytotoxic activities of these compounds were tested in several cell lines (EA.hy926, A549, BEAS-2B, MDA-MB-231, HT-29, MCF-7, and MCF-10A), and the relations between structure and cytotoxicity are discussed.

Influence of surface termination of ultrananocrystalline diamond films coated on titanium on response of human osteoblast cells: A proteome study.

Successful osseointegration, i.e. the fully functional connection of patient's bone and artificial implant depends on the response of the cells to the direct contact with the surface of the implant.

MeCP2 is a microsatellite binding protein that protects CA repeats from nucleosome invasion.

The Rett syndrome protein MeCP2 was described as a methyl-CpG-binding protein, but its exact function remains unknown. Here we show that mouse MeCP2 is a microsatellite binding protein that specifically recognizes hydroxymethylated CA repeats. Depletion of MeCP2 alters chromatin organization of CA repeats and lamina-associated domains and results in nucleosome accumulation on CA repeats and genome-wide transcriptional dysregulation.

Electrochemical, Tribological and Biocompatible Performance of Electron Beam Modified and Coated Ti6Al4V Alloy.

Vacuum cathodic arc TiN coatings with overlaying TiO film were deposited on polished and surface roughened by electron beam modification (EBM) Ti6Al4V alloy. The substrate microtopography consisted of long grooves formed by the liner scan of the electron beam with appropriate frequencies (500 (AR500) and 850 (AR850) Hz). EBM transformed the α + β Ti6Al4V mixed structure into a single α'-martensite phase.

Towards FAIR nanosafety data.

Nanotechnology is a key enabling technology with billions of euros in global investment from public funding, which include large collaborative projects that have investigated environmental and health safety aspects of nanomaterials, but the reuse of accumulated data is clearly lagging behind. Here we summarize challenges and provide recommendations for the efficient reuse of nanosafety data, in line with the recently established FAIR (findable, accessible, interoperable and reusable) guiding principles. We describe the FAIR-aligned Nanosafety Data Interface, with an aggregated findability, accessibility and interoperability across physicochemical, bio-nano interaction, human toxicity, omics, ecotoxicological and exposure data.

CpG Islands Shape the Epigenome Landscape.

Epigenetic modifications and nucleosome positioning play an important role in modulating gene expression. However, how the patterns of epigenetic modifications and nucleosome positioning are established around promoters is not well understood. Here, we have addressed these questions in a series of genome-wide experiments coupled to a novel bioinformatic analysis approach.

Resolution of R-loops by INO80 promotes DNA replication and maintains cancer cell proliferation and viability.

Collisions between the DNA replication machinery and co-transcriptional R-loops can impede DNA synthesis and are a major source of genomic instability in cancer cells. How cancer cells deal with R-loops to proliferate is poorly understood. Here we show that the ATP-dependent chromatin remodelling INO80 complex promotes resolution of R-loops to prevent replication-associated DNA damage in cancer cells.

Deregulated levels of RUVBL1 induce transcription-dependent replication stress.

Chromatin regulators control transcription and replication, however if and how they might influence the coordination of these processes still is largely unknown. RUVBL1 and the related ATPase RUVBL2 participate in multiple nuclear processes and are implicated in cancer. Here, we report that both the excess and the deficit of the chromatin regulator RUVBL1 impede DNA replication as a consequence of altered transcription.

The Chromatin Response to Double-Strand DNA Breaks and Their Repair.

Cellular DNA is constantly being damaged by numerous internal and external mutagenic factors. Probably the most severe type of insults DNA could suffer are the double-strand DNA breaks (DSBs). They sever both DNA strands and compromise genomic stability, causing deleterious chromosomal aberrations that are implicated in numerous maladies, including cancer.

Universal Codons with Enrichment from GC to AU Nucleotide Composition Reveal a Chronological Assignment from Early to Late Along with LUCA Formation.

The emergence of a primitive genetic code should be considered the most essential event during the origin of life. Almost a complete set of codons (as we know them) should have been established relatively early during the evolution of the last universal common ancestor (LUCA) from which all known organisms descended. Many hypotheses have been proposed to explain the driving forces and chronology of the evolution of the genetic code; however, none is commonly accepted.

Chromatin control in double strand break repair.

DNA double strand breaks (DSB) are the most deleterious type of damage inflicted on DNA by various environmental factors and as consequences of normal cellular metabolism. The multistep nature of DSB repair and the need to assemble large protein complexes at repair sites necessitate multiple chromatin changes there. This review focuses on the key findings of how chromatin regulators exert temporal and spatial control on DSB repair.

Structure of an H1-Bound 6-Nucleosome Array Reveals an Untwisted Two-Start Chromatin Fiber Conformation.

Chromatin adopts a diversity of regular and irregular fiber structures in vitro and in vivo. However, how an array of nucleosomes folds into and switches between different fiber conformations is poorly understood. We report the 9.

Possible Emergence of Sequence Specific RNA Aminoacylation via Peptide Intermediary to Initiate Darwinian Evolution and Code Through Origin of Life.

One of the most intriguing questions in biological science is how life originated on Earth. A large number of hypotheses have been proposed to explain it, each putting an emphasis on different events leading to functional translation and self-sustained system. Here, we propose a set of interactions that could have taken place in the prebiotic environment.