Age-dependent increase of perineuronal nets in the human hippocampus and precocious aging in epilepsy.

Objective: Perineuronal nets (PNN) are specialized extracellular matrix (ECM) components of the central nervous system, frequently accumulating at the surface of inhibitory GABAergic interneurons. While an altered distribution of PNN has been observed in neurological disorders including Alzheimer's disease, schizophrenia and epilepsy, their anatomical distribution also changes during physiological brain maturation and aging. Such an age-dependent shift was experimentally associated also with hippocampal engram formation during brain maturation.

Functionalization of Chlorotonils: Dehalogenil as Promising Lead Compound for In Vivo Application.

The natural product chlorotonil displays high potency against multidrug-resistant Gram-positive bacteria and Plasmodium falciparum. Yet, its scaffold is characterized by low solubility and oral bioavailability, but progress was recently made to enhance these properties. Applying late-stage functionalization, we aimed to further optimize the molecule.

The natural product chlorotonil A preserves colonization resistance and prevents relapsing Clostridioides difficile infection.

Clostridioides difficile infections (CDIs) remain a healthcare problem due to high rates of relapsing/recurrent CDIs (rCDIs). Breakdown of colonization resistance promoted by broad-spectrum antibiotics and the persistence of spores contribute to rCDI. Here, we demonstrate antimicrobial activity of the natural product class of chlorotonils against C.

Regio- and Stereoselective Epoxidation and Acidic Epoxide Opening of Antibacterial and Antiplasmodial Chlorotonils Yield Highly Potent Derivatives.

The rise of antimicrobial resistance poses a severe threat to public health. The natural product chlorotonil was identified as a new antibiotic targeting multidrug resistant Gram-positive pathogens and Plasmodium falciparum. Although chlorotonil shows promising activities, the scaffold is highly lipophilic and displays potential biological instabilities.

Multilobar unilateral hypoplasia with emphasis on the posterior quadrant and severe epilepsy in children with FCD ILAE Type 1A.

Objective: Focal cortical dysplasia (FCD) Type 1 and its three subtypes have yet not been fully characterized at the clinical, anatomopathological, and molecular level (International League Against Epilepsy [ILAE] FCD classification from 2011). We aimed to describe the clinical phenotype of patients with histopathologically confirmed FCD1A obtained from a single epilepsy center between 2002 and 2016.

Methods: Medical records were retrieved from the hospital's archive.

Insulating SiO under Centimeter-Scale, Single-Crystal Graphene Enables Electronic-Device Fabrication.

Graphene on SiO enables fabrication of Si-technology-compatible devices, but a transfer of these devices from other substrates and direct growth have severe limitations due to a relatively small grain size or device-contamination. Here, we show an efficient, transfer-free way to integrate centimeter-scale, single-crystal graphene, of a quality suitable for electronic devices, on an insulating SiO film. Starting with single-crystal graphene grown epitaxially on Ru(0001), a SiO film is grown under the graphene by stepwise intercalation of silicon and oxygen.

Sacrificing one visual hemifield during pediatric epilepsy surgery: Effects on visual search.

Objectives: To investigate early and late effects of planned surgically acquired homonymous hemianopias on visual search in children and adolescents.

Methods: This prospective study included five patients (5y 5 m-18y 0 m; 2 girls) with pharmaco-refractory epilepsies in whom one visual hemifield was sacrificed as part of the surgical strategy, and, as controls, seven patients (5y 11 m-18y 0 m; 6 girls) undergoing epilepsy surgeries not affecting the visual fields. Visual search was studied using the "Table Test", which is an everyday life-like visual search test.

Correlates of intellectual development before and after hemispherotomy: an analysis of 75 children and adolescents.

This study describes the intellectual development of 75 children and adolescents who underwent hemispherotomy. Furthermore, we aimed to reveal predicting factors on pre- and postsurgical development with a focus on the role of aetiology. We analysed presurgical and six-month postsurgical developmental and intellectual data of 75 patients (age range: 0.

Presurgical Language fMRI in Children, Adolescents and Young Adults : A Validation Study.

Purpose: To validate four established, child-friendly functional magnetic resonance imaging (fMRI) language tasks (word chain task [WCT], vowel identification task [VIT], synonym task [SYT] and beep story task [BST]) in a predominantly pediatric cohort.

Methods: Intracarotid amobarbital procedures (IAP) (n = 17) and unchanged language after hemispherotomy (n = 6) were used as gold standards. The fMRI activations of nine regions of interest (ROI) in the frontal, temporal and parietal lobes as well as in the cerebellum were visually assessed in 23 fMRI examinations (in total 117 fMRI task sessions) of 23 patients (age range 10.

Lipidated Stapled Peptides Targeting the Acyl Binding Protein UNC119.

The acyl-binding UNC119 proteins mediate the activation and transport of various N-myristoylated proteins. In particular, UNC119a plays a crucial role in the completion of cytokinesis. Herein, we report the use of a lipidated peptide originating from the UNC119 binding partner Gnat1 as the basis for the design of lipidated, stabilized α-helical peptides that target UNC119a.

Tunable giant magnetoresistance in a single-molecule junction.

Controlling electronic transport through a single-molecule junction is crucial for molecular electronics or spintronics. In magnetic molecular devices, the spin degree-of-freedom can be used to this end since the magnetic properties of the magnetic ion centers fundamentally impact the transport through the molecules. Here we demonstrate that the electron pathway in a single-molecule device can be selected between two molecular orbitals by varying a magnetic field, giving rise to a tunable anisotropic magnetoresistance up to 93%.

The cholesterol transfer protein GRAMD1A regulates autophagosome biogenesis.

Autophagy mediates the degradation of damaged proteins, organelles and pathogens, and plays a key role in health and disease. Thus, the identification of new mechanisms involved in the regulation of autophagy is of major interest. In particular, little is known about the role of lipids and lipid-binding proteins in the early steps of autophagosome biogenesis.

Addressing the properties of "Metallo-DNA" with a Ag(i)-mediated supramolecular duplex.

The silver-nucleoside complex [Ag(i)-(3-cytidine)], , self-assembles to form a supramolecular metal-mediated base-pair array highly analogous to those seen in metallo-DNA. A combination of complementary hydrogen-bonding, hydrophobic and argentophilic interactions drive the formation of a double-helix with a continuous silver core. Electrical measurements on show that despite having Ag···Ag distances within <5% of the metallic radii, the material is electrically insulating.

Small-Molecule Inhibition of the UNC-Src Interaction Impairs Dynamic Src Localization in Cells.

Interference with the signaling activity of the N-myristoylated nonreceptor protein tyrosine kinase Src is considered a viable approach in anti-cancer drug discovery. However, ATP-competitive Src inhibitors have not reached the clinic yet and alternative approaches are in high demand. The UNC119A/B proteins bind the myristoylated N terminus of Src and thereby mediate energy-driven spatial cycles that maintain Src enrichment at the plasma membrane, which is critical for Src signaling activity.

Locally Induced Spin States on Graphene by Chemical Attachment of Boron Atoms.

Pristine graphene is known to be nonmagnetic due to its π-conjugated electron system. However, we find that localized magnetic moments can be generated by chemically attaching boron atoms to the graphene sheets. Such spin-polarized states are evidenced by the spin-split of the density of states (DOS) peaks near the Fermi level in scanning tunneling spectroscopy (STS).

Electronic effects and fundamental physics studied in molecular interfaces.

Scanning probe instruments in conjunction with a very low temperature environment have revolutionized the ability of building, functionalizing, and analysing two dimensional interfaces in the last twenty years. In addition, the availability of fast, reliable, and increasingly sophisticated methods to simulate the structure and dynamics of these interfaces allow us to capture even very small effects at the atomic and molecular level. In this review we shall focus largely on metal surfaces and organic molecular compounds and show that building systems from the bottom up and controlling the physical properties of such systems is no longer within the realm of the desirable, but has become day to day reality in our best laboratories.

Output-oriented analysis of the wet mechanical processing of polyolefin-rich waste for feedstock recycling.

In recent years, an increasing number of studies have revealed that plastics and their components (e.g. plasticisers) pose an environmental risk.

Tuning the structure of aminoferrocene-based anticancer prodrugs to prevent their aggregation in aqueous solution.

Aminoferrocene-based prodrugs are activated in cancer cells by reactive oxygen species (ROS). They were shown to exhibit high cytotoxicity towards a variety of cancer cell lines and primary cancer cells, but remain not toxic towards non-malignant cells. However, these prodrugs have rather high lipophilicity leading to relatively low water solubility.

Evidence for Ultralow-Energy Vibrations in Large Organic Molecules.

The quantum efficiency or the rate of conversion of incident photon to free electron in photosynthesis is known to be extremely high. It has long been thought that the origin of this efficiency are molecular vibrations leading to a very fast separation of electrons and holes within the involved molecules. However, molecular vibrations are commonly in the range above 100 meV, which is too high for excitations in an ambient environment.

Small-Molecule Inhibition of the UNC119-Cargo Interaction.

N-Terminal myristoylation facilitates membrane binding and activity of proteins, in particular of Src family kinases, but the underlying mechanisms are only beginning to be understood. The chaperones UNC119A/B regulate the cellular distribution and signaling of N-myristoylated proteins. Selective small-molecule modulators of the UNC119-cargo interaction would be invaluable tools, but have not been reported yet.

Microscopic origin of chiral shape induction in achiral crystals.

In biomineralization, inorganic materials are formed with remarkable control of the shape and morphology. Chirality, as present in the biomolecular world, is therefore also common for biominerals. Biomacromolecules, like proteins and polysaccharides, are in direct contact with the mineral phase and act as modifiers during nucleation and crystal growth.

4-Azidobenzyl ferrocenylcarbamate as an anticancer prodrug activated under reductive conditions.

Aminoferrocene-based prodrugs are activated in the presence of cancer-specific amounts of reactive oxygen species, e.g. H2O2, with the formation of products of two types: Fe-containing complexes, which catalyze generation of HO and O2(-), and quinone methides, which alkylate glutathione and inhibit the antioxidative system of the cell.

Age Differences in Decoding Pain from the Facial Expression of Healthy Individuals and Patients with Dementia.

Objective: Patients with dementia, whose ability to provide self-report of pain is often impaired, are in crucial need of observers who can detect the patients' pain-indicative behaviors appropriately, to initiate treatment. The facial display of pain promises to be especially informative for that purpose. The age of the observer has been shown to have a critical influence on observational emotion recognition (with age-related decrements in facial emotion recognition) but has not yet been studied as such for pain recognition.

Revealing the atomic site-dependent g factor within a single magnetic molecule via the extended Kondo effect.

The site-dependent g factor of a single magnetic molecule, with intramolecular resolution, is demonstrated for the first time by low-temperature, high-magnetic-field scanning tunneling microscopy of dehydrogenated Mn-phthalocyanine molecules on Au(111). This is achieved by exploring the magnetic-field dependence of the extended Kondo effect at different atomic sites of the molecule. Importantly, an inhomogeneous distribution of the g factor inside a single molecule is revealed.

The origin of half-metallicity in conjugated electron systems--a study on transition-metal-doped graphyne.

We studied the mechanism of half-metallicity (HM) formation in transition-metal-doped conjugated carbon based structures by first-principles electronic structure simulations. It is found that the HM is a rather complex phenomenon, determined by the ligand field splitting of d-orbitals of the transition metal atoms, the exchange splitting and the number of valence electrons. Since most of the conjugated carbon based structures possess ligands with intermediate strength, the ordering of the d-orbital splitting is similar in all structures, and the HM properties evolve according to the number of valence electrons.