Autonomous Ultrafast Self‐Healing Hydrogels by pH‐Responsive Functional Nanofiber Gelators as Cell Matrices

The synthesis of hybrid hydrogels by pH‐controlled structural transition with exceptional rheological properties as cellular matrix is reported. “Depsi” peptide sequences are grafted onto a polypeptide backbone that undergo a pH‐induced intramolecular O–N–acyl migration at physiological conditions affording peptide nanofibers (PNFs) as supramolecular gelators. The polypeptide–PNF hydrogels are mechanically remarkably robust. They reveal exciting thixotropic behavior with immediate in situ recovery after exposure to various high strains over long periods and self‐repair of defects by instantaneous reassembly. High cytocompatibility, convenient functionalization by coassembly, and controlled enzymatic degradation but stability in 2D and 3D cell culture as demonstrated by the encapsulation of primary human umbilical vein endothelial cells and neuronal cells open many attractive opportunities for 3D tissue engineering and other biomedical applications.     

Mass Spectrometric Analysis of Cerebrospinal Fluid Ubiquitin in Alzheimer's Disease and Parkinsonian Disorders

1 Purpose

Dysfunctional proteostasis, with decreased protein degradation and an accumulation of ubiquitin into aggregated protein inclusions, is a feature of neurodegenerative diseases. Identifying new potential biomarkers in cerebrospinal fluid (CSF) reflecting this process could contribute important information on pathophysiology.

2 Experimental design

A developed method combining SPE and PRM‐MS is employed to monitor the concentration of ubiquitin in CSF from subjects with Alzheimer's disease (AD), Parkinson's disease (PD), and progressive supranuclear palsy (PSP). Four independent cross‐sectional studies are conducted, studies 1–4, including controls (n = 86) and participants with AD (n = 60), PD (n = 15), and PSP (n = 11).

3 Results

The method shows a repeatability and intermediate precision not exceeding 6.1 and 7.9%, respectively. The determined LOD is 0.1 nm and the LOQ range between 0.625 and 80 nm . The CSF ubiquitin concentration is 1.2–1.5‐fold higher in AD patients compared with controls in the three independent AD‐control studies (Study 1, p < 0.001; Study 2, p < 0.001; and Study 3, p = 0.003). In the fourth study, there is no difference in PD or PSP, compared to controls.

4 Conclusion and clinical relevance

CSF ubiquitin may reflect dysfunctional proteostasis in AD. The described method can be used for further exploration of ubiquitin as a potential biomarker in neurodegenerative diseases.     

Catalytic effects of metals of the iron subgroup on the chlorination of titanium carbide to form nanostructural carbon

The effect of the reaction temperature and the metals of an iron subgroup on the thermo-chemical treatment of titanium carbide with a chlorine gas and their influence on the carbon structure obtained thereby was studied. Different analytical methods such as porosity measurements, X-ray diffraction spectrometry and a high-resolution electron microscopy revealed the catalytic behaviour of the above-mentioned metals, which appeared to support the formation of graphitised carbon at much lower temperatures compared to those needed for the ordinary thermo-chemical chlorination of titanium carbide.     

Metal contamination at a wood preservation site: characterisation and experimental studies on remediation

The aim of this investigation was to determine the occurrence of As, Cu, Cr and Zn in the soil at an abandoned wood preservation unit and to examine some possible extractants for the contaminants in the soil. The mean As content of the contaminated surface soils (0-10 cm) was 186 mg kg(-1), where as the mean concentrations of Cu, Cr and Zn in soils from the contaminated area were 26, 29 and 91 mg kg(-1), respectively. The elevated As content in the mineral soils is related to adsorption of inorganic As phases in the fine grained fractions, which are characterised by large surface area and high positive surface charge under the current acidic conditions. Cu and Cr were found to be rather mobile, which is reflected in their lower abundance in soils and significant accumulation in sediments in the drainage leaving the area. The fine fraction of the soil (<0.125 mm) has an average metal content increased by nearly 34% as compared to the <2-mm fraction conventionally used for the analysis and assessment of soil contamination. The <2-mm fraction constitutes approximately 65% of the total weight while the fine fraction (<0.125 mm) constitutes approximately 10%. These facts, taken together, are essential for the choice of remediation measures. Oxalate solutions have been tested as extractants for soil remediation. Dark acid oxalate extraction dissolves the amorphous Al- and Fe-oxides and hydroxides and mobilises the adsorbed inorganic As species. Oxalate also acts as a ligand for the cationic heavy metals, releasing them from exchangeable sites. With a three-step sequential leaching, up to 98-99% of the metals could be removed. At lower concentrations and higher pH, the leaching decreased to approximately 70%.     

Designed amyloid beta peptide fibril - a tool for high-throughput screening of fibril inhibitors

Amyloid beta peptide (Abeta) fibril formation is widely believed to be the causative event of Alzheimer's disease pathogenesis. Therapeutic approaches are therefore in development that target various sites in the production and aggregation of Abeta. Herein we present a high-throughput screening tool to generate novel hit compounds that block Abeta fibril formation. This tool is an application for our fibril model (Abeta(16-37)Y(20)K(22)K(24))(4), which is a covalent assembly of four Abeta fragments. With this tool, screening studies are complete within one hour, as opposed to days with native Abeta(1-40). A Z' factor of 0.84+/-0.03 was determined for fibril formation and inhibition, followed by the reporter molecule thioflavin T. Herein we also describe the analysis of a broad range of reported inhibitors and non-inhibitors of Abeta fibril formation to test the validity of the system.     

Psychophysiological stress responses, muscle tension, and neck and shoulder pain among supermarket cashiers.

This study examined psychological and physiological stress, as well as muscle tension and musculoskeletal symptoms, among 72 female supermarket cashiers. Stress levels were found to be significantly elevated at work, as reflected in the catecholamines, blood pressure, heart rate, electromyographic (EMG) activity, and self-reports. Fifty cashiers (70%) suffering from neck-shoulder pain (trapezius myalgia) were found to have higher EMG activity at work and reported more tension after work. Women who kept a diary for 1 week and reported more musculoskeletal pain (above the median) were older, had higher blood pressure, and reported more work stress and psychosomatic symptoms. The elevated stress levels at work are consistent with data from workers involved in other types of repetitive tasks and can be important for the high prevalence of neck and shoulder symptoms among the cashiers. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ermittlung von Stabilisierungslasten im Holzbau

Calculation of lateral stability loads for timber constructions. Stability loads for lateral bracings are usually calculated by using a simplified method according to the standard for timber constructions. In this article two methods for an accurate calculation of stability loads for lateral bracings will be presented. The first possibility is based on the energy method and can be used for single‐span beams with continuous lateral support. Equations to determine the lateral loads for single‐span beams with constant normal forces or constant bending moments can be determined by using the energy method. Another possibility of verification is the computation of lateral stability loads using the 2^nd order flexural torsion theory for a three‐dimensional loaded beam with discrete lateral supports with any support and load cases by employing the transfer matrix method. The results of both methods will be compared in several examples.     

Oxokohlenstoffe und verwandte Verbindungen. 27. Synthese von Dihydrocyclobuta[a]naphthalen-1,2-dionen und Cyclobuta[a]naphthalen-1,2-dionen durch Anellierung von Alkoxy-(1-alkenyl)benzolen mit 3-Chlor-3-cyclobuten-1,2-dion. Anwendungsbereich und Grenzen

Oxocarbons and Related Compounds. 27. Synthesis of Dihydrocyclobuta[a]naphthalene-1,2-diones and Cyclobuta[a]naphthalene-1,2-diones via Annulation of Alkoxy-(1-alkenyl)benzenes with 3-Chloro-3-cyclobutene-1,2-dione. Scope and Limitations The reaction of alkoxy-(1-alkenyl)benzenes with semisquaric chloride ( 3 ) has been investigated systematically. 1,2-Dialkoxy- and 1-alkoxy'-2-alkoxy″-4-(1-alkenyl)benzenes ( 6a–j ) and ( 11a–i ) react with 3 to give the 3,4-dihydrocyclobuta[a]naphthalene-1,2-diones ( 8a–j ) and ( 12a–i ). Treatment of the dihydrocyclobuta[a]naphthalene-1,2-diones with 1.2 equiv. bromine effects dehydrogenation and affords cyclobuta[a]naphthalene-1,2-diones ( 9a–e ) and ( 13b–f ). Any efforts to extend this annulation reaction to dimethoxy-(1-alkenyl)benzenes with the methoxy groups in other than the 1,2-positions, e. g. 14a, b, 16a, b have been unsuccessful. The reaction of 1,2,3-trimethoxy-4-(1-propenyl) [and 4-(1-butenyl)]-benzenes ( 18a ) and ( 18b ) with semisquaric chloride ( 3 ) leads to the elimination of HCl and CH₃OH and gives 5,6-dimethoxy-3-methyl [and 3-ethyl]-cyclobuta[a]naphthalene-1,2-diones ( 20a ) and ( 20b ). The reaction pathway of this novel annulation reaction is discussed.     

Synthetic Peptide templates for molecular recognition: recent advances and applications

The creation of molecular systems that can mimic some of the properties of natural macromolecules is one of the major endeavors in contemporary protein chemistry. However, the construction of artificial proteins with predetermined structure and function is difficult on account of complex folding pathways. The use of topological peptide templates has been suggested to induce and stabilize defined secondary and tertiary structures. This is because the recent advances in the chemistry of coupling reagents, protecting groups, and solid-phase synthesis have made the chemical synthesis of peptides with conformationally controlled and complex structures feasible. Besides their use as structure-inducing devices, these peptide templates can also be utilized to construct novel structures with tailor-made functions. Herein, we present recent advances in the field of peptide-template-based approaches with particular emphasis on the demonstrated utility of this approach in molecular recognition, along with related applications.