Biomarkers for the Diagnosis of Alzheimer’s Disease in Clinical Practice: The Role of CSF Biomarkers during the Evolution of Diagnostic Criteria

Alzheimer’s disease (AD) is a progressive condition and the most common cause of dementia worldwide. The neuropathological changes characteristic of the disorder can be successfully detected before the development of full-blown AD. Early diagnosis of the disease constitutes a formidable challenge for clinicians. CSF biomarkers are the in vivo evidence of neuropathological changes developing in the brain of dementia patients. Therefore, measurement of their concentrations allows for improved accuracy of clinical diagnosis. Moreover, AD biomarkers may provide an indication of disease stage. Importantly, the CSF biomarkers of AD play a pivotal role in the new diagnostic criteria for the disease, and in the recent biological definition of AD by the National Institute on Aging, NIH and Alzheimer’s Association. Due to the necessity of collecting CSF by lumbar puncture, the procedure seems to be an important issue not only from a medical, but also a legal, viewpoint. Furthermore, recent technological advances may contribute to the automation of AD biomarkers measurement and may result in the establishment of unified cut-off values and reference limits. Moreover, a group of international experts in the field of AD biomarkers have developed a consensus and guidelines on the interpretation of CSF biomarkers in the context of AD diagnosis. Thus, technological advancement and expert recommendations may contribute to a more widespread use of these diagnostic tests in clinical practice to support a diagnosis of mild cognitive impairment (MCI) or dementia due to AD. This review article presents up-to-date data regarding the usefulness of CSF biomarkers in routine clinical practice and in biomarkers research.     

Eco-Sustainable Silk Fibroin/Pomegranate Peel Extract Film as an Innovative Green Material for Skin Repair

Skin disorders are widespread around the world, affecting people of all ages, and oxidative stress represents one of the main causes of alteration in the normal physiological parameters of skin cells. In this work, we combined a natural protein, fibroin, with antioxidant compounds extracted in water from pomegranate waste. We demonstrate the effective and facile fabrication of bioactive and eco-sustainable films of potential interest for skin repair. The blended films are visually transparent (around 90%); flexible; stable in physiological conditions and in the presence of trypsin for 12 days; able to release the bioactive compounds in a controlled manner; based on Fickian diffusion; and biocompatible towards the main skin cells, keratinocytes and fibroblasts. Furthermore, reactive oxygen species (ROS) production tests demonstrated the high capacity of our films to reduce the oxidative stress induced in cells, which is responsible for various skin diseases.     

Reorganization of the Brain Extracellular Matrix in Hippocampal Sclerosis

The extracellular matrix (ECM) is an important regulator of excitability and synaptic plasticity, especially in its highly condensed form, the perineuronal nets (PNN). In patients with drug-resistant mesial temporal lobe epilepsy (MTLE), hippocampal sclerosis type 1 (HS1) is the most common histopathological finding. This study aimed to evaluate the ECM profile of HS1 in surgically treated drug-resistant patients with MTLE in correlation to clinical findings. Hippocampal sections were immunohistochemically stained for aggrecan, neurocan, versican, chondroitin-sulfate (CS56), fibronectin, Wisteria floribunda agglutinin (WFA), a nuclear neuronal marker (NeuN), parvalbumin (PV), and glial-fibrillary-acidic-protein (GFAP). In HS1, besides the reduced number of neurons and astrogliosis, we found a significantly changed expression pattern of versican, neurocan, aggrecan, WFA-specific glycosylation, and a reduced number of PNNs. Patients with a lower number of epileptic episodes had a less intense diffuse WFA staining in Cornu Ammonis (CA) fields. Our findings suggest that PNN reduction, changed ECM protein, and glycosylation expression pattern in HS1 might be involved in the pathogenesis and persistence of drug-resistant MTLE by contributing to the increase of CA pyramidal neurons’ excitability. This research corroborates the validity of ECM molecules and their modulators as a potential target for the development of new therapeutic approaches to drug-resistant epilepsy.     

AlphaFold2: A Role for Disordered Protein/Region Prediction?

The development of AlphaFold2 marked a paradigm-shift in the structural biology community. Herein, we assess the ability of AlphaFold2 to predict disordered regions against traditional sequence-based disorder predictors. We find that AlphaFold2 performs well at discriminating disordered regions, but also note that the disorder predictor one constructs from an AlphaFold2 structure determines accuracy. In particular, a naïve, but non-trivial assumption that residues assigned to helices, strands, and H-bond stabilized turns are likely ordered and all other residues are disordered results in a dramatic overestimation in disorder; conversely, the predicted local distance difference test (pLDDT) provides an excellent measure of residue-wise disorder. Furthermore, by employing molecular dynamics (MD) simulations, we note an interesting relationship between the pLDDT and secondary structure, that may explain our observations and suggests a broader application of the pLDDT for characterizing the local dynamics of intrinsically disordered proteins and regions (IDPs/IDRs).     

Albumin Binds Doxorubicin via Self–Assembling Dyes as Specific Polymolecular Ligands

Congo red (CR) type self–assembled ribbon–like structures (SRLS) were previously shown to interact with some proteins, including albumin. SRLS also complex with some drugs with a flat, ring–shaped structure with aromatic characteristics, intercalating them into their ribbon structure. The combination of interaction with proteins and drug binding by SRLS enables the use of such systems for immunotargeting. It is especially interesting in the case of chemotherapeutic agents. The present experiments aimed to show that the model carrier system composed of supramolecular albumin and Congo red efficiently binds doxorubicin (Dox) and that the drug can be released at reduced pH. The presented results come from the studies on such complexes differing in the molar ratio of CR to Dox. The following methods were used for the analysis: electrophoresis, dialysis, gel filtration, spectral analysis, and analysis of the size of the hydrodynamic radius using the dynamic light scattering method (DLS). The applied methods confirmed the formation of the CR–Dox complex, with large dimensions and changed properties compared with free CR. The presented results show that albumin binds both CR and its complex with Dox. Various CR–Dox molar ratios, 5:1, 2:1, and 1:1, were analyzed. The confirmation of the possibility of releasing the drug from the carriers thus formed was also obtained. The presented research is important due to the search for optimal solutions for the use of SRLS in drug immunotargeting, with particular emphasis on chemotherapeutic agents.     

Influence of superplasticizers on pore solution composition and on expansion of concrete due to alkali-silica reaction

The use of superplasticizers (SP) is widespread in today’s concrete production. Usually, SP are used when specific demands in regard to workability, strength or durability have to be met. As they contain sodium sulphate, they have the potential to increase the alkalinity in the pore solution and the risk of damages due to alkali-silica reaction. In this study, the effect of two SP on the potential reactivity of concrete is examined by analyzing pore solutions of pastes and mortars and by measuring concrete expansion. The use of a naphthalene–sulphonate-based SP (Na content referred to liquid: 2.8%) leads to an increase in hydroxide concentration in the pore solution during the first two weeks going together with an accelerated concrete expansion during this period. The effects of a polycarboxylate-based SP (Na content referred to liquid: 0.5%) are less pronounced and do not result in an increased concrete expansion.     

Study of the adhesion of Staphylococcus aureus to coated glass substrates

The adhesion of Staphylococcus aureus was studied using a selection of laboratory-prepared and commercially available coated glass substrates using a simple methodology. Substrates were examined by scanning electron microscopy, atomic force microscopy and water droplet contact angles. It was found that microbial adhesion was independent of surface roughness, when this was of a lower magnitude than microbial size. It was also found that microbial adhesion was greater for hydrophilic surfaces than for hydrophobic ones, but that on a photoinduced superhydrophilic surface, microbes were more spread out—a potential benefit for more effective photocatalytic disinfection. It is suggested that hydrophobic and photoinduced superhydrophilic surface coatings both have potential as a means of reducing microbial fouling of surfaces.     

彩虹·洞——巴塞罗那Imaginarium儿童产品旗舰店

儿童总是喜爱玩耍的,神秘的洞穴更是对他们有着无穷的吸引力。在孩子的眼中,色彩是丰富世界的一个缩影。因此,迫庆一郎先生在设计巴塞罗那儿童品牌Imaginarium旗舰店时,就以洞穴·彩虹作为了设计的主题。     

Phytinsaure in Weizenkleien und Weizenkeimen. M?glichkeiten zur Entfernung der Phytinsaure

Zusammenfassung Kommerzielle Weizenkleien des Handels (9 Muster) enthielten zwischen 32 and 46 mg/g TS Phytinsäure, das entspricht einer 3- bis 5 fachen Anreicherung gegenüber Ganzkornweizen, bei Ballaststoffgehalten von 32 bis 47% FS. Weizenkeime des Handels (4 Muster) besaßen 15 bis 18 mg/g TS Phytinsäure bei Ballaststoffgehalten von 9–10% FS. Der Phytinsäuregehalt ließ sich auf unter 1% des Ausgangswertes reduzieren, wenn Weizenkleien und -keime mit Natriumcitratpuffer pH 5,25 1/2 h bei 40 °C extrahiert und mit Wasser nachgewaschen wurden. Der dabei entstehende erhebliche Substanzverlust von 34–47% bei Weizenkleien and 60–73% bei Weizenkeimen ging mit einer Erhöhung der Ballaststoffmenge (phytatfreie Weizenkleie: 55–65% FS, phytatfreie Weizenkeime: 18–26%) einher. Mit dieser sehr einfachen, schnellen Extraktion lassen sich also Weizenkleien praktisch phytinfrei herstellen, so daß mögliche negative ernährungsphysiologische Effekte bei zusätzlicher Anreicherung von Ballaststoffen ausgeschaltet werden können.

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Phytic acid in wheat bran and germ products. How to remove phytic acid from these products

Summary Commercial wheat bran (nine samples) and germ products (four samples) purchased from local shops were analysed for phytic acid, dietary fibre and ash contents. Phytic acid in wheat brans ranged over 32 to 46 mg/g dry mass and in wheat germ products over 15 to 18 mg/g dry mass, the dietary fibre contents ranged over 32 to 47% and 9 to 10%, respectively. The phytic acid level can be reduced to less than 1 % of the original content by extraction with sodium citrate buffer pH 5.25 for 0.5 h at 40 °C, followed by washing with water. As a consequence, 34–47% and 60–73% of the soluble material was lost from bran and germ products, respectively; coincidently the dietary fibre content increased to 55–65% in wheat brans and 18 to 26% in wheat germ products. Such a simple and fast method enables wheat brans to be produced practically free of phytic acid, resulting in the removal of possible detrimental effects of reduced mineral availibility by increasing dietary fibre levels.

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Veroffentl.-Nr. 5732 der Bundesforschungsanstalt für Getreideund Kartoffelverarbeitung, Detmold