Memory complaints and abilities among depressed older adults.

The relation between complaints of memory problems and memory test performance was examined among depressed (n?=?25) and nondepressed (n?=?25) adults over the age of 40 years. Depressed adults were diagnosed from interviews using Diagnostic and Statistical Manual of Mental Disorders (DSM-III) criteria and from responses to the Beck Depression Inventory. A dissociation between memory complaints and performance was observed. Depressed adults complained of greater problems in memory than nondepressed adults. However, the memory test performances of both groups were in the average-to-above-average range. These results are discussed in light of the role of self-deprecating cognitive distortions in the tendency of depressed individuals to negatively evaluate all their abilities, including their memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Targeting Mitochondria in Diabetes

Type 2 diabetes (T2D), one of the most prevalent noncommunicable diseases, is often preceded by insulin resistance (IR), which underlies the inability of tissues to respond to insulin and leads to disturbed metabolic homeostasis. Mitochondria, as a central player in the cellular energy metabolism, are involved in the mechanisms of IR and T2D. Mitochondrial function is affected by insulin resistance in different tissues, among which skeletal muscle and liver have the highest impact on whole-body glucose homeostasis. This review focuses on human studies that assess mitochondrial function in liver, muscle and blood cells in the context of T2D. Furthermore, different interventions targeting mitochondria in IR and T2D are listed, with a selection of studies using respirometry as a measure of mitochondrial function, for better data comparison. Altogether, mitochondrial respiratory capacity appears to be a metabolic indicator since it decreases as the disease progresses but increases after lifestyle (exercise) and pharmacological interventions, together with the improvement in metabolic health. Finally, novel therapeutics developed to target mitochondria have potential for a more integrative therapeutic approach, treating both causative and secondary defects of diabetes.     

Lipids in vascular function

Physiological and pathological vascular responses depend on the action of numerous intercellular mediators, ranging from hormones to gases like nitric oxide, proteins, and lipids. The last group consists not only of the different types of lipoproteins, but also includes a broad array of other lipophilic signaling molecules such as fatty acids, eicosanoids, phospholipids and their derivatives, sphingolipids and isoprenoids. Due to space limitations, it is impossible to discuss all the vascular effects of lipophilic mediators or compounds. Therefore, we will focus on one of the most important lipid-mediated diseases, atherosclerosis. Lipoproteins and especially their native or oxidized lipid compounds affect vascular function in many different ways, and these effects do not only modulate atherogenesis but are of paramount physiological and pathophysiological importance in other diseases, such as inflammation, tumor metastasis, or normal wound healing.     

Efficient stabilization of bulk fish oil rich in long‐chain polyunsaturated fatty acids

The aim of the present study was to systematically investigate the possibilities of stabilizing a bulk oil rich in long‐chain polyunsaturated fatty acids under ambient conditions. Combinations of different antioxidants (α‐, γ‐ and/or δ‐tocopherol, rosmarinic acid and rosemary extract rich in carnosic acid) as well as lecithin and citric acid were systematically investigated. Efficient stabilization was achieved by choosing a combination of tocopherols rich in γ‐ or δ‐tocopherol and low in α‐tocopherol, by including tocopherol‐sparing synergists like ascorbyl palmitate and carnosic acid from rosemary extract and metal‐chelating agents. For carnosic acid, a concentration of 400 mg/kg oil provides sufficient protection; the concentration of the metal chelator should be adapted to the concentration of metal ions present in the oil. As an alternative ingredient with metal‐chelating and tocopherol‐sparing activity, lecithin may be included in the formulation, but its poor solubility in bulk oils limits its use.     

Variation in the serotonin transporter gene modulates selective attention to threat.

The 5-HTTLPR is an insertion/deletion polymorphism in the promoter region of the serotonin transporter gene. Prior research has revealed associations between the short-allele variant of this polymorphism, enhanced self-reported negative emotionality, and hypersensitivity of fear relevant neural circuits. In a sample of 50 healthy women we examined the role of 5-HTTLPR for cognitive-affective processing of phylogenetical fear-relevant stimuli (spiders) in a dot probe task. In contrast to homozygote long-allele carriers (ll), participants carrying at least 1 short allele (ss and sl) selectively shifted attention toward pictures of spiders, when these were presented for a duration of 2,000 ms. These results argue for an involvement of 5-HTTLPR in cognitive processing of threatening stimuli and thus, underpin its general role for individual differences in negative affect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

One Question,Multiple Answers: Biochemical and Biophysical Screening Methods Retrieve Deviating Fragment Hit Lists

Fragment‐based lead discovery is gaining momentum in drug development. Typically, a hierarchical cascade of several screening techniques is consulted to identify fragment hits which are then analyzed by crystallography. Because crystal structures with bound fragments are essential for the subsequent hit‐to‐lead‐to‐drug optimization, the screening process should distinguish reliably between binders and non‐binders. We therefore investigated whether different screening methods would reveal similar collections of putative binders. First we used a biochemical assay to identify fragments that bind to endothiapepsin, a surrogate for disease‐relevant aspartic proteases. In a comprehensive screening approach, we then evaluated our 361‐entry library by using a reporter‐displacement assay, saturation‐transfer difference NMR, native mass spectrometry, thermophoresis, and a thermal shift assay. While the combined results of these screening methods retrieve 10 of the 11 crystal structures originally predicted by the biochemical assay, the mutual overlap of individual hit lists is surprisingly low, highlighting that each technique operates on different biophysical principles and conditions.     

Investigating the Role of Conformational Effects on Laccase Stability and Hyperactivation under Stress Conditions

Fungal laccase from Steccherinum ochraceum 1833 displays remarkable stability under different harsh conditions: organic/buffer mixtures, thermal treatment, and microwave radiation. The behavior is particularly significant in the light of the sharp inactivation observed for two different fungal laccases. Laccase from S. ochraceum 1833 also displays hyperactivation under mild thermal treatment (60 °C). Molecular dynamics simulations at 80 °C explained how this laccase retains the geometry of the electron transfer pathway, thereby assuring electron transfer through the copper ions and thus maintaining its catalytic activity at high temperature. Spectroscopic studies revealed that the thermal activation corresponds to specific conformational changes in the protein. The results indicate that this laccase is potentially applicable under denaturing conditions that might be beneficial for the biotransformation of recalcitrant substrates.     

Ribosomal Synthesis of Natural‐Product‐Like Bicyclic Peptides in Escherichia coli

Methods to access natural‐product‐like macrocyclic peptides can disclose new opportunities for the exploration of this important structural class for chemical biology and drug discovery applications. Here, the scope and mechanism of a novel strategy for directing the biosynthesis of thioether‐bridged bicyclic peptides in bacterial cells was investigated. This method entails split intein‐catalyzed head‐to‐tail cyclization of a ribosomally produced precursor peptide, combined with inter‐side‐chain crosslinking through a genetically encoded cysteine‐reactive amino acid. This strategy could be successfully applied to achieve formation of structurally diverse bicyclic peptides with high efficiency and selectivity in Escherichia coli. Insights into the sequence of reactions underlying the peptide bicyclization process were gained from time‐course experiments. Finally, the potential utility of this methodology toward the discovery of macrocyclic peptides with enhanced functional properties was demonstrated through the isolation of a bicyclic peptide with sub‐micromolar affinity for streptavidin.     

The Impact of Zeta Potential and Physicochemical Properties of TiO2‐Based Nanocomposites on Their Biological Activity

The aim of this research was to observe the relationship between zeta potential, morphology, surface area, porosity, chemical composition, and ecotoxicity of nanocomposite powders such as Au/TiO₂, Ag₂O/TiO₂, PdO/TiO₂, Ag/TiO₂/SiO₂, Ag/N(C)TiO₂, and SiO₂/TiO₂ from which Ag₂O/TiO₂, Ag/N(C)/TiO_2, and Ag/TiO₂/SiO₂ were exhibiting good antimicrobial properties. It was observed, that nanomaterials characterized by similar morphology and zeta potential revealed the similar toxic behavior. The samples of higher agglomeration and higher zeta potential, especially Ag/TiO₂/SiO₂ xerogel and TiO₂/SiO₂ aerogel were generally less ecotoxic to water organisms and plants. They were also not genotoxic in concentrations up to 500 and 250 mg/L, respectively.     

The kinetic evidence for the formation of multiple active species in a bis(phenoxy-imine) zirconium dichloride/MAO catalyst during ethylene polymerization

The effects of polymerization time and temperature on the molecular weight and molecular weight distribution of polyethylene, produced over homogeneous catalyst bis[N-(3-tert-butyl salicylidene)anilinato]zirconium(IV) dichloride ^tBu-L₂ZrCl₂/MAO have been studied. The data on the number of active centers (C_P) and propagation rate constants (k_P) at different polymerization time have been obtained as well. It was found that at a short polymerization time two types of active centers, producing low molecular weight PE (M_w = (4-10) × 10³ g mol⁻¹) are formed. The number of these centers was estimated to be 11% of total zirconium complex and their reactivity is very high (the k_P value was found to be 54 × 10³ L mol⁻¹ s⁻¹ at 35 °C). High initial activity of the catalyst fell with the increase in polymerization time, whereas the polydispersity values of the resulting PE increase due to formation of new centers, producing high molecular weight PE (M_w = (30-1300) × 10³ g mol⁻¹). It was found that the decrease in activity is caused by reducing the initial active centers number and lower reactivity of the new-formed centers (k_P = 17 × 10³ L mol⁻¹ s⁻¹).