The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans

FKBP5 encodes FK506-binding protein 5, a glucocorticoid receptor (GR)-binding protein implicated in various psychiatric disorders and alcohol withdrawal severity. The purpose of this study is to characterize alcohol preference and related phenotypes in Fkbp5 knockout (KO) mice and to examine the role of FKBP5 in human alcohol consumption. The following experiments were performed to characterize Fkpb5 KO mice. (1) Fkbp5 KO and wild-type (WT) EtOH consumption was tested using a two-bottle choice paradigm; (2) The EtOH elimination rate was measured after intraperitoneal (IP) injection of 2.0 g/kg EtOH; (3) Blood alcohol concentration (BAC) was measured after 3 h limited access of alcohol; (4) Brain region expression of Fkbp5 was identified using LacZ staining; (5) Baseline corticosterone (CORT) was assessed. Additionally, two SNPs, rs1360780 (C/T) and rs3800373 (T/G), were selected to study the association of FKBP5 with alcohol consumption in humans. Participants were college students (n = 1162) from 21–26 years of age with Chinese, Korean or Caucasian ethnicity. The results, compared to WT mice, for KO mice exhibited an increase in alcohol consumption that was not due to differences in taste sensitivity or alcohol metabolism. Higher BAC was found in KO mice after 3 h of EtOH access. Fkbp5 was highly expressed in brain regions involved in the regulation of the stress response, such as the hippocampus, amygdala, dorsal raphe and locus coeruleus. Both genotypes exhibited similar basal levels of plasma corticosterone (CORT). Finally, single nucleotide polymorphisms (SNPs) in FKBP5 were found to be associated with alcohol drinking in humans. These results suggest that the association between FKBP5 and alcohol consumption is conserved in both mice and humans.     

Alterations in Serum Polyunsaturated Fatty Acids and Eicosanoids in Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD)

Smoking is a major risk factor for several diseases including chronic obstructive pulmonary disease (COPD). To better understand the systemic effects of cigarette smoke exposure and mild to moderate COPD—and to support future biomarker development—we profiled the serum lipidomes of healthy smokers, smokers with mild to moderate COPD (GOLD stages 1 and 2), former smokers, and never-smokers (n = 40 per group) (ClinicalTrials.gov registration: {"type":"clinical-trial","attrs":{"text":"NCT01780298","term_id":"NCT01780298"}}NCT01780298). Serum lipidome profiling was conducted with untargeted and targeted mass spectrometry-based lipidomics. Guided by weighted lipid co-expression network analysis, we identified three main trends comparing smokers, especially those with COPD, with non-smokers: a general increase in glycero(phospho)lipids, including triglycerols; changes in fatty acid desaturation (decrease in ω-3 polyunsaturated fatty acids, and an increase in monounsaturated fatty acids); and an imbalance in eicosanoids (increase in 11,12- and 14,15-DHETs (dihydroxyeicosatrienoic acids), and a decrease in 9- and 13-HODEs (hydroxyoctadecadienoic acids)). The lipidome profiles supported classification of study subjects as smokers or non-smokers, but were not sufficient to distinguish between smokers with and without COPD. Overall, our study yielded further insights into the complex interplay between smoke exposure, lung disease, and systemic alterations in serum lipid profiles.     

Enhanced transport properties of Sn-substituted proton-conducting BaZr0.8Sc0.2O3–δ ceramic materials

High-temperature proton conductors based on acceptor-doped barium zirconate exhibit excellent chemical stability in atmospheres containing CO₂ or H₂O. However, due to their refractory nature, these conductors have a low grain growth rate, which negatively affects the overall electrical conductivity. A possible strategy for increasing the ionic conductivity of zirconates lies in the partial substitution of Zr-ions with other isovalent dopants. In this work, we carried out systematic studies of the crystal structure, microstructure, hydration capacity, transport, and thermal properties of BaZr_0.8–xSn_xSc_0.2O_3–δ (x = 0, 0.1, and 0.2). According to X-ray powder diffraction and scanning electron microscopy data, all studied ceramic samples have a cubic perovskite structure, whose average grain size decreases with tin doping. It is found that the composition with x = 0.1 exhibits the highest values in terms of total, ionic, grain, and grain-boundary conductivities. The complex analysis of the obtained data shows that a low-level substitution of Zr⁴⁺- with Sn⁴⁺-ions is a competent approach for designing new proton-conducting electrolytes attractive for high-temperature applications.     

Removal of lindane using electrokinetic soil flushing coupled with air stripping

Journal of Applied Electrochemistry - This paper evaluates the remediation of soil spiked with lindane using a combined treatment consisting of electrokinetic soil flushing (EKSF) with air...     

Electric Fatigue of Lead‐Free Piezoelectric Materials

A considerable body of knowledge now exists from studies involving the development of lead‐free piezoelectric ceramics and a number of high potential alternatives to current lead‐based materials have been identified. Stability under cyclic electric fields is an important property of piezoelectric materials. Here, we review the research to date which shows that fatigue under cyclic electrical loading is prevalent in many lead‐free piezoelectric ceramic compositions. However, the variety of compositions and mechanisms for piezoelectric behavior in these materials corresponds to significant variances in the nature of fatigue degradation and the likely mechanisms thereof, which do not directly parallel those of well‐studied lead‐based materials. In particular, the use of field‐induced phase changes as an actuation mechanism provides distinctive fatigue behaviors. Particular attention is given to fatigue of ferroelectric and relaxor (ergodic and nonergodic) structures and their dependence upon temperature and electric field and the potential design of materials with high fatigue resistance.     

Molecular Cross-Talk between Gravity- and Light-Sensing Mechanisms in Euglena gracilis

Euglena gracilis is a photosynthetic flagellate. To acquire a suitable position in its surrounding aquatic environment, it exploits light and gravity primarily as environmental cues. Several physiological studies have indicated a fine-tuned relationship between gravity sensing (gravitaxis) and light sensing in E. gracilis. However, the underlying molecular mechanism is largely unknown. The photoreceptor photoactivated adenylyl cyclase (PAC) has been studied for over a decade. Nevertheless, no direct/indirect interaction partner (upstream/downstream) has been reported for PAC. It has been shown that a specific protein, kinase A (PKA), showed to be involved in phototaxis and gravitaxis. The current study reports the localization of the specific PKA and its relationship with PAC.     

Treatment of Critical Size Femoral Bone Defects with Biomimetic Hybrid Scaffolds of 3D Plotted Calcium Phosphate Cement and Mineralized Collagen Matrix

To treat critical-size bone defects, composite materials and tissue-engineered bone grafts play important roles in bone repair materials. The purpose of this study was to investigate the bone regenerative potential of hybrid scaffolds consisting of macroporous calcium phosphate cement (CPC) and microporous mineralized collagen matrix (MCM). Hybrid scaffolds were synthetized by 3D plotting CPC and then filling with MCM (MCM-CPC group) and implanted into a 5 mm critical size femoral defect in rats. Defects left empty (control group) as well as defects treated with scaffolds made of CPC only (CPC group) and MCM only (MCM group) served as controls. Eight weeks after surgery, micro-computed tomography scans and histological analysis were performed to analyze the newly formed bone, the degree of defect healing and the activity of osteoclasts. Mechanical stability was tested by 3-point-bending of the explanted femora. Compared with the other groups, more newly formed bone was found within MCM-CPC scaffolds. The new bone tissue had a clamp-like structure which was fully connected to the hybrid scaffolds and thereby enhanced the biomechanical strength. Together, the biomimetic hybrid MCM-CPC scaffolds enhanced bone defect healing by improved osseointegration and their differentiated degradation provides spatial effects in the process of critical-bone defect healing.     

Analysis of microRNAs in Exosomes of Breast Cancer Patients in Search of Molecular Prognostic Factors in Brain Metastases

Brain metastases are the most severe tumorous spread during breast cancer disease. They are associated with a limited quality of life and a very poor overall survival. A subtype of extracellular vesicles, exosomes, are sequestered by all kinds of cells, including tumor cells, and play a role in cell-cell communication. Exosomes contain, among others, microRNAs (miRs). Exosomes can be taken up by other cells in the body, and their active molecules can affect the cellular process in target cells. Tumor-secreted exosomes can affect the integrity of the blood-brain barrier (BBB) and have an impact on brain metastases forming. Serum samples from healthy donors, breast cancer patients with primary tumors, or with brain, bone, or visceral metastases were used to isolate exosomes and exosomal miRs. Exosomes expressed exosomal markers CD63 and CD9, and their amount did not vary significantly between groups, as shown by Western blot and ELISA. The selected 48 miRs were detected using real-time PCR. Area under the receiver-operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified two miRs with the potential to serve as prognostic markers for brain metastases. Hsa-miR-576-3p was significantly upregulated, and hsa-miR-130a-3p was significantly downregulated in exosomes from breast cancer patients with cerebral metastases with AUC: 0.705 and 0.699, respectively. Furthermore, correlation of miR levels with tumor markers revealed that hsa-miR-340-5p levels were significantly correlated with the percentage of Ki67-positive tumor cells, while hsa-miR-342-3p levels were inversely correlated with tumor staging. Analysis of the expression levels of miRs in serum exosomes from breast cancer patients has the potential to identify new, non-invasive, blood-borne prognostic molecular markers to predict the potential for brain metastasis in breast cancer. Additional functional analyzes and careful validation of the identified markers are required before their potential future diagnostic use.     

Impact of Uremic Toxins on Endothelial Dysfunction in Chronic Kidney Disease: A Systematic Review

Patients with chronic kidney disease (CKD) are at a highly increased risk of cardiovascular complications, with increased vascular inflammation, accelerated atherogenesis and enhanced thrombotic risk. Considering the central role of the endothelium in protecting from atherogenesis and thrombosis, as well as its cardioprotective role in regulating vasorelaxation, this study aimed to systematically integrate literature on CKD-associated endothelial dysfunction, including the underlying molecular mechanisms, into a comprehensive overview. Therefore, we conducted a systematic review of literature describing uremic serum or uremic toxin-induced vascular dysfunction with a special focus on the endothelium. This revealed 39 studies analyzing the effects of uremic serum or the uremic toxins indoxyl sulfate, cyanate, modified LDL, the advanced glycation end products N-carboxymethyl-lysine and N-carboxyethyl-lysine, p-cresol and p-cresyl sulfate, phosphate, uric acid and asymmetric dimethylarginine. Most studies described an increase in inflammation, oxidative stress, leukocyte migration and adhesion, cell death and a thrombotic phenotype upon uremic conditions or uremic toxin treatment of endothelial cells. Cellular signaling pathways that were frequently activated included the ROS, MAPK/NF-κB, the Aryl-Hydrocarbon-Receptor and RAGE pathways. Overall, this review provides detailed insights into pathophysiological and molecular mechanisms underlying endothelial dysfunction in CKD. Targeting these pathways may provide new therapeutic strategies reducing increased the cardiovascular risk in CKD.     

Development and evaluation of surface treatments to enhance the fiber-matrix adhesion in PAN-based carbon fiber/liquid crystal polymer composites. Part I: Coupling agent and amine surface treatments

Several surface treatments, using both commercially available coupling agents and reagents containing multiple amines, were applied to commingled continuous as-received AS4 carbon reinforcing fiber/liquid crystal polymer (LCP) matrix fibers. Unidirectional composites (normally 60 vol% carbon fiber) were prepared from as-received and treated commingled fibers and characterized. To estimate the effect the effect of the treatments on fiber-matrix adhesion, short beam shear (SBS) tests were conducted, the failure surfaces were examined, and spectroscopic studies wee performed. The mean SBS strength of the as-received unidirectional AS4 carbon fiber/LCP matrix composite system was 49 MPa. The best coupling agent and amine treatments yielded increases in composite shear strength of ∼ 10 to 20%, relative to the as-received AS4/LCP system. For the amine treatments, ESCA and FTIR analyses suggested of both the carbon and LCP fibers may have caused the increased adhesion. Moreover, SEM analysis of the failure surfaces of SBS specimens from composites prepared with the treated fibers may have caused the increased adhesion. Moreover, SEM analysis of the failure surfaces of SBS specimens from composites prepared with the treated fibers (both with coupling agents and amines) showed that strong fiber-matrix adhesion was present. That is, failure occurred in the LCP matrix material.