Regional Differences in Neuroinflammation-Associated Gene Expression in the Brain of Sporadic Creutzfeldt–Jakob Disease Patients

Neuroinflammation is an essential part of neurodegeneration. Yet, the current understanding of neuroinflammation-associated molecular events in distinct brain regions of prion disease patients is insufficient to lay the ground for effective treatment strategies targeting this complex neuropathological process. To address this problem, we analyzed the expression of 800 neuroinflammation-associated genes to create a profile of biological processes taking place in the frontal cortex and cerebellum of patients who suffered from sporadic Creutzfeldt–Jakob disease. The analysis was performed using NanoString nCounter technology with human neuroinflammation panel+. The observed gene expression patterns were regionally and sub-regionally distinct, suggesting a variable neuroinflammatory response. Interestingly, the observed differences could not be explained by the molecular subtypes of sporadic Creutzfeldt–Jakob disease. Furthermore, analyses of canonical pathways and upstream regulators based on differentially expressed genes indicated an overlap between biological processes taking place in different brain regions. This suggests that even smaller-scale spatial data reflecting subtle changes in brain cells’ functional heterogeneity and their immediate pathologic microenvironments are needed to explain the observed differential gene expression in a greater detail.     

Dysregulation of Muscle-Specific MicroRNAs as Common Pathogenic Feature Associated with Muscle Atrophy in ALS,SMA and SBMA: Evidence from Animal Models and Human Patients

Motor neuron diseases (MNDs) are neurodegenerative disorders characterized by upper and/or lower MN loss. MNDs include amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and spinal and bulbar muscular atrophy (SBMA). Despite variability in onset, progression, and genetics, they share a common skeletal muscle involvement, suggesting that it could be a primary site for MND pathogenesis. Due to the key role of muscle-specific microRNAs (myomiRs) in skeletal muscle development, by real-time PCR we investigated the expression of miR-206, miR-133a, miR-133b, and miR-1, and their target genes, in G93A-SOD1 ALS, Δ7SMA, and KI-SBMA mouse muscle during disease progression. Further, we analyzed their expression in serum of SOD1-mutated ALS, SMA, and SBMA patients, to demonstrate myomiR role as noninvasive biomarkers. Our data showed a dysregulation of myomiRs and their targets, in ALS, SMA, and SBMA mice, revealing a common pathogenic feature associated with muscle impairment. A similar myomiR signature was observed in patients’ sera. In particular, an up-regulation of miR-206 was identified in both mouse muscle and serum of human patients. Our overall findings highlight the role of myomiRs as promising biomarkers in ALS, SMA, and SBMA. Further investigations are needed to explore the potential of myomiRs as therapeutic targets for MND treatment.     

Incorporation of conjugated linoleic acid and vaccenic acid into lipids from rat tissues and plasma

The objective of this study was to determine the incorporation of conjugated linoleic acid (CLA) into triacylglycerols (TAG) and phospholipids (PL) of tissues and plasma, and to interpret the role of dietary‐derived vaccenic acid (VA) in increasing the tissue content of CLA (c9,t11) and the influence on the fatty acid profile. We fed five groups of rats semi‐purified diets with varying levels of CLA and VA: control butter with low CLA (c9,t11) and VA; control butter added 5% CLA (c9,t11); control butter added 5% Tonalin [equal amount of CLA (c9,t11) and CLA (t10,c12)]; control butter added 5% VA; butter with high CLA (c9,t11) and VA (H‐CLA), for 3 weeks. The highest incorporation of CLA (c9,t11) was found in adipose tissue, and the lowest was observed in liver. Low intake of CLA (c9,t11) combined with high intake of VA resulted in a higher incorporation of CLA (c9,t11) in tissues due to the conversion of VA to CLA (c9,t11), compared to feeding CLA (c9,t11) without VA. However, in enterocytes, the proportion of CLA (c9,t11) was low after feeding VA, indicating no or only a minor conversion of VA to CLA (c9,t11) in the intestine. The incorporation of CLA (t10,c12) into TAG from plasma and tissues was generally much lower than that of the CLA (c9,t11) isomer, except in the enterocyte TAG, which had similar proportions of the two isomers.     

Numerical modelling of cold compaction of metal powder

A finite element programme has been developed for the analysis of porosity and stress distributions in a powder compact, based on rate-independent finite strain plasticity theory. The strain hardening versions of the Gurson model (J. Engng. Mater. Technol., 1977, 99, 2-15), the more recent FKM model (J. Mech. Phys. Solids, 1992, 40(5), 1139-1162), developed by Fleck, Kuhn and McMeeking, and a combination of the two models are used. The friction between the mould wall and the metal powder is modelled by a combination of Coulomb friction and a constant friction shear stress, since Coulomb friction is not realistic at high normal pressures. The finite element programme has been used to study the effects of friction, compaction method, and material parameters. Analyses for powder compacts of various geometries are presented to illustrate the method.     

Tuning the phase of circadian entrainment

The circadian clock coordinates daily physiological, metabolic and behavioural rhythms. These endogenous oscillations are synchronized with external cues (‘zeitgebers’), such as daily light and temperature cycles. When the circadian clock is entrained by a zeitgeber, the phase difference ψ between the phase of a clock-controlled rhythm and the phase of the zeitgeber is of fundamental importance for the fitness of the organism. The phase of entrainment ψ depends on the mismatch between the intrinsic period τ and the zeitgeber period T and on the ratio of the zeitgeber strength to oscillator amplitude. Motivated by the intriguing complexity of empirical data and by our own experiments on temperature entrainment of mouse suprachiasmatic nucleus (SCN) slices, we present a theory on how clock and zeitgeber properties determine the phase of entrainment. The wide applicability of the theory is demonstrated using mathematical models of different complexity as well as by experimental data. Predictions of the theory are confirmed by published data on Neurospora crassa strains for different period mismatches τ − T and varying photoperiods. We apply a novel regression technique to analyse entrainment of SCN slices by temperature cycles. We find that mathematical models can explain not only the stable asymptotic phase of entrainment, but also transient phase dynamics. Our theory provides the potential to explore seasonal variations of circadian rhythms, jet lag and shift work in forthcoming studies.     

International comparison of costs of a fatal casualty of road accidents in 1990 and 1999

The purpose of this study is to assemble information of costs per fatal casualty in traffic accidents, adopted by authorities in different countries. analyse and compare these figures as well as the methods used for estimating these values. A questionnaire was sent to 19 countries from which 11 gave information on cost per fatality and methods of valuation. The costs per fatality, usually defined as direct and indirect costs plus a value of safety per se, are compared both between countries and over time, 1990 and 1999, for each country. The average cost per fatality has increased between 1990 and 1999 (fixed prices) due to both changes in the methodology and changes of valuations. Great Britain, New Zealand, Sweden and the US conduct own willingness-to-pay (WTP) surveys, while the Netherlands and Norway make reviews of these studies. In Finland, the cost per fatality is a combination of the value of lost productivity and the cost of care for an institutionalised disabled person. In Australia, Austria, Germany and Switzerland, the cost per fatality is estimated as a value of lost productivity and an addition of a human cost based on compensation payments or insurance payments. Estimates from recently conducted WTP surveys or meta-analyses are considered in Austria, Finland and Sweden, however, not yet adopted as official values for use in road traffic planning.     

Biocompatibility of highly macroporous ceramic scaffolds: cell adhesion and morphology studies

Hydroxyapatite porous scaffolds can be used for tissue engineering applications since they can serve as templates for cell adhesion, proliferation and ultimately for tissue repair. One way to address this issue is to evaluate the cell adhesion using several characterization techniques namely, cytotoxicity assays and cell visualization. On the other hand, when using highly macroporous scaffolds some techniques may not be adequate for evaluation, such as MTT. In this work, cytotoxicity assay (MTS), scanning electron microscopy (SEM) and Confocal laser scanning microscopy (CLSM) were used to evaluate cell adhesion in highly macroporous hydroxyapatite scaffolds. It was possible to observe that some techniques were not suitable to evaluate cell adhesion. In addition, it was shown that for this kind of scaffolds, confocal laser scanning microscopy is a powerful tool for cell adhesion and proliferation evaluation.