Using New Camera-Based Technologies for Gait Analysis in Older Adults in Comparison to the Established GAITRite System

Various gait parameters can be used to assess the risk of falling in older adults. However, the state-of-the-art systems used to quantify gait parameters often come with high costs as well as training and space requirements. Gait analysis systems, which use mobile and commercially available cameras, can be an easily available, marker-free alternative. In a study with 44 participants (age ≥ 65 years), gait patterns were analyzed with three different systems: a pressure sensitive walkway system (GAITRite-System, GS) as gold standard, Motognosis Labs Software using a Microsoft Kinect Sensor (MKS), and a smartphone camera-based application (SCA). Intertrial repeatability showed moderate to excellent results for MKS (ICC(1,1) 0.574 to 0.962) for almost all measured gait parameters and moderate reliability in SCA measures for gait speed (ICC(1,1) 0.526 to 0.535). All gait parameters of MKS showed a high level of agreement with GS (ICC(2,k) 0.811 to 0.981). Gait parameters extracted with SCA showed poor reliability. The tested gait analysis systems based on different camera systems are currently only partially able to capture valid gait parameters. If the underlying algorithms are adapted and camera technology is advancing, it is conceivable that these comparatively simple methods could be used for gait analysis

Electronic Excited States of Tungsten(0) Arylisocyanides

W(CNAryl)_6 complexes containing 2,6-diisopropylphenyl isocyanide (CNdipp) are powerful photoreductants with strongly emissive long-lived excited states. These properties are enhanced upon appending another aryl ring, e.g., W(CNdippPh^(OMe)_2)_6; CNdippPh^(OMe)_2 = 4-(3,5-dimethoxyphenyl)-2,6-diisopropylphenylisocyanide (Sattler et al. J. Am. Chem. Soc. 2015, 137, 1198−1205). Electronic transitions and low-lying excited states of these complexes were investigated by time-dependent density functional theory (TDDFT); the lowest triplet state was characterized by time-resolved infrared spectroscopy (TRIR) supported by density functional theory (DFT). The intense absorption band of W(CNdipp)_6 at 460 nm and that of W(CNdippPh^(OMe)_2)_6 at 500 nm originate from transitions of mixed ππ*(C≡N–C)/MLCT(W → Aryl) character, whereby W is depopulated by ca. 0.4 e– and the electron-density changes are predominantly localized along two equatorial molecular axes. The red shift and intensity rise on going from W(CNdipp)_6 to W(CNdippPh^(OMe)_2)_6 are attributable to more extensive delocalization of the MLCT component. The complexes also exhibit absorptions in the 300–320 nm region, owing to W → C≡N MLCT transitions. Electronic absorptions in the spectrum of W(CNXy)_6 (Xy = 2,6-dimethylphenyl), a complex with orthogonal aryl orientation, have similar characteristics, although shifted to higher energies. The relaxed lowest W(CNAryl)_6 triplet state combines ππ* excitation of a trans pair of C≡N–C moieties with MLCT (0.21 e–) and ligand-to-ligand charge transfer (LLCT, 0.24–0.27 e–) from the other four CNAryl ligands to the axial aryl and, less, to C≡N groups; the spin density is localized along a single Aryl–N≡C–W–C≡N–Aryl axis. Delocalization of excited electron density on outer aryl rings in W(CNdippPh^(OMe)_2)_6 likely promotes photoinduced electron-transfer reactions to acceptor molecules. TRIR spectra show an intense broad bleach due to ν(C≡N), a prominent transient upshifted by 60–65 cm^(–1), and a weak down-shifted feature due to antisymmetric C≡N stretch along the axis of high spin density. The TRIR spectral pattern remains unchanged on the femtosecond-nanosecond time scale, indicating that intersystem crossing and electron-density localization are ultrafast (<100 fs)

Molecular characterization and evolution of a gene family encoding male-specific reproductive proteins in the African malaria vector Anopheles gambiae

<p>Abstract</p> <p>Background</p> <p>During copulation, the major Afro-tropical malaria vector <it>Anopheles gambiae </it>s.s. transfers male accessory gland (MAG) proteins to females as a solid mass (i.e. the "mating plug"). These proteins are postulated to function as important modulators of female post-mating responses. To understand the role of selective forces underlying the evolution of these proteins in the <it>A. gambiae </it>complex, we carried out an evolutionary analysis of gene sequence and expression divergence on a pair of paralog genes called <it>AgAcp34A-1 </it>and <it>AgAcp34A-2</it>. These encode MAG-specific proteins which, based on homology with <it>Drosophila</it>, have been hypothesized to play a role in sperm viability and function.</p> <p>Results</p> <p>Genetic analysis of 6 species of the <it>A. gambiae </it>complex revealed the existence of a third paralog (68-78% of identity), that we named <it>AgAcp34A-3</it>. FISH assays showed that this gene maps in the same division (34A) of chromosome-3R as the other two paralogs. In particular, immuno-fluorescence assays targeting the C-terminals of <it>AgAcp34A-2 </it>and <it>AgAcp34A-3 </it>revealed that these two proteins are localized in the posterior part of the MAG and concentrated at the apical portion of the mating plug. When transferred to females, this part of the plug lies in proximity to the duct connecting the spermatheca to the uterus, suggesting a potential role for these proteins in regulating sperm motility. <it>AgAcp34A-3 </it>is more polymorphic than the other two paralogs, possibly because of relaxation of purifying selection. Since both unequal crossing-over and gene conversion likely homogenized the members of this gene family, the interpretation of the evolutionary patterns is not straightforward. Although several haplotypes of the three paralogs are shared by most <it>A. gambiae </it>s.l. species, some fixed species-specific replacements (mainly placed in the N- and C-terminal portions of the secreted peptides) were also observed, suggesting some lineage-specific adaptation.</p> <p>Conclusions</p> <p>Progress in understanding the signaling cascade in the <it>A. gambiae </it>reproductive pathway will elucidate the interaction of this MAG-specific protein family with their female counterparts. This knowledge will allow a better evaluation of the relative importance of genes involved in the reproductive isolation and fertility of <it>A. gambiae </it>species and could help the interpretation of the observed evolutionary patterns.</p

Birth Weight and Adult IQ, but Not Anxious-Depressive Psychopathology, Are Associated with Cortical Surface Area: A Study in Twins

BACKGROUND: Previous research suggests that low birth weight (BW) induces reduced brain cortical surface area (SA) which would persist until at least early adulthood. Moreover, low BW has been linked to psychiatric disorders such as depression and psychological distress, and to altered neurocognitive profiles. AIMS: We present novel findings obtained by analysing high-resolution structural MRI scans of 48 twins; specifically, we aimed: i) to test the BW-SA association in a middle-aged adult sample; and ii) to assess whether either depression/anxiety disorders or intellectual quotient (IQ) influence the BW-SA link, using a monozygotic (MZ) twin design to separate environmental and genetic effects. RESULTS: Both lower BW and decreased IQ were associated with smaller total and regional cortical SA in adulthood. Within a twin pair, lower BW was related to smaller total cortical and regional SA. In contrast, MZ twin differences in SA were not related to differences in either IQ or depression/anxiety disorders. CONCLUSION: The present study supports findings indicating that i) BW has a long-lasting effect on cortical SA, where some familial and environmental influences alter both foetal growth and brain morphology; ii) uniquely environmental factors affecting BW also alter SA; iii) higher IQ correlates with larger SA; and iv) these effects are not modified by internalizing psychopathology.This work was supported by the Spanish SAF2008-05674, European Twins Study Network on Schizophrenia Research Training Network (grant number EUTwinsS; MRTN-CT-2006-035987), the Catalan 2014SGR1636 and the PIM2010-ERN- 00642 in frame of ERA-NET NEURON. A. Córdova- Palomera was funded by The National Council for Science and Technology (CONACyT, Mexico). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Automated workflow-based exploitation of pathway databases provides new insights into genetic associations of metabolite profiles

Background: Genome-wide association studies (GWAS) have identified many common single nucleotide polymorphisms (SNPs) that associate with clinical phenotypes, but these SNPs usually explain just a small part of the heritability and have relatively modest effect sizes. In contrast, SNPs that associate with metabolite levels generally explain a higher percentage of the genetic variation and demonstrate larger effect sizes. Still, the discovery of SNPs associated with metabolite levels is challenging since testing all metabolites measured in typical metabolomics studies with all SNPs comes with a severe multiple testing penalty. We have developed an automated workflow approach that utilizes prior knowledge of biochemical pathways present in databases like KEGG and BioCyc to generate a smaller SNP set relevant to the metabolite. This paper explores the opportunities and challenges in the analysis of GWAS of metabolomic phenotypes and provides novel insights into the genetic basis of metabolic variation through the re-analysis of published GWAS datasets. Results: Re-analysis of the published GWAS dataset from Illig et al. (Nature Genetics, 2010) using a pathway-based workflow (http://www.myexperiment.org/packs/319.html), confirmed previously identified hits and identified a new locus of human metabolic individuality, associating Aldehyde dehydrogenase family1 L1 (ALDH1L1) with serine/glycine ratios in blood. Replication in an independent GWAS dataset of phospholipids (Demirkan et al., PLoS Genetics, 2012) identified two novel loci supported by additional literature evidence: GPAM (Glycerol-3 phosphate acyltransferase) and CBS (Cystathionine beta-synthase). In addition, the workflow approach provided novel insight into the affected pathways and relevance of some of these gene-metabolite pairs in disease development and progression. Conclusions: We demonstrate the utility of automated exploitation of background knowledge present in pathway databases for the analysis of GWAS datasets of metabolomic phenotypes. We report novel loci and potential biochemical mechanisms that contribute to our understanding of the genetic basis of metabolic variation and its relationship to disease development and progression

Meta-Analysis of 28,141 Individuals Identifies Common Variants within Five New Loci That Influence Uric Acid Concentrations

Elevated serum uric acid levels cause gout and are a risk factor for cardiovascular disease and diabetes. To investigate the polygenetic basis of serum uric acid levels, we conducted a meta-analysis of genome-wide association scans from 14 studies totalling 28,141 participants of European descent, resulting in identification of 954 SNPs distributed across nine loci that exceeded the threshold of genome-wide significance, five of which are novel. Overall, the common variants associated with serum uric acid levels fall in the following nine regions: SLC2A9 (p = 5.2×10−201), ABCG2 (p = 3.1×10−26), SLC17A1 (p = 3.0×10−14), SLC22A11 (p = 6.7×10−14), SLC22A12 (p = 2.0×10−9), SLC16A9 (p = 1.1×10−8), GCKR (p = 1.4×10−9), LRRC16A (p = 8.5×10−9), and near PDZK1 (p = 2.7×10−9). Identified variants were analyzed for gender differences. We found that the minor allele for rs734553 in SLC2A9 has greater influence in lowering uric acid levels in women and the minor allele of rs2231142 in ABCG2 elevates uric acid levels more strongly in men compared to women. To further characterize the identified variants, we analyzed their association with a panel of metabolites. rs12356193 within SLC16A9 was associated with DL-carnitine (p = 4.0×10−26) and propionyl-L-carnitine (p = 5.0×10−8) concentrations, which in turn were associated with serum UA levels (p = 1.4×10−57 and p = 8.1×10−54, respectively), forming a triangle between SNP, metabolites, and UA levels. Taken together, these associations highlight additional pathways that are important in the regulation of serum uric acid levels and point toward novel potential targets for pharmacological intervention to prevent or treat hyperuricemia. In addition, these findings strongly support the hypothesis that transport proteins are key in regulating serum uric acid levels

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Oxidation and Reduction Reaction Kinetics of Mixed Cerium Zirconium Oxides

The oxidation and reduction of mixed cerium zirconium oxides, Ce1−xZrxO2, with x varied in the range 0−0.3 in steps of 0.05, in a low-pressure oxygen atmosphere were experimentally investigated. The experiments utilized a novel method developed by the authors, in which the samples are reduced and oxidized in a sealed vacuum chamber by irradiating them with a xenon arc lamp. The changes in pressure due to the release or consumption of oxygen are used to quantify the extent and rates of the reactions. The System can achieve heating rates in excess of 100 °C s−1, which is hundreds of times faster than is possible with a thermobalance. In addition, the gas phase transport is very rapid as it is driven by pressure gradients. The combined high heating rate and fast gas phase transport offers unique conditions in which to measure the actual kinetics of the reactions. The oxidation kinetics showed a strong dependence on the amount of Zr4+ in the samples, where the rate of oxidation decreased with increasing Zr4+ concentration. The effect of adding 2.5% Sm3+ or La3+ to the Ce0.85Zr0.15O2 was also investigated with the hope of improving the kinetics. The addition of La3+ to Ce0.85Zr0.15O2 was seen to offer an increase in the reaction rates, although the oxidation kinetics were still slower than that of pure CeO2. Finally, the reduction kinetic data are presented, but even with the optimal conditions the reduction reaction still appeared to be limited by the heating rate; thus, it was concluded that the reduction kinetics were too rapid to quantify by this method