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The mechanisms underlying improved insulin sensitivity after surgically-induced weight loss are still unclear. We monitored skeletal muscle metabolism in obese individuals before and over 52 weeks after metabolic surgery. Initial weight loss occurs in parallel with a decrease in muscle oxidative capacity and respiratory control ratio. Persistent elevation of intramyocellular lipid intermediates, likely resulting from unrestrained adipose tissue lipolysis, accompanies the lack of rapid changes in insulin sensitivity. Simultaneously, alterations in skeletal muscle expression of genes involved in calcium/lipid metabolism and mitochondrial function associate with subsequent distinct DNA methylation patterns at 52 weeks after surgery. Thus, initial unfavorable metabolic changes including insulin resistance of adipose tissue and skeletal muscle precede epigenetic modifications of genes involved in muscle energy metabolism and the long-term improvement of insulin sensitivity.
This survey on the theme of Geometry Education (including new technologies) focuses chiefly on the time span since 2008. Based on our review of the research literature published during this time span (in refereed journal articles, conference proceedings and edited books), we have jointly identified seven major threads of contributions that span from the early years of learning (pre-school and primary school) through to post-compulsory education and to the issue of mathematics teacher education for geometry. These threads are as follows: developments and trends in the use of theories; advances in the understanding of visuo spatial reasoning; the use and role of diagrams and gestures; advances in the understanding of the role of digital technologies; advances in the understanding of the teaching and learning of definitions; advances in the understanding of the teaching and learning of the proving process; and, moving beyond traditional Euclidean approaches. Within each theme, we identify relevant research and also offer commentary on future directions.
Many children show negative emotions related to mathematics and some even develop mathematics anxiety. The present study focused on the relation between negative emotions and arithmetical performance in children with and without developmental dyscalculia (DD) using an affective priming task. Previous findings suggested that arithmetic performance is influenced if an affective prime precedes the presentation of an arithmetic problem. In children with DD specifically, responses to arithmetic operations are supposed to be facilitated by both negative and mathematics-related primes (= negative math priming effect). We investigated mathematical performance, math anxiety, and the domain-general abilities of 172 primary school children (76 with DD and 96 controls). All participants also underwent an affective priming task which consisted of the decision whether a simple arithmetic operation (addition or subtraction) that was preceded by a prime (positive/negative/neutral or mathematics-related) was true or false. Our findings did not reveal a negative math priming effect in children with DD. Furthermore, when considering accuracy levels, gender, or math anxiety, the negative math priming effect could not be replicated. However, children with DD showed more math anxiety when explicitly assessed by a specific math anxiety interview and showed lower mathematical performance compared to controls. Moreover, math anxiety was equally present in boys and girls, even in the earliest stages of schooling, and interfered negatively with performance. In conclusion, mathematics is often associated with negative emotions that can be manifested in specific math anxiety, particularly in children with DD. Importantly, present findings suggest that in the assessed age group, it is more reliable to judge math anxiety and investigate its effects on mathematical performance explicitly by adequate questionnaires than by an affective math priming task.
Moving Beyond ERP Components
(2018)
Relationships between neuroimaging measures and behavior provide important clues about brain function and cognition in healthy and clinical populations. While electroencephalography (EEG) provides a portable, low cost measure of brain dynamics, it has been somewhat underrepresented in the emerging field of model-based inference. We seek to address this gap in this article by highlighting the utility of linking EEG and behavior, with an emphasis on approaches for EEG analysis that move beyond focusing on peaks or "components" derived from averaging EEG responses across trials and subjects (generating the event-related potential, ERP). First, we review methods for deriving features from EEG in order to enhance the signal within single-trials. These methods include filtering based on user-defined features (i.e., frequency decomposition, time-frequency decomposition), filtering based on data-driven properties (i.e., blind source separation, BSS), and generating more abstract representations of data (e.g., using deep learning). We then review cognitive models which extract latent variables from experimental tasks, including the drift diffusion model (DDM) and reinforcement learning (RL) approaches. Next, we discuss ways to access associations among these measures, including statistical models, data-driven joint models and cognitive joint modeling using hierarchical Bayesian models (HBMs). We think that these methodological tools are likely to contribute to theoretical advancements, and will help inform our understandings of brain dynamics that contribute to moment-to-moment cognitive function.
Ancient genomes have revolutionized our understanding of Holocene prehistory and, particularly, the Neolithic transition in western Eurasia. In contrast, East Asia has so far received little attention, despite representing a core region at which the Neolithic transition took place independently similar to 3 millennia after its onset in the Near East. We report genome-wide data from two hunter-gatherers from Devil's Gate, an early Neolithic cave site (dated to similar to 7.7 thousand years ago) located in East Asia, on the border between Russia and Korea. Both of these individuals are genetically most similar to geographically close modern populations from the Amur Basin, all speaking Tungusic languages, and, in particular, to the Ulchi. The similarity to nearby modern populations and the low levels of additional genetic material in the Ulchi imply a high level of genetic continuity in this region during the Holocene, a pattern that markedly contrasts with that reported for Europe.
The UK Biobank is a prospective study of 502,543 individuals, combining extensive phenotypic and genotypic data with streamlined access for researchers around the world(1). Here we describe the release of exome-sequence data for the first 49,960 study participants, revealing approximately 4 million coding variants (of which around 98.6% have a frequency of less than 1%). The data include 198,269 autosomal predicted loss-of-function (LOF) variants, a more than 14-fold increase compared to the imputed sequence. Nearly all genes (more than 97%) had at least one carrier with a LOF variant, and most genes (more than 69%) had at least ten carriers with a LOF variant. We illustrate the power of characterizing LOF variants in this population through association analyses across 1,730 phenotypes. In addition to replicating established associations, we found novel LOF variants with large effects on disease traits, includingPIEZO1on varicose veins,COL6A1on corneal resistance,MEPEon bone density, andIQGAP2andGMPRon blood cell traits. We further demonstrate the value of exome sequencing by surveying the prevalence of pathogenic variants of clinical importance, and show that 2% of this population has a medically actionable variant. Furthermore, we characterize the penetrance of cancer in carriers of pathogenicBRCA1andBRCA2variants. Exome sequences from the first 49,960 participants highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community. <br /> Exome sequences from the first 49,960 participants in the UK Biobank highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community.
Unicellular algae serve as models for the study and discovery of metabolic pathways, for the functional dissection of cell biological processes such as organellar division and cell motility, and for the identification of novel genes and gene functions. The recent completion of several algal genome sequences and expressed sequence tag collections and the establishment of nuclear and organellar transformation methods has opened the way for functional genomics approaches using algal model systems. The thermo-acidophilic unicellular red alga Galdieria sulphuraria represents a particularly interesting species for a genomics approach owing to its extraordinary metabolic versatility such as heterotrophic and mixotrophic growth on more than 50 different carbon sources and its adaptation to hot acidic environments. However, the ab initio prediction of genes required for unknown metabolic pathways from genome sequences is not trivial. A compelling strategy for gene identification is the comparison of similarly sized genomes of related organisms with different physiologies. Using this approach, candidate genes were identified that are critical to the metabolic versatility of Galdieria. Expressed sequence tags and high-throughput genomic sequence reads covering >70% of the G. sulphuraria genome were compared to the genome of the unicellular, obligate photoautotrophic red alga Cyanidioschyzon merolae. More than 30% of the Galdieria sequences did not relate to any of the Cyandioschyzon genes. A closer inspection of these sequences revealed a large number of membrane transporters and enzymes of carbohydrate metabolism that are unique to Galdieria. Based on these data, it is proposed that genes involved in the uptake of reduced carbon compounds and enzymes involved in their metabolism are crucial to the metabolic flexibility of G. sulphuraria
Savannas are globally important ecosystems of great significance to human economies. In these biomes, which are characterized by the co-dominance of trees and grasses, woody cover is a chief determinant of ecosystem properties(1-3). The availability of resources ( water, nutrients) and disturbance regimes ( fire, herbivory) are thought to be important in regulating woody cover(1,2,4,5), but perceptions differ on which of these are the primary drivers of savanna structure. Here we show, using data from 854 sites across Africa, that maximum woody cover in savannas receiving a mean annual precipitation (MAP) of less than similar to 650 mm is constrained by, and increases linearly with, MAP. These arid and semi-arid savannas may be considered 'stable' systems in which water constrains woody cover and permits grasses to coexist, while fire, herbivory and soil properties interact to reduce woody cover below the MAP- controlled upper bound. Above a MAP of similar to 650 mm, savannas are 'unstable' systems in which MAP is sufficient for woody canopy closure, and disturbances ( fire, herbivory) are required for the coexistence of trees and grass. These results provide insights into the nature of African savannas and suggest that future changes in precipitation(6) may considerably affect their distribution and dynamics
Moving beyond ERP components
(2018)
Relationships between neuroimaging measures and behavior provide important clues about brain function and cognition in healthy and clinical populations. While electroencephalography (EEG) provides a portable, low cost measure of brain dynamics, it has been somewhat underrepresented in the emerging field of model-based inference. We seek to address this gap in this article by highlighting the utility of linking EEG and behavior, with an emphasis on approaches for EEG analysis that move beyond focusing on peaks or "components" derived from averaging EEG responses across trials and subjects (generating the event-related potential, ERP). First, we review methods for deriving features from EEG in order to enhance the signal within single-trials. These methods include filtering based on user-defined features (i.e., frequency decomposition, time-frequency decomposition), filtering based on data-driven properties (i.e., blind source separation, BSS), and generating more abstract representations of data (e.g., using deep learning). We then review cognitive models which extract latent variables from experimental tasks, including the drift diffusion model (DDM) and reinforcement learning (RL) approaches. Next, we discuss ways to access associations among these measures, including statistical models, data-driven joint models and cognitive joint modeling using hierarchical Bayesian models (HBMs). We think that these methodological tools are likely to contribute to theoretical advancements, and will help inform our understandings of brain dynamics that contribute to moment-to-moment cognitive function.
Many children show negative emotions related to mathematics and some even develop mathematics anxiety. The present study focused on the relation between negative emotions and arithmetical performance in children with and without developmental dyscalculia (DD) using an affective priming task. Previous findings suggested that arithmetic performance is influenced if an affective prime precedes the presentation of an arithmetic problem. In children with DD specifically, responses to arithmetic operations are supposed to be facilitated by both negative and mathematics-related primes (= negative math priming effect). We investigated mathematical performance, math anxiety, and the domain-general abilities of 172 primary school children (76 with DD and 96 controls). All participants also underwent an affective priming task which consisted of the decision whether a simple arithmetic operation (addition or subtraction) that was preceded by a prime (positive/negative/neutral or mathematics-related) was true or false. Our findings did not reveal a negative math priming effect in children with DD. Furthermore, when considering accuracy levels, gender, or math anxiety, the negative math priming effect could not be replicated. However, children with DD showed more math anxiety when explicitly assessed by a specific math anxiety interview and showed lower mathematical performance compared to controls. Moreover, math anxiety was equally present in boys and girls, even in the earliest stages of schooling, and interfered negatively with performance. In conclusion, mathematics is often associated with negative emotions that can be manifested in specific math anxiety, particularly in children with DD. Importantly, present findings suggest that in the assessed age group, it is more reliable to judge math anxiety and investigate its effects on mathematical performance explicitly by adequate questionnaires than by an affective math priming task.
Sedimentary ancient DNA has been proposed as a key methodology for reconstructing biodiversity over time. Yet, despite the concentration of Earth’s biodiversity in the tropics, this method has rarely been applied in this region. Moreover, the taphonomy of sedimentary DNA, especially in tropical environments, is poorly understood. This study elucidates challenges and opportunities of sedimentary ancient DNA approaches for reconstructing tropical biodiversity. We present shotgun-sequenced metagenomic profiles and DNA degradation patterns from multiple sediment cores from Mubwindi Swamp, located in Bwindi Impenetrable Forest (Uganda), one of the most diverse forests in Africa. We describe the taxonomic composition of the sediments covering the past 2200 years and compare the sedimentary DNA data with a comprehensive set of environmental and sedimentological parameters to unravel the conditions of DNA degradation. Consistent with the preservation of authentic ancient DNA in tropical swamp sediments, DNA concentration and mean fragment length declined exponentially with age and depth, while terminal deamination increased with age. DNA preservation patterns cannot be explained by any environmental parameter alone, but age seems to be the primary driver of DNA degradation in the swamp. Besides degradation, the presence of living microbial communities in the sediment also affects DNA quantity. Critically, 92.3% of our metagenomic data of a total 81.8 million unique, merged reads cannot be taxonomically identified due to the absence of genomic references in public databases. Of the remaining 7.7%, most of the data (93.0%) derive from Bacteria and Archaea, whereas only 0–5.8% are from Metazoa and 0–6.9% from Viridiplantae, in part due to unbalanced taxa representation in the reference data. The plant DNA record at ordinal level agrees well with local pollen data but resolves less diversity. Our animal DNA record reveals the presence of 41 native taxa (16 orders) including Afrotheria, Carnivora, and Ruminantia at Bwindi during the past 2200 years. Overall, we observe no decline in taxonomic richness with increasing age suggesting that several-thousand-year-old information on past biodiversity can be retrieved from tropical sediments. However, comprehensive genomic surveys of tropical biota need prioritization for sedimentary DNA to be a viable methodology for future tropical biodiversity studies.
This study presents the evaluation of a computer-based learning program for children with developmental dyscalculia and focuses on factors affecting individual responsiveness. The adaptive training program Calcularis 2.0 has been developed according to current neuro-cognitive theory of numerical cognition. It aims to automatize number representations, supports the formation and access to the mental number line and trains arithmetic operations as well as arithmetic fact knowledge in expanding number ranges. Sixty-seven children with developmental dyscalculia from second to fifth grade (mean age 8.96 years) were randomly assigned to one of two groups (Calcularis group, waiting control group). Training duration comprised a minimum of 42 training sessions à 20 min within a maximum period of 13 weeks. Compared to the waiting control group, children of the Calcularis group demonstrated a higher benefit in arithmetic operations and number line estimation. These improvements were shown to be stable after a 3-months post training interval. In addition, this study examines which predictors accounted for training improvements. Results indicate that this self-directed training was especially beneficial for children with low math anxiety scores and without an additional reading and/or spelling disorder. In conclusion, Calcularis 2.0 supports children with developmental dyscalculia to improve their arithmetical abilities and their mental number line representation. However, it is relevant to further adapt the setting to the individual circumstances.
Fragestellung: Ziel war die Untersuchung des Verlaufs von Kindern mit Rechenstörungen bzw. Rechenschwächen. Neben der Persistenz wurden Auswirkungen von Rechenproblemen auf künftige Rechenleistungen sowie den Schulerfolg geprüft. Methodik: Für 2909 Schüler der 2. bis 5. Klasse liegen die Resultate standardisierter Rechen- und Intelligenztests vor. Ein Teil dieser Kinder ist nach 37 und 68 Mona-ten erneut untersucht worden. Ergebnisse: Die Prävalenz von Rechenstörungen betrug 1.4 %, Rechenschwächen traten bei 11.2 % auf. Rechen-probleme zeigten eine mittlere bis hohe Persistenz. Schüler mit Rechenschwäche blieben im Rechnen gut eine Standardabweichung hinter durchschnittlich und ca. eine halbe Standardabweichung hinter unterdurchschnittlich intelligenten Kontrollkindern zurück. Der allgemeine Schulerfolg rechenschwacher Probanden (definiert über Mathematiknote, Deutschnote und Schultyp) ähnelte dem der unterdurchschnittlich intelligenten Kontrollgruppe und blieb hinter dem Schulerfolg durchschnittlich intelligenter Kontrollkinder zurück. Eingangs ältere Probanden mit Rechenproblemen (4. bis 5. Klasse) wiesen eine schlechtere Prognose auf als Kinder, die zu Beginn die 2. oder 3. Klasse besuchten. Schluss-folgerungen: Rechenprobleme stellen ein ernsthaftes Entwicklungsrisiko dar. Längsschnittuntersuchungen, die Kinder mit streng definierter Rechenstörung bis ins Erwachsenenalter begleiten und Prädiktoren für unterschiedlich erfolgreiche Verläufe ermitteln, sind dringend notwendig.
Henne oder Ei
(2018)
Fragestellung: Ziel war die Untersuchung der Entwicklung und wechselseitigen Beziehung von Zahlen- und Mengenvorwissen (ZMW), Arbeitsgedächtnis (AG) und Intelligenz sowie deren Vorhersagekraft für die Rechenleistung in der ersten Klasse. Methodik: 1897 Kindergartenkinder nahmen an dieser Studie teil. Ein Teil dieser Kinder wurde 9 Monate später und erneut in der ersten Klasse untersucht. Ergebnisse: Während des Kindergartenjahres verbesserten sich die Kinder in allen untersuchten Leistungen. Reziproke Zusammenhänge zwischen den drei erhobenen Vorläuferfähigkeiten konnten nachgewiesen werden. Das ZMW erwies sich als guter Prädiktor für die AG- und Intelligenzleistung. Bei der Überprüfung der Vorhersage des Rechnens erwies sich das ZMW als bester Prädiktor der späteren Rechenleistung. Erwartungsgemäß zeigten die zu t1 erfassten allgemein-kognitiven Leistungen indirekte Effekte über das ZMW auf die Rechenleistung. Die Intelligenz und das AG zu t2 konnten direkt zur Vorhersage des Rechnens in der ersten Klasse beitragen. Schlussfolgerungen: Die Ergebnisse verdeutlichen, dass das AG und die Intelligenz zwar an dem Aufbau des ZMW beteiligt sind, aber vor allem selbst durch dieses vorhergesagt werden. Die Daten sprechen dafür das Potenzial des ZMWs in Trainingsprogrammen zu nutzen, durch dessen Förderung auch intellektuelle und Gedächtnisleistungen zunehmen können, die allesamt die schulische Rechenleistung positiv beeinflussen.
Dyskalkulie
(2017)
Hintergrund
Ausgeprägte Schwierigkeiten beim Erwerb der grundlegenden arithmetischen Fertigkeiten bei ansonsten durchschnittlichen Schulleistungen werden als Rechenstörung oder Dyskalkulie bezeichnet. Davon betroffen sind etwa 5 % der Grundschülerpopulation. Die Ursachen und die Symptome sind ebenso vielgestaltig wie die Methoden der differenziellen Förderung und Therapie.
Material und Methode
Selektive Literaturrecherche zur Rechenstörung aus verschiedenen mit dem Gegenstand befassten wissenschaftlichen Disziplinen.
Ergebnisse
Der Erwerb von Fähigkeiten zur Zahlenverarbeitung und zum Rechnen wird als ein erfahrungsabhängiger neuroplastischer Reifungsprozess verstanden, der zu einem komplexen, spezialisierten neuronalen Netzwerk führt und verschiedene kognitive Zahlenrepräsentationen hervorbringt. Die Entwicklung dieser domänenspezifischen Fähigkeiten ist abhängig von der Entwicklung domänenübergreifender Fähigkeiten, wie Aufmerksamkeit, Arbeitsgedächtnis, Sprache und visuell-räumlichen Fähigkeiten. Störungen dieser Reifungsprozesse können in verschiedenen Entwicklungsstadien unterschiedliche Komponenten der Entwicklung dieses komplexen kognitiven Systems betreffen und sind daher im klinischen Erscheinungsbild vielgestaltig. Sonderpädagogische, lerntherapeutische und ggf. medizinische Maßnahmen benötigen eine differenzielle Diagnostik und Indikationsstellung. Moderne computerbasierte Lernsoftware kann sowohl die schulische Didaktik als auch lerntherapeutische Vorgehensweisen unterstützen.
Schlussfolgerung
Frühzeitiges Erkennen sowie differenzielle und individualisierte Förderung können die Gefahr des Auftretens sekundärer emotionaler Störungen mindern. Die Diagnostik und die Behandlung der Rechenstörung sollten evidenzbasiert und leitlinienorientiert erfolgen sowie der Komplexität und Vielgestaltigkeit der Symptombildungen Rechnung tragen.
Enzymes of the xanthine oxidase family are among the best characterized mononuclear molybdenum enzymes. Open questions about their mechanism of transfer of an oxygen atom to the substrate remain. The enzymes share a molybdenum cofactor (Moco) with the metal ion binding a molybdopterin (MPT) molecule via its dithiolene function and terminal sulfur and oxygen groups. For xanthine dehydrogenase (XDH) from the bacterium Rhodobacter capsulatus, we used X-ray absorption spectroscopy to determine the Mo site structure, its changes in a pH range of 5-10, and the influence of amino acids (Glu730 and Gln179) close to Moco in wild-type (WT), Q179A, and E730A variants, complemented by enzyme kinetics and quantum chemical studies. Oxidized WT and Q179A revealed a similar Mo (VI) ion with each one MPT, Mo=O, Mo-O-, and Mo=S ligand, and a weak Mo-O(E730) bond at alkaline pH. Protonation of an oxo to a hydroxo (OH) ligand (pK similar to 6.8) causes inhibition of XDH at acidic pH, whereas deprotonated xanthine (pK similar to 8.8) is an inhibitor at alkaline pH. A similar acidic pK for the WT and Q179A. variants, as well as the metrical parameters of the Mo site and density functional theory calculations, suggested protonation at the equatorial oxo group. The sulfido was replaced with an oxo ligand in the inactive E730A variant, further showing another oxo and one Mo OH ligand at Mo, which are independent of pH. Our findings suggest a reaction mechanism for XDH in which an initial oxo rather than a hydroxo group and the sulfido ligand are essential for xanthine oxidation.
Ancient genomes have revolutionized our understanding of Holocene prehistory and, particularly, the Neolithic transition in western Eurasia. In contrast, East Asia has so far received little attention, despite representing a core region at which the Neolithic transition took place independently ~3 millennia after its onset in the Near East. We report genome-wide data from two hunter-gatherers from Devil’s Gate, an early Neolithic cave site (dated to ~7.7 thousand years ago) located in East Asia, on the border between Russia and Korea. Both of these individuals are genetically most similar to geographically close modern populations from the Amur Basin, all speaking Tungusic languages, and, in particular, to the Ulchi. The similarity to nearby modern populations and the low levels of additional genetic material in the Ulchi imply a high level of genetic continuity in this region during the Holocene, a pattern that markedly contrasts with that reported for Europe.