Sex, Diabetes Status and Cognition: Findings from the Study of Longevity in Diabetes

INTRODUCTION: Women comprise two-thirds of people with dementia, making female sex a significant dementia risk factor. Both type 1 diabetes (T1D) and type 2 diabetes (T2D) are known dementia risk factors with an increasing global incidence. Understanding whether subtle sex differences persist in cognitive function prior to dementia in the context of diabetes may help elucidate the magnitude of sex effects on dementia risk. RESEARCH DESIGN AND METHODS: We examined cross-sectional data from the Study of Longevity in Diabetes (SOLID), a prospective cohort study of members of Kaiser Permanente Northern California aged 60 years and older with T1D (n=758), T2D (n=232) and without either T1D or T2D (n=247). We used factor analysis to generate summary scores of cognitive domains and used regression analyses to examine the associations between sex and cognition adjusting for sociodemographic and cardiovascular confounders. RESULTS: We included 1237 participants (630 women and 607 men) with mean age 68 years. By design, the distribution of men and women in T1D, T2D and no diabetes was similar. Women had better cognitive performance than men in global cognition (β=0.21, 95% CI 0.16 to 0.26), language (β=0.08, 95% CI 0.004 to 0.15), executive function (β=0.13, 95% CI 0.05 to 0.20), episodic verbal memory (β=0.68, 95% CI 0.59 to 0.77) and attention (β=0.20, 95% CI 0.11 to 0.28) but not in episodic visual memory (β=0.006, 95% CI -0.07 to 0.09) adjusting for age and education independent of diabetes status. We did not find an interaction between sex and diabetes status for any of the cognitive outcomes. CONCLUSIONS: Women in late mid-life have better cognitive performance than men in many cognitive domains independent of the presence of T1D or T2D. Further work is required to understand whether these differences change over time or in older cohorts and to understand their relationship to subsequent dementia

On scrimshaw precursors: a 13th-century carved and engraved sperm whale tooth

In der einschlägigen Forschung zur Walfängervolkskunst des "Scrimshaw" - den seit den 1820er Jahren populär gewordenen Seemannsarbeiten speziell auf und aus Pottwal- und Walroßzahn, Barten und Walknochen - werden künstlerisch bearbeitete Gegenstände anderer Kulturen aus denselben Materialien als "Scrimshaw"-Vorläufer bezeichnet. Aus dem europäischen Mittelalter sind zwar zahlreiche Beispiele von Schnitzereien aus Walroßzahn und Walknochen bekannt, nicht jedoch aus Pottwalzahn, dem beinah stereotypen Werkstoff der "Scrimshander" des 19. und 20. Jahrhunderts. Der "Königsspiegel", ein um 1250/60 in Norwegen geschriebener pädagogischer Text, erwähnt gleichwohl Schnitzereien aus Pottwalzahn. Auch aus dem 16. und 17. Jahrhundert sind textliche Hinweise auf skandinavisches Kunstgewerbe aus den Zähnen dieses Meeressäugers bekannt. Im Anschluß an die Präsentation dieser Quellen wird ein konkretes Beispiel vorgestellt: Es handelt sich um ein beschnitztes und graviertes Salbenhorn aus Pottwalzahn, das sich in der Sammlung christlicher Kunst und Kultur des Museums der Universität Bergen, Norwegen, lnv. MA 437, befindet. Aus dem massiven Dentin wurde ein Greif herausgeschnitzt, der Ausguß wurde wie der Kopf eines gotischen Wasserspeiers gestaltet. Auf einer glatten Seitenfläche wurde später ein kleines Tondo mit Pflanzen- und Vogelmotiv eingraviert. Es trägt eine Inschrift, die vom Bergenser Museum als griechisch, hier aber als russisch identifiziert wurde, deren Sinn aber unklar bleibt. Anlass, die vom Museum vorgenommene Datierung des Zahns in das 13. Jahrhundert zu revidieren, besteht allerdings nicht

Designer diatom episomes delivered by bacterial conjugation.

Eukaryotic microalgae hold great promise for the bioproduction of fuels and higher value chemicals. However, compared with model genetic organisms such as Escherichia coli and Saccharomyces cerevisiae, characterization of the complex biology and biochemistry of algae and strain improvement has been hampered by the inefficient genetic tools. To date, many algal species are transformable only via particle bombardment, and the introduced DNA is integrated randomly into the nuclear genome. Here we describe the first nuclear episomal vector for diatoms and a plasmid delivery method via conjugation from Escherichia coli to the diatoms Phaeodactylum tricornutum and Thalassiosira pseudonana. We identify a yeast-derived sequence that enables stable episome replication in these diatoms even in the absence of antibiotic selection and show that episomes are maintained as closed circles at copy number equivalent to native chromosomes. This highly efficient genetic system facilitates high-throughput functional characterization of algal genes and accelerates molecular phytoplankton research

Genome-Scale Model Reveals Metabolic Basis of Biomass Partitioning in a Model Diatom

Diatoms are eukaryotic microalgae that contain genes from various sources, including bacteria and the secondary endosymbiotic host. Due to this unique combination of genes, diatoms are taxonomically and functionally distinct from other algae and vascular plants and confer novel metabolic capabilities. Based on the genome annotation, we performed a genome-scale metabolic network reconstruction for the marine diatom Phaeodactylum tricornutum. Due to their endosymbiotic origin, diatoms possess a complex chloroplast structure which complicates the prediction of subcellular protein localization. Based on previous work we implemented a pipeline that exploits a series of bioinformatics tools to predict protein localization. The manually curated reconstructed metabolic network iLB1027_lipid accounts for 1,027 genes associated with 4,456 reactions and 2,172 metabolites distributed across six compartments. To constrain the genome-scale model, we determined the organism specific biomass composition in terms of lipids, carbohydrates, and proteins using Fourier transform infrared spectrometry. Our simulations indicate the presence of a yet unknown glutamine-ornithine shunt that could be used to transfer reducing equivalents generated by photosynthesis to the mitochondria. The model reflects the known biochemical composition of P. tricornutum in defined culture conditions and enables metabolic engineering strategies to improve the use of P. tricornutum for biotechnological applications

Computer aided synthesis: a game theoretic approach

In this invited contribution, we propose a comprehensive introduction to game theory applied in computer aided synthesis. In this context, we give some classical results on two-player zero-sum games and then on multi-player non zero-sum games. The simple case of one-player games is strongly related to automata theory on infinite words. All along the article, we focus on general approaches to solve the studied problems, and we provide several illustrative examples as well as intuitions on the proofs.Comment: Invitation contribution for conference "Developments in Language Theory" (DLT 2017

Intestinal fungi contribute to development of alcoholic liver disease

This study was supported in part by NIH grants R01 AA020703, U01 AA021856 and by Award Number I01BX002213 from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development (to B.S.). K.H. was supported by a DFG (Deutsche Forschungsgemeinschaft) fellowship (HO/ 5690/1-1). S.B. was supported by a grant from the Swiss National Science Foundation (P2SKP3_158649). G.G. received funding from the Yale Liver Center NIH P30 DK34989 and R.B. from NIAAA grant U01 AA021908. A.K. received support from NIH grants RC2 AA019405, R01 AA020216 and R01 AA023417. G.D.B. is supported by funds from the Wellcome Trust. We acknowledge the Human Tissue and Cell Research (HTCR) Foundation for making human tissue available for research and Hepacult GmbH (Munich, Germany) for providing primary human hepatocytes for in vitro analyses. We thank Dr. Chien-Yu Lin Department of Medicine, Fu-Jen Catholic University, Taiwan for statistical analysis.Peer reviewedPublisher PD

Developing Brain Vital Signs: Initial Framework for Monitoring Brain Function Changes over Time

Clinical assessment of brain function relies heavily on indirect behavior-based tests. Unfortunately, behavior-based assessments are subjective and therefore susceptible to several confounding factors. Event-related brain potentials (ERPs), derived from electroencephalography (EEG), are often used to provide objective, physiological measures of brain function. Historically, ERPs have been characterized extensively within research settings, with limited but growing clinical applications. Over the past 20 years, we have developed clinical ERP applications for the evaluation of functional status following serious injury and/or disease. This work has identified an important gap: the need for a clinically accessible framework to evaluate ERP measures. Crucially, this enables baseline measures before brain dysfunction occurs, and might enable the routine collection of brain function metrics in the future much like blood pressure measures today. Here, we propose such a framework for extracting specific ERPs as potential “brain vital signs.” This framework enabled the translation/transformation of complex ERP data into accessible metrics of brain function for wider clinical utilization. To formalize the framework, three essential ERPs were selected as initial indicators: (1) the auditory N100 (Auditory sensation); (2) the auditory oddball P300 (Basic attention); and (3) the auditory speech processing N400 (Cognitive processing). First step validation was conducted on healthy younger and older adults (age range: 22–82 years). Results confirmed specific ERPs at the individual level (86.81–98.96%), verified predictable age-related differences (P300 latency delays in older adults, p < 0.05), and demonstrated successful linear transformation into the proposed brain vital sign (BVS) framework (basic attention latency sub-component of BVS framework reflects delays in older adults, p < 0.05). The findings represent an initial critical step in developing, extracting, and characterizing ERPs as vital signs, critical for subsequent evaluation of dysfunction in conditions like concussion and/or dementia

A Graph Based Backtracking Algorithm for Solving General CSPs

Many AI tasks can be formalized as constraint satisfaction problems (CSPs), which involve finding values for variables subject to constraints. While solving a CSP is an NP-complete task in general, tractable classes of CSPs have been identified based on the structure of the underlying constraint graphs. Much effort has been spent on exploiting structural properties of the constraint graph to improve the efficiency of finding a solution. These efforts contributed to development of a class of CSP solving algorithms called decomposition algorithms. The strength of CSP decomposition is that its worst-case complexity depends on the structural properties of the constraint graph and is usually better than the worst-case complexity of search methods. Its practical application is limited, however, since it cannot be applied if the CSP is not decomposable. In this paper, we propose a graph based backtracking algorithm called omega-CDBT, which shares merits and overcomes the weaknesses of both decomposition and search approaches