Characterizing the inhibition of mammalian intestinal α-glucosidases by enantiomeric iminosugars 1,4-dideoxy-1,4-imino-L-arabinatol and 1,4-dideoxy-1,4-imino-D-arabinatol

Sucrase isomaltase (SI) and maltase glucoamylase (MGAM) are both large Family 31 glycoside hydrolases with α-glucogenic activity (Cantarel et al., 2009; Lombard et al., 2014). Mammalian SI and MGAM, expressed predominantly in the small intestine, play essential roles in the process of starch digestion. Because their activities directly control the rate of α-glucogenesis in the small intestine, they also pose a useful target for the design of α-glucosidase inhibitors, a class of drugs useful for the treatment of type 2 diabetes and other metabolic disorders. The purpose of this work was to characterize inhibition kinetics for enantiomeric pyrrolidine iminosugars 1,4-dideoxy-1,4-imino-L-arabinatol (LAB-1) and 1,4-dideoxy-1,4-imino-D-arabinatol (DAB-1) with N- and C-terminal catalytic subunits of SI and MGAM, as well as for an additional C-terminal MGAM isoform, in the presence of three different substrates. Kinetic analysis indicates that LAB-1 is a more potent inhibitor of maltose and PNP-glucose hydrolysis than is DAB-1. Both mixed and competitive inhibition kinetics are observed for varying combinations of inhibitor, enzyme, and substrate. A general hypothesis regarding the binding of each of the two inhibitors is presented. Additionally, evidence for substrate inhibition of palatinose hydrolysis for Nt-SI and Nt-MGAM is reported and discussed

Virus found in a boreal lake links ssDNA and dsDNA viruses

Viruses have impacted the biosphere in numerous ways since the dawn of life. However, the evolution, genetic, structural, and taxonomic diversity of viruses remain poorly understood, in part because sparse sampling of the virosphere has concentrated mostly on exploring the abundance and diversity of dsDNA viruses. Furthermore, viral genomes are highly diverse, and using only the current sequence-based methods for classifying viruses and studying their phylogeny is complicated. Here we describe a virus, FLiP (Flavobacterium-infecting, lipid-containing phage), with a circular ssDNA genome and an internal lipid membrane enclosed in the icosahedral capsid. The 9,174-nt-long genome showed limited sequence similarity to other known viruses. The genetic data imply that this virus might use replication mechanisms similar to those found in other ssDNA replicons. However, the structure of the viral major capsid protein, elucidated at near-atomic resolution using cryo-electron microscopy, is strikingly similar to that observed in dsDNA viruses of the PRD1-adenovirus lineage, characterized by a major capsid protein bearing two beta-barrels. The strong similarity between FLiP and another member of the structural lineage, bacteriophage PM2, extends to the capsid organization (pseudo T = 21 dextro) despite the difference in the genetic material packaged and the lack of significant sequence similarity.Peer reviewe

Daddy's girl

A 10-minute short fictional film, funded by the UK Film Council, about a 10-year-old girl preparing for her newly blind father to come home from hospital. Children often explore problems through play; the film examines how adults might misinterpret this as "naughtiness". The film was shot in Skegness, Mablethorpe, Louth and Lincoln

Cognitive rehabilitation in multiple sclerosis: A systematic review

Abstract Background Cognitive impairment is a common clinical feature of multiple sclerosis (MS) at both the earlier and later stages of the disease, and has a significant impact on patients' functional status and quality of life. The need to address this deficit should be taken into account in clinical practice and research studies. Objective To conduct an updated systematic review of all published studies of cognitive rehabilitation interventions in people with MS, including studies with methodological shortcomings, to highlight major strengths and weaknesses in the field and to provide directions for future research. Search methods We searched electronic databases (PubMed and Web of Science) for articles published in English up until January 2014. The reference lists of all identified articles were also searched to complete the initial list of references. Data extraction Articles were categorized into outcome measures: cognition, imaging, mood, fatigue, quality of life and self-perceived cognitive deficits. All articles were reviewed independently and assessed according to predetermined criteria. Results A total of 33 studies met the inclusion criteria of which 4 were of Level II-1 and none was Level I. Although the majority of these studies reported some improvements in cognitive abilities (N = 31), the evidence which has been reported in the literature remains inconclusive and no definite conclusions can be drawn about the effect of different types of interventions on cognitive rehabilitation outcomes (recommendation C). Conclusions This review identified conflicting findings in the published literature about the effectiveness of various forms of cognitive rehabilitation techniques used in patients with MS. Studies with more rigorous methodology are therefore needed to clarify which form of cognitive rehabilitation may lead to greater clinical improvement

Cognitive rehabilitation, self-management, psychotherapeutic and caregiver support interventions in progressive neurodegenerative conditions: a scoping review

BACKGROUND: Despite their potentially significant impact, cognitive disability may be overlooked in a number of progressive neurodegenerative conditions, as other difficulties dominate the clinical picture. OBJECTIVE: We examined the extent, nature and range of the research evidence relating to cognitive rehabilitation, self-management, psychotherapeutic and caregiver support interventions in Parkinsonian disorders, multiple sclerosis (MS), frontotemporal dementias (FTD), motor neuron disease and Huntington’s disease. METHODS: Scoping review based on searches of MEDLINE and CINAHL up to 15 March 2016. RESULTS: We included 140 eligible papers. Over half of the studies, and almost all the randomised controlled trials, related to MS, while a number of single case studies described interventions for people with FTD. CR interventions addressed functional ability, communication and interaction, behaviour or memory. The majority of psychotherapy interventions involved cognitive behavioural therapy for depression or anxiety. Self-management interventions were mainly available for people with MS. There were few reports of interventions specific to caregivers. Numerous methodological challenges were identified. CONCLUSIONS: The limited range of studies for all conditions except MS suggests a need firstly to synthesise systematically the available evidence across conditions and secondly to develop well-designed studies to provide evidence about the effectiveness of CR and other psychological interventions

A Computer Vision Approach to Digit Recognition on Pulp Bales

This paper described a computer vision approach for recognizing quality and producer information of pulp bales from digit series stamped on pulp bales. The digit recognition consist of three stages: segmentation of digit series, features extraction, and classification. Segmentation of digit series is based on image thresholding and Randomized Hough Transform. Digit segmentation produces six digit windows. In features extraction two band-pass derivate of Gaussian filters are used, and the resulting gradient field histograms are used after normalization in classification of digits. The digit in the test can be classified 93% correct with a multiple layer perceptron network. Classification results with three other well known classifiers are also reported.JRC.(ISIS)-Institute For Systems, Informatics And Safet

Symmetry Reduction in FEM Optics Modeling of Single and Periodic Nanostructures

Numerical optics modeling is an invaluable tool in the design of nanostructures for nanophotonics applications where diffraction effects often lead to complex dependency between the nanostructure geometry and its optical properties and response. In order to analyze, design, and optimize such nanostructures, computationally efficient numerical optics modeling methods are required. One way to improve the numerical performance is to exploit symmetries found in many optics problems. By identifying equivalencies and restrictions arising from symmetry, it can be possible to simplify the problem at hand, which is the essence of symmetry reduction. However, applying symmetry reduction in optics modeling problems is not trivial. To the best of our knowledge, symmetry reduction has so-far been applied in finite element method (FEM) optics models only in those specific cases where an incident plane wave shares symmetries with the nanostructure geometry. In this work, we show how to extend the symmetry reduction of FEM optics models to the case of nonsymmetric plane-wave incidence, demonstrate such reduction with numerical examples of incident plane wave absorption in a single nanowire and a periodic nanowire array, and discuss the achieved gains in computational efficiency.Peer reviewe