Metformin treatment reduces motor and neuropsychiatric phenotypes in the zQ175 mouse model of Huntington disease

Ana Sanchis,María Adelaida García-Gimeno,Antonio José Cañada-Martínez,María Dolores Sequedo,José María Millán,Pascual Sanz,Rafael P. Vázquez-Manrique 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

Huntington disease is a neurodegenerative condition for which there is no cure to date. Activation of AMP-activated protein kinase has previously been shown to be beneficial in in vitro and in vivo models of Huntington’s disease. Moreover, a recent cross-sectional study demonstrated that treatment with metformin, a well-known activator of this enzyme, is associated with better cognitive scores in patients with this disease. We performed a preclinical study using metformin to treat phenotypes of the zQ175 mouse model of Huntington disease. We evaluated behavior (motor and neuropsychiatric function) and molecular phenotypes (aggregation of mutant huntingtin, levels of brain-derived neurotrophic factor, neuronal inflammation, etc.). We also used two models of polyglutamine toxicity in Caenorhabditis elegans to further explore potential mechanisms of metformin action. Our results provide strong evidence that metformin alleviates motor and neuropsychiatric phenotypes in zQ175 mice. Moreover, metformin intake reduces the number of nuclear aggregates of mutant huntingtin in the striatum. The expression of brain-derived neurotrophic factor, which is reduced in mutant animals, is partially restored in metformin-treated mice, and glial activation in mutant mice is reduced in metformin-treated animals. In addition, using worm models of polyglutamine toxicity, we demonstrate that metformin reduces polyglutamine aggregates and restores neuronal function through mechanisms involving AMP-activated protein kinase and lysosomal function. Our data indicate that metformin alleviates the progression of the disease and further supports AMP-activated protein kinase as a druggable target against Huntington’s disease.

Rheology and gel point of the enzymatic hydrolysis of urea in the presence of urease

R. Serrato-Millán,L. Medina-Torres,F. Calderas,B.L. España-Sánchez,M. Estevez,A.R. Hernandez-Martínez,M. Cruz-Soto,I.C. Sánchez,R. Gómez-García,I. Sánchez-Betancourt,M.C. Velasquillo-Martínez,G. Luna- 한국유변학회 2017 Korea-Australia rheology journal Vol.29 No.1

This study reports on the rheology of the gelation kinetics of raw chitosan (CTS) solutions (2% w/v) produced by enzymatic hydrolysis of urea at different urea concentrations (40, 50, 60, 80, and 100 mM) in the presence of urease at 1 U/mL. Viscoelastic parameters and pH values were evaluated during gelation process and the rheological properties of CTS hydrogels produced were monitored after 24 h at 37°C to simulate human body temperatures. pH measurements suggest that above some critical urea concentration (50 mM) the time required (tgel) to reach the critical pH gelation shows no dependence on urea concentration (tgel was ca. 70 minutes). Above 50 mM of urea concentration, CTS hydrogels exhibit an elastic modulus G' higher than the viscous modulus G'' with no frequency dependence characteristic of a gel behavior. Gelation kinetics analyzed by rheology suggest that the G' (i.e., structure) development depends on urea concentration during solution neutralization.

Status of the JEFF Nuclear Data Library

A. J. Koning,E. Bauge,C. J. Dean,E. Dupont,U. Fischer,R. A. Forrest,R. Jacqmin,H. Leeb,M. A. Kellett,R. W. Mills,C. Nordborg,M. Pescarini,Y. Rugama,P. Rullhusen 한국물리학회 2011 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.59 No.23

The status of the Joint Evaluated Fission and Fusion file (JEFF) is described. Recently, the JEFF-3.1.1 nuclear data library was released and shortly after adopted by the French nuclear power industry for inclusion in their production and analysis codes. Recent updates include actinide evaluations, materials evaluations that have emerged from various European nuclear data projects, the activation library, the decay data and fission yield sub-libraries, and fusion-related data files from the European F4E project. The revisions were motivated by the availability of new measurements, modelling capabilities and trends from integral experiments. Validations have been performed, mainly for criticality, reactivity temperature coefficients, fuel inventory, decay heat and shielding of thermal and fast systems. The next release of the library, JEFF-3.2, will be discussed. This will contain among others a significant increase of covariance data evaluations, modern evaluations for various structural materials, a larger emphasis on minor actinides and addition of high-quality gamma production data for many fission products.

Direct Determination of Field Emission across the Heterojunctions in a ZnO/Graphene Thin-Film Barristor

Mills, Edmund M.,Min, Bok Ki,Kim, Seong K.,Kim, Seong Jun,Kang, Min-A,Song, Wooseok,Myung, Sung,Lim, Jongsun,An, Ki-Seok,Jung, Jongwan,Kim, Sangtae American Chemical Society 2015 ACS APPLIED MATERIALS & INTERFACES Vol.7 No.33

<P>Graphene barristors are a novel type of electronic switching device with excellent performance, which surpass the low on–off ratios that limit the operation of conventional graphene transistors. In barristors, a gate bias is used to vary graphene’s Fermi level, which in turn controls the height and resistance of a Schottky barrier at a graphene/semiconductor heterojunction. Here we demonstrate that the switching characteristic of a thin-film ZnO/graphene device with simple geometry results from tunneling current across the Schottky barriers formed at the ZnO/graphene heterojunctions. Direct characterization of the current–voltage−temperature relationship of the heterojunctions by ac-impedance spectroscopy reveals that this relationship is controlled predominantly by field emission, unlike most graphene barristors in which thermionic emission is observed. This governing mechanism makes the device unique among graphene barristors, while also having the advantages of simple fabrication and outstanding performance.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/aamick/2015/aamick.2015.7.issue-33/acsami.5b03380/production/images/medium/am-2015-03380u_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/am5b03380'>ACS Electronic Supporting Info</A></P>

Next-generation approaches to the microbial ecology of food fermentations

( Nicholas A. Bokulich ),( David A. Mills ) 생화학분자생물학회(구 한국생화학분자생물학회) 2012 BMB Reports Vol.45 No.7

Food fermentations have enhanced human health since the dawn of time and remain a prevalent means of food processing and preservation. Due to their cultural and nutritional importance, many of these foods have been studied in detail using molecular tools, leading to enhancements in quality and safety. Furthermore, recent advances in high-throughput sequencing technology are revolutionizing the study of food microbial ecology, deepening insight into complex fermentation systems. This review provides insight into novel applications of select molecular techniques, particularly next-generation sequencing technology, for analysis of microbial communities in fermented foods. We present a guideline for integrated molecular analysis of food microbial ecology and a starting point for implementing next-generation analysis of food systems. [BMB Reports 2012;45(7): 377-389]

Telegerontology? and Mobile Robot Companion

J. C. Mill?n-Calenti,A. Maseda,A. Badii,T. Lorenzo,M. Villanueva,C. P?rez 한국노년학연구회 2009 한국 노년학연구 Vol.18 No.-

Technological progress and changes in society, together with an increasingly ageing population, especially in developed countries, have demanded solutions to the problems linked to this aging and the increasing number of elderly people. We describe two assistive systems being currently developed and improved; the first one `Telegerontology?” is a gerontological resource that through the Internet, facilitates different functionalities at home or in institutions such as physical and cognitive intervention, and providing support to professionals. The second one `CompanionAble” consists of an integrated system Smart-home and intelligent robot to give support to the elderly with mild cognitive impairment and their caregivers. The system, which can move about in the home, incorporates functionalities such as an application of cognitive stimulation, an event agenda and a video-conference system. In conclusion, we consider that though the evolution of new technologies for the support of elderly and/or disabled people has experienced a great advance in the last years, and despite new future system as Telegerontology? or CompanionAble, human being support is still necessary for achieving their objectives. This fact is very positive because we ensure the presence of a health professional behind each patient.

The P25 TiO₂/4-chlorophenol photocatalytic system: Spectral sensitivity or lamp artefact?

Lee, S.K.,Mills, A.,O'Rourke, C. Elsevier Sequoia 2017 Journal of photochemistry and photobiology Chemist Vol. No.

The photocatalysed mineralisation of 4-chlorophenol, 4-CP, by P25 TiO<SUB>2</SUB> is a well-studied photocatalytic system. A previous paper (Emeline et al., J. Phys. Chem. B, 2000, 104, 11202) reported an action spectrum, i.e. photonic efficiency, η, vs. excitation wavelength, λ(ex), for the P25/4-CP system, that exhibited a series of peaks and troughs which, it was proposed, provided evidence of P25 spectral sensitivity. However, in this re-examination it is shown that the peaks and troughs in the action spectrum occur in the regions of the troughs and peaks in the emission spectrum of the Xe/Hg lamp used by these researchers. The dependencies of η, and quantum yield, φ, upon incident light intensity, ρ, in semiconductor-sensitised photocatalytic systems are considered and a rationale provided that suggests the action spectrum reported by Emerline et al. is actually due to the variation in ρ in the emission spectrum of the Xe/Hg lamp. In order to test the latter hypothesis, the action spectrum of the same P25/4-CP system is determined, but this time using a Xe lamp; the latter action spectrum has no peaks and troughs and corresponds closely to that of the diffuse reflectance spectrum of the P25 dispersion as expected if there is no spectral sensitivity. This action spectrum, and similar results reported by others for this and other test pollutants, provides strong evidence that the claim of spectral sensitivity for the P25/4-CP system is unjustified, based on the reported action spectrum of Emeline et al., since the latter is due to the spectral variation in irradiance of the Xe/Hg excitation source employed in the original study.

An Overview of Seabed Storage Methods for Pipelines and Other Oil and Gas Equipment

( M. C. Fatah ),( A. Mills ),( A. Darwin ),( C. Selman ) 한국부식방식학회 2017 Corrosion Science and Technology Vol.16 No.2

In the construction of subsea oil and gas developments, it is increasingly common that subsea oil and gas equipment will be installed in subsea well before final hookup and production. Installation of wellheads, subsea hardware, pipelines, and surface facilities (platforms, FPSO, FLNG, connected terminals, or gas plants) are increasingly driven by independent cost and vessel availability schedules; this gives rise to requirements that the subsea facilities must be stored in the seabed for a specific time. In addition, schedule delays, particularly in the installation or startup of the connected platform, FPSO, FLNG, or onshore plant may cause unexpected extensions of the intended storage period. Currently, there are two methods commonly used for storage subsea facilities in the seabed: dry parking and wet parking. Each method has its own risks, challenges, and implications for the facility life and its integrity. The corrosion management and preservation method selection is a crucial factor to be considered in choosing the appropriate storage method and achieving a successful seabed storage. An overview of those factors is presented, along with a discussion on the internal corrosion threats and assessments.

Assistive Technologies for Supporting Elderly People at Home: Telegerontology?

P. Su?rez,J. C. Mill?n-Calenti,A. L?pez-Vilar?n,I. Gonz?lez-Abraldes,M. Villanueva-Sampayo,A. Maseda 한국노년학연구회 2010 한국 노년학연구 Vol.19 No.-

The aging of the population worldwide implies an increase in the number of cognitive impairment associated diseases in the elderly. On the other hand, the number of informal caregivers is decreasing and consequently, we must guarantee the existence of enough social and health services for all the population in the immediate future. The new technologies allow us the development of more advanced instruments for gerontological intervention for both patients and caregivers. These new systems help to prevent the lack of home assistance, and thanks to the Internet connection, we avoid the disadvantages of the geographic dispersion of the population. In this article, we describe Telegerontology?, a new home attention tool for patients and caregivers. It integrates different functionalities related to physical, cognitive and medical intervention it works like a family support thanks to the professionals/patients communication, and integrates an advanced emergency system within a domotic environment. This system improves the traditional telecare since it, actually, has more sophisticated services and a higher quality of home support.

Identification and Accurate Quantitation of Biological Oligosaccharide Mixtures

Strum, John S.,Kim, Jaehan,Wu, Shuai,De Leoz, Maria Lorna A.,Peacock, Kyle,Grimm, Rudolf,German, J. Bruce,Mills, David A.,Lebrilla, Carlito B. American Chemical Society 2012 ANALYTICAL CHEMISTRY - Vol.84 No.18

<P>Structure-specific characterization and quantitation is often required for effective functional studies of oligosaccharides. Inside the gut, HMOs are preferentially bound and catabolized by the beneficial bacteria. HMO utility by these bacteria employs structure-specific catabolism based on a number of glycosidases. Determining the activity of these enzymes requires accurate quantitation of a large number of structures. In this study, we describe a method for the quantitation of human milk oligosaccharide (HMO) structures employing LC/MS and isotopically labeled internal standards. Data analysis was accomplished with a newly developed software tool, LC/MS Searcher, that employs a reference structure library to process LC/MS data yielding structural identification with accurate quantitation. The method was used to obtain a meta-enzyme analysis of bacteria, the simultaneous characterization of all glycosidases employed by bacteria for the catabolism of milk oligosaccharides. Analysis of consumed HMO structures confirmed the utility of a β-1,3-galactosidase in <I>Bifidobacterium longum subsp. infantis</I> ATCC 15697 (<I>B. infantis</I>). In comparison, <I>Bifidobacterium breve</I> ATCC 15700 showed significantly less HMO catabolic activity compared to <I>B. infantis</I>.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancham/2012/ancham.2012.84.issue-18/ac301128s/production/images/medium/ac-2012-01128s_0002.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ac301128s'>ACS Electronic Supporting Info</A></P>