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  1. Article ; Online: Microbiome dynamics during the HI-SEAS IV mission, and implications for future crewed missions beyond Earth

    Alexander Mahnert / Cyprien Verseux / Petra Schwendner / Kaisa Koskinen / Christina Kumpitsch / Marcus Blohs / Lisa Wink / Daniela Brunner / Theodora Goessler / Daniela Billi / Christine Moissl-Eichinger

    Microbiome, Vol 9, Iss 1, Pp 1-

    2021  Volume 21

    Abstract: Abstract Background Human health is closely interconnected with its microbiome. Resilient microbiomes in, on, and around the human body will be key for safe and successful long-term space travel. However, longitudinal dynamics of microbiomes inside ... ...

    Abstract Abstract Background Human health is closely interconnected with its microbiome. Resilient microbiomes in, on, and around the human body will be key for safe and successful long-term space travel. However, longitudinal dynamics of microbiomes inside confined built environments are still poorly understood. Herein, we used the Hawaii Space Exploration Analog and Simulation IV (HI-SEAS IV) mission, a 1 year-long isolation study, to investigate microbial transfer between crew and habitat, in order to understand adverse developments which may occur in a future outpost on the Moon or Mars. Results Longitudinal 16S rRNA gene profiles, as well as quantitative observations, revealed significant differences in microbial diversity, abundance, and composition between samples of the built environment and its crew. The microbiome composition and diversity associated with abiotic surfaces was found to be rather stable, whereas the microbial skin profiles of individual crew members were highly dynamic, resulting in an increased microbiome diversity at the end of the isolation period. The skin microbiome dynamics were especially pronounced by a regular transfer of the indicator species Methanobrevibacter between crew members within the first 200 days. Quantitative information was used to track the propagation of antimicrobial resistance in the habitat. Together with functional and phenotypic predictions, quantitative and qualitative data supported the observation of a delayed longitudinal microbial homogenization between crew and habitat surfaces which was mainly caused by a malfunctioning sanitary facility. Conclusions This study highlights main routes of microbial transfer, interaction of the crew, and origins of microbial dynamics in an isolated environment. We identify key targets of microbial monitoring, and emphasize the need for defined baselines of microbiome diversity and abundance on surfaces and crew skin. Targeted manipulation to counteract adverse developments of the microbiome could be a highly important strategy to ensure safety during future space endeavors. Video abstract
    Keywords Confined built environments ; Isolation ; HI-SEAS ; Skin microbiome ; Indoor microbiome ; 16S rRNA gene amplicons ; Microbial ecology ; QR100-130
    Subject code 910
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Benefits of global mutant huntingtin lowering diminish over time in a Huntington’s disease mouse model

    Deanna M. Marchionini / Jeh-Ping Liu / Alberto Ambesi-Impiombato / Kimberly Kerker / Kim Cirillo / Mukesh Bansal / Rich Mushlin / Daniela Brunner / Sylvie Ramboz / Mei Kwan / Kirsten Kuhlbrodt / Karsten Tillack / Finn Peters / Leena Rauhala / John Obenauer / Jonathan R. Greene / Christopher Hartl / Vinod Khetarpal / Brenda Lager /
    Jim Rosinski / Jeff Aaronson / Morshed Alam / Ethan Signer / Ignacio Muñoz-Sanjuán / David Howland / Scott O. Zeitlin

    JCI Insight, Vol 7, Iss

    2022  Volume 20

    Abstract: We have developed an inducible Huntington’s disease (HD) mouse model that allows temporal control of whole-body allele-specific mutant huntingtin (mHtt) expression. We asked whether moderate global lowering of mHtt (~50%) was sufficient for long-term ... ...

    Abstract We have developed an inducible Huntington’s disease (HD) mouse model that allows temporal control of whole-body allele-specific mutant huntingtin (mHtt) expression. We asked whether moderate global lowering of mHtt (~50%) was sufficient for long-term amelioration of HD-related deficits and, if so, whether early mHtt lowering (before measurable deficits) was required. Both early and late mHtt lowering delayed behavioral dysfunction and mHTT protein aggregation, as measured biochemically. However, long-term follow-up revealed that the benefits, in all mHtt-lowering groups, attenuated by 12 months of age. While early mHtt lowering attenuated cortical and striatal transcriptional dysregulation evaluated at 6 months of age, the benefits diminished by 12 months of age, and late mHtt lowering did not ameliorate striatal transcriptional dysregulation at 12 months of age. Only early mHtt lowering delayed the elevation in cerebrospinal fluid neurofilament light chain that we observed in our model starting at 9 months of age. As small-molecule HTT-lowering therapeutics progress to the clinic, our findings suggest that moderate mHtt lowering allows disease progression to continue, albeit at a slower rate, and could be relevant to the degree of mHTT lowering required to sustain long-term benefits in humans.
    Keywords Neuroscience ; Medicine ; R
    Language English
    Publishing date 2022-10-01T00:00:00Z
    Publisher American Society for Clinical investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Multigram Synthesis and in Vivo Efficacy Studies of a Novel Multitarget Anti-Alzheimer’s Compound

    Irene Sola / Elisabet Viayna / Tània Gómez / Carles Galdeano / Matteo Cassina / Pelayo Camps / Margherita Romeo / Luisa Diomede / Mario Salmona / Pilar Franco / Mireille Schaeffer / Diego Colantuono / David Robin / Daniela Brunner / Nicole Taub / Birgit Hutter-Paier / Diego Muñoz-Torrero

    Molecules, Vol 20, Iss 3, Pp 4492-

    2015  Volume 4515

    Abstract: We describe the multigram synthesis and in vivo efficacy studies of a donepezil‒huprine hybrid that has been found to display a promising in vitro multitarget profile of interest for the treatment of Alzheimer’s disease (AD). Its synthesis features as ... ...

    Abstract We describe the multigram synthesis and in vivo efficacy studies of a donepezil‒huprine hybrid that has been found to display a promising in vitro multitarget profile of interest for the treatment of Alzheimer’s disease (AD). Its synthesis features as the key step a novel multigram preparative chromatographic resolution of intermediate racemic huprine Y by chiral HPLC. Administration of this compound to transgenic CL4176 and CL2006 Caenorhabditis elegans strains expressing human Aβ42, here used as simplified animal models of AD, led to a significant protection from the toxicity induced by Aβ42. However, this protective effect was not accompanied, in CL2006 worms, by a reduction of amyloid deposits. Oral administration for 3 months to transgenic APPSL mice, a well-established animal model of AD, improved short-term memory, but did not alter brain levels of Aβ peptides nor cortical and hippocampal amyloid plaque load. Despite the clear protective and cognitive effects of AVCRI104P4, the lack of Aβ lowering effect in vivo might be related to its lower in vitro potency toward Aβ aggregation and formation as compared with its higher anticholinesterase activities. Further lead optimization in this series should thus focus on improving the anti-amyloid/anticholinesterase activity ratio.
    Keywords disease-modifying anti-Alzheimer drugs ; multitarget drugs ; neuroprotection ; animal models of Alzheimer’s disease ; multigram preparative chromatographic resolution ; Organic chemistry ; QD241-441 ; Chemistry ; QD1-999 ; Science ; Q
    Subject code 540
    Language English
    Publishing date 2015-03-01T00:00:00Z
    Publisher Multidisciplinary Digital Publishing Institute
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Comprehensive Analysis of the 16p11.2 Deletion and Null Cntnap2 Mouse Models of Autism Spectrum Disorder.

    Daniela Brunner / Patricia Kabitzke / Dansha He / Kimberly Cox / Lucinda Thiede / Taleen Hanania / Emily Sabath / Vadim Alexandrov / Michael Saxe / Elior Peles / Alea Mills / Will Spooren / Anirvan Ghosh / Pamela Feliciano / Marta Benedetti / Alice Luo Clayton / Barbara Biemans

    PLoS ONE, Vol 10, Iss 8, p e

    2015  Volume 0134572

    Abstract: Autism spectrum disorder comprises several neurodevelopmental conditions presenting symptoms in social communication and restricted, repetitive behaviors. A major roadblock for drug development for autism is the lack of robust behavioral signatures ... ...

    Abstract Autism spectrum disorder comprises several neurodevelopmental conditions presenting symptoms in social communication and restricted, repetitive behaviors. A major roadblock for drug development for autism is the lack of robust behavioral signatures predictive of clinical efficacy. To address this issue, we further characterized, in a uniform and rigorous way, mouse models of autism that are of interest because of their construct validity and wide availability to the scientific community. We implemented a broad behavioral battery that included but was not restricted to core autism domains, with the goal of identifying robust, reliable phenotypes amenable for further testing. Here we describe comprehensive findings from two known mouse models of autism, obtained at different developmental stages, using a systematic behavioral test battery combining standard tests as well as novel, quantitative, computer-vision based systems. The first mouse model recapitulates a deletion in human chromosome 16p11.2, found in 1% of individuals with autism. The second mouse model harbors homozygous null mutations in Cntnap2, associated with autism and Pitt-Hopkins-like syndrome. Consistent with previous results, 16p11.2 heterozygous null mice, also known as Del(7Slx1b-Sept1)4Aam weighed less than wild type littermates displayed hyperactivity and no social deficits. Cntnap2 homozygous null mice were also hyperactive, froze less during testing, showed a mild gait phenotype and deficits in the three-chamber social preference test, although less robust than previously published. In the open field test with exposure to urine of an estrous female, however, the Cntnap2 null mice showed reduced vocalizations. In addition, Cntnap2 null mice performed slightly better in a cognitive procedural learning test. Although finding and replicating robust behavioral phenotypes in animal models is a challenging task, such functional readouts remain important in the development of therapeutics and we anticipate both our positive and negative findings ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 150
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Crowdsourcing digital health measures to predict Parkinson’s disease severity

    Solveig K. Sieberts / Jennifer Schaff / Marlena Duda / Bálint Ármin Pataki / Ming Sun / Phil Snyder / Jean-Francois Daneault / Federico Parisi / Gianluca Costante / Udi Rubin / Peter Banda / Yooree Chae / Elias Chaibub Neto / E. Ray Dorsey / Zafer Aydın / Aipeng Chen / Laura L. Elo / Carlos Espino / Enrico Glaab /
    Ethan Goan / Fatemeh Noushin Golabchi / Yasin Görmez / Maria K. Jaakkola / Jitendra Jonnagaddala / Riku Klén / Dongmei Li / Christian McDaniel / Dimitri Perrin / Thanneer M. Perumal / Nastaran Mohammadian Rad / Erin Rainaldi / Stefano Sapienza / Patrick Schwab / Nikolai Shokhirev / Mikko S. Venäläinen / Gloria Vergara-Diaz / Yuqian Zhang / the Parkinson’s Disease Digital Biomarker Challenge Consortium / Yuanjia Wang / Yuanfang Guan / Daniela Brunner / Paolo Bonato / Lara M. Mangravite / Larsson Omberg

    npj Digital Medicine, Vol 4, Iss 1, Pp 1-

    the Parkinson’s Disease Digital Biomarker DREAM Challenge

    2021  Volume 12

    Abstract: Abstract Consumer wearables and sensors are a rich source of data about patients’ daily disease and symptom burden, particularly in the case of movement disorders like Parkinson’s disease (PD). However, interpreting these complex data into so-called ... ...

    Abstract Abstract Consumer wearables and sensors are a rich source of data about patients’ daily disease and symptom burden, particularly in the case of movement disorders like Parkinson’s disease (PD). However, interpreting these complex data into so-called digital biomarkers requires complicated analytical approaches, and validating these biomarkers requires sufficient data and unbiased evaluation methods. Here we describe the use of crowdsourcing to specifically evaluate and benchmark features derived from accelerometer and gyroscope data in two different datasets to predict the presence of PD and severity of three PD symptoms: tremor, dyskinesia, and bradykinesia. Forty teams from around the world submitted features, and achieved drastically improved predictive performance for PD status (best AUROC = 0.87), as well as tremor- (best AUPR = 0.75), dyskinesia- (best AUPR = 0.48) and bradykinesia-severity (best AUPR = 0.95).
    Keywords Computer applications to medicine. Medical informatics ; R858-859.7
    Subject code 006
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Human glia can both induce and rescue aspects of disease phenotype in Huntington disease

    Abdellatif Benraiss / Su Wang / Stephanie Herrlinger / Xiaojie Li / Devin Chandler-Militello / Joseph Mauceri / Hayley B. Burm / Michael Toner / Mikhail Osipovitch / Qiwu Jim Xu / Fengfei Ding / Fushun Wang / Ning Kang / Jian Kang / Paul C. Curtin / Daniela Brunner / Martha S. Windrem / Ignacio Munoz-Sanjuan / Maiken Nedergaard /
    Steven A. Goldman

    Nature Communications, Vol 7, Iss 1, Pp 1-

    2016  Volume 13

    Abstract: The contribution of glia to Huntington's disease is unclear. The authors show that human glial progenitor cells (GPCs) expressing mutant huntingtin impair motor performance when engrafted into wild type mice, and wild type human GPCs ameliorate disease ... ...

    Abstract The contribution of glia to Huntington's disease is unclear. The authors show that human glial progenitor cells (GPCs) expressing mutant huntingtin impair motor performance when engrafted into wild type mice, and wild type human GPCs ameliorate disease phenotypes when engrafted into an HD mouse model.
    Keywords Science ; Q
    Language English
    Publishing date 2016-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Comprehensive behavioral testing in the R6/2 mouse model of Huntington's disease shows no benefit from CoQ10 or minocycline.

    Liliana B Menalled / Monica Patry / Natalie Ragland / Phillip A S Lowden / Jennifer Goodman / Jennie Minnich / Benjamin Zahasky / Larry Park / Janet Leeds / David Howland / Ethan Signer / Allan J Tobin / Daniela Brunner

    PLoS ONE, Vol 5, Iss 3, p e

    2010  Volume 9793

    Abstract: Previous studies of the effects of coenzyme Q10 and minocycline on mouse models of Huntington's disease have produced conflicting results regarding their efficacy in behavioral tests. Using our recently published best practices for husbandry and testing ... ...

    Abstract Previous studies of the effects of coenzyme Q10 and minocycline on mouse models of Huntington's disease have produced conflicting results regarding their efficacy in behavioral tests. Using our recently published best practices for husbandry and testing for mouse models of Huntington's disease, we report that neither coenzyme Q10 nor minocycline had significant beneficial effects on measures of motor function, general health (open field, rotarod, grip strength, rearing-climbing, body weight and survival) in the R6/2 mouse model. The higher doses of minocycline, on the contrary, reduced survival. We were thus unable to confirm the previously reported benefits for these two drugs, and we discuss potential reasons for these discrepancies, such as the effects of husbandry and nutrition.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2010-03-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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