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  • 1
    Language: English
    In: The Journal of biological chemistry, 10 August 2012, Vol.287(33), pp.27290-301
    Description: Diverse stresses including starvation and muscle disuse cause skeletal muscle atrophy. However, the molecular mechanisms of muscle atrophy are complex and not well understood. Here, we demonstrate that growth arrest and DNA damage-inducible 45a protein (Gadd45a) is a critical mediator of muscle atrophy. We identified Gadd45a through an unbiased search for potential downstream mediators of the stress-inducible, pro-atrophy transcription factor ATF4. We show that Gadd45a is required for skeletal muscle atrophy induced by three distinct skeletal muscle stresses: fasting, muscle immobilization, and muscle denervation. Conversely, forced expression of Gadd45a in muscle or cultured myotubes induces atrophy in the absence of upstream stress. We show that muscle-specific ATF4 knock-out mice have a reduced capacity to induce Gadd45a mRNA in response to stress, and as a result, they undergo less atrophy in response to fasting or muscle immobilization. Interestingly, Gadd45a is a myonuclear protein that induces myonuclear remodeling and a comprehensive program for muscle atrophy. Gadd45a represses genes involved in anabolic signaling and energy production, and it induces pro-atrophy genes. As a result, Gadd45a reduces multiple barriers to muscle atrophy (including PGC-1α, Akt activity, and protein synthesis) and stimulates pro-atrophy mechanisms (including autophagy and caspase-mediated proteolysis). These results elucidate a critical stress-induced pathway that reprograms muscle gene expression to cause atrophy.
    Keywords: Gene Expression Regulation ; Stress, Physiological ; Cell Cycle Proteins -- Metabolism ; Cell Nucleus -- Metabolism ; Muscle Proteins -- Metabolism ; Muscle, Skeletal -- Metabolism ; Muscular Atrophy -- Metabolism ; Nuclear Proteins -- Metabolism
    E-ISSN: 1083-351X
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  • 2
    In: Movement Disorders, August 2015, Vol.30(9), pp.1229-1236
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1002/mds.26251/abstract Byline: Yu Zhang, I-Wei Wu, Shannon Buckley, Christopher S. Coffey, Eric Foster, Susan Mendick, John Seibyl, John Seibyl Keywords: Parkinson's disease; MRI; diffusion tensor imaging; diffusion tensor tractography; nigrostriatal pathway Abstract Background Parkinson's disease (PD) is histopathologically characterized by the loss of dopamine neurons in the substantia nigra pars compacta. The depletion of these neurons is thought to reduce the dopaminergic function of the nigrostriatal pathway, as well as the neural fibers that link the substantia nigra to the striatum (putamen and caudate), causing a dysregulation in striatal activity that ultimately leads to lack of movement control. Based on diffusion tensor imaging, visualizing this pathway and measuring alterations of the fiber integrity remain challenging. The objectives were to 1) develop a diffusion tensor tractography protocol for reliably tracking the nigrostriatal fibers on multicenter data; 2) test whether the integrities measured by diffusion tensor imaging of the nigrostriatal fibers are abnormal in PD; and 3) test whether abnormal integrities of the nigrostriatal fibers in PD patients are associated with the severity of motor disability and putaminal dopamine binding ratios. Methods Diffusion tensor tractography was performed on 50 drug-naive PD patients and 27 healthy control subjects from the international multicenter Parkinson's Progression Marker Initiative. Results Tractography consistently detected the nigrostriatal fibers, yielding reliable diffusion measures. Fractional anisotropy, along with radial and axial diffusivity of the nigrostriatal tract, showed systematic abnormalities in patients. In addition, variations in fractional anisotropy and radial diffusivity of the nigrostriatal tract were associated with the degree of motor deficits in PD patients. Conclusion Taken together, the findings imply that the diffusion tensor imaging characteristic of the nigrostriatal tract is potentially an index for detecting and staging of early PD. [c] 2015 International Parkinson and Movement Disorder Society Article Note: Relevant conflicts of interest/financial disclosures: Dr. Yu Zhang has no disclosures to report. Ms. I-Wei Wu has no disclosures to report. Mr. Shannon Buckley has no disclosures to report. Dr. Christopher S. Coffey has no disclosure to report. Dr. Eric Foster has no disclosures to report. Ms. Susan Mendick has no disclosures to report. Dr. John Seibyl has received research funding from Michael J. Fox Foundation for Parkinson's Research, consulting fees from GE Healthcare, Navidea Biopharmaceuticals, and Piramal Imaging. He has equity interest in Molecular Neuroimaging, LLC. Dr. Norbert Schuff receives research funding from Michael J. Fox Foundation for Parkinson's Research, National Institutes of Health, Department of Defense, and consulting honoraria from Eli Lilly. Funding agencies: The study was supported by the funding partners of the Parkinson's Progression Marker Initiative (PPMI) group. PPMI is sponsored by the Michael J. Fox Foundation for Parkinson's Research (MJFF) and is co-funded by MJFF, Abbot, Avid Radiopharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Covance, Elan Corporation, Eli Lilly & Co., F. Hoffman-La Roche, Ltd., GE Healthcare, Genentech, GlaxoSmithKline, Lundbeck, Merck, MesoScale, Pfizer and UCB. The study was also supported by an NIH grant (P41 EB015904). Full financial disclosures and author roles may be found in the online version of this article. The statistical analysis was conducted by Dr. Norbert Schuff, PhD..sub.1,2 Supporting information: Additional Supporting Information may be found in the online version of this article Additional Supporting Information may be found in the online version of this article at the publisher's web-site. CAPTION(S): Supporting Information
    Keywords: Parkinson'S Disease ; Mri ; Diffusion Tensor Imaging ; Diffusion Tensor Tractography ; Nigrostriatal Pathway
    ISSN: 0885-3185
    E-ISSN: 1531-8257
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  • 3
    Language: English
    In: PLoS ONE, 01 January 2016, Vol.11(10), p.e0165540
    Description: This study aimed to identify the utility of diffusion tensor imaging (DTI) in measuring the regional distribution of abnormal microstructural progression in patients with Parkinson's disease who were enrolled in the Parkinson's progression marker initiative (PPMI). One hundred and twenty two de-novo PD patients (age = 60.5±9) and 50 healthy controls (age = 60.6±11) had DTI scans at baseline and 12.6±1 months later. Automated image processing included an intra-subject registration of all time points and an inter-subjects registration to a brain atlas. Annualized rates of DTI variations including fractional anisotropy (FA), radial (rD) and axial (aD) diffusivity were estimated in a total of 118 white matter and subcortical regions of interest. A mixed effects model framework was used to determine the degree to which DTI changes differed in PD relative to changes in healthy subjects. Significant DTI changes were also tested for correlations with changes in clinical measures, dopaminergic imaging and CSF biomarkers in PD patients. Compared to normal aging, PD was associated with higher rates of FA reduction, rD and aD increases predominantly in the substantia nigra, midbrain and thalamus. The highest rates of FA reduction involved the substantia nigra (3.6±1.4%/year from baseline, whereas the highest rates of increased diffusivity involved the thalamus (rD: 8.0±2.9%/year, aD: 4.0±1.5%/year). In PD patients, high DTI changes in the substantia nigra correlated with increasing dopaminergic deficits as well as with declining α-synuclein and total tau protein concentrations in cerebrospinal fluid. Increased DTI rates in the thalamus correlated with progressive decline in global cognition in PD. The results suggest that higher rates of regional microstructural degeneration are potential markers of PD progression.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 4
    In: Diabetes Care, 2018, Vol.41(5), p.1001-1008
    Description: OBJECTIVE Attaining glycemic targets without severe hypoglycemic events (SHEs) is a challenging treatment goal for patients with type 1 diabetes complicated by impaired awareness of hypoglycemia (IAH). The CIT Consortium Protocol 07 (CIT-07) trial showed islet transplantation to be an effective treatment for subjects with IAH and intractable SHEs. We evaluated health-related quality of life (HRQOL), functional health status, and health utility before and after pancreatic islet transplantation in CIT-07 trial participants. RESEARCH DESIGN AND METHODS Four surveys, the Diabetes Distress Scale (DDS), the Hypoglycemic Fear Survey (HFS), the Short Form 36 Health Survey (SF-36), and the EuroQoL 5 Dimensions (EQ-5D), were administered repeatedly before and after islet transplantation. Summary statistics and longitudinal modeling were used to describe changes in survey scores from baseline and to characterize change in relation to a minimally important difference (MID) threshold of half an SD. RESULTS Improvements in condition-specific HRQOL met the MID threshold. Reductions from baseline in the DDS total score and its four DDS subscales (all P ≤ 0.0013) and in the HFS total score and its two subscales (all P 〈 0.0001) were observed across all time points. Improvements were observed after both 1 and 2 years for the EQ-5D visual analog scale (both P 〈 0.0001). CONCLUSIONS In CIT-07, 87.5% of the subjects achieved the primary end point of freedom from SHE along with glycemic control (HbA 1c 〈7% [〈53 mmol/mol]) at 1 year post–initial islet transplantation. The same subjects reported consistent, statistically significant, and clinically meaningful improvements in condition-specific HRQOL as well as self-assessments of overall health.
    Keywords: 0407 ; Clinical Care/Education/Nutrition/Psychosocial Research
    ISSN: 0149-5992
    E-ISSN: 1935-5548
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  • 5
    Language: English
    In: Journal of Infectious Diseases, Sept 1, 2013, Vol.208(5), p.720(8)
    Keywords: Haemophilus Influenzae -- Genetic Aspects ; Haemophilus Influenzae -- Research ; Genetic Variation -- Research
    ISSN: 0022-1899
    Source: Cengage Learning, Inc.
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  • 6
    Article
    Article
    In: Nature, 1990, Vol.343(6259), p.600
    Description: SIR-Capabilities in scanning tunnelling and atomic force microscopy (STM and AFM) depend on probe-tip properties, but tip properties are at present poorly controlled; suitable tips have poor reproducibility at the atomic level. AFMs with tips characterized...
    Keywords: New York ; Atomic Force Microscopy ; Tips ; Ligands ; Reproducibility ; Atomic Force Microscopy ; Microscopy ; Binding Sites ; Spring Constant ; Deformation ; Personal Communication ; Proteins;
    ISSN: 0028-0836
    E-ISSN: 1476-4687
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  • 7
    In: Movement Disorders, June 2015, Vol.30(7), pp.919-927
    Description: UNLABELLED: This study was undertaken to determine the prevalence and correlates of cognitive impairment (CI) and neuropsychiatric symptoms (NPS) in early, untreated patients with Parkinson's disease (PD).BACKGROUND: Both CI and NPS are common in PD and impact disease course and quality of life. However, limited knowledge is available about cognitive abilities and NPS.METHODS: Parkinson's Progression Markers Initiative (PPMI) is a multi-site study of early, untreated PD patients and healthy controls (HCs), the latter with normal cognition. At baseline, participants were assessed with a neuropsychological battery and for symptoms of depression, anxiety, impulse control disorders (ICDs), psychosis, and apathy.RESULTS: Baseline data of 423 PD patients and 196 HCs yielded no between-group differences in demographic characteristics. Twenty-two percent of PD patients met the PD-recommended screening cutoff for CI on the Montral Cognitive Assessment (MoCA), but only 9% met detailed neuropsychological testing criteria for mild cognitive impairment (MCI)-level impairment. The PD patients were more depressed than HCs (P 〈 0.001), with twice as many (14% vs. 7%) meeting criteria for clinically significant depressive symptoms. The PD patients also experienced more anxiety (P 〈 0.001) and apathy (P 〈 0.001) than HCs. Psychosis was uncommon in PD (3%), and no between-group difference was seen in ICD symptoms (P = 0.51).CONCLUSIONS: Approximately 10% of PD patients in the early, untreated disease state met traditional criteria of CI, which is a lower frequency compared with previous studies. Multiple dopaminergic-dependent NPS are also more common in these patients compared with the general population, but others associated with dopamine replacement therapy are not or are rare. Future analyses of this cohort will examine biological predictors and the course of CI and NPS. © 2015 International Parkinson and Movement Disorder Society.
    Keywords: Anxiety ; Apathy ; Cognition ; Depression ; Impulse Control Disorder ; Parkinson'S Disease ; Psychosis
    ISSN: 0885-3185
    E-ISSN: 1531-8257
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  • 8
    Language: English
    In: BMC Genomics, 01 June 2011, Vol.12(1), p.290
    Description: Abstract Background Honey bees are a mainstay of agriculture, contributing billions of dollars through their pollination activities. Bees have been a model system for sociality and group behavior for decades but only recently have molecular techniques been brought to study this fascinating and valuable organism. With the release of the first draft of its genome in 2006, proteomics of bees became feasible and over the past five years we have amassed in excess of 5E+6 MS/MS spectra. The lack of a consolidated platform to organize this massive resource hampers our ability, and that of others, to mine the information to its maximum potential. Results Here we introduce the Honey Bee PeptideAtlas, a web-based resource for visualizing mass spectrometry data across experiments, providing protein descriptions and Gene Ontology annotations where possible. We anticipate that this will be helpful in planning proteomics experiments, especially in the selection of transitions for selected reaction monitoring. Through a proteogenomics effort, we have used MS/MS data to anchor the annotation of previously undescribed genes and to re-annotate previous gene models in order to improve the current genome annotation. Conclusions The Honey Bee PeptideAtlas will contribute to the efficiency of bee proteomics and accelerate our understanding of this species. This publicly accessible and interactive database is an important framework for the current and future analysis of mass spectrometry data.
    Keywords: Biology
    ISSN: 1471-2164
    E-ISSN: 1471-2164
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  • 9
    Language: English
    In: International Journal of Communications, Network and Systems Sciences (IJCNS), Feb, 2010, Vol.3(2), p.107(9)
    Description: NOAA (National Oceanic and Atmospheric Administration)--LEO environmental satellites provide continuous coverage of Earth, supplying high-resolution global meteorological, oceanic and space observation data. In addition, these satellites are part of the international COSPAS--SARSAT program, which aides search and rescue teams worldwide. The USA segment, referred to as SARSAT (Search and Rescue Satellite Aided Tracking) system, is designed to provide distress alert and location data to assist on search and rescue operations. SARSAT locates distress beacons (406MHz) activated at distress locations. The system calculates a location of the distress event using Doppler processing techniques. Processed data is continuously retransmitted through the SARSAT downlink to Local User Terminals (LUT) when satellites are in view. The downlink adjacent interference is expected when two satellites operate in close proximity and share the same frequency. The downlinks of all SARSAT LEO satellites use the same 1544.5 MHz frequency. In cases where the satellites are within the main lobe of the local user terminal antenna, transmissions from adjacent satellites act as interference to one-another, effectively decreasing the signal-to-noise ratio of the desired downlink. This can result in missed distress beacon bursts or no stored solutions received at the LUT, consequently no data is provided about a distress location. Analysis on interference prediction, impacts on system operation and recommendations for mitigating interference periods where the duration may be significant, are presented in this paper. Keywords: LEO, LUT, Beacon, Doppler, Satellite, Adjacent, Interference
    Keywords: Doppler Effect -- Usage ; Optical Interference -- Analysis ; Satellite Communications -- Analysis
    ISSN: 1913-3715
    Source: Cengage Learning, Inc.
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  • 10
    In: Respirology, January 2014, Vol.19(1), pp.116-121
    Description: On a population basis, influenza activity is associated with asthma hospitalizations in the United States, and this association can be exploited to more accurately forecast asthma admissions. Our results suggest that improvements in influenza surveillance, prevention and treatment may help predict and decrease hospitalizations of asthma patients.
    Keywords: Asthma ; Forecasting ; Health‐Care Utilization ; Influenza ; Resource Allocation
    ISSN: 1323-7799
    E-ISSN: 1440-1843
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