7 research outputs found
\u3ci\u3eParamecium bursaria\u3c/i\u3e Chlorella Virus 1 Proteome Reveals Novel Architectural and Regulatory Features of a Giant Virus
The 331 kilobase pairs chlorovirus PBCV-1 genome was re-sequenced and annotated to correct errors in the original 15 year old sequence; forty codons was considered the minimum protein size of an open reading frame. PBCV-1 encodes 416 predicted protein encoding sequences and 11 tRNAs. A proteome analysis was also conducted on highly purified PBCV-1 virions using two mass-spectrometry based protocols. The mass spectrometry-derived data were compared to PBCV-1 and its host Chlorella variabilis NC64A predicted proteomes. Combined, these analyses revealed 148 unique virus-encoded proteins associated with the virion (about 35% of the coding capacity of the virus) and one host protein. Some of these proteins appear to be structural/architectural, whereas others have enzymatic, chromatin modification and signal transduction functions. Most (106) of these proteins have no known function or homologs in the existing gene databases except as orthologs with other chloroviruses, phycodnaviruses and nuclear-cytoplasmic large DNA viruses. The genes encoding these proteins are dispersed throughout the virus genome and most are transcribed late or early late in the infection cycle, which is consistent with virion morphogenesis
Reversing cognitive–motor impairments in Parkinson’s disease patients using a computational modelling approach to deep brain stimulation programming
Deep brain stimulation in the subthalamic nucleus is an effective and safe surgical procedure that has been shown to reduce the motor dysfunction of patients with advanced Parkinson’s disease. Bilateral subthalamic nucleus deep brain stimulation, however, has been associated with declines in cognitive and cognitive–motor functioning. It has been hypothesized that spread of current to nonmotor areas of the subthalamic nucleus may be responsible for declines in cognitive and cognitive–motor functioning. The aim of this study was to assess the cognitive–motor performance in advanced Parkinson’s disease patients with subthalamic nucleus deep brain stimulation parameters determined clinically (Clinical) to settings derived from a patient-specific computational model (Model). Data were collected from 10 patients with advanced Parkinson’s disease bilaterally implanted with subthalamic nucleus deep brain stimulation systems. These patients were assessed off medication and under three deep brain stimulation conditions: Off, Clinical or Model based stimulation. Clinical stimulation parameters had been determined based on clinical evaluations and were stable for at least 6 months prior to study participation. Model-based parameters were selected to minimize the spread of current to nonmotor portions of the subthalamic nucleus using Cicerone Deep Brain Stimulation software. For each stimulation condition, participants performed a working memory (n-back task) and motor task (force tracking) under single- and dual-task settings. During the dual-task, participants performed the n-back and force-tracking tasks simultaneously. Clinical and Model parameters were equally effective in improving the Unified Parkinson’s disease Rating Scale III scores relative to Off deep brain stimulation scores. Single-task working memory declines, in the 2-back condition, were significantly less under Model compared with Clinical deep brain stimulation settings. Under dual-task conditions, force tracking was significantly better with Model compared with Clinical deep brain stimulation. In addition to better overall cognitive–motor performance associated with Model parameters, the amount of power consumed was on average less than half that used with the Clinical settings. These results indicate that the cognitive and cognitive–motor declines associated with bilateral subthalamic nucleus deep brain stimulation may be reversed, without compromising motor benefits, by using model-based stimulation parameters that minimize current spread into nonmotor regions of the subthalamic nucleus
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Implementation of preemptive DNA sequence–based pharmacogenomics testing across a large academic medical center: The Mayo-Baylor RIGHT 10K Study
The Mayo-Baylor RIGHT 10K Study enabled preemptive, sequence-based pharmacogenomics (PGx)-driven drug prescribing practices in routine clinical care within a large cohort. We also generated the tools and resources necessary for clinical PGx implementation and identified challenges that need to be overcome. Furthermore, we measured the frequency of both common genetic variation for which clinical guidelines already exist and rare variation that could be detected by DNA sequencing, rather than genotyping.Targeted oligonucleotide-capture sequencing of 77 pharmacogenes was performed using DNA from 10,077 consented Mayo Clinic Biobank volunteers. The resulting predicted drug response–related phenotypes for 13 genes, including CYP2D6 and HLA, affecting 21 drug–gene pairs, were deposited preemptively in the Mayo electronic health record.For the 13 pharmacogenes of interest, the genomes of 79% of participants carried clinically actionable variants in 3 or more genes, and DNA sequencing identified an average of 3.3 additional conservatively predicted deleterious variants that would not have been evident using genotyping.Implementation of preemptive rather than reactive and sequence-based rather than genotype-based PGx prescribing revealed nearly universal patient applicability and required integrated institution-wide resources to fully realize individualized drug therapy and to show more efficient use of health care resources