The Time Course of ERP Differences Between Musicians and Nonmusicians in Major-Minor Classification of Melodies

Identification and classification of cis-regulatory elements in the amphipod crustacean Parhyale hawaiensis

10.1101/2021.09.16.460328 ◽

2021 ◽

Author(s):

Dennis A Sun ◽

Nipam H Patel

Keyword(s):

Gene Expression ◽

Genome Annotation ◽

Time Course ◽

Regulatory Elements ◽

Rna Seq ◽

Genome Wide ◽

Long Read ◽

Amphipod Crustacean ◽

Accessible Chromatin

AbstractEmerging research organisms enable the study of biology that cannot be addressed using classical “model” organisms. The development of novel data resources can accelerate research in such animals. Here, we present new functional genomic resources for the amphipod crustacean Parhyale hawaiensis, facilitating the exploration of gene regulatory evolution using this emerging research organism. We use Omni-ATAC-Seq, an improved form of the Assay for Transposase-Accessible Chromatin coupled with next-generation sequencing (ATAC-Seq), to identify accessible chromatin genome-wide across a broad time course of Parhyale embryonic development. This time course encompasses many major morphological events, including segmentation, body regionalization, gut morphogenesis, and limb development. In addition, we use short- and long-read RNA-Seq to generate an improved Parhyale genome annotation, enabling deeper classification of identified regulatory elements. We leverage a variety of bioinformatic tools to discover differential accessibility, predict nucleosome positioning, infer transcription factor binding, cluster peaks based on accessibility dynamics, classify biological functions, and correlate gene expression with accessibility. Using a Minos transposase reporter system, we demonstrate the potential to identify novel regulatory elements using this approach, including distal regulatory elements. This work provides a platform for the identification of novel developmental regulatory elements in Parhyale, and offers a framework for performing such experiments in other emerging research organisms.Primary Findings-Omni-ATAC-Seq identifies cis-regulatory elements genome-wide during crustacean embryogenesis-Combined short- and long-read RNA-Seq improves the Parhyale genome annotation-ImpulseDE2 analysis identifies dynamically regulated candidate regulatory elements-NucleoATAC and HINT-ATAC enable inference of nucleosome occupancy and transcription factor binding-Fuzzy clustering reveals peaks with distinct accessibility and chromatin dynamics-Integration of accessibility and gene expression reveals possible enhancers and repressors-Omni-ATAC can identify known and novel regulatory elements

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Pharmacokinetics and pharmacodynamics of natalizumab in pediatric patients with RRMS

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000591 ◽

2019 ◽

Vol 6 (5) ◽

pp. e591 ◽

Cited By ~ 1

Author(s):

Angelo Ghezzi ◽

Giancarlo Comi ◽

Luigi Maria Grimaldi ◽

Lucia Moiola ◽

Carlo Pozzilli ◽

...

Keyword(s):

Safety Profile ◽

Time Course ◽

Pediatric Patients ◽

Short Term ◽

Elimination Phase ◽

Relapsing Remitting ◽

Distribution Phase

ObjectiveThis phase I study investigated pharmacokinetic (PK) and pharmacodynamic (PD) profiles of natalizumab in pediatric patients with relapsing-remitting MS (RRMS).MethodsPediatric patients with RRMS who were prescribed natalizumab 300 mg IV every 4 weeks were enrolled. Blood samples were collected on days 1, 2, 8, 15, and 22 and at weeks 4, 8, 12, and 16 to estimate PK parameters; PD properties were evaluated by measuring α4-integrin saturation and lymphocyte counts over time. Natalizumab's safety profile was also evaluated.ResultsPK parameters were similar to those reported in adult patients; natalizumab concentrations peaked approximately 1 day after infusion in most of the participants (Cmax 142.9 μg/mL, AUClast 47389.4 hr*μg/mL), followed by a biphasic decline with a rapid distribution phase and a slow elimination phase, with a terminal half-life of 215.1 hours. In terms of PD, both time course and magnitude of α4-integrin saturation and increase in lymphocyte counts were similar to those observed in adults. During the 16-week study follow-up, 3 adverse events attributed to natalizumab were observed; no unexpected safety events occurred.ConclusionsPK profile, α4-integrin saturation, lymphocyte counts, and safety observed in these pediatric patients are comparable to those reported in adults.Classification of evidenceThis study provides Class I evidence that natalizumab PK/PD parameters and safety profile are similar in adults and pediatric patients in the short term. Longer studies, also including a larger number of younger subjects (aged 10–12 years), are required to further inform about long-term PK and PD parameters in pediatric patients with MS.

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Alignment of time course gene expression data and the classification of developmentally driven genes with hidden Markov models

BMC Bioinformatics ◽

10.1186/s12859-015-0634-9 ◽

2015 ◽

Vol 16 (1) ◽

Cited By ~ 3

Author(s):

Sean Robinson ◽

Garique Glonek ◽

Inge Koch ◽

Mark Thomas ◽

Christopher Davies

Keyword(s):

Gene Expression ◽

Hidden Markov Models ◽

Gene Expression Data ◽

Time Course ◽

Markov Models ◽

Hidden Markov ◽

Expression Data

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Classification of patients from time-course gene expression

Biostatistics ◽

10.1093/biostatistics/kxs027 ◽

2012 ◽

Vol 14 (1) ◽

pp. 87-98 ◽

Cited By ~ 10

Author(s):

Y. Zhang ◽

R. Tibshirani ◽

R. Davis

Keyword(s):

Gene Expression ◽

Time Course

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Time course of glatiramer acetate efficacy in patients with RRMS in the GALA study

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000327 ◽

2017 ◽

Vol 4 (2) ◽

pp. e327 ◽

Cited By ~ 3

Author(s):

Mat D. Davis ◽

Natalia Ashtamker ◽

Joshua R. Steinerman ◽

Volker Knappertz

Keyword(s):

Glatiramer Acetate ◽

Time Course ◽

Low Frequency ◽

Controlled Clinical Trials ◽

Double Blind ◽

T2 Lesions ◽

Relapsing Remitting ◽

Data Censoring ◽

Post Hoc

Objective:To determine the time to efficacy onset of glatiramer acetate (GA) 40 mg/mL 3-times-weekly formulation (GA40).Methods:This post hoc analysis of data from the 1-year, double-blind, placebo-controlled phase of the Glatiramer Acetate Low-Frequency Administration study (NCT01067521) of GA40 in patients with relapsing-remitting MS (RRMS) sought to determine the timing of efficacy onset using a novel data-censoring approach.Results:Compared with placebo-treated patients, those receiving GA40 exhibited a >30% reduction in the accumulated annualized relapse rate (ARR) within 2 months of initiating treatment and generally sustained this treatment difference during the 1-year study. Similarly, the proportion of GA40-treated patients who remained relapse-free was distinctly greater by month 2 and continued to increase up to a 10.8% difference at the end of the study. In addition, GA40 treatment was associated with a significant reduction in the number of gadolinium-enhancing T1 lesions and new/enlarging T2 lesions by month 6, with full treatment effect observed after 1 year.Conclusions:GA40 contributes to efficacy within 2 months of the start of treatment in patients with RRMS. These results are consistent with the observed time to efficacy onset for patients treated with GA 20 mg/mL daily in previous randomized, placebo-controlled clinical trials.Classification of evidence:This study provides Class II evidence that for patients with RRMS, a 3-times-weekly formulation of GA 40 mg/mL leads to a >30% reduction in the ARR within 2 months.

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Temporal change in Syndecan-1 as a therapeutic target and a biomarker for the severity classification of COVID-19

Thrombosis Journal ◽

10.1186/s12959-021-00308-4 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Fumihiro Ogawa ◽

Yasufumi Oi ◽

Kento Nakajima ◽

Reo Matsumura ◽

Tomoki Nakagawa ◽

...

Keyword(s):

Clinical Data ◽

Therapeutic Target ◽

Time Course ◽

Temporal Change ◽

Medical Center ◽

Laboratory Data ◽

University Hospital ◽

Endothelial Glycocalyx ◽

Severity Classification

Abstract Background Coronavirus disease 2019 (COVID-19) pneumonitis associated with severe respiratory failure is associated with high mortality. The pathogenesis of COVID-19 is associated with microembolism or microvascular endothelial injuries. Here, we report that syndecan-1 (SDC-1), a component of the endothelial glycocalyx, may be a biomarker of severity classification for COVID-19 related to endothelial injury. Methods and analysis We analyzed the data of COVID-19 patients for 1 year from February 2020 at Yokohama City University Hospital and Yokohama City University Medical Center Hospital. We selected COVID-19 patients who required admission care, including intensive care, and analyzed the classification of severe and critical COVID-19 retrospectively, using various clinical data and laboratory data with SDC-1 by ELISA. Results We analyzed clinical and laboratory data with SDC-1 in five severe COVID-19 and ten critical COVID-19 patients. In the two groups, their backgrounds were almost the same. In laboratory data, the LDH, CHE, and CRP levels showed significant differences in each group (P = 0.032, P < 0.0001, and P = 0.007, respectively) with no significant differences in coagulation-related factors (platelet, PT-INR, d-dimer, ISTH score; P = 0.200, 0.277, 0.655, and 0.36, respectively). For the clinical data, the SOFA score was significantly different from admission day to day 14 of admission (p < 0.0001). The SDC-1 levels of critical COVID-19 patients were significantly higher on admission day and all-time course compared with the levels of severe COVID-19 patients (P = 0.009 and P < 0.0001, respectively). Conclusions Temporal change of SDC-1 levels closely reflect the severity of COVID-19, therefore, SDC-1 may be a therapeutic target and a biomarker for the severity classification of Covid-19.

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Time course and diagnostic utility of NfL, tau, GFAP, and UCH-L1 in subacute and chronic TBI

Neurology ◽

10.1212/wnl.0000000000009985 ◽

2020 ◽

Vol 95 (6) ◽

pp. e623-e636 ◽

Cited By ~ 5

Author(s):

Pashtun Shahim ◽

Adam Politis ◽

Andre van der Merwe ◽

Brian Moore ◽

Vindhya Ekanayake ◽

...

Keyword(s):

Time Course ◽

Injury Severity ◽

Diffusion Tensor ◽

Characteristic Curve ◽

Class Iii ◽

Neurofilament Light ◽

Prognostic Utility ◽

Severe Tbi ◽

And Diffusion

ObjectiveTo determine whether neurofilament light (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin C-terminal hydrolase-L1 (UCH-L1) measured in serum relate to traumatic brain injury (TBI) diagnosis, injury severity, brain volume, and diffusion tensor imaging (DTI) measures of traumatic axonal injury (TAI) in patients with TBI.MethodsPatients with TBI (n = 162) and controls (n = 68) were prospectively enrolled between 2011 and 2019. Patients with TBI also underwent serum, functional outcome, and imaging assessments at 30 (n = 30), 90 (n = 48), and 180 (n = 59) days, and 1 (n = 84), 2 (n = 57), 3 (n = 46), 4 (n = 38), and 5 (n = 29) years after injury.ResultsAt enrollment, patients with TBI had increased serum NfL compared to controls (p < 0.0001). Serum NfL decreased over the course of 5 years but remained significantly elevated compared to controls. Serum NfL at 30 days distinguished patients with mild, moderate, and severe TBI from controls with an area under the receiver-operating characteristic curve (AUROC) of 0.84, 0.92, and 0.92, respectively. At enrollment, serum GFAP was elevated in patients with TBI compared to controls (p < 0.001). GFAP showed a biphasic release in serum, with levels decreasing during the first 6 months of injury but increasing over the subsequent study visits. The highest AUROC for GFAP was measured at 30 days, distinguishing patients with moderate and severe TBI from controls (both 0.89). Serum tau and UCH-L1 showed weak associations with TBI severity and neuroimaging measures. Longitudinally, serum NfL was the only biomarker that was associated with the likely rate of MRI brain atrophy and DTI measures of progression of TAI.ConclusionsSerum NfL shows greater diagnostic and prognostic utility than GFAP, tau, and UCH-L1 for subacute and chronic TBI.Classification of evidenceThis study provides Class III evidence that serum NfL distinguishes patients with mild TBI from healthy controls.

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Annual Changes in Serum Syndecan-1 as a Therapeutic Target and a Biomarker for the Severity Classification of COVID-19

10.21203/rs.3.rs-484578/v1 ◽

2021 ◽

Author(s):

Fumihiro Ogawa ◽

Yasufumi Oi ◽

Kento Nakajima ◽

Reo Matsumura ◽

Tomoki Nakagawa ◽

...

Keyword(s):

Clinical Data ◽

Therapeutic Target ◽

Time Course ◽

Medical Center ◽

Laboratory Data ◽

University Hospital ◽

Endothelial Glycocalyx ◽

Severity Classification ◽

Annual Changes

Abstract Background: Coronavirus disease 2019 (COVID-19) pneumonitis associated with severe respiratory failure is associated with high mortality. The pathogenesis of COVID-19 is associated with microemboli or microvascular endothelial injuries. Here, we report that serum syndecan-1 (SDC-1), a component of the endothelial glycocalyx, may be a biomarker of severity classification for COVID-19 related to endothelial injury.Methods and analysis: We analyzed the data of COVID-19 patients for one year from February 2020 at Yokohama City University Hospital and Yokohama City University Medical Center Hospital. We selected COVID-19 patients who required admission care, including intensive care, and analyzed the classification of severe and critical COVID-19 retrospectively, using various clinical data and laboratory data with serum SDC-1 by ELISA. Results: We analyzed clinical and laboratory data with SDC-1 in five severe COVID-19 and ten critical COVID-19 patients. In the two groups, their backgrounds were almost the same. In laboratory data, the LDH, CHE, and CRP levels showed significant differences in each group (P=0.032, P <0.0001, and P = 0.007, respectively) with no significant differences in coagulation-related factors (platelet, PT-INR, D-dimer, ISTH score; P=0.200, 0.277, 0.655, and 0.36, respectively). For the clinical data, the SOFA score was significantly different from admission day to day 14 of admission (p<0.0001). The SDC-1 levels of critical COVID-19 patients were significantly higher on admission day and all-time course compared with the levels of severe COVID-19 patients (P=0.009 and P <0.0001, respectively).Conclusions: Annual changes in serum SDC-1 levels closely reflect the severity of COVID-19, therefore, serum SDC-1 may be a therapeutic target and a biomarker for the severity classification of Covid-19.

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Parameter extraction and classification of three cortical neuron types reveals two distinct adaptation mechanisms

Journal of Neurophysiology ◽

10.1152/jn.00408.2011 ◽

2012 ◽

Vol 107 (6) ◽

pp. 1756-1775 ◽

Cited By ~ 48

Author(s):

Skander Mensi ◽

Richard Naud ◽

Christian Pozzorini ◽

Michael Avermann ◽

Carl C. H. Petersen ◽

...

Keyword(s):

Large Scale ◽

Time Course ◽

Cortical Cell ◽

Reversal Potential ◽

Cell Types ◽

Parameter Extraction ◽

Spiking Neurons ◽

Model Parameters ◽

Adaptation Mechanisms

Cortical information processing originates from the exchange of action potentials between many cell types. To capture the essence of these interactions, it is of critical importance to build mathematical models that reflect the characteristic features of spike generation in individual neurons. We propose a framework to automatically extract such features from current-clamp experiments, in particular the passive properties of a neuron (i.e., membrane time constant, reversal potential, and capacitance), the spike-triggered adaptation currents, as well as the dynamics of the action potential threshold. The stochastic model that results from our maximum likelihood approach accurately predicts the spike times, the subthreshold voltage, the firing patterns, and the type of frequency-current curve. Extracting the model parameters for three cortical cell types revealed that cell types show highly significant differences in the time course of the spike-triggered currents and moving threshold, that is, in their adaptation and refractory properties but not in their passive properties. In particular, GABAergic fast-spiking neurons mediate weak adaptation through spike-triggered currents only, whereas regular spiking excitatory neurons mediate adaptation with both moving threshold and spike-triggered currents. GABAergic nonfast-spiking neurons combine the two distinct adaptation mechanisms with reduced strength. Differences between cell types are large enough to enable automatic classification of neurons into three different classes. Parameter extraction is performed for individual neurons so that we find not only the mean parameter values for each neuron type but also the spread of parameters within a group of neurons, which will be useful for future large-scale computer simulations.

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