scholarly journals Single platelet variability governs population sensitivity and initiates intrinsic heterotypic behaviours

2020 ◽  
Author(s):  
Maaike S. A. Jongen ◽  
Ben D. MacArthur ◽  
Nicola A. Englyst ◽  
Jonathan West
Keyword(s):  
Large Scale ◽  
Function Analysis ◽  
Population Level ◽  
Human Platelets ◽  
Droplet Microfluidics ◽  
Community Effects ◽  
Platelet Response ◽  
Thrombin Activation ◽  
Health And Disease ◽  
Population Sensitivity

AbstractDroplet microfluidics combined with flow cytometry was used for high throughput single platelet function analysis. A large-scale sensitivity continuum was shown to be a general feature of human platelets from individual donors, with hypersensitive platelets coordinating significant sensitivity gains in bulk platelet populations and shown to direct aggregation in droplet-confined minimal platelet systems. Sensitivity gains scaled with agonist potency (convulxin>TRAP-14>ADP) and reduced the collagen and thrombin activation threshold required for platelet population polarization into pro-aggregatory and pro-coagulant states. The heterotypic platelet response results from an intrinsic behavioural program. The method and findings invite future discoveries into the nature of hypersensitive platelets and how community effects produce population level behaviours in health and disease.

scholarly journals An optical observational cluster mass function at z ∼ 1 with the ORELSE survey

2021 ◽  
Vol 502 (3) ◽  
pp. 3942-3954
Author(s):  
D Hung ◽  
B C Lemaux ◽  
R R Gal ◽  
A R Tomczak ◽  
L M Lubin ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Large Scale ◽  
Near Infrared ◽  
Function Analysis ◽  
Voronoi Tessellation ◽  
Cosmological Parameters ◽  
Mass Range ◽  
Mass Function ◽  
Cluster Mass ◽  
Theoretical Mass

ABSTRACT We present a new mass function of galaxy clusters and groups using optical/near-infrared (NIR) wavelength spectroscopic and photometric data from the Observations of Redshift Evolution in Large-Scale Environments (ORELSE) survey. At z ∼ 1, cluster mass function studies are rare regardless of wavelength and have never been attempted from an optical/NIR perspective. This work serves as a proof of concept that z ∼ 1 cluster mass functions are achievable without supplemental X-ray or Sunyaev-Zel’dovich data. Measurements of the cluster mass function provide important contraints on cosmological parameters and are complementary to other probes. With ORELSE, a new cluster finding technique based on Voronoi tessellation Monte Carlo (VMC) mapping, and rigorous purity and completeness testing, we have obtained ∼240 galaxy overdensity candidates in the redshift range 0.55 < z < 1.37 at a mass range of 13.6 < log (M/M⊙) < 14.8. This mass range is comparable to existing optical cluster mass function studies for the local universe. Our candidate numbers vary based on the choice of multiple input parameters related to detection and characterization in our cluster finding algorithm, which we incorporated into the mass function analysis through a Monte Carlo scheme. We find cosmological constraints on the matter density, Ωm, and the amplitude of fluctuations, σ8, of $\Omega _{m} = 0.250^{+0.104}_{-0.099}$ and $\sigma _{8} = 1.150^{+0.260}_{-0.163}$. While our Ωm value is close to concordance, our σ8 value is ∼2σ higher because of the inflated observed number densities compared to theoretical mass function models owing to how our survey targeted overdense regions. With Euclid and several other large, unbiased optical surveys on the horizon, VMC mapping will enable optical/NIR cluster cosmology at redshifts much higher than what has been possible before.

scholarly journals 214 Longitudinal Changes in Sleep Duration, Timing, Variability, and Stages during the COVID-19 Pandemic: Large-Scale Fitbit Data

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A86-A86
Author(s):  
Michael Grandner ◽  
Naghmeh Rezaei
Keyword(s):  
New York ◽  
Los Angeles ◽  
San Francisco ◽  
Sleep Duration ◽  
Large Scale ◽  
Age Groups ◽  
Population Level ◽  
Sleep Stages ◽  
Longitudinal Changes ◽  
Timing Variability

Abstract Introduction The COVID-19 pandemic has resulted in societal-level changes to sleep and other behavioral patterns. Objective, longitudinal data would allow for a greater understanding of sleep-related changes at the population level. Methods N= 163,524 deidentified active Fitbit users from 6 major US cities contributed data, representing areas particularly hard-hit by the pandemic (Chicago, Houston, Los Angeles, New York, San Francisco, and Miami). Sleep variables extracted include nightly and weekly mean sleep duration and bedtime, variability (standard deviation) of sleep duration and bedtime, and estimated arousals and sleep stages. Deviation from similar timeframes in 2019 were examined. All analyses were performed in Python. Results These data detail how sleep duration and timing changed longitudinally, stratified by age group and gender, relative to previous years’ data. Overall, 2020 represented a significant departure for all age groups and both men and women (P<0.00001). Mean sleep duration increased in nearly all groups (P<0.00001) by 5-11 minutes, compared to a mean decrease of 5-8 minutes seen over the same period in 2019. Categorically, sleep duration increased for some and decreased for others, but more extended than restricted. Sleep phase shifted later for nearly all groups (p<0.00001). Categorically, bedtime was delayed for some and advanced for others, though more delayed than advanced. Duration and bedtime variability decreased, owing largely to decreased weekday-weekend differences. WASO increased, REM% increased, and Deep% decreased. Additional analyses show stratified, longitudinal changes to sleep duration and timing mean and variability distributions by month, as well as effect sizes and correlations to other outcomes. Conclusion The pandemic was associated with increased sleep duration on average, in contrast to 2019 when sleep decreased. The increase was most profound among younger adults, especially women. The youngest adults also experienced the greatest bedtime delay, in line with extensive school-start-times and chronotype data. When given the opportunity, the difference between weekdays and weekends became smaller, with occupational implications. Sleep staging data showed that slightly extending sleep minimally impacted deep sleep but resulted in a proportional increase in REM. Wakefulness during the night also increased, suggesting increased arousal despite greater sleep duration. Support (if any) This research was supported by Fitbit, Inc.

MIC-Drop: A platform for large-scale in vivo CRISPR screens

Science ◽  
2021 ◽  
pp. eabi8870
Author(s):  
Saba Parvez ◽  
Chelsea Herdman ◽  
Manu Beerens ◽  
Korak Chakraborti ◽  
Zachary P. Harmer ◽  
...  
Keyword(s):  
Large Scale ◽  
Cultured Cells ◽  
Cardiac Development ◽  
Droplet Microfluidics ◽  
Model Organisms ◽  
Genetic Screens ◽  
Large Numbers ◽  
And Function ◽  
Genome Scale

CRISPR-Cas9 can be scaled up for large-scale screens in cultured cells, but CRISPR screens in animals have been challenging because generating, validating, and keeping track of large numbers of mutant animals is prohibitive. Here, we report Multiplexed Intermixed CRISPR Droplets (MIC-Drop), a platform combining droplet microfluidics, single-needle en masse CRISPR ribonucleoprotein injections, and DNA barcoding to enable large-scale functional genetic screens in zebrafish. The platform can efficiently identify genes responsible for morphological or behavioral phenotypes. In one application, we show MIC-Drop can identify small molecule targets. Furthermore, in a MIC-Drop screen of 188 poorly characterized genes, we discover several genes important for cardiac development and function. With the potential to scale to thousands of genes, MIC-Drop enables genome-scale reverse-genetic screens in model organisms.

scholarly journals A Potential of microRNAs for High-Content Screening

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Andrius Serva ◽  
Christoph Claas ◽  
Vytaute Starkuviene
Keyword(s):  
Large Scale ◽  
Cellular Processes ◽  
Comprehensive Knowledge ◽  
Functional Models ◽  
Rapid Accumulation ◽  
Health And Disease ◽  
Temporal And Spatial ◽  
And Function ◽  
Functional Analyses ◽  
Immense Potential

In the last years miRNAs have increasingly been recognised as potent posttranscriptional regulators of gene expression. Possibly, miRNAs exert their action on virtually any biological process by simultaneous regulation of numerous genes. The importance of miRNA-based regulation in health and disease has inspired research to investigate diverse aspects of miRNA origin, biogenesis, and function. Despite the recent rapid accumulation of experimental data, and the emergence of functional models, the complexity of miRNA-based regulation is still far from being well understood. In particular, we lack comprehensive knowledge as to which cellular processes are regulated by which miRNAs, and, furthermore, how temporal and spatial interactions of miRNAs to their targets occur. Results from large-scale functional analyses have immense potential to address these questions. In this review, we discuss the latest progress in application of high-content and high-throughput functional analysis for the systematic elucidation of the biological roles of miRNAs.

Studies on the Organisation of Glycoproteins and Proteins in Human Platelet Membranes

1979 ◽  
Author(s):  
A.T. Nurden ◽  
D. Dupuis ◽  
H. de la Baume ◽  
J.P. Caen
Keyword(s):  
Human Platelet ◽  
Membrane Vesicles ◽  
Human Platelets ◽  
Cross Linking ◽  
Platelet Response ◽  
Membrane Glycoproteins ◽  
Sh Groups ◽  
Sds Page ◽  
The Cross ◽  
Neighbour Analysis

Addition of wheat germ agglutinin (WGA) (50 ug/ml) to washed human platelets (3 x 108/ml) resulted in platelet activation and the release of l4C-5HT within the same time scale as 0.05 units/ml thrombin. In contrast, succinyl-WGA (100 ug/ml) induced no platelet response. The increased valency of WGA (4) compared with succinyl-WGA (2) suggests that the activation is induced through the cross-linking (immobilisation ?) of closely associated receptors in the membrane. This finding induced us to attempt to cross-link and thereby identify adjacent molecules in the membrane by “near-neighbour” analysis. Constituent -SH groups were oxidised employing Cu2+/phenanthroline or diamide as catalysts, and polymers formed as a result of intermolecular -S-S- formation between adjacent molecules were identified by SDS-PAGE. Although previous reports have shown that the major human platelet membrane glycoproteins contain -SH groups, no apparent cross-linking of the glycoproteins was located following the incubation of either washed platelets or isolated membranes with Cu2+/phenanthroline or diamide. However bidimensional SDS-PAGE (1st dimension non-reduced, 2nd dimension reduced) showed the presence of several protein polymers including complexes formed by the cross-linking of 3 large polypeptides of M. Wt. 250 000, 220 000 and 200 000. These components were easily eluted from membrane vesicles at pH 10 and may represent closely associated constituents at the cytoplasmic surface of the plasma membrane.

scholarly journals Hidden in plain sight: What remains to be discovered in the eukaryotic proteome?

2018 ◽  
Author(s):  
Valerie Wood ◽  
Antonia Lock ◽  
Midori A. Harris ◽  
Kim Rutherford ◽  
Jürg Bähler ◽  
...  
Keyword(s):  
Gene Ontology ◽  
Fission Yeast ◽  
Genome Sequencing ◽  
Large Scale ◽  
Biological Process ◽  
Blind Spot ◽  
Model Organisms ◽  
Biological Processes ◽  
Health And Disease

AbstractThe first decade of genome sequencing stimulated an explosion in the characterization of unknown proteins. More recently, the pace of functional discovery has slowed, leaving around 20% of the proteins even in well-studied model organisms without informative descriptions of their biological roles. Remarkably, many uncharacterized proteins are conserved from yeasts to human, suggesting that they contribute to fundamental biological processes. To fully understand biological systems in health and disease, we need to account for every part of the system. Unstudied proteins thus represent a collective blind spot that limits the progress of both basic and applied biosciences.We use a simple yet powerful metric based on Gene Ontology (GO) biological process terms to define characterized and uncharacterized proteins for human, budding yeast, and fission yeast. We then identify a set of conserved but unstudied proteins in S. pombe, and classify them based on a combination of orthogonal attributes determined by large-scale experimental and comparative methods. Finally, we explore possible reasons why these proteins remain neglected, and propose courses of action to raise their profile and thereby reap the benefits of completing the catalog of proteins’ biological roles.

scholarly journals Nonlinear visuoauditory integration in the mouse superior colliculus

2021 ◽  
Author(s):  
Shinya Ito ◽  
Yufei Si ◽  
Alan M. Litke ◽  
David A. Feldheim
Keyword(s):  
Superior Colliculus ◽  
Sensory Integration ◽  
Large Scale ◽  
Temporal Dynamics ◽  
Critical Role ◽  
Sensory Information ◽  
Population Level ◽  
Object Identification ◽  
Response Properties ◽  
The Individual

AbstractSensory information from different modalities is processed in parallel, and then integrated in associative brain areas to improve object identification and the interpretation of sensory experiences. The Superior Colliculus (SC) is a midbrain structure that plays a critical role in integrating visual, auditory, and somatosensory input to assess saliency and promote action. Although the response properties of the individual SC neurons to visuoauditory stimuli have been characterized, little is known about the spatial and temporal dynamics of the integration at the population level. Here we recorded the response properties of SC neurons to spatially restricted visual and auditory stimuli using large-scale electrophysiology. We then created a general, population-level model that explains the spatial, temporal, and intensity requirements of stimuli needed for sensory integration. We found that the mouse SC contains topographically organized visual and auditory neurons that exhibit nonlinear multisensory integration. We show that nonlinear integration depends on properties of auditory but not visual stimuli. We also find that a heuristically derived nonlinear modulation function reveals conditions required for sensory integration that are consistent with previously proposed models of sensory integration such as spatial matching and the principle of inverse effectiveness.

scholarly journals How do you measure up? Methods to assess linkage quality

2017 ◽  
Vol 1 (1) ◽  
Author(s):  
Anna Ferrante ◽  
James Boyd ◽  
Sean Randall ◽  
Adrian Brown ◽  
James Semmens
Keyword(s):  
Record Linkage ◽  
Service Use ◽  
Performance Metrics ◽  
Population Level ◽  
Additional Information ◽  
Linkage Quality ◽  
Health And Disease ◽  
The Impact ◽  
Quality Process

ABSTRACT ObjectivesRecord linkage is a powerful technique which transforms discrete episode data into longitudinal person-based records. These records enable the construction and analysis of complex pathways of health and disease progression, and service use. Achieving high linkage quality is essential for ensuring the quality and integrity of research based on linked data. The methods used to assess linkage quality will depend on the volume and characteristics of the datasets involved, the processes used for linkage and the additional information available for quality assessment. This paper proposes and evaluates two methods to routinely assess linkage quality. ApproachLinkage units currently use a range of methods to measure, monitor and improve linkage quality; however, no common approach or standards exist. There is an urgent need to develop “best practices” in evaluating, reporting and benchmarking linkage quality. In assessing linkage quality, of primary interest is in knowing the number of true matches and non-matches identified as links and non-links. Any misclassification of matches within these groups introduces linkage errors. We present efforts to develop sharable methods to measure linkage quality in Australia. This includes a sampling-based method to estimate both precision (accuracy) and recall (sensitivity) following record linkage and a benchmarking method - a transparent and transportable methodology to benchmark the quality of linkages across different operational environments. ResultsThe sampling-based method achieved estimates of linkage quality that were very close to actual linkage quality metrics. This method presents as a feasible means of accurately estimating matching quality and refining linkages in population level linkage studies. The benchmarking method provides a systematic approach to estimating linkage quality with a set of open and shareable datasets and a set of well-defined, established performance metrics. The method provides an opportunity to benchmark the linkage quality of different record linkage operations. Both methods have the potential to assess the inter-rater reliability of clerical reviews. ConclusionsBoth methods produce reliable estimates of linkage quality enabling the exchange of information within and between linkage communities. It is important that researchers can assess risk in studies using record linkage techniques. Understanding the impact of linkage quality on research outputs highlights a need for standard methods to routinely measure linkage quality. These two methods provide a good start to the quality process, but it is important to identify standards and good practices in all parts of the linkage process (pre-processing, standardising activities, linkage, grouping and extracting).

Sign in / Sign up

Export Citation Format

Share Document