scholarly journals Genetic polymorphisms in COMT and BDNF influence synchronization dynamics of human neuronal oscillations

2021 ◽  
Author(s):  
Jaana Simola ◽  
Felix Siebenhühner ◽  
Vladislav Myrov ◽  
Katri Kantojärvi ◽  
Tiina Paunio ◽  
...  
Keyword(s):  
Genetic Polymorphisms ◽  
Large Scale ◽  
Computational Modelling ◽  
Individual Variability ◽  
Neuronal Oscillations ◽  
Scale Free ◽  
Oscillatory Dynamics ◽  
Local Oscillation ◽  
Temporal Correlations ◽  
Oscillation Dynamics

Neuronal oscillations, their inter-areal synchronization and scale-free dynamics constitute fundamental mechanisms for cognition by regulating communication in neuronal networks. These oscillatory dynamics have large inter-individual variability that is partly heritable. However, the genetic underpinnings of oscillatory dynamics have remained poorly understood. We recorded resting-state magnetoencephalography (MEG) from 82 participants and investigated whether oscillation dynamics were influenced by genetic polymorphisms in Catechol-O-methyltransferase ( COMT ) Val 158 Met and brain-derived neurotrophic factor ( BDNF ) Val 66 Met. Both COMT and BDNF polymorphisms influenced local oscillation amplitudes and their long-range temporal correlations (LRTCs), while only BDNF polymorphism affected the strength of large-scale synchronization. Brain criticality framework and computational modelling of near-critical synchronization dynamics suggested that COMT and BDNF polymorphisms influenced local oscillations via differences in net excitation-inhibition balance. Our findings demonstrate that COMT and BDNF genetic polymorphisms contribute to inter-individual variability in local and large-scale synchronization dynamics of neuronal oscillations.

scholarly journals Dynamic relationships between spontaneous and evoked electrophysiological activity

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Soren Wainio-Theberge ◽  
Annemarie Wolff ◽  
Georg Northoff
Keyword(s):  
Neural Activity ◽  
Large Scale ◽  
Behavioral Outcomes ◽  
Low Frequencies ◽  
Scale Free ◽  
Non Invasive ◽  
Spontaneous Neural Activity ◽  
Electrophysiological Signals ◽  
Evoked Activity ◽  
Dynamic Relationships

AbstractSpontaneous neural activity fluctuations have been shown to influence trial-by-trial variation in perceptual, cognitive, and behavioral outcomes. However, the complex electrophysiological mechanisms by which these fluctuations shape stimulus-evoked neural activity remain largely to be explored. Employing a large-scale magnetoencephalographic dataset and an electroencephalographic replication dataset, we investigate the relationship between spontaneous and evoked neural activity across a range of electrophysiological variables. We observe that for high-frequency activity, high pre-stimulus amplitudes lead to greater evoked desynchronization, while for low frequencies, high pre-stimulus amplitudes induce larger degrees of event-related synchronization. We further decompose electrophysiological power into oscillatory and scale-free components, demonstrating different patterns of spontaneous-evoked correlation for each component. Finally, we find correlations between spontaneous and evoked time-domain electrophysiological signals. Overall, we demonstrate that the dynamics of multiple electrophysiological variables exhibit distinct relationships between their spontaneous and evoked activity, a result which carries implications for experimental design and analysis in non-invasive electrophysiology.

scholarly journals The role of the renin–angiotensin–aldosterone system in preeclampsia: genetic polymorphisms and microRNA

2013 ◽  
Vol 50 (2) ◽  
pp. R53-R66 ◽  
Author(s):  
Jie Yang ◽  
Jianyu Shang ◽  
Suli Zhang ◽  
Hao Li ◽  
Huirong Liu
Keyword(s):  
Genetic Polymorphisms ◽  
Large Scale ◽  
Salt Water ◽  
Prognostic Significance ◽  
Neonatal Morbidity ◽  
Well Being ◽  
Normal Pregnancy ◽  
Placental Perfusion ◽  
Familial Predisposition ◽  
Increased Risk

The compensatory alterations in the rennin–angiotensin–aldosterone system (RAAS) contribute to the salt–water balance and sufficient placental perfusion for the subsequent well-being of the mother and fetus during normal pregnancy and is characterized by an increase in almost all the components of RAAS. Preeclampsia, however, breaks homeostasis and leads to a disturbance of this delicate equilibrium in RAAS both for circulation and the uteroplacental unit. Despite being a major cause for maternal and neonatal morbidity and mortality, the pathogenesis of preeclampsia remains elusive, where RAAS has been long considered to be involved. Epidemiological studies have indicated that preeclampsia is a multifactorial disease with a strong familial predisposition regardless of variations in ethnic, socioeconomic, and geographic features. The heritable allelic variations, especially the genetic polymorphisms in RAAS, could be the foundation for the genetics of preeclampsia and hence are related to the development of preeclampsia. Furthermore, at a posttranscriptional level, miRNA can interact with the targeted site within the 3′-UTR of the RAAS gene and thereby might participate in the regulation of RAAS and the pathology of preeclampsia. In this review, we discuss the recent achievements of genetic polymorphisms, as well as the interactions between maternal and fetal genotypes, and miRNA posttranscriptional regulation associated with RAAS in preeclampsia. The results are controversial but utterly inspiring and attractive in terms of potential prognostic significance. Although many studies suggest positive associations with genetic mutations and increased risk for preeclampsia, more meticulously designed large-scale investigations are needed to avoid the interference from different variations.

Advanced CFD Simulations of free-surface flows around modern sailing yachts using a newly developed openFOAM solver

2016 ◽  
Author(s):  
Janek Meyer ◽  
Hannes Renzsch ◽  
Kai Graf ◽  
Thomas Slawig
Keyword(s):  
Free Surface ◽  
Large Scale ◽  
Breaking Waves ◽  
Free Surface Flows ◽  
Body Motion ◽  
Computational Time ◽  
Efficient Computation ◽  
Surface Flows ◽  
Scale Free ◽  
Wide Range

While plain vanilla OpenFOAM has strong capabilities with regards to quite a few typical CFD-tasks, some problems actually require additional bespoke solvers and numerics for efficient computation of high-quality results. One of the fields requiring these additions is the computation of large-scale free-surface flows as found e.g. in naval architecture. This holds especially for the flow around typical modern yacht hulls, often planing, sometimes with surface-piercing appendages. Particular challenges include, but are not limited to, breaking waves, sharpness of interface, numerical ventilation (aka streaking) and a wide range of flow phenomenon scales. A new OF-based application including newly implemented discretization schemes, gradient computation and rigid body motion computation is described. In the following the new code will be validated against published experimental data; the effect on accuracy, computational time and solver stability will be shown by comparison to standard OF-solvers (interFoam / interDyMFoam) and Star CCM+. The code’s capabilities to simulate complex “real-world” flows are shown on a well-known racing yacht design.

BDV-syndrome: An emerging syndrome with profound obesity and neurodevelopmental delay resembling Prader-Willi syndrome

2021 ◽  
Author(s):  
Elisabeth Bosch ◽  
Moritz Hebebrand ◽  
Bernt Popp ◽  
Theresa Penger ◽  
Bettina Behring ◽  
...  
Keyword(s):  
Clinical Features ◽  
Large Scale ◽  
Hypogonadotropic Hypogonadism ◽  
Computational Modelling ◽  
Prader Willi Syndrome ◽  
Loss Of Function ◽  
Human Phenotype ◽  
Neurodevelopmental Delay ◽  
Missense Variants ◽  
Severely Obese

Abstract Context CPE encodes carboxypeptidase E, an enzyme which converts proneuropeptides and propeptide hormones to bioactive forms. It is widely expressed in the endocrine and central nervous system. To date, four individuals from two families with core clinical features including morbid obesity, neurodevelopmental delay and hypogonadotropic hypogonadism, harbouring biallelic loss-of-function CPE variants, were reported. Objective We describe four affected individuals from three unrelated consanguineous families, two siblings of Syrian, one of Egyptian and one of Pakistani descent, all harbouring novel homozygous CPE loss-of-function variants. Methods After excluding Prader-Willi syndrome, exome sequencing was performed in both Syrian siblings. The variants identified in the other two individuals were reported as research variants in a large scale exome study and in ClinVar database. Computational modelling of all possible missense alterations allowed assessing CPE tolerance to missense variants. Results All affected individuals were severely obese with neurodevelopmental delay and other endocrine anomalies. Three individuals from two families shared the same CPE homozygous truncating variant c.361C>T, p.(Arg121*), while the fourth carried the c.994del, p.(Ser333Alafs*22) variant. Comparison of clinical features with previously described cases and standardization according to the Human Phenotype Ontology indicated a recognisable clinical phenotype, which we termed Blakemore-Durmaz-Vasileiou (BDV) syndrome. Computational analysis indicated high conservation of CPE domains and intolerance to missense changes. Conclusions Biallelic truncating CPE variants are associated with BDV syndrome, a clinically recognisable monogenic recessive syndrome with childhood-onset obesity, neurodevelopmental delay, hypogonadotropic hypogonadism and hypothyroidism. BDV syndrome resembles Prader-Willi syndrome. Our findings suggested that missense variants may also be clinically relevant.

scholarly journals Subclinical Hypothyroidism and Cardiovascular Risk – An Overview of Current Understanding

2010 ◽  
Vol 7 (1) ◽  
pp. 53 ◽  
Author(s):  
Ulla Feldt Rasmussen ◽  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Subclinical Hypothyroidism ◽  
Large Scale ◽  
Thyroid Stimulating Hormone ◽  
Individual Variability ◽  
Overt Hypothyroidism ◽  
Therapeutic Trial ◽  
Treatment Benefit

Subclinical or mild hypothyroidism is often associated with adverse cardiovascular risk factors, such as high cholesterol, together with hypertension, endothelial dysfunction and other atherosclerotic cardiovascular risk factors. The ischaemic abnormalities are probably related to long-term consequences of a slowly progressing development of hypothyroidism. In recent years, it has become evident that a consensus on the exact limits for cut-off between normal and subclinically hypothyroid individuals is not currently possible. The main reasons for this are differences for measurement of serum thyroid-stimulating hormone (TSH), that reference populations are very different and that a person’s intra-individual variability is much narrower than any population-based interval. Finally, the prevalence of subclinical hypothyroidism varies from 4 to 17% in different normal populations. Available evidence indicates that patients with subclinical hypothyroidism have developed or are at risk of developing an adverse cardiovascular profile and subclinical hypothyroidism is most likely a mild variant of overt hypothyroidism. There is currently no evidence for a treatment benefit, but studies to demonstrate the expected minor improvements have not been performed on a sufficiently large scale. Patients should be informed about the disease and based on a combined clinical and laboratory judgement, should be offered a therapeutic trial in case of even vague symptoms.

scholarly journals Fear signaling in the prelimbic-amygdala circuit: a computational modeling and recording study

2013 ◽  
Vol 110 (4) ◽  
pp. 844-861 ◽  
Author(s):  
Sandeep Pendyam ◽  
Christian Bravo-Rivera ◽  
Anthony Burgos-Robles ◽  
Francisco Sotres-Bayon ◽  
Gregory J. Quirk ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Fear Conditioning ◽  
Large Scale ◽  
Conditioned Fear ◽  
Individual Variability ◽  
Biophysical Model ◽  
Human Homolog ◽  
Lateral Amygdala ◽  
Internal Inhibition ◽  
Β Blocker

The acquisition and expression of conditioned fear depends on prefrontal-amygdala circuits. Auditory fear conditioning increases the tone responses of lateral amygdala neurons, but the increase is transient, lasting only a few hundred milliseconds after tone onset. It was recently reported that that the prelimbic (PL) prefrontal cortex transforms transient lateral amygdala input into a sustained PL output, which could drive fear responses via projections to the lateral division of basal amygdala (BL). To explore the possible mechanisms involved in this transformation, we developed a large-scale biophysical model of the BL-PL network, consisting of 850 conductance-based Hodgkin-Huxley-type cells, calcium-based learning, and neuromodulator effects. The model predicts that sustained firing in PL can be derived from BL-induced release of dopamine and norepinephrine that is maintained by PL-BL interconnections. These predictions were confirmed with physiological recordings from PL neurons during fear conditioning with the selective β-blocker propranolol and by inactivation of BL with muscimol. Our model suggests that PL has a higher bandwidth than BL, due to PL's decreased internal inhibition and lower spiking thresholds. It also suggests that variations in specific microcircuits in the PL-BL interconnection can have a significant impact on the expression of fear, possibly explaining individual variability in fear responses. The human homolog of PL could thus be an effective target for anxiety disorders.

scholarly journals A gravitational puzzle

2011 ◽  
Vol 369 (1957) ◽  
pp. 4998-5002
Author(s):  
Robert R. Caldwell
Keyword(s):  
Gravitational Lensing ◽  
Large Scale ◽  
Current Data ◽  
Cosmic Acceleration ◽  
Late Time ◽  
Microwave Background ◽  
Scale Free ◽  
Cosmological Observations ◽  
Stress Energy ◽  
The Relationship

The challenge to understand the physical origin of the cosmic acceleration is framed as a problem of gravitation. Specifically, does the relationship between stress–energy and space–time curvature differ on large scales from the predictions of general relativity. In this article, we describe efforts to model and test a generalized relationship between the matter and the metric using cosmological observations. Late-time tracers of large-scale structure, including the cosmic microwave background, weak gravitational lensing, and clustering are shown to provide good tests of the proposed solution. Current data are very close to proving a critical test, leaving only a small window in parameter space in the case that the generalized relationship is scale free above galactic scales.

A Stochastic Parameter Perturbation Method to Represent Uncertainty in a Microphysics Scheme

2021 ◽  
Author(s):  
Gregory Thompson ◽  
Judith Berner ◽  
Maria Frediani ◽  
Jason A. Otkin ◽  
Sarah M. Griffin
Keyword(s):  
Land Surface ◽  
Large Scale ◽  
Random Perturbation ◽  
Longwave Radiation ◽  
Parameter Uncertainties ◽  
Microphysics Scheme ◽  
Convective Systems ◽  
Temporal Correlations ◽  
Precipitation Characteristics ◽  
The Impact

AbstractCurrent state-of-the art regional numerical weather forecasts are run at horizontal grid spacings of a few kilometers, which permits medium to large-scale convective systems to be represented explicitly in the model. With the convection parameterization no longer active, much uncertainty in the formulation of subgrid-scale processes moves to other areas such as the cloud microphysical, turbulence, and land-surface parameterizations. The goal of this study is to investigate experiments with stochastically-perturbed parameters (SPP) within a microphysics parameterization and the model’s horizontal diffusion coefficients. To estimate the “true” uncertainty due to parameter uncertainty, the magnitudes of the perturbations are chosen as realistic as possible and not with purposeful intent of maximal forecast impact as some prior work has done. Spatial inhomogeneities and temporal persistence are represented using a random perturbation pattern with spatial and temporal correlations. The impact on the distributions of various hydrometeors, precipitation characteristics, and solar/longwave radiation are quantified for a winter and summer case. In terms of upscale error growth, the impact is relatively small and consists primarily of triggering atmospheric instabilities in convectively unstable regions. In addition, small in situ changes with potentially large socio-economic impacts are observed in the precipitation characteristics such as maximum hail size. Albeit the impact of introducing physically-based parameter uncertainties within the bounds of aerosol uncertainties is small, their influence on the solar and longwave radiation balances may still have important implications for global model simulations of future climate scenarios.

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