Biology subjects

Kennedy, J.

Publications and source records attributed to Kennedy, J..

5 recordsLinked to original sources

bioRxiv2018

Theta-Gamma Cascades and Running Speed

The local field potentials (LFPs) of the hippocampus are primarily generated by the spatiotemporal accretion of electrical currents via activated synapses. Oscillations in the hippocampal LFP at theta and gamma frequencies are prominent during awake-behavior and have demonstrated several behavioral correlates. In particular, both oscillations have been observed to increase in amplitude and frequency as a function of running velocity. Previous investigations, however, have examined the relationship between velocity and each of these oscillation bands separately. Based on energy cascade models where \"...perturbations of slow frequencies cause a cascade of energy dissipation at all frequency scales\" (Buzsaki 2006), we hypothesized that the cross-frequency interactions between theta and gamma should increase as a function of velocity. We examined these relationships across multiple layers of the CA1 subregion and found a reliable correlation between the power of theta and the power of gamma, indicative of an amplitude-amplitude relationship. Moreover, there was an increase in the coherence between the power of gamma and the phase of theta, demonstrating increased phase-amplitude coupling with velocity. Finally, at higher velocities, phase entrainment between theta and gamma becomes stronger. These results have important implications and provide new insights regarding how theta and gamma are integrated for neuronal circuit dynamics, with coupling strength determined by the excitatory drive within the hippocampus.

neuroscience↗

bioRxiv2017

Serial quantification of brain oxygenation in acute stroke using streamlined-qBOLD

It has been proposed that metabolic markers of baseline brain oxygenation have a role to play in the early identification of the ischemic penumbra. Streamlined-qBOLD is a magnetic resonance imaging technique that does not require exogenous contrast. It is a refinement of the quantitative BOLD methodology that provides a simplified approach to mapping and quantifying baseline brain oxygenation related parameters (reversible transverse relaxation rate (R2'), deoxygenated blood volume (DBV) and deoxyhaemoglobin concentration ([dHb])) in a clinically relevant manner. Streamlined-qBOLD was applied to an exploratory cohort of acute stroke patients in a serial imaging study. Detailed voxel-level analysis was used to quantify the metabolic profile of ischaemic tissue on presentation and investigate these metrics in relation to tissue outcome. Individual patient examples illustrate the appropriate interpretation of R2', DBV and [dHb] in acute stroke and demonstrate the ability of this method to deliver regional information related to oxygen metabolism in the ischaemic tissue. Regional analysis confirms that R2', DBV and [dHb] vary between regions of ischaemia with different tissue outcomes.

neuroscience↗

bioRxiv2017

Mitochondrial DNA SNPs associated with Schizophrenia exhibit Highly Variable Inter-allelic Haplogroup Affiliation and Nuclear Genogeographic Affinity: Bi-Genomic Linkage Disequilibrium raises Major Concerns for Link to Disease

Mitochondria play a significant role in human diseases. However, disease associations with mitochondrial DNA (mtDNA) SNPs have proven difficult to replicate. A reanalysis of eight schizophrenia-associated mtDNA SNPs, in 23,743 normal Danes and 2,538 schizophrenia patients, revealed marked inter-allelic differences in haplogroup affiliation and nuclear ancestry, genogeophraphic affinity (GGA). This bi-genomic linkage disequilibrium (2GLD) could entail population stratification. Only two mitochondrial SNPs, m. 15043A and m. 15218G, were significantly associated with schizophrenia. However, these associations disappeared when corrected for haplogroup affiliation. The extensive 2GLD documented is a major concern when interpreting historic as well as designing future mtDNA association studies.

genomics↗

bioRxiv2017

Complex spatio-temporal distribution and genogeographic affinity of mitochondrial DNA haplogroups in 24,216 Danes

Mitochondrial DNA (mtDNA) haplogroups (hgs) are evolutionarily conserved sets of mtDNA SNP-haplotypes with characteristic geographical distribution. Associations of hgs with disease and physiological characteristics have been reported, but have frequently not been reproducible. Using 418 mtDNA SNPs on the PsychChip (Illumina), we assessed the spatio-temporal distribution of mtDNA hgs in Denmark in DNA isolated from 24,642 geographically un-biased dried blood spots (DBS), collected from 1981 to 2005 through the Danish National Neonatal Screening program. Geno-geographic affinity (ancestry background) was established with ADMIXTURE using a reference of 100K+ autosomal SNPs in 2,248 individuals from nine populations. The hg distribution was typically Northern European, and hgs were highly variable based on median-joining analysis, suggesting multiple founder events. Considerable heterogeneity and variation in autosomal geno-geographic affinity was observed. Thus, individuals with hg H exhibited 95 %, and U hgs 38.2 % - 92.5 %, Danish ancestry. Significant clines between geographical regions and rural and metropolitan populations were found. Over 25 years, macro-hg L increased from 0.2 % to 1.2 % (p = 1.1*E-10), and M from 1 % to 2.4 % (p = 3.7*E-8). Hg U increased among the R macro-hg from 14.1 % to 16.5 % (p = 1.9*E-3). Geno-geographic affinity, geographical skewedness, and sub-hg distribution suggested that the L, M and U increases are due to immigration. The complex spatio-temporal dynamics and geno-geographic heterogeneity of mtDNA in the Danish population reflect repeated migratory events and, in later years, net immigration. Such complexity may explain the often contradictory and population-specific reports of mito-genomic association with disease.

genomics↗

bioRxiv2017

CiliaCarta: An Integrated And Validated Compendium Of Ciliary Genes

The cilium is an essential organelle at the surface of most mammalian cells whose dysfunction causes a wide range of genetic diseases collectively called ciliopathies. The current rate at which new ciliopathy genes are identified suggests that many ciliary components remain undiscovered. We generated and rigorously analyzed genomic, proteomic, transcriptomic and evolutionary data and systematically integrated these using Bayesian statistics into a predictive score for ciliary function. This resulted in 285 candidate ciliary genes. We found experimental evidence of ciliary associations for 24 out of 36 analyzed candidate proteins. In addition, we show that OSCP1, which has previously been implicated in two distinct non-ciliary functions, causes a cilium dysfunction phenotype when depleted in zebrafish. The candidate list forms the basis of CiliaCarta, a comprehensive ciliary compendium covering 836 genes. The resource can be used to objectively prioritize candidate genes in whole exome or genome sequencing of ciliopathy patients and can be accessed at http://bioinformatics.bio.uu.nl/john/syscilia/ciliacarta/.

bioinformatics↗