scholarly journals Biallelic Variants in KIF17 Associated with Microphthalmia and Coloboma Spectrum

2021 ◽  
Vol 22 (9) ◽  
pp. 4471
Author(s):  
Antonella Riva ◽  
Antonella Gambadauro ◽  
Valeria Dipasquale ◽  
Celeste Casto ◽  
Maria Domenica Ceravolo ◽  
...  
Keyword(s):  
Genomic Dna ◽  
Outer Segment ◽  
Low Frequency ◽  
Compound Heterozygous ◽  
Ocular Abnormalities ◽  
Very Low Frequency ◽  
Healthy Mother ◽  
Compound Heterozygous Variants ◽  
Population Databases

Microphthalmia, anophthalmia, and coloboma (MAC) are a group of congenital eye anomalies that can affect one or both eyes. Patients can present one or a combination of these ocular abnormalities in the so called “MAC spectrum”. The KIF17 gene encodes the kinesin-like protein Kif17, a microtubule-based, ATP-dependent, motor protein that is pivotal for outer segment development and disc morphogenesis in different animal models, including mice and zebrafish. In this report, we describe a Sicilian family with two siblings affected with congenital coloboma, microphthalmia, and a mild delay of motor developmental milestones. Genomic DNA from the siblings and their unaffected parents was sequenced with a clinical exome that revealed compound heterozygous variants in the KIF17 gene (NM_020816.4: c.1255C > T (p.Arg419Trp); c.2554C > T (p.Arg852Cys)) segregating with the MAC spectrum phenotype of the two affected siblings. Variants were inherited from the healthy mother and father, are present at a very low-frequency in genomic population databases, and are predicted to be deleterious in silico. Our report indicates the potential co-segregation of these biallelic KIF17 variants with microphthalmia and coloboma, highlighting a potential conserved role of this gene in eye development across different species.

Role of Dominance Status in Shock-Stimulated Agonistic Behavior

1971 ◽  
Vol 29 (3) ◽  
pp. 768-770 ◽  
Author(s):  
G. McA. Kimbrell ◽  
D. Chesler
Keyword(s):  
High Frequency ◽  
Agonistic Behavior ◽  
Defensive Behavior ◽  
Low Frequency ◽  
Behavior Patterns ◽  
Dominance Status ◽  
Very Low Frequency ◽  
The Relationship ◽  
Shock Situation

To clarify the relationship between dominance status and frequency of specific sub-classes of agonistic behavior in response to foot shock, 30 mice were selected on the basis of high- or low-dominance status and paired in a foot-shock situation. Dominant pairs exhibit a high frequency of defensive behavior patterns whereas submissive pairs exhibit a very low frequency of defensive patterns.

Very-low-frequency oscillations in heart rate and blood pressure in periodic breathing: role of the cardiovascular limb of the hypoxic chemoreflex

2000 ◽  
Vol 99 (2) ◽  
pp. 125 ◽  
Author(s):  
Darrel P. FRANCIS ◽  
L. Ceri DAVIES ◽  
Keith WILLSON ◽  
Piotr PONIKOWSKI ◽  
Andrew J.S. COATS ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Low Frequency ◽  
Periodic Breathing ◽  
Very Low Frequency ◽  
Low Frequency Oscillations

scholarly journals Plasma Waves in the Inner Magnetosphere

2021 ◽  
pp. 85-119
Author(s):  
Hannu E. J. Koskinen ◽  
Emilia K. J. Kilpua
Keyword(s):  
Radiation Belt ◽  
Low Frequency ◽  
Plasma Waves ◽  
Mhd Waves ◽  
Particle Interactions ◽  
Inner Magnetosphere ◽  
Very Low Frequency ◽  
Link Type ◽  
Wave Modes

AbstractUnderstanding the role of plasma waves, extending from magnetohydrodynamic (MHD) waves at ultra-low-frequency (ULF) oscillations in the millihertz range to very-low-frequency (VLF) whistler-mode emissions at frequencies of a few kHz, is necessary in studies of sources and losses of radiation belt particles. In order to make this theoretically heavy part of the book accessible to a reader, who is not familiar with wave–particle interactions, we have divided the treatise into three chapters. In the present chapter we introduce the most important wave modes that are critical to the dynamics of radiation belts. The drivers of these waves are discussed in Chap. 10.1007/978-3-030-82167-8_5 and the roles of the wave modes as sources and losses of radiation belt particles are dealt with in Chap. 10.1007/978-3-030-82167-8_6.

scholarly journals Analysis of common and rare VPS13C variants in late-onset Parkinson disease

2020 ◽  
Vol 6 (1) ◽  
pp. 385 ◽  
Author(s):  
Uladzislau Rudakou ◽  
Jennifer A. Ruskey ◽  
Lynne Krohn ◽  
Sandra B. Laurent ◽  
Dan Spiegelman ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Genome Wide Association Study ◽  
Late Onset ◽  
Meta Analysis ◽  
Compound Heterozygous ◽  
Tagging Snp ◽  
Targeted Next Generation Sequencing ◽  
Compound Heterozygous Variants ◽  
Reduced Risk

ObjectiveWe aimed to study the role of coding VPS13C variants in a large cohort of patients with late-onset Parkinson disease (PD) (LOPD).MethodsVPS13C and its untranslated regions were sequenced using targeted next-generation sequencing in 1,567 patients with PD and 1,667 controls from 3 cohorts. Association tests of rare potential homozygous and compound heterozygous variants and burden tests for rare heterozygous variants were performed. Common variants were analyzed using logistic regression adjusted for age and sex in each of the cohorts, followed by a meta-analysis.ResultsNo biallelic carriers of rare VPS13C variants were found among patients, and 2 carriers of compound heterozygous variants were found in 2 controls. There was no statistically significant burden of rare (minor allele frequency [MAF] <1%) or very rare (MAF <0.1%) coding VPS13C variants in PD. A VPS13C haplotype including the p.R153H-p.I398I-p.I1132V-p.Q2376Q variants was nominally associated with a reduced risk for PD (meta-analysis of the tagging SNP p.I1132V [odds ratio = 0.48, 95% confidence interval = 0.28–0.82, p = 0.0052]). This haplotype was not in linkage disequilibrium with the known genome-wide association study top hit.ConclusionsOur results do not support a role for rare heterozygous or biallelic VPS13C variants in LOPD. Additional genetic replication and functional studies are needed to examine the role of the haplotype identified here associated with reduced risk for PD.

scholarly journals Analysis of common and rare VPS13C variants in late onset Parkinson disease

2019 ◽  
Author(s):  
Uladzislau Rudakou ◽  
Jennifer A. Ruskey ◽  
Lynne Krohn ◽  
Sandra B. Laurent ◽  
Dan Spiegelman ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Late Onset ◽  
Meta Analysis ◽  
Compound Heterozygous ◽  
Tagging Snp ◽  
Targeted Next Generation Sequencing ◽  
Functional Studies ◽  
Compound Heterozygous Variants ◽  
Reduced Risk

AbstractObjectiveWe aimed to study the role of coding VPS13C variants in a large cohort of late-onset PD (LOPD) patients.MethodsVPS13C and its untranslated regions were sequenced using targeted next-generation sequencing in 1,567 PD patients and 1,667 controls from 3 cohorts. Association tests of rare potential homozygous and compound heterozygous variants and burden tests for rare heterozygous variants were performed. Common variants were analyzed using logistic regression adjusted for age and sex in each of the cohorts, followed by a meta-analysis.ResultsNo bi-allelic carriers of rare VPS13C variants were found among patients and two carriers of compound heterozygous variants were found in two controls. There was no statistically significant burden of rare (MAF<1%) or very rare (MAF<0.1%) coding VPS13C variants in PD. A VPS13C haplotype including the p.R153H-p.I398I-p.I1132V-p.Q2376Q variants was nominally associated with a reduced risk for PD (meta-analysis of the tagging SNP p.I1132V (OR=0.48, 95%CI=0.28-0.82, p=0.0052). This haplotype was not in linkage disequilibrium (LD) with the known genome-wide association study (GWAS) top hit.ConclusionsOur results do not support a role for rare heterozygous or bi-allelic VPS13C variants in LOPD. Additional genetic replication and functional studies are needed to examine the role of the haplotype identified here associated with reduced risk for PD.

Role of sinoaortic afferents in modulating BP and pulse-interval spectral characteristics in unanesthetized cats

1991 ◽  
Vol 261 (6) ◽  
pp. H1811-H1818 ◽  
Author(s):  
M. Di Rienzo ◽  
G. Parati ◽  
P. Castiglioni ◽  
S. Omboni ◽  
A. U. Ferrari ◽  
...  
Keyword(s):  
Spectral Analysis ◽  
High Frequency ◽  
Spectral Characteristics ◽  
Low Frequency ◽  
Pulse Interval ◽  
Very Low Frequency ◽  
Variability Pattern ◽  
Spectral Components ◽  
Related Increase

Sinoaortic denervation (SAD) is accompanied by an increase in blood pressure (BP) and a reduction in pulse-interval (PI) variance. Little is known, however, about the effect of SAD on the complex BP and PI variability pattern, which is identified by spectral analysis. In nine unanesthetized cats in which intra-arterial BP was monitored before and 7-10 days after SAD, spectral powers (estimated by fast Fourier transform) were calculated for the low frequency (LF, 0.025-0.07 Hz), midfrequency (MF, 0.07-0.14 Hz), and high frequency (HF, 0.14-0.60 Hz) band. The very low frequency (VLF) BP and PI components (VLF less than 0.025 Hz) were also estimated. SAD increased systolic BP variance and decreased PI variance. The reduction of PI variance was paralleled by significant and marked reductions in all PI powers including the VLF components. In contrast, the increase in systolic BP variance was accompanied by a marked increase in LF power, a decrease in MF power, and no change in HF power. The VLF BP components increased after SAD for frequencies between 0.025 and 0.0012 Hz, whereas a sudden marked reduction was observed below 0.0012 Hz. Similar results were obtained for diastolic BP powers. Thus the reduction in PI variance induced by SAD is paralleled by a reduction in all PI fluctuations identified by spectral analysis. This is not the case for the SAD-related increase in BP variance, which is accompanied by an increase, no change, or even a reduction in the different BP spectral components.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Case Report: Novel Compound Heterozygous Variants in TRIOBP Associated With Congenital Deafness in a Chinese Family

2021 ◽  
Vol 12 ◽  
Author(s):  
Cong Zhou ◽  
Yuanyuan Xiao ◽  
Hanbing Xie ◽  
Jing Wang ◽  
Shanling Liu
Keyword(s):  
Autosomal Recessive ◽  
Actin Binding ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Pathogenic Variants ◽  
Heterozygous Carriers ◽  
Compound Heterozygous Variants ◽  
And Function ◽  
Population Databases ◽  
Generation Sequencing

Autosomal recessive non-syndromic deafness-28 (DFNB28) is characterized by prelingual, profound sensorineural hearing loss (HL). The disease is related to variants of the TRIOBP gene. TRIO and F-actin binding protein (TRIOBP) plays crucial roles in modulating the assembly of the actin cytoskeleton and are responsible for the proper structure and function of stereocilia in the inner ear. This study aimed to identify pathogenic variants in a patient with HL. Genomic DNA obtained from a 33-year-old woman with HL was evaluated using a disease-targeted gene panel. Using next generation sequencing and bioinformatics analysis, we identified two novel TRIOBP c.1170delC (p.S391Pfs*488) and c.3764C &gt; G (p.S1255*) variants. Both parents of the patient were heterozygous carriers of the gene. The two variants have not been reported in general population databases or published literature. The findings of this study will broaden the spectrum of pathogenic variants in the TRIOBP gene.

The photoreceptor cytoskeleton visualized

1992 ◽  
Vol 50 (1) ◽  
pp. 480-481
Author(s):  
Beth Burnside
Keyword(s):  
Outer Segment ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Cell Polarization ◽  
Synaptic Proteins ◽  
Cell Functions ◽  
Vertebrate Photoreceptor ◽  
Numerous Cell ◽  
Turn Over

The vertebrate photoreceptor provides a drammatic example of cell polarization. Specialized to carry out phototransduction at its distal end and to synapse with retinal interneurons at its proximal end, this long slender cell has a uniquely polarized morphology which is reflected in a similarly polarized cytoskeleton. Membranes bearing photopigment are localized in the outer segment, a modified sensory cilium. Sodium pumps which maintain the dark current critical to photosensory transduction are anchored along the inner segment plasma membrane between the outer segment and the nucleus.Proximal to the nucleus is a slender axon terminating in specialized invaginating synapses with other neurons of the retina. Though photoreceptor diameter is only 3-8u, its length from the tip of the outer segment to the synapse may be as great as 200μ. This peculiar linear cell morphology poses special logistical problems and has evoked interesting solutions for numerous cell functions. For example, the outer segment membranes turn over by means of a unique mechanism in which new disks are continuously added at the proximal base of the outer segment, while effete disks are discarded at the tip and phagocytosed by the retinal pigment epithelium. Outer segment proteins are synthesized in the Golgi near the nucleus and must be transported north through the inner segment to their sites of assembly into the outer segment, while synaptic proteins must be transported south through the axon to the synapse.The role of the cytoskeleton in photoreceptor motile processes is being intensely investigated in several laboratories.

The Attenuation of Very Low Frequency Brain Oscillations in Transitions from a Rest State to Active Attention

2009 ◽  
Vol 23 (4) ◽  
pp. 191-198 ◽  
Author(s):  
Suzannah K. Helps ◽  
Samantha J. Broyd ◽  
Christopher J. James ◽  
Anke Karl ◽  
Edmund J. S. Sonuga-Barke
Keyword(s):  
Brain Activity ◽  
Sampling Rate ◽  
Low Frequency ◽  
Future Research ◽  
Adhd Symptoms ◽  
Default Mode ◽  
Very Low Frequency ◽  
Wide Range ◽  
Interference Hypothesis ◽  
Mode Interference

Background: The default mode interference hypothesis ( Sonuga-Barke & Castellanos, 2007 ) predicts (1) the attenuation of very low frequency oscillations (VLFO; e.g., .05 Hz) in brain activity within the default mode network during the transition from rest to task, and (2) that failures to attenuate in this way will lead to an increased likelihood of periodic attention lapses that are synchronized to the VLFO pattern. Here, we tested these predictions using DC-EEG recordings within and outside of a previously identified network of electrode locations hypothesized to reflect DMN activity (i.e., S3 network; Helps et al., 2008 ). Method: 24 young adults (mean age 22.3 years; 8 male), sampled to include a wide range of ADHD symptoms, took part in a study of rest to task transitions. Two conditions were compared: 5 min of rest (eyes open) and a 10-min simple 2-choice RT task with a relatively high sampling rate (ISI 1 s). DC-EEG was recorded during both conditions, and the low-frequency spectrum was decomposed and measures of the power within specific bands extracted. Results: Shift from rest to task led to an attenuation of VLFO activity within the S3 network which was inversely associated with ADHD symptoms. RT during task also showed a VLFO signature. During task there was a small but significant degree of synchronization between EEG and RT in the VLFO band. Attenuators showed a lower degree of synchrony than nonattenuators. Discussion: The results provide some initial EEG-based support for the default mode interference hypothesis and suggest that failure to attenuate VLFO in the S3 network is associated with higher synchrony between low-frequency brain activity and RT fluctuations during a simple RT task. Although significant, the effects were small and future research should employ tasks with a higher sampling rate to increase the possibility of extracting robust and stable signals.

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