Characterization of the ZFX family of transcription factors that bind downstream of the start site of CpG island promoters

Our study focuses on a family of ubiquitously expressed human C₂H₂ zinc finger proteins comprised of ZFX, ZFY and ZNF711. Although their protein structure suggests that ZFX, ZFY and ZNF711 are transcriptional regulators, the mechanisms by which they influence transcription have not yet been elucidated. We used CRISPR-mediated deletion to create bi-allelic knockouts of ZFX and/or ZNF711 in female HEK293T cells (which naturally lack ZFY). We found that loss of either ZFX or ZNF711 reduced cell growth and that the double knockout cells have major defects in proliferation. RNA-seq analysis revealed that thousands of genes showed altered expression in the double knockout clones, suggesting that these TFs are critical regulators of the transcriptome. To gain insight into how these TFs regulate transcription, we created mutant ZFX proteins and analyzed them for DNA binding and transactivation capability. We found that zinc fingers 11–13 are necessary and sufficient for DNA binding and, in combination with the N terminal region, constitute a functional transactivator. Our functional analyses of the ZFX family provides important new insights into transcriptional regulation in human cells by members of the large, but under-studied family of C₂H₂ zinc finger proteins

Application of the Linux cluster for exhaustive window haplotype analysis using the FBAT and Unphased programs

Background: Genetic association studies have been used to map disease-causing genes. A newly introduced statistical method, called exhaustive haplotype association study, analyzes genetic information consisting of different numbers and combinations of DNA sequence variations along a chromosome. Such studies involve a large number of statistical calculations and subsequently high computing power. It is possible to develop parallel algorithms and codes to perform the calculations on a high performance computing (HPC) system. However, most existing commonly-used statistic packages for genetic studies are non-parallel versions. Alternatively, one may use the cutting-edge technology of grid computing and its packages to conduct non-parallel genetic statistical packages on a centralized HPC system or distributed computing systems. In this paper, we report the utilization of a queuing scheduler built on the Grid Engine and run on a Rocks Linux cluster for our genetic statistical studies. Results: Analysis of both consecutive and combinational window haplotypes was conducted by the FBAT (Laird et al., 2000) and Unphased (Dudbridge, 2003) programs. The dataset consisted of 26 loci from 277 extended families (1484 persons). Using the Rocks Linux cluster with 22 compute-nodes, FBAT jobs performed about 14.4–15.9 times faster, while Unphased jobs performed 1.1–18.6 times faster compared to the accumulated computation duration. Conclusion: Execution of exhaustive haplotype analysis using non-parallel software packages on a Linux-based system is an effective and efficient approach in terms of cost and performance

Differential regulation of the Drosophila sleep homeostat by circadian and arousal inputs.

One output arm of the sleep homeostat in Drosophila appears to be a group of neurons with projections to the dorsal fan-shaped body (dFB neurons) of the central complex in the brain. However, neurons that regulate the sleep homeostat remain poorly understood. Using neurogenetic approaches combined with Ca2+ imaging, we characterized synaptic connections between dFB neurons and distinct sets of upstream sleep-regulatory neurons. One group of the sleep-promoting upstream neurons is a set of circadian pacemaker neurons that activates dFB neurons via direct glutaminergic excitatory synaptic connections. Opposing this population, a group of arousal-promoting neurons downregulates dFB axonal output with dopamine. Co-activating these two inputs leads to frequent shifts between sleep and wake states. We also show that dFB neurons release the neurotransmitter GABA and inhibit octopaminergic arousal neurons. We propose that dFB neurons integrate synaptic inputs from distinct sets of upstream sleep-promoting circadian clock neurons, and arousal neurons

Publish or Practice? An Examination of Librarians' Contributions to Research

This article examines authorship of LIS literature in the context of practitioner and non-practitioner production of published research. For this study, 4,827 peer-reviewed articles from twenty LIS journals published between 1956 and 2011 were examined to determine the percentage of articles written by practitioners. The study identified a decrease in the proportion of articles authored by practitioners between 2006 and 2011. Topic analysis of articles revealed subtle yet distinct differences in research subject matter between practitioner-authored and non-practitioner-authored articles. If present trends continue, the character of LIS literature may shift away from many issues relating to practical librarianship

Uplink Sensing Using CSI Ratio in Perceptive Mobile Networks

Uplink sensing in perceptive mobile networks (PMNs), which uses uplink communication signals for sensing the environment around a base station, faces challenging issues of clock asynchronism and the requirement of a line-of-sight (LOS) path between transmitters and receivers. The channel state information (CSI) ratio has been applied to resolve these issues, however, current research on the CSI ratio is limited to Doppler estimation in a single dynamic path. This paper proposes an advanced parameter estimation scheme that can extract multiple dynamic parameters, including Doppler frequency, angle-of-arrival (AoA), and delay, in a communication uplink channel and completes the localization of multiple moving targets. Our scheme is based on the multi-element Taylor series of the CSI ratio that converts a nonlinear function of sensing parameters to linear forms and enables the applications of traditional sensing algorithms. Using the truncated Taylor series, we develop novel multiple-signal-classification grid searching algorithms for estimating Doppler frequencies and AoAs and use the least-square method to obtain delays. Both experimental and simulation results are provided, demonstrating that our proposed scheme can achieve good performances for sensing both single and multiple dynamic paths, without requiring the presence of a LOS path

The Effect of a Hyperdynamic Circulation on Tissue Doppler Values: A Simulation in Young Adults during Exercise

Left ventricular tissue Doppler imaging (TDI) velocities are used to monitor systolic and diastolic function, but it is not known how these may change in a hyperdynamic circulation, as often occurs in anesthesia and critical care medicine. Twenty-six healthy young volunteers were recruited and left ventricular systolic and diastolic tissue Doppler velocities measured at rest, light exercise, strenuous exercise, and recovery (10 minutes after exercise). At rest, TDI velocities significantly decreased from base to apex (P < .001). Within basal, mid, and apical sections, systolic and diastolic peak velocities differed between segments (P < .05), except for systolic middle (P = .094) and late diastolic apical velocities (P = .257). Basal septal velocities differed from basal lateral, for systolic (P = .041) but not diastolic peak values. Inferobasal radial values differed from basal lateral values for both systolic and diastolic velocities (P < .05). Both systolic and diastolic TDI velocities increased significantly in all segments in a proportionate manner with a hyperdynamic circulation