LONGO: An R package for interactive gene length dependent analysis for neuronal identity

Motivation: Reprogramming somatic cells into neurons holds great promise to model neuronal development and disease. The efficiency and success rate of neuronal reprogramming, however, may vary between different conversion platforms and cell types, thereby necessitating an unbiased, systematic approach to estimate neuronal identity of converted cells. Recent studies have demonstrated that long genes (\u3e100 kb from transcription start to end) are highly enriched in neurons, which provides an opportunity to identify neurons based on the expression of these long genes. Results: We have developed a versatile R package, LONGO, to analyze gene expression based on gene length. We propose a systematic analysis of long gene expression (LGE) with a metric termed the long gene quotient (LQ) that quantifies LGE in RNA-seq or microarray data to validate neuronal identity at the single-cell and population levels. This unique feature of neurons provides an opportunity to utilize measurements of LGE in transcriptome data to quickly and easily distinguish neurons from non-neuronal cells. By combining this conceptual advancement and statistical tool in a user-friendly and interactive software package, we intend to encourage and simplify further investigation into LGE, particularly as it applies to validating and improving neuronal differentiation and reprogramming methodologies. Availability and implementation: LONGO is freely available for download at https://github.com/biohpc/longo. Supplementary information: Supplementary data are available at Bioinformatics online

FE65 as a link between VLDLR and APP to regulate their trafficking and processing

<p>Abstract</p> <p>Background</p> <p>Several studies found that FE65, a cytoplasmic adaptor protein, interacts with APP and LRP1, altering the trafficking and processing of APP. We have previously shown that FE65 interacts with the ApoE receptor, ApoER2, altering its trafficking and processing. Interestingly, it has been shown that FE65 can act as a linker between APP and LRP1 or ApoER2. In the present study, we tested whether FE65 can interact with another ApoE receptor, VLDLR, thereby altering its trafficking and processing, and whether FE65 can serve as a linker between APP and VLDLR.</p> <p>Results</p> <p>We found that FE65 interacted with VLDLR using GST pull-down and co-immunoprecipitation assays in COS7 cells and in brain lysates. This interaction occurs via the PTB1 domain of FE65. Co-transfection with FE65 and full length VLDLR increased secreted VLDLR (sVLDLR); however, the levels of VLDLR C-terminal fragment (CTF) were undetectable as a result of proteasomal degradation. Additionally, FE65 increased cell surface levels of VLDLR. Moreover, we identified a novel complex between VLDLR and APP, which altered trafficking and processing of both proteins. Furthermore, immunoprecipitation results demonstrated that the presence of FE65 increased the interaction between APP and VLDLR <it>in vitro </it>and <it>in vivo</it>.</p> <p>Conclusions</p> <p>These data suggest that FE65 can regulate VLDLR trafficking and processing. Additionally, the interaction between VLDLR and APP altered both protein's trafficking and processing. Finally, our data suggest that FE65 serves as a link between VLDLR and APP. This novel interaction adds to a growing body of literature indicating trimeric complexes with various ApoE Receptors and APP.</p

Finite element modeling and in vivo analysis of electrode configurations for selective stimulation of pudendal afferent fibers

<p>Abstract</p> <p>Background</p> <p>Intraurethral electrical stimulation (IES) of pudendal afferent nerve fibers can evoke both excitatory and inhibitory bladder reflexes in cats. These pudendovesical reflexes are a potential substrate for restoring bladder function in persons with spinal cord injury or other neurological disorders. However, the complex distribution of pudendal afferent fibers along the lower urinary tract presents a challenge when trying to determine the optimal geometry and position of IES electrodes for evoking these reflexes. This study aimed to determine the optimal intraurethral electrode configuration(s) and locations for selectively activating targeted pudendal afferents to aid future preclinical and clinical investigations.</p> <p>Methods</p> <p>A finite element model (FEM) of the male cat urethra and surrounding structures was generated to simulate IES with a variety of electrode configurations and locations. The activating functions (AFs) along pudendal afferent branches innervating the cat urethra were determined. Additionally, the thresholds for activation of pudendal afferent branches were measured in α-chloralose anesthetized cats.</p> <p>Results</p> <p>Maximum AFs evoked by intraurethral stimulation in the FEM and in vivo threshold intensities were dependent on stimulation location and electrode configuration.</p> <p>Conclusions</p> <p>A ring electrode configuration is ideal for IES. Stimulation near the urethral meatus or prostate can activate the pudendal afferent fibers at the lowest intensities, and allowed selective activation of the dorsal penile nerve or cranial sensory nerve, respectively. Electrode location was a more important factor than electrode configuration for determining stimulation threshold intensity and nerve selectivity.</p

Scanned Potential Microscopy of Edge and Bulk Currents in the Quantum Hall Regime

Using an atomic force microscope as a local voltmeter, we measure the Hall voltage profile in a 2D electron gas in the quantum Hall (QH) regime. We observe a linear profile in the bulk of the sample in the transition regions between QH plateaus and a distinctly nonlinear profile on the plateaus. In addition, localized voltage drops are observed at the sample edges in the transition regions. We interpret these results in terms of theories of edge and bulk currents in the QH regime.Comment: 4 pages, 5 figure

Disruption of cholinergic neurotransmission, within a cognitive challenge paradigm, is indicative of Aβ-related cognitive impairment in preclinical Alzheimer’s disease after a 27-month delay interval

Background Abnormal beta-amyloid (Aβ) is associated with deleterious changes in central cholinergic tone in the very early stages of Alzheimer’s disease (AD), which may be unmasked by a cholinergic antagonist (J Prev Alzheimers Dis 1:1–4, 2017). Previously, we established the scopolamine challenge test (SCT) as a “cognitive stress test” screening measure to identify individuals at risk for AD (Alzheimer’s & Dementia 10(2):262–7, 2014) (Neurobiol. Aging 36(10):2709-15, 2015). Here we aim to demonstrate the potential of the SCT as an indicator of cognitive change and neocortical amyloid aggregation after a 27-month follow-up interval. Methods Older adults (N = 63, aged 55–75 years) with self-reported memory difficulties and first-degree family history of AD completed the SCT and PET amyloid imaging at baseline and were then seen for cognitive testing at 9, 18, and 27 months post-baseline. Repeat PET amyloid imaging was completed at the time of the 27-month exam. Results Significant differences in both cognitive performance and in Aβ neocortical burden were observed between participants who either failed vs. passed the SCT at baseline, after a 27-month follow-up period. Conclusions Cognitive response to the SCT (Alzheimer’s & Dementia 10(2):262–7, 2014) at baseline is related to cognitive change and PET amyloid imaging results, over the course of 27 months, in preclinical AD. The SCT may be a clinically useful screening tool to identify individuals who are more likely to both have positive evidence of amyloidosis on PET imaging and to show measurable cognitive decline over several years

Development of a PbWO4 Detector for Single-Shot Positron Annihilation Lifetime Spectroscopy at the GBAR Experiment

We have developed a PbWO4 (PWO) detector with a large dynamic range to measure the intensity of a positron beam and the absolute density of the ortho-positronium (o-Ps) cloud it creates. A simulation study shows that a setup based on such detectors may be used to determine the angular distribution of the emission and reflection of o-Ps to reduce part of the uncertainties of the measurement. These will allow to improve the precision in the measurement of the cross-section for the (anti)hydrogen formation by (anti)proton-positronium charge exchange and to optimize the yield of antihydrogen ion which is an essential parameter in the GBAR experiment

Effects of residual hardware impairments on secure NOMA-based cooperative systems

Non-orthogonal multiple access (NOMA) has been proposed as a promising technology that is capable of improving the spectral efficiency of fifth-generation wireless networks and beyond. However, in practical communication scenarios, transceiver architectures inevitably suffer from radio frequency (RF) front-end related impairments that cause non-negligible performance degradation. This issue can be addressed by analog and digital signal processing algorithms, however, inevitable aspects of this approach such as time-varying hardware characteristics and imperfect compensation schemes result to detrimental residual distortions. In the present contribution we investigate the physical layer security of NOMA- based amplify-and-forward relay systems under such realistically incurred residual hardware impairment (RHI) effects. Exact and asymptotic analytic expressions for the corresponding outage probability (OP) and intercept probability (IP) of the considered setup over multipath fading channels are derived and corroborated by respective simulation results. Based on this, it is shown that RHI affects both the legitimate users and eavesdroppers by increasing the OP and decreasing the IP. For a fixed OP, RHI generally increases the corresponding IP, thereby reducing the secure performance of the system. Further interesting insights are provided, verifying the importance of the offered results for the effective design and deployment of secure cooperative communication systems

Atomic and electronic reconstruction at van der Waals interface in twisted bilayer graphene

Control of the interlayer twist angle in two-dimensional (2D) van der Waals (vdW) heterostructures enables one to engineer a quasiperiodic moir\'e superlattice of tunable length scale. In twisted bilayer graphene (TBG), the simple moir\'e superlattice band description suggests that the electronic band width can be tuned to be comparable to the vdW interlayer interaction at a 'magic angle', exhibiting strongly correlated behavior. However, the vdW interlayer interaction can also cause significant structural reconstruction at the interface by favoring interlayer commensurability, which competes with the intralayer lattice distortion. Here we report the atomic scale reconstruction in TBG and its effect on the electronic structure. We find a gradual transition from incommensurate moir\'e structure to an array of commensurate domain structures as we decrease the twist angle across the characteristic crossover angle, $\theta_c$ ~1\deg. In the twist regime smaller than $\theta_c$ where the atomic and electronic reconstruction become significant, a simple moir\'e band description breaks down. Upon applying a transverse electric field, we observe electronic transport along the network of one-dimensional (1D) topological channels that surround the alternating triangular gapped domains, providing a new pathway to engineer the system with continuous tunability

Biofabrication : reappraising the definition of an evolving field

Biofabrication is an evolving research field that has recently received significant attention. In particular, the adoption of Biofabrication concepts within the field of Tissue Engineering and Regenerative Medicine has grown tremendously, and has been accompanied by a growing inconsistency in terminology. This article aims at clarifying the position of Biofabrication as a research field with a special focus on its relation to and application for Tissue Engineering and Regenerative Medicine. Within this context, we propose a refined working definition of Biofabrication, including Bioprinting and Bioassembly as complementary strategies within Biofabrication