bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity-dependent decline and recovery of synaptic transmission in central parts of surviving primary afferents after their peripheral cut
Authors: Le Bon-Jégo Morgane , Cabirol Marie-Jeanne , Cattaert Daniel 
Published: July 2022

AbstractWhereas axons deprived of their nucleus degenerate within a few days in Mammals, they survive for several months in Crustacean. However, it is not known if central synapses from sensory axons may preserve their molecular machinery in the absence of spiking activity, after peripheral axotomy, which suppress their nucleus. Using electrophysiology techniques and electron microscopy imaging we report that 1) Electron microscopy analysis confirms previous observations that glial cell nucleus present in sensory nerve, proliferate an migrate to axon tubes, in which they form close contact with surviving axons; 2) after peripheral axotomy performed in vivo on Coxo-Basipodite chordotonal organ (CBCO) sensory nerve does not convey any sensory message, but antidromic volleys are observed; 3) Central synaptic transmission to motoneurons (MNs) progressively declines over #200 days (90% of monosynaptic excitatory transmission is lost after 3 weeks, whereas 60% of polysynaptic inhibitory transmission persist up to 6 months). After #200 days no transmission is observed anymore; 4) However, this total loss is only apparent, because repetitive electrical stimulation of the sensory nerve in vitro progressively restores first inhibitory post-synaptic potentials (IPSPs) then excitatory post-synaptic potentials (EPSPs); 5) The loss of synaptic transmission can be prevented by in vivo chronic sensory nerve stimulation; 6) Using simulations based on the geometric arrangements of synapses of the monosynaptic excitatory transmission and disynaptic inhibitory pathways, we have shown that antidromic activity in CBCO nerve could play a role in maintenance of synaptic function of inhibitory pathways to MNs, but not on monosynaptic excitatory transmission to MNs. Taken together, our study confirms the key role of glial nucleus in axon survival, that machinery for spike conduction and synaptic release even if no activity is present for several months. After long silence periods (>6 months) spike conduction and synaptic function can still be restored by electrical activity.
Evaluating the efficacy of multi-echo ICA denoising on model-based fMRI
Authors: Steel Adam , Garcia Brenda D. , Silson Edward H. , Robertson Caroline E. 
Published: July 2022

AbstractfMRI is an indispensable tool for neuroscience investigation, but this technique is limited by multiple sources of physiological and measurement noise. These noise sources are particularly problematic for analysis techniques that require high signal-to-noise ratio for stable model fitting, such as voxel-wise modeling. Multi-echo data acquisition in combination with echo-time dependent ICA denoising (ME-ICA) represents one promising strategy to mitigate physiological and hardware-related noise sources as well as motion-related artifacts. However, most studies employing ME-ICA to date are resting-state fMRI studies, and therefore we have a limited understanding of the impact of ME-ICA on task or model-based fMRI paradigms. Here, we addressed this knowledge gap by comparing data quality and model fitting performance on data acquired during a visual population receptive field (pRF) mapping paradigm (N=13 participants) after using one of three preprocessing procedures: ME-ICA, optimally combined multi-echo data without ICA-denoising, and typical single echo processing. As expected, multi-echo fMRI improved temporal signal-to-noise compared to single echo fMRI, with ME-ICA amplifying the improvement compared to optimal combination alone. However, unexpectedly, this boost in temporal signal-to-noise did not directly translate to improved model fitting performance: compared to single echo acquisition, model fitting was only improved after ICA-denoising. Specifically, compared to single echo acquisition, ME-ICA resulted in improved variance explained by our pRF model throughout the visual system, including anterior regions of the temporal and parietal lobes where SNR is typically low, while optimal combination without ICA did not. ME-ICA also improved reliability of parameter estimates compared to single echo and optimally combined multi-echo data without ICA-denoising. Collectively, these results suggest that ME-ICA is effective for denoising task-based fMRI data for modeling analyses and maintains the integrity of the original data. Therefore, ME-ICA may be beneficial for complex fMRI experiments, including task fMRI studies, voxel-wise modeling, and naturalistic paradigms.
CCR5 deficiency normalizes TIMP levels, working memory, and gamma oscillation power in APOE4 targeted replacement mice
Authors: Greco Griffin A. , Rock Mitchell , Amontree Matthew , Lanfranco Maria Fe , Korthas Holly , Hong Sung Hyeok , Turner R. Scott , Rebeck G. William , Conant Katherine 
Published: July 2022

AbstractTheAPOE4allele increases the risk for Alzheimer’s disease (AD) in a dose-dependent manner and is also associated with cognitive decline in non-demented elderly controls. In mice with targeted gene replacement (TR) of murineAPOEwith humanAPOE3orAPOE4, the latter show reduced neuronal dendritic complexity and impaired learning.APOE4TR mice also show reduced gamma oscillation power and sharp wave ripple (SWR) abundance, neuronal population activities important to learning and memory. Published work has shown that brain extracellular matrix (ECM) can reduce neuroplasticity as well as gamma power and SWR abundance, while attenuation of ECM can instead enhance these endpoints. In the present study we examine human cerebrospinal fluid (CSF) samples fromAPOE3andAPOE4individuals and brain lysates fromAPOE3andAPOE4TR mice for levels of ECM effectors that can increase matrix deposition and restrict neuroplasticity. We find that CCL5, a molecule linked to ECM deposition in liver and kidney, is increased in CSF samples fromAPOE4individuals. Levels of tissue inhibitor of metalloproteinases (TIMPs), which inhibit the activity of ECM-degrading enzymes, are also increased inAPOE4CSF as well as protein lysates fromAPOE4TR mice. Importantly, as compared to wildtype/APOE4heterozygotes, CCR5 knockout/APOE4heterozygotes show reduced TIMP levels and enhanced EEG gamma power. The latter also show improved learning and memory, suggesting that the CCR5/CCL5 axis could represent a therapeutic target forAPOE4individuals.
Machine Learning Electroencephalography Biomarkers Predictive of Epworth Sleepiness Scale
Authors: Araujo Matheus , Ghosn Samer , Wang Lu , Hariadi Nengah , Wells Samantha , Carl Saab Y , Mehra Reena 
Published: July 2022

AbstractExcessive daytime sleepiness (EDS) causes difficulty in concentrating and continuous fatigue during the day. In a clinical setting, the assessment and diagnosis of EDS relies mostly on subjective questionnaires and verbal reports, which compromises the effectiveness of available therapies. In this study, we used a computational pipeline for the automated, rapid, high-throughput and objective analysis of retrospective encephalography (EEG) data to develop objective, surrogate biomarkers for EDS, thereby defining the quantitative EEG changes in individuals with High Epworth Sleepiness Scale (ESS) (n=31), compared to a group of individuals with Low ESS (n=41) at Cleveland Clinic. Signal processing of EEG showed significantly different EEG features in the Low ESS group compared to High ESS, including power enhancement in the alpha and beta bands, and attenuation in the delta and theta bands. Moreover, machine learning algorithms trained on the binary classification of High vs Low ESS reached >80% accuracy. These results demonstrate that EEG data contain information in the form of rhythmic activity that could be leveraged for the quantitative assessment of EDS using machine learning.
Pixel size limit of the PRIMA implants: from humans to rodents and back
Authors: Wang Bing-Yi , Chen Zhijie Charles , Bhuckory Mohajeet , Goldstein Anna Kochnev , Palanker Daniel 
Published: July 2022

AbstractObjectiveRetinal prostheses aim at restoring sight in patients with retinal degeneration by electrically stimulating the inner retinal neurons. Clinical trials with patients blinded by atrophic Age-related Macular Degeneration (AMD) using the PRIMA subretinal implant, a 2×2 mm array of 100μm-wide photovoltaic pixels, have demonstrated a prosthetic visual acuity closely matching the pixel size. Further improvement in resolution requires smaller pixels, which necessitates more intense stimulation.ApproachHere, we examine the lower limit of the pixel size for PRIMA implants by modeling the electric field, leveraging the clinical benchmarks, as well as using a preclinical animal data to assess the stimulation strength and contrast of various patterns. Visually evoked potentials were measured in RCS rats with photovoltaic implants of 100 and 75μm pixels and compared to clinical thresholds with 100 μm pixels. Electrical stimulation model calibrated by these clinical and rodent data was used to predict the performance of the implant with smaller pixels.Main ResultsWe found that PRIMA implants with 75μm pixels under the maximum safe near-infrared (880nm) illumination of 8 mW/mm2 with 30% duty cycle (10ms pulses at 30Hz) should provide a similar perceptual brightness as with 100 μm pixels under 3 mW/mm2 irradiance, used in the current clinical trials. Contrast of the Landolt C pattern scaled down to 75μm pixels is also similar under such illumination to that with 100μm pixels in clinical settings, increasing the maximum acuity from 20/420 to 20/300.SignificanceComputational model of the photovoltaic subretinal prosthesis defines the minimum pixel size of the PRIMA implants as 75μm. Increasing the implant width from 2 to 3 mm and reducing the pixel size from 100 to 75μm will nearly quadrupole the number of pixels and thereby should significantly improve the visual performance. Smaller pixels of the same bipolar flat geometry would require excessively intense illumination, and therefore a different pixel design should be considered for further improvement in resolution.
Online grocery shopping during the COVID-19 pandemic - perspectives of adolescents and young adults
Authors: Brandt Eric J , Hadler Nicole , Locher Ione , Hoffs Charlie T , Waselewski Marika E , Chang Tammy 
Published: July 2022

ABSTRACTObjectiveTo assess perspectives of online grocery shopping during the COVID-19 pandemic among youth, rural residents, and Supplemental Nutrition Assistance Program (SNAP) participants.DesignOpen-ended text message survey data. Survey questions assessed rates of use and perspectives of online grocery shopping among youth and their families during the COVID-19 pandemic. Qualitative analysis of survey data from 875 participants (response rate=76.4%) to identify themes in experience with multivariable logistic regression to test associations between online grocery shopping (pickup, delivery, or either) with rurality and SNAP participation.SettingUnited StatesParticipantsNationwide text-messaging poll of youth (14-24 years-old) recruited to meet benchmarks based on the American Community Survey.ResultsDuring the pandemic online grocery shopping was used frequently (46.7%). Safety and convenience were the primary reasons for preferring a shopping mode (in-person or online). Most online shoppers had positive experiences (59.4%), primarily due to convenience; negative experiences (28.3%) were from inaccuracies, inconveniences of the process, and delivery costs. Rural and suburban residence was associated with higher pickup (OR 2.02 and 1.51, respectively, p=.03) and lower delivery use (OR 0.33 and 0.72, respectively, p=.003) compared to urban residence. SNAP participation was not associated with any type of online grocery shopping.ConclusionsOnline grocery shopping is common among youth and their families regardless of rurality or SNAP participation, but there are several youth-identified areas for improvement.GRAPHICAL ABSTRACT
Brain dynamics predictive of response to psilocybin for treatment-resistant depression
Authors: Vohryzek Jakub , Cabral Joana , Lord Louis-David , Fernandes Henrique M , Roseman Leor , Nutt David J , Carhart-Harris Robin L , Deco Gustavo , Kringelbach Morten L 
Published: July 2022

AbstractPsilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here we leveraged the differential outcome in responders and non-responders to psilocybin (10mg and 25mg, 7 days apart) therapy for depression - to gain new insights into regions and networks implicated in the restoration of healthy brain dynamics. We used whole-brain modelling to fit the spatiotemporal brain dynamics at rest in both responders and non-responders before treatment. Dynamic sensitivity analysis of systematic perturbation of these models enabled us to identify specific brain regions implicated in a transition from a depressive brain state to a heathy one. Binarizing the sample into treatment responders (>50% reduction in depressive symptoms) versus non-responders enabled us to identify a subset of regions implicated in this change. Interestingly, these regions correlate with in vivo density maps of serotonin receptors 5-HT2A and 5-HT1A, which psilocin, the active metabolite of psilocybin, has an appreciable affinity for, and where it acts as a full-to-partial agonist. Serotonergic transmission has long been associated with depression and our findings provide causal mechanistic evidence for the role of brain regions in the recovery from depression via psilocybin.
Slice’N’Dice: Maximising the value of predicted models for structural biologists
Authors: Simpkin Adam J. , Elliott Luc G. , Stevenson Kyle , Krissinel Eugene , Rigden Daniel J. , Keegan Ronan M. 
Published: July 2022

AbstractWith the advent of next generation modelling methods, such as AlphaFold2, structural biologists are increasingly using predicted structures as search models for Molecular Replacement (MR) when experimental structures of homologues are unavailable. Inaccuracy in domain-domain orientations is often a key limitation when using predicted models for MR. Slice’N’Dice is a software package designed to address this issue by first slicing models into distinct structural units and then automatically placing the slices using Phaser. The slicing step can use AlphaFold2’s predicted aligned error (PAE), or can operate via a variety of Cα atom clustering algorithms, extending applicability to structures of any origin. The number of splits can be selected by the user. Slice’N’Dice is available in CCP4 8.0 and is currently being adapted for cryo-EM use cases.
Developmental spontaneous activity promotes sensory domains, frequency tuning and proper gain in central auditory circuits
Authors: Kersbergen Calvin J. , Babola Travis A. , Rock Jason , Bergles Dwight E. 
Published: July 2022

SummaryNeurons that process sensory information exhibit bursts of electrical activity during development, providing early training to circuits that will later encode similar features of the external world. In the mammalian auditory system, this intrinsically generated activity emerges from the cochlea prior to hearing onset, but its role in maturation of auditory circuitry remains poorly understood. We show that selective disruption of cochlear supporting cell spontaneous activity suppressed patterned burst firing of central auditory neurons without impacting cell survival or acoustic thresholds. However, neurons within the inferior colliculus of these mice exhibited enhanced acoustic sensitivity and broader frequency tuning, resulting in wider isofrequency lamina. Despite this enhanced neural responsiveness, total tone-responsive regions of the midbrain and cortex were substantially smaller. Thus, loss of pre-hearing cochlear activity causes profound changes in neural encoding of sound, with important implications for restoration of hearing in individuals that experience disrupted activity during this critical developmental period.
Photovoltaic Implant Simulator Reveals the Resolution Limits in Subretinal Prosthesis
Authors: Chen Zhijie Charles , Wang Bing-Yi , Goldstein Anna Kochnev , Butt Emma , Mathieson Keith , Palanker Daniel 
Published: July 2022

AbstractObjectiveThe photovoltaic subretinal prosthesis, PRIMA, restores central vision in patients blinded by atrophic age-related macular degeneration (AMD), with a resolution closely matching the 100 µm pixel size of the implant. Improvement in resolution requires smaller pixels, but the resultant electric field may not provide sufficient stimulation strength in the inner nuclear layer (INL) or may lead to excessive crosstalk between neighboring electrodes, giving low contrast stimulation patterns. We study approaches to shaping the electric field in the retina for prosthetic vision with higher resolution and improved contrast.ApproachWe present a new computational framework, RPSim, that efficiently computes the electric field in the retina generated by a photovoltaic implant with thousands of electrodes. Leveraging the PRIMA clinical results as a benchmark, we use RPSim to predict the stimulus strength and contrast of the electric field in the retina with various pixel designs and stimulation patterns.Main resultsWe demonstrate that by utilizing monopolar pixels as both, anodes and cathodes to suppress crosstalk, most patients may achieve resolution no worse than 48 µm. Closer proximity between the electrodes and the INL, achieved with pillar electrodes, enhances the stimulus strength and contrast and may enable 24 µm resolution with 20 µm pixels, at least in some patients.SignificanceA resolution of 24 µm on the retina corresponds to a visual acuity of 20/100, which is over 4 times higher than the current best prosthetic acuity of 20/438, promising a significant improvement of central vision for many AMD patients.
Genetic requirements for repair of lesions caused by single genomic ribonucleotides in S phase
Authors: Schindler Natalie , Tonn Matthias , Kellner Vanessa , Fung Jia Jun , Lockhart Arianna , Vydzhak Olga , Juretschke Thomas , Möckel Stefanie , Beli Petra , Khmelinskii Anton , Luke Brian 
Published: July 2022

AbstractSingle ribonucleoside monophosphates (rNMPs) are transiently present in eukaryotic genomes. The RNase H2-dependent ribonucleotide excision repair (RER) pathway ensures error-free genomic rNMP removal. In pathological conditions, genomic rNMP levels can rise and persist. If these rNMPs hydrolyse in, or prior to, S phase, toxic single-ended double-strand breaks (seDSBs) can occur upon an encounter with replication forks. How such rNMP-derived seDSB lesions are repaired is unclear. We employed a cell cycle phase restricted allele of RNase H2 as a genetic tool to induce nicks at rNMPs specifically in S phase to generate such lesions and study their repair. Here, we introduce a network of genes that maintain DNA integrity when rNMP-derived nick lesions arise during DNA replication. We use genetic methods to characterise the molecular requirements of a Top1-independent, rNMP-derived nick lesion repair (NLR). In NLR, the RAD52 epistasis group becomes essential for homology-directed repair (HDR). Moreover, the previously described Rtt101Mms1-Mms22 dependent ubiquitylation of histone H3 is essential for NLR in cells with high rNMP load, and loss of Rtt101Mms1-Mms22 combined with RNase H2 dysfunction leads to compromised cellular fitness. We discuss the genetic NLR network in the context of human disease, where cancer therapies may be able to exploit these synthetic lethalities.
Modeling Hippocampal Spatial Cells in Rodents navigating in 3D environments
Authors: Aziz Azra , Patil Bharat Kailas , Lakshmikanth Kailash , Sreeharsha Peesapati S S , Mukhopadhay Ayan , Chakravarthy V Srinivasa 
Published: July 2022

AbstractStudies on the neural correlates of navigation in 3D environments are plagued by several unresolved issues. For example, experimental studies show markedly different place cell responses in rats and bats, both navigating in 3D environments. In an effort to understand this divergence, we propose a deep autoencoder network to model the place cells and grid cells in a simulated agent navigating in a 3D environment. We also explore the possibility of a vital role that Head Direction (HD) tuning plays in determining the isotropic or anisotropic nature of the observed place fields in different species. The input layer to the autoencoder network model is the HD layer which encodes the agent’s HD in terms of azimuth (θ) and pitch angles (ϕ). The output of this layer is given as input to the Path Integration (PI) layer, which integrates velocity information into the phase of oscillating neural activity. The output of the PI layer is modulated and passed through a low pass filter to make it purely a function of space before passing it to an autoencoder. The bottleneck layer of the autoencoder model encodes the spatial cell like responses. Both grid cell and place cell like responses are observed. The proposed model is verified using two experimental studies with two 3D environments in each. This model paves the way for a holistic approach of using deep networks to model spatial cells in 3D navigation.
Unexpected long-term retention of subcutaneous beeswax implants and additional notes on dose and composition from four testosterone implant studies
Authors: Boersma Jordan , McQueen Alexandra , Peters Anne , Welklin Joseph F. , Khalil Sarah , Quispe René , Goymann Wolfgang , Schwabl Hubert 
Published: July 2022

ABSTRACTExperimental manipulations of testosterone have advanced our understanding of the hormonal control of traits across vertebrates. Implants are commonly used to supplement testosterone and other hormones to organisms, as they can be readily scaled to produce desired hormone levels in circulation. Concerns about pharmacological (i.e. unnatural) doses of traditional silastic implants led to innovation in implant methods, with time-release pellets and beeswax implants proposed as solutions. A study comparing silastic, time-release pellets, and beeswax implants found the latter to be most effective in delivering a physiologically relevant dose. One proposed advantage to subcutaneous beeswax implants is that they are expected to degrade within the body, thus removing the obligation to recapture implanted individuals in the field. However, few studies have reported on dosage and no published literature has examined the assumption that beeswax implants readily degrade as expected. Here we present time-release androgen data in relation to implants containing varying levels of testosterone from four separate implant studies. In addition, we report long-term persistence of subcutaneous implants, including two cases of implants being retained for > 2 years. Finally, we offer recommendations on the composition and implementation of beeswax implants to aid the pursuit of minimally invasive and physiologically relevant manipulations of circulating hormones.
Integrated single-nucleus and spatial transcriptomics captures transitional states in soybean nodule symbiosis establishment
Authors: Liu Zhijian , Kong Xiangying , Long Yanping , Zhang Hong , Jia Jinbu , Qiu Lijuan , Zhai Jixian , Yan Zhe 
Published: July 2022

AbstractLegumes form symbiosis with rhizobium leading to the development of nitrogen-fixing nodules. By integrating single-nucleus and spatial transcriptomics, we established a cell atlas of soybean nodules and roots. In central infected zone of nodule, we found that uninfected cells specialize into functionally distinct sub-groups during nodule development and revealed a transitional subtype of infected cells with enriched nodulation-related genes. Overall, our results provide a single-cell perspective for understanding rhizobium-legume symbiosis.