bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternative somatic and germline gene-regulatory strategies during starvation-induced developmental arrest
Authors: Webster Amy K. , Chitrakar Rojin , Baugh L. Ryan 
Published: May 2021

SUMMARYNutrient availability governs growth and quiescence, and many animals arrest development when starved. Somatic and germline cells have distinct functions and constraints, suggesting different regulatory mechanisms contribute to an integrated starvation response. UsingC. elegansL1 arrest as a model, we show that gene expression changes deep into starvation. Surprisingly, relative expression of germline-enriched genes increases for days. We conditionally degraded the large subunit of RNA Polymerase II and found that early but not late somatic transcription is required for survival and that germline transcription does not affect survival. Expression analysis revealed that thousands of genes are continuously transcribed in the soma, though their absolute abundance declines, while the germ line is transcriptionally quiescent with extreme transcript stability. This work reveals alternative somatic and germline gene-regulatory strategies during starvation, with the soma relying on a robust transcriptional response to support immediate survival while the germ line relies on transcriptional quiescence and mRNA stability to maintain future reproductive success.
Preserved motor memory in Parkinson’s disease
Authors: Lahlou Soraya , Gabitov Ella , Owen Lucy , Shohamy Daphna , Sharp Madeleine 
Published: May 2021

ABSTRACTPatients with Parkinson’s disease, who lose the dopaminergic projections to the striatum, are impaired in certain aspects of motor learning. Recent evidence suggests that, in addition to its role in motor performance, the striatum plays a key role in the memory of motor learning. Whether Parkinson’s patients have impaired motor memory and whether motor memory is modulated by dopamine at the time of initial learning is unknown. To address these questions, we measured memory of a learned motor sequence in Parkinson’s patients who were either On or Off their dopaminergic medications. We compared them to a group of older and younger controls. Contrary to our predictions, motor memory was not impaired in patients compared to older controls, and was not influenced by dopamine state at the time of initial learning. To probe post-learning consolidation processes, we also tested whether learning a new sequence shortly after learning the initial sequence would interfere with later memory. We found that, in contrast to younger adults, neither older adults nor patients were susceptible to this interference. These findings suggest that motor memory is preserved in Parkinson’s patients and raise the possibility that motor memory in patients is supported by compensatory non-dopamine sensitive mechanisms. Furthermore, given the similar performance characteristics observed in the patients and older adults and the absence of an effect of dopamine, these results raise the possibility that aging and Parkinson’s disease affect motor memory in similar ways.
Ultraspecific somatic SNV and indel detection in single neurons using primary template-directed amplification
Authors: Luquette Lovelace J. , Miller Michael B. , Zhou Zinan , Bohrson Craig L. , Galor Alon , Lodato Michael A. , Gawad Charles , West Jay , Walsh Christopher A. , Park Peter J. 
Published: May 2021

AbstractPrimary template-directed amplification (PTA) is an improved amplification technique for single-cell DNA sequencing. We generated whole-genome analysis of 76 single neurons and developed SCAN2, a computational method to accurately identify both clonal and non-clonal somatic (i.e., limited to a single neuron) single nucleotide variants (SNVs) and small insertions and deletions (indels) using PTA data. Our analysis confirms an increase in non-clonal somatic mutation in single neurons with age, but revises estimates for the rate of this accumulation to be 15 SNVs per year. We also identify artifacts in other amplification methods. Most importantly, we show that somatic indels also increase by at least 2 indels per year per neuron and that indels may have a larger impact on gene function than somatic SNVs in human neurons.
Intracortical probe arrays with silicon backbone and microelectrodes on thin polyimide wings enable long-term stable recordings in vivo
Authors: Kilias Antje , Lee Yu-Tao , Froriep Ulrich P. , Moser Dominik , Holzhammer Tobias , Egert Ulrich , Fang Weileun , Paul Oliver , Ruther Patrick 
Published: May 2021

AbstractObjectiveRecording and stimulating neuronal activity across different brain regions requires interfacing at multiple sites using dedicated tools while tissue reactions at the recording sites often prevent their successful long-term application. This implies the technological challenge of developing complex probe geometries while keeping the overall footprint minimal, and of selecting materials compatible with neural tissue. While the potential of soft materials in reducing tissue response is uncontested, the implantation of these materials is often limited to reliably target neuronal structures across large brain volumes.ApproachWe report on the development of a new multi-electrode array exploiting the advantages of soft and stiff materials by combining 7-μm-thin polyimide wings carrying platinum electrodes with a silicon backbone enabling a safe probe implantation. The probe fabrication applies microsystems technologies in combination with a temporal wafer fixation method for rear side processing, i.e., grinding and deep reactive ion etching, of slender probe shanks and electrode wings. The wing-type neural probes are chronically implanted into the entorhinal-hippocampal formation in the mouse forin vivorecordings of freely behaving animals.Main resultsProbes comprising the novel wing-type electrodes have been realized and characterized in view of their electrical performance and insertion capability. Chronic electrophysiologicalin vivorecordings of the entorhinal-hippocampal network in the mouse of up to 104 days demonstrated a stable yield of channels containing identifiable multi-unit and single-unit activity outperforming probes with electrodes residing on a Si backbone.SignificanceThe innovative fabrication process using a process compatible, temporary wafer bonding allowed to realize new Michigan style probe arrays. The wing-type probe design enables a precise probe insertion into brain tissue and long-term stable recordings of unit activity due to the application of a stable backbone and 7-μm-thin probe wings provoking locally a minimal tissue response and protruding from the glial scare of the backbone.
The effect of habitat type on population distribution and abundance of Rothschild’s Giraffe (Giraffa camelopardalis rothschildi) in Ruma National Park and Mwea National Reserve in Kenya
Authors: Gathuku George N. , Chiawo David O. , Warui Charles M. , Gichuki Cecilia M. , Ngare Innocent O. 
Published: May 2021

ABSTRACTThe Rothschild’s giraffe is currently listed as vulnerable by the International Union for Conservation of Nature (IUCN). This is attributed to the loss of habitat due to human activities. This study examined the effect of habitat type on population structure and distribution of Rothschild’s giraffe in Ruma National Park (RNP) and Mwea National Reserve (MNR) in Kenya. The study employed road transects to collect data on the number, age class and sex distribution in three habitat types, open, medium and closed. Data was collected along three road transects of equal lengths measuring 14.2 km in each site (RNP and MNR) for comparison. A driving speed of 20 km per hour was maintained along each transect for standardization of survey effort and a maximum giraffe detection rate. Photographic capture of the coat patterns of the right side of all the giraffes sighted within 500 m from the transect was done for identification of age classes. The field visits were replicated 12 times for each transect giving 36 replications for each site spread equally through wet and dry seasons from March 2017 to November 2018. The effect of habitat type on population structure and distribution was analysed using ANOVA and Tukey HSD to test for significant differences. T-test was used to compare the mean population size of giraffe across the wet and dry seasons. Coat pattern analysis for age class identification was done using WildID software. The findings indicated that MNR had more males to females compared to RNP that registered more females and calves. Habitat type had a significant effect on the distribution of giraffes. The giraffe population showed a preference for medium habitat types. The findings are key for the management of habitat quality for giraffe populations at the interface where conservation areas overlap with human land use.
Crossbill: an open access single objective light-sheet microscopy platform
Authors: Kumar Manish , Kishore Sandeep , McLean David L. , Kozorovitskiy Yevgenia 
Published: May 2021

AbstractWe present an open access scanned oblique plane microscopy platformCrossbill. It combines a new optical configuration, open hardware assembly, a systematic alignment protocol, and dedicated control software to provide a compact, versatile, high resolution single objective light-sheet microscopy platform. The demonstrated configuration yields the most affordable sub-micron resolution oblique plane microscopy system to date. We add galvanometer enabled tilt-invariant lateral scan for multi-plane, multi-Hz volumetric imaging capability. A precision translation stage extends stitched field of view to centimeter scale. The accompanying open software is optimized forCrossbilland can be easily extended to include alternative configurations. UsingCrossbill, we demonstrate large volume structural fluorescence imaging with sub-micron lateral resolution in zebrafish and mouse brain sections.Crossbillis also capable of multiplane functional imaging, and time-lapse imaging. We suggest multiple alternative configurations to extendCrossbillto diverse microscopy applications.
EEG biomarkers of free recall
Authors: Katerman B. S. , Li Y. , Pazdera J. K. , Keane C. , Kahana M. J. 
Published: May 2021

AbstractBrain activity in the moments leading up to spontaneous verbal recall provide a window into the cognitive processes underlying memory retrieval. But these same recordings also subsume neural signals unrelated to mnemonic retrieval, such as response-related motor activity. Here we examined spectral EEG biomarkers of memory retrieval under an extreme manipulation of mnemonic demands: subjects either recalled items after a few seconds or after several days. This manipulation helped to isolate EEG components specifically related to long-term memory retrieval. In the moments immediately preceding recall we observed increased theta (4-8 Hz) power (+T), decreased alpha (8-20 Hz) power (-A), and increased gamma (40-128 Hz) power (+G), with this spectral pattern (+T-A+G) distinguishing the long-delay and immediate recall conditions. As subjects vocalized the same set of studied words in both conditions, we interpret the spectral +T-A+G as a biomarker of episodic memory retrieval.
Hierarchical, Memory-based Movement Models for Translocated Elk (Cervus canadensis)
Authors: Falcón-Cortés Andrea , Boyer Denis , Merrill Evelyn , Frair Jacqueline L. , Morales Juan Manuel 
Published: May 2021

AbstractThe use of spatial memory is well documented in many animal species and has been shown to be critical for the emergence of spatial learning. Adaptive behaviors based on learning can emerge thanks to an interdependence between the acquisition of information over time and movement decisions. The study of how spatio-ecological knowledge is constructed throughout the life of an individual has not been carried out in a quantitative and comprehensive way, hindered by the lack of knowledge of the information an animal already has of its environment at the time monitoring begins. Identifying how animals use memory to make beneficial decisions is fundamental to developing a general theory of animal movement and space use. Here we propose several mobility models based on memory and perform hierarchical Bayesian inference on 11-month trajectories of 21 elk after they were released in a completely new environment. Almost all the observed animals exhibited preferential returns to previously visited patches, such that memory and random exploration phases occurred. Memory decay was mild or negligible over the study period. The fact that individual elk rapidly become used to a relatively small number of patches was consistent with the hypothesis that they seek places with predictable resources and reduced mortality risks such as predation.
Modularity and connectivity of nest structure scale with colony size
Authors: Miller Julie S. , Wan Emma , O’Fallon Sean , Pinter-Wollman Noa 
Published: May 2021

ABSTRACTLarge body sizes have evolved structures to facilitate resource transport. Like unitary organisms, social insect colonies must transport information and resources. Colonies with more individuals may experience transport challenges similar to large-bodied organisms. In ant colonies, transport occurs in the nest, which may consist of structures that facilitate movement. We examine three attributes of nests that might have evolved to mitigate transport challenges related to colony size: (1) subdivision - nests of species with large colonies are more subdivided to reduce crowd viscosity; (2) branching - nest tunnels increase branching in species with large colonies to reduce travel distances; and (3) short-cuts – nests of species with large colonies have cross-linking tunnels to connect distant parts of the nest and create alternative routes. We test these hypotheses by comparing nest structures of species with different colony sizes in phylogenetically controlled meta-analyses. Our findings support the hypothesis that nest subdivision and branching evolved to mitigate transport challenges related to colony size. Nests of species with large colonies contain more chambers and branching tunnels. The similarity in how ant nests and bodies of unitary organisms have evolved in response to increasing size suggests common solutions across taxa and levels of biological organization.
High-density spinal cord stimulation selectively activates lower urinary tract afferents
Authors: Jantz Maria K , Gopinath Chaitanya , Kumar Ritesh , Chin Celine , Wong Liane , Ogren John I , Fisher Lee E , McLaughlin Bryan L , Gaunt Robert A 
Published: May 2021

AbstractEpidural spinal cord stimulation (SCS) has recently been reported as a potential intervention to improve limb and autonomic functions, with lumbar stimulation improving locomotion and thoracic stimulation regulating blood pressure. We asked whether sacral SCS could be used to target the lower urinary tract. Here we show that high-density epidural SCS over the sacral spinal cord and cauda equina of anesthetized cats evokes responses in nerves innervating the bladder and urethra and that these nerves can be activated selectively. Sacral epidural SCS always recruited the pelvic and pudendal nerves and selectively recruited these nerves in all but one animal. Individual branches of the pudendal nerve were always recruited as well. Electrodes that selectively recruited specific peripheral nerves were spatially clustered on the arrays, suggesting anatomically organized sensory pathways. This selective recruitment demonstrates a mechanism to directly modulate bladder and urethral function through known reflex pathways, which could be used to restore bladder and urethral function after injury or disease.
GhostiPy: an efficient signal processing and spectral analysis toolbox for large data
Authors: Chu Joshua P. , Kemere Caleb T. 
Published: May 2021

AbstractRecent technological advances have enabled neural recordings consisting of hundreds to thousands of channels. As the pace of these developments continues to grow rapidly, it is imperative to have fast, flexible tools supporting the analysis of neural data gathered by such large scale modalities. Here we introduceghostipy(generalhubofspectraltechniquesinPython), a Python open source software toolbox implementing various signal processing and spectral analyses including optimal digital filters and time-frequency transforms.ghostipyprioritizes performance and efficiency by using parallelized, blocked algorithms. As a result, it is able to outperform commercial software in both time and space complexity for high channel count data and can handle out-of-core computation in a user-friendly manner. Overall, our software suite reduces frequently encountered bottlenecks in the experimental pipeline, and we believe this toolset will enhance both the portability and scalability of neural data analysis.
q-mer analysis: a generalized method for analyzing RNA-Seq data
Authors: Shoji Tatsuma , Sato Yoshiharu 
Published: May 2021

AbstractRNA-Seq data are usually summarized by counting the number of transcript reads aligned to each gene. However, count-based methods do not take alignment information, where and how each read was mapped in the gene, into account. This information is essential to characterize samples accurately. In this study, we developed a method to summarize RNA-Seq data without losing alignment information. To include alignment information, we introduce “q-mer analysis,” which summarizes RNA-Seq data with 4q kinds of q-length oligomers. Using publicly available RNA-Seq datasets, we demonstrate that at least q ≧ 9 is required for capturing alignment information inHomo sapiens. Furthermore, principal component analysis showed that q-mer analysis with q = 14 linearly distinguished samples from controls, while a count-based method failed. These results indicate that alignment information is essential to characterize transcriptomics samples. In conclusion, we introduce q-mer analysis to include alignment information in RNA-Seq analysis and demonstrate the superiority of q-mer analysis over count-based methods in that q-mer analysis can distinguish case samples from controls. Combining RNA-Seq research with q-mer analysis could be useful for identifying distinguishing transcriptomic features that could provide hypotheses for disease mechanisms.
Diverse Hotspot Thermal Profiling Methods Detect Phosphorylation-Dependent Changes in Protein Stability
Authors: Stein Benjamin D. , Huang Jun X. , Wu David , Cantley Lewis C. , Moellering Raymond E. 
Published: May 2021

AbstractHotspot thermal profiling (HTP) methods utilize modified-peptide level information in order to interrogate proteoform-specific stability inside of live cells. The first demonstration of HTP involved the integration of phosphopeptide enrichment into a TMT-based, single-LC separation thermal profiling workflow1. Here we present a new ‘label-fractionate-enrich’ (LFE)-HTP method that involves high-pH reverse phase fractionation of TMT-labeled peptides prior to phosphopeptide enrichment, followed by peptide detection and quantitation using multi-notch LC-MS3. We find that LFE-HTP, while more resource intensive, improves the depth and precision of (phospho)proteoform coverage relative to the initial published HTP workflow. The fraction of detected phosphorylation sites that are significantly perturbed in this new dataset are consistent with those seen in our previous study, as well as those published by others, when compared head-to-head with the same analysis pipelines. Likewise, many ‘hotspot’ phosphorylation sites identified in our paper are consistently reproduced by LFE-HTP as well as other modified HTP methods. The LFE-HTP dataset contains many novel ‘hotspot’ phosphorylation sites that regulate the stability of diverse proteins, including phosphosites in the central glycolytic enzyme Aldolase A that are associated with monomer-to-oligomer formation, enzymatic activity and metabolic regulation in cancer cells. Our comparative analyses confirm that several variants of the HTP method can track modified proteoforms in live cells to detect and prioritize PTM-dependent changes in protein stability that may be associated with function.
Foxd3 controls heterochromatin-mediated silencing of repeat elements in mouse embryonic stem cells and represses the 2-cell transcription program
Authors: Puri Deepika , Koschorz Birgit , Engist Bettina , Onishi-Seebacher Megumi , Ryan Devon , Montavon Thomas 
Published: May 2021

AbstractRepeat element transcription plays a vital role in early embryonic development. Expression of repeats such as MERVL characterises mouse embryos at the 2-cell stage, and defines a 2-cell-like cell (2CLC) population in a mouse embryonic stem cell culture. Repeat element sequences contain binding sites for numerous transcription factors. We identify the forkhead domain transcription factor FOXD3 as a regulator of repeat element transcription in mouse embryonic stem cells. FOXD3 binds to and recruits the histone methyltransferase SUV39H1 to MERVL and major satellite repeats, consequentially repressing the transcription of these repeats by the establishment of the H3K9me3 heterochromatin modification. Notably, depletion of FOXD3 leads to the de-repression of MERVL and major satellite repeats as well as a subset of genes expressed in the 2-cell state, shifting the balance between the stem cell and 2-cell like population in culture. Thus, FOXD3 acts as a negative regulator of repeat transcription, ascribing a novel function to this transcription factor.
Oligomerization-driven MLKL ubiquitylation antagonises necroptosis
Authors: Liu Zikou , Dagley Laura F. , Shield-Artin Kristy , Young Samuel N. , Bankovacki Aleksandra , Wang Xiangyi , Tang Michelle , Howitt Jason , Stafford Che A. , Nachbur Ueli , Fitzgibbon Cheree , Garnish Sarah E. , Webb Andrew I. , Komander David , Murphy James M. , Hildebrand Joanne M. , Silke John 
Published: May 2021

AbstractMixed lineage kinase domain-like (MLKL) is the executioner in the caspase-independent form of programmed cell death called necroptosis. Receptor Interacting serine/threonine Protein Kinase 3 (RIPK3) phosphorylates MLKL, triggering MLKL oligomerization, membrane translocation and membrane disruption. MLKL also undergoes ubiquitylation during necroptosis, yet neither the mechanism nor significance of this event have been demonstrated. Here we show that necroptosis-specific, multi-mono-ubiquitylation of MLKL occurs following its activation and oligomerization. Ubiquitylated MLKL accumulates in a digitonin insoluble cell fraction comprising plasma/organellar membranes and protein aggregates. This ubiquitylated form is diminished by a plasma membrane located deubiquitylating enzyme. MLKL is ubiquitylated on at least 4 separate lysine residues once oligomerized, and this correlates with proteasome- and lysosome-dependent turnover. Using a MLKL-DUB fusion strategy, we show that constitutive removal of ubiquitin from MLKL licences MLKL auto-activity independent of necroptosis signalling in mouse and human cells. Therefore, besides its role in the kinetic regulation of MLKL-induced death following an exogenous necroptotic stimulus, ubiquitylation also contributes to the restraint of basal levels of activated MLKL to avoid errant cell death.