bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recruitment of Neuronal KCNQ2/3 Channels to Membrane Microdomains by Palmitoylation of Alzheimer’s Disease-Related Protein BACE1
Authors: Dai Gucan 
Published: October 2020

ABSTRACTβ-secretase 1 (β-site amyloid precursor protein (APP)-cleaving enzyme 1, BACE1) plays a crucial role in the amyloidogenesis of Alzheimer’s Disease (AD). BACE1 was also discovered to act like an auxiliary subunit to modulate neuronal KCNQ2/3 channels independent of its proteolytic function. BACE1 is palmitoylated at its carboxyl-terminal region, which brings BACE1 to ordered, cholesterol-rich membrane microdomains (lipid rafts). However, the physiological consequences of this specific localization of BACE1 remain elusive. Using spectral Förster Resonance Energy Transfer (FRET), BACE1 and KCNQ2/3 channels were confirmed to form a signaling complex, a phenomenon that was relatively independent of the palmitoylation of BACE1. Nevertheless, palmitoylation of BACE1 was required for recruitment of KCNQ2/3 channels to lipid-raft domains. Two fluorescent probes designated L10 and S15, were used to label lipid-raft and non-raft domains of the plasma membrane, respectively. Coexpressing BACE1 substantially elevated the FRET between L10 and KCNQ2/3 whereas the BACE1-4C/A quadruple mutation failed to produce this effect. In contrast, BACE1 had no significant effect on the FRET between S15 probes and KCNQ2/3 channels. A reduction of BACE1-dependent FRET between raft-targeting L10 probes and KCNQ2/3 channels by applying cholesterol-extracting reagent methyl-β-cyclodextrin (MβCD), raft-disrupting general anesthetics, or pharmacological inhibitors of palmitoylation all supported our hypothesis of the palmitoylation-dependent and raft-specific localization of KCNQ2/3 channels. Furthermore, mutating the four carboxyl-terminal cysteines (4C/A) of BACE1 abolished the BACE1-dependent increase of FRET between KCNQ2/3 and a lipid raft-specific protein caveolin 1. Collectively, we propose how the AD-related protein BACE1 underlies the localization of a neuronal potassium channel.
Sequence- and structure-specific cytosine-5 mRNA methylation by NSUN6
Authors: Selmi Tommaso , Hussain Shobbir , Dietmann Sabine , Heiss Matthias , Carter Jean-Michel , Dennison Rebecca , Flad Sophia , Huang Ya-Lin , Kellner Stefanie , Bornelöv Susanne , Frye Michaela 
Published: October 2020

ABSTRACTMethylation is the most common internal modification in mRNA. While the highly abundant N6-methyladonsine (m6A) modification affects most aspects of mRNA function, the precise functions of the rarer 5-methylcytosine (m5C) remains largely unknown. Here, we map m5C in the human transcriptome using methylation-dependent individual-nucleotide resolution cross-linking and immunoprecipitation (miCLIP) combined with RNA bisulfite sequencing. We identify NSUN6 as a methyltransferase with strong substrate specificity towards mRNA. NSUN6 primarily targeted three prime untranslated regions (3’UTR) at the consensus sequence motif CTCCA, located in loops of hairpin structures. Knockout and rescue experiments revealed that only mRNA methylation sites containing the consensus motif depended on the presence of NSUN6. Furthermore, ribosome profiling demonstrated that NSUN6-specific consensus motifs marked translation termination. However, even though NSUN6-methylated mRNAs were reduced in NSUN6 knockout cells, NSUN6 was dispensable for mouse embryonic development. Thus, our study identifies NSUN6 as methyltransferase targeting mRNA in a sequence- and structure-specific manner.
The cerebellar clock: predicting and timing somatosensory touch
Authors: Andersen Lau M. , Dalal Sarang S. 
Published: October 2020

0AbstractThe prediction of sensory feedback is known to involve the cerebellum, but its precise nature and timing have remained unclear due to the scarcity of time-sensitive cerebellar neuroimaging studies. We here, using magnetoencephalography in human participants, investigated the working hypothesis that one function of the cerebellum is to predict exactly when rhythmic stimuli are expected to impinge on sensory receptors.We compared the cerebellum’s response between somatosensory omissions embedded in perfectly rhythmic versus jittered trains of stimulation. At the precise moment that an omitted stimulus would have appeared, the cerebellum exhibited a beta band (14-30 Hz) response that was stronger when preceded by a perfectly rhythmic sequence. Meanwhile, the rhythm of new stimulation sequences induced theta band (4-7 Hz) activity in the cerebellum.Our results provide evidence that the cerebellum acts as a clock that entrains to rhythmic stimuli, likely for the purpose of detecting any deviations from that rhythm.
GABA quantification in human anterior cingulate cortex
Authors: Weis Jan , Persson Jonas , Frick Andreas , Åhs Fredrik , Versluis Maarten , Alamidi Daniel 
Published: October 2020

Abstractγ-Aminobutyric acid (GABA) is a primary inhibitory neurotransmitter in the human brain. It has been shown that altered GABA concentration plays an important role in a variety of psychiatric and neurological disorders. The main purpose of this study was to propose a combination of PRESS and MEGA-PRESS acquisitions for absolute GABA quantification and to compare GABA estimations obtained using total choline (tCho), total creatine (tCr), and total N-acetyl aspartate (tNAA) as the internal concentration references with water referenced quantification. The second aim was to demonstrate the fitting approach of MEGA-PRESS spectra with QuasarX algorithm using a basis set of GABA, glutamate, glutamine, and NAA in vitro spectra. Thirteen volunteers were scanned with the MEGA-PRESS sequence at 3T. Interleaved water referencing was used for quantification, B0drift correction and to update the carrier frequency of RF pulses in real time. Reference metabolite concentrations were acquired using a PRESS sequence with short TE (30 ms) and long TR (5000 ms). Absolute concentration were corrected for cerebrospinal fluid, gray and white matter water fractions and relaxation effects. Water referenced GABA estimations were significantly higher compared to the values obtained by metabolite references. We conclude that QuasarX algorithm together with the basis set of in vitro spectra improves reliability of GABA+ fitting. The proposed GABA quantification method with PRESS and MEGA-PRESS acquisitions enables the utilization of tCho, tCr, and tNAA as internal concentration references. The use of different concentration references have a good potential to improve the reliability of GABA estimation.
Control of synaptic transmission and neuronal excitability in the parabrachial nucleus
Authors: Cramer Nathan , Silva-Cardoso Gleice Kelli , Keller Asaf 
Published: October 2020

AbstractThe parabrachial nucleus (PB) is a hub for aversive behaviors, including those related to pain. We have shown that the expression of chronic pain is causally related to amplified activity of PB neurons, and to changes in synaptic inhibition of these neurons. These findings indicate that regulation of synaptic activity in PB may modulate pain perception and be involved in the pathophysiology of chronic pain. Here, we identify the roles in PB of signaling pathways that modulate synaptic functions. In pharmacologically isolated lateral PB neurons in acute mouse slices, we find that baclofen, a GABABreceptor agonist, suppresses the frequency of miniature inhibitory and excitatory postsynaptic currents (mIPSCs and mEPSC). Activation of µ-opioid peptide receptors with DAMGO had similar effects, while the k-opioid peptide receptor agonist U-69593 suppressed mIPSC release but had no consistent effects on mEPSCs. Activation of cannabinoid type 1 receptors with WIN 55,212-2 reduced the frequency of both inhibitory and excitatory synaptic events, while the CB1 antagonist AM251 had opposite effects on mIPSC and mEPSC frequencies. AM251 increased the frequency of inhibitory events but led to a reduction in excitatory events through a GABABmediated mechanism. Although none of the treatments produced a consistent effect on mIPSC or mEPSC amplitudes, baclofen and DAMGO both reliably activated a postsynaptic conductance. Together, these results demonstrate that signaling pathways known to modulate nociception, alter synaptic transmission and neuronal excitability in the lateral parabrachial nucleus and provide a basis for investigating the contributions of these systems to the development and maintenance of chronic pain.HighlightsThe parabrachial nucleus (PB) is a hub for processing interoceptive and exteroceptive noxious stimuli, including pain.Synaptic activity in PB is abnormal in chronic pain.Synaptic activity in PB is regulated by presynaptic and postsynapticGABAB,opioid µ and k, and cannabinoid CB1 receptors.GABAergic presynaptic terminals are most potently regulated by these receptors.Changes in the strength of these modulatory pathways may contribute to increased PB excitability and, consequently, chronic pain.
Inducible mechanisms of disease tolerance provide an alternative strategy of acquired immunity to malaria
Authors: Nahrendorf Wiebke , Ivens Alasdair , Spence Philip J. 
Published: October 2020

SummaryImmunity to malaria is often considered slow to develop but this only applies to defense mechanisms that function to eliminate parasites (resistance). In contrast, immunity to severe disease can be acquired quickly and without the need for improved pathogen control (tolerance). We show that a single malaria episode is sufficient to induce host adaptations that can minimise inflammation, prevent tissue damage and avert endothelium activation, a hallmark of severe disease. Furthermore, monocytes are functionally reprogrammed in tolerised hosts to prevent their differentiation into inflammatory macrophages and instead promote mechanisms of stress tolerance to protect their niche. This alternative fate is not underpinned by epigenetic reprogramming of bone marrow progenitors but is imprinted within the remodelled spleen. Crucially, all of these adaptations operate independently of pathogen load and limit the damage caused by malaria parasites in subsequent infections. Inducible mechanisms of disease tolerance therefore provide an alternative strategy of acquired immunity.
Arabidopsis ACINUS is O-glycosylated and regulates transcription and alternative splicing of regulators of reproductive transitions
Authors: Bi Yang , Deng Zhiping , Ni Weimin , Shretha Ruben , Savage Dasha , Hartwig Thomas , Patil Sunita , Hong Su Hyun , Oses-Prieto Juan A. , Li Kathy H. , Quail Peter H , Burlingame Alma L , Xu Shou-Ling , Wang Zhi-Yong 
Published: October 2020

AbstractO-GlcNAc modification plays important roles in metabolic regulation of cellular status. Two homologs of O-GlcNAc transferase, SECRET AGENT (SEC) and SPINDLY (SPY), which have O-GlcNAc and O-fucosyl transferase activities, respectively, are essential inArabidopsisbut have largely unknown cellular targets. Here we show that AtACINUS is O-GlcNAcylated and O-fucosylated and mediates regulation of transcription, alternative splicing (AS), and developmental transitions. Knocking-out both AtACINUS and its distant paralog AtPININ causes severe growth defects including dwarfism, delayed seed germination and flowering, and abscisic acid (ABA) hypersensitivity. Transcriptomic and protein-DNA/RNA interaction analyses demonstrate that AtACINUS represses transcription of the flowering repressorFLCand mediates AS ofABH1andHAB1, two negative regulators of ABA signaling. Proteomic analyses show AtACINUS’s O-GlcNAcylation, O-fucosylation, and association with splicing factors, chromatin remodelers, and transcriptional regulators. Some AtACINUS/AtPININ-dependent AS events are altered in thesecandspymutants, demonstrating a function of O-glycosylation in regulating alternative RNA splicing.
NT-mini, a recombinant tool for the study of Neurotrypsin functionality
Authors: Canciani Anselmo , Capitanio Cristina , Stanga Serena , Faravelli Silvia , Kienlen-Campard Pascal , Forneris Federico 
Published: October 2020

AbstractNeurotrypsin (NT) is a highly specific nervous system multi-domain serine-protease best known for its selective processing of the potent synaptic organiser agrin. Its enzymatic activity is thought to influence processes of synaptic plasticity, with its deregulation causing accelerated neuromuscular junction (NMJ) degeneration or contributing to forms of mental retardation. Something which, based on the available literature, likely stems from NT-based regulation of agrin signalling. However, dissecting the exact biological implications of NT-agrin interplay is difficult, owing to the scarce molecular detail regarding NT activity and NT-agrin interactions. The difficult recombinant production of NT in its catalytically competent form is at the base of these limitations, and is currently constraining a more detailed molecular, biochemical and structural characterisation of the NT-agrin system. We have developed a novel strategy to reliably produce and purify a truncated but catalytically competent variant of NT called NT-mini. The characterisation of our construct highlighted almost wild type-like behaviour with comparable specificity, and conservation of modulation by calcium and heparin despite the lack of several accessory domains. With the data obtained from NT-mini it was then possible to identify NT’s heparin-binding domain, and discover a novel putative Zinc-based modulation of NT. Additionally, NT-mini allowed us to investigate the effect of NT activity on myotube formation in controlled cell-based experiments, evidencing a negative impact on myoblast fusion dependant on enzymatic activity. Collectively, this shows the viability of NT-mini as a model to study NT functionality, allowing to expand bothin-vitroand “in-cellulo” investigations and providing a foundation to unravel the molecular underpinnings and biological significance of NT-agrin interactions.
Novel taxa of Acidobacteriota involved in seafloor sulfur cycling
Authors: Flieder Mathias , Buongiorno Joy , Herbold Craig W. , Hausmann Bela , Rattei Thomas , Lloyd Karen G. , Loy Alexander , Wasmund Kenneth 
Published: October 2020

AbstractAcidobacteriota are widespread and often abundant in marine sediments, yet their metabolic and ecological properties are poorly understood. Here, we examined metabolisms and distributions of Acidobacteriota in marine sediments of Svalbard by functional predictions from metagenome-assembled genomes (MAGs), amplicon sequencing of 16S rRNA and dissimilatory sulfite reductase (dsrB) genes and transcripts, and gene expression analyses of tetrathionate-amended microcosms. Acidobacteriota were the second most abundantdsrB-harboring (averaging 13%) phylum after Desulfobacterota in Svalbard sediments, and represented 4% ofdsrBtranscripts on average. We propose two new Acidobacteriota genera,CandidatusSulfomarinibacter (class Thermoanaerobaculia, ‘sub-division 23’) andCa. Polarisedimenticola (‘sub-division 22’), with distinct genetic properties that may explain their distributions in biogeochemically distinct fjord sediments.Ca. Sulfomarinibacter encodes flexible respiratory routes, with potential for oxygen, nitrous oxide, metal-oxide, tetrathionate, sulfur and sulfite/sulfate respiration, and possibly sulfur disproportionation. Potential nutrients and energy include cellulose, proteins, cyanophycin, hydrogen and acetate. ACa. Polarisedimenticola MAG encodes enzymes to degrade proteins, and to reduce oxygen, nitrate, sulfur/polysulfide and metal-oxides. 16S rRNA gene and transcript profiling showedCa. Sulfomarinibacter members were relatively abundant and transcriptionally active in sulfidic fjord sediments, whileCa. Polarisedimenticola members were more relatively abundant in metal-rich fjord sediments. Overall, we reveal various physiological features of uncultured marine Acidobacteriota that indicate fundamental roles in seafloor biogeochemical cycling.
The replicative amplification of MITEs and their impact on rice trait variability
Authors: Castanera Raul , Vendrell-Mir Pol , Bardil Amélie , Carpentier Marie-Christine , Panaud Olivier , Casacuberta Josep M. 
Published: October 2020

AbstractTransposable elements (TEs) are a rich source of genetic variability. Among TEs, Miniature Inverted- repeat Transposable Elements (MITEs) are of particular interest as they are present in high copy numbers in plant genomes and are closely associated with genes. MITEs are deletion derivatives of class II transposons, and can be mobilized by the transposases encoded by the latters through a typical cut-and-paste mechanism. However, this mechanism cannot account for the high copy number MITEs attain in plant genomes, and the mechanism by which MITEs amplify remains elusive.We present here an analysis of 103,109 Transposon Insertion Polymorphisms (TIPs) in 1,059O. sativagenomes representing the main rice population groups. We show that an important fraction of MITE insertions has been fixed in rice concomitantly with rice domestication. However, another fraction of MITE insertions is present at low frequencies. We performed MITE TIP-GWAS to study the impact of these elements on agronomically important traits and found that these elements uncover more trait associations than SNPs on important phenotypes such as grain width. Finally, using SNP-GWAS and TIP-GWAS we provide evidences of the replicative amplification of MITEs, suggesting a mechanism of amplification uncoupled from the typical cut-and-paste mechanism of class II transposons.
Performance of a rapid SARS-COV-2 serology test in whole blood and separated plasma
Authors: Vemulapati S. 
Published: October 2020

AbstractRapid SARS-COV-2 related serology testing can help identify and manage the spread of infection in decentralized testing environments but the limitation in performance of existing tests in blood has restricted implementation of testing at the point-of-care. Optimization of existing rapid tests in whole blood will require significant effort in the short-term and there is a need for solutions to help bridge the gap in performance between plasma and whole blood. We demonstrate here the implementation of the H.E.R.M.E.S platform, a portable plasma separation system that can enhance the performance of blood-based diagnostic testing, with a commercially available SARS-COV-2 IgG/IgM serology rapid diagnostic test (RDT) in a blinded study with 61 human samples. We compare the performance of the RDT in whole blood and separated plasma and highlight that plasma yields a 39% increase in positivity agreement with PCR in samples collected from patients with early infections. We further legitimize the increase in positivity agreement rate with the help of an independent evaluation by 10 previously untrained users. The H.E.R.M.E.S plasma separation system circumvents the need for assay optimization in whole blood and furthers the legitimacy of incorporating SARS-COV-2 serology RDTs at the point-of-care. The data highlighted in this work makes a compelling case for the incorporation of the H.E.R.M.E.S system in large scale efforts to perform SARS-COV-2 serology testing in decentralized testing environments.
Multiscale communication in cortico-cortical networks
Authors: Bazinet Vincent , Vos de Wael Reinder , Hagmann Patric , Bernhardt Boris C. , Misic Bratislav 
Published: October 2020

AbstractSignaling in brain networks unfolds over multiple topological scales. Areas may exchange information over local circuits, encompassing direct neighbours and areas with similar functions, or over global circuits, encompassing distant neighbours with dissimilar functions. Here we study how the organization of cortico-cortical networks mediate localized and global communication by parametrically tuning the range at which signals are transmitted on the white matter connectome. By investigating the propensity for brain areas to communicate with their neighbors across multiple scales, we naturally reveal their functional diversity. We find that unimodal regions show preference for local communication and multimodal regions show preferences for global communication. We show that these preferences manifest as region- and scale-specific structure-function coupling. Namely, the functional connectivity of unimodal regions emerges from monosynaptic communication in small-scale circuits, while the functional connectivity of transmodal regions emerges from polysynaptic communication in large-scale circuits. Altogether, the present findings reveal how functional hierarchies emerge from hidden but highly structured multiscale connection patterns.
Predicting thrust of aircraft using artificial neural networks
Authors: Yildirim Dalkiran Fatma , Toraman Mustafa 
Published: October 2020

Purpose
The purpose of this study is to make artificial neural network (ANN)-based prediction about thrust using the flight control parameters of aircrafts.

Design/methodology/approach
In today’s transportation, airplanes have an important place because of their safety, quality and speed. One of the most important parameters affecting the secure flying of aircrafts is the thrust value of aircraft engines. Determining the optimum thrust value should be investigated. If thrust value is less than optimum level, the flight safety runs a risk. Otherwise, fuel consumption goes high and some unwanted vibrations occur that cause uncomfortable flight. In this study, multi-layer perceptron ANNs, which are one of the intelligent optimization methods and frequently used in the literature, are preferred to predict the optimum thrust value during take-off, cruise and landing. The actual flight data, which is taken from the black box of an Airbus A319 aircraft, is used to train ANN models using back propagation algorithms. Velocity, altitude and ambient temperature values of the aircraft are selected as inputs and the thrust value is selected as output. During the training process of ANN, eight different training algorithms with different structures are used to figure out optimum ANN model with minimum error.

Findings
Different ANN models were trained using eight different training algorithms. The ANN model with minimum error has multi-layer perceptron structure, which is trained using Levenberg–Marquardt (LM) algorithm.

Research limitations/implications
To obtain the ANN structure with minimum error training, process takes more than a day depending on the capacity of a computer for LM training algorithm. But after training process, the trained ANN model produces sufficient output in a few milliseconds.

Practical implications
Totally 15,670 input-output data sets are obtained from an Airbus A319 aircraft. 12,889 of them are used as training data and the rest of the data sets, selected randomly are used as test data. Test data sets are never used in training phase, and the obtained results show that the ANN model successfully predicts thrust value using unseen input data.

Social implications
The ANN could be used as an alternative method to predict other flight control parameters of aircrafts.

Originality/value
To the best of authors’ knowledge, this study is the first example in literature to predict the thrust value of the aircraft using ANN.