bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anesthesia alters cortical spike sequences in rodent visual cortex
Authors: Tanabe Sean , Lee Heonsoo , Wang Shiyong , Hudetz Anthony G. 
Published: December 2022

ABSTRACTRecurring spike sequences are thought to underlie cortical computations and may be essential for information processing in the conscious state. How anesthesia at graded levels may influence spontaneous and stimulus-related spike sequences in visual cortex has not been systematically examined. We recorded extracellular single-unit activity in the rat primary visual cortexin vivoduring wakefulness and three levels of anesthesia produced by desflurane. The latencies of spike sequences within 0~200ms from the onset of spontaneous UP states and visual flash-evoked responses were compared. During wakefulness, spike latency patterns linked to the local field potential theta cycle were similar to stimulus-evoked patterns. Under anesthesia, spontaneous UP state sequences differed from flash-evoked sequences due to the recruitment of low-firing excitatory neurons to the UP state. Flash-evoked spike sequences showed higher reliability and longer latency when stimuli were applied during DOWN states compared to UP states. At deeper levels, anesthesia altered both UP state and flash-evoked spike sequences by selectively suppressing inhibitory neuron firing. The results reveal anesthesia-induced complex changes in cortical firing sequences that may influence visual information processing.
Air-seq: Measuring air metagenomic diversity in an agricultural ecosystem
Authors: Giolai Michael , Verweij Walter , Pearson Neil , Nicholson Paul , Leggett Richard M. , Clark Matthew D. 
Published: December 2022

AbstractBackgroundAll species shed DNA into their environment during life or in death providing an opportunity to monitor biodiversity via its environmental DNA. Biodiversity monitoring using environmental DNA based technologies has become an important tool in understanding ecosystems. In recent years promising progress for non-invasive and, more importantly, non-destructive monitoring has been made by combining the retrieval of information transmitted by released environmental DNA with high-throughput sequencing technologies. Important ecosystems under continuous threat by disease but essential for food supplies are agricultural systems, often farmed as large monocultures and so highly vulnerable to disease outbreaks. Pest and pathogen monitoring in agricultural ecosystems is therefore key for efficient and early disease prevention and management. Air is rich in biodiversity, but has the lowest DNA concentration of all environmental media and yet it is required for windborne spread by many of the world’s most damaging crop pathogens. Our work and recent research suggests that ecosystems can be monitored efficiently using airborne nucleic acid information.ResultsHere we show that the airborne DNA of microbes can be recovered, sequenced and taxonomically classified, including down to the species level. Monitoring a field growing key crops we show that Air-seq can identify the presence of agriculturally significant pathogens and quantify their changing abundance over a period of 1.5 months often correlating with weather variables.ConclusionWe add to the evidence that aerial environmental DNA can be used as a source for biomonitoring in agricultural and more general terrestrial ecosystems. The ability to detect fluxes and occurrence patterns of species and strains with high throughput sample processing and analysis technologies highlights the value of airborne environmental DNA in monitoring biodiversity changes and tracking of taxa of human interest or concern.
Effect of field strength on RF power deposition near conductive leads: A simulation study of SAR in DBS lead models during MRI at 1.5 T - 10.5 T
Authors: Kazemivalipour Ehsan , Sadeghi-Tarakameh Alireza , Keil Boris , Eryaman Yigitcan , Atalar Ergin , Golestanirad Laleh 
Published: December 2022

AbstractBackgroundSince the advent of magnetic resonance imaging (MRI) nearly four decades ago, there has been a quest for ever-higher magnetic field strengths. Strong incentives exist to do so, as increasing the magnetic field strength increases the signal-to-noise ratio of images. However, ensuring patient safety becomes more challenging at high and ultrahigh field MRI (i.e., ≥3 T) compared to lower fields. The problem is exacerbated for patients with conductive implants, such as those with deep brain stimulation (DBS) devices, as excessive local heating can occur around implanted lead tips. Despite extensive effort to assess radio frequency (RF) heating of implants during MRI at 1.5 T, a comparative study that systematically examines the effects of field strength and various exposure limits on RF heating is missing.PurposeThis study aims to perform numerical simulations that systematically compare RF power deposition near DBS lead models during MRI at common clinical and ultra-high field strengths, namely 1.5, 3, 7, and 10.5 T. Furthermore, we assess the effects of different exposure constraints on RF power deposition by imposing limits on either the B1+or global head specific absorption rate (SAR) as these two exposure limits commonly appear in MRI guidelines.MethodsWe created 33 unique DBS lead models based on postoperative computed tomography (CT) images of patients with implanted DBS devices and performed electromagnetic simulations to evaluate the SAR of RF energy in the tissue surrounding lead tips during RF exposure at frequencies ranging from 64 MHz (1.5 T) to 447 MHz (10.5 T). The RF exposure was implemented via realistic MRI RF coil models created based on physical prototypes built in our institutions. We systematically examined the distribution of local SAR at different frequencies with the input coil power adjusted to either limit the B1+or the global head SAR.ResultsThe MRI RF coils at higher resonant frequencies generated lower SARs around the lead tips when the global head SAR was constrained. The trend was reversed when the constraint was imposed on B1+.ConclusionAt higher static fields, MRI is not necessarily more dangerous than at lower fields for patients with conductive leads. Specifically, when a conservative safety criterion, such as constraints on the global SAR, is imposed, coils at a higher resonant frequency tend to generate a lower local SAR around implanted leads due to the decreased B1+and, by proxy,Efield levels.
De novo protein design by inversion of the AlphaFold structure prediction network
Authors: Goverde Casper , Wolf Benedict , Khakzad Hamed , Rosset Stéphane , Correia Bruno E. 
Published: December 2022

AbstractDe novoprotein design enhances our understanding of the principles that govern protein folding and interactions, and has the potential to revolutionize biotechnology through the engineering of novel protein functionalities. Despite recent progress in computational design strategies,de novodesign of protein structures remains challenging, given the vast size of the sequence-structure space. AlphaFold2 (AF2), a state-of-the-art neural network architecture, achieved remarkable accuracy in predicting protein structures from amino acid sequences. This raises the question whether AF2 has learned the principles of protein folding sufficiently for de novo design. Here, we sought to answer this question by inverting the AF2 network, using the prediction weight set and a loss function to bias the generated sequences to adopt a target fold. Initial design trials resulted in de novo designs with an overrepresentation of hydrophobic residues on the protein surface compared to their natural protein family, requiring additional surface optimization. In silico validation of the designs showed protein structures with the correct fold, a hydrophilic surface and a densely packed hydrophobic core. In vitro validation showed that several designs were folded and stable in solution with high melting temperatures. In summary, our design workflow solely based on AF2 does not seem to fully capture basic principles of de novo protein design, as observed in the protein surface’s hydrophobic vs. hydrophilic patterning. However, with minimal post-design intervention, these pipelines generated viable sequences as assessed experimental characterization. Thus such pipelines show the potential to contribute to solving outstanding challenges in de novo protein design.
Albatrosses employ orientation and routing strategies similar to yacht racers
Authors: Goto Yusuke , Weimerskirch Henri , Fukaya Keiichi , Yoda Ken , Naruoka Masaru , Sato Katsufumi 
Published: December 2022

AbstractThe way goal-oriented birds adjust their travel direction and route in response to wind significantly affects their travel costs. This is expected to be particularly pronounced in pelagic seabirds, which utilize a wind-dependent flight style called dynamic soaring. Dynamic soaring seabirds in situations without a definite goal, e.g. searching for prey, are known to preferentially fly with tail-to-side winds to increase the speed and search area, and reduce travel costs. However, little is known about their reaction to wind when heading to a definite goal, such as homing. Homing tracks of wandering albatrosses (Diomedea exulans) vary from beelines to zigzags, which are similar to those of sailboats. Here, given that both albatrosses and sailboats travel slower in headwinds and tailwinds, we tested whether the time-minimizing strategies used by yacht racers can be compared to the locomotion patterns of wandering albatrosses. We predicted that when the goal is located upwind or downwind, albatrosses should deviate their travel directions from the goal on the microscale and increase the number of turns on the macroscale. Both hypotheses were supported by track data from albatrosses and racing yachts in the Southern Ocean confirming that albatrosses qualitatively employ the same strategy as yacht racers. Nevertheless, albatrosses did not strictly minimize their travel time, likely making their flight robust against wind fluctuations to reduce flight costs. Our study provides the first empirical evidence of tacking in albatrosses and demonstrates that man-made movement strategies provide a new perspective on the laws underlying wildlife movement.
Role of HAO2 in rats with chronic kidney disease by regulating fatty acid metabolic processes in renal tissue
Authors: Li Xunjia , Liu Chengxuan , Yang Aimin , Shen Youfeng , Xu Jian , Zuo Deyu 
Published: December 2022

AbstractFibrosis is a progressive, often irreversible histologic manifestation of chronic and end-stage renal disease. In this study, single-cell transcriptome sequencing technology was used to sequence and analyze blood and kidney tissue cells in normal control rats and rats with chronic kidney disease (CKD), focusing on key cell populations and functional enrichment to explore the pathogenesis of CKD. Oil red O staining and ELISA were used to detect lipid droplets and free fat acid (FFA). RT-PCR, WB were used to verify the differential gene HAO2 and fatty acid metabolic process in tissue to ensure the reliability of single-cell sequencing results. We successfully established a single-cell transcriptome atlas of blood and kidney tissue in rats with CKD, which were annotated into 14 cell subsets (MPCs, PT, Tc, DCT, B-IC, A-IC, CNT, ALOH, BC, Neu, Endo, Pla, NKT, Baso) according to marker gene, and the integrated single-cell atlas of rats showed a significant increase and decrease of MPCs and PTs in the model group, respectively. Functional analysis found extensive enrichment of metabolic-related pathways in PT cells, includes fatty acid metabolic process, cellular amino acid metabolic process and generation of precursor metabolites and energy. Immunohistochemical experiments determined that the differential gene HAO2 was localized in the renal tubules, and its expression was significantly reduced in model group compared with control, and oil red O staining showed that lipid droplets increased in the model group. ELISA assay showed that ATP content decreased in the model group and FFA increased in the model group. ACOX1, PPARα, PGC1α were decreased in the model group, while genes and proteins were increased after overexpression of HAO2, and the AMPK and ACC phosphorylated proteins were increased. Therefore, HAO2 may be an important regulator of fatty acid metabolic processes in CKD, and overexpression of HAO2 can enhance fatty acid metabolism by promoting fatty acid oxidation pathway.
Using Social Media to Help Understand Long COVID Patient Reported Health Outcomes: A Natural Language Processing Approach
Authors: Dolatabadi Elham , Moyano Diana , Bales Michael , Spasojevic Sofija , Bhambhoria Rohan , Bhatti Junaid , Debnath Shyamolima , Hoell Nicholas , Li Xin , Leng Celine , Nanda Sasha , Saab Jad , Sahak Esmat , Sie Fanny , Uppal Sara , Vadlamudi Nirma Khatri , Vladimirova Antoaneta , Yakimovich Artur , Yang Xiaoxue , Kocak Sedef Akinli , Cheung Angela M. 
Published: December 2022

AbstractBackgroundThere remains significant uncertainty in the definition of the long COVID disease, its expected clinical course, and its impact on daily functioning. Social media platforms can generate valuable insights into patient-reported health outcomes as the content is produced at high resolution by patients and caregivers, representing experiences that may be unavailable to most clinicians.ObjectiveWe aim to determine the validity and effectiveness of advanced NLP approaches built to derive insight into Long COVID-related patient-reported health outcomes from social media platforms.MethodologyWe use Transformer-based BERT models to extract and normalize long COVID Symptoms and Conditions (SyCo) from English posts on Twitter and Reddit. Furthermore, we estimate the occurrence and co-occurrence of SyCo terms at any point or across time and locations. Finally, we compare the extracted health outcomes with human annotations and highly utilized clinical outcomes grounded in the medical literature.ResultBased on our findings, the top three most commonly occurring groups of long COVID symptoms are systemic (such as “fatigue”), neuropsychiatric (such as “anxiety” and “brain fog”), and respiratory (such as “shortness of breath”). Regarding the co-occurring symptoms, the pair of ‘fatigue & headaches’ is most common. In addition, we show that other conditions, such as infection, hair loss, and weight loss, as well as mentions of other diseases, such as flu, cancer, or Lyme disease, are among the top reported terms by social media users.ConclusionThe outcome of our social media-derived pipeline is comparable with the outcomes of peer-reviewed articles relevant to long COVID symptoms. Overall, this study provides unique insights into patient-reported health outcomes from long COVID and valuable information about the patient’s journey that can help healthcare providers anticipate future needs.
Expression of substance P, NPY and their Receptors Is Altered in Major Depression
Authors: Barde Swapnali , Aguila Julio , Zhong Wen , Solarz Anna , Mei Irene , Prud’homme Josee , Palkovits Miklos , Turecki Gustavo , Mulder Jan , Uhlén Mathias , Nagy Corina , Mechawar Naguib , Hedlund Eva , Hökfelt Tomas 
Published: December 2022

ABSTRACTBACKGROUNDMajor depressive disorder (MDD) is a serious disease and a burden to patients, families and society. Rodent experiments and human studies suggest that several neuropeptide systems, including substance P(SP)/tachykinin, neuropeptide Y(NPY) and their G protein-coupled receptors are involved in mood regulation.METHODSWe assessed the transcript levels (qPCR) of SP/tachykinin and NPY systems in five regions from postmortem brains of male and female depressed subjects who committed suicide (DSS) and controls: dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), the dorsal raphe nucleus (DRN), locus coeruleus (LC) and medullary raphe nuclei (MRN). We also analysed human LC neurons isolated using LCM with Smart-seq2 RNA sequencing.RESULTSTranscripts for all nine members were detected in male and female controls with marked regional variations of the raw CT values and with the highest levels for several tachykinin and tachykinin receptor transcripts in the DRN and forNPYandNPYRtranscripts in the PFC regions. Significant sex differences for controls were recorded only in the DRN (NPYR2>in females)andLC (TAC3andNPY>in females). Elevated expression in DSS was recorded in (i) DLPFC forSP, TACandTAC3in females,SPin males, andNPYR1in both sexes; and (ii) LC for all tachykinin family transcripts in females,SP, TACR1andTACR3in males,NPYin both sexes, andNPYR1in males.CONCLUSIONSThe selective perturbation of neuropeptide systems in MDD patients may assist in the search for novel treatment strategies for subjects afflicted by this grave disorder.
Transcriptional Responses of Cancer Cells to Heat Shock-Inducing Stimuli Involve Amplification of Robust HSF1 Binding
Authors: Dastidar Sayantani Ghosh , De Kumar Bony , Lauckner Bo , Parrello Damien , Perley Danielle , Vlasenok Maria , Tyagi Antariksh , Koney Nii Koney-Kwaku , Abbas Ata , Nechaev Sergei 
Published: December 2022

ABSTRACTResponses of cells to signals are increasingly discovered to involve the binding of sequence-specific transcription factors outside of known target genes. We wanted to determine to what extent the genome-wide binding and function of a transcription factor are shaped by the cell type versus the stimulus. To do so, we induced the Heat Shock Response pathway in two distant cell lines with two different stimuli and related the binding of its master regulator HSF1 to nascent RNA and chromatin accessibility. We show that HSF1 binding patterns robustly retain their identity under different magnitudes of activation so that common HSF1 binding is globally associated with stimulus-specific transcription outcomes. HSF1-induced increase in DNA accessibility was modest in scale but occurred predominantly at remote genomic sites. Apart from regulating transcription at existing elements including promoters and enhancers, responses to heat shock may directly engage inactive chromatin.
Is mild ADHD beneficial? Brain criticality peaks at intermediate ADHD symptom scores across the population
Authors: Haque Hamed , Hirvonen Jonni , Wang Sheng H. , Simola Jaana , Morales-Muñoz Isabel , Cowley Benjamin U. , Palva J. Matias , Palva Satu 
Published: December 2022

AbstractAttention-deficit/hyperactivity disorder (ADHD) is characterized by a continuum of symptoms including inattentiveness, hyperfocus, and hyperactivity, that are manifested,e.g., in increased reaction-time variability in continuous performance tasks (CPTs). Framework of brain criticality posits that brains operate in an extended regime of critical-like dynamics where neuronal and behavioral processes exhibit scale-free long-range temporal correlations (LRTCs) across hundreds of seconds. Whether shifts across critical-like brain states and parallel changes in LRTCs underlie ADHD symptoms has remained unexplored. We investigated whether brain-state shifts towards excitation-dominated dynamics and associated changes in LRTCs could explain ADHD symptoms and their continuum across individuals. We measured brain activity with magnetoencephalography (MEG) during resting and two CPTs from adult participants diagnosed with ADHD (N= 34) and neurotypical controls (NC) (N= 36) and characterized criticality with LRTCs of neuronal oscillations. ADHD patients exhibited stronger LRTCs than NC in low (5-20 Hz) and high (30-100 Hz) frequencies and dichotomous task effects. High-frequency LRTCs were positively correlated with ADHD symptoms, while beta-band (20-30 Hz) activity exhibited a quadratic correlation, peaking at moderate scores across the ADHD and NC cohorts being smaller for low and high scores. We demonstrate that ADHD is associated with shifts in brain criticality in resting-and task-state brain dynamics. Individuals with intermediate symptom scores across the NC and ADHD cohorts operated at peak criticality that is associated with a several functional benefits The progressive shift towards the supercritical side of the critical regime becomes detrimental only at moderate and severe symptoms.
GABA excitatory actions in cerebrospinal-fluid contacting neurones of adult mouse spinal cord
Authors: Riondel Priscille , Jurčić Nina , Trouslard Jérôme , Wanaverbecq Nicolas , Seddik Riad 
Published: December 2022

AbstractSpinal cerebrospinal fluid-contacting neurons (CSF-cNs) form an evolutionary conserved bipolar cells population localized around the central canal of all vertebrates. CSF-cNs were shown to express molecular markers of neuronal immaturity into adulthood, however the functional relevance of their incomplete maturation remains unknown. Neuronal maturation is classically associated with the expression of the K+-Cl-cotransporter 2 (KCC2), allowing chloride (Cl-) extrusion and hyperpolarising GABA transmission. Here, we show no detectable expression of KCC2 in CSF-cNs of adult mouse spinal cord. Accordingly, lack of KCC2 expression results in low Cl-extrusion capacity in CSF-cNs under high Cl-load in whole-cell patch-clamp. Using cell-attached recordings, we found that activation of ionotropic GABAAreceptors induced a dominant depolarising effect in 70% of CSF-cNs recorded with intact intracellular chloride concentration. Moreover, in these cells, depolarising GABA-responses can drive action potentials as well as intracellular calcium elevations by activating voltage-gated calcium channels. CSF-cNs express the Na+-K+-Cl-cotransporter 1 (NKCC1) involved in Cl-uptake and its inhibition by bumetanide blocked the GABA-induced calcium transients in CSF-cNs. Finally, we show that activation of metabotropic GABABreceptors did not mediate hyperpolarisation in spinal CSF-cNs, presumably due to the lack of expression of G protein-coupled inwardly rectifying potassium (GIRK) channels. Together, these findings outline CSF-cNs as a unique neuronal population in adult spinal cord with immature Cl-homeostasis and no hyperpolarising GABAergic signalling but rather generation of excitation and intracellular calcium modulation. GABA may therefore promote CSF-cNs maturation and integration into the existing spinal circuit.Key pointsCSF contacting neurones (CSF-cNs) are located around the central canal of spinal cord across all vertebrates.CSF-cNs express canonical markers of immature neurons during adulthood in mice but the impact of such persistent immaturity on their chloride (Cl-) homeostasis as well as GABAergic signalling were not addressed yet.Here, we show that spinal CSF-cNs express the Na+-K+-Cl-cotransporter 1 (NKCC1) involved in Cl-uptake but not the K+-Cl-cotransporter 2 (KCC2) classically allowing Cl-extrusion.As a result of intracellular Cl-accumulation, GABA does not mediate inhibition in most CSF-cNs but rather excitation and intracellular Ca2+elevations through the activation of voltage-gated Ca2+channels.Excitatory GABAergic signalling associated with intracellular calcium modulation may underlie the maturation and integration of CSF-cNs into the spinal circuit of adult mice.