bluuebunny/crossref_metadata_2025_split huggingface dataset:
Local field potentials and single unit dynamics in motor cortex of unconstrained macaques during different behavioral states
Authors: Yun Richy , Rembado Irene , Perlmutter Steve I. , Rao Rajesh P. N. , Fetz Eberhard E. 
Published: May 2022

AbstractDifferent sleep states have been shown to be vital for a variety of brain function, including learning, memory, and skill consolidation. However, our understanding of neural dynamics during sleep and the role of prominent LFP frequency bands remain incomplete. To elucidate such dynamics and changes between different behavioral states we collected multichannel LFP and spike data in primary motor cortex of unconstrained macaques for up to 24 hours using the Neurochip3. Each 8 second bin of time was classified into awake and moving (Move), awake and at rest (Rest), REM sleep (REM), or non-REM sleep (NREM) by using dimensionality reduction and clustering on the average spectral density and the acceleration of the head. LFP power showed high delta during NREM, high theta during REM, and high beta when the animal was awake. Cross-frequency phase-amplitude coupling typically showed higher coupling for deeper sleep between all pairs of frequency bands. Two notable exceptions were high delta-high gamma and theta-high gamma coupling during Move, and high theta-beta coupling during REM. Sorted single units showed decreased firing rate with deeper sleep, though with higher “bursty” patterns during NREM compared to other states. Spike-LFP synchrony showed high delta synchrony during Move, and higher coupling with all other frequency bands with deeper sleep.These results altogether are consistent with previous findings showing reactivation of cortical circuitry during sleep, which may be moderated by delta band LFP.
Bacterial catabolic system of acetovanillone and acetosyringone useful for upgrading aromatic compounds obtained through chemical lignin depolymerization
Authors: Higuchi Yudai , Kamimura Naofumi , Takenami Hiroki , Kikuiri Yusei , Yasuta Chieko , Tanatani Kenta , Shobuda Toru , Otsuka Yuichiro , Nakamura Masaya , Sonoki Tomonori , Masai Eiji 
Published: May 2022

ABSTRACTAcetovanillone is a major aromatic monomer produced in oxidative/base-catalyzed lignin depolymerization. However, the production of chemical products from acetovanillone has not been explored due to the lack of information on the microbial acetovanillone catabolic system. Here acvABCDEF was identified as specifically induced genes during the growth of Sphingobium sp. strain SYK-6 cells with acetovanillone and these genes were essential for SYK-6 growth on acetovanillone and acetosyringone (a syringyl-type acetophenone derivative). AcvAB and AcvF produced in Escherichia coli phosphorylated acetovanillone/acetosyringone and dephosphorylated the phosphorylated acetovanillone/acetosyringone, respectively. AcvCDE produced in Sphingobium japonicum UT26S converted the dephosphorylated phosphorylated acetovanillone/acetosyringone intermediate into vanilloyl acetic acid/3- (4-hydroxy-3,5-dimethoxyphenyl)-3-oxopropanoic acid through carboxylation. To demonstrate the feasibility of producing cis,cis-muconic acid from acetovanillone, a metabolic modification on a mutant of Pseudomonas sp. strain NGC7 that accumulates cis,cis-muconic acid from catechol was performed. The resulting strain expressing vceA and vceB required for converting vanilloyl acetic acid to vanillic acid and aroY encoding protocatechuic acid decarboxylase in addition to acvABCDEF successfully converted 1.2 mM acetovanillone to approximate equimolar cis,cis-muconic acid. Our results are expected to help improve the yield and purity of value-added chemical production from lignin through biological funneling.IMPORTANCEIn the alkaline oxidation of lignin, aromatic aldehydes (vanillin, syringaldehyde, and p-hydroxybenzaldehyde), aromatic acids (vanillic acid, syringic acid, and p- hydroxybenzoic acid), and acetophenone-related compounds (acetovanillone, acetosyringone, and 4’-hydroxyacetophenone) are produced as major aromatic monomers. Also, base-catalyzed depolymerization of guaiacyl lignin resulted in vanillin, vanillic acid, guaiacol, and acetovanillone as primary aromatic monomers. To date, microbial catabolic systems of vanillin, vanillic acid, and guaiacol have been well characterized, and the production of value-added chemicals from them has also been explored. However, due to the lack of information on the microbial acetovanillone and acetosyringone catabolic system, chemical production from acetovanillone and acetosyringone has not been achieved. This is the first study to elucidate the acetovanillone/acetosyringone catabolic system, and to demonstrate the potential of using these genes for value-added chemicals production from these compounds.
Elevated CD47 is a hallmark of dysfunctional aged muscle stem cells that can be targeted to augment regeneration
Authors: Porpiglia Ermelinda , Mai Thach , Kraft Peggy , Holbrook Colin A. , de Morree Antoine , Gonzalez Veronica D. , Hilgendorf Keren , Fresard Laure , Trejo Angelica , Bhimaraju Sriram , Jackson Peter K. , Fantl Wendy J. , Blau Helen M. 
Published: May 2022

SUMMARYIn aging, skeletal muscle strength and regenerative capacity declines due, in part, to functional impairment of muscle stem cells (MuSCs), yet the underlying mechanisms remain elusive. Here we capitalize on mass-cytometry to identify high CD47 expression as a hallmark of dysfunctional MuSCs (CD47hi) with impaired regenerative capacity that predominate with aging. The prevalent CD47hi MuSC subset suppresses the residual functional CD47lo MuSC subset through a paracrine signaling loop, leading to impaired proliferation. We uncover that elevated CD47 levels on aged MuSCs result from increased U1 snRNA expression, which disrupts alternative polyadenylation. The deficit in aged MuSC function in regeneration can be overcome either by morpholino-mediated blocking of CD47 alternative polyadenylation or antibody blockade of CD47 signaling, leading to improved regeneration in aged mice, with therapeutic implications. Our findings highlight a previously unrecognized age-dependent alteration in CD47 levels and function in MuSCs, which underlies reduced muscle repair in aging.
Decoding violated sensory expectations from the auditory cortex of anaesthetized mice: Hierarchical recurrent neural network depicts separate ‘danger’ and ‘safety’ units
Authors: O’Reilly Jamie A. , Angsuwatanakul Thanate , Wehrman Jordan 
Published: May 2022

AbstractThe ability to respond appropriately to sensory information received from the external environment is among the most fundamental capabilities of central nervous systems. In the auditory domain, processes underlying this behaviour are studied by measuring auditory-evoked electrophysiology during sequences of sounds with predetermined regularities. Identifying neural correlates of ensuing auditory novelty responses is supported by research in experimental animals. In the present study, we reanalysed epidural field potential recordings from the auditory cortex of anaesthetised mice during frequency and intensity oddball stimulation. Multivariate pattern analysis (MVPA) and hierarchical recurrent neural network (RNN) modelling were adopted to explore these data with greater resolution than previously considered using conventional methods. Time-wise and generalised temporal decoding MVPA approaches revealed previously underestimated asymmetry between responses to sound-level transitions in the intensity oddball paradigm, in contrast with tone frequency changes. After training, the cross-validated RNN model architecture with four hidden layers produced output waveforms in response to simulated auditory inputs that were strongly correlated with grand-average auditory-evoked potential waveforms (r2 > 0.9). Units in hidden layers were classified based on their temporal response properties and characterised using principal component analysis and sample entropy. These demonstrated spontaneous alpha rhythms, sound onset and offset responses, and putative ‘safety’ and ‘danger’ units activated by relatively inconspicuous and salient changes in auditory inputs, respectively. The hypothesised existence of corresponding biological neural sources is naturally derived from this model. If proven, this would have significant implications for prevailing theories of auditory processing.
Cortical tracking of lexical speech units in a multi-talker background is immature in school-aged children
Authors: Niesen Maxime , Bourguignon Mathieu , Bertels Julie , Vander Ghinst Marc , Wens Vincent , Goldman Serge , De Tiege Xavier 
Published: May 2022

AbstractChildren have more difficulty perceiving speech in noise than adults. Whether these difficulties relate to immature processing of prosodic or linguistic elements of the attended speech is still unclear. To address the impact of noise on linguistic processing per se, we assessed how acoustic noise impacts the cortical tracking of intelligible speech devoid of prosody in school-aged children and adults.Twenty adults and twenty children (7-9 years) listened to synthesized French monosyllabic words presented at 2.5 Hz, either randomly or in 4-word hierarchical structures wherein 2 words formed a phrase, and 2 phrases formed a sentence, with or without babble noise. Neuromagnetic responses to words, phrases and sentences were identified and source-localized.Children and adults displayed significant cortical tracking of words in all conditions, and of phrases and sentences only when words formed meaningful sentences. In children compared with adults, cortical tracking of linguistic units was lower for all units in conditions without noise, and similarly impacted by the addition of babble noise for phrase and sentence units. Critically, when there was noise, adults increased the cortical tracking of monosyllabic words in the inferior frontal gyri but children did not.This study demonstrates that the difficulties of school-aged children in understanding speech in a multi-talker background might be partly due to an immature identification of lexical but not supra-lexical linguistic units.HighlightsChildren track the hierarchical linguistic units of clear speech devoid of prosodyThis cortical tracking is left-hemisphere dominant as the adult brainBabble noise reduces cortical tracking of sentences in children and adultsUnlike adults, children are not able to enhance cortical tracking of words in noise
Content-aware image restoration improves spatiotemporal resolution in luminescence microscopy
Authors: Boothe Tobias , Ivanković Mario , Grohme Markus A. , Rink Jochen C. 
Published: May 2022

AbstractLuminescence microscopy is a powerful tool in biomedical imaging applications due to its intrinsically high signal to noise ratio. However, luminescence signal detection requires longer exposure times than fluorescence imaging and is consequently less suited for applications requiring high temporal resolution or throughput. Here we demonstrate that content-aware image restoration can drastically reduce the exposure time requirements in luminescence imaging, thus overcoming one of the major limitations of the technique.
High fat diet changes bacterial signatures in the murine pancreas
Authors: Scheithauer Torsten P.M. , Davids Mark , Winkelmeijer Maaike , Havik Stefan , Nieuwdorp Max , Herrema Hilde , van Raalte Daniël H. 
Published: May 2022

AbstractHyperglycemia is caused by failure of pancreatic beta cells. Beta-cell inflammation contributes to beta-cell dysfunction, however (primary) immunogenic triggers are in large unknown. The gut microbiota is one potential source of pro-inflammatory molecules. A high-fat diet treatment increases pro-inflammatory bacteria in the gut microbiome, parts of which could migrate to the pancreatic beta-cell. In the present study, the bacterial DNA signature in the pancreas and intestine of C57BL6/J mice was analyzed. Mice were fed a high-fat diet (60% kcal fat) or a regular chow diet for 12 weeks. We took several precautions to avoid and map contamination. The gut microbiota was affected by high-fat diet as following: We observed several common intestinal ASVs in the pancreatic tissue. Although the pancreatic ASVs do not correlate exactly with the gut ASVs, our data implicate that the pancreas contains bacterial DNA and that this signature is altered in high-fat diet fed mice (PERMONOVA, p = 0.037; betadisper, p=0.029). Gut derived bacterial DNA might end up in the pancreas at some point in time. Hence, this work supports the concept of translocation of bacterial DNA to the pancreas, which might contribute to inflammation and dysfunction of pancreatic beta-cells.
Off-target integron activity leads to rapid plasmid compensatory evolution in response to antibiotic selection pressure
Authors: Souque Célia , Escudero José A. , MacLean R.Craig 
Published: May 2022

AbstractIntegrons are mobile genetic elements that have played an important role in the dissemination of antibiotic resistance. Under stress, the integron can generate combinatorial variation in resistance cassette expression by cassette re-shuffling, accelerating the evolution of resistance. However, the flexibility of the integron integrase site recognition motif hints at potential off-target effects of the integrase on the rest of the genome that may have important evolutionary consequences. Here we test this hypothesis by selecting for increased piperacillin resistance populations of P.aeruginosa with a mobile integron containing a hard-to-mobilise beta-lactamase cassette to minimize the potential for adaptive cassette re-shuffling. We found that integron activity can both decrease overall survival rate but also improve the fitness of the surviving populations. Off-target inversions mediated by the integron accelerated plasmid adaptation by disrupting costly conjugative genes otherwise mutated in control populations lacking a functional integrase. Plasmids containing integron-mediated inversions were associated with lower plasmid costs and higher stability than plasmids carrying mutations, albeit at a cost of reduced conjugative ability. These findings highlight the potential for integrons to create structural variation that can drive bacterial evolution, and they provide an interesting example showing how antibiotic pressure can drive the loss of conjugative genes.
A Novel Y-Shaped, S-O-N-O-S-Bridged Crosslink between Three Residues C22, C44, and K61 Is a Redox Switch of the SARS-CoV-2 Main Protease
Authors: Yang Kai S. , Kuo Syuan-Ting Alex , Blankenship Lauren R. , Sheng Yan J. , Sankaran Banumathi , Li Pingwei , Fierke Carol A. , Russell David H. , Yan Xin , Xu Shiqing , Liu Wenshe Ray 
Published: May 2022

ABSTRACTAs the COVID-19 pathogen, SARS-CoV-2 relies on its main protease (MPro) for pathogenesis and replication. During the crystallographic analyses of MPro crystals that were exposed to the air, a uniquely Y-shaped, S-O-N-O-S-bridged posttranslational crosslink that connects three residues C22, C44, and K61 at their side chains was frequently observed. As a novel posttranslational modification, this crosslink serves as a redox switch to regulate the catalytic activity of MPro, a demonstrated drug target of COVID-19. The formation of this linkage leads to a much more opened active site that can be potentially targeted for the development of novel SARS-CoV-2 antivirals. The inactivation of MPro by this crosslink indicates that small molecules that lock MPro in the crosslinked form can be potentially used with other active site-targeting molecules such as paxlovid for synergistic effects in inhibiting the SARS-CoV-2 viral replication. Therefore, this new finding reveals a unique aspect of the SARS-CoV-2 pathogenesis and is potentially paradigm-shifting in our current understanding of the function of MPro and the development of its inhibitors as COVID-19 antivirals.
New insights from short and long reads sequencing to explore cytochrome b variants of Plasmopara viticola populations collected in vineyard and related to resistance to complex III inhibitors
Authors: Cherrad Semcheddine , Gillet Benjamin , Dellinger Julien , Bellaton Lalie , Roux Pascale , Hernandez Catalina , Steva Hervé , Perrier Lauriane , Hughes Sandrine , Vacher Sébastien 
Published: May 2022

AbstractDowny mildew is caused by Plasmopara viticola, an obligate oomycete plant pathogen, a devasting disease for grapevine. To preserve plants from the disease, complex III inhibitors are among the widely used fungicides that specifically target the mitochondrial cytochrome b (cytb) of the pathogen to block cellular respiration mechanisms. In French vineyard, P. viticola developed resistance against a first category of these fungicides, the Quinone outside inhibitors, by exhibiting a single amino acid substitution G143A in its cytb mitochondrial sequence. Their usage was restricted and another kind of fungicides, Quinone inside inhibitors, targeting the same gene and highly effective against oomycetes, were used instead. Recently however, less sensitive P. viticola populations were detected after treatments with some inhibitors, in particular ametoctradin and cyazofamid. By isolating resistant single-sporangia strains of P. viticola to these fungicides, we characterized new variants in cytb sequences associated with cyazofamid resistance: a point mutation (L201S) and more strikingly, two insertions (E203-DE-V204, E203-VE-V204). In parallel with classical tools, pyrosequencing and RT-PCR, we then benchmarked both short and long-reads NGS technologies (Ion Torrent, Illumina, Oxford Nanopore Technologies) to sequence the complete cytb with the prospect to detect and assess the proportion of resistant variants of P. viticola at a natural population scale. Eighteen populations collected from French vineyard fields in 2020 were analysed: 12 show a variable proportion of G143A, 11 of E203-DE-V204 and 7 populations of the S34L variant that confers resistance to ametoctradin. Interestingly, long reads were able to identify variants, including SNPs, with confidence and detect a small proportion of P. viticola showing several variants along the same cytb sequence. Altogether, NGS appear promising methods to evaluate pathogen resistance towards fungicides related to cytb modifications at a population scale in the field. This approach could be rapidly a robust decision-support management tool for vineyard in future.
Aβ42 and Aβ40 oligomers form transient and persistent pores with different time evolutions and toxicities
Authors: Shah Syed Islamuddin , Parker Ian , Ullah Ghanim , Demuro Angelo 
Published: May 2022

AbstractIn Alzheimer’s disease (AD), formation of harmful self-gating pores formed by the insertion of amyloid beta oligomers (AβOs) into the plasma membrane have been shown to cause disruption of Ca2+ homeostasis, leading to neuronal malfunctioning and degeneration. Among different isoforms, the most studied Aβ40 and Aβ42 are also believed to be the most toxic ones. Using single channel imaging, we show that both isoforms can form functionally distinct populations of Ca2+ permeable pores, we named transient and persistent pores. The transient pores could be seen only for a few tens of milliseconds, while persistent pores can be observed for more than an hour. However, while the Ca2+-toxicity of pores formed by Aβ42Os tend to increase over time by displaying higher open probability and larger Ca2+ permeability, pores formed by Aβ40Os show opposite time dependent behavior. We conclude that although both isoforms can form Ca2+ permeable pores in the cell’s plasma membrane, pores due to Aβ42Os display worsening Ca2+ toxicity over time.
5’ Untranslated mRNA Regions Allow Bypass of Host Cell Translation Inhibition by Legionella pneumophila
Authors: Lipo Erion , Asrat Seblewongel , Huo Wenwen , Sol Asaf , Fraser Christopher S. , Isberg Ralph R. 
Published: May 2022

AbstractLegionella pneumophila grows within membrane-bound vacuoles in alveolar macrophages during human disease. Pathogen manipulation of the host cell is driven by bacterial proteins translocated through a type IV secretion system (T4SS). Although host protein synthesis during infection is arrested by the action of several of these translocated effectors, translation of a subset of host proteins predicted to restrict the pathogen is maintained. To identify the spectrum of host proteins selectively synthesized after L. pneumophila challenge, macrophages infected with the pathogen were allowed to incorporate the amino acid analog azidohomoalanine (AHA) during a two-hour time window, and newly synthesized macrophage proteins were isolated by orthogonal chemistry followed by mass spectrometry. Among the proteins isolated were interferon-stimulated genes (ISGs) as well as proteins translated from highly abundant transcripts. Surprisingly, a large number of the identified proteins were from low abundance transcripts. These proteins were predicted to be among the most efficiently translated per unit transcript in the cell based on ribosome profiling datasets. To determine if high ribosome loading was a consequence of efficient translation initiation, the 5’ untranslated regions (5’UTR) of transcripts having the highest and lowest predicted loading levels were inserted upstream of a reporter, and translation efficiency was determined in response to L. pneumophila challenge. The efficiency of reporter expression largely correlated with predicted ribosome loading and lack of secondary structure. Therefore, determinants in the 5’UTR allow selected host cell transcripts to overcome a pathogen-driven translation blockade.
Displacement and dissociation of oligonucleotides during DNA hairpin closure under strain
Authors: Ding Fangyuan , Cocco Simona , Raj Saurabh , Manosas Maria , Spiering Michelle M. , Bensimon David , Allemand Jean-François , Croquette Vincent 
Published: May 2022

ABSTRACTThe simple hybridization kinetic of an oligonucleotide to its template is a fundamental step in many biological processes such as replication arrest, CRISPR recognition, DNA sequencing, DNA origami, etc. Although approaches exist that address special cases of this problem, there are no simple general prediction schemes. In this work, we have measured experimentally, with no fluorescent labelling, the displacement of an oligonucleotide from its substrate in two situations: one corresponding to oligonucleotide binding/unbinding on ssDNA and one where the oligonucleotide is displaced by the refolding of a dsDNA fork. In this second situation, the fork is expelling the oligonucleotide thus reducing significantly its residence time. To account for our data in these two situations, we have constructed a mathematical model, based on the known nearest neighbor dinucleotide free energies, and provided a good estimate of the residence times of different oligonucleotides (DNA, RNA, LNA) with various length in different experimental conditions (force, temperature, buffer conditions, presence of mismatches, etc.). This study provides a foundation for the dynamics of oligonucleotide displacement, a process of importance in a number of biological and bioengineering contexts.