bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unravelling individual rhythmic abilities using machine learning
Authors: Bella Simone Dalla , Janaqi Stefan , Benoit Charles-Etienne , Farrugia Nicolas , Bégel Valentin , Verga Laura , Harding Eleanor E. , Kotz Sonja A. 
Published: March 2023

AbstractHumans can easily extract the rhythm of a complex sound, like music, and move to its regular beat, for example in dance. These abilities are modulated by musical training and vary significantly in untrained individuals. The causes of this variability are multidimensional and typically hard to grasp with single tasks. To date we lack a comprehensive model capturing the rhythmic fingerprints of both musicians and non-musicians. Here we harnessed machine learning to extract a parsimonious model of rhythmic abilities, based on the behavioral testing (with perceptual and motor tasks) of individuals with and without formal musical training (n= 79). We demonstrate that the variability of rhythmic abilities, and their link with formal and informal music experience, can be successfully captured by profiles including a minimal set of behavioral measures. These profiles can shed light on individual variability in healthy and clinical populations, and provide guidelines for personalizing rhythm-based interventions.
Lasiodiplodiaspecies associated with mango (Mangifera indicaL.) decline in Burkina Faso and influence of climatic factors on the disease distribution
Authors: Dianda Oumarou Zoéyandé , Wonni Issa , Ouédraogo Léonard , Sankara Philippe , Tollenaere Charlotte , Del Ponte Emerson M. , Fernandez Diana 
Published: March 2023

AbstractDieback or decline caused byLasiodiplodiaspp. is a major disease of mango trees (Mangifera indicaL.). The main objectives of this study were to identifyLasiodiplodiaspecies associated with mango decline in Burkina Faso, and to asses the climatic and edaphic factors affecting the geographic distribution of the disease in the country. The genetic diversity of 47Lasiodiplodiaisolates was studied based on sequence data of the translation elongation factor 1-alpha gene (tef1-a) and the rDNA internal transcribed spacer region (ITS). Phylogeny analyses grouped the isolates from Burkina Faso with 6 differentLasiodiplodiaspecies, includingL. euphorbicolathat accounted for 36 of the 47 isolates.Lasiodiplodiaisolates tested on mango seedlings induced the typical dieback symptoms. Disease incidence and severity were generally higher in the drier and warmer regions (eastern) of the country. This study provides the required information to establish control strategies against mango decline in Burkina Faso.
EphrinA5 regulates cell motility by modulating the targeting of DNMT1 to theNcam1promoter via lncRNA/DNA triplex formation
Authors: Yildiz Can Bora , Kundu Tathagata , Gehrmann Julia , Koesling Jannis , Ravaei Amin , Jakovcevski Mira , Pensold Daniel , Zimmermann Olav , Rossetti Giulia , Costa Ivan G. , Zimmer-Bensch Geraldine 
Published: March 2023

AbstractCell-cell communication is mediated by membrane receptors and their cognate ligands, such as the Eph/ephrin system, and dictates physiological processes, including cell proliferation and migration. However, whether and how Eph/ephrin signaling culminates in transcriptional regulation is largely unknown. Epigenetic mechanisms are key for integrating external “signals”, e.g., from neighboring cells, into the transcriptome. We have previously reported that ephrinA5 stimulation of immortalized cerebellar granule (CB) cells elicits transcriptional changes of lncRNAs and protein-coding genes. LncRNAs represent important adaptors for epigenetic writers through which they regulate gene expression. Here, we investigate the interaction of lncRNA with protein-coding genes by the combined power ofin silicomodeling of RNA/DNA interactions and respective wet lab approaches, in the context of ephrinA5-dependent regulation of cellular motility. We found thatSnhg15, a cancer-related lncRNA, forms a triplex structure with theNcam1promoter and interacts with DNMT1. EphrinA5 stimulation leads to reducedSnhg15expression, diminishedSnhg15/DNMT1 interaction and decreased DNMT1 association with theNcam1promoter. These findings can explain the attenuatedNcam1promoter methylation and elevatedNcam1expression that in turn elicits decreased cell motility of CB cells. Hence, we propose that ephrinA5 influences gene transcription via lncRNA-targeted DNA methylation underlying the regulation of cellular motility.
Evidence for adaptive evolution towards high magnetic sensitivity of potential magnetoreceptor in songbirds
Authors: Langebrake Corinna , Manthey Georg , Frederiksen Anders , Lugo Ramos Juan S. , Dutheil Julien Y. , Chetverikova Raisa , Solov’yov Ilia , Mouritsen Henrik , Liedvogel Miriam 
Published: March 2023

AbstractMigratory birds possess remarkable accuracy in orientation and navigation, which involves various compass systems including the magnetic compass. Identifying the primary magnetosensor remains a fundamental open question. Cryptochromes (Cry) have been shown to be magnetically sensitive, specifically Cry4 shows enhanced magnetic sensitivity in migratory songbirds compared to resident species. Here, we investigate cryptochromes and their potential involvement in magnetoreception in a phylogenetic framework, integrating molecular evolutionary analyses with protein dynamics modeling. We base our analysis on 363 bird genomes and associate different selection regimes with migratory behaviour. We show that Cry4 is characterized by strong positive selection and high variability, typical characteristics of sensor proteins. We identify key sites that likely facilitated the evolution of a highly optimized sensory protein for night time compass orientation in songbirds and a potential functional shift or specialisation. Additionally, we show that Cry4 was lost in hummingbirds, parrots and Tyranni (Suboscines) and thus identified a natural comparative gene knockout, which can be used to test the function of Cry4 in birds. In contrast, the other two cryptochromes Cry1 and Cry2, were highly conserved in all species, indicating basal, non-sensory functions. Our results strengthen the hypothesised role of Cry4 as sensor protein in (night)-migratory songbirds.
Binding of the TRF2 iDDR motif to RAD50 highlights a convergent evolutionary strategy to inactivate MRN at telomeres
Authors: Khayat Freddy , Alshmery Majedh , Pal Mohinder , Oliver Antony W. , Bianchi Alessandro 
Published: March 2023

ABSTRACTTelomeres protect chromosome ends from unscheduled DNA repair, including from the MRN (MRE11, RAD50, NBS1) complex, which plays a critical role in the processing of double-stranded DNA breaks (DSBs). MRN orchestrates activation of the ATM kinase in the cellular DNA damage response (DDR), promotes DNA end-tethering aiding the nonhomologous end joining (NHEJ) pathway, and initiates DSB resection through the MRE11 nuclease. A previously identified protein motif (MIN, for MRN inhibitor) downregulates MRN activity via binding to RAD50 and has independently arisen at least twice, through convergent evolution of telomeric proteins Rif2 and Taz1, in budding and fission yeast respectively. We now provide a third example of convergent evolution for this binding mechanism for MRN at telomeres, by demonstrating that the iDDR motif of the human shelterin protein TRF2 binds to human RAD50 at the same site engaged by the MIN motif in the yeast proteins, despite lacking sequence homology. Modelling for the human CtIP interaction with RAD50 (necessary for activation of MRE11), and for the budding and fission yeast counterparts Sae2 and Ctp1, indicates that the interaction is mutually exclusive with binding of the iDDR/MIN motifs, pointing to a conserved mechanism for inhibition of MRN nuclease activity at telomeres.
Molecular mechanisms of inorganic-phosphate release from the core and barbed end of actin filaments
Authors: Oosterheert Wout , Blanc Florian E.C. , Roy Ankit , Belyy Alexander , Hofnagel Oliver , Hummer Gerhard , Bieling Peter , Raunser Stefan 
Published: March 2023

AbstractThe release of inorganic phosphate (Pi) from actin filaments constitutes a key step in their regulated turnover, which is fundamental to many cellular functions. However, the molecular mechanisms underlying Pirelease from both the core and barbed end of actin filaments remain unclear. Here, we combine cryo-EM with molecular dynamics simulations andin vitroreconstitution to demonstrate how actin releases Pithrough a ‘molecular backdoor’. While constantly open at the barbed end, the backdoor is predominantly closed in filament-core subunits and only opens transiently through concerted backbone movements and rotameric rearrangements of residues close to the nucleotide binding pocket. This mechanism explains why Piescapes rapidly from the filament end and yet slowly from internal actin subunits. In an actin variant associated with nemaline myopathy, the backdoor is predominantly open in filament-core subunits, resulting in greatly accelerated Pirelease after polymerization and filaments with drastically shortened ADP-Picaps. This demonstrates that the Pirelease rate from F-actin is controlled by steric hindrance through the backdoor rather than by the disruption of the ionic bond between Piand Mg2+at the nucleotide-binding site. Our results provide the molecular basis for Pirelease from actin and exemplify how a single, disease-linked point mutation distorts the nucleotide state distribution and atomic structure of the actin filament.
Inducible protein degradation as a strategy to identify Phosphoprotein Phosphatase 6 substrates in RAS-mutant colorectal cancer cells
Authors: Mariano Natasha C. , Rusin Scott F. , Nasa Isha , Kettenbach Arminja N. 
Published: March 2023

AbstractProtein phosphorylation is an essential regulatory mechanism that controls most cellular processes, including cell cycle progression, cell division, and response to extracellular stimuli, among many others, and is deregulated in many diseases. Protein phosphorylation is coordinated by the opposing activities of protein kinases and protein phosphatases. In eukaryotic cells, most serine/threonine phosphorylation sites are dephosphorylated by members of the Phosphoprotein Phosphatase (PPP) family. However, we only know for a few phosphorylation sites which specific PPP dephosphorylates them. Although natural compounds such as calyculin A and okadaic acid inhibit PPPs at low nanomolar concentrations, no selective chemical PPP inhibitors exist. Here, we demonstrate the utility of endogenous tagging of genomic loci with an auxin-inducible degron (AID) as a strategy to investigate specific PPP signaling. Using Protein Phosphatase 6 (PP6) as an example, we demonstrate how rapidly inducible protein degradation can be employed to identify dephosphorylation SITES and elucidate PP6 biology. Using genome editing, we introduce AID-tags into each allele of the PP6 catalytic subunit (PP6c) in DLD-1 cells expressing the auxin receptor Tir1. Upon rapid auxin-induced degradation of PP6c, we perform quantitative mass spectrometry-based proteomics and phosphoproteomics to identify PP6 substrates in mitosis. PP6 is an essential enzyme with conserved roles in mitosis and growth signaling. Consistently, we identify candidate PP6c-dependent phosphorylation sites on proteins implicated in coordinating the mitotic cell cycle, cytoskeleton, gene expression, and mitogen-activated protein kinase (MAPK) and Hippo signaling. Finally, we demonstrate that PP6c opposes the activation of large tumor suppressor 1 (LATS1) by dephosphorylating Threonine 35 (T35) on Mps One Binder (MOB1), thereby blocking the interaction of MOB1 and LATS1. Our analyses highlight the utility of combining genome engineering, inducible degradation, and multiplexed phosphoproteomics to investigate signaling by individual PPPs on a global level, which is currently limited by the lack of tools for specific interrogation.
Metabolic benefits of 17α-estradiol in liver are partially mediated by ERβ in male mice
Authors: Mondal Samim Ali , Mann Shivani N. , van der Linden Carl , Sathiaseelan Roshini , Kamal Maria , Das Snehasis , Bubak Matthew P. , Logan Sreemathi , Miller Benjamin F. , Stout Michael B. 
Published: March 2023

ABSTRACTMetabolic dysfunction underlies several chronic diseases. Dietary interventions can reverse metabolic declines and slow aging but remaining compliant is difficult. 17α-estradiol (17α-E2) treatment improves metabolic parameters and slows aging in male mice without inducing significant feminization. We recently reported that estrogen receptor α is required for the majority of 17α-E2-mediated benefits in male mice, but that 17α-E2 also attenuates fibrogenesis in liver, which is regulated by estrogen receptor β (ERβ)-expressing hepatic stellate cells (HSC). The current studies sought to determine if 17α-E2-mediated benefits on systemic and hepatic metabolism are ERβ-dependent. We found that 17α-E2 treatment reversed obesity and related systemic metabolic sequela in both male and female mice, but this was partially blocked in female, but not male, ERβKO mice. ERβ ablation in male mice attenuated 17α-E2-mediated benefits on hepatic stearoyl-coenyzme A desaturase 1 (SCD1) and transforming growth factor β1 (TGF-β1) production, which play critical roles in HSC activation and liver fibrosis. We also found that 17α-E2 treatment suppresses SCD1 production in cultured hepatocytes and hepatic stellate cells, indicating that 17α-E2 directly signals in both cell-types to suppress drivers of steatosis and fibrosis. We conclude that ERβ partially controls 17α-E2-mediated benefits on systemic metabolic regulation in female, but not male, mice, and that 17α-E2 likely signals through ERβ in HSCs to attenuate pro-fibrotic mechanisms.
A highly conserved and globally prevalent cryptic plasmid is among the most numerous mobile genetic elements in the human gut
Authors: Fogarty Emily C , Schechter Matthew S , Lolans Karen , Sheahan Madeline L. , Veseli Iva , Moore Ryan , Kiefl Evan , Moody Thomas , Rice Phoebe A , Yu Michael K , Mimee Mark , Chang Eugene B , Mclellan Sandra L , Willis Amy D , Comstock Laurie E , Eren A Murat 
Published: March 2023

ABSTRACTPlasmids are extrachromosomal genetic elements that often encode fitness enhancing features. However, many bacteria carry ‘cryptic’ plasmids that do not confer clear beneficial functions. We identified one such cryptic plasmid, pBI143, which is ubiquitous across industrialized gut microbiomes, and is 14 times as numerous as crAssphage, currently established as the most abundant genetic element in the human gut. The majority of mutations in pBI143 accumulate in specific positions across thousands of metagenomes, indicating strong purifying selection. pBI143 is monoclonal in most individuals, likely due to the priority effect of the version first acquired, often from one’s mother. pBI143 can transfer between Bacteroidales and although it does not appear to impact bacterial host fitnessin vivo, can transiently acquire additional genetic content. We identified important practical applications of pBI143, including its use in identifying human fecal contamination and its potential as an inexpensive alternative for detecting human colonic inflammatory states.
Activity-dependent subcellular compartmentalization of dendritic mitochondria structure in CA1 pyramidal neurons
Authors: Virga Daniel M. , Hamilton Stevie , Osei Bertha , Morgan Abigail , Zamponi Emiliano , Park Natalie J. , Hewitt Victoria L. , Zhang David , Gonzalez Kevin C. , Bloss Erik , Polleux Franck , Lewis Tommy L. 
Published: March 2023

ABSTRACTNeuronal mitochondria play important roles beyond ATP generation, including Ca2+uptake, and therefore have instructive roles in synaptic function and neuronal response properties. Mitochondrial morphology differs significantly in the axon and dendrites of a given neuronal subtype, but in CA1 pyramidal neurons (PNs) of the hippocampus, mitochondria within the dendritic arbor also display a remarkable degree of subcellular, layer- specific compartmentalization. In the dendrites of these neurons, mitochondria morphology ranges from highly fused and elongated in the apical tuft, to more fragmented in the apical oblique and basal dendritic compartments, and thus occupy a smaller fraction of dendritic volume than in the apical tuft. However, the molecular mechanisms underlying this striking degree of subcellular compartmentalization of mitochondria morphology are unknown, precluding the assessment of its impact on neuronal function. Here, we demonstrate that this compartment-specific morphology of dendritic mitochondria requires activity-dependent, Camkk2- dependent activation of AMPK and its ability to phosphorylate two direct effectors: the pro-fission Drp1 receptor Mff and the recently identified anti-fusion, Opa1-inhibiting protein, Mtfr1l. Our study uncovers a new activity- dependent molecular mechanism underlying the extreme subcellular compartmentalization of mitochondrial morphology in dendrites of neuronsin vivothrough spatially precise regulation of mitochondria fission/fusion balance.
Dual roles for nucleus accumbens core dopamine D1-expressing neurons projecting to the substantia nigra pars reticulata in limbic and motor control
Authors: Attachaipanich Suthinee , Ozawa Takaaki , Macpherson Tom , Hikida Takatoshi 
Published: March 2023

AbstractThe nucleus accumbens (NAc) is a critical component of a limbic basal ganglia circuit that is thought to play an important role in decision-making and the processing of rewarding stimuli. As part of this circuit, dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) of the NAc core are known to send a major projection to the substantia nigra pars reticulata (SNr). However, the functional role of this SNr-projecting NAc D1-MSNs (NAcD1-MSN-SNr) pathway is still largely uncharacterized. Moreover, as the SNr is thought to belong to both limbic and motor information processing basal ganglia loops, it is possible that the NAcD1-MSN-SNr pathway may be able to influence both limbic and motor functions. In this study we investigated the effect of optogenetic activation of the NAcD1-MSN-SNr pathway on reward-learning and locomotor behavior. Stimulation of the axon terminals of NAc core D1-MSNs in the SNr induced a preference for a laser-paired location, self-stimulation via a laser-paired lever, and augmented instrumental responding for a liquid reward-paired lever. Additionally, stimulation was observed to increase locomotor behavior when delivered bilaterally and induced contralateral turning behavior when delivered unilaterally. These findings indicate that the NAcD1-MSN-SNr pathway is able to control both reward learning and motor behaviors.
A structural vista of phosducin-like PhLP2A-chaperonin TRiC cooperation during the ATP-driven folding cycle
Authors: Park Junsun , Kim Hyunmin , Gestaut Daniel , Lim Seyeon , Leitner Alexander , Frydman Judith , Roh Soung-Hun 
Published: March 2023

AbstractProper cellular proteostasis, essential for viability, requires a network of chaperones and cochaperones. ATP-dependent chaperonin TRiC/CCT partners with cochaperones prefoldin (PFD) and phosducin-like proteins (PhLPs) to facilitate the folding of essential eukaryotic proteins. Using cryoEM and biochemical analyses, we determine the ATP-driven cycle of TRiC-PFD-PhLP2A interaction. In the open TRiC state, PhLP2A binds to the chamber’s equator while its N-terminal H3-domain binds to the apical domains of CCT3/4, thereby displacing PFD from TRiC. ATP-induced TRiC closure rearranges the contacts of PhLP2A domains within the closed chamber. In the presence of substrate, actin and PhLP2A segregate into opposing chambers, each binding to the positively charged inner surfaces formed by CCT1/3/6/8. Notably, actin induces a conformational change in PhLP2A, causing its N-terminal helices to extend across the inter-ring interface to directly contact a hydrophobic groove in actin. Our findings reveal an ATP-driven PhLP2A structural rearrangement cycle within the TRiC chamber to facilitate folding.Highlights-Structural analysis of TRiC-mediated folding cycle with cochaperones PhLP2A and PFD.-The interactions of PhLP2A and PFD with TRiC are mutually exclusive.-PhLP2A domains interact in a subunit-specific manner with the TRiC chamber.-PhLP2A domains are rearranged in ATP-closed TRiC to contact actin across the ring interface
Live-cell imaging provides direct evidence for a threshold in CDK activity at the G2/M transition
Authors: Sugiyama Hironori , Goto Yuhei , Kondo Yohei , Coudreuse Damien , Aoki Kazuhiro 
Published: March 2023

SummaryCyclin-dependent kinase (CDK) plays an essential role in determining the temporal ordering of the cell cycle phases. However, despite significant progress in studying regulators of CDK, it remains elusive how they coordinately affect CDK activity at the single-cell level and how CDK controls the temporal order of cell cycle events. This could be due to the lack of tools to monitor CDK activity in living cells. Here, we elucidate the dynamics of CDK activity in fission yeast and mammalian cells by using a newly developed CDK activity biosensor, Eevee-spCDK, based on Förster Resonance Energy Transfer (FRET). Taking advantage of this system, we unravel the profile of CDK activity in vegetatively growingS. pombecells. Thus, we detect a transient increase in S phase followed by a gradual increment during G2 phase. CDK activity then reaches its maximum in early M phase and rapidly decreases at mitotic exit. During G2 phase, CDK activity exhibits a biphasic pattern,i.e., an early slow increase and a late fast rise prior to the G2/M phase transition, as predicted from mathematical studies. Remarkably, although CDK activity does not necessarily correlate with cyclin levels, we find that it converges to the same level around mitotic onset in several mutant backgrounds, includingpom1Δcells andwee1orcdc25overexpressing cells. These data provide the first direct evidence that cells enter M phase when CDK activity reaches a high threshold, consistent with the quantitative model of cell cycle progression in fission yeast.
A reflection on contemporary myths of women's football: a historical analysis
Authors: Cooper Christine 
Published: March 2023

PurposeThis study aims to provide a social accounting of early women's football as a form of consciousness raising, and to provide a platform to raise questions about the path of the future of the women's game.Design/methodology/approachNewspaper archival materials supplemented by books and journal articles.FindingsBritish woman's football was repressed for 50 years by the football association.Research limitations/implicationsThis is a discussion paper, rather than a full academic manuscript.Practical implicationsThis paper is designed to enable questions to be raised about equality, and what that means in 2022.Social implicationsThere is an opportunity to reconsider a “feminine” version of the field of football.Originality/valueThere is an opportunity to use feminist theories to consider the past and future of women's football.