bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recursive self-embedded vocal motifs in wild orangutans
Authors: Lameira Adriano R. , Hardus Madeleine E. , Ravignani Andrea , Raimondi Teresa , Gamba Marco 
Published: April 2023

AbstractRecursive procedures that allow placing a vocal signal inside another of similar kind provide a neuro-computational blueprint for syntax and phonology in spoken language and human song. There are, however, no known vocal sequences among nonhuman primates arranged in self-embedded patterns that evince vocal recursion or potential insipient or evolutionary transitional forms thereof, suggesting a neuro-cognitive transformation exclusive to humans. Here, we uncover that wild flanged male orangutan long calls feature rhythmically isochronous call sequences nested within isochronous call sequences, consistent with two hierarchical strata. Remarkably, three temporally and acoustically distinct call rhythms in the lower stratum were not related to the overarching rhythm at the higher stratum by any low multiples, which suggests that these recursive structures were neither the result of parallel non-hierarchical procedures or anatomical artifacts of bodily constrains or resonances. Findings represent a case of temporally recursive hominid vocal combinatorics in the absence syntax, semantics, phonology or music. Second-order combinatorics, ‘sequences within sequences’, involving hierarchically organized and cyclically structured vocal sounds in ancient hominids may have preluded the evolution of recursion in modern language-able humans.
A humanin vitroneuronal model for studying homeostatic plasticity at the network level
Authors: Yuan Xiuming , Puvogel Sofía , van Rhijn Jon-Ruben , Esteve-Codina Anna , Meijer Mandy , Rouschop Simon , van Hugte Eline J.H. , Oudakker Astrid , Schoenmaker Chantal , Schubert Dirk , Franke Barbara , Nadif Kasri Nael 
Published: April 2023

SummaryMechanisms that underlie homeostatic plasticity have been extensively investigated at single-cell levels in animal models, but are less well understood at the network level. Here, we used microelectrode arrays to characterize neuronal networks following induction of homeostatic plasticity in human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons co-cultured with rat astrocytes. Chronic suppression of neuronal activity through tetrodotoxin (TTX) elicited a time-dependent network re-arrangement. Increased expression of AMPA receptors and the elongation of axon initial segments were associated with increased network excitability following TTX treatment. Transcriptomic profiling of TTX-treated neurons revealed up-regulated genes related to extracellular matrix organization, while down-regulated genes related to cell communication; also astrocytic gene expression was found altered. Overall, our study shows that hiPSC-derived neuronal networks provide a reliablein vitroplatform to measure and characterize homeostatic plasticity at network and single-cell level; this platform can be extended to investigate altered homeostatic plasticity in brain disorders.
What AlphaFold tells us about cohesin’s retention on and release from chromosomes
Authors: Nasmyth Kim A. , Lee Byung-Gil , Roig Maurici B. , Löwe Jan 
Published: April 2023

ABSTRACTCohesin is a trimeric complex containing a pair of SMC proteins (Smc1 and Smc3) whose ATPase domains at the end of long coiled coils (CC) are interconnected by Scc1. During interphase, it organizes chromosomal DNA topology by extruding loops in a manner dependent on Scc1’s association with two large hook shaped proteins called SA (yeast: Scc3) and Nipbl (Scc2). The latter’s replacement by Pds5 recruits Wapl, which induces release from chromatin via a process requiring dissociation of Scc1’s N-terminal domain (NTD) from Smc3. If blocked by Esco (Eco)-mediated Smc3 acetylation, cohesin containing Pds5 merely maintains pre-existing loops, but a third fate occurs during DNA replication, when Pds5-containing cohesin associates with Sororin and forms structures that hold sister DNAs together. How Wapl induces and Sororin blocks release has hitherto remained mysterious. In the twenty years since their discovery, not a single testable hypothesis has been proposed as to their role. Here, AlphaFold 2 (AF) three-dimensional protein structure predictions lead us to propose formation of a quarternary complex between Wapl, SA, Pds5, and Scc1’s NTD, in which the latter is juxtaposed with (and subsequently sequestered by) a highly conserved cleft within Wapl’s C-terminal domain (CTD). AF also reveals how Scc1’s dissociation from Smc3 arises from a distortion of Smc3’s CC induced by engagement of SMC ATPase domains, how Esco acetyl transferases are recruited to Smc3 by Pds5, and how Sororin prevents release by binding to the Smc3/Scc1 interface. Our hypotheses explain the phenotypes of numerous existing mutations and are highly testable.
Reversal of cell, circuit and seizure phenotypes in a mouse model ofDNM1epileptic encephalopathy
Authors: Bonnycastle K. , Dobson K.L. , Blumrich E-M. , Gajbhiye A. , Davenport E.C. , Pronot M. , Steinruecke M. , Trost M. , Gonzalez-Sulser A. , Cousin M.A. 
Published: April 2023

AbstractPathogenic heterozygous missense mutations in theDNM1gene result in a novel form of epileptic encephalopathy.DNM1encodes for the large GTPase dynamin-1, an enzyme with an obligatory role in the endocytosis of synaptic vesicles (SVs) at mammalian nerve terminals. PathogenicDNM1mutations cluster within regions required for its essential GTPase activity, implicating disruption of this enzyme activity as being central to epileptic encephalopathy. We reveal that the most prevalent pathogenic mutation ofDNM1, R237W, disrupts dynamin-1 enzyme activity and SV endocytosis when overexpressed in central neurons. To determine how this dominant-negative heterozygous mutant impacted cell, circuit and behaviour when expressed from its endogenous locus, we generated a mouse carrying the R237W mutation. Neurons isolated from heterozygous mice displayed dysfunctional SV endocytosis, which translated into altered excitatory neurotransmission and seizure-like phenotypes. Importantly, these phenotypes were corrected at the cell, circuit andin vivolevel by the drug, BMS-204352, which accelerates SV endocytosis. This study therefore provides the first direct link between dysfunctional SV endocytosis and epilepsy, and importantly reveals that SV endocytosis is a viable therapeutic route for monogenic intractable epilepsies.
In vivostructure probing of RNA inArchaea: Novel insights into the ribosome structure ofMethanosarcina acetivorans
Authors: Williams Allison M. , Jolley Elizabeth A. , Santiago-Martínez Michel Geovanni , Chan Cheong Xin , Gutell Robin R. , Ferry James G. , Bevilacqua Philip C. 
Published: April 2023

AbstractStructure probing combined with next-generation sequencing (NGS) has provided novel insights into RNA structure-function relationships. To date such studies have focused largely on bacteria and eukaryotes, with little attention given to the third domain of life, archaea. Furthermore, functional RNAs have not been extensively studied in archaea, leaving open questions about RNA structure and function within this domain of life. With archaeal species being diverse and having many similarities to both bacteria and eukaryotes, the archaea domain has the potential to be an evolutionary bridge. In this study, we introduce a method for probing RNA structurein vivoin the archaea domain of life. We investigated the structure of ribosomal RNA (rRNA) fromMethanosarcina acetivorans, a well-studied anaerobic archaeal species, grown with either methanol or acetate. After probing the RNAin vivowith dimethyl sulfate (DMS), Structure-seq2 libraries were generated, sequenced, and analyzed. We mapped the reactivity of DMS onto the secondary structure of the ribosome, which we determined independently with comparative analysis, and confirmed the accuracy of DMS probing inM. acetivorans. Accessibility of the rRNA to DMS in the two carbon sources was found to be quite similar, although some differences were found. Overall, this study establishes the Structure-seq2 pipeline in the archaea domain of life and informs about ribosomal structure withinM. acetivorans.
MicroRNA-Mediated Obstruction of Stem-loop Alternative Splicing (MIMOSAS): a global mechanism for the regulation of alternative splicing
Authors: Ruan Kai , Perez German Farinas , Liu Jiaqi , Kubat Miroslav , Hofacker Ivo , Wuchty Stefan , Zhai R. Grace 
Published: April 2023

AbstractWhile RNA secondary structures are critical to regulate alternative splicing of long-range pre-mRNA, the factors that modulate RNA structure and interfere with the recognition of the splice sites are largely unknown. Previously, we identified a small, non-coding microRNA that sufficiently affects stable stem structure formation ofNmnatpre-mRNA to regulate the outcomes of alternative splicing. However, the fundamental question remains whether such microRNA-mediated interference with RNA secondary structures is a global molecular mechanism for regulating mRNA splicing. We designed and refined a bioinformatic pipeline to predict candidate microRNAs that potentially interfere with pre-mRNA stem-loop structures, and experimentally verified splicing predictions of three different long-range pre-mRNAs in theDrosophilamodel system. Specifically, we observed that microRNAs can either disrupt or stabilize stem-loop structures to influence splicing outcomes. Our study suggests that MicroRNA-Mediated Obstruction of Stem-loop Alternative Splicing (MIMOSAS) is a novel regulatory mechanism for the transcriptome-wide regulation of alternative splicing, increases the repertoire of microRNA function and further indicates cellular complexity of post-transcriptional regulation.One-Sentence SummaryMicroRNA-Mediated Obstruction of Stem-loop Alternative Splicing (MIMOSAS) is a novel regulatory mechanism for the transcriptome-wide regulation of alternative splicing.
Nociception in chicken embryos, Part I: Analysis of cardiovascular responses to a mechanical noxious stimulus
Authors: Weiss Larissa , Saller Anna M. , Werner Julia , Süß Stephanie C. , Reiser Judith , Kollmansperger Sandra , Anders Malte , Fenzl Thomas , Schusser Benjamin , Baumgartner Christine 
Published: April 2023

AbstractWhile it is assumed that chicken embryos acquire the ability for nociception during the developmental period in the egg, an exact time point has not yet been specified. This study aimed to determine the onset of nociception during embryonic development in chicken. Changes in blood pressure and heart rate (HR) in response to a mechanical noxious stimulus at the base of the beak versus a light touch on the beak in chicken embryos between embryonic days (EDs) 7 and 18 were examined. Mean arterial pressure (MAP) was the most sensitive parameter for assessing cardiovascular responses. Significant changes in MAP in response to a noxious stimulus were detected in embryos at ED16 to ED18, while significant changes in HR were observed on ED17 and ED18. Infiltration anesthesia with the local anesthetic lidocaine significantly reduced reactions in MAP on ED18, so the cardiovascular changes can be assumed to be nociceptive responses.
A data-driven approach for enhancing forest productivity by accounting for indirect genetic effects
Authors: Ferreira Filipe M. , Chaves Saulo F. S. , Bhering Leonardo L. , Alves Rodrigo S. , Takahashi Elizabete K. , Resende Marcos D. V. , Souza João E. , Gezan Salvador A. , Viana José M. S. , Fernandes Samuel B. , Dias Kaio O. G. 
Published: April 2023

AbstractMaintaining the past decades current genetic gains for tree species is a challenging task for foresters and tree breeders due to biotic and abiotic factors. Planting a mixture of genotypes or clonal composites can be an alternative to increase the phytosanitary security and yield of forest plantations. These clonal composites are more complex than monocultures due to inter-genotypic competition and indirect genetic effects that can affect the total heritable variation. This study aims to understand how indirect genetic effects can impact the response to selection and how the stand composition can be used to explore these effects and enhance forest yield. We used a clonally trial ofEucalyptus urophylla×Eucalyptus grandishybrids in a randomized complete block design with 24 replications, containing a single tree per plot evaluated for mean annual increment at 3 and 6 years. We focus on partitioning the genetic variation of trees into direct and indirect genetic effects based on competition intensity factors. We identified clones as aggressive, homeostatic, and sensitive based on the magnitude of indirect genetic effects. By accounting for indirect genetic effects, for mean annual increment, the total heritability decreased 39 and 44% for 3 and 6 years, respectively. We proposed a workflow that uses the direct and indirect genetic effect to predict the mean value of clonal composite combinations and to select the one with highest yield. Our methodology accounted for spatial variability and interplot competition that can contribute to the total heritable variance and response to selection in forest trials. Based on the models evaluated, the clones are easily classified according to their deviation from the indirect genetic effects mean. Also, we extract useful information to predict different clonal composites compositions, their expected average performance, and define the best recommended combination to be planted in large scale.
Visualization oftranshomophilic interaction of clustered protocadherin in neurons
Authors: Hoshino Natsumi , Kanadome Takashi , Itoh Mizuho , Kaneko Ryosuke , Inoue Yukiko U. , Inoue Takayoshi , Hirabayashi Takahiro , Watanabe Masahiko , Matsuda Tomoki , Nagai Takeharu , Tarusawa Etsuko , Yagi Takeshi 
Published: April 2023

AbstractClustered protocadherin (Pcdh) functions as a cell recognition molecule through the homophilic interaction in CNS. However, its interactions have yet not been visualized in neurons. We previously reported PcdhγB2-FRET probes to be applicable only for cell lines. Herein, we newly designed PcdhγB2-FRET probes by fusing FRET donor and acceptor fluorescent proteins to a single PcdhγB2 molecule and succeeded in visualizing PcdhγB2 homophilic interaction in cultured hippocampal neurons. The γB2-FRET probe localized in the soma and neurites, and FRET signals were observed at contact sites between neurites and eliminated by EGTA addition. Live imaging revealed that the FRET-negative γB2 signals were rapidly moving along neurites and soma, whereas the FRET-positive signals remained in place. We observed that the γB2 proteins at synapses rarely interact homophilically. The γB2-FRET probe would allow us to elucidate the function of the homophilic interaction and the cell recognition mechanism.Significance StatementWe visualize the Pcdh homophilic interaction using a novel FRET-based probe, and reveal that the homophilically interacting Pcdh proteins are found at contact sites between the neurites and roots of neurites from the soma, and are stable at a location. Additionally, in neurons, Pcdh proteins are located at synapses but rarely interact homophilically.
ENOD93 interacts with cytochrome c oxidase altering respiratory ATP production and root growth in plants
Authors: Lee Chun Pong , Le Xuyen H. , Gawryluk Ryan M.R. , Casaretto José A. , Rothstein Steven J. , Millar A. Harvey 
Published: April 2023

AbstractThe early nodulin 93 (ENOD93) gene family in plants can regulate biological nitrogen fixation in legumes and nitrogen use efficiency in cereals but its molecular function is unknown. We show profile hidden Markov models define ENOD93 as a distant homolog of the N-terminal domain of RESPIRATORY SUPERCOMPLEX FACTOR 2 (RCF2). RCF2 is reported to regulate cytochrome oxidase (CIV) influencing the generation of a mitochondria proton motive force in yeast. Knockout ofenod93in Arabidopsis leads to a short root phenotype. ENOD93 is associated with a protein complex the size of CIV in isolated mitochondria but neither CIV abundance nor its activity in ruptured organelles changed inenod93. However, a progressive loss of ADP-dependent respiration rate was observed inenod93mitochondria which could be fully recovered in complemented lines. Mitochondrial membrane potential was higher inenod93but ATP synthesis and ADP depletion rates progressively decreased. Respiration rate of wholeenod93seedlings was elevated and root ADP content was nearly double that in WT without a change in ATP content. These altered energetic states correlated with elevated respiratory substrate levels in roots ofenod93compared to WT and complemented lines. Overexpression of ENOD93 lowered ATP content in roots and increased the abundance of a range of amino acids in both roots and leaves. We propose that two previously unconnected gene families in plants, ENOD93 and HYPOXIA INDUCED GENE DOMAIN, are the functional equivalent of yeast RCF2 but have remained undiscovered in many eukaryotic lineages because they are encoded in two separate genes.Highlight significanceWe identify the enigmatic early nodulin ENOD93 gene family as the plant homolog of the N-terminal regulatory domain of the yeast RESPIRATORY SUPERCOMPLEX 2 (RCF2) of the mitochondrial oxidative phosphorylation system and provide biochemical and physiological evidence of its role in plant ATP production, broadly explaining the role of ENOD93 in plants.
Cross regulation in a three-component cell envelope stress signaling system ofBrucella
Authors: Chen Xingru , Alakavuklar Melene A. , Fiebig Aretha , Crosson Sean 
Published: April 2023

AbstractA multi-layered structure known as the cell envelope separates the controlled interior of bacterial cells from a fluctuating physical and chemical environment. The transcription of genes that determine cell envelope structure and function is commonly regulated by two-component signaling systems (TCS), comprising a sensor histidine kinase and a cognate response regulator. To identify TCS genes that contribute to cell envelope function in the intracellular mammalian pathogen,Brucella ovis, we subjected a collection of non-essential TCS deletion mutants to compounds that disrupt cell membranes and the peptidoglycan cell wall. Our screen led to the discovery of three TCS proteins that coordinately function to confer resistance to cell envelope stressors and to supportB. ovisreplication in the intracellular niche. This tripartite regulatory system includes the known cell envelope regulator, CenR, and a previously uncharacterized TCS, EssR-EssS, which is widely conserved inAlphaproteobacteria. The CenR and EssR response regulators bind a shared set of sites on theB. ovischromosomes to control transcription of an overlapping set of genes with cell envelope functions. CenR directly interacts with EssR and functions to stimulate phosphoryl transfer from the EssS kinase to EssR, while CenR and EssR control the cellular levels of each other via a post-transcriptional mechanism. Our data provide evidence for a new mode of TCS cross-regulation in which a non-cognate response regulator affects both the activity and protein levels of a cognate TCS protein pair.ImportanceAs intracellular pathogens,Brucellamust contend with a variety of host-derived stressors when infecting a host cell. The inner membrane, cell wall, and outer membrane — i.e. the cell envelope — ofBrucellaprovides a critical barrier to host assault. A conserved regulatory mechanism known as two-component signaling (TCS) commonly controls transcription of genes that determine the structure and biochemical composition of the cell envelope during stress. We report the identification of previously uncharacterized TCS genes that determineB. ovisfitness in the presence of cell envelope disruptors and within infected mammalian host cells. Our study reveals a new molecular mechanism of TCS-dependent gene regulation, and thereby advances fundamental understanding of transcriptional regulatory processes in bacteria.
EGFR+lung adenocarcinomas coopt alveolar macrophage metabolism and function to support EGFR signaling and growth
Authors: Kuhlmann-Hogan Alexandra , Cordes Thekla , Xu Ziyan , Traina Kacie A. , Robles-Oteíza Camila , Ayeni Deborah , Kwong Elizabeth M. , Levy Stellar R. , Nobari Mathew , Cheng George Z. , Shaw Reuben , Leibel Sandra L. , Metallo Christian M. , Politi Katerina , Kaech Susan M. 
Published: April 2023

AbstractThe limited efficacy of currently approved immunotherapies in EGFR-mutant lung adenocarcinoma (LUAD) underscores the need to better understand mechanisms governing local immunosuppression. Elevated surfactant and GM-CSF secretion from the transformed epithelium induces tumor-associated alveolar macrophages (TA-AM) to proliferate and support tumor growth by rewiring inflammatory functions and lipid metabolism. TA-AM properties are driven by increased GM-CSF—PPARγ signaling and inhibition of airway GM-CSF or PPARγ in TA-AMs suppresses cholesterol efflux to tumor cells, which impairs EGFR phosphorylation and restrains LUAD progression. In the absence of TA-AM metabolic support, LUAD cells compensate by increasing cholesterol synthesis, and blocking PPARγ in TA-AMs simultaneous with statin therapy further suppresses tumor progression and increases T cell effector functions. These results reveal new therapeutic combinations for immunotherapy resistant EGFR-mutant LUADs and demonstrate how such cancer cells can metabolically co-opt TA-AMs through GM-CSF—PPARγ signaling to provide nutrients that promote oncogenic signaling and growth.
Bird communities in a selectively logged tropical montane forest are dominated by small, low-elevation species
Authors: Chanda Ritobroto , Rai Shambu , Tamang Bharat , Munda Binod , Pradhan D.K. , Rai Mangal , Biswakarma Aman , Srinivasan Umesh 
Published: April 2023

AbstractTropical montane forests are critical centres of terrestrial biodiversity and endemism, and face a range of threats, including selective logging and climate change. However, few studies have explored the joint influence of these threats, particularly in tropical mountains, despite how crucial it is to understand the cumulative impact of forest loss and climate change on biodiversity. We used mist-netting and bird ringing data from a long-term (10-year) community and population monitoring program to examine how the composition of the mid-elevation Eastern Himalayan understorey bird community changed in the mid-elevation primary and logged forest. Because logged forest is warmer than primary forest, we hypothesised that the bird community would shift towards lower elevation species, with a faster transition in logged forest. Further, because logged forest has lower arthropod abundance, we hypothesised that the primary forest community would have larger species than the logged forest community. Our study shows that the bird community in the logged forest shifted towards lower-elevation species than in the primary forest (although this was not statistically significant). Moreover, we found that smaller species were better able to colonise warmer logged forest, whereas larger species reached higher densities in primary forest. These trends are likely to be driven by climate change causing upslope range shifts and logged forest selecting for species that are likely to tolerate the consequently altered abiotic (higher temperatures) and biotic (lower resources) environment. These findings have significant implications for understanding the impacts of forest loss and climate change on biodiversity, particularly in tropical montane forests.