bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel
Authors: Mo Xiaoyi , Pang Peiyuan , Wang Yulin , Jiang Dexiang , Zhang Mengyu , Li Yang , Wang Peiyu , Geng Qizhi , Xie Chang , Du Hai-Ning , Zhong Bo , Li Dongdong , Yao Jing 
Published: March 2022

AbstractTransient receptor potential vanilloid 2 (TRPV2) is a multimodal ion channel widely regulating central and peripheral functions. Its important involvement in immune responses has been suggested such as in the macrophages’ phagocytosis process. However, the endogenous signaling cascades controlling the gating of TRPV2 remain to be understood. Here, we report that enhancing tyrosine phosphorylation remarkably alters the chemical and thermal sensitivities of TRPV2 endogenously expressed in rat bone marrow-derived macrophages. We identify that the protein tyrosine kinase JAK1 mediates TRPV2 phosphorylation at the molecular sites Tyr(335), Tyr(471), and Tyr(525). JAK1 phosphorylation is required for maintaining TRPV2 activity and the phagocytic ability of macrophages. We further show that TRPV2 phosphorylation is dynamically balanced by protein tyrosine phosphatase non-receptor type 1 (PTPN1). PTPN1 inhibition increases TRPV2 phosphorylation, further reducing the activation temperature threshold to ∼40 °C. Our data thus unveil an intrinsic mechanism where the phosphorylation/dephosphorylation dynamic balance sets the basal chemical and thermal sensitivity of TRPV2. Targeting this pathway will aid therapeutic interventions in physiopathological contexts.
Effects of dopamine D2 and opioid receptor antagonism on the trade-off between model-based and model-free behavior in healthy volunteers
Authors: Mikus Nace , Korb Sebastian , Massaccesi Claudia , Gausterer Christian , Graf Irene , Willeit Matthäus , Eisenegger Christoph , Lamm Claus , Silani Giorgia , Mathys Chris 
Published: March 2022

AbstractOur daily behaviour requires a flexible arbitration between actions we do out of habit and actions that are directed towards a specific goal. Drugs that target opioid and dopamine receptors are notorious for inducing maladaptive habitual drug consumption, yet how the opioidergic and dopaminergic neurotransmitter systems contribute to the arbitration between habitual and goal-directed behaviour is poorly understood. By combining pharmacological challenges with a well-established decision-making task and a novel computational model, we show that the administration of the D2 dopamine receptor antagonist amisulpride led to an increase in goal-directed or ‘model-based’ relative to habitual or ‘model-free’ behaviour, whereas the non-selective opioid receptor antagonist naltrexone had no appreciable effect. These findings highlight the distinct functional contributions of dopamine and opioid receptors to goal-directed and habitual behaviour and support the notion that D2 receptor antagonists promote stabilisation of goal-relevant information.
Myo1e knockout in the adult podocytes leads to proteinuria but has less severe consequences for kidney function than Myo1e loss during renal development
Authors: Chase Sharon E. , Krendel Mira 
Published: March 2022

AbstractMyosin 1e (Myo1e) is expressed in specialized epithelial cells in the kidney (podocytes) and plays an important role in renal filtration. Knockout of Myo1e in mice and mutations in the MYO1E gene in humans cause proteinuria and disrupt the ultrastructure of glomeruli, the initial segments of renal nephrons that are responsible for selective excretion of waste products without the loss of proteins from the bloodstream. Previous studies have demonstrated that the loss of Myo1e early in development results in severe defects in renal function in mice and may lead to end-stage renal disease in patients homozygous for MYO1E mutations. However, little is known about the effects of Myo1e loss later in life. In this study, we used inducible knockout of Myo1e in mouse podocytes to examine the effects of Myo1e loss from the adult kidneys. We have found that Myo1e loss after the completion of renal development causes proteinuria and podocyte defects but the effects are milder and more variable compared to the effects of Myo1e knockout in developing podocytes. These findings indicate that Myo1e plays an important role in podocyte development and differentiation but may also contribute to the maintenance of the glomerular barrier in the adult kidneys.
Diversity in DNA sequence, structure, and heterozygosity of nuclear rRNA gene region in Neopyropia yezoensis
Authors: Mizutani Yukino , Nagano Yukio , Kimura Kei , Kobayashi Genta , Kawamura Yoshio 
Published: March 2022

AbstractDNA sequence reads of Neopyropia yezoensis (susabi-nori), its relative N. tenera (asakusa-nori), and their hybrids available in the sequence read archive produced assembled sequences of the nuclear rRNA gene region for 82 samples. Analysis of the assembled sequences revealed structural differences in the region of nuclear rRNA genes, with 17 forms depending on the presence or absence of introns and their lengths. The samples were divided into three groups based on differences in DNA sequences: Japanese N. yezoensis, Chinese N. yezoensis, and N. tenera/hybrids of N. tenera and N. yezoensis that exist in both countries. Despite genetic differentiation, the Japanese and Chinese N. yezoensis exhibit common structural forms. One sample of Chinese N. yezoensis presented almost 1:1 heterozygosity, whereas five other samples of Chinese N. yezoensis showed non-1:1 heterozygosity. In the latter case, neither the ratio of alleles nor the ratio of the number of introns was 1:1, suggesting the existence of an ongoing mechanism to eliminate the nuclear rRNA gene region on one of the homologous chromosomes in N. yezoensis.
Dynamic causal modelling shows a prominent role of local inhibition in alpha power modulation in higher visual cortex
Authors: Van de Steen Frederik , Pinotsis Dimitris , Devos Wouter , Colenbier Nigel , Bassez Iege , Friston Karl , Marinazzo Daniele 
Published: March 2022

AbstractDuring resting-state EEG recordings, alpha activity is more prominent over the posterior cortex in eyes-closed (EC) conditions compared to eyes-open (EO). In this study, we characterized the difference in spectra between EO and EC conditions using dynamic causal modelling. Specifically, we investigated the role of intrinsic and extrinsic connectivity—within the visual cortex—in generating EC-EO alpha power differences over posterior electrodes. The primary visual cortex (V1) and the bilateral middle temporal visual areas (V5) were equipped with bidirectional extrinsic connections using a canonical microcircuit. The states of four intrinsically coupled subpopulations—within each occipital source—were also modelled. Using Bayesian model selection, we tested whether modulations of the intrinsic connections in V1, V5 or extrinsic connections (or a combination thereof) provided the best evidence for the data. In addition, using parametric empirical Bayes (PEB), we estimated group averages under the winning model. Bayesian model selection showed that the winning model contained both extrinsic connectivity modulations, as well as intrinsic connectivity modulations in all sources. The PEB analysis revealed increased extrinsic connectivity during EC. Overall, we found a reduction in the inhibitory intrinsic connections during EC. The results suggest that the intrinsic modulations in V5 played the most important role in producing EC-EO alpha differences, suggesting an intrinsic disinhibition in higher order visual cortex, during EC resting state.Author summaryOne of the strongest signals that can be measured using EEG are so called alpha rhythms. These are neural oscillations that fall within the 8-12Hz frequency range. Alpha rhythms are most prominent when the eyes are closed and are seen at the electrodes placed at the back of the head. In this study, we studied the mechanism of alpha rhythms changes when going from eyes-open to an eyes-closed state. We used a biologically plausible model including different neural populations. We focused on modelling connections within and between different neural sources of the visual cortex and how they are modulated when going from eyes-open to an eyes closed state. We found evidence that inhibitory neurons play an important role in alpha rhythms.
The innovation of the symbiosome has enhanced the evolutionary stability of nitrogen fixation in legumes
Authors: de Faria Sergio M. , Ringelberg Jens J. , Gross Eduardo , Koenen Erik J.M. , Cardoso Domingos , Ametsitsi George K.D. , Akomatey John , Maluk Marta , Tak Nisha , Gehlot Hukam S. , Wright Kathryn M. , Teaumroong Neung , Songwattana Pongpan , de Lima Haroldo C. , Prin Yves , Zartmann Charles , Sprent Janet I. , Ardley Julie , Hughes Colin E. , James Euan K. 
Published: March 2022

SummaryNitrogen-fixing symbiosis is globally important in ecosystem functioning and agriculture, yet the evolutionary history of nodulation remains the focus of considerable debate. Recent evidence suggesting a single origin of nodulation followed by massive parallel evolutionary losses raises questions about why a few lineages in the N2-fixing clade retained nodulation and diversified as stable nodulators while most did not. Within legumes, nodulation is restricted to the two most diverse subfamilies, Papilionoideae and Caesalpinioideae, which show stable retention of nodulation across their core clades.We characterize two nodule anatomy types across 128 species in 56 of the 150 genera of the legume subfamily Caesalpinioideae: 1) fixation thread nodules (FTs), where nitrogen-fixing bacteroids are retained within the apoplast in modified infection threads and 2) symbiosomes, where rhizobia are symplastically internalized in the host cell cytoplasm within membrane-bound symbiosomes.Using a robust phylogenomic tree based on 997 genes from 146 caesalpinioid genera, we show that losses of nodulation are more prevalent in lineages with FTs.We propose that evolution of the symbiosome allows for a more intimate and enduring symbiosis through greater compartmentalisation of their rhizobial microsymbionts, resulting in greater evolutionary stability of nodulation across this species-rich pantropical clade of legumes.
Elaboration of a MALDI-TOF Mass Spectrometry-based Assay of Parkin Activity and High-Throughput screening platform for Parkin Activators
Authors: Traynor Ryan , Moran Jennifer , Stevens Michael , Knebel Axel , Behrouz Bahareh , Merchant Kalpana , Hastie C. James , Davies Paul , Muqit Miratul M. K. , De Cesare Virginia 
Published: March 2022

AbstractParkinson’s disease (PD) is a progressive neurological disorder that manifests clinically as alterations in movement (bradykinesia, postural instability, loss of balance, and resting tremors) as well as multiple non-motor symptoms including but not limited to cognitive and autonomic abnormalities. Mitochondrial dysfunction has been linked to sporadic PD and loss-of-function mutations in genes encoding the ubiquitin E3 ligase Parkin and protein kinase, PTEN-induced kinase 1 (PINK1), that regulate mitophagy, are causal for familial and juvenile PD1-3. Among several therapeutic approaches being explored to treat or improve PD patient’s prognosis, the use of small molecules able to reinstate or boost Parkin activity represents a potential pharmacological treatment strategy4. A major barrier is the lack of high throughput platforms based on robust and accurate quantification of Parkin activity in vitro. Here we present two different and complementary Matrix Assisted Laser Desorption/Ionization-Time of Flight mass spectrometry (MALDI-TOF MS) based approaches for the quantification of Parkin E3 ligase activity in vitro. These methods recapitulate distinct aspects of ubiquitin conjugation: Parkin auto-ubiquitylation and Parkin-catalysed discharge on lysine residues. Both approaches are scalable for high-throughput primary screening to facilitate the identification of Parkin modulators.
Alternative 3′ UTRs contributes to post-transcriptional gene expression regulation under high salt stress
Authors: Wang Taotao , Ye Wenbin , Zhang Jiaxiang , Li Han , Zeng Weike , Zhu Sheng , Ji Guoli , Wu Xiaohui , Ma Liuyin 
Published: March 2022

ABSTRACTHigh salt stress continually challenges growth and survival of many plants, but the underlying molecular basis is not fully explored. Alternative polyadenylation (APA) produces mRNAs with different 3′UTRs (alternative 3′UTRs) to regulate gene expression at post-transcriptional level. However, the roles of such process in response to salt stress remain elusive. Here, we reported that alternative 3′UTRs responded to high salt stress in the halophyte-Spartina alterniflora, which tolerant to hash salt environment. High salt stress induced the global APA and increased the prevalence of APA events. Strikingly, high salt stress significantly led to 3′ UTR lengthening of 207 transcripts through increasing the usage of distal poly(A) sites. Transcripts with alternative 3′ UTRs were mainly enriched in salt stress related ion transporters. Alternative 3′ UTRs of SaHKT1 increased RNA stability and protein synthesis in vivo. Regulatory AU-rich elements were identified in the alternative 3′ UTRs and alternative 3′ UTRs increased protein level of SaHKT1 in an AU-rich element dependent manner. Finally, 3′ UTR lengthening might result from variations in poly(A) signals and poly(A) factors. Overall, these results suggest that APA is a potential novel high salt stress responsive mechanism by modulating mRNA 3′ UTR length. These results also reveal complex regulator roles of alternative 3′ UTRs coupling alternative polyadenylation and regulatory elements at post-transcriptional level in plants.One sentence summaryAlternative 3′ UTRs acts as a potential novel mechanism in gene expression regulation of high salt tolerant genes
Connecting the Dots: PHF13 and cohesin promote polymer-polymer phase separation of chromatin into chromosomes
Authors: Rossi Francesca , Buschow Rene , Glaser Laura V. , Schubert Tobias , Staege Hannah , Grimme Astrid , Will Hans , Milke Thorsten , Vingron Martin , Chiariello Andrea M. , Kinkley Sarah 
Published: March 2022

SummaryHow interphase chromatin compacts into mitotic chromosomes has eluded researchers for over a century. Here we show that PHF13, a tightly regulated H3K4me epigenetic reader, and cohesin, a mediator of chromatin architecture, cooperate to drive polymer-polymer-phase-separation (PPPS) and higher order compaction of chromatin into chromosomes. PHF13 interacts with cohesin, shows similar dynamics during mitosis, and their co-depletion dramatically impairs mitotic condensation. Mechanistically, we demonstrate that PHF13 stabilizes cohesin chromatin interactions and that itself oligomerizes, resulting in a polymer with increased chromatin avidity and the ability to bridge neighboring and distant nucleosomes. Consistently, molecular dynamic simulations modelling the ability of PHF13 and cohesin to drive chromatin phase separations recapitulated our in vivo observations and are in line with 2-step condensation models.
The evolution of ageing in cooperative breeders
Authors: Kreider Jan J. , Kramer Boris H. , Komdeur Jan , Pen Ido 
Published: March 2022

AbstractCooperatively breeding animals live longer than their solitary counterparts. The traditional explanation for this is that cooperative breeding evolves more readily in long-lived species. Here, we reverse this argument and show that long lifespans are an evolutionary consequence of cooperative breeding. Natural selection favours a delayed onset of senescence in cooperative breeders, relative to solitary breeders, because cooperative breeders have a delayed age of first reproduction due to reproductive queueing. Especially long lifespans evolve in cooperative breeders with age-dependent reproductive queueing. Finally, we show that lower genetic relatedness among group members leads to the evolution of longer lifespans. This is because selection against higher mortality is weaker when mortality reduces competition between relatives. Our results link the evolutionary theory of ageing with kin selection theory, demonstrating that the evolution of ageing in cooperative breeders is driven by the timing of reproduction and kin structure within breeding territories.
Efficient quantification of lipid packing defect sensing by amphipathic peptides; comparing Martini 2 & 3 with CHARMM36
Authors: van Hilten Niek , Stroh Kai Steffen , Risselada Herre Jelger 
Published: March 2022

AbstractIn biological systems, proteins can be attracted to curved or stretched regions of lipid bilayers by sensing hydrophobic defects in the lipid packing on the membrane surface. Here, we present an efficient end-state free energy calculation method to quantify such sensing in molecular dynamics simulations. We illustrate that lipid packing defect sensing can be defined as the difference in mechanical work required to stretch a membrane with and without a peptide bound to the surface. We also demonstrate that a peptide’s ability to concurrently induce excess leaflet area (tension) and elastic softening – a property we call the ‘characteristic area of sensing’ (CHAOS) – and lipid packing sensing behavior are in fact two sides of the same coin. In essence, defect sensing displays a peptide’s propensity to generate tension. The here-proposed mechanical pathway is equally accurate yet, computationally, about 40 times less costly than the commonly used alchemical pathway (thermodynamic integration), allowing for more feasible free energy calculations in atomistic simulations. This enabled us to directly compare the Martini 2 and 3 coarse-grained and the CHARMM36 atomistic force-fields in terms of relative binding free energies for six representative peptides including the curvature sensor ALPS and two antiviral amphipathic helices (AH). We observed that Martini 3 qualitatively reproduces experimental trends, whilst producing substantially lower (relative) binding free energies and shallower membrane insertion depths compared to atomistic simulations. In contrast, Martini 2 tends to overestimate (relative) binding free energies. Finally, we offer a glimpse into how our end-state based free energy method can enable the inverse design of optimal lipid packing defect sensing peptides when used in conjunction with our recently developed Evolutionary Molecular Dynamics (Evo-MD) method. We argue that these optimized defect sensors – aside from their biomedical and biophysical relevance – can provide valuable targets for the development of lipid force-fields.TOC Graphic
Pinch2 is a novel regulator of myelination in the Central Nervous System
Authors: Paes de Faria J , Vale-Silva RS , Fässler R , Werner HB , Relvas JB 
Published: March 2022

AbstractThe extensive morphological changes of oligodendrocytes during axon ensheathment and myelination involve assembly of the Ilk-Parvin-Pinch (IPP) heterotrimeric complex of proteins to relay essential mechanical and biochemical signals between integrins and the actin cytoskeleton. Binding of Pinch 1 and 2 isoforms to Ilk is mutually exclusive and allows the formation of distinct IPP complexes with specific signaling properties. Using tissue-specific conditional gene ablation in mice, we reveal an essential role for Pinch2 during central nervous system myelination. UnlikePinch1-gene ablation, loss ofPinch2in oligodendrocytes results in hypermyelination and in the formation of pathological myelin outfoldings in white matter regions. These structural changes concurred with inhibition of Rho GTPases RhoA and Cdc42 activities and phenocopied aspects of myelin pathology observed in corresponding mouse mutants. We propose a dual role for Pinch2 in preventing excess of myelin wraps through RhoA-dependent control of membrane growth and in fostering myelin stability via Cdc42-dependent organization of cytoskeletal septins. Together, these findings indicate that IPP-containing Pinch2 is a novel critical cell-autonomous molecular hub ensuring synchronous control of key signaling networks during developmental myelination.Summary statementPinch proteins are core components of a ternary protein complex comprising Ilk and Parvin (IPP). This work identifies Pinch2 as key regulator of the formation and maturation of CNS myelin.
What the flip? What the P-N flip can tell us about proactive suppression
Authors: Tam Joyce , Callahan-Flintoft Chloe , Wyble Brad 
Published: March 2022

AbstractIt has been debated whether salient distractors in visual search can be proactively suppressed to completely prevent attentional capture, as the occurrence of proactive suppression implies that the initial shift of attention is not entirely driven by physical salience. While the presence of a Pd component in the EEG (associated with suppression) without a preceding N2pc component (associated with selection) has been used as evidence for proactive suppression, the link between these ERPs and the underlying mechanisms is not always clear. This is exemplified in two recent papers that observed the same waveform pattern, where an early Pd-like component flipped to a N2pc-like component, but provided very different interpretations (Drisdelle & Eimer, Psychophysiology, 58(9), 1-12, 2021; Kerzel & Burra, Journal of Cognitive Neuroscience, 32(6), 1170-1183, 2020). Using RAGNAROC (Wyble et al., Psychological Review, 127(6), 1163-1198, 2020), a computational model of reflexive attention, we successfully simulated this ERP pattern with minimal changes to its existing architecture, providing a parsimonious and mechanistic explanation for this flip in the EEG that is unique from both of the previous interpretations. Our account supports the occurrence of proactive suppression and demonstrates the benefits of incorporating computational modelling into theory building.
A dynamic framework for sustainable open innovation in the food industry
Authors: Venturelli Andrea , Caputo Andrea , Pizzi Simone , Valenza Giuseppe 
Published: March 2022

PurposeThis study aims to take a holistic perspective to investigate how open innovation supports sustainability and the contribution to the Unite Nations (UN) Sustainable Development Goals (SDGs).Design/methodology/approachThe study is based on an in-depth single case study of Andriani SpA, a leading Italian company in the food industry. The case is built by triangulating data from direct observations, documentary analysis and semi-structured interviews.FindingsThe findings show an organization that has developed its competitive advantage by adopting open innovation to embed sustainability in its strategy and business model. The case study complements the understanding of how open innovation can effectively drive strategic renewal and innovation activities to address sustainability objectives in the food industry.Originality/valueThis study contributes to theoretical development by offering new and insightful explanations of firms' strategic behaviour and coevolution toward sustainability via open innovation. It provides practitioners, policymakers, researchers and students with reflections and inspiration about how open innovation may be deployed to support a holistic strategic renewal aimed at sustainability objectives, such as the SDGs, in the food industry.