bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iron associated lipid peroxidation in Alzheimer’s disease is increased in lipid rafts with decreased ferroptosis suppressors, tested by chelation in mice
Authors: Thorwald Max A. , Godoy-Lugo Jose A. , Garcia Gilberto , Silva Justine , Kim Minhoo , Christensen Amy , Mack Wendy J. , Head Elizabeth , O’Day Peggy A. , Benayoun Bérénice A. , Morgan Todd E. , Pike Christian J. , Higuchi-Sanabria Ryo , Forman Henry Jay , Finch Caleb E. 
Published: March 2023

ABSTRACTIron-mediated cell death (ferroptosis) is a proposed mechanism of Alzheimer’s disease (AD) pathology. While iron is essential for basic biological functions, its reactivity generates oxidants which contribute to cell damage and death. To further resolve mechanisms of iron-mediated toxicity in AD, we analyzed postmortem human brain and ApoEFAD mice. AD brains had decreased antioxidant enzymes, including those mediated by glutathione (GSH). Subcellular analyses of AD brains showed greater oxidative damage and lower antioxidant enzymes in lipid rafts, the site of amyloid processing, than in the non-raft membrane fraction. ApoE4 carriers had lower lipid raft yield with greater membrane oxidation. The hypothesized role of iron to AD pathology was tested in ApoEFAD mice by iron chelation with deferoxamine, which decreased fibrillar amyloid and lipid peroxidation, together with increased GSH-mediated antioxidants. These novel molecular pathways in iron mediated damage during AD.Graphical AbstractHypothesis: AD brain lipid peroxidation is driven by increased brain iron and decreased antioxidant defenses. Schema shows proteins that mediate iron metabolism in relation to lipid peroxidation (HNE) and antioxidant defenses in prefrontal cortex. AD-associated increase (red), decrease (blue), or no change (grey), relative to cognitively normal elderly controls. Aβ; amyloid beta, ALDH2; alcohol dehydrogenase, APP; amyloid precursor protein, DMT1; divalent metal transporter 1; FPN, ferroportin; FSP1, ferroptosis suppressor protein 1, which requires the quinol cycle to attenuate lipid peroxidation; FTH1, ferritin heavy chain; FTL; ferritin light chain; GCLC, glutathione cysteine ligase catalytic subunit; GCLM, glutathione cysteine ligase modulator; GPx4, glutathione peroxidase 4; GSH, glutathione; GSSG, glutathione disulfide; GSTA4, glutathione S-transferase A4; HMOX; heme oxygenase; IRP, iron regulatory protein; LAT1, large neutral amino acid transporter 1; LOOH, Lipid hydroperoxides; Nrf2, Nuclear factor erythroid 2-related factor 2; Prdx6, peroxiredoxin 6; TF, transferrin, TfR; Transferrin receptor; xCT, cysteine-glutamate antiporter.
Two haplotype-resolved genomes of highly heterozygous AAB allotriploid bananas provide insights into subgenome asymmetric evolution and banana wilt control
Authors: Xie Wen-Zhao , Zheng Yu-Yu , He Weidi , Bi Fangcheng , Li Yaoyao , Dou Tongxin , Zhou Run , Guo Yi-Xiong , Deng Guiming , Zhang Wen-Hui , Yuan Min-Hui , Sanz-Jimenez Pablo , Zhu Xi-Tong , Xu Xin-Dong , Zhou Zu-Wen , Zhou Zhi-Wei , Feng Jia-Wu , Liu Siwen , Li Chunyu , Yang Qiaosong , Hu Chunhua , Gao Huijun , Dong Tao , Dang Jiangbo , Guo Qigao , Cai Wenguo , Zhang Jianwei , Yi Ganjun , Song Jia-Ming , Sheng Ou , Chen Ling-Ling 
Published: March 2023

ABSTRACTBananas (Musaspp.) are one of the most important tropical fruits and staple food, which are of great significance to human societies. Plantain and Silk are two important banana subgroups, which are both triploid hybrids (AAB) between the wild diploidMusa acuminataandM. balbisiana. In this study, we reported the first haplotype-resolved genome assembly of Plantain and Silk bananas with genome size of approximately 1.4 Gb. We discovered widespread asymmetric evolution in the subgenomes of Plantain and Silk, which could be linked to frequent homologous exchanges (HEs) events. This is the first study to uncover the genetic makeup of triploid banana and verify that subgenome B harbors a rich source of resistance genes. Of the 88,078 and 94,988 annotated genes in Plantain and Silk, only 58.5% and 59.4% were present in all three subgenomes, with >50% genes containing differently expressed alleles in different haplotypes. We also found that Plantain is more resistant to banana Fusarium wilt, exhibiting a much faster defense response after pathogenic fungi infection. Many differentially expressed genes in abscisic acid, ethylene, jasmonic acid and salicylic acid pathways were identified in Plantain. Our analysis revealed that MpMYB36 promotes the biosynthesis of secondary cell wall and deposition of lignin by directly binding to the promoter of MpPAL and MpHCT, which allows Plantain to inhibit the penetration of early infection. Moreover, the insertion of the key carotenoid synthesis gene (CRTISO) may be the potential genetic basis for the richness of carotenoids in Plantain. Our study provides an unprecedented genomic basis for basic research and the development of elite germplasm in cultivated bananas.
RecA-NT homology motif in ImuB is essential for mycobacterial ImuA’-ImuB protein interaction and mutasome function
Authors: Santos Joana A. , Timinskas Kęstutis , Lamers Meindert H. , Venclovas Česlovas , Warner Digby F. , Gessner Sophia J. 
Published: March 2023

ABSTRACTThe mycobacterial mutasome – minimally comprising ImuA’, ImuB, and DnaE2 proteins – has been implicated in DNA damage-induced mutagenesis inMycobacterium tuberculosis. ImuB, predicted to enable mutasome function via its interaction with the β clamp, is a catalytically inactive member of the Y-family of DNA polymerases. Like other members of the Y family, ImuB features a recently identified amino acid motif with homology to the RecA-N-terminus (RecA-NT). In RecA, the motif mediates oligomerization of RecA monomers into RecA filaments. Given the role of ImuB in the mycobacterial mutasome, we hypothesized that the ImuB RecA-NT motif might mediate its interaction with ImuA’, a RecA homolog of unknown function. To investigate this possibility, we constructed a panel ofimuBalleles in which RecA-NT was removed, or mutated. Results from microbiological and biochemical assays indicate that RecA-NT is critical for the interaction of ImuB with ImuA’. A region downstream of RecA-NT (ImuB-C) also appears to stabilize the ImuB-ImuA’ interaction, but its removal does not prevent complex formation. In contrast, replacing two key hydrophobic residues of RecA-NT, L378 and V383, is sufficient to disrupt ImuA’-ImuB interaction. To our knowledge, this constitutes the first experimental evidence showing the role of the RecA-NT motif in mediating the interaction between a Y-family member and a RecA homolog.
Tau seeding and spreading in vivo is supported by both AD-derived fibrillar and oligomeric tau
Authors: Mate de Gerando Anastasie , Welikovitch Lindsay A , Khasnavis Anita , Commins Caitlin , Glynn Calina , Chun Joshua E , Perbet Romain , Hyman Bradley T 
Published: March 2023

AbstractInsoluble fibrillar tau, the primary constituent of neurofibrillary tangles, has traditionally been thought to be the biologically active, toxic form of tau mediating neurodegeneration in Alzheimer’s disease. More recent studies have implicated soluble oligomeric tau species, referred to as high molecular weight (HMW) due to its properties on size exclusion chromatography, in tau propagation across neural systems. These two forms of tau have never been directly compared. We prepared sarkosyl insoluble and HMW tau from the frontal cortex of Alzheimer patients and compared their properties using a variety of biophysical and bioactivity assays. Sarkosyl insoluble fibrillar tau is comprised of abundant paired helical filaments (PHF) as quantified by electron microscopy (EM), and is more resistant to proteinase K, compared to HMW tau which is mostly in an oligomeric form. Sarkosyl insoluble and HMW tau are nearly equivalent in potency in a HEK cell bioactivity assay for seeding aggregates and their injection reveals similar local uptake into hippocampal neurons in PS19 Tau transgenic mice. However, the HMW preparation appears to be far more potent in inducing a glial response including Clec7a-positive rod-microglia in the absence of neurodegeneration or synapse loss and promotes more rapid propagation of misfolded tau to distal, anatomically connected regions, such as entorhinal and perirhinal cortices. These data suggest that soluble HMW tau has similar properties to fibrillar sarkosyl insoluble tau with regard to tau seeding potential but may be equal or even more bioactive with respect to propagation across neural systems and activation of glial responses, both relevant tau-related Alzheimer phenotypes.
A quantitative description for optical mass measurement of single biomolecules
Authors: Becker Jan , Peters Jack S. , Crooks Ivor , Helmi Seham , Synakewicz Marie , Schuler Benjamin , Kukura Philipp 
Published: March 2023

AbstractLabel-free detection of single biomolecules in solution has been achieved using a variety of experimental approaches over the past decade. Yet, our understanding of the magnitude of the optical contrast and its relationship to the underlying atomic structure, as well as the achievable measurement sensitivity and precision remain poorly defined. Here, we use a Fourier optics approach combined with an atomic structure-based molecular polarizability model to simulate mass photometry experiments from first principles. We find excellent agreement between several key experimentally-determined parameters such as optical contrast-to-mass conversion, achievable mass accuracy and molecular shape/orientation dependence. This allows us to determine detection sensitivity and measurement precision that is mostly independent of the optical detection approach chosen, resulting in a general framework for light-based single molecule detection and quantification.
Intermolecular proteolytic processing of SPRING and Site-1-protease regulate SREBP signaling
Authors: Hendrix Sebastian , Tan Josephine M.E. , Ndoj Klevis , Valiloo Masoud , Zijlstra Lobke F. , Ottenhoff Roelof , Seidah Nabil G. , Loregger Anke , Zelcer Noam 
Published: March 2023

AbstractThe SREBP transcription factors are central regulators of fatty acid and cholesterol metabolism. Produced as membrane-resident precursor proteins in the ER, their transcriptional activation requires the cholesterol-dependent translocation to the Golgi, and subsequent proteolytic cleavage by S1P, a type-I transmembrane protein. S1P is produced as a proprotein convertase that needs to undergo autocatalytic cleavage to attain its mature form in the Golgi, in a process that is not fully elucidated. We have recently identified SPRING (C12ORF49) as a novel regulator of the SREBP pathway and reported that S1P activity and retrograde recycling of the SREBP chaperone SCAP are affected. Here, we demonstrate that SPRING and S1P interact and that in co-transfection experiments in mammalian cells this facilitates the autocatalytic activation of S1PA→Cform. Accordingly, S1PA→Cprocessing of stably overexpressed S1P in SPRINGKOcells is attenuated, but not abolished, and does not rescue SREBP signaling. Reciprocally, we identified a conserved S1P cleavage site in SPRING, and demonstrate that cleavage of SPRING results in secretion of the SPRING ectodomain. SPRING cleavage is S1P-specific and can be pharmacologically inhibited by S1P inhibitors or by mutating the S1P cleavage site. Functional analysis revealed that the SPRING ectodomain was sufficient to support S1PA→Cprocessing and SREBP signaling, but that SPRING cleavage is not a prerequisite for this. In conclusion, our study reveals a complex interplay between the proteolytic activation of S1P and SPRING yet suggests that this is not the primary mechanism underlying the role of SPRING in SREBP signaling.
Mitochondria induce anisotropy and delays in action potential conduction
Authors: Castelfranco Ann , Alcami Pepe 
Published: March 2023

AbstractThe internal resistance of axons to ionic current flow affects the speed of action potential propagation. As biological cables, axons contain mitochondria which are necessary to support axonal function with energy supply. Although we would expect mitochondria to increase the internal resistance to current flow, their impact on the conduction velocity of action potentials has remained elusive. To investigate the impact of mitochondria on action potential propagation in the small non-myelinated fibers found in the vertebrate brain, we combined computational modeling and electron microscopy from the axons found in the premotor pathway that controls the production of birdsong with submillisecond precision. Mitochondria occupancy of axonal cross-sections ranged from 5 to 73% (average: 29%) in the ∼ 0.2-0.7 μm diameter non-myelinated axons connecting song premotor nuclei HVC and RA in canaries. Interestingly, this occupancy depends on axonal diameter: axonal cross-section occupancy by mitochondria was larger in small axons, with an average occupancy of ∼46% for axons with diameters smaller than 300 nm and ∼21% for larger diameters. Computational modeling showed that when the propagating action potential meets a mitochondrion, the conduction velocity decreases and the action potential is delayed by tenths of microseconds to microseconds. This effect is stronger in small axons given their larger cross section mitochondrial occupancy and cumulates delays of tenths of milliseconds along the whole pathway linking HVC and RA. Finally, we modeled the impact of varying densities of mitochondria on action potential propagation along the songbird premotor pathway. In summary, our model shows that axonal mitochondria induce the anisotropic propagation of action potentials, and that this effect cumulates a typical delay in the order of tenths of milliseconds over distances of mms. By partially occupying axoplasm, mitochondria constitute a biological design constraint that delays information processing in the small-diameter unmyelinated axons found in the vertebrate brain.
A new ferrocene derivative blocks KRAS localization and function by oxidative modification at His95
Authors: Rehl Kristen M. , Selvakumar Jayaraman , Hoang Don , Arumugam Kuppuswamy , Gorfe Alemayehu A. , Cho Kwang-jin 
Published: March 2023

AbstractRas proteins are membrane-bound GTPases that regulate essential cellular processes at the plasma membrane (PM). Constitutively active mutations of K-Ras, one of the three Ras isoforms in mammalian cells, are frequently found in human cancers. Ferrocene derivatives, which elevate cellular reactive oxygen species (ROS), have shown to block the growth of non-small cell lung cancers (NSCLCs) harboring oncogenic mutant K-Ras. Here, we developed and tested a novel ferrocene derivative on the growth of human pancreatic ductal adenocarcinoma (PDAC) and NSCLC. Our compound inhibited the growth of K-Ras-dependent PDAC and NSCLC and abrogated the PM binding and signaling of K-Ras, but not other Ras isoforms. These effects were reversed upon antioxidant supplementation, suggesting a ROS-mediated mechanism. We further identified K-Ras His95 residue in the G-domain as being involved in the ferrocene-induced K-Ras PM dissociation via oxidative modification. Together, our studies demonstrate that the redox system directly regulates K-Ras PM binding and signaling via oxidative modification at the His95, and proposes a role of oncogenic mutant K-Ras in the recently described antioxidant-induced metastasis in K-Ras-driven lung cancers.
Emergence of Bow-tie Architecture in Evolving Feedforward Networks
Authors: Itoh Thoma , Kondo Yohei , Aoki Kazuhiro , Saito Nen 
Published: March 2023

AbstractBow-tie architecture is a layered network structure that has a narrow middle layer with multiple inputs and outputs. Such structures are widely seen in the molecular networks in cells, suggesting that a universal evolutionary mechanism underlies the emergence of bow-tie architecture. The previous theoretical studies have implemented evolutionary simulations of the feedforward network to satisfy a given input–output goal, and proposed that the bow-tie architecture emerges when the ideal input– output relation is given as a rank-deficient matrix with mutations in network link strength in a multiplicative manner. Here, we report that the bow-tie network inevitably appears when the link intensities representing molecular interactions are small at the initial condition of the evolutionary simulation, regardless of the rank of the goal matrix. Our dynamical system analysis clarifies the mechanisms underlying the emergence of the bow-tie structure. Further, we demonstrate that the increase in the input–output matrix facilitates the emergence of bow-tie architecture even when starting from strong network links. Our data suggest that bow-tie architecture emerges as a side effect of evolution rather than as a result of evolutionary adaptation.Author SummaryMany biological networks including gene regulatory networks, metabolic networks, and signaling networks, show a characteristic hierarchical structure known as the bow-tie architecture. This architecture consists of a narrow middle layer with multiple inputs and outputs. Understanding why bow-tie architecture has universally appeared through evolution may provide insight into the design principle of a network within a cell. The universality of the bow-tie structure has so far been explained by the adaptive advantages such as high evolvability and capability to classify the inputs. However, our computer simulation demonstrates that the bow-tie structure inevitably emerges even without functional advantages when the molecular interactions within the network are weak at the initial condition of the evolution. We also demonstrate that an increase in the number of inputs (i.e., receptors) and outputs (i.e., downstream genes) leads to the emergence of bow-tie architecture, even when evolution starts from a strong molecular interaction. Although many previous studies have discussed the adaptive properties of bow-tie architecture, our findings suggest that bow-tie architecture is a byproduct of evolution rather than a result of evolutionary adaptation.
The structure of the tetraploid sour cherry ‘Schattenmorelle’ (Prunus cerasusL.) genome reveals insights into its segmental allopolyploid nature
Authors: Wöhner Thomas W. , Emeriewen Ofere F. , Wittenberg Alexander H.J. , Nijbroek Koen , Wang Rui Peng , Blom Evert-Jan , Keilwagen Jens , Berner Thomas , Hoff Katharina J. , Gabriel Lars , Thierfeldt Hannah , Almolla Omar , Barchi Lorenzo , Schuster Mirko , Lempe Janne , Peil Andreas , Flachowsky Henryk 
Published: March 2023

AbstractSour cherry (Prunus cerasusL.) is an economically important allotetraploid cherry species believed to have evolved in the Caspian Sea and Black Sea regions. How, when and where exactly the evolution of this species took place is unclear. It resulted from a hybridization of the tetraploid ground cherry (Prunus fruticosaPall.) and an unreduced (2n) pollen of the diploid ancestor sweet cherry (P. aviumL.). Some indications implement that the genome of sour cherry is segmental allopolyploid, but how it is structured and to what extent is unknown. To get an insight, the genome of the sour cherry cultivar ‘Schattenmorelle’ was sequenced at ~400x using Illumina NovaSeqTMshort-read and Oxford Nanopore long-read technologies (ONT R9.4.1 PromethION). Additionally, the transcriptome of ‘Schattenmorelle’ was sequenced using PacBio Sequel II SMRT cell sequencing at ~300x. The final assembly resulted in a ~629 Mbp long pseudomolecule reference genome, which could be separated into two subgenomes each split into eight chromosomes. SubgenomePceS_a which originates fromP. aviumhas a length of 269 Mbp, whereas subgenomePceS_f which originates fromP. fruticosahas a length of 299.5 Mbp. The length of unassembled contigs was 60 Mbp. The genome of the sour cherry shows a size-reduction compared to the genomes of its ancestral species. It also shows traces of homoeologous sequence exchanges throughout the genome. Comparative positional sequence and protein analyses provided evidence that the genome of sour cherry is segmental allotetraploid and that it has evolved in a very recent event in the past.
Changes in large-scale neural networks under stress are linked to affective reactivity to stress in real life
Authors: Tutunji Rayyan , Krentz Martin , Kogias Nikos , de Voogd Lycia , Krause Florian , Vassena Eliana , Hermans Erno J. 
Published: March 2023

AbstractControlled laboratory stress induction procedures are very effective in inducing physiological and subjective stress. However, whether such stress responses are representative for stress reactivity in real life is not clear. Using a combined within-subject functional MRI laboratory stress and ecological momentary assessment stress paradigm, we investigated dynamic shifts in large-scale neural network configurations under stress and how these relate to affective reactivity to stress in real life. Laboratory stress induction resulted in significantly increased cortisol levels, and shifts in task-driven neural activity including increased salience network (SN) activation in an oddball task and decreased default mode network activity in a memory retrieval task. Crucially, individuals showing increased SN reactivity specifically in the early phase of the acute stress response also expressed increased affective reactivity in real life. Our findings provide (correlational) evidence that real-life affective stress reactivity is driven primarily by vigilant attentional reorienting mechanisms associated with SN.
Bioregionalization: From Wallace and Humboldt to deep-time paleoregion dynamics
Authors: Briega-Álvarez Andrea , Siebert Heike , Rodríguez Miguel Ángel , Varela Sara 
Published: March 2023

AbstractBioregionalization methods allow us to classify and map biogeographic units using data on species composition and traits. Here, we reviewed the evolution of the field during the last 70 years, seeking to summarize its history, and identify gaps and future avenues for research. Our results show that the aim of the studies using bioregionalization methods changed in time. First, bioregionalization were used to unveil the drivers of the observed spatial patterns of biodiversity on Earth, and to understand the role of dispersal limitations on the evolutionary history of clades, but recently, these methods are mostly used for conservation management. Further, data used to map biodiversity regions, the ones that we are now defining conservation strategies, are taxonomically and geographically biased, with a large percentage of the papers using vertebrate data from developed continents/countries. Finally, we show how key papers in the field, the ones with most citations, heavily depend on expert criteria and non-reproducible workflows, preventing direct comparison of maps of bioregions from different papers. Following our findings, we identified 3 gaps for the advance in the field, 1) We need to move beyond maps of vertebrate composition. Ideally, we need to increase the taxonomic diversity of the studies, but also to add other type of information, like data on species traits, genetic diversity, or phylogenetic distances. 2) we need reproducible and standardized methods 3) we need to further explore the temporal dimension of bioregions, to understand how they evolved through time.