bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stress granules, RNA-binding proteins and polyglutamine diseases: too much aggregation?
Authors: Marcelo Adriana , Koppenol Rebekah , de Almeida Luís Pereira , Matos Carlos A. , Nóbrega Clévio 
Published: June 2021

AbstractStress granules (SGs) are membraneless cell compartments formed in response to different stress stimuli, wherein translation factors, mRNAs, RNA-binding proteins (RBPs) and other proteins coalesce together. SGs assembly is crucial for cell survival, since SGs are implicated in the regulation of translation, mRNA storage and stabilization and cell signalling, during stress. One defining feature of SGs is their dynamism, as they are quickly assembled upon stress and then rapidly dispersed after the stress source is no longer present. Recently, SGs dynamics, their components and their functions have begun to be studied in the context of human diseases. Interestingly, the regulated protein self-assembly that mediates SG formation contrasts with the pathological protein aggregation that is a feature of several neurodegenerative diseases. In particular, aberrant protein coalescence is a key feature of polyglutamine (PolyQ) diseases, a group of nine disorders that are caused by an abnormal expansion of PolyQ tract-bearing proteins, which increases the propensity of those proteins to aggregate. Available data concerning the abnormal properties of the mutant PolyQ disease-causing proteins and their involvement in stress response dysregulation strongly suggests an important role for SGs in the pathogenesis of PolyQ disorders. This review aims at discussing the evidence supporting the existence of a link between SGs functionality and PolyQ disorders, by focusing on the biology of SGs and on the way it can be altered in a PolyQ disease context.
Pump-probe X-ray holographic imaging of laser-induced cavitation bubbles with femtosecond FEL pulses
Authors: Vassholz M. , Hoeppe H. P. , Hagemann J. , Rosselló J. M. , Osterhoff M. , Mettin R. , Kurz T. , Schropp A. , Seiboth F. , Schroer C. G. , Scholz M. , Möller J. , Hallmann J. , Boesenberg U. , Kim C. , Zozulya A. , Lu W. , Shayduk R. , Schaffer R. , Madsen A. , Salditt T. 
Published: June 2021

AbstractCavitation bubbles can be seeded from a plasma following optical breakdown, by focusing an intense laser in water. The fast dynamics are associated with extreme states of gas and liquid, especially in the nascent state. This offers a unique setting to probe water and water vapor far-from equilibrium. However, current optical techniques cannot quantify these early states due to contrast and resolution limitations. X-ray holography with single X-ray free-electron laser pulses has now enabled a quasi-instantaneous high resolution structural probe with contrast proportional to the electron density of the object. In this work, we demonstrate cone-beam holographic flash imaging of laser-induced cavitation bubbles in water with nanofocused X-ray free-electron laser pulses. We quantify the spatial and temporal pressure distribution of the shockwave surrounding the expanding cavitation bubble at time delays shortly after seeding and compare the results to numerical simulations.
Unique and universal dew-repellency of nanocones
Authors: Lecointre Pierre , Laney Sophia , Michalska Martyna , Li Tao , Tanguy Alexandre , Papakonstantinou Ioannis , Quéré David 
Published: June 2021

AbstractSurface structuring provides a broad range of water-repellent materials known for their ability to reflect millimetre-sized raindrops. Dispelling water at the considerably reduced scale of fog or dew, however, constitutes a significant challenge, owing to the comparable size of droplets and structures. Nonetheless, a surface comprising nanocones was recently reported to exhibit strong anti-fogging behaviour, unlike pillars of the same size. To elucidate the origin of these differences, we systematically compare families of nanotexture that transition from pillars to sharp cones. Through environmental electron microscopy and modelling, we show that microdroplets condensing on sharp cones adopt a highly non-adhesive state, even at radii as low as 1.5 µm, contrasting with the behaviour on pillars where pinning results in impedance of droplet ejection. We establish the antifogging abilities to be universal over the range of our cone geometries, which speaks to the unique character of the nanocone geometry to repel dew. Truncated cones are finally shown to provide both pinning and a high degree of hydrophobicity, opposing characteristics that lead to a different, yet efficient, mechanism of dew ejection that relies on multiple coalescences.
A DNA packaging motor inchworms along one strand allowing it to adapt to alternative double-helical structures
Authors: Castillo Juan P. , B. Tong Alexander , Tafoya Sara , Jardine Paul J. , Bustamante Carlos 
Published: June 2021

AbstractRing ATPases that translocate disordered polymers possess lock-washer architectures that they impose on their substrates during transport via a hand-over-hand mechanism. Here, we investigate the operation of ring motors that transport ordered, helical substrates, such as the bacteriophage ϕ29 dsDNA packaging motor. This pentameric motor alternates between an ATP loading dwell and a hydrolysis burst wherein it packages one turn of DNA in four steps. When challenged with DNA-RNA hybrids and dsRNA, the motor matches its burst to the shorter helical pitches, keeping three power strokes invariant while shortening the fourth. Intermittently, the motor loses grip on the RNA-containing substrates, indicating that it makes optimal load-bearing contacts with dsDNA. To rationalize these observations, we propose a helical inchworm translocation mechanism in which, during each cycle, the motor increasingly adopts a lock-washer structure during the ATP loading dwell and successively regains its planar form with each power stroke during the burst.
Bladder cancer therapy using a conformationally fluid tumoricidal peptide complex
Authors: Brisuda Antonín , Ho James C. S. , Kandiyal Pancham S. , Ng Justin T-Y. , Ambite Ines , Butler Daniel S. C. , Háček Jaromir , Wan Murphy Lam Yim , Tran Thi Hien , Nadeem Aftab , Tran Tuan Hiep , Hastings Anna , Storm Petter , Fortunati Daniel L. , Esmaeili Parisa , Novotna Hana , Horňák Jakub , Mu Y. G. , Mok K. H. , Babjuk Marek , Svanborg Catharina 
Published: June 2021

AbstractPartially unfolded alpha-lactalbumin forms the oleic acid complex HAMLET, with potent tumoricidal activity. Here we define a peptide-based molecular approach for targeting and killing tumor cells, and evidence of its clinical potential (ClinicalTrials.gov NCT03560479). A 39-residue alpha-helical peptide from alpha-lactalbumin is shown to gain lethality for tumor cells by forming oleic acid complexes (alpha1-oleate). Nuclear magnetic resonance measurements and computational simulations reveal a lipid core surrounded by conformationally fluid, alpha-helical peptide motifs. In a single center, placebo controlled, double blinded Phase I/II interventional clinical trial of non-muscle invasive bladder cancer, all primary end points of safety and efficacy of alpha1-oleate treatment are reached, as evaluated in an interim analysis. Intra-vesical instillations of alpha1-oleate triggers massive shedding of tumor cells and the tumor size is reduced but no drug-related side effects are detected (primary endpoints). Shed cells contain alpha1-oleate, treated tumors show evidence of apoptosis and the expression of cancer-related genes is inhibited (secondary endpoints). The results are especially encouraging for bladder cancer, where therapeutic failures and high recurrence rates create a great, unmet medical need.
Curvature in the reproductive tract alters sperm–surface interactions
Authors: Raveshi Mohammad Reza , Abdul Halim Melati S. , Agnihotri Sagar N. , O’Bryan Moira K. , Neild Adrian , Nosrati Reza 
Published: June 2021

AbstractThe fallopian tube is lined with a highly complex folded epithelium surrounding a lumen that progressively narrows. To study the influence of this labyrinthine complexity on sperm behavior, we use droplet microfluidics to create soft curved interfaces over a range of curvatures corresponding to the in vivo environment. We reveal a dynamic response mechanism in sperm, switching from a progressive surface-aligned motility mode at low curvatures (larger droplets), to an aggressive surface-attacking mode at high curvatures (smaller droplets of <50 µm-radius). We show that sperm in the attacking mode swim ~33% slower, spend 1.66-fold longer at the interface and have a 66% lower beating amplitude than in the progressive mode. These findings demonstrate that surface curvature within the fallopian tube alters sperm motion from a faster surface aligned locomotion in distal regions to a prolonged physical contact with the epithelium near the site of fertilization, the latter being known to promote capacitation and fertilization competence.
HIRA stabilizes skeletal muscle lineage identity
Authors: Esteves de Lima Joana , Bou Akar Reem , Machado Léo , Li Yuefeng , Drayton-Libotte Bernadette , Dilworth F. Jeffrey , Relaix Frédéric 
Published: June 2021

AbstractThe epigenetic mechanisms coordinating the maintenance of adult cellular lineages and the inhibition of alternative cell fates remain poorly understood. Here we show that targeted ablation of the histone chaperone HIRA in myogenic cells leads to extensive transcriptional modifications, consistent with a role in maintaining skeletal muscle cellular identity. We demonstrate that conditional ablation of HIRA in muscle stem cells of adult mice compromises their capacity to regenerate and self-renew, leading to tissue repair failure. Chromatin analysis of Hira-deficient cells show a significant reduction of histone variant H3.3 deposition and H3K27ac modification at regulatory regions of muscle genes. Additionally, we find that genes from alternative lineages are ectopically expressed in Hira-mutant cells via MLL1/MLL2-mediated increase of H3K4me3 mark at silent promoter regions. Therefore, we conclude that HIRA sustains the chromatin landscape governing muscle cell lineage identity via incorporation of H3.3 at muscle gene regulatory regions, while preventing the expression of alternative lineage genes.
Synergistic immunotherapy of glioblastoma by dual targeting of IL-6 and CD40
Authors: Yang Fan , He Zhenqiang , Duan Hao , Zhang Duo , Li Juehui , Yang Huijuan , Dorsey Jay F. , Zou Wei , Nabavizadeh S. Ali , Bagley Stephen J. , Abdullah Kalil , Brem Steven , Zhang Lin , Xu Xiaowei , Byrne Katelyn T. , Vonderheide Robert H. , Gong Yanqing , Fan Yi 
Published: June 2021

AbstractImmunologically-cold tumors including glioblastoma (GBM) are refractory to checkpoint blockade therapy, largely due to extensive infiltration of immunosuppressive macrophages (Mϕs). Consistent with a pro-tumor role of IL-6 in alternative Mϕs polarization, we here show that targeting IL-6 by genetic ablation or pharmacological inhibition moderately improves T-cell infiltration into GBM and enhances mouse survival; however, IL-6 inhibition does not synergize PD-1 and CTLA-4 checkpoint blockade. Interestingly, anti-IL-6 therapy reduces CD40 expression in GBM-associated Mϕs. We identify a Stat3/HIF-1α-mediated axis, through which IL-6 executes an anti-tumor role to induce CD40 expression in Mϕs. Combination of IL-6 inhibition with CD40 stimulation reverses Mϕ-mediated tumor immunosuppression, sensitizes tumors to checkpoint blockade, and extends animal survival in two syngeneic GBM models, particularly inducing complete regression of GL261 tumors after checkpoint blockade. Thus, antibody cocktail-based immunotherapy that combines checkpoint blockade with dual-targeting of IL-6 and CD40 may offer exciting opportunities for GBM and other solid tumors.
PRMT5-mediated arginine methylation activates AKT kinase to govern tumorigenesis
Authors: Yin Shasha , Liu Liu , Brobbey Charles , Palanisamy Viswanathan , Ball Lauren E. , Olsen Shaun K. , Ostrowski Michael C. , Gan Wenjian 
Published: June 2021

AbstractAKT is involved in a number of key cellular processes including cell proliferation, apoptosis and metabolism. Hyperactivation of AKT is associated with many pathological conditions, particularly cancers. Emerging evidence indicates that arginine methylation is involved in modulating AKT signaling pathway. However, whether and how arginine methylation directly regulates AKT kinase activity remain unknown. Here we report that protein arginine methyltransferase 5 (PRMT5), but not other PRMTs, promotes AKT activation by catalyzing symmetric dimethylation of AKT1 at arginine 391 (R391). Mechanistically, AKT1-R391 methylation cooperates with phosphatidylinositol 3,4,5 trisphosphate (PIP3) to relieve the pleckstrin homology (PH)-in conformation, leading to AKT1 membrane translocation and subsequent activation by phosphoinositide-dependent kinase-1 (PDK1) and the mechanistic target of rapamycin complex 2 (mTORC2). As a result, deficiency in AKT1-R391 methylation significantly suppresses AKT1 kinase activity and tumorigenesis. Lastly, we show that PRMT5 inhibitor synergizes with AKT inhibitor or chemotherapeutic drugs to enhance cell death. Altogether, our study suggests that R391 methylation is an important step for AKT activation and its oncogenic function.
Dynamics of replication origin over-activation
Authors: Fu Haiqing , Redon Christophe E. , Thakur Bhushan L. , Utani Koichi , Sebastian Robin , Jang Sang-Min , Gross Jacob M. , Mosavarpour Sara , Marks Anna B. , Zhuang Sophie Z. , Lazar Sarah B. , Rao Mishal , Mencer Shira T. , Baris Adrian M. , Pongor Lorinc S. , Aladjem Mirit I. 
Published: June 2021

AbstractSafeguards against excess DNA replication are often dysregulated in cancer, and driving cancer cells towards over-replication is a promising therapeutic strategy. We determined DNA synthesis patterns in cancer cells undergoing partial genome re-replication due to perturbed regulatory interactions (re-replicating cells). These cells exhibited slow replication, increased frequency of replication initiation events, and a skewed initiation pattern that preferentially reactivated early-replicating origins. Unlike in cells exposed to replication stress, which activated a novel group of hitherto unutilized (dormant) replication origins, the preferred re-replicating origins arose from the same pool of potential origins as those activated during normal growth. Mechanistically, the skewed initiation pattern reflected a disproportionate distribution of pre-replication complexes on distinct regions of licensed chromatin prior to replication. This distinct pattern suggests that circumventing the strong inhibitory interactions that normally prevent excess DNA synthesis can occur via at least two pathways, each activating a distinct set of replication origins.
An infrastructure with user-centered presentation data model for integrated management of materials data and services
Authors: Liu Shilong , Su Yanjing , Yin Haiqing , Zhang Dawei , He Jie , Huang Haiyou , Jiang Xue , Wang Xuan , Gong Haiyan , Li Zhuang , Xiu Hao , Wan Jiawang , Zhang Xiaotong 
Published: June 2021

AbstractWith scientific research in materials science becoming more data intensive and collaborative after the announcement of the Materials Genome Initiative, the need for modern data infrastructures that facilitate the sharing of materials data and analysis tools is compelling in the materials community. In this paper, we describe the challenges of developing such infrastructure and introduce an emerging architecture with high usability. We call this architecture the Materials Genome Engineering Databases (MGED). MGED provides cloud-hosted services with features to simplify the process of collecting datasets from diverse data providers, unify data representation forms with user-centered presentation data model, and accelerate data discovery with advanced search capabilities. MGED also provides a standard service management framework to enable finding and sharing of tools for analyzing and processing data. We describe MGED’s design, current status, and how MGED supports integrated management of shared data and services.
Spontaneous preterm birth: the underpinnings in the maternal and fetal genomes
Authors: Bhattacharjee Esha , Maitra Arindam 
Published: June 2021

AbstractPreterm birth (PTB) is a major cause of neonatal mortality and health complications in infants. Elucidation of its genetic underpinnings can lead to improved understanding of the biological mechanisms and boost the development of methods to predict PTB. Although recent genome-based studies of both mother and fetus have identified several genetic loci which might be implicated in PTB, these results suffer from a lack of consistency across multiple studies and populations. Moreover, results of functional validation of most of these findings are unavailable. Since medically indicated preterm deliveries have well-known heterogeneous causes, we have reviewed only those studies which investigated spontaneous preterm birth (sPTB) and have attempted to suggest probable biological mechanisms by which the implicated genetic factors might result in sPTB. We expect our review to provide a panoramic view of the genetics of sPTB.
Transcriptomic analysis of cork during seasonal growth highlights regulatory and developmental processes from phellogen to phellem formation
Authors: Fernández-Piñán Sandra , Boher Pau , Soler Marçal , Figueras Mercè , Serra Olga 
Published: June 2021

AbstractThe phellogen or cork cambium stem cells that divide periclinally and outwardly specify phellem or cork. Despite the vital importance of phellem in protecting the radially-growing plant organs and wounded tissues, practically only the suberin biosynthetic process has been studied molecularly so far. Since cork oak (Quercus suber) phellogen is seasonally activated and its proliferation and specification to phellem cells is a continuous developmental process, the differentially expressed genes during the cork seasonal growth served us to identify molecular processes embracing from phellogen to mature differentiated phellem cell. At the beginning of cork growth (April), cell cycle regulation, meristem proliferation and maintenance and processes triggering cell differentiation were upregulated, showing an enrichment of phellogenic cells from which phellem cells are specified. Instead, at maximum (June) and advanced (July) cork growth, metabolic processes paralleling the phellem cell chemical composition, such as the biosynthesis of suberin, lignin, triterpenes and soluble aromatic compounds, were upregulated. Particularly in July, polysaccharides- and lignin-related secondary cell wall processes presented a maximal expression, indicating a cell wall reinforcement in the later stages of cork formation, presumably related with the initiation of latecork development. The putative function of relevant genes identified are discussed in the context of phellem ontogeny.
Defensive freezing and its relation to approach–avoidance decision-making under threat
Authors: Klaassen Felix H. , Held Leslie , Figner Bernd , O’Reilly Jill X. , Klumpers Floris , de Voogd Lycia D. , Roelofs Karin 
Published: June 2021

AbstractSuccessful responding to acutely threatening situations requires adequate approach–avoidance decisions. However, it is unclear how threat-induced states—like freezing-related bradycardia—impact the weighing of the potential outcomes of such value-based decisions. Insight into the underlying computations is essential, not only to improve our models of decision-making but also to improve interventions for maladaptive decisions, for instance in anxiety patients and first-responders who frequently have to make decisions under acute threat. Forty-two participants made passive and active approach–avoidance decisions under threat-of-shock when confronted with mixed outcome-prospects (i.e., varying money and shock amounts). Choice behavior was best predicted by a model including individual action-tendencies and bradycardia, beyond the subjective value of the outcome. Moreover, threat-related bradycardia (high-vs-low threat) interacted with subjective value, depending on the action-context (passive-vs-active). Specifically, in action-contexts incongruent with participants’ intrinsic action-tendencies, stronger bradycardia related to diminished effects of subjective value on choice across participants. These findings illustrate the relevance of testing approach–avoidance decisions in relatively ecologically valid conditions of acute and primarily reinforced threat. These mechanistic insights into approach–avoidance conflict-resolution may inspire biofeedback-related techniques to optimize decision-making under threat. Critically, the findings demonstrate the relevance of incorporatinginternalpsychophysiological states andexternalaction-contexts into models of approach–avoidance decision-making.
Cooperation patterns of members in networks during co-creation
Authors: Yang Kunhao , Fujisaki Itsuki , Ueda Kazuhiro 
Published: June 2021

AbstractCooperation (i.e., co-creation) has become the principal way of carrying out creative activities in modern society. In co-creation, different participants can play two completely different roles based on two different behaviours: some participants are the originators who generate initial contents, while others are the revisors who provide revisions or coordination. In this study, we investigated different participants’ roles (i.e., the originator vs. the revisor) in co-creation and how these roles affected the final cooperation-group outcome. By using cooperation networks to represent cooperative relationships among participants, we found that peripheral members (i.e., those in the periphery of the cooperation networks) and core members (i.e., those in the centre of the cooperation networks) played the roles of originators and revisors, respectively, mainly affecting the quantity versus the quality of their creative outcomes. These results were robust across the three different datasets and the three different indicators defining core and peripheral members. Previous studies have considered cooperation behaviours to be homogeneous, ignoring that different participants may play different roles in co-creation. This study discusses patterns of cooperation among participants based on a model in which different roles in co-creation are considered. Thus, this research advances the understanding of how co-creation occurs in networks.
Biomechanical forces enhance directed migration and activation of bone marrow-derived dendritic cells
Authors: Kang Ji-Hun , Lee Hyun Joo , Kim Ok-Hyeon , Yun Yong Ju , Seo Young-Jin , Lee Hyun Jung 
Published: June 2021

AbstractMechanical forces are pervasive in the inflammatory site where dendritic cells (DCs) are activated to migrate into draining lymph nodes. For example, fluid shear stress modulates the movement patterns of DCs, including directness and forward migration indices (FMIs), without chemokine effects. However, little is known about the effects of biomechanical forces on the activation of DCs. Accordingly, here we fabricated a microfluidics system to assess how biomechanical forces affect the migration and activity of DCs during inflammation. Based on the structure of edema, we proposed and experimentally analyzed a novel concept for a microchip model that mimicked such vascular architecture. The intensity of shear stress generated in our engineered chip was found as 0.2–0.6 dyne/cm2by computational simulation; this value corresponded to inflammation in tissues. In this platform, the directness and FMIs of DCs were significantly increased, whereas the migration velocity of DCs was not altered by shear stress, indicating that mechanical stimuli influenced DC migration. Moreover, DCs with shear stress showed increased expression of the DC activation markers MHC class I and CD86 compared with DCs under static conditions. Taken together, these data suggest that the biomechanical forces are important to regulate the migration and activity of DCs.