bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokine receptor cluster size impacts its endocytosis and signaling
Authors: Salavessa Laura , Lagache Thibault , Malardé Valérie , Grassart Alexandre , Olivo-Marin Jean-Christophe , Canette Alexis , Trichet Michael , Sansonetti Philippe J. , Sauvonnet Nathalie 
Published: September 2021

Significance
The IL-2R is a key receptor of the immune system, promoting both immunity and tolerance through activation of signaling cascades on lymphocytes. This receptor induces responses that include T cell expansion, development and suppression of autoreactive lymphocytes, being critical in the prevention of autoimmune diseases. These functions are regulated by the internalization and intracellular trafficking of IL-2R, which undergoes a coat-independent mechanism of endocytosis. Our work shows that clustering of IL-2R at the cell surface is fundamental in the efficient internalization of the receptor and that an optimal cluster size is required for this. Disorganization of IL-2R clustering, through perturbation of the actin cytoskeleton or membrane cholesterol, affects endocytosis and modifies IL-2–induced signaling.
Quantum teleportation of physical qubits into logical code spaces
Authors: Luo Yi-Han , Chen Ming-Cheng , Erhard Manuel , Zhong Han-Sen , Wu Dian , Tang Hao-Yang , Zhao Qi , Wang Xi-Lin , Fujii Keisuke , Li Li , Liu Nai-Le , Nemoto Kae , Munro William J. , Lu Chao-Yang , Zeilinger Anton , Pan Jian-Wei 
Published: September 2021

Significance
Quantum teleportation and quantum error correction play crucial roles in fault-tolerant quantum computing. Here, we implemented error-correctable quantum teleportation to manipulate a logical qubit and observed the protection of quantum information. Our work presents a useful technology for scalable quantum computing and can serve as a quantum simulator for holographic quantum gravity.
Scaffolding mechanism of arrestin-2 in the cRaf/MEK1/ERK signaling cascade
Authors: Qu Changxiu , Park Ji Young , Yun Min Woo , He Qing-tao , Yang Fan , Kim Kiae , Ham Donghee , Li Rui-rui , Iverson T. M. , Gurevich Vsevolod V. , Sun Jin-Peng , Chung Ka Young 
Published: September 2021

Significance
In addition to desensitizing and internalizing G protein–coupled receptors, arrestins mediate ERK1/2 activation by scaffolding three kinases: ERK1/2, MEK1, and Raf. The structural mechanism by which arrestins scaffold the ERK1/2 signaling cascade remains undetermined. Here, we investigated the mechanism of arrestin-2 scaffolding of the cRaf-MEK1-ERK2 signaling module. We identified the binding interfaces of arrestin-2 and these three kinases. We found that the binding of ERK2 and MEK1 was affected by the activation status of arrestin-2, and its interactions with MEK1 and ERK2 were affected by ATP. These results provide insights into the general scaffolding mechanism of the ERK1/2 cascade.
Near-germline human monoclonal antibodies neutralize and protect against multiple arthritogenic alphaviruses
Authors: Malonis Ryan J. , Earnest James T. , Kim Arthur S. , Angeliadis Matthew , Holtsberg Frederick W. , Aman M. Javad , Jangra Rohit K. , Chandran Kartik , Daily Johanna P. , Diamond Michael S. , Kielian Margaret , Lai Jonathan R. 
Published: September 2021

Significance
Arthritogenic alphaviruses, such as Chikungunya virus (CHIKV) and Mayaro virus (MAYV), cause febrile illness, rash, and a debilitating chronic polyarthritis in humans. Currently, there are no approved vaccines or antiviral therapies for the prevention or treatment of alphavirus infection. Here, we identified and characterized 33 monoclonal antibodies (mAbs) from a CHIKV-convalescent donor that cross-react with other arthritogenic alphaviruses. We demonstrate that five broadly neutralizing mAbs can inhibit multiple arthritogenic alphaviruses and map their epitopes through binding and viral escape mutant analysis. Finally, we show that two mAbs, DC2.M16 and DC2.M357, protect against alphavirus disease in mice. These studies inform our understanding of how the human immune system combats alphavirus infection and may guide the development of antiviral treatments and vaccines.
CREBA and CREBB in two identified neurons gate long-term memory formation in
Drosophila
Authors: Lin Hsuan-Wen , Chen Chun-Chao , de Belle J. Steven , Tully Tim , Chiang Ann-Shyn 
Published: September 2021

Significance
Most animals record only labile memories of single events, whereas the formation of persistent long-term memories (LTMs) usually requires recurrent experiences. Our study distinguishes these different memory types through a deconvolution of molecular/biochemical processes within specific neurons of an identified memory circuit. A training-responsive gene activator, CREBA, engages paired DAL neurons in this circuit by promoting protein synthesis–dependent LTMs, which can otherwise be antagonized by CREBB repressor proteins. Increased CREBA expression or elevated membrane excitability enhances LTMs even after only one training cycle. These findings exemplify a circuit gating mechanism via cellular changes in specific single neurons to distinguish one-time experiences from multiple sessions of learning for storage as persistent memory.
Differential ligand-selective control of opposing enzymatic activities within a bifunctional c-di-GMP enzyme
Authors: Patterson Dayna C. , Ruiz Myrrh Perez , Yoon Hyerin , Walker Johnnie A. , Armache Jean-Paul , Yennawar Neela H. , Weinert Emily E. 
Published: September 2021

SignificanceBifunctional enzymes are widely distributed throughout bacteria and are involved in modulating bacterial phenotypes; however, regulatory mechanisms that control the activities of the opposing output domains have remained elusive. Studies on DcpG demonstrate that binding of ligands to the sensor globin domain differentially affect GGDEF and EAL domain activities and highlight a role for protein conformational changes in modulating enzymatic activity. Unusual sensor globin domain characteristics, including heme midpoint potentials, are likely important for the unique regulatory properties of DcpG. AsPaenibacillus dendritiformisresponds to changes in the gaseous environment by modulating biofilm formation, DcpG is likely important in modulating physiological responses to changes in O2and NO levels, identifying a role for heme sensor signaling in the bacterium.
Cancer-associated mutations in the p85α N-terminal SH2 domain activate a spectrum of receptor tyrosine kinases
Authors: Li Xinran , Lau Amy Y. T. , Ng Angel S. N. , Aldehaiman Abdullah , Zhou Yuan , Ng Patrick K. S. , Arold Stefan T. , Cheung Lydia W. T. 
Published: September 2021

Significance
Phosphoinositide 3-kinase activation typically occurs following stimulation by upstream receptor tyrosine kinases (RTKs), which alleviate p110α inhibition by p85α. p85α and p110α driver mutations have been reported to activate p110α by disrupting the inhibitory interface between p85α and p110α. This study revealed that driver mutations in the p85α N-terminal SH2 domain can enhance p110α activity by inducing the activation of multiple RTKs. Furthermore, combination treatment with RTK and AKT inhibitors provides synergistic therapeutic efficacy. This previously uncharacterized oncogenic mechanism presents the exploitable vulnerability of a class of p85α mutant tumors.
Localized blood–brain barrier opening in infiltrating gliomas with MRI-guided acoustic emissions–controlled focused ultrasound
Authors: Anastasiadis Pavlos , Gandhi Dheeraj , Guo Yutong , Ahmed Abdul-Kareem , Bentzen Soren M. , Arvanitis Costas , Woodworth Graeme F. 
Published: September 2021

SignificanceThe blood–brain barrier (BBB) is a critical obstacle to delivering most therapeutics into the brain. In this study, we report combined MRI, histological, and real-time acoustic emissions monitoring findings from a Phase 0 clinical trial examining microbubble-enhanced transcranial focused ultrasound for controlled BBB opening in patients with infiltrating gliomas. The data revealed the capability of this technology to provide safe, controlled, and tightly monitored BBB opening through the intact skull. Our findings demonstrate the capability of this technology to tune BBB opening in real-time, creating opportunities for improved treatment of brain tumors.
Rational design of ASCT2 inhibitors using an integrated experimental-computational approach
Authors: Garibsingh Rachel-Ann A. , Ndaru Elias , Garaeva Alisa A. , Shi Yueyue , Zielewicz Laura , Zakrepine Paul , Bonomi Massimiliano , Slotboom Dirk J. , Paulino Cristina , Grewer Christof , Schlessinger Avner 
Published: September 2021

SignificanceThe glutamine transporter ASCT2 is an emerging therapeutic target for various cancer types. Here, we use an integrated computational and experimental approach to develop unique ASCT2 inhibitors targeting a conformational state useful for rational drug design. We apply computational chemistry tools such as molecular docking and molecular dynamics simulations, in combination with structure determination with cryo-electron microscopy and synthetic chemistry, to design multiple ASCT2 inhibitors. Our results reveal a unique mechanism of stereospecific inhibition of ASCT2 and highlight the utility of combining state-of-the-art computational and experimental approaches in characterizing challenging human membrane protein targets.
Complement C5 inhibition protects against hemolytic anemia and acute kidney injury in anthrax peptidoglycan-induced sepsis in baboons
Authors: Keshari Ravi Shankar , Popescu Narcis Ioan , Silasi Robert , Regmi Girija , Lupu Cristina , Simmons Joe H. , Ricardo Alonso , Coggeshall K. Mark , Lupu Florea 
Published: September 2021

Significance
Late-stage anthrax leads to sepsis, characterized by uncontrolled host responses that contribute to organ damage and death. Using a nonhuman primate model, we demonstrate that bacterial wall peptidoglycan is the major trigger of complement activation. Terminal complement activation products promote secondary hemolytic uremic syndrome (HUS), characterized by hemolytic anemia, toxic accumulation of iron in the kidneys, and subsequent acute renal injury. Inhibition of C5 cleavage and subsequent formation of the lytic terminal complex C5b-9 prevented intravascular hemolysis and heme cytotoxicity and protected against peptidoglycan-induced acute kidney failure. Overall, treatment with C5 inhibitor significantly improved the survival of baboons with sepsis, suggesting a potentially important strategy to treat HUS secondary to gram-positive bacterial infections.
Diphthamide promotes TOR signaling by increasing the translation of proteins in the TORC1 pathway
Authors: Zhang Yugang , Lin Zhewang , Zhu Julia , Wang Miao , Lin Hening 
Published: September 2021

Significance
Diphthamide is a posttranslational modification that has been known since the 1970s. It is conserved in all eukaryotic cells, and its biosynthesis requires at least seven proteins. However, its exact biological function has remained unclear. Our results demonstrate that diphthamide promotes target of rapamycin (TOR) signaling by promoting the translation of two proteins in the target of rapamycin complex 1 (TORC1) pathway that contain slippery sequences in their messenger RNA (mRNA). Our finding explained why diphthamide is evolutionarily conserved and why it is crucial in animal development. Our results also suggest that regulating the translation of slippery sequences by diphthamide could be a widely used mechanism to tune translation in eukaryotes, which is different from the recoding hypothesis.
A simple model for control of COVID-19 infections on an urban campus
Authors: Brown Robert A. 
Published: September 2021

Significance
A simple model shows that control of COVID-19 infection driven by asymptomatic transmission on an urban, residential college campus is possible by instituting comprehensive public health protocols founded on surveillance testing and contact tracing. The model gives expressions for the number of infections expected as a function of these protocols and compares well with data from a large residential university for fall 2020.
On the microstructural origin of brain white matter hydraulic permeability
Authors: Vidotto Marco , Bernardini Andrea , Trovatelli Marco , De Momi Elena , Dini Daniele 
Published: September 2021

Significance
Unveiling the mechanisms that drive mass transport in brain tissue is fundamental, not only to plan accurate surgical procedures, but also to shed light on the way solutes move in the extracellular space during the physiological or pathological state. The relation between the white matter (WM) spatial organization and relevant parameters such as permeability is still an unsolved question. Here, we simulate the interstitial flow between the axons of two WM areas reconstructed through three-dimensional electron microscopy imaging. We show that the permeability computed parallel to the axons is significantly higher than the one calculated perpendicularly and that corpus callosum exhibits a higher permeability than fornix, hence demonstrating the importance of the anisotropic and heterogeneous behavior of WM.
Deep-time climate legacies affect origination rates of marine genera
Authors: Mathes Gregor H. , Kiessling Wolfgang , Steinbauer Manuel J. 
Published: September 2021

SignificanceThe effect of climate change on biodiversity is dependent on previous climatic trends. For example, climate warming is more deleterious when added to a long-term warming trend. We tested how the interaction of short- and long-term climate change affects origination rates through time. Using data from the marine fossil record, we show that origination rates in the last 485 million years tend to increase when climate cooling is superimposed on longer-term cooling trends. These findings might clarify the ongoing debate on the relationship between climate and origination and underline the complexity of evolutionary dynamics and the presence of intricate interactions in Earth’s system.
Comparative genomics provides insights into the aquatic adaptations of mammals
Authors: Yuan Yuan , Zhang Yaolei , Zhang Peijun , Liu Chang , Wang Jiahao , Gao Haiyu , Hoelzel A. Rus , Seim Inge , Lv Meiqi , Lin Mingli , Dong Lijun , Gao Haoyang , Yang Zixin , Caruso Francesco , Lin Wenzhi , da Fonseca Rute R. , Wang Ding , Wang Xianyan , Rasmussen Marianne H. , Liu Mingming , Zheng Jinsong , Zhao Liyuan , Campos Paula F. , Kang Hui , Iversen Maria , Song Yue , Guo Xinyu , Guo Jiao , Qin Yating , Pan Shanshan , Xu Qiwu , Meng Lingfeng , A Yunga , Liu Shanshan , Lee Simon Ming-Yuen , Liu Xin , Xu Xun , Yang Huanming , Fan Guangyi , Wang Kun , Li Songhai 
Published: September 2021

SignificanceDivergent lineages can respond to common environmental factors through convergent processes involving shared genomic components or pathways, but the molecular mechanisms are poorly understood. Here, we provide genomic resources and insights into the evolution of mammalian lineages adapting to aquatic life. Our data suggest convergent evolution, for example, in association with thermoregulation through genes associated with a surface heat barrier (NFIA) and internal heat exchange (SEMA3E). Combined with the support of previous reports showing that the UCP1 locus has been lost in many marine mammals independently, our results suggest that the thermostatic strategy of marine mammals shifted from enhancing heat production to limiting heat loss.
Quantitative evaluation of the feasibility of sampling the ice plumes at Enceladus for biomarkers of extraterrestrial life
Authors: New James S. , Kazemi Bahar , Spathis Vassilia , Price Mark C. , Mathies Richard A. , Butterworth Anna L. 
Published: September 2021

Significance
The search for organic biosignatures indicative of life elsewhere in our solar system is an exciting quest that, if successful, will have a profound impact on our biological uniqueness. Saturn’s icy moon Enceladus is a promising location for a second occurrence of life due to its salty subsurface ocean. Plumes that jet out through the ice surface vents provide an enticing opportunity to sample the underlying ocean for biomarkers. The experiments reported here provide accurate modeling of our ability to fly through these plumes to efficiently and nondestructively gather ice particles for biomolecular analysis. Our measured efficiencies demonstrate that Saturn and/or Enceladus orbital missions will gather sufficient ice to make meaningful measurement of biosignatures in the Enceladus plumes.
Climate variability and density-dependent population dynamics: Lessons from a simple High Arctic ecosystem
Authors: Fauteux Dominique , Stien Audun , Yoccoz Nigel G. , Fuglei Eva , Ims Rolf A. 
Published: September 2021

SignificanceWhether the renowned population cycles of small mammals in northern food webs are driven by bottom-up (plant–herbivore) or top-down (predator–prey) interactions is still a debated question but crucial to our understanding of their ecological functions and response to climate change. A long-term study of a graminivorous vole population in an exceptionally simple High Arctic food web allowed us to identify which population dynamics features are present without top-down regulation. Unique features were high-amplitude, noncyclic population fluctuations driven by a combination of stochastic weather events and season-specific density dependence likely arising from plant–herbivore interactions. That such features are not present in more complex food webs points to the importance of top-down regulation in small mammal populations.
The vitellogenin receptor functionality of the migratory locust depends on its phosphorylation by juvenile hormone
Authors: Jing Yu-Pu , Wen Xinpeng , Li Lunjie , Zhang Shanjing , Zhang Ci , Zhou Shutang 
Published: September 2021

Significance
During vitellogenesis of oviparous animals, vitellogenin receptor (VgR)–mediated endocytosis is crucial for the incorporation of yolk proteins into oocytes. VgR also serves as a gatekeeper for vertical transmission of pathogenic microbes and symbionts. Juvenile hormone (JH) acts as a gonadotrophic hormone and stimulates this process in many insect species, but the regulatory mechanisms remain elusive. We find that JH activates the GPCR-PLC-PKC-ι cascade and phosphorylates VgR in an EGF-precursor homology domain. Endosomal acidification leads to VgR dephosphorylation. Phosphorylation is essential for VgR to translocate from oocyte cytoplasm to the membrane to bind with vitellogenin on the membrane and to internalize vitellogenin in oocytes. Moreover, JH-promoted VgR phosphorylation for intracellular recycling and vitellogenin deposition is evolutionarily conserved across divergent insect orders.
Individualistic culture increases economic mobility in the United States
Authors: Leonard Bryan , Smith Steven M. 
Published: September 2021

Significance
While previous cross-national comparisons have shown that individualistic societies are associated with more innovation, growth, and income mobility than collectivist societies, our analysis, operating at a finer spatial resolution, demonstrates the relationship also holds within a country and provides new insights into the mechanisms. Our finding—that children who grow up in US counties with a stronger historically determined culture of individualism have greater upward mobility—identifies a significant component of the persistent “causal effect of place” that is not explained by other political and economic variables. With suggestive evidence that informal channels explain more of the result, this study also highlights the need for ongoing work to measure culture and its transmission.
Two-step deswelling in the Volume Phase Transition of thermoresponsive microgels
Authors: Del Monte Giovanni , Truzzolillo Domenico , Camerin Fabrizio , Ninarello Andrea , Chauveau Edouard , Tavagnacco Letizia , Gnan Nicoletta , Rovigatti Lorenzo , Sennato Simona , Zaccarelli Emanuela 
Published: September 2021

Significance
Microgels, colloidal-scale polymer networks, are the prototype soft colloids. When the constituent polymers are thermoresponsive, they undergo a volume phase transition (VPT) from a swollen to a collapsed state at a characteristic temperature, close to ambient one, of great appeal for several applications. To describe this phenomenon, microgels are usually treated as neutral, but here we show that electrostatics needs to be taken into account. In particular, deswelling occurs via a two-step, rather than a homogeneous, particle collapse, mainly driven by peripheral charges located on the microgel corona, for which we also establish a unifying framework encompassing all studied microgels. Our work thus provides a change of perspective to describe these fascinating systems.
Conceptual-based design of an ultrabroadband microwave metamaterial absorber
Authors: Qu Sichao , Hou Yuxiao , Sheng Ping 
Published: September 2021

Significance
While microwave absorption is a widely pursued topic, a conceptual-based design can offer a theoretical basis for generalization and improvements. We offer a design recipe for ultrabroadband absorption based on the use of electrical dipole resonance in a metallic ring to generate, via interaction with its image resonance, two high-impedance resonances. Impedance matching over the frequency range in between the two resonances is obtained by adding resistance to the metallic ring. To extend the absorption to an ultrabroadband spectrum, we employ a double-layer self-similar structure in conjunction with absorption of the diffracted waves at the higher frequency end. The resulting absorber pushes the overall performance close to the causality limit over a large absorption bandwidth.
Engineering hydrogels with homogeneous mechanical properties for controlling stem cell lineage specification
Authors: Xue Bin , Tang Dehua , Wu Xin , Xu Zhengyu , Gu Jie , Han Yueying , Zhu Zhenshu , Qin Meng , Zou Xiaoping , Wang Wei , Cao Yi 
Published: September 2021

Significance
Hydrogels are extensively used for cell culture, tissue engineering, and flexible electronics. In all of these applications, mechanical properties of hydrogels play an important role. Although tremendous studies have been devoted to optimizing the stiffness, strain, toughness, and dynamic mechanical response, the mechanical homogeneity of hydrogels has rarely been considered. By developing a general strategy to control the mechanical homogeneity of hydrogels, here we show that nanoscale variation in matrix stiffness can considerably affect the lineage specification of human embryonic stem cells. Inhomogeneous hydrogels suppress mechanotransduction and facilitate stemness maintenance, while homogenous hydrogels promote mechanotransduction and osteogenic differentiation. Therefore, engineering hydrogels with controllable and well-defined nanoscale homogeneity may have considerable implications in stem cell culture and regenerative medicine.
Interspecies activation correlations reveal functional correspondences between marmoset and human brain areas
Authors: Hori Yuki , Cléry Justine C. , Selvanayagam Janahan , Schaeffer David J. , Johnston Kevin D. , Menon Ravi S. , Everling Stefan 
Published: September 2021

Significance
The common marmoset has enormous promise as a nonhuman primate model. While resting-state functional MRI (fMRI) has provided evidence for a similar organization of marmoset and human cortices, the technique cannot be used to map the functional correspondences of brain regions between species. Here, we used movie-driven fMRI in marmosets and humans to identify whole-brain functional correspondences between the two primate species. In particular, we describe functional correlates for the well-known human face, body, and scene patches in marmosets. We find that these networks have a similar organization in both species, suggesting a largely conserved organization of higher-order visual areas between marmoset monkeys and humans.