bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective posttranslational inhibition of CaVβ1-associated voltage-dependent calcium channels with a functionalized nanobody
Authors: Morgenstern Travis J. , Nirwan Neha , Hernández-Ochoa Erick O. , Bibollet Hugo , Choudhury Papiya , Laloudakis Yianni D. , Ben Johny Manu , Bannister Roger A. , Schneider Martin F. , Minor Daniel L. , Colecraft Henry M. 
Published: December 2022

AbstractCa2+ influx through high-voltage-activated calcium channels (HVACCs) controls diverse cellular functions. A critical feature enabling a singular signal, Ca2+ influx, to mediate disparate functions is diversity of HVACC pore-forming α1 and auxiliary CaVβ1–CaVβ4 subunits. Selective CaVα1 blockers have enabled deciphering their unique physiological roles. By contrast, the capacity to post-translationally inhibit HVACCs based on CaVβ isoform is non-existent. Conventional gene knockout/shRNA approaches do not adequately address this deficit owing to subunit reshuffling and partially overlapping functions of CaVβ isoforms. Here, we identify a nanobody (nb.E8) that selectively binds CaVβ1 SH3 domain and inhibits CaVβ1-associated HVACCs by reducing channel surface density, decreasing open probability, and speeding inactivation. Functionalizing nb.E8 with Nedd4L HECT domain yielded Chisel-1 which eliminated current through CaVβ1-reconstituted CaV1/CaV2 and native CaV1.1 channels in skeletal muscle, strongly suppressed depolarization-evoked Ca2+ influx and excitation-transcription coupling in hippocampal neurons, but was inert against CaVβ2-associated CaV1.2 in cardiomyocytes. The results introduce an original method for probing distinctive functions of ion channel auxiliary subunit isoforms, reveal additional dimensions of CaVβ1 signaling in neurons, and describe a genetically-encoded HVACC inhibitor with unique properties.
The transcription factor DDIT3 is a potential driver of dyserythropoiesis in myelodysplastic syndromes
Authors: Berastegui Nerea , Ainciburu Marina , Romero Juan P. , Garcia-Olloqui Paula , Alfonso-Pierola Ana , Philippe Céline , Vilas-Zornoza Amaia , San Martin-Uriz Patxi , Ruiz-Hernández Raquel , Abarrategi Ander , Ordoñez Raquel , Alignani Diego , Sarvide Sarai , Castro-Labrador Laura , Lamo-Espinosa José M. , San-Julian Mikel , Jimenez Tamara , López-Cadenas Félix , Muntion Sandra , Sanchez-Guijo Fermin , Molero Antonieta , Montoro Maria Julia , Tazón Bárbara , Serrano Guillermo , Diaz-Mazkiaran Aintzane , Hernaez Mikel , Huerga Sofía , Bewicke-Copley Findlay , Rio-Machin Ana , Maurano Matthew T. , Díez-Campelo María , Valcarcel David , Rouault-Pierre Kevin , Lara-Astiaso David , Ezponda Teresa , Prosper Felipe 
Published: December 2022

AbstractMyelodysplastic syndromes (MDS) are hematopoietic stem cell (HSC) malignancies characterized by ineffective hematopoiesis, with increased incidence in older individuals. Here we analyze the transcriptome of human HSCs purified from young and older healthy adults, as well as MDS patients, identifying transcriptional alterations following different patterns of expression. While aging-associated lesions seem to predispose HSCs to myeloid transformation, disease-specific alterations may trigger MDS development. Among MDS-specific lesions, we detect the upregulation of the transcription factor DNA Damage Inducible Transcript 3 (DDIT3). Overexpression of DDIT3 in human healthy HSCs induces an MDS-like transcriptional state, and dyserythropoiesis, an effect associated with a failure in the activation of transcriptional programs required for normal erythroid differentiation. Moreover, DDIT3 knockdown in CD34+ cells from MDS patients with anemia is able to restore erythropoiesis. These results identify DDIT3 as a driver of dyserythropoiesis, and a potential therapeutic target to restore the inefficient erythroid differentiation characterizing MDS patients.
Optical-resolution functional gastrointestinal photoacoustic endoscopy based on optical heterodyne detection of ultrasound
Authors: Liang Yizhi , Fu Wubing , Li Qiang , Chen Xiaolong , Sun Huojiao , Wang Lidai , Jin Long , Huang Wei , Guan Bai-Ou 
Published: December 2022

AbstractPhotoacoustic endoscopy shows promise in the detection of gastrointestinal cancer, inflammation, and other lesions. High-resolution endoscopic imaging of the hemodynamic response necessitates a small-sized, high-sensitivity ultrasound sensor. Here, we utilize a laser ultrasound sensor to develop a miniaturized, optical-resolution photoacoustic endoscope. The sensor can boost the acoustic response by a gain factor of ωo/Ω (the frequency ratio of the signal light and measured ultrasound) by measuring the acoustically induced optical phase change. As a result, we achieve a noise-equivalent pressure density (NEPD) below 1.5 mPa·Hz−1/2 over the measured range of 5 to 25 MHz. The heterodyne phase detection using dual-frequency laser beams of the sensor can offer resistance to thermal drift and vibrational perturbations. The endoscope is used to in vivo image a rat rectum and visualize the oxygen saturation changes during acute inflammation, which can hardly be observed with other imaging modalities.
A changing thermal regime revealed from shallow to deep basalt source melting in the Moon
Authors: Srivastava Yash , Basu Sarbadhikari Amit , Day James M. D. , Yamaguchi Akira , Takenouchi Atsushi 
Published: December 2022

AbstractSample return missions have provided the basis for understanding the thermochemical evolution of the Moon. Mare basalt sources are likely to have originated from partial melting of lunar magma ocean cumulates after solidification from an initially molten state. Some of the Apollo mare basalts show evidence for the presence in their source of a late-stage radiogenic heat-producing incompatible element-rich layer, known for its enrichment in potassium, rare-earth elements, and phosphorus (KREEP). Here we show the most depleted lunar meteorite, Asuka-881757, and associated mare basalts, represent ancient (~3.9 Ga) partial melts of KREEP-free Fe-rich mantle. Petrological modeling demonstrates that these basalts were generated at lower temperatures and shallower depths than typical Apollo mare basalts. Calculated mantle potential temperatures of these rocks suggest a relatively cooler mantle source and lower surface heat flow than those associated with later-erupted mare basalts, suggesting a fundamental shift in melting regime in the Moon from ~3.9 to ~3.3 Ga.
Noradrenergic signaling mediates cortical early tagging and storage of remote memory
Authors: Fan Xiaocen , Song Jiachen , Ma Chaonan , Lv Yanbo , Wang Feifei , Ma Lan , Liu Xing 
Published: December 2022

AbstractThe neocortical prefrontal memory engram generated during initial learning is critical for remote episodic memory storage, however, the nature of early cortical tagging remains unknown. Here we found that in mice, increased norepinephrine (NE) release from the locus coeruleus (LC) to the medial prefrontal cortex (mPFC) during contextual fear conditioning (CFC) was critical for engram tagging and remote memory storage, which was regulated by the ventrolateral periaqueductal grey. β-Blocker infusion, or knockout of β1-adrenergic receptor (β1-AR) in the mPFC, impaired the storage of remote CFC memory, which could not be rescued by activation of LC-mPFC NE projection. Remote memory retrieval induced the activation of mPFC engram cells that were tagged during CFC. Inhibition of LC-mPFC NE projection or β1-AR knockout impaired mPFC engram tagging. Juvenile mice had fewer LC NE neurons than adults and showed deficiency in mPFC engram tagging and remote memory of CFC. Activation of β1-AR signaling promoted mPFC early tagging and remote memory storage in juvenile mice. Our data demonstrate that activation of LC NEergic signaling during CFC memory encoding mediates engram early tagging in the mPFC and systems consolidation of remote memory.
Closed-loop chemical recycling of cross-linked polymeric materials based on reversible amidation chemistry
Authors: Qin Bo , Liu Siyuan , Huang Zehuan , Zeng Lingda , Xu Jiang-Fei , Zhang Xi 
Published: December 2022

AbstractClosed-loop chemical recycling provides a solution to the end-of-use problem of synthetic polymers. However, it remains a major challenge to design dynamic bonds, capable of effective bonding and reversible cleaving, for preparing chemically recyclable cross-linked polymers. Herein, we report a dynamic maleic acid tertiary amide bond based upon reversible amidation reaction between maleic anhydrides and secondary amines. This dynamic bond allows for the construction of polymer networks with tailorable and robust mechanical properties, covering strong elastomers with a tensile strength of 22.3 MPa and rigid plastics with a yield strength of 38.3 MPa. Impressively, these robust polymeric materials can be completely depolymerized in an acidic aqueous solution at ambient temperature, leading to efficient monomer recovery with >94% separation yields. Meanwhile, the recovered monomers can be used to remanufacture cross-linked polymeric materials without losing their original mechanical performance. This work unveils a general approach to design polymer networks with tunable mechanical performance and closed-loop recyclability, which will open a new avenue for sustainable polymeric materials.
Visualizing the transiently populated closed-state of human HSP90 ATP binding domain
Authors: Henot Faustine , Rioual Elisa , Favier Adrien , Macek Pavel , Crublet Elodie , Josso Pierre , Brutscher Bernhard , Frech Matthias , Gans Pierre , Loison Claire , Boisbouvier Jerome 
Published: December 2022

AbstractHSP90 are abundant molecular chaperones, assisting the folding of several hundred client proteins, including substrates involved in tumor growth or neurodegenerative diseases. A complex set of large ATP-driven structural changes occurs during HSP90 functional cycle. However, the existence of such structural rearrangements in apo HSP90 has remained unclear. Here, we identify a metastable excited state in the isolated human HSP90α ATP binding domain. We use solution NMR and mutagenesis to characterize structures of both ground and excited states. We demonstrate that in solution the HSP90α ATP binding domain transiently samples a functionally relevant ATP-lid closed state, distant by more than 30 Å from the ground state. NMR relaxation enables to derive information on the kinetics and thermodynamics of this interconversion, while molecular dynamics simulations establish that the ATP-lid in closed conformation is a metastable exited state. The precise description of the dynamics and structures sampled by human HSP90α ATP binding domain provides information for the future design of new therapeutic ligands.
Engineering antiviral immune-like systems for autonomous virus detection and inhibition in mice
Authors: Wang Yidan , Xu Ying , Tan Chee Wah , Qiao Longliang , Chia Wan Ni , Zhang Hongyi , Huang Qin , Deng Zhenqiang , Wang Ziwei , Wang Xi , Shen Xurui , Liu Canyu , Pei Rongjuan , Liu Yuanxiao , Xue Shuai , Kong Deqiang , Anderson Danielle E. , Cai Fengfeng , Zhou Peng , Wang Lin-Fa , Ye Haifeng 
Published: December 2022

AbstractThe ongoing COVID-19 pandemic has demonstrated that viral diseases represent an enormous public health and economic threat to mankind and that individuals with compromised immune systems are at greater risk of complications and death from viral diseases. The development of broad-spectrum antivirals is an important part of pandemic preparedness. Here, we have engineer a series of designer cells which we term autonomous, intelligent, virus-inducible immune-like (ALICE) cells as sense-and-destroy antiviral system. After developing a destabilized STING-based sensor to detect viruses from seven different genera, we have used a synthetic signal transduction system to link viral detection to the expression of multiple antiviral effector molecules, including antiviral cytokines, a CRISPR-Cas9 module for viral degradation and the secretion of a neutralizing antibody. We perform a proof-of-concept study using multiple iterations of our ALICE system in vitro, followed by in vivo functionality testing in mice. We show that dual output ALICESaCas9+Ab system delivered by an AAV-vector inhibited viral infection in herpetic simplex keratitis (HSK) mouse model. Our work demonstrates that viral detection and antiviral countermeasures can be paired for intelligent sense-and-destroy applications as a flexible and innovative method against virus infection.
An ionic vinylene-linked three-dimensional covalent organic framework for selective and efficient trapping of ReO4− or 99TcO4−
Authors: Zhang Cheng-Rong , Cui Wei-Rong , Yi Shun-Mo , Niu Cheng-Peng , Liang Ru-Ping , Qi Jia-Xin , Chen Xiao-Juan , Jiang Wei , Liu Xin , Luo Qiu-Xia , Qiu Jian-Ding 
Published: December 2022

AbstractThe synthesis of ionic olefin linked three-dimensional covalent organic frameworks (3D COFs) is greatly challenging given the hardness of the formation of stable carbon-carbon double bonds (–C = C–). Herein, we report a general strategy for designing porous positively charged sp2carbon-linked 3D COFs through the Aldol condensation promoted by quaternization. The obtained 3D COFs, namely TFPM-PZI and TAPM-PZI, showed impressive chemical stability. Furthermore, the positively charged frameworks with regular porosity endow 3D ionic COFs with selective capture radioactive ReO4−/TcO4−and great removal efficiency in simulated Hanford waste. This research not only broadens the category of 3D COFs but also promotes the application of COFs as efficient functional materials.
Biofilms preserve the transmissibility of a multi-drug resistance plasmid
Authors: Metzger Genevieve A. , Ridenhour Benjamin J. , France Michael , Gliniewicz Karol , Millstein Jack , Settles Matthew L. , Forney Larry J. , Stalder Thibault , Top Eva M. 
Published: December 2022

AbstractSelf-transmissible multidrug resistance (MDR) plasmids are a major health concern because they can spread antibiotic resistance to pathogens. Even though most pathogens form biofilms, little is known about how MDR plasmids persist and evolve in biofilms. We hypothesize that (i) biofilms act as refugia of MDR plasmids by retaining them in the absence of antibiotics longer than well-mixed planktonic populations and that (ii) the evolutionary trajectories that account for the improvement of plasmid persistence over time differ between biofilms and planktonic populations. In this study, we evolvedAcinetobacter baumanniiwith an MDR plasmid in biofilm and planktonic populations with and without antibiotic selection. In the absence of selection, biofilm populations were better able to maintain the MDR plasmid than planktonic populations. In planktonic populations, plasmid persistence improved rapidly but was accompanied by a loss of genes required for the horizontal transfer of plasmids. In contrast, in biofilms, most plasmids retained their transfer genes, but on average, plasmid, persistence improved less over time. Our results showed that biofilms can act as refugia of MDR plasmids and favor the horizontal mode of plasmid transfer, which has important implications for the spread of MDR.
Bulk RNA sequencing analysis of developing human induced pluripotent cell-derived retinal organoids
Authors: Agarwal Devansh , Kuhns Rian , Dimitriou Christos N. , Barlow Emmalyn , Wahlin Karl J. , Enke Ray A. 
Published: December 2022

AbstractRetinogenesis involves the transformation of the anterior developing brain into organized retinal lamellae coordinated by intricate gene signalling networks. This complex process has been investigated in several model organisms such as birds, fish, mammals and amphibians, yet many facets of retinal development are different in humans and remain unexplored. In this regard, human pluripotent stem cell (hPSC)-derived 3D retinal organoids and Next Generation Sequencing (NGS) have emerged as key technologies that have facilitated the discovery of previously unknown details about cell fate specification and gene regulation in the retina. Here we utilized hPSCs integrated with fluorescent reporter genes (SIX6-p2A-eGFP/CRX-p2A-h2b-mRuby3) to generate retinal organoids and carry out bulk RNA sequencing of samples encompassing the majority of retinogenesis (D0-D280). This data set will serve as a valuable reference for the vision research community to characterize differentially expressed genes in the developing human eye.
Filamentation in low pressure conditions
Authors: Peña Jessica , Reyes Danielle , Richardson Martin 
Published: December 2022

AbstractFilamentation is favorable for many long-range outdoor laser applications, some of which require propagation to or at high altitudes. Understanding how the filamentation process and filament properties are impacted by the low pressure conditions present at high altitudes is essential in designing effective applications. The scaling of filament preconditions with pressure is considered. An increase in critical power and decrease in transition numerical aperture (NA) is predicted to occur with a drop in pressure, indicating that nonlinear pulse propagation and filamentation at high altitudes requires higher energy and a longer assisted focal length than sea level filamentation. A summary of pressure-scaled filament properties is also presented. New simulations demonstrate filamentation at pressures as low as 0.0035 atm (38.5 km altitude) is possible.
Obesity is associated with myelin oligodendrocyte glycoprotein antibody-associated disease in acute optic neuritis
Authors: Stiebel-Kalish Hadas , Rubarth Kerstin , Shouchane-Blum Karny , Tiosano Alon , Lotan Itay , Hellmann Mark A. , Wilf-Yarkoni Adi , Bialer Omer , Flanagan Eoin P. , Pittock Sean J. , Bhatti M. Tariq , Schmitz-Hübsch Tanja , Paul Friedemann , Asseyer Susanna , Chen John J. 
Published: December 2022

AbstractOptic neuritis (ON) is a frequent presentation at onset of multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). The pathophysiology underlying these diseases, especially MOGAD, is still being elucidated. While obesity has been reported to potentially be a risk factor for MS, this has not been explored in NMOSD or MOGAD. We aimed to investigate a possible association between obesity (body mass index [BMI] > 30 kg/m2) in patients with MOGAD, aquaporin 4-IgG positive NMOSD (AQP4-IgG+ NMOSD) or MS. In this multicenter non-interventional retrospective study, data was collected from patients with a first ever demyelinating attack of ON subsequently diagnosed with MOGAD (n = 44), AQP4-IgG+ NMOSD (n = 49) or MS (n = 90) between 2005 and 2020. The following data was collected: age, sex, ethnicity, BMI (documented before corticosteroid treatment), and the ON etiology after diagnostic work-up. A mixed model analysis was performed to assess the potential of obesity or BMI to predict MOGAD-ON, and to distinguish MOGAD-ON from AQP4-IgG+ NMOSD-ON and MS-ON. Main outcome measures included BMI in patients with acute ON and subsequent diagnosis of MOGAD, AQP4-IgG+ NMOSD or MS. A higher BMI was significantly associated with a diagnosis of MOGAD-ON (p < 0.001); in MOGAD patients the mean BMI was 31.6 kg/m2 (standard deviation (SD) 7.2), while the mean BMI was 24.7 kg/m2 (SD 5.3) in AQP4-IgG+ NMOSD patients, and 26.9 kg/m2 (SD 6.2) in MS patients. Mixed-effects multinomial logistic regression, adjusted for age and sex, with obesity as a binary variable, revealed that obesity was associated with a higher odds ratio (OR) of a subsequent MOGAD diagnosis (OR 5.466, 95% CI [2.039, 14.650], p = 0.001) in contradistinction with AQP4-IgG+ NMOSD. This study suggests an association between obesity and MOGAD. Our findings require further exploration, but could have significant pathophysiologic implications if confirmed in larger prospective studies.
Mask images on Twitter increase during COVID-19 mandates, especially in Republican counties
Authors: Lin Xiaofeng , Kernell Georgia , Groeling Tim , Joo Jungseock , Luo Jun , Steinert-Threlkeld Zachary C. 
Published: December 2022

AbstractWearing masks reduces the spread of COVID-19, but compliance with mask mandates varies across individuals, time, and space. Accurate and continuous measures of mask wearing, as well as other health-related behaviors, are important for public health policies. This article presents a novel approach to estimate mask wearing using geotagged Twitter image data from March through September, 2020 in the United States. We validate our measure using public opinion survey data and extend the analysis to investigate county-level differences in mask wearing. We find a strong association between mask mandates and mask wearing—an average increase of 20%. Moreover, this association is greatest in Republican-leaning counties. The findings have important implications for understanding how governmental policies shape and monitor citizen responses to public health crises.
A comparison of node vaccination strategies to halt SIR epidemic spreading in real-world complex networks
Authors: Sartori F. , Turchetto M. , Bellingeri M. , Scotognella F. , Alfieri R. , Nguyen N.-K.-K. , Le T.-T. , Nguyen Q. , Cassi D. 
Published: December 2022

AbstractWe compared seven node vaccination strategies in twelve real-world complex networks. The node vaccination strategies are modeled as node removal on networks. We performed node vaccination strategies both removing nodes according to the initial network structure, i.e., non-adaptive approach, and performing partial node rank recalculation after node removal, i.e., semi-adaptive approach. To quantify the efficacy of each vaccination strategy, we used three epidemic spread indicators: the size of the largest connected component, the total number of infected at the end of the epidemic, and the maximum number of simultaneously infected individuals. We show that the best vaccination strategies in the non-adaptive and semi-adaptive approaches are different and that the best strategy also depends on the number of available vaccines. Furthermore, a partial recalculation of the node centrality increases the efficacy of the vaccination strategies by up to 80%.
Identification and characterization of proteins that form the inner core Ixodes scapularis tick attachment cement layer
Authors: Mulenga Albert , Radulovic Zeljko , Porter Lindsay , Britten Taylor Hollman , Kim Tae Kwon , Tirloni Lucas , Gaithuma Alex Kiarie , Adeniyi-Ipadeola Grace O. , Dietrich Jolene K. , Moresco James J. , Yates John R. 
Published: December 2022

AbstractIxodes scapularis long-term blood feeding behavior is facilitated by a tick secreted bio adhesive (tick cement) that attaches tick mouthparts to skin tissue and prevents the host from dislodging the attached tick. Understanding tick cement formation is highly sought after as its disruption will prevent tick feeding. This study describes proteins that form the inner core layer of I. scapularis tick cement as disrupting these proteins will likely stop formation of the outer cortical layer. The inner core cement layer completes formation by 24 h of tick attachment. Thus, we used laser-capture microdissection to isolate cement from cryosections of 6 h and 24 h tick attachment sites and to distinguish between early and late inner core cement proteins. LC–MS/MS analysis identified 138 tick cement proteins (TCPs) of which 37 and 35 were unique in cement of 6 and 24 h attached ticks respectively. We grouped TCPs in 14 functional categories: cuticular protein (16%), tick specific proteins of unknown function, cytoskeletal proteins, and enzymes (13% each), enzymes (10%), antioxidant, glycine rich, scaffolding, heat shock, histone, histamine binding, proteases and protease inhibitors, and miscellaneous (3–6% each). Gene ontology analysis confirm that TCPs are enriched for bio adhesive properties. Our data offer insights into tick cement bonding patterns and set the foundation for understanding the molecular basis of I. scapularis tick cement formation.