bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acan downregulation in parvalbumin GABAergic cells reduces spontaneous recovery of fear memories
Authors: Lavertu-Jolin Marisol , Chattopadhyaya Bidisha , Chehrazi Pegah , Carrier Denise , Wünnemann Florian , Leclerc Séverine , Dumouchel Félix , Robertson Derek , Affia Hicham , Saba Kamal , Gopal Vijaya , Patel Anant Bahadur , Andelfinger Gregor , Pineyro Graçiela , Di Cristo Graziella 
Published: May 2023

AbstractWhile persistence of fear memories is essential for survival, a failure to inhibit fear in response to harmless stimuli is a feature of anxiety disorders. Extinction training only temporarily suppresses fear memory recovery in adults, but it is highly effective in juvenile rodents. Maturation of GABAergic circuits, in particular of parvalbumin-positive (PV+) cells, restricts plasticity in the adult brain, thus reducing PV+cell maturation could promote the suppression of fear memories following extinction training in adults. Epigenetic modifications such as histone acetylation control gene accessibility for transcription and help couple synaptic activity to changes in gene expression. Histone deacetylase 2 (Hdac2), in particular, restrains both structural and functional synaptic plasticity. However, whether and how Hdac2 controls the maturation of postnatal PV+cells is not well understood. Here, we show that PV+- cell specificHdac2deletion limits spontaneous fear memory recovery in adult mice, while enhancing PV+cell bouton remodeling and reducing perineuronal net aggregation around PV+cells in prefrontal cortex and basolateral amygdala. Prefrontal cortex PV+cells lackingHdac2, show reduced expression ofAcan, a critical perineuronal net component, which is rescued by Hdac2 re-expression. Pharmacological inhibition of Hdac2 before extinction training is sufficient to reduce both spontaneous fear memory recovery andAcanexpression in wild-type adult mice, while these effects are occluded in PV+-cell specificHdac2conditional knockout mice. Finally, a brief knock-down ofAcanexpression mediated by intravenous siRNA delivery before extinction training but after fear memory acquisition is sufficient to reduce spontaneous fear recovery in wild-type mice. Altogether, these data suggest that controlled manipulation of PV+cells by targeting Hdac2 activity, or the expression of its downstream effectorAcan, promotes the long-term efficacy of extinction training in adults.
Retinoic acid receptor β modulates mechanosensing and invasion in pancreatic cancer cells via myosin light chain 2
Authors: Matellan Carlos , Lachowski Dariusz , Cortes Ernesto , Chiam Kai Ning , Krstic Aleksandar , Thorpe Stephen D. , del Río Hernández Armando E. 
Published: May 2023

AbstractPancreatic ductal adenocarcinoma (PDAC) is the most common and lethal form of pancreatic cancer, characterised by stromal remodelling, elevated matrix stiffness and high metastatic rate. Retinoids, compounds derived from vitamin A, have a history of clinical use in cancer for their anti-proliferative and differentiation effects, and more recently have been explored as anti-stromal therapies in PDAC for their ability to induce mechanical quiescence in cancer associated fibroblasts. Here, we demonstrate that retinoic acid receptor β (RAR-β) transcriptionally represses myosin light chain 2 (MLC-2) expression in pancreatic cancer cells. As a key regulatory component of the contractile actomyosin machinery, MLC-2 downregulation results in decreased cytoskeletal stiffness and traction force generation, impaired response to mechanical stimuli via mechanosensing and reduced ability to invade through the basement membrane. This work highlights the potential of retinoids to target the mechanical drivers of pancreatic cancer.
KLF5 and p53 comprise an incoherent feed-forward loop directing cell-fate decisions following stress
Authors: Yang Yizeng , Bhargava Dharmendra , Chen Xiao , Zhou Taicheng , Dursuk Gizem , Jiang Wenpeng , Wang Jinshen , Zong Zhen , Katz Sharyn I. , Lomberk Gwen A. , Urrutia Raul A. , Katz Jonathan P. 
Published: May 2023

AbstractIn response to stress, cells make a critical decision to arrest or undergo apoptosis, mediated in large part by the tumor suppressor p53. Yet the mechanisms of these cell fate decisions remain largely unknown, particularly in normal cells. Here, we define an incoherent feed-forward loop in non-transformed human squamous epithelial cells involving p53 and the zinc-finger transcription factor KLF5 that dictates responses to differing levels of cellular stress from UV irradiation or oxidative stress. In normal unstressed human squamous epithelial cells, KLF5 complexes with SIN3A and HDAC2 repress TP53, allowing cells to proliferate. With moderate stress, this complex is disrupted, and TP53 is induced; KLF5 then acts as a molecular switch for p53 function by transactivating AKT1 and AKT3, which direct cells toward survival. By contrast, severe stress results in KLF5 loss, such that AKT1 and AKT3 are not induced, and cells preferentially undergo apoptosis. Thus, in human squamous epithelial cells, KLF5 gates the response to UV or oxidative stress to determine the p53 output of growth arrest or apoptosis.
Bifurcation behaviors shape how continuous physical dynamics solves discrete Ising optimization
Authors: Wang Juntao , Ebler Daniel , Wong K. Y. Michael , Hui David Shui Wing , Sun Jie 
Published: May 2023

AbstractSimulating physical dynamics to solve hard combinatorial optimization has proven effective for medium- to large-scale problems. The dynamics of such systems is continuous, with no guarantee of finding optimal solutions of the original discrete problem. We investigate the open question of when simulated physical solvers solve discrete optimizations correctly, with a focus on coherent Ising machines (CIMs). Having established the existence of an exact mapping between CIM dynamics and discrete Ising optimization, we report two fundamentally distinct bifurcation behaviors of the Ising dynamics at the first bifurcation point: either all nodal states simultaneously deviate from zero (synchronized bifurcation) or undergo a cascade of such deviations (retarded bifurcation). For synchronized bifurcation, we prove that when the nodal states are uniformly bounded away from the origin, they contain sufficient information for exactly solving the Ising problem. When the exact mapping conditions are violated, subsequent bifurcations become necessary and often cause slow convergence. Inspired by those findings, we devise a trapping-and-correction (TAC) technique to accelerate dynamics-based Ising solvers, including CIMs and simulated bifurcation. TAC takes advantage of early bifurcated “trapped nodes” which maintain their sign throughout the Ising dynamics to reduce computation time effectively. Using problem instances from open benchmark and random Ising models, we validate the superior convergence and accuracy of TAC.
Aerosol breezes drive cloud and precipitation increases
Authors: Leung Gabrielle R. , van den Heever Susan C. 
Published: May 2023

AbstractAerosol-cloud interactions are a major source of uncertainty in weather and climate models. These interactions and associated precipitation feedbacks are modulated by spatial distributions of aerosols on global and regional scales. Aerosols also vary on mesoscales, including around wildfires, industrial regions, and cities, but the impacts of variability on these scales are understudied. Here, we first present observations of covarying mesoscale aerosol and cloud distributions on the mesoscale. Then, using a high-resolution process model, we show that horizontal aerosol gradients of order 100 km drive a thermally-direct circulation we call an “aerosol breeze”. We find that aerosol breezes support initiation of clouds and precipitation over the low-aerosol portion of the gradient while suppressing their development on the high-aerosol end. Aerosol gradients also enhance domain-wide cloudiness and precipitation, compared with homogenous distributions of the same aerosol mass, leading to potential biases in models that do not adequately represent this mesoscale aerosol heterogeneity.
State-level macro-economic factors moderate the association of low income with brain structure and mental health in U.S. children
Authors: Weissman David G. , Hatzenbuehler Mark L. , Cikara Mina , Barch Deanna M. , McLaughlin Katie A. 
Published: May 2023

AbstractMacrostructural characteristics, such as cost of living and state-level anti-poverty programs relate to the magnitude of socioeconomic disparities in brain development and mental health. In this study we leveraged data from the Adolescent Brain and Cognitive Development (ABCD) study from 10,633 9-11 year old youth (5115 female) across 17 states. Lower income was associated with smaller hippocampal volume and higher internalizing psychopathology. These associations were stronger in states with higher cost of living. However, in high cost of living states that provide more generous cash benefits for low-income families, socioeconomic disparities in hippocampal volume were reduced by 34%, such that the association of family income with hippocampal volume resembled that in the lowest cost of living states. We observed similar patterns for internalizing psychopathology. State-level anti-poverty programs and cost of living may be confounded with other factors related to neurodevelopment and mental health. However, the patterns were robust to controls for numerous state-level social, economic, and political characteristics. These findings suggest that state-level macrostructural characteristics, including the generosity of anti-poverty policies, are potentially relevant for addressing the relationship of low income with brain development and mental health.
More than one quarter of Africa’s tree cover is found outside areas previously classified as forest
Authors: Reiner Florian , Brandt Martin , Tong Xiaoye , Skole David , Kariryaa Ankit , Ciais Philippe , Davies Andrew , Hiernaux Pierre , Chave Jérôme , Mugabowindekwe Maurice , Igel Christian , Oehmcke Stefan , Gieseke Fabian , Li Sizhuo , Liu Siyu , Saatchi Sassan , Boucher Peter , Singh Jenia , Taugourdeau Simon , Dendoncker Morgane , Song Xiao-Peng , Mertz Ole , Tucker Compton J. , Fensholt Rasmus 
Published: May 2023

AbstractThe consistent monitoring of trees both inside and outside of forests is key to sustainable land management. Current monitoring systems either ignore trees outside forests or are too expensive to be applied consistently across countries on a repeated basis. Here we use the PlanetScope nanosatellite constellation, which delivers global very high-resolution daily imagery, to map both forest and non-forest tree cover for continental Africa using images from a single year. Our prototype map of 2019 (RMSE = 9.57%, bias = −6.9%). demonstrates that a precise assessment of all tree-based ecosystems is possible at continental scale, and reveals that 29% of tree cover is found outside areas previously classified as tree cover in state-of-the-art maps, such as in croplands and grassland. Such accurate mapping of tree cover down to the level of individual trees and consistent among countries has the potential to redefine land use impacts in non-forest landscapes, move beyond the need for forest definitions, and build the basis for natural climate solutions and tree-related studies.
Machine learning-driven multifunctional peptide engineering for sustained ocular drug delivery
Authors: Hsueh Henry T. , Chou Renee Ti , Rai Usha , Liyanage Wathsala , Kim Yoo Chun , Appell Matthew B. , Pejavar Jahnavi , Leo Kirby T. , Davison Charlotte , Kolodziejski Patricia , Mozzer Ann , Kwon HyeYoung , Sista Maanasa , Anders Nicole M. , Hemingway Avelina , Rompicharla Sri Vishnu Kiran , Edwards Malia , Pitha Ian , Hanes Justin , Cummings Michael P. , Ensign Laura M. 
Published: May 2023

AbstractSustained drug delivery strategies have many potential benefits for treating a range of diseases, particularly chronic diseases that require treatment for years. For many chronic ocular diseases, patient adherence to eye drop dosing regimens and the need for frequent intraocular injections are significant barriers to effective disease management. Here, we utilize peptide engineering to impart melanin binding properties to peptide-drug conjugates to act as a sustained-release depot in the eye. We develop a super learning-based methodology to engineer multifunctional peptides that efficiently enter cells, bind to melanin, and have low cytotoxicity. When the lead multifunctional peptide (HR97) is conjugated to brimonidine, an intraocular pressure lowering drug that is prescribed for three times per day topical dosing, intraocular pressure reduction is observed for up to 18 days after a single intracameral injection in rabbits. Further, the cumulative intraocular pressure lowering effect increases ~17-fold compared to free brimonidine injection. Engineered multifunctional peptide-drug conjugates are a promising approach for providing sustained therapeutic delivery in the eye and beyond.
Theory-guided design of high-entropy alloys with enhanced strength-ductility synergy
Authors: Pei Zongrui , Zhao Shiteng , Detrois Martin , Jablonski Paul D. , Hawk Jeffrey A. , Alman David E. , Asta Mark , Minor Andrew M. , Gao Michael C. 
Published: May 2023

AbstractMetallic alloys have played essential roles in human civilization due to their balanced strength and ductility. Metastable phases and twins have been introduced to overcome the strength-ductility tradeoff in face-centered cubic (FCC) high-entropy alloys (HEAs). However, there is still a lack of quantifiable mechanisms to predict good combinations of the two mechanical properties. Here we propose a possible mechanism based on the parameter κ, the ratio of short-ranged interactions between closed-pack planes. It promotes the formation of various nanoscale stacking sequences and enhances the work-hardening ability of the alloys. Guided by the theory, we successfully designed HEAs with enhanced strength and ductility compared with other extensively studied CoCrNi-based systems. Our results not only offer a physical picture of the strengthening effects but can also be used as a practical design principle to enhance the strength-ductility synergy in HEAs.
Specific, sensitive and quantitative protein detection by in-gel fluorescence
Authors: Fuchs Adrian C. D. 
Published: May 2023

AbstractRecombinant proteins in complex solutions are typically detected with tag-specific antibodies in Western blots. Here we describe an antibody-free alternative in which tagged proteins are detected directly in polyacrylamide gels. For this, the highly specific protein ligase Connectase is used to selectively fuse fluorophores to target proteins carrying a recognition sequence, the CnTag. Compared to Western blots, this procedure is faster, more sensitive, offers a better signal-to-noise ratio, requires no optimization for different samples, allows more reproducible and accurate quantifications, and uses freely available reagents. With these advantages, this method represents a promising alternative to the state of the art and may facilitate studies on recombinant proteins.
Giant electrically tunable magnon transport anisotropy in a van der Waals antiferromagnetic insulator
Authors: Qi Shaomian , Chen Di , Chen Kangyao , Liu Jianqiao , Chen Guangyi , Luo Bingcheng , Cui Hang , Jia Linhao , Li Jiankun , Huang Miaoling , Song Yuanjun , Han Shiyi , Tong Lianming , Yu Peng , Liu Yi , Wu Hongyu , Wu Shiwei , Xiao Jiang , Shindou Ryuichi , Xie X. C. , Chen Jian-Hao 
Published: May 2023

AbstractAnisotropy is a manifestation of lowered symmetry in material systems that have profound fundamental and technological implications. For van der Waals magnets, the two-dimensional (2D) nature greatly enhances the effect of in-plane anisotropy. However, electrical manipulation of such anisotropy as well as demonstration of possible applications remains elusive. In particular, in-situ electrical modulation of anisotropy in spin transport, vital for spintronics applications, has yet to be achieved. Here, we realized giant electrically tunable anisotropy in the transport of second harmonic thermal magnons (SHM) in van der Waals anti-ferromagnetic insulator CrPS4 with the application of modest gate current. Theoretical modeling found that 2D anisotropic spin Seebeck effect is the key to the electrical tunability. Making use of such large and tunable anisotropy, we demonstrated multi-bit read-only memories (ROMs) where information is inscribed by the anisotropy of magnon transport in CrPS4. Our result unveils the potential of anisotropic van der Waals magnons for information storage and processing.
Construction of Zn-doped RuO2 nanowires for efficient and stable water oxidation in acidic media
Authors: Zhang Dafeng , Li Mengnan , Yong Xue , Song Haoqiang , Waterhouse Geoffrey I. N. , Yi Yunfei , Xue Bingjie , Zhang Dongliang , Liu Baozhong , Lu Siyu 
Published: May 2023

AbstractOxygen evolution reaction catalysts capable of working efficiently in acidic media are highly demanded for the commercialization of proton exchange membrane water electrolysis. Herein, we report a Zn-doped RuO2nanowire array electrocatalyst with outstanding catalytic performance for the oxygen evolution reaction under acidic conditions. Overpotentials as low as 173, 304, and 373 mV are achieved at 10, 500, and 1000 mA cm−2, respectively, with robust stability reaching to 1000 h at 10 mA cm−2. Experimental and theoretical investigations establish a clear synergistic effect of Zn dopants and oxygen vacancies on regulating the binding configurations of oxygenated adsorbates on the active centers, which then enables an alternative Ru−Zn dual-site oxide path of the reaction. Due to the change of reaction pathways, the energy barrier of rate-determining step is reduced, and the over-oxidation of Ru active sites is alleviated. As a result, the catalytic activity and stability are significantly enhanced.
Photocatalyzed regioselective hydrosilylation for the divergent synthesis of geminal and vicinal borosilanes
Authors: Kong Degong , Zhang Muliang , Zhang Yuchao , Yu Zhenyang , Cao Hui , Wu Jie 
Published: May 2023

AbstractGeminal and vicinal borosilanes are useful building blocks in synthetic chemistry and material science. Hydrosilylation/hydroborylation of unsaturated systems offer expedient access to these motifs. In contrast to the well-established transition-metal-catalyzed methods, radical approaches are rarely explored. Herein we report the synthesis of geminal borosilanes from α-selective hydrosilylation of alkenyl boronates via photoinduced hydrogen atom transfer (HAT) catalysis. Mechanistic studies implicate that the α-selectivity originates from a kinetically favored radical addition and an energetically favored HAT process. We further demonstrate selective synthesis of vicinal borosilanes through hydrosilylation of allyl boronates via 1,2-boron radical migration. These strategies exhibit broad scopes across primary, secondary, and tertiary silanes and various boron compounds. The synthetic utility is evidenced by access to multi-borosilanes in a diverse fashion and scaling up by continuous-flow synthesis.
Fueling sentinel node via reshaping cytotoxic T lymphocytes with a flex-patch for post-operative immuno-adjuvant therapy
Authors: Li Bei , Wang Guohao , Miao Kai , Zhang Aiping , Sun Liangyu , Yu Xinwang , Lei Josh Haipeng , Xie Lisi , Yan Jie , Li Wenxi , Deng Chu-Xia , Dai Yunlu 
Published: May 2023

AbstractClinical updates suggest conserving metastatic sentinel lymph nodes (SLNs) of breast cancer (BC) patients during surgery; however, the immunoadjuvant potential of this strategy is unknown. Here we leverage an immune-fueling flex-patch to animate metastatic SLNs with personalized antitumor immunity. The flex-patch is implanted on the postoperative wound and spatiotemporally releases immunotherapeutic anti-PD-1 antibodies (aPD-1) and adjuvants (magnesium iron-layered double hydroxide, LDH) into the SLN. Genes associated with citric acid cycle and oxidative phosphorylation are enriched in activated CD8+ T cells (CTLs) from metastatic SLNs. Delivered aPD-1 and LDH confer CTLs with upregulated glycolytic activity, promoting CTL activation and cytotoxic killing via metal cation-mediated shaping. Ultimately, CTLs in patch-driven metastatic SLNs could long-termly maintain tumor antigen-specific memory, protecting against high-incidence BC recurrence in female mice. This study indicates a clinical value of metastatic SLN in immunoadjuvant therapy.
Electromagnetic levitation containerless processing of metallic materials in microgravity: thermophysical properties
Authors: Mohr M. , Dong Y. , Bracker G. P. , Hyers R. W. , Matson D. M. , Zboray R. , Frison R. , Dommann A. , Neels A. , Xiao X. , Brillo J. , Busch R. , Novakovic R. , Srirangam P. , Fecht H.-J. 
Published: May 2023

AbstractTransitions from the liquid to the solid state of matter are omnipresent. They form a crucial step in the industrial solidification of metallic alloy melts and are greatly influenced by the thermophysical properties of the melt. Knowledge of the thermophysical properties of liquid metallic alloys is necessary in order to gain a tight control over the solidification pathway, and over the obtained material structure of the solid. Measurements of thermophysical properties on ground are often difficult, or even impossible, since liquids are strongly influenced by earth’s gravity. Another problem is the reactivity of melts with container materials, especially at high temperature. Finally, deep undercooling, necessary to understand nucleus formation and equilibrium as well as non-equilibrium solidification, can only be achieved in a containerless environment. Containerless experiments in microgravity allow precise benchmark measurements of thermophysical properties. The electromagnetic levitator ISS-EML on the International Space Station (ISS) offers perfect conditions for such experiments. This way, data for process simulations is obtained, and a deeper understanding of nucleation, crystal growth, microstructural evolution, and other details of the transformation from liquid to solid can be gained. Here, we address the scientific questions in detail, show highlights of recent achievements, and give an outlook on future work.
Nono deficiency impedes the proliferation and adhesion of H9c2 cardiomyocytes through Pi3k/Akt signaling pathway
Authors: Lei Yu-Qing , Ye Zhou-Jie , Wei Ya-Lan , Zhu Li-Ping , Zhuang Xu-Dong , Wang Xin-Rui , Cao Hua 
Published: May 2023

AbstractCongenital heart disease (CHD) is the most common type of birth defect and the main noninfectious cause of death during the neonatal stage. The non-POU domain containing, octamer-binding gene, NONO, performs a variety of roles involved in DNA repair, RNA synthesis, transcriptional and post-transcriptional regulation. Currently, hemizygous loss-of-function mutation of NONO have been described as the genetic origin of CHD. However, essential effects of NONO during cardiac development have not been fully elucidated. In this study, we aim to understand role of Nono in cardiomyocytes during development by utilizing the CRISPR/Cas9 gene editing system to deplete Nono in the rat cardiomyocytes H9c2. Functional comparison of H9c2 control and knockout cells showed that Nono deficiency suppressed cell proliferation and adhesion. Furthermore, Nono depletion significantly affected the mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis, resulting in H9c2 overall metabolic deficits. Mechanistically we demonstrated that the Nono knockout impeded the cardiomyocyte function by attenuating phosphatidyl inositol 3 kinase-serine/threonine kinase (Pi3k/Akt) signaling via the assay for transposase-accessible chromatin using sequencing in combination with RNA sequencing. From these results we propose a novel molecular mechanism of Nono to influence cardiomyocytes differentiation and proliferation during the development of embryonic heart. We conclude that NONO may represent an emerging possible biomarkers and targets for the diagnosis and treatment of human cardiac development defects.