bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early impairment of cortical circuit plasticity and connectivity in the 5XFAD Alzheimer’s disease mouse model
Authors: Chen Chang , Ma Xiaokuang , Wei Jing , Shakir Neha , Zhang Jessica K. , Zhang Le , Nehme Antoine , Cui Yuehua , Ferguson Deveroux , Bai Feng , Qiu Shenfeng 
Published: September 2022

AbstractGenetic risk factors for neurodegenerative disorders, such as Alzheimer’s disease (AD), are expressed throughout the life span. How these risk factors affect early brain development and function remain largely unclear. Analysis of animal models with high constructive validity for AD, such as the 5xFAD mouse model, may provide insights on potential early neurodevelopmental effects that impinge on adult brain function and age-dependent degeneration. The 5XFAD mouse model over-expresses human amyloid precursor protein (APP) and presenilin 1 (PS1) harboring five familial AD mutations. It is unclear how the expression of these mutant proteins affects early developing brain circuits. We found that the prefrontal cortex (PFC) layer 5 (L5) neurons in 5XFAD mice exhibit transgenic APP overloading at an early post-weaning age. Impaired synaptic plasticity (long-term potentiation, LTP) was seen at 6–8 weeks age in L5 PFC circuit, which was correlated with increased intracellular APP. APP overloading was also seen in L5 pyramidal neurons in the primary visual cortex (V1) during the critical period of plasticity (4–5 weeks age). Whole-cell patch clamp recording in V1 brain slices revealed reduced intrinsic excitability of L5 neurons in 5XFAD mice, along with decreased spontaneous miniature excitatory and inhibitory inputs. Functional circuit mapping using laser scanning photostimulation (LSPS) combined with glutamate uncaging uncovered reduced excitatory synaptic connectivity onto L5 neurons in V1, and a more pronounced reduction in inhibitory connectivity, indicative of altered excitation and inhibition during VC critical period. Lastly, in vivo single-unit recording in V1 confirmed that monocular visual deprivation-induced ocular dominance plasticity during critical period was impaired in 5XFAD mice. Our study reveals plasticity deficits across multiple cortical regions and indicates altered early cortical circuit developmental trajectory as a result of mutant APP/PS1 over-expression.
Single nucleus transcriptomic analysis of rat nucleus accumbens reveals cell type-specific patterns of gene expression associated with volitional morphine intake
Authors: Reiner Benjamin C. , Zhang Yafang , Stein Lauren M. , Perea Emilie Dávila , Arauco-Shapiro Gabriella , Ben Nathan Jennifer , Ragnini Kael , Hayes Matthew R. , Ferraro Thomas N. , Berrettini Wade H. , Schmidt Heath D. , Crist Richard C. 
Published: September 2022

AbstractOpioid exposure is known to cause transcriptomic changes in the nucleus accumbens (NAc). However, no studies to date have investigated cell type-specific transcriptomic changes associated with volitional opioid taking. Here, we use single nucleus RNA sequencing (snRNAseq) to comprehensively characterize cell type-specific alterations of the NAc transcriptome in rats self-administering morphine. One cohort of male Brown Norway rats was injected with acute morphine (10 mg/kg, i.p.) or saline. A second cohort of rats was allowed to self-administer intravenous morphine (1.0 mg/kg/infusion) for 10 consecutive days. Each morphine-experienced rat was paired with a yoked saline control rat. snRNAseq libraries were generated from NAc punches and used to identify cell type-specific gene expression changes associated with volitional morphine taking. We identified 1106 differentially expressed genes (DEGs) in the acute morphine group, compared to 2453 DEGs in the morphine self-administration group, across 27 distinct cell clusters. Importantly, we identified 1329 DEGs that were specific to morphine self-administration. DEGs were identified in novel clusters of astrocytes, oligodendrocytes, and D1R- and D2R-expressing medium spiny neurons in the NAc. Cell type-specific DEGs includedRgs9,Celf5,Oprm1, andPde10a. Upregulation ofRgs9andCelf5in D2R-expressing neurons was validated by RNAscope. Approximately 85% of all oligodendrocyte DEGs, nearly all of which were associated with morphine taking, were identified in two subtypes. Bioinformatic analyses identified cell type-specific upstream regulatory mechanisms of the observed transcriptome alterations and downstream signaling pathways, including both novel and previously identified molecular pathways. These findings show that volitional morphine taking is associated with distinct cell type-specific transcriptomic changes in the rat NAc and highlight specific striatal cell populations and novel molecular substrates that could be targeted to reduce compulsive opioid taking.
A novel cyclic γ-AApeptide-based long-acting pan-coronavirus fusion inhibitor with potential oral bioavailability by targeting two sites in spike protein
Authors: Xue Songyi , Wang Xinling , Wang Lei , Xu Wei , Xia Shuai , Sun Lujia , Wang Shaohui , Shen Ning , Yang Ziqi , Huang Bo , Li Sihao , Cao Chuanhai , Calcul Laurent , Sun Xingmin , Lu Lu , Cai Jianfeng , Jiang Shibo 
Published: September 2022

AbstractThe receptor-binding domain (RBD) in S1 subunit and heptad repeat 1 (HR1) domain in S2 subunit of SARS-CoV-2 spike (S) protein are the targets of neutralizing antibodies (nAbs) and pan-coronavirus (CoV) fusion inhibitory peptides, respectively. However, neither nAb- nor peptide-based drugs can be used orally. In this study, we screened a one-bead-two-compound (OBTC) cyclic γ-AApeptide library against SARS-CoV-2 S protein and identified a hit: S-20 with potent membrane fusion inhibitory activity, but moderate selectivity index (SI). After modification, one derivative, S-20-1, exhibited improved fusion inhibitory activity and SI (>1000). S-20-1 could effectively inhibit infection by pseudotyped and authentic SARS-CoV-2 and pseudotyped variants of concern (VOCs), including B.1.617.2 (Delta) and B.1.1.529 (Omicron), as well as MERS-CoV, SARS-CoV, HCoV-OC43, HCoV-229E, and HCoV-NL63. It could also inhibit infection of a pseudotyped SARS-related coronavirus WIV1 (SARSr-CoV-WIV1) from bats. Intranasal application of S-20-1 to mice before or after challenge with HCoV-OC43 or SARS-CoV-2 provided significant protection from infection. Importantly, S-20-1 was highly resistant to proteolytic degradation, had long half-life, and possessed favorable oral bioavailability. Mechanistic studies suggest that S-20-1 binds with high affinity to RBD in S1 and HR1 domain in S2 of SARS-CoV-2 S protein. Thus, with its pan-CoV fusion and entry inhibitory activity by targeting two sites in S protein, desirable half-life, and promising oral bioavailability, S-20-1 is a potential candidate for further development as a novel therapeutic and prophylactic drug against infection by SARS-CoV-2 and its variants, as well as future emerging and reemerging CoVs.
A genomic deletion encompassing CRYBB2-CRYBB2P1 is responsible for autosomal recessive congenital cataracts
Authors: Irum Bushra , Kabir Firoz , Shoshany Nadav , Khan Shahid Y. , Rauf Bushra , Naeem Muhammad Asif , Qaiser Tanveer A. , Riazuddin Sheikh , Hejtmancik J. Fielding , Riazuddin S. Amer 
Published: September 2022

AbstractHere we report a consanguineous Pakistani family with multiple affected individuals with autosomal recessive congenital cataract (arCC). Exclusion analysis established linkage to chromosome 22q, and Sanger sequencing coupled with PCR-based chromosome walking identified a large homozygous genomic deletion. Our data suggest that this deletion leads to CRYBB2-CRYBB2P1 fusion, consisting of exons 1–5 of CRYBB2 and exon 6 of CRYBB2P1, the latter of which harbors the c.463 C > T (p.Gln155*) mutation, and is responsible for arCC.
Drivers and distribution of global ocean heat uptake over the last half century
Authors: Huguenin Maurice F. , Holmes Ryan M. , England Matthew H. 
Published: September 2022

AbstractSince the 1970s, the ocean has absorbed almost all of the additional energy in the Earth system due to greenhouse warming. However, sparse observations limit our knowledge of where ocean heat uptake (OHU) has occurred and where this heat is stored today. Here, we equilibrate a reanalysis-forced ocean-sea ice model, using a spin-up that improves on earlier approaches, to investigate recent OHU trends basin-by-basin and associated separately with surface wind trends, thermodynamic properties (temperature, humidity and radiation) or both. Wind and thermodynamic changes each explain ~ 50% of global OHU, while Southern Ocean forcing trends can account for almost all of the global OHU. This OHU is enabled by cool sea surface temperatures and sensible heat gain when atmospheric thermodynamic properties are held fixed, while downward longwave radiation dominates when winds are fixed. These results address long-standing limitations in multidecadal ocean-sea ice model simulations to reconcile estimates of OHU, transport and storage.
Ultra-depleted hydrogen isotopes in hydrated glass record Late Cretaceous glaciation in Antarctica
Authors: Nelson Demian A. , Cottle John M. , Bindeman Ilya N. , Camacho Alfredo 
Published: September 2022

AbstractThe Early Jurassic Butcher Ridge Igneous Complex (BRIC) in the Transantarctic Mountains contains abundant and variably hydrated silicic glass which has the potential to preserve a rich paleoclimate record. Here we present Fourier Transform Infrared Spectroscopic data that indicates BRIC glasses contain up to ~8 wt.% molecular water (H2Om), and low (<0.8 wt.%) hydroxyl (OH) component, interpreted as evidence for secondary hydration by meteoric water. BRIC glasses contain the most depleted hydrogen isotopes yet measured in terrestrial rocks, down to δD = −325 ‰. In situ 40Ar/39Ar geochronology of hydrated glasses with ultra-depleted δD values yield ages from 105 Ma to 72 Ma with a peak at c. 91.4 Ma. Combined, these data suggest hydration of BRIC glasses by polar glacial ice and melt water during the Late Cretaceous, contradicting paleoclimate reconstructions of this period that suggest Antarctica was ice-free and part of a global hot greenhouse.
Parallel triplet formation pathways in a singlet fission material
Authors: Maity Nilabja , Kim Woojae , Panjwani Naitik A. , Kundu Arup , Majumder Kanad , Kasetty Pranav , Mishra Divji , Bittl Robert , Nagesh Jayashree , Dasgupta Jyotishman , Musser Andrew J. , Patil Satish 
Published: September 2022

AbstractHarvesting long-lived free triplets in high yields by utilizing organic singlet fission materials can be the cornerstone for increasing photovoltaic efficiencies potentially. However, except for polyacenes, which are the most studied systems in the singlet fission field, spin-entangled correlated triplet pairs and free triplets born through singlet fission are relatively poorly characterized. By utilizing transient absorption and photoluminescence spectroscopy in supramolecular aggregate thin films consisting of Hamilton-receptor-substituted diketopyrrolopyrrole derivatives, we show that photoexcitation gives rise to the formation of spin-0 correlated triplet pair 1(TT) from the lower Frenkel exciton state. The existence of 1(TT) is proved through faint Herzberg-Teller emission that is enabled by vibronic coupling and correlated with an artifact-free triplet-state photoinduced absorption in the near-infrared. Surprisingly, transient electron paramagnetic resonance reveals that long-lived triplets are produced through classical intersystem crossing instead of 1(TT) dissociation, with the two pathways in competition. Moreover, comparison of the triplet-formation dynamics in J-like and H-like thin films with the same energetics reveals that spin-orbit coupling mediated intersystem crossing persists in both. However, 1(TT) only forms in the J-like film, pinpointing the huge impact of intermolecular coupling geometry on singlet fission dynamics.
Rab35 governs apicobasal polarity through regulation of actin dynamics during sprouting angiogenesis
Authors: Francis Caitlin R. , Kincross Hayle , Kushner Erich J. 
Published: September 2022

AbstractIn early blood vessel development, trafficking programs, such as those using Rab GTPases, are tasked with delivering vesicular cargo with high spatiotemporal accuracy. However, the function of many Rab trafficking proteins remain ill-defined in endothelial tissue; therefore, their relevance to blood vessel development is unknown. Rab35 has been shown to play an enigmatic role in cellular behaviors which differs greatly between tissue-type and organism. Importantly, Rab35 has never been characterized for its potential contribution in sprouting angiogenesis; thus, our goal was to map Rab35’s primary function in angiogenesis. Our results demonstrate that Rab35 is critical for sprout formation; in its absence, apicobasal polarity is entirely lost in vitro and in vivo. To determine mechanism, we systematically explored established Rab35 effectors and show that none are operative in endothelial cells. However, we find that Rab35 partners with DENNd1c, an evolutionarily divergent guanine exchange factor, to localize to actin. Here, Rab35 regulates actin polymerization through limiting Rac1 and RhoA activity, which is required to set up proper apicobasal polarity during sprout formation. Our findings establish that Rab35 is a potent brake of actin remodeling during blood vessel development.
MAD2L2 promotes replication fork protection and recovery in a shieldin-independent and REV3L-dependent manner
Authors: Paniagua Inés , Tayeh Zainab , Falcone Mattia , Hernández Pérez Santiago , Cerutti Aurora , Jacobs Jacqueline J. L. 
Published: September 2022

AbstractProtection of stalled replication forks is essential to prevent genome instability, a major driving force of tumorigenesis. Several key regulators of DNA double-stranded break (DSB) repair, including 53BP1 and RIF1, have been implicated in fork protection. MAD2L2, also known as REV7, plays an important role downstream of 53BP1/RIF1 by counteracting resection at DSBs in the recently discovered shieldin complex. The ability to bind and counteract resection at exposed DNA ends at DSBs makes MAD2L2/shieldin a prime candidate for also suppressing nucleolytic processing at stalled replication forks. However, the function of MAD2L2/shieldin outside of DNA repair is unknown. Here we address this by using genetic and single-molecule analyses and find that MAD2L2 is required for protecting and restarting stalled replication forks. MAD2L2 loss leads to uncontrolled MRE11-dependent resection of stalled forks and single-stranded DNA accumulation, which causes irreparable genomic damage. Unexpectedly, MAD2L2 limits resection at stalled forks independently of shieldin, since fork protection remained unaffected by shieldin loss. Instead, MAD2L2 cooperates with the DNA polymerases REV3L and REV1 to promote fork stability. Thus, MAD2L2 suppresses aberrant nucleolytic processing both at DSBs and stalled replication forks by differentially engaging shieldin and REV1/REV3L, respectively.
Structural and functional characterization of NEMO cleavage by SARS-CoV-2 3CLpro
Authors: Hameedi Mikhail A. , T. Prates Erica , Garvin Michael R. , Mathews Irimpan I. , Amos B. Kirtley , Demerdash Omar , Bechthold Mark , Iyer Mamta , Rahighi Simin , Kneller Daniel W. , Kovalevsky Andrey , Irle Stephan , Vuong Van-Quan , Mitchell Julie C. , Labbe Audrey , Galanie Stephanie , Wakatsuki Soichi , Jacobson Daniel 
Published: September 2022

AbstractIn addition to its essential role in viral polyprotein processing, the SARS-CoV-2 3C-like protease (3CLpro) can cleave human immune signaling proteins, like NF-κB Essential Modulator (NEMO) and deregulate the host immune response. Here, in vitro assays show that SARS-CoV-2 3CLpro cleaves NEMO with fine-tuned efficiency. Analysis of the 2.50 Å resolution crystal structure of 3CLpro C145S bound to NEMO226–234reveals subsites that tolerate a range of viral and host substrates through main chain hydrogen bonds while also enforcing specificity using side chain hydrogen bonds and hydrophobic contacts. Machine learning- and physics-based computational methods predict that variation in key binding residues of 3CLpro-NEMO helps explain the high fitness of SARS-CoV-2 in humans. We posit that cleavage of NEMO is an important piece of information to be accounted for, in the pathology of COVID-19.
Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity
Authors: Huyghe A. , Furlan G. , Schroeder J. , Cascales E. , Trajkova A. , Ruel M. , Stüder F. , Larcombe M. , Yang Sun Y. Bo , Mugnier F. , De Matteo L. , Baygin A. , Wang J. , Yu Y. , Rama N. , Gibert B. , Kielbassa J. , Tonon L. , Wajda P. , Gadot N. , Brevet M. , Siouda M. , Mulligan P. , Dante R. , Liu P. , Gronemeyer H. , Mendoza-Parra M. , Polo J. M. , Lavial F. 
Published: September 2022

AbstractCoordinated changes of cellular plasticity and identity are critical for pluripotent reprogramming and oncogenic transformation. However, the sequences of events that orchestrate these intermingled modifications have never been comparatively dissected. Here, we deconvolute the cellular trajectories of reprogramming (via Oct4/Sox2/Klf4/c-Myc) and transformation (via Ras/c-Myc) at the single-cell resolution and reveal how the two processes intersect before they bifurcate. This approach led us to identify the transcription factor Bcl11b as a broad-range regulator of cell fate changes, as well as a pertinent marker to capture early cellular intermediates that emerge simultaneously during reprogramming and transformation. Multiomics characterization of these intermediates unveiled a c-Myc/Atoh8/Sfrp1 regulatory axis that constrains reprogramming, transformation and transdifferentiation. Mechanistically, we found that Atoh8 restrains cellular plasticity, independent of cellular identity, by binding a specific enhancer network. This study provides insights into the partitioned control of cellular plasticity and identity for both regenerative and cancer biology.
Gene expression profiles of specific chicken skeletal muscles
Authors: Kui Hua , Ran Bo , Yang Maosen , Shi Xin , Luo Yingyu , Wang Yujie , Wang Tao , Li Diyan , Shuai Surong , Li Mingzhou 
Published: September 2022

AbstractThe chicken provides large amounts of protein for the human diet and is also used as a model organism for biomedical research. Increasing meat production is an important goal in the poultry industry and skeletal muscles have highly diverse origins, shapes, metabolic features, and physical functions. Previous gene expression atlases have largely ignored the differences among diverse types of skeletal muscles; therefore, comprehensive transcriptional maps of all skeletal muscles are needed to improve meat production traits. In this study, we sequenced 58 samples from 10 different skeletal muscles of 42-day-old White Plymouth Rock chickens. We also measured myofiber diameter and generated myofiber-type datasets of these 10 tissues. We generated 418.4 Gb high-quality bulk RNA-Seq data from four or six biological replicates of each skeletal muscle (four replicates from extraocular samples) (approximately 7.4 Gb per sample). This dataset provides valuable information for understanding the muscle fiber characteristics of White Plymouth Rock chickens. Furthermore, our data can be used as a model for heterogeneity analysis between tissues with similar properties.
Spatiotemporal heterogeneity of land subsidence in Beijing
Authors: Duan Guangyao , Gong Huili , Chen Beibei , Li Xiaojuan , Pan Xingyao , Shi Min , Zhang Hang 
Published: September 2022

AbstractLand subsidence induced by groundwater level decline has spatiotemporal variations. Taking the Interferometric Synthetic Aperture Radar (InSAR) results and the groundwater subsidence data acquired by the monitoring stations as the source material, this paper aims to reveal the spatiotemporal heterogeneity of groundwater-land subsidence in Beijing plain by using the Wind Rose Map (WRM) method and the Change Point Analysis (CPA) method. The WRM results show that the amount and variation in subsidence differs in different directions. This method detected the formation of new subsidence centers and the slowdown of land subsidence in 2008. The CPA results show that obvious changes are detected in subsidence development at the Wangsiying (WSY), Tianzhu (TZ) and Wangjing (WJ) stations. However, there is a relatively stable trend of groundwater decline and land subsidence at the Tianzhu (TZ) station. The stages of land subsidence development show a significant response to groundwater. Moreover, changes in land subsidence also show delayed response behind the changes in groundwater level. The time-lag could be affected by the variation in amplitude of the groundwater level.
Increasing typhoon impact and economic losses due to anthropogenic warming in Southeast China
Authors: Huang Mingfeng , Wang Qing , Liu Maofeng , Lin Ning , Wang Yifan , Jing Renzhi , Sun Jianping , Murakami Hiroyuki , Lou Wenjuan 
Published: September 2022

AbstractDespite a variety of studies on the tropical cyclone (TC) response to climate change, few of them have examined the projected damages of future TCs. Here we quantify the impact of anthropogenic warming on TC-induced damages in the late twenty-first century along the coasts of Southeast China based on convection-permitting TC simulations and machine-learning-based damage models. We found that if the area’s 10 super typhoons between 2013 and 2019 were to occur at the end of the century under the high emissions RCP8.5 scenario, they would have on average a 12% ± 4% increase in landfall intensity, 25% ± 23% increase in precipitation, and 128% ± 70% increase in economic losses, compared to historical simulations. We also found a significant increase in the full risk profile. The estimated typhoon loss with a 50-year return period for Zhejiang, Fujian, Guangdong, and Hainan (four most typhoon-prone provinces among the seven provinces in the region) would increase by 71%, 170%, 20%, and 85%, respectively, towards the end of the century even under the lower emissions RCP4.5 pathway. Our findings imply the need to design effective local hazard mitigation measures to reduce future typhoon risks.
Tau isoform-specific enhancement of L-type calcium current and augmentation of afterhyperpolarization in rat hippocampal neurons
Authors: Stan Georgiana F. , Church Timothy W. , Randall Ellie , Harvey Jenna R. M. , Brown Jon T. , Wilkinson Kevin A. , Hanley Jonathan G. , Marrion Neil V. 
Published: September 2022

AbstractAccumulation of tau is observed in dementia, with human tau displaying 6 isoforms grouped by whether they display either 3 or 4 C-terminal repeat domains (3R or 4R) and exhibit no (0N), one (1N) or two (2N) N terminal repeats. Overexpression of 4R0N-tau in rat hippocampal slices enhanced the L-type calcium (Ca2+) current-dependent components of the medium and slow afterhyperpolarizations (AHPs). Overexpression of both 4R0N-tau and 4R2N-tau augmented CaV1.2-mediated L-type currents when expressed in tsA-201 cells, an effect not observed with the third 4R isoform, 4R1N-tau. Current enhancement was only observed when the pore-forming subunit was co-expressed with CaVβ3 and not CaVβ2a subunits. Non-stationary noise analysis indicated that enhanced Ca2+ channel current arose from a larger number of functional channels. 4R0N-tau and CaVβ3 were found to be physically associated by co-immunoprecipitation. In contrast, the 4R1N-tau isoform that did not augment expressed macroscopic L-type Ca2+ current exhibited greatly reduced binding to CaVβ3. These data suggest that physical association between tau and the CaVβ3 subunit stabilises functional L-type channels in the membrane, increasing channel number and Ca2+ influx. Enhancing the Ca2+-dependent component of AHPs would produce cognitive impairment that underlie those seen in the early phases of tauopathies.