bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholinergic neurons in the basal forebrain are involved in behavioral abnormalities associated with Cul3 deficiency: Role of prefrontal cortex projections in cognitive deficits
Authors: Rapanelli Maximiliano , Wang Wei , Hurley Edward , Feltri Maria Laura , Pittenger Christopher , Frick Luciana Romina , Yan Zhen 
Published: January 2023

AbstractLoss-of-function mutations of the gene Cul3 have been identified as a risk factor for autism-spectrum disorder (ASD), but the pathogenic mechanisms are not well understood. Conditional Cul3 ablation in cholinergic neurons of mice (ChatCRECul3F/+) recapitulated ASD-like social and sensory gating phenotypes and caused significant cognitive impairments, with diminished activity of cholinergic neurons in the basal forebrain (BF). Chemogenetic inhibition of BF cholinergic neurons in healthy mice induced similar social and cognitive deficits. Conversely, chemogenetic stimulation of BF cholinergic neurons in ChatCRECul3F/+ mice reversed abnormalities in sensory gating and cognition. Cortical hypofunction was also found after ChAT-specific Cul3 ablation and stimulation of cholinergic projections from the BF to the prefrontal cortex (PFC) mitigated cognitive deficits. Overall, we demonstrate that cholinergic dysfunction due to Cul3 deficiency is involved in ASD-like behavioral abnormalities, and that BF cholinergic neurons are particularly critical for cognitive component through their projections to the PFC.
The impact of COVID-19 on dental care in New York State and Georgia
Authors: Puskas Caroline , Morse Stephen S. 
Published: January 2023

AbstractIntroduction During the COVID-19 pandemic, there was an unprecedented and forced closure of dental offices worldwide. As American state recommendations differed considerably during this period, this research strives to better define the effects of this pause on dental care.Materials and methods A 16-question Qualtrics survey was sent to the membership of the New York State Dental Association (NYSDA) and Georgia Dental Association (GDA). Licenced, actively practising dental members of the NYSDA and GDA (n = 680) answered questions about their practice demographics, appointment cancellations, reopening times and the volume of individual dental procedures performed from 1 March through to 1 August 2020, compared to the same five-month period in 2019.Results Demographic characteristics of respondent NYSDA and GDA members were statistically similar. Nonetheless, NYSDA members reported significantly larger decreases in provision of all types of dental procedures, except for antibiotic prescription, including prophylaxis, elective care, emergency dental care and speciality procedures.Discussion and conclusions All dental procedures declined significantly during the COVID-19 pandemic, with greater decrease in New York than in Georgia. This study raises concerns about the negative impact of the pandemic on oral public health and mandates both further research and clinical strategies to mitigate against this future risk.
Chromosome territory reorganization through artificial chromosome fusion is compatible with cell fate determination and mouse development
Authors: Wang Yuang , Qu Zhen , Fang Yi , Chen Yulong , Peng Jiayin , Song Jiawen , Li Jinsong , Shi Jiantao , Zhou Jin-Qiu , Zhao Yun 
Published: January 2023

AbstractChromosomes occupy discrete spaces in the interphase cell nucleus, called chromosome territory. The structural and functional relevance of chromosome territory remains elusive. We fused chromosome 15 and 17 in mouse haploid embryonic stem cells (haESCs), resulting in distinct changes of territories in the cognate chromosomes, but with little effect on gene expression, pluripotency and gamete functions of haESCs. The karyotype-engineered haESCs were successfully implemented in generating heterozygous (2n = 39) and homozygous (2n = 38) mouse models. Mice containing the fusion chromosome are fertile, and their representative tissues and organs display no phenotypic abnormalities, suggesting unscathed development. These results indicate that the mammalian chromosome architectures are highly resilient, and reorganization of chromosome territories can be readily tolerated during cell differentiation and mouse development.
Socioeconomic factors predict population changes of large carnivores better than climate change or habitat loss
Authors: Johnson Thomas F. , Isaac Nick J. B. , Paviolo Agustin , González-Suárez Manuela 
Published: January 2023

AbstractLand-use and climate change have been linked to changes in wildlife populations, but the role of socioeconomic factors in driving declines, and promoting population recoveries, remains relatively unexplored. Here, we evaluate potential drivers of population changes observed in 50 species of some of the world’s most charismatic and functionally important fauna—large mammalian carnivores. Our results reveal that human socioeconomic development is more associated with carnivore population declines than habitat loss or climate change. Rapid increases in socioeconomic development are linked to sharp population declines, but, importantly, once development slows, carnivore populations have the potential to recover. The context- and threshold-dependent links between human development and wildlife population health are challenges to the achievement of the UN Sustainable development goals.
Long-term statins administration exacerbates diabetic nephropathy via ectopic fat deposition in diabetic mice
Authors: Huang Tong-sheng , Wu Teng , Wu Yan-di , Li Xing-hui , Tan Jing , Shen Cong-hui , Xiong Shi-jie , Feng Zi-qi , Gao Sai-fei , Li Hui , Cai Wei-bin 
Published: January 2023

AbstractStatins play an important role in the treatment of diabetic nephropathy. Increasing attention has been given to the relationship between statins and insulin resistance, but many randomized controlled trials confirm that the therapeutic effects of statins on diabetic nephropathy are more beneficial than harmful. However, further confirmation of whether the beneficial effects of chronic statin administration on diabetic nephropathy outweigh the detrimental effects is urgently needed. Here, we find that long-term statin administration may increase insulin resistance, interfere with lipid metabolism, leads to inflammation and fibrosis, and ultimately fuel diabetic nephropathy progression in diabetic mice. Mechanistically, activation of insulin-regulated phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway leads to increased fatty acid synthesis. Furthermore, statins administration increases lipid uptake and inhibits fatty acid oxidation, leading to lipid deposition. Here we show that long-term statins administration exacerbates diabetic nephropathy via ectopic fat deposition in diabetic mice.
Differential sensing with arrays of de novo designed peptide assemblies
Authors: Dawson William M. , Shelley Kathryn L. , Fletcher Jordan M. , Scott D. Arne , Lombardi Lucia , Rhys Guto G. , LaGambina Tania J. , Obst Ulrike , Burton Antony J. , Cross Jessica A. , Davies George , Martin Freddie J. O. , Wiseman Francis J. , Brady R. Leo , Tew David , Wood Christopher W. , Woolfson Derek N. 
Published: January 2023

AbstractDifferential sensing attempts to mimic the mammalian senses of smell and taste to identify analytes and complex mixtures. In place of hundreds of complex, membrane-bound G-protein coupled receptors, differential sensors employ arrays of small molecules. Here we show that arrays of computationally designed de novo peptides provide alternative synthetic receptors for differential sensing. We use self-assembling α-helical barrels (αHBs) with central channels that can be altered predictably to vary their sizes, shapes and chemistries. The channels accommodate environment-sensitive dyes that fluoresce upon binding. Challenging arrays of dye-loaded barrels with analytes causes differential fluorophore displacement. The resulting fluorimetric fingerprints are used to train machine-learning models that relate the patterns to the analytes. We show that this system discriminates between a range of biomolecules, drink, and diagnostically relevant biological samples. As αHBs are robust and chemically diverse, the system has potential to sense many analytes in various settings.
Rabphilin-3A undergoes phase separation to regulate GluN2A mobility and surface clustering
Authors: Yang Lei , Wei Mengping , Wang Yangzhen , Zhang Jingtao , Liu Sen , Liu Mengna , Wang Shanshan , Li Ke , Dong Zhaoqi , Zhang Chen 
Published: January 2023

AbstractN-methyl-D-aspartate receptors (NMDARs) are essential for excitatory neurotransmission and synaptic plasticity. GluN2A and GluN2B, two predominant Glu2N subunits of NMDARs in the hippocampus and the cortex, display distinct clustered distribution patterns and mobility at synaptic and extrasynaptic sites. However, how GluN2A clusters are specifically organized and stabilized remains poorly understood. Here, we found that the previously reported GluN2A-specific binding partner Rabphilin-3A (Rph3A) has the ability to undergo phase separation, which relies on arginine residues in its N-terminal domain. Rph3A phase separation promotes GluN2A clustering by binding GluN2A’s C-terminal domain. A complex formed by Rph3A, GluN2A, and the scaffolding protein PSD95 promoted Rph3A phase separation. Disrupting Rph3A’s phase separation suppressed the synaptic and extrasynaptic surface clustering, synaptic localization, stability, and synaptic response of GluN2A in hippocampal neurons. Together, our results reveal the critical role of Rph3A phase separation in determining the organization and stability of GluN2A in the neuronal surface.
Structural insights into the elevator-type transport mechanism of a bacterial ZIP metal transporter
Authors: Zhang Yao , Jiang Yuhan , Gao Kaifu , Sui Dexin , Yu Peixuan , Su Min , Wei Guo-Wei , Hu Jian 
Published: January 2023

AbstractThe Zrt-/Irt-like protein (ZIP) family consists of ubiquitously expressed divalent metal transporters critically involved in maintaining systemic and cellular homeostasis of zinc, iron, and manganese. Here, we present a study on a prokaryotic ZIP from Bordetella bronchiseptica (BbZIP) by combining structural biology, evolutionary covariance, computational modeling, and a variety of biochemical assays to tackle the issue of the transport mechanism which has not been established for the ZIP family. The apo state structure in an inward-facing conformation revealed a disassembled transport site, altered inter-helical interactions, and importantly, a rigid body movement of a 4-transmembrane helix (TM) bundle relative to the other TMs. The computationally generated and biochemically validated outward-facing conformation model revealed a slide of the 4-TM bundle, which carries the transport site(s), by approximately 8 Å toward the extracellular side against the static TMs which mediate dimerization. These findings allow us to conclude that BbZIP is an elevator-type transporter.
Greenhouse warming and internal variability increase extreme and central Pacific El Niño frequency since 1980
Authors: Gan Ruyu , Liu Qi , Huang Gang , Hu Kaiming , Li Xichen 
Published: January 2023

AbstractEl Niño has been recorded to change its properties since the 1980s, characterized by more common extreme El Niño and Central Pacific (CP) El Niño events. However, it is still unclear whether such change is externally forced or part of the natural variability. Here, we find that the frequency of the extreme and CP El Niño events also increased during the period 1875–1905, when the anthropogenic CO2 concentration was relatively lower, but with a positive phase of the Atlantic Multidecadal Oscillation (AMO). Models and palaeoclimate proxies reveal that a positive AMO enhances the zonal sea surface temperature gradient in the CP, which strengthens zonal advective feedback, favoring extreme and CP El Niño development. Moreover, we estimate that internal variability contributed to ~65% of the increasingly extreme and CP El Niño events, while anthropogenic forcing has made our globe experience ~1 more extreme and ~2 more CP events over the past four decades.
A three-terminal magnetic thermal transistor
Authors: Castelli Lorenzo , Zhu Qing , Shimokusu Trevor J. , Wehmeyer Geoff 
Published: January 2023

AbstractThree-terminal thermal analogies to electrical transistors have been proposed for use in thermal amplification, thermal switching, or thermal logic, but have not yet been demonstrated experimentally. Here, we design and fabricate a three-terminal magnetic thermal transistor in which the gate temperature controls the source-drain heat flow by toggling the source-drain thermal conductance from ON to OFF. The centimeter-scale thermal transistor uses gate-temperature dependent magnetic forces to actuate motion of a thermally conducting shuttle, providing thermal contact between source and drain in the ON state while breaking contact in the OFF state. We measure source-drain thermal switch ratios of 109 ± 44 in high vacuum with gate switching temperatures near 25 °C. Thermal measurements show that small heat flows into the gate can be used to drive larger heat flows from source to drain, and that the switching is reversible over >150 cycles. Proof-of-concept thermal circuit demonstrations show that magnetic thermal transistors can enable passive or active heat flow routing or can be combined to create Boolean thermal logic gates. This work will allow thermal researchers to explore the behavior of nonlinear thermal circuits using three-terminal transistors and will motivate further research developing thermal transistors for advanced thermal control.
Elevated temperature and CO2 strongly affect the growth strategies of soil bacteria
Authors: Ruan Yang , Kuzyakov Yakov , Liu Xiaoyu , Zhang Xuhui , Xu Qicheng , Guo Junjie , Guo Shiwei , Shen Qirong , Yang Yunfeng , Ling Ning 
Published: January 2023

AbstractThe trait-based strategies of microorganisms appear to be phylogenetically conserved, but acclimation to climate change may complicate the scenario. To study the roles of phylogeny and environment on bacterial responses to sudden moisture increases, we determine bacterial population-specific growth rates by 18O-DNA quantitative stable isotope probing (18O-qSIP) in soils subjected to a free-air CO2 enrichment (FACE) combined with warming. We find that three growth strategies of bacterial taxa – rapid, intermediate and slow responders, defined by the timing of the peak growth rates – are phylogenetically conserved, even at the sub-phylum level. For example, members of class Bacilli and Sphingobacteriia are mainly rapid responders. Climate regimes, however, modify the growth strategies of over 90% of species, partly confounding the initial phylogenetic pattern. The growth of rapid bacterial responders is more influenced by phylogeny, whereas the variance for slow responders is primarily explained by environmental conditions. Overall, these results highlight the role of phylogenetic and environmental constraints in understanding and predicting the growth strategies of soil microorganisms under global change scenarios.
Efficient stabilization of cyanonaphthalene by fast radiative cooling and implications for the resilience of small PAHs in interstellar clouds
Authors: Stockett Mark H. , Bull James N. , Cederquist Henrik , Indrajith Suvasthika , Ji MingChao , Navarro Navarrete José E. , Schmidt Henning T. , Zettergren Henning , Zhu Boxing 
Published: January 2023

AbstractAfter decades of searching, astronomers have recently identified specific Polycyclic Aromatic Hydrocarbons (PAHs) in space. Remarkably, the observed abundance of cyanonaphthalene (CNN, C10H7CN) in the Taurus Molecular Cloud (TMC-1) is six orders of magnitude higher than expected from astrophysical modeling. Here, we report unimolecular dissociation and radiative cooling rate coefficients of the 1-CNN isomer in its cationic form. These results are based on measurements of the time-dependent neutral product emission rate and kinetic energy release distributions produced from an ensemble of internally excited 1-CNN+ studied in an environment similar to that in interstellar clouds. We find that Recurrent Fluorescence – radiative relaxation via thermally populated electronic excited states – efficiently stabilizes 1-CNN+, owing to a large enhancement of the electronic transition probability by vibronic coupling. Our results help explain the anomalous abundance of CNN in TMC-1 and challenge the widely accepted picture of rapid destruction of small PAHs in space.
3D RNA-scaffolded wireframe origami
Authors: Parsons Molly F. , Allan Matthew F. , Li Shanshan , Shepherd Tyson R. , Ratanalert Sakul , Zhang Kaiming , Pullen Krista M. , Chiu Wah , Rouskin Silvi , Bathe Mark 
Published: January 2023

AbstractHybrid RNA:DNA origami, in which a long RNA scaffold strand folds into a target nanostructure via thermal annealing with complementary DNA oligos, has only been explored to a limited extent despite its unique potential for biomedical delivery of mRNA, tertiary structure characterization of long RNAs, and fabrication of artificial ribozymes. Here, we investigate design principles of three-dimensional wireframe RNA-scaffolded origami rendered as polyhedra composed of dual-duplex edges. We computationally design, fabricate, and characterize tetrahedra folded from an EGFP-encoding messenger RNA and de Bruijn sequences, an octahedron folded with M13 transcript RNA, and an octahedron and pentagonal bipyramids folded with 23S ribosomal RNA, demonstrating the ability to make diverse polyhedral shapes with distinct structural and functional RNA scaffolds. We characterize secondary and tertiary structures using dimethyl sulfate mutational profiling and cryo-electron microscopy, revealing insight into both global and local, base-level structures of origami. Our top-down sequence design strategy enables the use of long RNAs as functional scaffolds for complex wireframe origami.
Brain Data Standards - A method for building data-driven cell-type ontologies
Authors: Tan Shawn Zheng Kai , Kir Huseyin , Aevermann Brian D. , Gillespie Tom , Harris Nomi , Hawrylycz Michael J. , Jorstad Nikolas L. , Lein Ed S. , Matentzoglu Nicolas , Miller Jeremy A. , Mollenkopf Tyler S. , Mungall Christopher J. , Ray Patrick L. , Sanchez Raymond E. A. , Staats Brian , Vermillion Jim , Yadav Ambika , Zhang Yun , Scheuermann Richard H. , Osumi-Sutherland David 
Published: January 2023

AbstractLarge-scale single-cell ‘omics profiling is being used to define a complete catalogue of brain cell types, something that traditional methods struggle with due to the diversity and complexity of the brain. But this poses a problem: How do we organise such a catalogue - providing a standard way to refer to the cell types discovered, linking their classification and properties to supporting data? Cell ontologies provide a partial solution to these problems, but no existing ontology schemas support the definition of cell types by direct reference to supporting data, classification of cell types using classifications derived directly from data, or links from cell types to marker sets along with confidence scores. Here we describe a generally applicable schema that solves these problems and its application in a semi-automated pipeline to build a data-linked extension to the Cell Ontology representing cell types in the Primary Motor Cortex of humans, mice and marmosets. The methods and resulting ontology are designed to be scalable and applicable to similar whole-brain atlases currently in preparation.
Optimization of tamoxifen solubility in carbon dioxide supercritical fluid and investigating other molecular targets using advanced artificial intelligence models
Authors: Alshahrani Saad M. , Alshetaili Abdullah S. , Alfadhel Munerah M. , Belal Amany , Abourehab Mohammad A. S. , Al Saqr Ahmed , Almutairy Bjad K. , Venkatesan Kumar , Alsubaiyel Amal M. , Pishnamazi Mahboubeh 
Published: January 2023

AbstractParticle size, shape and morphology can be considered as the most significant functional parameters, their effects on increasing the performance of oral solid dosage formulation are indisputable. Supercritical Carbon dioxide fluid (SCCO2) technology is an effective approach to control the above-mentioned parameters in oral solid dosage formulation. In this study, drug solubility measuring is investigated based on artificial intelligence model using carbon dioxide as a common supercritical solvent, at different pressure and temperature, 120–400 bar, 308–338 K. The results indicate that pressure has a strong effect on drug solubility. In this investigation, Decision Tree (DT), Adaptive Boosted Decision Trees (ADA-DT), and Nu-SVR regression models are used for the first time as a novel model on the available data, which have two inputs, including pressure, X1 = P(bar) and temperature, X2 = T(K). Also, output is Y = solubility. With an R-squared score, DT, ADA-DT, and Nu-SVR showed results of 0.836, 0.921, and 0.813. Also, in terms of MAE, they showed error rates of 4.30E−06, 1.95E−06, and 3.45E−06. Another metric is RMSE, in which DT, ADA-DT, and Nu-SVR showed error rates of 4.96E−06, 2.34E−06, and 5.26E−06, respectively. Due to the analysis outputs, ADA-DT selected as the best and novel model and the find optimal outputs can be shown via vector: (x1 = 309, x2 = 317.39, Y1 = 7.03e−05).
Effect of climatic environment on immunological features of rheumatoid arthritis
Authors: Kondo Yuya , Abe Saori , Toko Hirofumi , Hirota Tomoya , Takahashi Hiroyuki , Shimizu Masaru , Noma Hisashi , Tsuboi Hiroto , Matsumoto Isao , Inaba Toshiro , Sumida Takayuki 
Published: January 2023

AbstractThe aim of this study was to clarify the effect of climatic environment on the immunological features of rheumatoid arthritis (RA). Blood samples were collected from patients with RA and healthy controls (HCs), matched by age and sex, living in two locations, Tsukuba and Karuizawa, which differ in their altitude and average air temperature and atmospheric pressure. Analysis of peripheral blood mononuclear cells (PBMCs) revealed that the proportion of T and B cell subpopulations in HCs and RA patients were significantly different between two sites. Inverse probability weighting adjustment with propensity scores was used to control for potential confounding factors. The results revealed that, in comparison with RA patients in Tsukuba, those in Karuizawa showed a significant increase in cTh1, cTfh1, and Tph cells, and significant decrease in cTh17, cTh17.1, and CD8+ Treg in T cell subpopulations, and a significant increase in DNB, DN1, DN2, and class-switched memory B cells, and a significant decrease in unswitched memory B, naïve B cells, and ABCs in B cell subpopulations. Our results suggest the possibility that climatic environment might have an effect on immune cell proportion and function, and be related to the pathogenic mechanism of RA.