bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive context biases perceptual selection during binocular rivalry
Authors: Denison Rachel , Silver Michael 
Published: January 2023

AbstractPrediction may be a fundamental principle of sensory processing, such that the brain continuously generates predictions about forthcoming sensory information. However, little is known about how prediction contributes to the selection of a conscious percept from among competing alternatives. Here, we used binocular rivalry to investigate the effects of prediction on perceptual selection. In binocular rivalry, incompatible images presented to the two eyes result in a perceptual alternation between the images, even though the visual stimuli remain constant. If predictive signals influence the competition between neural representations of rivalrous images, this influence should generate a bias in perceptual selection that depends on predictive context. To manipulate predictive context, we developed a novel binocular rivalry paradigm in which orthogonal rivalrous test gratings were immediately preceded by rotating gratings presented identically to the two eyes. One of the rivalrous gratings had an orientation that was consistent with the preceding rotation direction (it was the expected next image in the series), and the other had an inconsistent orientation. We found that human observers were more likely to perceive the consistent grating, suggesting that predictive context biased selection in favor of the predicted percept. This prediction effect depended on only recent stimulus history, and it could be dissociated from another stimulus history effect related to orientation-specific adaptation. Since binocular rivalry between orthogonal gratings is thought to be resolved at an early stage of visual processing, these results suggest that predictive signals may exist at low levels of the visual processing hierarchy and that these signals can bias conscious perception. In the future, this paradigm could be used to test whether visual percepts are generated from the combination of prior information and incoming sensory information according to Bayesian principles.
Ten reasons NOT to fix the numerical value of the Avogadro constant
Authors: Wheatley Nigel 
Published: January 2023

AbstractThis discussion paper, circulated in advance of the 17th meeting of the Consultative Committee for Amount of Substance, addresses the proposed redefinition of the mole in terms of a fixed numerical value for the Avogadro constant. It gives ten reasons why the Avogadro constant should not be given a fixed numerical value in the International System of Units, noting that there would be no metrological benefit from such a change, and that the proposed redefinition would be more conceptually complex that the current one and divorced from practical measurement and historical background. As the conditions for redefinition of the kilogram have not been met, and no mise en pratique has been produced for the proposed new definition, the paper concludes that the proposal should be rejected.
Dnmt1/Tet2-mediated changes in Cmip methylation regulate the development of nonalcoholic fatty liver disease by controlling the Gbp2-Pparγ-CD36 axis
Authors: Lee Jangho , Song Ji-Hye , Park Jae-Ho , Chung Min-Yu , Lee Seung-Hyun , Jeon Sae-Bom , Park So Hee , Hwang Jin-Taek , Choi Hyo-Kyoung 
Published: January 2023

AbstractDynamic alteration of DNA methylation leads to various human diseases, including nonalcoholic fatty liver disease (NAFLD). Although C-Maf-inducing protein (Cmip) has been reported to be associated with NAFLD, its exact underlying mechanism remains unclear. Here, we aimed to elucidate this mechanism in NAFLD in vitro and in vivo. We first identified alterations in the methylation status of theCmipintron 1 region in mouse liver tissues with high-fat high-sucrose diet-induced NAFLD. Knockdown of DNA methyltransferase (Dnmt) 1 significantly increased Cmip expression. Chromatin immunoprecipitation assays of AML12 cells treated with oleic and palmitic acid (OPA) revealed that Dnmt1 was dissociated and that methylation of H3K27me3 was significantly decreased in theCmipintron 1 region. Conversely, the knockdown of Tet methylcytosine dioxygenase 2 (Tet2) decreased Cmip expression. Following OPA treatment, the CCCTC-binding factor (Ctcf) was recruited, and H3K4me3 was significantly hypermethylated. IntravenousCmipsiRNA injection ameliorated NAFLD pathogenic features inob/obmice. Additionally,PparγandCd36expression levels were dramatically decreased in the livers ofob/obmice administered siCmip, and RNA sequencing revealed that Gbp2 was involved.Gbp2knockdown also induced a decrease inPparγandCd36expression, resulting in the abrogation of fatty acid uptake into cells. Our data demonstrate that Cmip and Gbp2 expression levels are enhanced in human liver tissues bearing NAFLD features. We also show that Dnmt1–Trt2/Ctcf-mediated reversible modulation ofCmipmethylation regulates the Gbp2–Pparγ–Cd36 signaling pathway, indicating the potential ofCmipas a novel therapeutic target for NAFLD.
Impaired OTUD7A-dependent Ankyrin regulation mediates neuronal dysfunction in mouse and human models of the 15q13.3 microdeletion syndrome
Authors: Unda Brianna K. , Chalil Leon , Yoon Sehyoun , Kilpatrick Savannah , Irwin Courtney , Xing Sansi , Murtaza Nadeem , Cheng Anran , Brown Chad , Afonso Alexandria , McCready Elizabeth , Ronen Gabriel M. , Howe Jennifer , Caye-Eude Aurélie , Verloes Alain , Doble Brad W. , Faivre Laurence , Vitobello Antonio , Scherer Stephen W. , Lu Yu , Penzes Peter , Singh Karun K. 
Published: January 2023

AbstractCopy number variations (CNVs) are associated with psychiatric and neurodevelopmental disorders (NDDs), and most, including the recurrent 15q13.3 microdeletion disorder, have unknown disease mechanisms. We used a heterozygous 15q13.3 microdeletion mouse model and patient iPSC-derived neurons to reveal developmental defects in neuronal maturation and network activity. To identify the underlying molecular dysfunction, we developed a neuron-specific proximity-labeling proteomics (BioID2) pipeline, combined with patient mutations, to target the 15q13.3 CNV genetic driverOTUD7A.OTUD7Ais an emerging independent NDD risk gene with no known function in the brain, but has putative deubiquitinase function. The OTUD7A protein–protein interaction network included synaptic, axonal, and cytoskeletal proteins and was enriched for ASD and epilepsy risk genes (Ank3, Ank2, SPTAN1, SPTBN1). The interactions between OTUD7A and Ankyrin-G (Ank3) and Ankyrin-B (Ank2) were disrupted by an epilepsy-associatedOTUD7AL233F variant. Further investigation of Ankyrin-G in mouse and human 15q13.3 microdeletion and OTUD7AL233F/L233Fmodels revealed protein instability, increased polyubiquitination, and decreased levels in the axon initial segment, while structured illumination microscopy identified reduced Ankyrin-G nanodomains in dendritic spines. Functional analysis of human 15q13.3 microdeletion and OTUD7AL233F/L233Fmodels revealed shared and distinct impairments to axonal growth and intrinsic excitability. Importantly, restoring OTUD7A or Ankyrin-G expression in 15q13.3 microdeletion neurons led to a reversal of abnormalities. These data reveal a critical OTUD7A-Ankyrin pathway in neuronal development, which is impaired in the 15q13.3 microdeletion syndrome, leading to neuronal dysfunction. Furthermore, our study highlights the utility of targeting CNV genes using cell type-specific proteomics to identify shared and unexplored disease mechanisms across NDDs.
A distal super-enhancer activates oncogenic ETS2 via recruiting MECOM in inflammatory bowel disease and colorectal cancer
Authors: Chen Yongheng , Ying Ying , Wang Maolin , Ma Canjie , Jia Min , Shi Liang , Wang Shilan , Zheng Xiangyi , Chen Wei , Shu Xing-sheng 
Published: January 2023

AbstractAbnormal activities of distal cis-regulatory elements (CREs) contribute to the initiation and progression of cancer. Gain of super-enhancer (SE), a highly active distal CRE, is essential for the activation of key oncogenes in various cancers. However, the mechanism of action for most tumor-specific SEs still largely remains elusive. Here, we report that a candidate oncogeneETS2was activated by a distal SE in inflammatory bowel disease (IBD) and colorectal cancer (CRC). The SE physically interacted with theETS2promoter and was required for the transcription activation ofETS2. Strikingly, theETS2-SE activity was dramatically upregulated in both IBD and CRC tissues when compared to normal colon controls and was strongly correlated with the level ofETS2expression. The tumor-specific activation ofETS2-SE was further validated by increased enhancer RNA transcription from this region in CRC. Intriguingly, a known IBD-risk SNP resides in theETS2-SE and the genetic variant modulated the level ofETS2expression through affecting the binding of an oncogenic transcription factor MECOM. Silencing ofMECOMinduced significant downregulation ofETS2in CRC cells, and the level ofMECOMandETS2correlated well with each other in CRC and IBD samples. Functionally, MECOM and ETS2 were both required for maintaining the colony-formation and sphere-formation capacities of CRC cells and MECOM was crucial for promoting migration. Taken together, we uncovered a novel disease-specific SE that distantly drives oncogenicETS2expression in IBD and CRC and delineated a mechanistic link between non-coding genetic variation and epigenetic regulation of gene transcription.
A comprehensive single-cell map of T cell exhaustion-associated immune environments in human breast cancer
Authors: Tietscher Sandra , Wagner Johanna , Anzeneder Tobias , Langwieder Claus , Rees Martin , Sobottka Bettina , de Souza Natalie , Bodenmiller Bernd 
Published: January 2023

AbstractImmune checkpoint therapy in breast cancer remains restricted to triple negative patients, and long-term clinical benefit is rare. The primary aim of immune checkpoint blockade is to prevent or reverse exhausted T cell states, but T cell exhaustion in breast tumors is not well understood. Here, we use single-cell transcriptomics combined with imaging mass cytometry to systematically study immune environments of human breast tumors that either do or do not contain exhausted T cells, with a focus on luminal subtypes. We find that the presence of a PD-1highexhaustion-like T cell phenotype is associated with an inflammatory immune environment with a characteristic cytotoxic profile, increased myeloid cell activation, evidence for elevated immunomodulatory, chemotactic, and cytokine signaling, and accumulation of natural killer T cells. Tumors harboring exhausted-like T cells show increased expression of MHC-I on tumor cells and of CXCL13 on T cells, as well as altered spatial organization with more immature rather than mature tertiary lymphoid structures. Our data reveal fundamental differences between immune environments with and without exhausted T cells within luminal breast cancer, and show that expression of PD-1 and CXCL13 on T cells, and MHC-I – but not PD-L1 – on tumor cells are strong distinguishing features between these environments.
Molecular subtypes of ALS are associated with differences in patient prognosis
Authors: Eshima Jarrett , O’Connor Samantha A. , Marschall Ethan ,   NYGC ALS Consortium, Bowser Robert , Plaisier Christopher L. , Smith Barbara S. 
Published: January 2023

AbstractAmyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with poorly understood clinical heterogeneity, underscored by significant differences in patient age at onset, symptom progression, therapeutic response, disease duration, and comorbidity presentation. We perform a patient stratification analysis to better understand the variability in ALS pathology, utilizing postmortem frontal and motor cortex transcriptomes derived from 208 patients. Building on the emerging role of transposable element (TE) expression in ALS, we consider locus-specific TEs as distinct molecular features during stratification. Here, we identify three unique molecular subtypes in this ALS cohort, with significant differences in patient survival. These results suggest independent disease mechanisms drive some of the clinical heterogeneity in ALS.
Structure of the Sec14 domain of Kalirin reveals a distinct class of lipid-binding module in RhoGEFs
Authors: Li Yunfeng , Pustovalova Yulia , Doukov Tzanko I. , Hoch Jeffrey C. , Mains Richard E. , Eipper Betty A. , Hao Bing 
Published: January 2023

AbstractGated entry of lipophilic ligands into the enclosed hydrophobic pocket in stand-alone Sec14 domain proteins often links lipid metabolism to membrane trafficking. Similar domains occur in multidomain mammalian proteins that activate small GTPases and regulate actin dynamics. The neuronal RhoGEF Kalirin, a central regulator of cytoskeletal dynamics, contains a Sec14 domain (KalbSec14) followed by multiple spectrin-like repeats and catalytic domains. Previous studies demonstrated that Kalirin lacking its Sec14 domain fails to maintain cell morphology or dendritic spine length, yet whether and how KalbSec14interacts with lipids remain unknown. Here, we report the structural and biochemical characterization of KalbSec14. KalbSec14adopts a closed conformation, sealing off the canonical ligand entry site, and instead employs a surface groove to bind a limited set of lysophospholipids. The low-affinity interactions of KalbSec14with lysolipids are expected to serve as a general model for the regulation of Rho signaling by other Sec14-containing Rho activators.
Automatic purpose-driven basis set truncation for time-dependent Hartree–Fock and density-functional theory
Authors: Han Ruocheng , Mattiat Johann , Luber Sandra 
Published: January 2023

AbstractReal-time time-dependent density-functional theory (RT-TDDFT) and linear response time-dependent density-functional theory (LR-TDDFT) are two important approaches to simulate electronic spectra. However, the basis sets used in such calculations are usually the ones designed mainly for electronic ground state calculations. In this work, we propose a systematic and robust scheme to truncate the atomic orbital (AO) basis set employed in TDDFT and TD Hartree–Fock (TDHF) calculations. The truncated bases are tested for both LR- and RT-TDDFT as well as RT-TDHF approaches, and provide an acceleration up to an order of magnitude while the shifts of excitation energies of interest are generally within 0.2 eV. The procedure only requires one extra RT calculation with 1% of the total propagation time and a simple modification on basis set file, which allows an instant application in any quantum chemistry package supporting RT-/LR-TDDFT calculations. Aside from the reduced computational effort, this approach also offers valuable insight into the effect of different basis functions on computed electronic excitations and further ideas on the design of basis sets for special purposes.
Benchmarking commonly used software suites and analysis workflows for DIA proteomics and phosphoproteomics
Authors: Lou Ronghui , Cao Ye , Li Shanshan , Lang Xiaoyu , Li Yunxia , Zhang Yaoyang , Shui Wenqing 
Published: January 2023

AbstractA plethora of software suites and multiple classes of spectral libraries have been developed to enhance the depth and robustness of data-independent acquisition (DIA) data processing. However, how the combination of a DIA software tool and a spectral library impacts the outcome of DIA proteomics and phosphoproteomics data analysis has been rarely investigated using benchmark data that mimics biological complexity. In this study, we create DIA benchmark data sets simulating the regulation of thousands of proteins in a complex background, which are collected on both an Orbitrap and a timsTOF instruments. We evaluate four commonly used software suites (DIA-NN, Spectronaut, MaxDIA and Skyline) combined with seven different spectral libraries in global proteome analysis. Moreover, we assess their performances in analyzing phosphopeptide standards and TNF-α-induced phosphoproteome regulation. Our study provides a practical guidance on how to construct a robust data analysis pipeline for different proteomics studies implementing the DIA technique.
Inhibition of histone methyltransferase Smyd3 rescues NMDAR and cognitive deficits in a tauopathy mouse model
Authors: Williams Jamal B. , Cao Qing , Wang Wei , Lee Young-Ho , Qin Luye , Zhong Ping , Ren Yong , Ma Kaijie , Yan Zhen 
Published: January 2023

AbstractPleiotropic mechanisms have been implicated in Alzheimer’s disease (AD), including transcriptional dysregulation, protein misprocessing and synaptic dysfunction, but how they are mechanistically linked to induce cognitive deficits in AD is unclear. Here we find that the histone methyltransferase Smyd3, which catalyzes histone H3 lysine 4 trimethylation (H3K4me3) to activate gene transcription, is significantly elevated in prefrontal cortex (PFC) of AD patients and P301S Tau mice, a model of tauopathies. A short treatment with the Smyd3 inhibitor, BCI-121, rescues cognitive behavioral deficits, and restores synaptic NMDAR function and expression in PFC pyramidal neurons of P301S Tau mice. Fbxo2, which encodes an E3 ubiquitin ligase controlling the degradation of NMDAR subunits, is identified as a downstream target of Smyd3. Smyd3-induced upregulation of Fbxo2 in P301S Tau mice is linked to the increased NR1 ubiquitination. Fbxo2 knockdown in PFC leads to the recovery of NMDAR function and cognitive behaviors in P301S Tau mice. These data suggest an integrated mechanism and potential therapeutic strategy for AD.
Direct and indirect effects of the COVID-19 pandemic on mortality in Switzerland
Authors: Riou Julien , Hauser Anthony , Fesser Anna , Althaus Christian L. , Egger Matthias , Konstantinoudis Garyfallos 
Published: January 2023

AbstractThe direct and indirect impact of the COVID-19 pandemic on population-level mortality is of concern to public health but challenging to quantify. Using data for 2011–2019, we applied Bayesian models to predict the expected number of deaths in Switzerland and compared them with laboratory-confirmed COVID-19 deaths from February 2020 to April 2022 (study period). We estimated that COVID-19-related mortality was underestimated by a factor of 0.72 (95% credible interval [CrI]: 0.46–0.78). After accounting for COVID-19 deaths, the observed mortality was −4% (95% CrI: −8 to 0) lower than expected. The deficit in mortality was concentrated in age groups 40–59 (−12%, 95%CrI: −19 to −5) and 60–69 (−8%, 95%CrI: −15 to −2). Although COVID-19 control measures may have negative effects, after subtracting COVID-19 deaths, there were fewer deaths in Switzerland during the pandemic than expected, suggesting that any negative effects of control measures were offset by the positive effects. These results have important implications for the ongoing debate about the appropriateness of COVID-19 control measures.
A population-based matched cohort study of major congenital anomalies following COVID-19 vaccination and SARS-CoV-2 infection
Authors: Calvert Clara , Carruthers Jade , Denny Cheryl , Donaghy Jack , Hopcroft Lisa E. M. , Hopkins Leanne , Goulding Anna , Lindsay Laura , McLaughlin Terry , Moore Emily , Taylor Bob , Loane Maria , Dolk Helen , Morris Joan , Auyeung Bonnie , Bhaskaran Krishnan , Gibbons Cheryl L. , Katikireddi Srinivasa Vittal , O’Leary Maureen , McAllister David , Shi Ting , Simpson Colin R. , Robertson Chris , Sheikh Aziz , Stock Sarah J. , Wood Rachael 
Published: January 2023

AbstractEvidence on associations between COVID-19 vaccination or SARS-CoV-2 infection and the risk of congenital anomalies is limited. Here we report a national, population-based, matched cohort study using linked electronic health records from Scotland (May 2020-April 2022) to estimate the association between COVID-19 vaccination and, separately, SARS-CoV-2 infection between six weeks pre-conception and 19 weeks and six days gestation and the risk of [1] any major congenital anomaly and [2] any non-genetic major congenital anomaly. Mothers vaccinated in this pregnancy exposure period mostly received an mRNA vaccine (73.7% Pfizer-BioNTech BNT162b2 and 7.9% Moderna mRNA-1273). Of the 6731 babies whose mothers were vaccinated in the pregnancy exposure period, 153 had any anomaly and 120 had a non-genetic anomaly. Primary analyses find no association between any vaccination and any anomaly (adjusted Odds Ratio [aOR] = 1.01, 95% Confidence Interval [CI] = 0.83-1.24) or non-genetic anomalies (aOR = 1.00, 95% CI = 0.81-1.22). Primary analyses also find no association between SARS-CoV-2 infection and any anomaly (aOR = 1.02, 95% CI = 0.66-1.60) or non-genetic anomalies (aOR = 0.94, 95% CI = 0.57-1.54). Findings are robust to sensitivity analyses. These data provide reassurance on the safety of vaccination, in particular mRNA vaccines, just before or in early pregnancy.
Formation and degradation of strongly reducing cyanoarene-based radical anions towards efficient radical anion-mediated photoredox catalysis
Authors: Kwon Yonghwan , Lee Jungwook , Noh Yeonjin , Kim Doyon , Lee Yungyeong , Yu Changhoon , Roldao Juan Carlos , Feng Siyang , Gierschner Johannes , Wannemacher Reinhold , Kwon Min Sang 
Published: January 2023

AbstractCyanoarene-based photocatalysts (PCs) have attracted significant interest owing to their superior catalytic performance for radical anion mediated photoredox catalysis. However, the factors affecting the formation and degradation of cyanoarene-based PC radical anion (PC•‒) are still insufficiently understood. Herein, we therefore investigate the formation and degradation of cyanoarene-based PC•‒ under widely-used photoredox-mediated reaction conditions. By screening various cyanoarene-based PCs, we elucidate strategies to efficiently generate PC•‒ with adequate excited-state reduction potentials (Ered*) via supra-efficient generation of long-lived triplet excited states (T1). To thoroughly investigate the behavior of PC•‒ in actual photoredox-mediated reactions, a reductive dehalogenation is carried out as a model reaction and identified the dominant photodegradation pathways of the PC•‒. Dehalogenation and photodegradation of PC•‒ are coexistent depending on the rate of electron transfer (ET) to the substrate and the photodegradation strongly depends on the electronic and steric properties of the PCs. Based on the understanding of both the formation and photodegradation of PC•‒, we demonstrate that the efficient generation of highly reducing PC•‒ allows for the highly efficient photoredox catalyzed dehalogenation of aryl/alkyl halides at a PC loading as low as 0.001 mol% with a high oxygen tolerance. The present work provides new insights into the reactions of cyanoarene-based PC•‒ in photoredox-mediated reactions.
Wireless dielectrophoresis trapping and remote impedance sensing via resonant wireless power transfer
Authors: Ertsgaard Christopher T. , Kim Minki , Choi Jungwon , Oh Sang-Hyun 
Published: January 2023

AbstractNearly all biosensing platforms can be described using two fundamental steps—collection and detection. Target analytes must be delivered to a sensing element, which can then relay the transduced signal. For point-of-care technologies, where operation is to be kept simple, typically the collection step is passive diffusion driven—which can be slow or limiting under low concentrations. This work demonstrates an integration of both active collection and detection by using resonant wireless power transfer coupled to a nanogap capacitor. Nanoparticles suspended in deionized water are actively trapped using wireless dielectrophoresis and positioned within the most sensitive fringe field regions for wireless impedance-based detection. Trapping of 40 nm particles and larger is demonstrated using a 3.5 VRMS, 1 MHz radiofrequency signal delivered over a distance greater than 8 cm from the nanogap capacitor. Wireless trapping and release of 1 µm polystyrene beads is simultaneously detected in real-time over a distance of 2.5 cm from the nanogap capacitor. Herein, geometric scaling strategies coupled with optimal circuit design is presented to motivate combined collection and detection biosensing platforms amenable to wireless and/or smartphone operation.