bluuebunny/crossref_metadata_2025 huggingface dataset:
Doctoral clinical psychology student commentary on common myths about CBT: lessons learned for competency-based training
Authors: Dessert Ashton , Lynch Aadila , McMillon Ashley , Terrill Madeline , MacNeil Brad A.
Published: March 2023

Effective methods for training and education in the dissemination of evidence-based treatments is a priority. This commentary provides doctoral clinical psychology graduate student authors perspectives on common myths about cognitive behavioural therapy (CBT). Three myths were identified and considered: (1) CBT does not value the therapeutic relationship; (2) CBT is overly rigid; and (3) exposure techniques are cruel. Graduate students were engaged in a competency-based course in Cognitive Behavioural Approaches to Psychotherapy at an American Psychological Association (APA)-accredited doctoral clinical psychology program. The origins of common myths identified by graduate students included a lack of in-depth coverage of CBT and brief video segments provided during introductory courses, lived experience with CBT, and pre-determined views of manualized treatment and exposure techniques. Myth-addressing factors discussed by graduate students included holding space at the start of training for a discussion of attitudes about CBT, specific learning activities, and course content described in this commentary. Finally, self-reported changes in graduate students’ attitudes and behaviour following the course included a more favourable view of CBT as valuing the therapeutic relationship, as well as implementation of resources provided, and techniques learned and practised at practicum settings. Limitations and lessons learned are discussed through the lens of a model of adult learning that may be applied to future graduate training in evidence-based therapies like CBT.

Key learning aims

(1)

To understand common myths about cognitive behavioural therapy (CBT) that doctoral students in clinical psychology hold prior to entering a course in CBT.

(2)

To understand the possible origins of these myths, factors that may address their impacts, and changes in attitudes and behaviour among graduate students as a result.

(3)

To examine the lessons learned that can be applied to future training in evidence-based therapies like CBT.
Whose bread I eat, their song I sing? How the gender of MPs influences the use of oversight mechanisms in government and opposition
Authors: Kroeber Corinna , Krauss Svenja
Published: March 2023

This article is the first to show that gender shapes the degree to which legislators use formal mechanisms to oversee government activities. Extensive scholarly work has analysed the use of oversight instruments, especially regarding who monitors whom. Whether, how, and why the conformity of men and women with institutional roles differs, has not yet received scholarly attention. We hypothesise that women become more active than men in overseeing the executive when in opposition while reducing their monitoring activities even more strongly than men when in government because of different social roles ascribed to men and women as well as differences in risk aversity between sexes. We analyse panel data for three oversight tools from the GermanBundestagbetween 1949 and 2013 to test this proposition. Our findings imply that characteristics of political actors influence even a strongly institutionalised process as oversight and further clarify the gender bias in political representation.
Oral pyrroloquinoline quinone (PQQ) during pregnancy increases cardiomyocyte endowment in spontaneous IUGR guinea pigs
Authors: Mattern Jordan , Gemmell Andrew , Allen Paige E. , Mathers Katherine E. , Regnault Timothy R.H. , Stansfield Brian K.
Published: March 2023

Background:

Intrauterine growth restriction (IUGR) exerts a negative impact on developing cardiomyocytes and emerging evidence suggests activation of oxidative stress pathways plays a key role in this altered development. Here, we provided pregnant guinea pig sows with PQQ, an aromatic tricyclic o-quinone that functions as a redox cofactor antioxidant, during the last half of gestation as a potential antioxidant intervention for IUGR-associated cardiomyopathy.

Methods:

Pregnant guinea pig sows were randomly assigned to receive PQQ or placebo at mid gestation and fetuses were identified as spontaneous IUGR (spIUGR) or normal growth (NG) near term yielding four cohorts: NG ± PQQ and spIUGR ± PQQ. Cross sections of fetal left and right ventricles were prepared and cardiomyocyte number, collagen deposition, proliferation (Ki67) and apoptosis (TUNEL) were analyzed.

Results:

Cardiomyocyte endowment was reduced in spIUGR fetal hearts when compared to NG; however, PQQ exerted a positive effect on cardiomyocyte number in spIUGR hearts. Cardiomyocytes undergoing proliferation and apoptosis were more common in spIUGR ventricles when compared with NG animals, which was significantly reduced with PQQ supplementation. Similarly, collagen deposition was increased in spIUGR ventricles and was partially rescued in PQQ-treated spIUGR animals.

Conclusion:

The negative influence of spIUGR on cardiomyocyte number, apoptosis, and collagen deposition during parturition can be suppressed by antenatal administration of PQQ to pregnant sows. These data identify a novel therapeutic intervention for irreversible spIUGR-associated cardiomyopathy.
Observations of Dynamical Flux Ropes and Active Multiple X‐Line Reconnection at Earth's Magnetopause
Authors: Zhong Z. H. , Lei G. Y. , Zhou M. , Zhang M. , Tang R. X. , Graham D. B. , Pang Y. , Deng X. H. , Khotyaintsev Yu. V.
Published: March 2023

This paper presents the magnetospheric multiscale (MMS) observations of three flux ropes (FRs) sequentially in a reconnection exhaust at Earth's magnetopause. Three active X‐lines, which are responsible for the formation of these FRs, were also detected by MMS, providing strong evidence that the FRs were generated by multiple X‐line reconnection. We find that the core field inside the FRs considerably affects the Hall current in the adjacent X‐lines. The intense core field of the FRs deflected the electron outflow jet, forming the electron‐scale Hall magnetic field on the magnetosheath side. Additionally, an active secondary reconnection was observed at the center of one FR. This secondary reconnection split the FR into two smaller FRs and produced sharp density gradients and intense fluctuations of electric field and current within the FR. These observations advance the understanding of the formation and evolution of FRs during multiple X‐line reconnection at magnetopause.
Using Space‐Based CO2 and NO2 Observations to Estimate Urban CO2 Emissions
Authors: Yang Emily G. , Kort Eric A. , Ott Lesley E. , Oda Tomohiro , Lin John C.
Published: March 2023

As the majority of fossil fuel carbon dioxide (CO2) emissions originate from cities, the use of novel techniques to leverage available satellite observations of CO2 and proxy species to constrain urban CO2 is of great importance. In this study, we seek to empirically determine relationships between satellite observations of CO2 and the proxy species nitrogen dioxide (NO2), applying these relationships to NO2 fields to generate NO2‐derived CO2 fields (NDCFs) from which CO2 emissions can be estimated. We first establish this method using simulations of CO2 and NO2 for the cities of Buenos Aires, Melbourne, and Mexico City, finding that the method is viable throughout the year. For the same three cities, we next calculate empirical relationships (slopes) between co‐located observations of NO2 from the Tropospheric Monitoring Instrument and Snapshot Area Mode observations of CO2 from Orbiting Carbon Observatory‐3. Applying varying combinations of slopes to generate NDCFs, we evaluate methodological uncertainties for each slope application method and use a simple mass balance method to estimate CO2 emissions from NDCFs. We demonstrate monthly urban CO2 emissions estimates that are comparable to emissions inventory estimates. We additionally prove the utility of our method by demonstrating how large uncertainties at a grid cell level (equivalent to ∼1–3 ppm) can be reduced substantially when aggregating emissions estimates from NDCFs generated from all NO2 swaths (about 1%–6%). Rather than rely on prior knowledge of emission ratios, our method circumvents such assumptions and provides a valuable observational constraint on urban CO2 emissions.
Testing universality of Feynman-Tan relation in interacting Bose gases using high-order Bragg spectra
Authors: Wang Yunfei , Du Huiying , Li Yuqing , Mei Feng , Hu Ying , Xiao Liantuan , Ma Jie , Jia Suotang
Published: March 2023

The Feynman-Tan relation, obtained by combining the Feynman energy relation with the Tan’s two-body contact, can explain the excitation spectra of strongly interacting 39K Bose-Einstein condensate (BEC). Since the shift of excitation resonance in the Feynman-Tan relation is inversely proportional to atomic mass, the test of whether this relation is universal for other atomic systems is significant for describing the effect of interaction in strongly correlated Bose gases. Here we measure the high-momentum excitation spectra of 133Cs BEC with widely tunable interactions by using the second- and third-order Bragg spectra. We observe the backbending of frequency shift of excitation resonance with increasing interaction, and even the shift changes its sign under the strong interactions in the high-order Bragg spectra. Our finding shows good agreement with the prediction based on the Feynman-Tan relation. Our results provide significant insights for understanding the profound properties of strongly interacting Bose gases.
Supplementation with α-ketoglutarate improved the efficacy of anti-PD1 melanoma treatment through epigenetic modulation of PD-L1
Authors: Liu Nian , Zhang Jianglin , Yan Mingjie , Chen Lihui , Wu Jie , Tao Qian , Yan Bei , Chen Xiang , Peng Cong
Published: March 2023

Patients with advanced melanoma have shown an improved outlook after anti-PD1 therapy, but the low response rate restricts clinical benefit; therefore, enhancing anti-PD1 therapeutic efficacy remains a major challenge. Here, our findings showed a significantly increased abundance of α-KG in healthy controls, anti-PD1-sensitive melanoma-bearing mice, and anti-PD1-sensitive melanoma patients; moreover, supplementation with α-KG enhanced the efficacy of anti-PD1 immunotherapy and increased PD-L1 expression in melanoma tumors via STAT1/3. We also found that supplementation with α-KG significantly increased the activity of the methylcytosine dioxygenases TET2/3, which led to an increased 5-hydroxymethylcytosine (5-hmC) level in the PD-L1 promoter. As a consequence, STAT1/3 binding to the PD-L1 promoter was stabilized to upregulate PD-L1 expression. Importantly, single-cell sequencing of preclinical samples and analysis of clinical data revealed that TET2/3-STAT1/3-CD274 signaling was associated with sensitivity to anti-PD1 treatment in melanoma. Taken together, our results provide novel insight into α-KG’s function in anti-PD1 treatment of melanoma and suggest supplementation with α-KG as a novel promising strategy to improve the efficacy of anti-PD1 therapy.
Variant spectrum of PIEZO1 and KCNN4 in Japanese patients with dehydrated hereditary stomatocytosis
Authors: Nakahara Erina , Yamamoto Keiko Shimojima , Ogura Hiromi , Aoki Takako , Utsugisawa Taiju , Azuma Kenko , Akagawa Hiroyuki , Watanabe Kenichiro , Muraoka Michiko , Nakamura Fumihiko , Kamei Michi , Tatebayashi Koji , Shinozuka Jun , Yamane Takahisa , Hibino Makoto , Katsura Yoshiya , Nakano-Akamatsu Sonoko , Kadowaki Norimitsu , Maru Yoshiro , Ito Etsuro , Ohga Shouichi , Yagasaki Hiroshi , Morioka Ichiro , Yamamoto Toshiyuki , Kanno Hitoshi
Published: March 2023

Hereditary stomatocytosis (HSt) is a type of congenital hemolytic anemia caused by abnormally increased cation permeability of erythrocyte membranes. Dehydrated HSt (DHSt) is the most common subtype of HSt and is diagnosed based on clinical and laboratory findings related to erythrocytes. PIEZO1 and KCNN4 have been recognized as causative genes, and many related variants have been reported. We analyzed the genomic background of 23 patients from 20 Japanese families suspected of having DHSt using a target capture sequence and identified pathogenic/likely pathogenic variants of PIEZO1 or KCNN4 in 12 families.
Precise characterization of a corridor-shaped structure in Khufu’s Pyramid by observation of cosmic-ray muons
Authors: Procureur Sébastien , Morishima Kunihiro , Kuno Mitsuaki , Manabe Yuta , Kitagawa Nobuko , Nishio Akira , Gomez Hector , Attié David , Sakakibara Ami , Hikata Kotaro , Moto Masaki , Mandjavidze Irakli , Magnier Patrick , Lehuraux Marion , Benoit Théophile , Calvet Denis , Coppolani Xavier , Kebbiri Mariam , Mas Philippe , Helal Hany , Tayoubi Mehdi , Marini Benoit , Serikoff Nicolas , Anwar Hamada , Steiger Vincent , Takasaki Fumihiko , Fujii Hirofumi , Satoh Kotaro , Kodama Hideyo , Hayashi Kohei , Gable Pierre , Guerriero Emmanuel , Mouret Jean-Baptiste , Elnady Tamer , Elshayeb Yasser , Elkarmoty Mohamed
Published: March 2023

Khufu’s Pyramid is one of the largest archaeological monument all over the world, which still holds many mysteries. In 2016 and 2017, the ScanPyramids team reported on several discoveries of previously unknown voids by cosmic-ray muon radiography that is a non-destructive technique ideal for the investigation of large-scale structures. Among these discoveries, a corridor-shaped structure has been observed behind the so-called Chevron zone on the North face, with a length of at least 5 meters. A dedicated study of this structure was thus necessary to better understand its function in relation with the enigmatic architectural role of this Chevron. Here we report on new measurements of excellent sensitivity obtained with nuclear emulsion films from Nagoya University and gaseous detectors from CEA, revealing a structure of about 9 m length with a transverse section of about 2.0 m by 2.0 m.
Maternal SARS-CoV-2 vaccination and infant protection against SARS-CoV-2 during the first six months of life
Authors: Zerbo Ousseny , Ray G. Thomas , Fireman Bruce , Layefsky Evan , Goddard Kristin , Lewis Edwin , Ross Pat , Omer Saad , Greenberg Mara , Klein Nicola P.
Published: March 2023

We examined the effectiveness of maternal vaccination against SARS-CoV-2 infection in 30,311 infants born at Kaiser Permanente Northern California from December 15, 2020, to May 31, 2022. Using Cox regression, the effectiveness of ≥2 doses of COVID-19 vaccine received during pregnancy was 84% (95% confidence interval [CI]: 66, 93), 62% (CI: 39, 77) and 56% (CI: 34,71) during months 0–2, 0–4 and 0- 6 of a child’s life, respectively, in the Delta variant period. In the Omicron variant period, the effectiveness of maternal vaccination in these three age intervals was 21% (CI: −21,48), 14% (CI: −9,32) and 13% (CI: −3,26), respectively. Over the entire study period, the incidence of hospitalization for COVID-19 was lower during the first 6 months of life among infants of vaccinated mothers compared with infants of unvaccinated mothers (21/100,000 person-years vs. 100/100,000 person-years). Maternal vaccination was protective, but protection was lower during Omicron than during Delta. Protection during both periods decreased as infants aged.
Structural features discriminating hybrid histidine kinase Rec domains from response regulator homologs
Authors: Brüderlin Mitchell , Böhm Raphael , Fadel Firas , Hiller Sebastian , Schirmer Tilman , Dubey Badri N.
Published: March 2023

In two-component systems, the information gathered by histidine kinases (HKs) are relayed to cognate response regulators (RRs). Thereby, the phosphoryl group of the auto-phosphorylated HK is transferred to the receiver (Rec) domain of the RR to allosterically activate its effector domain. In contrast, multi-step phosphorelays comprise at least one additional Rec (Recinter) domain that is typically part of the HK and acts as an intermediary for phosphoryl-shuttling. While RR Rec domains have been studied extensively, little is known about discriminating features of Recinter domains. Here we study the Recinter domain of the hybrid HK CckA by X-ray crystallography and NMR spectroscopy. Strikingly, all active site residues of the canonical Rec-fold are pre-arranged for phosphoryl-binding and BeF3- binding does not alter secondary or quaternary structure, indicating the absence of allosteric changes, the hallmark of RRs. Based on sequence-covariation and modeling, we analyze the intra-molecular DHp/Rec association in hybrid HKs.
Expectation violations enhance neuronal encoding of sensory information in mouse primary visual cortex
Authors: Tang Matthew F. , Kheradpezhouh Ehsan , Lee Conrad C. Y. , Dickinson J. Edwin , Mattingley Jason B. , Arabzadeh Ehsan
Published: March 2023

The response of cortical neurons to sensory stimuli is shaped both by past events (adaptation) and the expectation of future events (prediction). Here we employed a visual stimulus paradigm with different levels of predictability to characterise how expectation influences orientation selectivity in the primary visual cortex (V1) of male mice. We recorded neuronal activity using two-photon calcium imaging (GCaMP6f) while animals viewed sequences of grating stimuli which either varied randomly in their orientations or rotated predictably with occasional transitions to an unexpected orientation. For single neurons and the population, there was significant enhancement in the gain of orientation-selective responses to unexpected gratings. This gain-enhancement for unexpected stimuli was prominent in both awake and anaesthetised mice. We implemented a computational model to demonstrate how trial-to-trial variability in neuronal responses were best characterised when adaptation and expectation effects were combined.
Fine mapping spatiotemporal mechanisms of genetic variants underlying cardiac traits and disease
Authors: D’Antonio Matteo , Nguyen Jennifer P. , Arthur Timothy D. ,   iPSCORE Consortium, Arias Angelo D. , Arthur Timothy D. , Benaglio Paola , Berggren W. Travis , Borja Victor , Belmonte Juan Carlos Izpisua , Cook Megan , D’Antonio Matteo , DeBoever Christopher , Diffenderfer Kenneth E. , Donovan Margaret K. R. , Farnam KathyJean , Frazer Kelly A. , Fujita Kyohei , Garcia Melvin , Harismendy Olivier , Henson Benjamin A. , Jakubosky David , Jepsen Kristen , Li He , Matsui Hiroko , Nariai Naoki , Nguyen Jennifer P. , O’Connor Daniel T. , Okubo Jonathan , Panopoulos Athanasia D. , Rao Fengwen , Reyna Joaquin , Salgado Bianca , Smith Erin N. , Sohmer Josh , Yost Shawn , Young Greenwald William W. , Matsui Hiroko , D’Antonio-Chronowska Agnieszka , Frazer Kelly A.
Published: March 2023

The causal variants and genes underlying thousands of cardiac GWAS signals have yet to be identified. Here, we leverage spatiotemporal information on 966 RNA-seq cardiac samples and perform an expression quantitative trait locus (eQTL) analysis detecting eQTLs considering both eGenes and eIsoforms. We identify 2,578 eQTLs associated with a specific developmental stage-, tissue- and/or cell type. Colocalization between eQTL and GWAS signals of five cardiac traits identified variants with high posterior probabilities for being causal in 210 GWAS loci. Pulse pressure GWAS loci are enriched for colocalization with fetal- and smooth muscle- eQTLs; pulse rate with adult- and cardiac muscle- eQTLs; and atrial fibrillation with cardiac muscle- eQTLs. Fine mapping identifies 79 credible sets with five or fewer SNPs, of which 15 were associated with spatiotemporal eQTLs. Our study shows that many cardiac GWAS variants impact traits and disease in a developmental stage-, tissue- and/or cell type-specific fashion.
A covalent BTK ternary complex compatible with targeted protein degradation
Authors: Schiemer James , Maxwell Andrew , Horst Reto , Liu Shenping , Uccello Daniel P. , Borzilleri Kris , Rajamohan Nisha , Brown Matthew F. , Calabrese Matthew F.
Published: March 2023

Targeted protein degradation using heterobifunctional chimeras holds the potential to expand target space and grow the druggable proteome. Most acutely, this provides an opportunity to target proteins that lack enzymatic activity or have otherwise proven intractable to small molecule inhibition. Limiting this potential, however, is the remaining need to develop a ligand for the target of interest. While a number of challenging proteins have been successfully targeted by covalent ligands, unless this modification affects form or function, it may lack the ability to drive a biological response. Bridging covalent ligand discovery with chimeric degrader design has emerged as a potential mechanism to advance both fields. In this work, we employ a set of biochemical and cellular tools to deconvolute the role of covalent modification in targeted protein degradation using Bruton’s tyrosine kinase. Our results reveal that covalent target modification is fundamentally compatible with the protein degrader mechanism of action.
Membrane-localized expression, production and assembly of Vibrio parahaemolyticus T3SS2 provides evidence for transertion
Authors: Kaval Karan Gautam , Chimalapati Suneeta , Siegel Sara D. , Garcia Nalleli , Jaishankar Jananee , Dalia Ankur B. , Orth Kim
Published: March 2023

It has been proposed that bacterial membrane proteins may be synthesized and inserted into the membrane by a process known as transertion, which involves membrane association of their encoding genes, followed by coupled transcription, translation and membrane insertion. Here, we provide evidence supporting that the pathogen Vibrio parahaemolyticus uses transertion to assemble its type III secretion system (T3SS2), to inject virulence factors into host cells. We propose a two-step transertion process where the membrane-bound co-component receptor (VtrA/VtrC) is first activated by bile acids, leading to membrane association and expression of its target gene, vtrB, located in the T3SS2 pathogenicity island. VtrB, the transmembrane transcriptional activator of T3SS2, then induces the localized expression and membrane assembly of the T3SS2 structural components and its effectors. We hypothesize that the proposed transertion process may be used by other enteric bacteria for efficient assembly of membrane-bound molecular complexes in response to extracellular signals.
Viscoelastic coarsening of quasi-2D foam
Authors: Guidolin Chiara , Mac Intyre Jonatan , Rio Emmanuelle , Puisto Antti , Salonen Anniina
Published: March 2023

Foams are unstable jammed materials. They evolve over timescales comparable to their “time of use", which makes the study of their destabilisation mechanisms crucial for applications. In practice, many foams are made from viscoelastic fluids, which are observed to prolong their lifetimes. Despite their importance, we lack understanding of the coarsening mechanism in such systems. We probe the effect of continuous phase viscoelasticity on foam coarsening with foamed emulsions. We show that bubble size evolution is strongly slowed down and foam structure hugely impacted. The main mechanisms responsible are the absence of continuous phase redistribution and a non-trivial link between foam structure and mechanical properties. These combine to give spatially heterogeneous coarsening. Beyond their importance in the design of foamy materials, the results give a macroscopic vision of phase separation in a viscoelastic medium.
Turning dead leaves into an active multifunctional material as evaporator, photocatalyst, and bioplastic
Authors: Fang Siyuan , Lyu Xingyi , Tong Tian , Lim Aniqa Ibnat , Li Tao , Bao Jiming , Hu Yun Hang
Published: March 2023

Large numbers of leaves fall on the earth each autumn. The current treatments of dead leaves mainly involve completely destroying the biocomponents, which causes considerable energy consumption and environmental issues. It remains a challenge to convert waste leaves into useful materials without breaking down their biocomponents. Here, we turn red maple dead leaves into an active three-component multifunctional material by exploiting the role of whewellite biomineral for binding lignin and cellulose. Owing to its intense optical absorption spanning the full solar spectrum and the heterogeneous architecture for effective charge separation, films of this material show high performance in solar water evaporation, photocatalytic hydrogen production, and photocatalytic degradation of antibiotics. Furthermore, it also acts as a bioplastic with high mechanical strength, high-temperature tolerance, and biodegradable features. These findings pave the way for the efficient utilization of waste biomass and innovations of advanced materials.
Ligand-specific changes in conformational flexibility mediate long-range allostery in the lac repressor
Authors: Glasgow Anum , Hobbs Helen T. , Perry Zion R. , Wells Malcolm L. , Marqusee Susan , Kortemme Tanja
Published: March 2023

Biological regulation ubiquitously depends on protein allostery, but the regulatory mechanisms are incompletely understood, especially in proteins that undergo ligand-induced allostery with few structural changes. Here we used hydrogen-deuterium exchange with mass spectrometry (HDX/MS) to map allosteric effects in a paradigm ligand-responsive transcription factor, the lac repressor (LacI), in different functional states (apo, or bound to inducer, anti-inducer, and/or DNA). Although X-ray crystal structures of the LacI core domain in these states are nearly indistinguishable, HDX/MS experiments reveal widespread differences in flexibility. We integrate these results with modeling of protein-ligand-solvent interactions to propose a revised model for allostery in LacI, where ligand binding allosterically shifts the conformational ensemble as a result of distinct changes in the rigidity of secondary structures in the different states. Our model provides a mechanistic basis for the altered function of distal mutations. More generally, our approach provides a platform for characterizing and engineering protein allostery.
Inferring neuron-neuron communications from single-cell transcriptomics through NeuronChat
Authors: Zhao Wei , Johnston Kevin G. , Ren Honglei , Xu Xiangmin , Nie Qing
Published: March 2023

Neural communication networks form the fundamental basis for brain function. These communication networks are enabled by emitted ligands such as neurotransmitters, which activate receptor complexes to facilitate communication. Thus, neural communication is fundamentally dependent on the transcriptome. Here we develop NeuronChat, a method and package for the inference, visualization and analysis of neural-specific communication networks among pre-defined cell groups using single-cell expression data. We incorporate a manually curated molecular interaction database of neural signaling for both human and mouse, and benchmark NeuronChat on several published datasets to validate its ability in predicting neural connectivity. Then, we apply NeuronChat to three different neural tissue datasets to illustrate its functionalities in identifying interneural communication networks, revealing conserved or context-specific interactions across different biological contexts, and predicting communication pattern changes in diseased brains with autism spectrum disorder. Finally, we demonstrate NeuronChat can utilize spatial transcriptomics data to infer and visualize neural-specific cell-cell communication.
N6-methyladenosine of Spi2a attenuates inflammation and sepsis-associated myocardial dysfunction in mice
Authors: Wang Xiangyu , Ding Yan , Li Ran , Zhang Rujun , Ge Xuejun , Gao Ruifang , Wang Miao , Huang Yubing , Zhang Fang , Zhao Bin , Liao Wang , Du Jie
Published: March 2023

Bacteria-triggered sepsis is characterized by systemic, uncontrolled inflammation in affected individuals. Controlling the excessive production of pro-inflammatory cytokines and subsequent organ dysfunction in sepsis remains challenging. Here, we demonstrate that Spi2a upregulation in lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages reduces the production of pro-inflammatory cytokines and myocardial impairment. In addition, exposure to LPS upregulates the lysine acetyltransferase, KAT2B, to promote METTL14 protein stability through acetylation at K398, leading to the increased m6A methylation of Spi2a in macrophages. m6A-methylated Spi2a directly binds to IKKβ to impair IKK complex formation and inactivate the NF-κB pathway. The loss of m6A methylation in macrophages aggravates cytokine production and myocardial damage in mice under septic conditions, whereas forced expression of Spi2a reverses this phenotype. In septic patients, the mRNA expression levels of the human orthologue SERPINA3 negatively correlates with those of the cytokines, TNF, IL-6, IL-1β and IFNγ. Altogether, these findings suggest that m6A methylation of Spi2a negatively regulates macrophage activation in the context of sepsis.
rRNA methylation by Spb1 regulates the GTPase activity of Nog2 during 60S ribosomal subunit assembly
Authors: Sekulski Kamil , Cruz Victor Emmanuel , Weirich Christine S. , Erzberger Jan P.
Published: March 2023

Biogenesis of the large ribosomal (60S) subunit involves the assembly of three rRNAs and 46 proteins, a process requiring approximately 70 ribosome biogenesis factors (RBFs) that bind and release the pre-60S at specific steps along the assembly pathway. The methyltransferase Spb1 and the K-loop GTPase Nog2 are essential RBFs that engage the rRNA A-loop during sequential steps in 60S maturation. Spb1 methylates the A-loop nucleotide G2922 and a catalytically deficient mutant strain (spb1D52A) has a severe 60S biogenesis defect. However, the assembly function of this modification is currently unknown. Here, we present cryo-EM reconstructions that reveal that unmethylated G2922 leads to the premature activation of Nog2 GTPase activity and capture a Nog2-GDP-AlF4− transition state structure that implicates the direct involvement of unmodified G2922 in Nog2 GTPase activation. Genetic suppressors and in vivo imaging indicate that premature GTP hydrolysis prevents the efficient binding of Nog2 to early nucleoplasmic 60S intermediates. We propose that G2922 methylation levels regulate Nog2 recruitment to the pre-60S near the nucleolar/nucleoplasmic phase boundary, forming a kinetic checkpoint to regulate 60S production. Our approach and findings provide a template to study the GTPase cycles and regulatory factor interactions of the other K-loop GTPases involved in ribosome assembly.
Wearable perovskite solar cells by aligned liquid crystal elastomers
Authors: Huang Zengqi , Li Lin , Wu Tingqing , Xue Tangyue , Sun Wei , Pan Qi , Wang Huadong , Xie Hongfei , Chi Jimei , Han Teng , Hu Xiaotian , Su Meng , Chen Yiwang , Song Yanlin
Published: March 2023

In a flexible perovskite solar cell, the bottom interface between perovskite and the electron-transporting layer is critical in determining its efficiency and reliability. High defect concentrations and crystalline film fracturing at the bottom interface substantially reduce the efficiency and operational stability. In this work, a liquid crystal elastomer interlayer is intercalated into a flexible device with the charge transfer channel toughened by the aligned mesogenic assembly. The molecular ordering is instantly locked upon photopolymerization of liquid crystalline diacrylate monomers and dithiol-terminated oligomers. The optimized charge collection and the minimized charge recombination at the interface boost the efficiency up to 23.26% and 22.10% for rigid and flexible devices, respectively. The liquid crystal elastomer-induced suppression of phase segregation endows the unencapsulated device maintaining >80% of the initial efficiency for 1570 h. Moreover, the aligned elastomer interlayer preserves the configuration integrity with remarkable repeatability and mechanical robustness, which enables the flexible device to retain 86% of its original efficiency after 5000 bending cycles. The flexible solar cell chips are further integrated into a wearable haptic device with microneedle-based arrays of sensors to demonstrate a pain sensation system in virtual reality.
TGFβ-mediated MMP13 secretion drives myoepithelial cell dependent breast cancer progression
Authors: Gibson Shayin V. , Tomas Bort Elena , Rodríguez-Fernández Lucía , Allen Michael D. , Gomm Jennifer J. , Goulding Iain , auf dem Keller Ulrich , Agnoletto Andrea , Brisken Cathrin , Peck Barrie , Cameron Angus J. , Marshall John F. , Jones J. Louise , Carter Edward P. , Grose Richard P.
Published: March 2023

Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer. Virtually all women with DCIS are treated, despite evidence suggesting up to half would remain with stable, non-threatening, disease. Overtreatment thus presents a pressing issue in DCIS management. To understand the role of the normally tumour suppressive myoepithelial cell in disease progression we present a 3D in vitro model incorporating both luminal and myoepithelial cells in physiomimetic conditions. We demonstrate that DCIS-associated myoepithelial cells promote striking myoepithelial-led invasion of luminal cells, mediated by the collagenase MMP13 through a non-canonical TGFβ – EP300 pathway. In vivo, MMP13 expression is associated with stromal invasion in a murine model of DCIS progression and is elevated in myoepithelial cells of clinical high-grade DCIS cases. Our data identify a key role for myoepithelial-derived MMP13 in facilitating DCIS progression and point the way towards a robust marker for risk stratification in DCIS patients.
LRRK2 and GBA1 variant carriers have higher urinary bis(monacylglycerol) phosphate concentrations in PPMI cohorts
Authors: Merchant Kalpana M. , Simuni Tanya , Fedler Janel , Caspell-Garcia Chelsea , Brumm Michael , Nudelman Kelly N. H. , Tengstrandt Elizabeth , Hsieh Frank , Alcalay Roy N. , Coffey Christopher , Chahine Lana , Foroud Tatiana , Singleton Andrew , Weintraub Daniel , Hutten Samantha , Sherer Todd , Mollenhauer Brit , Siderowf Andrew , Tanner Caroline , Marek Ken ,   the Parkinson’s Progression Markers Initiative
Published: March 2023

We quantified concentrations of three isoforms of the endolysosomal lipid, bis(monoacylglycerol) phosphate (BMP) in the urine of deeply phenotyped cohorts in the Parkinson’s Progression Markers Initiative: LRRK2 G2019S PD (N = 134) and non-manifesting carriers (NMC) (G2019S+ NMC; N = 182), LRRK2 R1441G PD (N = 15) and R1441G+ NMC (N = 15), GBA1 N409S PD (N = 76) and N409S+ NMC (N = 178), sporadic PD (sPD, N = 379) and healthy controls (HC) (N = 190). The effects of each mutation and disease status were analyzed using nonparametric methods. Longitudinal changes in BMP levels were analyzed using linear mixed models. At baseline, all LRRK2 carriers had 3–7× higher BMP levels compared to HC, irrespective of the disease status. GBA1 N409S carriers also showed significant, albeit smaller, elevation (~30–40%) in BMP levels compared to HC. In LRRK2 G2019S PD, urinary BMP levels remained stable over two years. Furthermore, baseline BMP levels did not predict disease progression as measured by striatal DaT imaging, MDS-UPDRS III Off, or MoCA in any of the cohorts. These data support the utility of BMP as a target modulation biomarker in therapeutic trials of genetic and sPD but not as a prognostic or disease progression biomarker.
Glycolysis-enhancing α1-adrenergic antagonists modify cognitive symptoms related to Parkinson’s disease
Authors: Weber Matthew A. , Sivakumar Kartik , Tabakovic Ervina E. , Oya Mayu , Aldridge Georgina M. , Zhang Qiang , Simmering Jacob E. , Narayanan Nandakumar S.
Published: March 2023

Terazosin is an α1-adrenergic receptor antagonist that enhances glycolysis and increases cellular ATP by binding to the enzyme phosphoglycerate kinase 1 (PGK1). Recent work has shown that terazosin is protective against motor dysfunction in rodent models of Parkinson’s disease (PD) and is associated with slowed motor symptom progression in PD patients. However, PD is also characterized by profound cognitive symptoms. We tested the hypothesis that terazosin protects against cognitive symptoms associated with PD. We report two main results. First, in rodents with ventral tegmental area (VTA) dopamine depletion modeling aspects of PD-related cognitive dysfunction, we found that terazosin preserved cognitive function. Second, we found that after matching for demographics, comorbidities, and disease duration, PD patients newly started on terazosin, alfuzosin, or doxazosin had a lower hazard of being diagnosed with dementia compared to tamsulosin, an α1-adrenergic receptor antagonist that does not enhance glycolysis. Together, these findings suggest that in addition to slowing motor symptom progression, glycolysis-enhancing drugs protect against cognitive symptoms of PD.
Romanian young adult perceptions on using heated tobacco products following exposure to direct marketing methods
Authors: Chirila Sergiu , Antohe Adriana , Isar Cristina , Panaitescu Catalina , Malpass Alice
Published: March 2023

Heated tobacco products have a rapid uptake, especially among young people, mostly where advertising is unregulated, as is the case in Romania. This qualitative study explores the influence of direct marketing methods of heated tobacco products on young people, their perception and behaviour towards smoking. We have carried out 19 interviews with smokers of heated tobacco products (HTPs) or/and combustible cigarettes (CCs) or non-smokers (NS), aged 18–26. Using the thematic analysis, we have identified three overarching themes: (1) people, places, and subjects of marketing, (2) engagement with risk narratives and (3) social body, family bonds, and autonomous self. Even if most of the participants have been exposed to a mix of marketing methods, they did not acknowledge the influence that marketing has on their decision to experience smoking. Young adults’ decision to use heated tobacco products seems to be influenced by a cluster of reasons: overcoming the legislation gap which prohibits indoor use of combustible cigarettes but not heated tobacco products; the attractivity of the product (novelty, inviting appearance, technological appeal and price) and presumed less damaging effects on health.
Experimental metrology beyond the standard quantum limit for a wide resources range
Authors: Cimini Valeria , Polino Emanuele , Belliardo Federico , Hoch Francesco , Piccirillo Bruno , Spagnolo Nicolò , Giovannetti Vittorio , Sciarrino Fabio
Published: March 2023

Adopting quantum resources for parameter estimation discloses the possibility to realize quantum sensors operating at a sensitivity beyond the standard quantum limit. Such an approach promises to reach the fundamental Heisenberg scaling as a function of the employed resources N in the estimation process. Although previous experiments demonstrated precision scaling approaching Heisenberg-limited performances, reaching such a regime for a wide range of N remains hard to accomplish. Here, we show a method that suitably allocates the available resources permitting them to reach the same power law of Heisenberg scaling without any prior information on the parameter. We demonstrate experimentally such an advantage in measuring a rotation angle. We quantitatively verify sub-standard quantum limit performances for a considerable range of N (O(30,000)) by using single-photon states with high-order orbital angular momentum, achieving an error reduction, in terms of the obtained variance, >10 dB below the standard quantum limit. Such results can be applied to different scenarios, opening the way to the optimization of resources in quantum sensing.
Enhanced star formation through the high-temperature formation of H2 on carbonaceous dust grains
Authors: Grieco Francesco , Theulé Patrice , De Looze Ilse , Dulieu François
Published: March 2023

The microphysics of molecular hydrogen formation has an influence on galactic-scale star-formation rates over cosmic time. H2 is the cooling agent needed to initiate the cloud collapse regulating the star-formation efficiency. H2 formation is inefficient in the gas phase under typical interstellar conditions, requiring dust grain surfaces to act as catalysts. Small carbonaceous grains with sizes from roughly 4 to 100–200 Å, including polycyclic aromatic hydrocarbons (PAHs), have been shown to increase the H2 formation rates due to their large surface-to-volume ratios. H2 formation rates on PAHs were previously thought to reduce above temperatures of 50 K and H atom recombination was believed to be highly efficient only below 20 K. Until now, both laboratory experiments and theoretical modelling have suggested that H2 cannot form on grains with temperatures above 100 K. Here we report evidence, through direct laboratory measurements, of the highly efficient formation of H2 at temperatures up to 250 K on carbonaceous surfaces mimicking interstellar dust. By pushing their formation towards warmer temperatures, the H2 molecules could start contributing substantially to the cooling of warmer gas (temperatures of roughly 50–250 K). This will have a marked impact on our understanding of H2 formation in nearby galaxies and its efficiency in high-redshift galaxies where the Cosmic Microwave Background already pushes dust temperatures to more than 20 K.
The impact of satellite trails on Hubble Space Telescope observations
Authors: Kruk Sandor , García-Martín Pablo , Popescu Marcel , Aussel Ben , Dillmann Steven , Perks Megan E. , Lund Tamina , Merín Bruno , Thomson Ross , Karadag Samet , McCaughrean Mark J.
Published: March 2023

The recent launch of low Earth orbit satellite constellations is creating a growing threat for astronomical observations with ground-based telescopes1–10 that has alarmed the astronomical community 11–16. Observations affected by artificial satellites can become unusable for scientific research, wasting a growing fraction of the research budget on costly infrastructures and mitigation efforts. Here we report the first measurements, to our knowledge, of artificial satellite contamination on observations from a low Earth orbit made with the Hubble Space Telescope. With the help of volunteers on a citizen science project (www.asteroidhunter.org) and a deep learning algorithm, we scanned the archive of Hubble Space Telescope images taken between 2002 and 2021. We find that a fraction of 2.7% of the individual exposures with a typical exposure time of 11 minutes are crossed by satellites and that the fraction of satellite trails in the images increases with time. This fraction depends on the size of the field of view, exposure time, filter used and pointing. With the growing number of artificial satellites currently planned, the fraction of Hubble Space Telescope images crossed by satellites will increase in the next decade and will need further close study and monitoring.
Pangenomic analysis identifies structural variation associated with heat tolerance in pearl millet
Authors: Yan Haidong , Sun Min , Zhang Zhongren , Jin Yarong , Zhang Ailing , Lin Chuang , Wu Bingchao , He Min , Xu Bin , Wang Jing , Qin Peng , Mendieta John Pablo , Nie Gang , Wang Jianping , Jones Chris S. , Feng Guangyan , Srivastava Rakesh K. , Zhang Xinquan , Bombarely Aureliano , Luo Dan , Jin Long , Peng Yuanying , Wang Xiaoshan , Ji Yang , Tian Shilin , Huang Linkai
Published: March 2023

Pearl millet is an important cereal crop worldwide and shows superior heat tolerance. Here, we developed a graph-based pan-genome by assembling ten chromosomal genomes with one existing assembly adapted to different climates worldwide and captured 424,085 genomic structural variations (SVs). Comparative genomics and transcriptomics analyses revealed the expansion of the RWP-RK transcription factor family and the involvement of endoplasmic reticulum (ER)-related genes in heat tolerance. The overexpression of one RWP-RK gene led to enhanced plant heat tolerance and transactivated ER-related genes quickly, supporting the important roles of RWP-RK transcription factors and ER system in heat tolerance. Furthermore, we found that some SVs affected the gene expression associated with heat tolerance and SVs surrounding ER-related genes shaped adaptation to heat tolerance during domestication in the population. Our study provides a comprehensive genomic resource revealing insights into heat tolerance and laying a foundation for generating more robust crops under the changing climate.
Transcription of MERVL retrotransposons is required for preimplantation embryo development
Authors: Sakashita Akihiko , Kitano Tomohiro , Ishizu Hirotsugu , Guo Youjia , Masuda Harumi , Ariura Masaru , Murano Kensaku , Siomi Haruhiko
Published: March 2023

Zygotic genome activation (ZGA) is a critical postfertilization step that promotes totipotency and allows different cell fates to emerge in the developing embryo. MERVL (murine endogenous retrovirus-L) is transiently upregulated at the two-cell stage during ZGA. Although MERVL expression is widely used as a marker of totipotency, the role of this retrotransposon in mouse embryogenesis remains elusive. Here, we show that full-length MERVL transcripts, but not encoded retroviral proteins, are essential for accurate regulation of the host transcriptome and chromatin state during preimplantation development. Both knockdown and CRISPRi-based repression of MERVL result in embryonic lethality due to defects in differentiation and genomic stability. Furthermore, transcriptome and epigenome analysis revealed that loss of MERVL transcripts led to retention of an accessible chromatin state at, and aberrant expression of, a subset of two-cell-specific genes. Taken together, our results suggest a model in which an endogenous retrovirus plays a key role in regulating host cell fate potential.
The Three Terms Task - an open benchmark to compare human and artificial semantic representations
Authors: Borghesani V. , Armoza J. , Hebart M. N. , Bellec P. , Brambati S. M.
Published: March 2023

Word processing entails retrieval of a unitary yet multidimensional semantic representation (e.g.,a lemon’s colour, flavour, possible use) and has been investigated in both cognitive neuroscience and artificial intelligence. To enable the direct comparison of human and artificial semantic representations, and to support the use of natural language processing (NLP) for computational modelling of human understanding, a critical challenge is the development of benchmarks of appropriate size and complexity. Here we present a dataset probing semantic knowledge with a three-terms semantic associative task: which of two target words is more closely associated with a given anchor (e.g.,is lemon closer to squeezer or sour?). The dataset includes both abstract and concrete nouns for a total of 10,107 triplets. For the 2,255 triplets with varying levels of agreement among NLP word embeddings, we additionally collected behavioural similarity judgments from 1,322 human raters. We hope that this openly available, large-scale dataset will be a useful benchmark for both computational and neuroscientific investigations of semantic knowledge.