bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carbonized polymer dots enhanced stability and flexibility of quasi-2D perovskite photodetector
Authors: Tan Mingrui , Li Mingbian , Pan Wanting , Feng Xiaopeng , He Yuhong , Liu Junjun , Dong Fengxia , Wei Haotong , Yang Bai 
Published: October 2022

AbstractQuasi-2D perovskites have been demonstrated to be competitive materials in the photodetection fields due to the enhanced moisture stability by large organic cations. However, as the increasing demands of modern technology, it is still challenging to combine the flexibility with the capability of weak light detection in a low-cost way. Here, amides, carboxylic acids, and anhydrides groups-rich carbonized polymer dots (CPDs) were employed to fill in the perovskite grain boundaries, which can passivate the point defects of perovskite by coordinating with the unbonded Pb atoms, and reduce the leakage current. Weak light detection capability was demonstrated by directly resolving light with an intensity of 10.1 pW cm−2. More importantly, the stretchable polymer chains on CPDs strongly interact with perovskite ions through multiple supramolecular interactions, and extend the stretchable properties to the perovskite/CPDs composites, which can maintain the integral structure stability during the deformation of perovskite crystals and restricted any crack by releasing the film strain. Our fabricated devices show extraordinary flexible stability in the bending-dependent response tests. The viscoelasticity of CPDs improves the bending stability of the flexible quasi-2D perovskite photodetectors, and device performance shows no degradation after bending 10000 times, comparable or even outperforming the dominating flexible photodetectors.
Fyn nanoclustering requires switching to an open conformation and is enhanced by FTLD-Tau biomolecular condensates
Authors: Martínez-Mármol Ramón , Small Christopher , Jiang Anmin , Palliyaguru Tishila , Wallis Tristan P. , Gormal Rachel S. , Sibarita Jean-Baptiste , Götz Jürgen , Meunier Frédéric A. 
Published: October 2022

AbstractFyn is a Src kinase that controls critical signalling cascades and has been implicated in learning and memory. Postsynaptic enrichment of Fyn underpins synaptotoxicity in dementias such as Alzheimer’s disease and frontotemporal lobar degeneration with Tau pathology (FTLD-Tau). The FLTD P301L mutant Tau is associated with a higher propensity to undergo liquid–liquid phase separation (LLPS) and form biomolecular condensates. Expression of P301L mutant Tau promotes aberrant trapping of Fyn in nanoclusters within hippocampal dendrites by an unknown mechanism. Here, we used single-particle tracking photoactivated localisation microscopy to demonstrate that the opening of Fyn into its primed conformation promotes its nanoclustering in dendrites leading to increased Fyn/ERK/S6 downstream signalling. Preventing the auto-inhibitory closed conformation of Fyn through phospho-inhibition or through perturbation of its SH3 domain increased Fyn’s nanoscale trapping, whereas inhibition of the catalytic domain had no impact. By combining pharmacological and genetic approaches, we demonstrate that P301L Tau enhanced both Fyn nanoclustering and Fyn/ERK/S6 signalling via its ability to form biomolecular condensates. Together, our findings demonstrate that Fyn alternates between a closed and an open conformation, the latter being enzymatically active and clustered. Furthermore, pathogenic immobilisation of Fyn relies on the ability of P301L Tau to form biomolecular condensates, thus highlighting the critical importance of LLPS in controlling nanoclustering and downstream intracellular signalling events.
A one-year follow-up study of treatment-compliant suicide attempt survivors: relationship of CYP2D6-CYP2C19 and polypharmacy with suicide reattempts
Authors: Peñas-Lledó Eva M. , Guillaume Sebastien , de Andrés Fernando , Cortés-Martínez Ana , Dubois Jonathan , Kahn Jean Pierre , Leboyer Marion , Olié Emilie , LLerena Adrián , Courtet Philippe 
Published: October 2022

AbstractThis study of a cohort of 1-year treatment-compliant survivors of a suicide attempt examined for the first time whether a highCYP2D6-CYP2C19metabolic capacity (pharmacogenes related to psychopathology, suicide, and attempt severity) and/or polypharmacy treatments predicted repeat suicide attempts, adjusting for sociodemographic and clinical factors as confounders. Of the 461 (63% women) consecutively hospitalized patients who attempted suicide and were evaluated and treated after an index attempt, 191 (67.5% women) attended their 6- and 12-month follow-up sessions. Clinicians were blinded to the activity scores (AS) of their genotypes, which were calculated as the sum of the values assigned to each allele (CYP2C19 *2,*17;CYP2D6 *3,*4,*4xN,*5,*6,*10,wtxN). No differences were found in polypharmacy prescription patterns and the variability ofCYP2D6andCYP2C19genotypes between adherents and dropouts, but the formers were older, with a higher frequency of anxiety and bipolar disorders and fewer alcohol and substance use disorders. The risk of reattempts was higher forCYP2D6ultrarapid (AS > 2) metabolizers (β = 0.561,p = 0.005) and violent suicide survivors (β = −0.219,p = 0.042) if the attempt occurred during the first 6-month period, individuals with an increased number of MINI DSM-IV Axis I mental disorders (β = 0.092,p = 0.032) during the second 6-month period and individuals with a combined highCYP2D6-CYP2C19metabolic capacity (AS > 4) (β = 0.345,p = 0.024) and an increased use of drugs other than antidepressants, anxiolytics-depressants and antipsychotics-lithium (β = 0.088,p = 0.005) in multiple repeaters during both periods. CYP2D6 and CYP2C19 rapid metabolism and polypharmacy treatment for somatic comorbidities must be considered to prevent the severe side effects of short-term multiple suicide reattempts after a previous attempt.
Positive moods are all alike? Differential affect amplification effects of ‘elated’ versus ‘calm’ mental imagery in young adults reporting hypomanic-like experiences
Authors: Vannucci Caterina , Bonsall Michael B. , Di Simplicio Martina , Cairns Aimee , Holmes Emily A. , Burnett Heyes Stephanie 
Published: October 2022

AbstractPositive mood amplification is a hallmark of the bipolar disorder spectrum (BPDS). We need better understanding of cognitive mechanisms contributing to such elevated mood. Generation of vivid, emotionally compelling mental imagery is proposed to act as an ‘emotional amplifier’ in BPDS. We used a positive mental imagery generation paradigm to manipulate affect in a subclinical BPDS-relevant sample reporting high (n = 31) vs. low (n = 30) hypomanic-like experiences on the Mood Disorder Questionnaire (MDQ). Participants were randomized to an ‘elated’ or ‘calm’ mental imagery condition, rating their momentary affect four times across the experimental session. We hypothesized greater affect increase in the high (vs. low) MDQ group assigned to the elated (vs. calm) imagery generation condition. We further hypothesized that affect increase in the high MDQ group would be particularly apparent in the types of affect typically associated with (hypo)mania, i.e., suggestive of high activity levels. Mixed model and time-series analysis showed that for the high MDQ group, affect increased steeply and in a sustained manner over time in the ‘elated’ imagery condition, and more shallowly in ‘calm’. The low-MDQ group did not show this amplification effect. Analysis of affect clusters showed high-MDQ mood amplification in the ‘elated’ imagery condition was most pronounced for active affective states. This experimental model of BPDS-relevant mood amplification shows evidence that positive mental imagery drives changes in affect in the high MDQ group in a targeted manner. Findings inform cognitive mechanisms of mood amplification, and spotlight prevention strategies targeting elated imagery, while potentially retaining calm imagery to preserve adaptive positive emotionality.
How does the genomic naive public perceive whole genomic testing for health purposes? A scoping review
Authors: Sherburn Isabella A. , Finlay Keri , Best Stephanie 
Published: October 2022

AbstractThe benefits of genomic testing are primarily reported in rare disease, cancer diagnosis and disease management. However, as research into its application in common, more complex conditions grows, as well as the increased prevalence of carrier screening programs, the genomic naive public is more likely to be offered testing in future. To promote social acceptability and ethical application of this technology, it is essential that public perceptions of genomics are considered. Previous studies, however, have primarily focussed on the views of those with genetic conditions or those undergoing genetic testing. The aim of this scoping review is to investigate the genomic naive public’s perceptions of clinical genomics and clinical genomic testing. Embase, MEDLINE and PubMed databases were searched, with a total of 3460 articles identified. Data analysis was organised according to the nonadoption, abandonment, scale-up, spread, and sustainability (NASSS) framework. Sixteen full-text articles were included in the final analysis. Most of the studies used questionnaires to determine attitudes of the public toward clinical genomics (n = 12). Public perceptions were found to underpin technology (Domain 2), value proposition (Domain 3), the adopter system (Domain 4) and the wider context (Domain 6) of the NASSS framework, highlighting its importance when considering implementation of an innovative technology such as genomic testing. Our study shows public perceptions are diverse, and highlights the need for more studies on the views of underrepresented groups and the impact of cultural contexts on perceptions.
A synthetic transcription platform for programmable gene expression in mammalian cells
Authors: Chen William C. W. , Gaidukov Leonid , Lai Yong , Wu Ming-Ru , Cao Jicong , Gutbrod Michael J. , Choi Gigi C. G. , Utomo Rachel P. , Chen Ying-Chou , Wroblewska Liliana , Kellis Manolis , Zhang Lin , Weiss Ron , Lu Timothy K. 
Published: October 2022

AbstractPrecise, scalable, and sustainable control of genetic and cellular activities in mammalian cells is key to developing precision therapeutics and smart biomanufacturing. Here we create a highly tunable, modular, versatile CRISPR-based synthetic transcription system for the programmable control of gene expression and cellular phenotypes in mammalian cells. Genetic circuits consisting of well-characterized libraries of guide RNAs, binding motifs of synthetic operators, transcriptional activators, and additional genetic regulatory elements express mammalian genes in a highly predictable and tunable manner. We demonstrate the programmable control of reporter genes episomally and chromosomally, with up to 25-fold more activity than seen with the EF1α promoter, in multiple cell types. We use these circuits to program the secretion of human monoclonal antibodies and to control T-cell effector function marked by interferon-γ production. Antibody titers and interferon-γ concentrations significantly correlate with synthetic promoter strengths, providing a platform for programming gene expression and cellular function in diverse applications.
Flexibility of functional neuronal assemblies supports human memory
Authors: Umbach Gray , Tan Ryan , Jacobs Joshua , Pfeiffer Brad E. , Lega Bradley 
Published: October 2022

AbstractEpisodic memories, or consciously accessible memories of unique events, represent a key aspect of human cognition. Evidence from rodent models suggests that the neural representation of these complex memories requires cooperative firing of groups of neurons on short time scales, organized by gamma oscillations. These co-firing groups, termed “neuronal assemblies,” represent a fundamental neurophysiological unit supporting memory. Using microelectrode data from neurosurgical patients, we identify neuronal assemblies in the human MTL and show that they exhibit consistent organization in their firing pattern based on gamma phase information. We connect these properties to memory performance across recording sessions. Finally, we describe how human neuronal assemblies flexibly adjust over longer time scales. Our findings provide key evidence linking assemblies to human episodic memory for the first time.
Direct visualization of Rashba-split bands and spin/orbital-charge interconversion at KTaO3 interfaces
Authors: Varotto Sara , Johansson Annika , Göbel Börge , Vicente-Arche Luis M. , Mallik Srijani , Bréhin Julien , Salazar Raphaël , Bertran François , Fèvre Patrick Le , Bergeal Nicolas , Rault Julien , Mertig Ingrid , Bibes Manuel 
Published: October 2022

AbstractRashba interfaces have emerged as promising platforms for spin-charge interconversion through the direct and inverse Edelstein effects. Notably, oxide-based two-dimensional electron gases display a large and gate-tunable conversion efficiency, as determined by transport measurements. However, a direct visualization of the Rashba-split bands in oxide two-dimensional electron gases is lacking, which hampers an advanced understanding of their rich spin-orbit physics. Here, we investigate KTaO3 two-dimensional electron gases and evidence their Rashba-split bands using angle resolved photoemission spectroscopy. Fitting the bands with a tight-binding Hamiltonian, we extract the effective Rashba coefficient and bring insight into the complex multiorbital nature of the band structure. Our calculations reveal unconventional spin and orbital textures, showing compensation effects from quasi-degenerate band pairs which strongly depend on in-plane anisotropy. We compute the band-resolved spin and orbital Edelstein effects, and predict interconversion efficiencies exceeding those of other oxide two-dimensional electron gases. Finally, we suggest design rules for Rashba systems to optimize spin-charge interconversion performance.
Untangling the threads of cellulose mercerization
Authors: Sawada Daisuke , Nishiyama Yoshiharu , Shah Riddhi , Forsyth V. Trevor , Mossou Estelle , O’Neill Hugh Michael , Wada Masahisa , Langan Paul 
Published: October 2022

AbstractNaturally occurring plant cellulose, our most abundant renewable resource, consists of fibers of long polymer chains that are tightly packed in parallel arrays in either of two crystal phases collectively referred to as cellulose I. During mercerization, a process that involves treatment with sodium hydroxide, cellulose goes through a conversion to another crystal form called cellulose II, within which every other chain has remarkably changed direction. We designed a neutron diffraction experiment with deuterium labelling in order to understand how this change of cellulose chain direction is possible. Here we show that during mercerization of bacterial cellulose, chains fold back on themselves in a zigzag pattern to form crystalline anti-parallel domains. This result provides a molecular level understanding of one of the most widely used industrial processes for improving cellulosic materials.
Sublinear scaling of the cellular proteome with ploidy
Authors: Yahya G. , Menges P. , Amponsah P. S. , Ngandiri D. A. , Schulz D. , Wallek A. , Kulak N. , Mann M. , Cramer P. , Savage V. , Räschle M. , Storchova Z. 
Published: October 2022

AbstractPloidy changes are frequent in nature and contribute to evolution, functional specialization and tumorigenesis. Analysis of model organisms of different ploidies revealed that increased ploidy leads to an increase in cell and nuclear volume, reduced proliferation, metabolic changes, lower fitness, and increased genomic instability, but the underlying mechanisms remain poorly understood. To investigate how gene expression changes with cellular ploidy, we analyzed isogenic series of budding yeasts from 1N to 4N. We show that mRNA and protein abundance scales allometrically with ploidy, with tetraploid cells showing only threefold increase in protein abundance compared to haploids. This ploidy-dependent sublinear scaling occurs via decreased rRNA and ribosomal protein abundance and reduced translation. We demonstrate that the activity of Tor1 is reduced with increasing ploidy, which leads to diminished rRNA gene repression via a Tor1-Sch9-Tup1 signaling pathway. mTORC1 and S6K activity are also reduced in human tetraploid cells and the concomitant increase of the Tup1 homolog Tle1 downregulates the rDNA transcription. Our results suggest that the mTORC1-Sch9/S6K-Tup1/TLE1 pathway ensures proteome remodeling in response to increased ploidy.
A medium-entropy transition metal oxide cathode for high-capacity lithium metal batteries
Authors: Pei Yi , Chen Qing , Wang Meiyu , Zhang Pengjun , Ren Qingyong , Qin Jingkai , Xiao Penghao , Song Li , Chen Yu , Yin Wen , Tong Xin , Zhen Liang , Wang Peng , Xu Cheng-Yan 
Published: October 2022

AbstractThe limited capacity of the positive electrode active material in non-aqueous rechargeable lithium-based batteries acts as a stumbling block for developing high-energy storage devices. Although lithium transition metal oxides are high-capacity electrochemical active materials, the structural instability at high cell voltages (e.g., >4.3 V) detrimentally affects the battery performance. Here, to circumvent this issue, we propose a Li1.46Ni0.32Mn1.2O4-x (0 < x < 4) material capable of forming a medium-entropy state spinel phase with partial cation disordering after initial delithiation. Via physicochemical measurements and theoretical calculations, we demonstrate the structural disorder in delithiated Li1.46Ni0.32Mn1.2O4-x, the direct shuttling of Li ions from octahedral sites to the spinel structure and the charge-compensation Mn3+/Mn4+ cationic redox mechanism after the initial delithiation. When tested in a coin cell configuration in combination with a Li metal anode and a LiPF6-based non-aqueous electrolyte, the Li1.46Ni0.32Mn1.2O4-x-based positive electrode enables a discharge capacity of 314.1 mA h g−1 at 100 mA g−1 with an average cell discharge voltage of about 3.2 V at 25 ± 5 °C, which results in a calculated initial specific energy of 999.3 Wh kg−1 (based on mass of positive electrode’s active material).
Suppression of heterotopic ossification in fibrodysplasia ossificans progressiva using AAV gene delivery
Authors: Yang Yeon-Suk , Kim Jung-Min , Xie Jun , Chaugule Sachin , Lin Chujiao , Ma Hong , Hsiao Edward , Hong Jaehyoung , Chun Hyonho , Shore Eileen M. , Kaplan Frederick S. , Gao Guangping , Shim Jae-Hyuck 
Published: October 2022

AbstractHeterotopic ossification is the most disabling feature of fibrodysplasia ossificans progressiva, an ultra-rare genetic disorder for which there is currently no prevention or treatment. Most patients with this disease harbor a heterozygous activating mutation (c.617 G > A;p.R206H) in ACVR1. Here, we identify recombinant AAV9 as the most effective serotype for transduction of the major cells-of-origin of heterotopic ossification. We use AAV9 delivery for gene replacement by expression of codon-optimized human ACVR1, ACVR1R206H allele-specific silencing by AAV-compatible artificial miRNA and a combination of gene replacement and silencing. In mouse skeletal cells harboring a conditional knock-in allele of human mutant ACVR1 and in patient-derived induced pluripotent stem cells, AAV gene therapy ablated aberrant Activin A signaling and chondrogenic and osteogenic differentiation. In Acvr1(R206H) knock-in mice treated locally in early adulthood or systemically at birth, trauma-induced endochondral bone formation was markedly reduced, while inflammation and fibroproliferative responses remained largely intact in the injured muscle. Remarkably, spontaneous heterotopic ossification also substantially decreased in in Acvr1(R206H) knock-in mice treated systemically at birth or in early adulthood. Collectively, we develop promising gene therapeutics that can prevent disabling heterotopic ossification in mice, supporting clinical translation to patients with fibrodysplasia ossificans progressiva.
Harnessing bioengineered microbes as a versatile platform for space nutrition
Authors: Llorente Briardo , Williams Thomas C. , Goold Hugh D. , Pretorius Isak S. , Paulsen Ian T. 
Published: October 2022

AbstractHuman enterprises through the solar system will entail long-duration voyages and habitation creating challenges in maintaining healthy diets. We discuss consolidating multiple sensory and nutritional attributes into microorganisms to develop customizable food production systems with minimal inputs, physical footprint, and waste. We envisage that a yeast collection bioengineered for one-carbon metabolism, optimal nutrition, and diverse textures, tastes, aromas, and colors could serve as a flexible food-production platform. Beyond its potential for supporting humans in space, bioengineered microbial-based food could lead to a new paradigm for Earth’s food manufacturing that provides greater self-sufficiency and removes pressure from natural ecosystems.
CryoEM structural exploration of catalytically active enzyme pyruvate carboxylase
Authors: López-Alonso Jorge Pedro , Lázaro Melisa , Gil-Cartón David , Choi Philip H. , Dodu Alexandra , Tong Liang , Valle Mikel 
Published: October 2022

AbstractPyruvate carboxylase (PC) is a tetrameric enzyme that contains two active sites per subunit that catalyze two consecutive reactions. A mobile domain with an attached prosthetic biotin links both reactions, an initial biotin carboxylation and the subsequent carboxyl transfer to pyruvate substrate to produce oxaloacetate. Reaction sites are at long distance, and there are several co-factors that play as allosteric regulators. Here, using cryoEM we explore the structure of active PC tetramers focusing on active sites and on the conformational space of the oligomers. The results capture the mobile domain at both active sites and expose catalytic steps of both reactions at high resolution, allowing the identification of substrates and products. The analysis of catalytically active PC tetramers reveals the role of certain motions during enzyme functioning, and the structural changes in the presence of additional cofactors expose the mechanism for allosteric regulation.
Heat-inactivated modified vaccinia virus Ankara boosts Th1 cellular and humoral immunity as a vaccine adjuvant
Authors: Yang Ning , Garcia Aitor , Meyer Cindy , Tuschl Thomas , Merghoub Taha , Wolchok Jedd D. , Deng Liang 
Published: October 2022

AbstractProtein or peptide-based subunit vaccines have generated excitement and renewed interest in combating human cancer or COVID-19 outbreak. One major concern for subunit vaccine application is the weak immune responses induced by protein or peptides. Developing novel and effective vaccine adjuvants are critical for the success of subunit vaccines. Here we explored the potential of heat-inactivated MVA (heat-iMVA) as a vaccine adjuvant. Heat-iMVA dramatically enhances T cell responses and antibodies responses, mainly toward Th1 immune responses when combined with protein or peptide-based immunogen. The adjuvant effect of Heat-iMVA is stronger than live MVA and is dependent on the cGAS/STING-mediated cytosolic DNA-sensing pathway. In a therapeutic vaccination model based on tumor neoantigen peptide vaccine, Heat-iMVA significantly extended the survival and delayed tumor growth. When combined with SARS-CoV-2 spike protein, Heat-iMVA induced more robust spike-specific antibody production and more potent neutralization antibodies. Our results support that Heat-iMVA can be developed as a safe and potent vaccine adjuvant for subunit vaccines against cancer or SARS-CoV-2.