bluuebunny/crossref_metadata_2025 huggingface dataset:
Newman on emotion and cognition in the Grammar of Assent
Authors: Emrich Emma
Published: August 2023

This article considers the role of emotion in John Henry Newman's Grammar of Assent by distinguishing five different ways (or ‘models’) in which the emotions play a positive epistemic role in relation to cognition. The most important of these, the Cognitive-Emotion Model, offers a new account of Newman's crucial idea of real assent, one that stresses the primary role of the emotions in real assent rather than imagination. This model helps to explain the nature of real assent by highlighting Newman's portrayal of an emotional way of knowing an object that is personal or individual, incommunicable, vivid, and motive. In this study of the relations between emotion and cognition I hope to highlight unexplored aspects of the nature of real assent and the importance of the role of emotion in it and hope to show how Newman's epistemology offers a rich framework for exploring the positive epistemic contributions of the emotions.
You could be immaterial (or not)
Authors: Bailey Andrew M.
Published: August 2023

Materialists about human persons say that we are, and must be, wholly material beings. Substance dualists say that we are, and must be, wholly immaterial. In this article, I take issue with the ‘and must be’ bits. Both materialists and substance dualists would do well to reject modal extensions of their views and instead opt for contingent doctrines, or doctrines that are silent about those modal extensions. Or so I argue.
Severe COVID-19 classified by simple covid risk index is associated with higher levels of advanced oxidation protein products and 8-hydroxy 2 deoxyguanosine
Authors: Satała Joanna , Woźniak Agnieszka , Fabiś Mateusz , Gorzelak-Pabiś Paulina , Pawlos Agnieszka , Fabiś Jarosław , Broncel Marlena , Woźniak Ewelina
Published: August 2023

SARS-CoV-2 has become one of the most important and challenging medical research topics in recent years. The presence of endothelial dysfunction, immune thrombosis, and oxidative stress contributes to complications and requires more extended hospitalisation of patients. In this article, we focused on analysing the impact of oxidative stress on the severity of COVID-19 infection. The study group consisted of 72 patients with laboratory-confirmed SARS-CoV enrolled. The patients were divided into moderate and severe diseases according to the SCRI (Simple Covid Risk Index, including lymphocyte/D-dimer ratio). Using the ELISA kit, we determined the level of AOPP and 8-OHdG. Patients with severe COVID-19 had higher levels of both AOPP (P < 0.05) and 8-OHdG (P < 0.05) compared to patients with moderate disease. Albumin levels were significantly lower (P < 0.001), although fibrinogen (P < 0.01), D-dimer (P < 0.001), and TF (P < 0.05) levels were higher in severe patients than in moderate course. AOPP/Alb was also higher among severe patients (P < 0.05). Our data suggest a potential role for AOPP and 8-OHdG in predicting the outcome of SARS-CoV-2 patients. Elevated AOPP levels were associated with increased Dimer-D, TF, and vWF activity levels.
CROSS-REFERENCE BETWEEN LOGIC AND PSYCHOLOGY IN IBN SĪNĀ’S THEORY OF EXPERIENCE (TAǦRIBA)
Authors: Hoki Yu
Published: August 2023

Cet article démontre que la théorie de l’expérience (taǧriba) d’Ibn Sīnā nécessite une référence croisée entre la logique et la psychologie. Suivant la tradition linguistique basrane, il paraphrase les noms dérivés (ism muštaqq) dans la formule li-x y (« y appartient à x ») : par exemple, ʿālim (« savoir ») est paraphrasé en lahu ʿilm (« un acte de savoir lui appartient »). Sa théorie de l’expérience emploie cette formule pour arranger les phénomènes observés dans une certaine forme de syllogisme et décrire les fonctions des sens internes du cerveau. Ibn Sīnā arrange les phénomènes observés dans la formule li-x y ou la proposition dont un prédicat est un nom dérivé de y. En même temps, il soutient que le sens du souvenir est impliqué dans le processus de l’expérience. Le souvenir est un sens interne du cerveau, qui préserve maʿnā perçue par le sens de l’estimation. L’estimation consiste à percevoir maʿnā (y) qui est inhérente à un sujet (x), et à porter un jugement sur x en fonction de y. Ainsi, dans ce processus, l’analyse des noms dérivés range les phénomènes observés dans un ordre rationnel, et le sens interne établit la causalité entre l’appréhension et l’affirmation logique. L’article se termine par une discussion sur la relation de cette philosophie avec la médecine.
Cannabis use may attenuate neurocognitive performance deficits resulting from methamphetamine use disorder
Authors: Rogers Jeffrey M. , Grant Igor , Marcondes Maria Cecilia G. , Morgan Erin E. , Cherner Mariana , Ellis Ronald J. , Letendre Scott L. , Heaton Robert K. , Iudicello Jennifer E.
Published: August 2023

Objective:

Methamphetamine and cannabis are two widely used, and frequently co-used, substances with possibly opposing effects on the central nervous system. Evidence of neurocognitive deficits related to use is robust for methamphetamine and mixed for cannabis. Findings regarding their combined use are inconclusive. We aimed to compare neurocognitive performance in people with lifetime cannabis or methamphetamine use disorder diagnoses, or both, relative to people without substance use disorders.

Method:

423 (71.9% male, aged 44.6 ± 14.2 years) participants, stratified by presence or absence of lifetime methamphetamine (M−/M+) and/or cannabis (C−/C+) DSM-IV abuse/dependence, completed a comprehensive neuropsychological, substance use, and psychiatric assessment. Neurocognitive domain T-scores and impairment rates were examined using multiple linear and binomial regression, respectively, controlling for covariates that may impact cognition.

Results:

Globally, M+C+ performed worse than M−C− but better than M+C−. M+C+ outperformed M+C− on measures of verbal fluency, information processing speed, learning, memory, and working memory. M−C+ did not display lower performance than M−C− globally or on any domain measures, and M−C+ even performed better than M−C− on measures of learning, memory, and working memory.

Conclusions:

Our findings are consistent with prior work showing that methamphetamine use confers risk for worse neurocognitive outcomes, and that cannabis use does not appear to exacerbate and may even reduce this risk. People with a history of cannabis use disorders performed similarly to our nonsubstance using comparison group and outperformed them in some domains. These findings warrant further investigation as to whether cannabis use may ameliorate methamphetamine neurotoxicity.
Process Data in Computer-Based Assessment
Authors: Lindner Marlit Annalena , Greiff Samuel
Published: August 2023

Abstract: This editorial provides a comprehensive framework and overview of potential uses and next steps in research on process data in computer-based assessments, expanding toward broad perspectives on the field and an exploration of future directions and emerging trends. After briefly reflecting on the evolution of process data use in research and assessment practice, we discuss three key challenges, namely (1) the theoretical grounding and validation of process data indicators, (2) assessment design for process data, and (3) ethical standards. By considering best practice approaches in all three areas and current discussions in the literature, we conclude that a focus is needed on the following three areas: (1) strong, holistic theoretical frameworks for validating process data, (2) reliable, standardized data collections, preferably with a top-down approach to developing test items and preregistered hypotheses, and (3) ethical norms for data collection, data use, and guidelines for responsible inference, including restraints in decisions based on process data.
Rainfall and Salinity Effects on Future Pacific Climate Change
Authors: Kim Hyuna , Timmermann Axel , Lee Sun‐Seon , Schloesser Fabian
Published: August 2023

Most climate models simulate an intensified eastern equatorial Pacific warming in response to increasing greenhouse gas concentrations. So far, the proposed mechanisms have focused on thermodynamic aspects such as the spatial inhomogeneity of evaporative feedbacks, and future increases in upper ocean thermal stratification, partly intensified by projected Walker circulation weakening. Here we show, using earth system model freshwater perturbation experiments, that the simulated future rainfall intensification along the equator plays an important role in tropical climate change. Associated negative equatorial salinity anomalies of about −0.6 permil, which are very similar to the projected late 21st century salinity anomalies in CMIP6 SSP585 scenario, strengthen upper ocean stratification in the Pacific which leads to a flattening of the thermocline, shoaling of the equatorial undercurrent, and major shifts in tropical ocean dynamics. The resulting eastern basin equatorial warming also contributes to a marked weakening of the Pacific Walker circulation. Our analysis illustrates the importance of rainfall and salinity changes in the tropical climate system with relevance for understanding both, patterns of future climate change as well as the El Niño Southern Oscillation phenomenon.
Metasomatism and Slow Slip: Talc Production Along the Flat Subduction Plate Interface Beneath Mexico (Guerrero)
Authors: Lindquist P. C. , Condit C. B. , Hoover W. F. , Hernández‐Uribe D. , Guevara V. E.
Published: August 2023

Talc‐rich rocks are common in exhumed subduction zone terranes and may explain geophysical observations of the subduction zone interface, particularly beneath Guerrero, Mexico, where the Cocos plate subducts horizontally beneath North America and episodic tremor and slow slip (ETS) occurs. We present petrologic models exploring (a) the degree of silica metasomatism required to produce talc in serpentinized peridotites at the pressure‐temperature conditions of the plate interface beneath Guerrero and (b) the amount of silica‐bearing water produced by rocks from the subducting Cocos plate and the location of fluid pulses. We estimate the volumes of talc produced by the advection of silica‐rich fluids into serpentinized peridotites at the plate interface over the history of the flat‐slab system. In the ETS‐hosting region, serpentinites must achieve ∼43 wt. % SiO2 to stabilize talc, but minor additions of silica beyond this produce large volumes of talc. Our models of Cocos plate dehydration predict that water flux into the interface averages 3.9 × 104 kg m−2 Myr−1 but suggest that only where subducting basalts undergo major dehydration reactions will sufficient amounts of silica‐rich fluids be produced to drive significant metasomatism. We suggest that talc produced by advective transport of aqueous silica alone cannot account for geophysical interpretations of km‐thick zones of talc‐rich rocks beneath Guerrero, although silica‐bearing fluids that migrate along the plate interface may promote broader metasomatism. Regions of predicted talc production do, however, overlap with the spatial occurrence of ETS, consistent with models of slow slip based on the frictional deformation of metasomatic lithologies.
Comment on “Inner Core Rotation Captured by Earthquake Doublets and Twin Stations” by Yang and Song
Authors: Tian Dongdong , Wen Lianxing
Published: August 2023

Yang & Song (2022, https://doi.org/10.1029/2022GL098393) first claimed existence of Earth's inner core differential rotation based on the waveform similarity of two neighboring stations AAK and KZA across an earthquake doublet and then postulated a local velocity gradient at the top of the inner core based on the difference of PKiKP‐PKIKP differential times between the stations and inferred inner core differential rotation rate. In this comment, we collectively analyze the seismic data in the region and add the data of another nearby station HORS into analysis. HORS and KZA, located in an opposite direction away from AAK, consistently exhibit high waveform similarity. Collective analysis of seismic data demonstrates the invalidity of both their logic of claiming existence of inner core differential rotation and their postulation of “a local inner core gradient” to infer differential rotation. Localized and episodic inner core surface change provides a physically consistent explanation to the seismic data.
Reduced smooth muscle-fibroblasts transformation potentially decreases intestinal wound healing and colitis-associated cancer in ageing mice
Authors: Liu Yi , Ji Yanhong , Jiang Ruiyi , Fang Chao , Shi Gang , Cheng Lin , Zuo Yinan , Ye Yixin , Su Xiaolan , Li Junshu , Wang Huiling , Wang Yuan , Lin Yi , Dai Lei , Zhang Shuang , Deng Hongxin
Published: August 2023

Cancer and impaired tissue wound healing with ageing are closely related to the quality of life of the elderly population. Given the increased incidence of cancer and the population ageing trend globally, it is very important to explore how ageing impairs tissue wound healing and spontaneous cancer. In a murine model of DSS-induced acute colitis and AOM/DSS-induced colitis-associated cancer (CAC), we found ageing significantly decreases intestinal wound healing and simultaneous CAC initiation, although ageing does not affect the incidence of AOM-induced, sporadic non-inflammatory CRC. Mechanistically, reduced fibroblasts were observed in the colitis microenvironment of ageing mice. Through conditional lineage tracing, an important source of fibroblasts potentially derived from intestinal smooth muscle cells (ISMCs) was identified orchestrating intestinal wound healing and CAC initiation in young mice. However, the number of transformed fibroblasts from ISMCs significantly decreased in ageing mice, accompanied by decreased intestinal wound healing and decreased CAC initiation. ISMCs-fibroblasts transformation in young mice and reduction of this transformation in ageing mice were also confirmed by ex-vivo intestinal muscular layer culture experiments. We further found that activation of YAP/TAZ in ISMCs is required for the transformation of ISMCs into fibroblasts. Meanwhile, the reduction of YAP/TAZ activation in ISMCs during intestinal wound healing was observed in ageing mice. Conditional knockdown of YAP/TAZ in ISMCs of young mice results in reduced fibroblasts in the colitis microenvironment, decreased intestinal wound healing and decreased CAC initiation, similar to the phenotype of ageing mice. In addition, the data from intestine samples derived from inflammatory bowel disease (IBD) patients show that activation of YAP/TAZ also occurs in ISMCs from these patients. Collectively, our work reveals an important role of the ageing stromal microenvironment in intestinal wound healing and CAC initiation. Furthermore, our work also identified a potential source of fibroblasts involved in colitis and CAC.
Physiological and evolutionary contexts of a new symbiotic species from the nitrogen-recycling gut community of turtle ants
Authors: Béchade Benoît , Cabuslay Christian S , Hu Yi , Mendonca Caroll M , Hassanpour Bahareh , Lin Jonathan Y , Su Yangzhou , Fiers Valerie J , Anandarajan Dharman , Lu Richard , Olson Chandler J , Duplais Christophe , Rosen Gail L , Moreau Corrie S , Aristilde Ludmilla , Wertz John T , Russell Jacob A
Published: August 2023

While genome sequencing has expanded our knowledge of symbiosis, role assignment within multi-species microbiomes remains challenging due to genomic redundancy and the uncertainties of in vivo impacts. We address such questions, here, for a specialized nitrogen (N) recycling microbiome of turtle ants, describing a new genus and species of gut symbiont—Ischyrobacter davidsoniae (Betaproteobacteria: Burkholderiales: Alcaligenaceae)—and its in vivo physiological context. A re-analysis of amplicon sequencing data, with precisely assigned Ischyrobacter reads, revealed a seemingly ubiquitous distribution across the turtle ant genus Cephalotes, suggesting ≥50 million years since domestication. Through new genome sequencing, we also show that divergent I. davidsoniae lineages are conserved in their uricolytic and urea-generating capacities. With phylogenetically refined definitions of Ischyrobacter and separately domesticated Burkholderiales symbionts, our FISH microscopy revealed a distinct niche for I. davidsoniae, with dense populations at the anterior ileum. Being positioned at the site of host N-waste delivery, in vivo metatranscriptomics and metabolomics further implicate I. davidsoniae within a symbiont-autonomous N-recycling pathway. While encoding much of this pathway, I. davidsoniae expressed only a subset of the requisite steps in mature adult workers, including the penultimate step deriving urea from allantoate. The remaining steps were expressed by other specialized gut symbionts. Collectively, this assemblage converts inosine, made from midgut symbionts, into urea and ammonia in the hindgut. With urea supporting host amino acid budgets and cuticle synthesis, and with the ancient nature of other active N-recyclers discovered here, I. davidsoniae emerges as a central player in a conserved and impactful, multipartite symbiosis.
Validation of the molecular international prognostic scoring system in patients with myelodysplastic syndromes defined by international consensus classification
Authors: Lee Wan-Hsuan , Tsai Ming-Tao , Tsai Cheng-Hong , Tien Feng-Ming , Lo Min-Yen , Tseng Mei-Hsuan , Kuo Yuan-Yeh , Liu Ming-Chih , Yang Yi-Tsung , Chen Jui-Che , Tang Jih-Luh , Sun Hsun-I , Chuang Yi-Kuang , Lin Liang-In , Chou Wen-Chien , Lin Chien-Chin , Hou Hsin-An , Tien Hwei-Fang
Published: August 2023

Myelodysplastic syndromes (MDS) have varied prognoses and require a risk-adapted treatment strategy for treatment optimization. Recently, a molecular prognostic model (Molecular International Prognostic Scoring System [IPSS-M]) that combines clinical parameters, cytogenetic abnormalities, and mutation topography was proposed. This study validated the IPSS-M in 649 patients with primary MDS (based on the 2022 International Consensus Classification [ICC]) and compared its prognostic power to those of the IPSS and revised IPSS (IPSS-R). Overall, 42.5% of the patients were reclassified and 29.3% were up-staged from the IPSS-R. After the reclassification, 16.9% of the patients may receive different treatment strategies. The IPSS-M had greater discriminative potential than the IPSS-R and IPSS. Patients with high, or very high-risk IPSS-M might benefit from allogeneic hematopoietic stem cell transplantation. IPSS-M, age, ferritin level, and the 2022 ICC categorization predicted outcomes independently. After analyzing demographic and genetic features, complementary genetic analyses, including KMT2A-PTD, were suggested for accurate IPSS-M categorization of patients with ASXL1, TET2, STAG2, RUNX1, SF3B1, SRSF2, DNMT3A, U2AF1, and BCOR mutations and those classified as MDS, not otherwise specified with single lineage dysplasia/multi-lineage dysplasia based on the 2022 ICC. This study confirmed that the IPSS-M can better risk-stratified MDS patients for optimized therapeutic decision-making.
Effects of COVID-19 vaccination and previous infection on Omicron SARS-CoV-2 infection and relation with serology
Authors: de Gier Brechje , Huiberts Anne J. , Hoeve Christina E. , den Hartog Gerco , van Werkhoven Henri , van Binnendijk Rob , Hahné Susan J. M. , de Melker Hester E. , van den Hof Susan , Knol Mirjam J.
Published: August 2023

An increasing proportion of the population has acquired immunity through COVID-19 vaccination and previous SARS-CoV-2 infection, i.e., hybrid immunity, possibly affecting the risk of new infection. We aim to estimate the protective effect of previous infections and vaccinations on SARS-CoV-2 Omicron infection, using data from 43,257 adult participants in a prospective community-based cohort study in the Netherlands, collected between 10 January 2022 and 1 September 2022. Our results show that, for participants with 2, 3 or 4 prior immunizing events (vaccination or previous infection), hybrid immunity is more protective against infection with SARS-CoV-2 Omicron than vaccine-induced immunity, up to at least 30 weeks after the last immunizing event. Differences in risk of infection are partly explained by differences in anti-Spike RBD (S) antibody concentration, which is associated with risk of infection in a dose-response manner. Among participants with hybrid immunity, with one previous pre-Omicron infection, we do not observe a relevant difference in risk of Omicron infection by sequence of vaccination(s) and infection. Additional immunizing events increase the protection against infection, but not above the level of the first weeks after the previous event.
Structural basis for a degenerate tRNA identity code and the evolution of bimodal specificity in human mitochondrial tRNA recognition
Authors: Kuhle Bernhard , Hirschi Marscha , Doerfel Lili K. , Lander Gabriel C. , Schimmel Paul
Published: August 2023

Animal mitochondrial gene expression relies on specific interactions between nuclear-encoded aminoacyl-tRNA synthetases and mitochondria-encoded tRNAs. Their evolution involves an antagonistic interplay between strong mutation pressure on mtRNAs and selection pressure to maintain their essential function. To understand the molecular consequences of this interplay, we analyze the human mitochondrial serylation system, in which one synthetase charges two highly divergent mtRNASer isoacceptors. We present the cryo-EM structure of human mSerRS in complex with mtRNASer(UGA), and perform a structural and functional comparison with the mSerRS-mtRNASer(GCU) complex. We find that despite their common function, mtRNASer(UGA) and mtRNASer(GCU) show no constrain to converge on shared structural or sequence identity motifs for recognition by mSerRS. Instead, mSerRS evolved a bimodal readout mechanism, whereby a single protein surface recognizes degenerate identity features specific to each mtRNASer. Our results show how the mutational erosion of mtRNAs drove a remarkable innovation of intermolecular specificity rules, with multiple evolutionary pathways leading to functionally equivalent outcomes.
Theory predicts UV/vis-to-IR photonic down conversion mediated by excited state vibrational polaritons
Authors: Terry Weatherly Connor K. , Provazza Justin , Weiss Emily A. , Tempelaar Roel
Published: August 2023

This work proposes a photophysical phenomenon whereby ultraviolet/visible (UV/vis) excitation of a molecule involving a Franck-Condon (FC) active vibration yields infrared (IR) emission by strong coupling to an optical cavity. The resulting UV/vis-to-IR photonic down conversion process is mediated by vibrational polaritons in the electronic excited state potential. It is shown that the formation of excited state vibrational polaritons (ESVP) via UV/vis excitation only involve vibrational modes with both a non-zero FC activity and IR activity in the excited state. Density functional theory calculations are used to identify 1-Pyreneacetic acid as a molecule with this property and the dynamics of ESVP are modeled. Overall, this work introduces an avenue of polariton chemistry where excited state dynamics are influenced by the formation of vibrational polaritons. Along with this, the UV/vis-to-IR photonic down conversion is potentially useful in both sensing excited state vibrations and quantum transduction schemes.
Dynamics of cortical contrast adaptation predict perception of signals in noise
Authors: Angeloni Christopher F. , Młynarski Wiktor , Piasini Eugenio , Williams Aaron M. , Wood Katherine C. , Garami Linda , Hermundstad Ann M. , Geffen Maria N.
Published: August 2023

Neurons throughout the sensory pathway adapt their responses depending on the statistical structure of the sensory environment. Contrast gain control is a form of adaptation in the auditory cortex, but it is unclear whether the dynamics of gain control reflect efficient adaptation, and whether they shape behavioral perception. Here, we trained mice to detect a target presented in background noise shortly after a change in the contrast of the background. The observed changes in cortical gain and behavioral detection followed the dynamics of a normative model of efficient contrast gain control; specifically, target detection and sensitivity improved slowly in low contrast, but degraded rapidly in high contrast. Auditory cortex was required for this task, and cortical responses were not only similarly affected by contrast but predicted variability in behavioral performance. Combined, our results demonstrate that dynamic gain adaptation supports efficient coding in auditory cortex and predicts the perception of sounds in noise.
Profiling cell envelope-antibiotic interactions reveals vulnerabilities to β-lactams in a multidrug-resistant bacterium
Authors: Hogan Andrew M. , Rahman A. S. M. Zisanur , Motnenko Anna , Natarajan Aakash , Maydaniuk Dustin T. , León Beltina , Batun Zayra , Palacios Armando , Bosch Alejandra , Cardona Silvia T.
Published: August 2023

The cell envelope of Gram-negative bacteria belonging to the Burkholderia cepacia complex (Bcc) presents unique restrictions to antibiotic penetration. As a consequence, Bcc species are notorious for causing recalcitrant multidrug-resistant infections in immunocompromised individuals. Here, we present the results of a genome-wide screen for cell envelope-associated resistance and susceptibility determinants in a Burkholderia cenocepacia clinical isolate. For this purpose, we construct a high-density, randomly-barcoded transposon mutant library and expose it to 19 cell envelope-targeting antibiotics. By quantifying relative mutant fitness with BarSeq, followed by validation with CRISPR-interference, we profile over a hundred functional associations and identify mediators of antibiotic susceptibility in the Bcc cell envelope. We reveal connections between β-lactam susceptibility, peptidoglycan synthesis, and blockages in undecaprenyl phosphate metabolism. The synergy of the β-lactam/β-lactamase inhibitor combination ceftazidime/avibactam is primarily mediated by inhibition of the PenB carbapenemase. In comparison with ceftazidime, avibactam more strongly potentiates the activity of aztreonam and meropenem in a panel of Bcc clinical isolates. Finally, we characterize in Bcc the iron and receptor-dependent activity of the siderophore-cephalosporin antibiotic, cefiderocol. Our work has implications for antibiotic target prioritization, and for using additional combinations of β-lactam/β-lactamase inhibitors that can extend the utility of current antibacterial therapies.
Single-cell analysis reveals region-heterogeneous responses in rhesus monkey spinal cord with complete injury
Authors: Fan Yongheng , Wu Xianming , Han Sufang , Zhang Qi , Sun Zheng , Chen Bing , Xue Xiaoyu , Zhang Haipeng , Chen Zhenni , Yin Man , Xiao Zhifeng , Zhao Yannan , Dai Jianwu
Published: August 2023

Spinal cord injury (SCI) leads to severe sensory and motor dysfunction below the lesion. However, the cellular dynamic responses and heterogeneity across different regions below the lesion remain to be elusive. Here, we used single-cell transcriptomics to investigate the region-related cellular responses in female rhesus monkeys with complete thoracic SCI from acute to chronic phases. We found that distal lumbar tissue cells were severely impacted, leading to degenerative microenvironments characterized by disease-associated microglia and oligodendrocytes activation alongside increased inhibitory interneurons proportion following SCI. By implanting scaffold into the injury sites, we could improve the injury microenvironment through glial cells and fibroblast regulation while remodeling spared lumbar tissues via reduced inhibitory neurons proportion and improved phagocytosis and myelination. Our findings offer crucial pathological insights into the spared distal tissues and proximal tissues after SCI, emphasizing the importance of scaffold-based treatment approaches targeting heterogeneous microenvironments.
Small molecule branched-chain ketoacid dehydrogenase kinase (BDK) inhibitors with opposing effects on BDK protein levels
Authors: Roth Flach Rachel J. , Bollinger Eliza , Reyes Allan R. , Laforest Brigitte , Kormos Bethany L. , Liu Shenping , Reese Matthew R. , Martinez Alsina Luis A. , Buzon Leanne , Zhang Yuan , Bechle Bruce , Rosado Amy , Sahasrabudhe Parag V. , Knafels John , Bhattacharya Samit K. , Omoto Kiyoyuki , Stansfield John C. , Hurley Liam D. , Song LouJin , Luo Lina , Breitkopf Susanne B. , Monetti Mara , Cunio Teresa , Tierney Brendan , Geoly Frank J. , Delmore Jake , Siddall C. Parker , Xue Liang , Yip Ka N. , Kalgutkar Amit S. , Miller Russell A. , Zhang Bei B. , Filipski Kevin J.
Published: August 2023

Branched chain amino acid (BCAA) catabolic impairments have been implicated in several diseases. Branched chain ketoacid dehydrogenase (BCKDH) controls the rate limiting step in BCAA degradation, the activity of which is inhibited by BCKDH kinase (BDK)-mediated phosphorylation. Screening efforts to discover BDK inhibitors led to identification of thiophene PF-07208254, which improved cardiometabolic endpoints in mice. Structure-activity relationship studies led to identification of a thiazole series of BDK inhibitors; however, these inhibitors did not improve metabolism in mice upon chronic administration. While the thiophenes demonstrated sustained branched chain ketoacid (BCKA) lowering and reduced BDK protein levels, the thiazoles increased BCKAs and BDK protein levels. Thiazoles increased BDK proximity to BCKDH-E2, whereas thiophenes reduced BDK proximity to BCKDH-E2, which may promote BDK degradation. Thus, we describe two BDK inhibitor series that possess differing attributes regarding BDK degradation or stabilization and provide a mechanistic understanding of the desirable features of an effective BDK inhibitor.
Auranofin targets UBA1 and enhances UBA1 activity by facilitating ubiquitin trans-thioesterification to E2 ubiquitin-conjugating enzymes
Authors: Yan Wenjing , Zhong Yongwang , Hu Xin , Xu Tuan , Zhang Yinghua , Kales Stephen , Qu Yanyan , Talley Daniel C. , Baljinnyam Bolormaa , LeClair Christopher A. , Simeonov Anton , Polster Brian M. , Huang Ruili , Ye Yihong , Rai Ganesha , Henderson Mark J. , Tao Dingyin , Fang Shengyun
Published: August 2023

UBA1 is the primary E1 ubiquitin-activating enzyme responsible for generation of activated ubiquitin required for ubiquitination, a process that regulates stability and function of numerous proteins. Decreased or insufficient ubiquitination can cause or drive aging and many diseases. Therefore, a small-molecule enhancing UBA1 activity could have broad therapeutic potential. Here we report that auranofin, a drug approved for the treatment of rheumatoid arthritis, is a potent UBA1 activity enhancer. Auranofin binds to the UBA1’s ubiquitin fold domain and conjugates to Cys1039 residue. The binding enhances UBA1 interactions with at least 20 different E2 ubiquitin-conjugating enzymes, facilitating ubiquitin charging to E2 and increasing the activities of seven representative E3s in vitro. Auranofin promotes ubiquitination and degradation of misfolded ER proteins during ER-associated degradation in cells at low nanomolar concentrations. It also facilitates outer mitochondrial membrane-associated degradation. These findings suggest that auranofin can serve as a much-needed tool for UBA1 research and therapeutic exploration.
A HIF independent oxygen-sensitive pathway for controlling cholesterol synthesis
Authors: Dickson Anna S. , Pauzaite Tekle , Arnaiz Esther , Ortmann Brian M. , West James A. , Volkmar Norbert , Martinelli Anthony W. , Li Zhaoqi , Wit Niek , Vitkup Dennis , Kaser Arthur , Lehner Paul J. , Nathan James A.
Published: August 2023

Cholesterol biosynthesis is a highly regulated, oxygen-dependent pathway, vital for cell membrane integrity and growth. In fungi, the dependency on oxygen for sterol production has resulted in a shared transcriptional response, resembling prolyl hydroxylation of Hypoxia Inducible Factors (HIFs) in metazoans. Whether an analogous metazoan pathway exists is unknown. Here, we identify Sterol Regulatory Element Binding Protein 2 (SREBP2), the key transcription factor driving sterol production in mammals, as an oxygen-sensitive regulator of cholesterol synthesis. SREBP2 degradation in hypoxia overrides the normal sterol-sensing response, and is HIF independent. We identify MARCHF6, through its NADPH-mediated activation in hypoxia, as the main ubiquitin ligase controlling SREBP2 stability. Hypoxia-mediated degradation of SREBP2 protects cells from statin-induced cell death by forcing cells to rely on exogenous cholesterol uptake, explaining why many solid organ tumours become auxotrophic for cholesterol. Our findings therefore uncover an oxygen-sensitive pathway for governing cholesterol synthesis through regulated SREBP2-dependent protein degradation.
Scalable trapping of single nanosized extracellular vesicles using plasmonics
Authors: Hong Chuchuan , Ndukaife Justus C.
Published: August 2023

Heterogeneous nanoscale extracellular vesicles (EVs) are of significant interest for disease detection, monitoring, and therapeutics. However, trapping these nano-sized EVs using optical tweezers has been challenging due to their small size. Plasmon-enhanced optical trapping offers a solution. Nevertheless, existing plasmonic tweezers have limited throughput and can take tens of minutes for trapping for low particle concentrations. Here, we present an innovative approach called geometry-induced electrohydrodynamic tweezers (GET) that overcomes these limitations. GET generates multiple electrohydrodynamic potentials, allowing parallel transport and trapping of single EVs within seconds. By integrating nanoscale plasmonic cavities at the center of each GET trap, single EVs can be placed near plasmonic cavities, enabling instant plasmon-enhanced optical trapping upon laser illumination without detrimental heating effects. These non-invasive scalable hybrid nanotweezers open new horizons for high-throughput tether-free plasmon-enhanced single EV trapping and spectroscopy. Other potential areas of impact include nanoplastics characterization, and scalable hybrid integration for quantum photonics.
Modular assembly of indole alkaloids enabled by multicomponent reaction
Authors: Li Jiaming , Lai Zhencheng , Zhang Weiwei , Zeng Linwei , Cui Sunliang
Published: August 2023

Indole alkaloids are one of the largest alkaloid classes, proving valuable structural moiety in pharmaceuticals. Although methods for the synthesis of indole alkaloids are constantly explored, the direct single-step synthesis of these chemical entities with broad structural diversity remains a formidable challenge. Herein, we report a modular assembly of tetrahydrocarboline type of indole alkaloids from simple building blocks in a single step while showing broad compatibility with medicinally relevant functionality. In this protocol, the 2-alkylated or 3-alkylated indoles, formaldehyde, and amine hydrochlorides could undergo a one-pot reaction to deliver γ-tetrahydrocarbolines or β-tetrahydrocarbolines directly. A wide scope of these readily available starting materials is applicable in this process, and numerous structural divergent tetrahydrocarbolines could be achieved rapidly. The control reaction and deuterium-labelling reaction are conducted to probe the mechanism. And mechanistically, this multicomponent reaction relies on a multiple alkylamination cascade wherein an unusual C(sp3)–C(sp3) connection was involved in this process. This method could render rapid access to pharmaceutically interesting compounds, greatly enlarge the indole alkaloid library and accelerate the lead compound optimization thus facilitating drug discovery.
Pines’ demon observed as a 3D acoustic plasmon in Sr2RuO4
Authors: Husain Ali A. , Huang Edwin W. , Mitrano Matteo , Rak Melinda S. , Rubeck Samantha I. , Guo Xuefei , Yang Hongbin , Sow Chanchal , Maeno Yoshiteru , Uchoa Bruno , Chiang Tai C. , Batson Philip E. , Phillips Philip W. , Abbamonte Peter
Published: August 2023

The characteristic excitation of a metal is its plasmon, which is a quantized collective oscillation of its electron density. In 1956, David Pines predicted that a distinct type of plasmon, dubbed a ‘demon’, could exist in three-dimensional (3D) metals containing more than one species of charge carrier1. Consisting of out-of-phase movement of electrons in different bands, demons are acoustic, electrically neutral and do not couple to light, so have never been detected in an equilibrium, 3D metal. Nevertheless, demons are believed to be critical for diverse phenomena including phase transitions in mixed-valence semimetals2, optical properties of metal nanoparticles3, soundarons in Weyl semimetals4 and high-temperature superconductivity in, for example, metal hydrides3,5–7. Here, we present evidence for a demon in Sr2RuO4 from momentum-resolved electron energy-loss spectroscopy. Formed of electrons in the β and γ bands, the demon is gapless with critical momentum qc = 0.08 reciprocal lattice units and room-temperature velocity v = (1.065 ± 0.12) × 105 m s−1 that undergoes a 31% renormalization upon cooling to 30 K because of coupling to the particle–hole continuum. The momentum dependence of the intensity of the demon confirms its neutral character. Our study confirms a 67-year old prediction and indicates that demons may be a pervasive feature of multiband metals.
Abrogation of greater graft failure risk of female-to-male liver transplantation with donors older than 40 years or graft macrosteatosis greater than 5%
Authors: Han Sangbin , Kwon Ji Hye , Lee Kyo Won , Lee Sanghoon , Choi Gyu Sung , Kim Jong Man , Ko Justin Sangwook , Gwak Mi Sook , Kim Gaab Soo , Ha Sang Yun , Joh Jae-Won
Published: August 2023

Greater graft-failure-risk of female-to-male liver transplantation (LT) is thought to be due to acute decrease in hepatic-estrogen-signaling. Our previous research found evidence that female hepatic-estrogen-signaling decreases after 40 years or with macrosteatosis. Thus, we hypothesized that inferiority of female-to-male LT changes according to donor-age and macrosteatosis. We stratified 780 recipients of grafts from living-donors into four subgroups by donor-age and macrosteatosis and compared graft-failure-risk between female-to-male LT and other LTs within each subgroup using Cox model. In recipients with ≤ 40 years non-macrosteatotic donors, graft-failure-risk was significantly greater in female-to-male LT than others (HR 2.03 [1.18–3.49], P = 0.011). Within the subgroup of recipients without hepatocellular carcinoma, the inferiority of female-to-male LT became greater (HR 4.75 [2.02–11.21], P < 0.001). Despite good graft quality, 1y-graft-failure-probability was 37.9% (23.1%–57.9%) in female-to-male LT within this subgroup while such exceptionally high probability was not shown in any other subgroups even with worse graft quality. When donor was > 40 years or macrosteatotic, graft-failure-risk was not significantly different between female-to-male LT and others (P > 0.60). These results were in agreement with the estrogen receptor immunohistochemistry evaluation of donor liver. In conclusion, we found that the inferiority of female-to-male LT was only found when donor was ≤ 40 years and non-macrosteatotic. Abrogation of the inferiority when donor was > 40 years or macrosteatotic suggests the presence of dominant contributors for post-transplant graft-failure other than graft quality/quantity and supports the role of hepatic-estrogen-signaling mismatch on graft-failure after female-to-male LT.
Development of Ni–Mo carbide catalyst for production of syngas and CNTs by dry reforming of biogas
Authors: Saconsint Supanida , Srifa Atthapon , Koo-Amornpattana Wanida , Assabumrungrat Suttichai , Sano Noriaki , Fukuhara Choji , Ratchahat Sakhon
Published: August 2023

Biogas has been widely regarded as a promising source of renewable energy. Recently, the direct conversion of biogas over heterogeneous catalysts for the simultaneous production of syngas and carbon nanotubes exhibits a high potential for full utilization of biogas with great benefits. Involving the combined dry reforming of methane and catalytic decomposition of methane, the efficiency of process is strongly depended on the catalyst activity/stability, mainly caused by carbon deposition. In this study, Ni–Mo catalyst is engineered to provide a life-long performance and perform high activity in the combined process. The surface modification of catalysts by a controlled carburization pretreatment is proposed for the first time to produce a carbide catalyst along with improving the catalyst stability as well as the reactivity for direct conversion of biogas. The performance of as-prepared carbide catalysts is investigated with comparison to the oxide and metallic ones. As a result, the Ni–Mo2C catalyst exhibited superior activity and stability over its counterparts, even though the condensed nanocarbon was largely grown and covered on the surface. In addition, up to 82% of CH4 conversion and 93% of CO2 conversion could remain almost constant at 800 °C throughout the entire test period of 3 h under a high flowrate inlet stream of pure biogas at 48,000 cm3 g−1 h−1. The XPS spectra of catalysts confirmed that the presence of Mo2C species on the catalyst surface could promote the stability and reactivity of the catalyst, resulting in higher productivity of carbon nanotubes over a longer time.
Serum folate associated with nonalcoholic fatty liver disease and advanced hepatic fibrosis
Authors: Chen Hao-Kai , Luo Jing , Li Xiu-Juan , Liao Wan-Zhe , Hu Yu-Qi , Guo Xu-Guang
Published: August 2023

The role played by serum folate in the progression of nonalcoholic fatty liver disease (NAFLD) remains controversial. The purpose of this study was to investigate the association of serum folate with NAFLD and advanced liver fibrosis (AHF). We conducted a cross-sectional study with 5417 participants using 2011–2018 NHANES data. Multiple logistic regression analysis and propensity score matching analysis were used to investigate the association of serum folate with NAFLD and AHF. In the completely adjusted model, participants in the high serum folate group had a 27% (OR 0.73, 95% CI 0.62, 0.87, p = 0.0003) and 53% (OR 0.47, 95% CI 0.35, 0.63, p < 0.0001) lower odds of suffering from NAFLD and AHF, respectively, compared to the low serum folate group. The similar results in propensity score matching further validated the above association. Stratified analysis showed that the negative correlation of serum folate with NAFLD and AHF demonstrated a broad consistency across populations. The results of this study indicate that higher serum folate level was associated with lower odds of NAFLD and AHF among US adults. Further prospective studies are necessary due to the limitations of cross-sectional studies.
Altered structural connectivity in olfactory disfunction after mild COVID-19 using probabilistic tractography
Authors: Bispo Diógenes Diego de Carvalho , Brandão Pedro Renato de Paula , Pereira Danilo Assis , Maluf Fernando Bisinoto , Dias Bruna Arrais , Paranhos Hugo Rafael , von Glehn Felipe , de Oliveira Augusto César Penalva , Soares Alexandre Anderson de Sousa Munhoz , Descoteaux Maxime , Regattieri Neysa Aparecida Tinoco
Published: August 2023

We aimed to investigate changes in olfactory bulb volume and brain network in the white matter (WM) in patients with persistent olfactory disfunction (OD) following COVID-19. A cross-sectional study evaluated 38 participants with OD after mild COVID-19 and 24 controls, including Sniffin' Sticks identification test (SS-16), MoCA, and brain magnetic resonance imaging. Network-Based Statistics (NBS) and graph theoretical analysis were used to explore the WM. The COVID-19 group had reduced olfactory bulb volume compared to controls. In NBS, COVID-19 patients showed increased structural connectivity in a subnetwork comprising parietal brain regions. Regarding global network topological properties, patients exhibited lower global and local efficiency and higher assortativity than controls. Concerning local network topological properties, patients had reduced local efficiency (left lateral orbital gyrus and pallidum), increased clustering (left lateral orbital gyrus), increased nodal strength (right anterior orbital gyrus), and reduced nodal strength (left amygdala). SS-16 test score was negatively correlated with clustering of whole-brain WM in the COVID-19 group. Thus, patients with OD after COVID-19 had relevant WM network dysfunction with increased connectivity in the parietal sensory cortex. Reduced integration and increased segregation are observed within olfactory-related brain areas might be due to compensatory plasticity mechanisms devoted to recovering olfactory function.
Synergic quantum generative machine learning
Authors: Bartkiewicz Karol , Tulewicz Patrycja , Roik Jan , Lemr Karel
Published: August 2023

We introduce a new approach towards generative quantum machine learning significantly reducing the number of hyperparameters and report on a proof-of-principle experiment demonstrating our approach. Our proposal depends on collaboration between the generators and discriminator, thus, we call it quantum synergic generative learning. We present numerical evidence that the synergic approach, in some cases, compares favorably to recently proposed quantum generative adversarial learning. In addition to the results obtained with quantum simulators, we also present experimental results obtained with an actual programmable quantum computer. We investigate how a quantum computer implementing generative learning algorithm could learn the concept of a maximally-entangled state. After completing the learning process, the network is able both to recognize and to generate an entangled state. Our approach can be treated as one possible preliminary step to understanding how the concept of quantum entanglement can be learned and demonstrated by a quantum computer.
Suppression of 1/f noise in graphene due to anisotropic mobility fluctuations induced by impurity motion
Authors: Kamada Masahiro , Zeng Weijun , Laitinen Antti , Sarkar Jayanta , Yeh Sheng-Shiuan , Tappura Kirsi , Seppä Heikki , Hakonen Pertti
Published: August 2023

Low frequency resistance variations due to mobility fluctuations is one of the key factors of 1/f noise in metallic conductors. According to theory, such noise in a two-dimensional (2D) device can be suppressed to zero at small magnetic fields, implying important technological benefits for low noise 2D devices. In this work, we provide evidence of anisotropic mobility fluctuations by demonstrating a strong field-induced suppression of noise in a high-mobility graphene Corbino disk, even though the device displays only a tiny amount of 1/f noise inherently. The suppression of the 1/f noise depends on charge density, showing less non-uniform mobility fluctuations away from the Dirac point with charge puddles. We model our results using an approach based on impurity clustering dynamics and find our results consistent with the 1/f noise induced by scattering of carriers on mobile impurities forming clusters.
UV exposure to PET microplastics increases their downward mobility in stormwater biofilters undergoing freeze–thaw cycles
Authors: Gunther Haley J. , Das Tonoy K. , Leonard Jamie , Koutnik Vera S. , El Rassi Lea A. , Tang Zilong , Mohanty Sanjay K.
Published: August 2023

An increase in microplastic weathering under UV lights decreases their surface hydrophilicity by the formation of polar groups and increases their mobility in the stormwater biofilter under freeze–thaw cycles.
A high-performance TPGDA/PETEA composite gel polymer electrolyte for lithium metal batteries
Authors: Chen Zhifu , Pei Quan , An Zhitao , Tong Yiting , Zhang Qingfeng , Xie Shuhong
Published: August 2023

A gel electrolyte formed by in situ polymerization of a precursor solution with TPGDA and PETEA monomers on a PI membrane containing LLZTO particles, is found to exhibit excellent electrochemical performance.
Selective oxidation of substituted phenols with Co–N–C catalysts fabricated via low temperature heat treatment
Authors: Guo Bairui , Du Zhongtian , Shen Xiaoyu , Han Mengjing , Zhao Yanbin , Luo Jingjie , Liang Changhai
Published: August 2023

Efficient heterogeneous Co(ii) species were fabricated via pyrolysis at 400 °C, rather than generally at 600–1000 °C.