bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBranched 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

AbstractUBA1 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

AbstractCholesterol 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

AbstractHeterogeneous 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

AbstractIndole 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

AbstractThe 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

AbstractGreater 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

AbstractBiogas 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

AbstractThe 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

AbstractWe 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

AbstractWe 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

AbstractLow 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.
Gammapy: A Python package for gamma-ray astronomy
Authors: Donath Axel , Terrier Régis , Remy Quentin , Sinha Atreyee , Nigro Cosimo , Pintore Fabio , Khélifi Bruno , Olivera-Nieto Laura , Ruiz Jose Enrique , Brügge Kai , Linhoff Maximilian , Contreras Jose Luis , Acero Fabio , Aguasca-Cabot Arnau , Berge David , Bhattacharjee Pooja , Buchner Johannes , Boisson Catherine , Carreto Fidalgo David , Chen Andrew , de Bony de Lavergne Mathieu , de Miranda Cardoso José Vinicius , Deil Christoph , Füßling Matthias , Funk Stefan , Giunti Luca , Hinton Jim , Jouvin Léa , King Johannes , Lefaucheur Julien , Lemoine-Goumard Marianne , Lenain Jean-Philippe , López-Coto Rubén , Mohrmann Lars , Morcuende Daniel , Panny Sebastian , Regeard Maxime , Saha Lab , Siejkowski Hubert , Siemiginowska Aneta , Sipőcz Brigitta M. , Unbehaun Tim , van Eldik Christopher , Vuillaume Thomas , Zanin Roberta 
Published: August 2023

Context.Traditionally, TeV-γ-ray astronomy has been conducted by experiments employing proprietary data and analysis software. However, the next generation ofγ-ray instruments, such as the Cherenkov Telescope Array Observatory (CTAO), will be operated as open observatories. Alongside the data, they will also make the associated software tools available to a wider community. This necessity prompted the development of open, high-level, astronomical software customized for high-energy astrophysics.Aims.In this article, we present Gammapy, an open-source Python package for the analysis of astronomicalγ-ray data, and illustrate the functionalities of its first long-term-support release, version 1.0. Built on the modern Python scientific ecosystem, Gammapy provides a uniform platform for reducing and modeling data from differentγ-ray instruments for many analysis scenarios. Gammapy complies with several well-established data conventions in high-energy astrophysics, providing serialized data products that are interoperable with other software packages.Methods.Starting from event lists and instrument response functions, Gammapy provides functionalities to reduce these data by binning them in energy and sky coordinates. Several techniques for background estimation are implemented in the package to handle the residual hadronic background affecting γ-ray instruments. After the data are binned, the flux and morphology of one or moreγ-ray sources can be estimated using Poisson maximum likelihood fitting and assuming a variety of spectral, temporal, and spatial models. Estimation of flux points, likelihood profiles, and light curves is also supported.Results.After describing the structure of the package, we show, using publicly available gamma-ray data, the capabilities of Gammapy in multiple traditional and novelγ-ray analysis scenarios, such as spectral and spectro-morphological modeling and estimations of a spectral energy distribution and a light curve. Its flexibility and its power are displayed in a final multi-instrument example, where datasets from different instruments, at different stages of data reduction, are simultaneously fitted with an astrophysical flux model.
Quelle agroforesterie dans les oliveraies de Tunisie ? Analyse des associations de cultures pratiquées et des perceptions des agriculteurs
Authors: Rezgui Ferdaous , Ben Yahmed Jihène , Leauthaud Crystele 
Published: August 2023

L’association de cultures avec les oliviers – arbre emblématique de la région – est une pratique ancienne en Méditerranée. Cette agroforesterie est reconnue pour fournir de multiples services écosystémiques. En Tunisie, l’un des plus importants pays producteurs d’huile d’olive, les systèmes agroforestiers à base d’oliviers sont peu documentés. Ce travail vise à caractériser les principaux systèmes oléicoles agroforestiers existants au nord et au centre du pays, et à comprendre les raisons qui sous-tendent leur adoption. Pour ce faire, une analyse cartographique a d’abord été réalisée pour appréhender la diversité des milieux oléicoles à l’échelle nationale. Vingt-et-un systèmes oléicoles différents ont été identifiés. Sur cette base, un diagnostic agronomique sur deux sites représentatifs de cette diversité a permis de caractériser la structure des systèmes agroforestiers à l’échelle parcellaire. Cinq types de systèmes agroforestiers à base d’oliviers se distinguent en fonction du choix des espèces associées : cultures maraîchères, polyculture, arbres fruitiers, pâturage pour le cheptel et grandes cultures. Une série d’enquêtes a enfin été réalisée auprès d’agriculteurs pour comprendre les choix d’agencement de ces systèmes et la perception qu’ils en ont. Leur mise en place et les pratiques culturales des agriculteurs sont souvent déterminées par des contraintes économiques ou foncières, et non d’intérêts agronomiques et environnementaux.