bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decoding metabolic signatures in Alzheimer’s disease: a mitochondrial perspective
Authors: Bano Daniele , Ehninger Dan , Bagetta Giacinto 
Published: December 2023

AbstractAlzheimer’s disease (AD) is one of the most prevalent age-related neurodegenerative diseases and accounts for the majority of dementia cases worldwide. Tremendous ongoing efforts of basic and clinical research have expanded our knowledge on AD and its complex multifactorial pathogenesis. For sporadic AD, it is widely assumed that silent and early symptomatic stages initiate decades before the irreversible decline in cognitive abilities that ultimately lead to debilitating conditions. In addition to amyloid plaques and tau-containing neurofibrillary tangles as the most prominent hallmarks of AD lesions within the affected brain areas, we now possess a broader collection of pathological signatures that are associated with AD development and progression. In this regard, there is a substantial body of evidence suggesting that hypometabolism occurs in the brains of individuals at the prodromal stage before dementia is diagnosed, which may reflect an early role of metabolic dysfunction in AD. This perspective surveys the vast literature and critically assesses the current evidence demonstrating a mitochondrial contribution to AD. Additionally, we discuss our interpretations of the reported mitochondrial signatures and consider how altered mitochondrial bioenergetics may be an additional risk factor for AD pathogenesis.
Safety and tolerability of intravitreal umedaptanib pegol (anti-FGF2) for neovascular age-related macular degeneration (nAMD): a phase 1, open-label study
Authors: Pereira Daniel S. , Akita Kazumasa , Bhisitkul Robert B. , Nishihata Toshiaki , Ali Yusuf , Nakamura Emiko , Nakamura Yoshikazu 
Published: December 2023

Abstract
Objective
To evaluate the efficacy and safety of a single-dose intravitreal umedaptanib pegol (anti-FGF2, investigational new drug) for the treatment of neovascular age-related macular degeneration (nAMD).

Methods
Nine participants who had a diagnosis of refractory nAMD were enrolled and received a single intravitreal injection of umedaptanib pegol at increasing doses of 0.2, 1.0 or 2.0 mg in the study eye.

Results
All three doses of umedaptanib pegol evaluated in the study were safe and well tolerated. No severe adverse event (AE) was observed in the study. There was an improvement in retinal fluid measured by central subfield thickness (CST) in most subjects. Remarkably, all three subjects who received 2.0 mg/eye showed improvement of more than 150 μm.

Conclusions
Intravitreal umedaptanib pegol was safe, well tolerated, and demonstrated an indication of bioactivity in participants that have persistent subretinal fluid refractory to the treatment with anti-VEGFs.
A simple method for developing lysine targeted covalent protein reagents
Authors: Gabizon Ronen , Tivon Barr , Reddi Rambabu N. , van den Oetelaar Maxime C. M. , Amartely Hadar , Cossar Peter J. , Ottmann Christian , London Nir 
Published: December 2023

AbstractPeptide-based covalent probes can target shallow protein surfaces not typically addressable using small molecules, yet there is a need for versatile approaches to convert native peptide sequences into covalent binders that can target a broad range of residues. Here we report protein-based thio-methacrylate esters—electrophiles that can be installed easily on unprotected peptides and proteins via cysteine side chains, and react efficiently and selectively with cysteine and lysine side chains on the target. Methacrylate phosphopeptides derived from 14-3-3-binding proteins irreversibly label 14-3-3σ via either lysine or cysteine residues, depending on the position of the electrophile. Methacrylate peptides targeting a conserved lysine residue exhibit pan-isoform binding of 14-3-3 proteins both in lysates and in extracellular media. Finally, we apply this approach to develop protein-based covalent binders. A methacrylate-modified variant of the colicin E9 immunity protein irreversibly binds to the E9 DNAse, resulting in significantly higher thermal stability relative to the non-covalent complex. Our approach offers a simple and versatile route to convert peptides and proteins into potent covalent binders.
Soybean reduced internode 1 determines internode length and improves grain yield at dense planting
Authors: Li Shichen , Sun Zhihui , Sang Qing , Qin Chao , Kong Lingping , Huang Xin , Liu Huan , Su Tong , Li Haiyang , He Milan , Fang Chao , Wang Lingshuang , Liu Shuangrong , Liu Bin , Liu Baohui , Fu Xiangdong , Kong Fanjiang , Lu Sijia 
Published: December 2023

AbstractMajor cereal crops have benefitted from Green Revolution traits such as shorter and more compact plants that permit high-density planting, but soybean has remained relatively overlooked. To balance ideal soybean yield with plant height under dense planting, shortening of internodes without reducing the number of nodes and pods is desired. Here, we characterized a short-internode soybean mutant, reduced internode 1 (rin1). Partial loss of SUPPRESSOR OF PHYA 105 3a (SPA3a) underlies rin1. RIN1 physically interacts with two homologs of ELONGATED HYPOCOTYL 5 (HY5), STF1 and STF2, to promote their degradation. RIN1 regulates gibberellin metabolism to control internode development through a STF1/STF2–GA2ox7 regulatory module. In field trials, rin1 significantly enhances grain yield under high-density planting conditions comparing to its wild type of elite cultivar. rin1 mutants therefore could serve as valuable resources for improving grain yield under high-density cultivation and in soybean–maize intercropping systems.
Selective ring expansion and C−H functionalization of azulenes
Authors: Park Sangjune , Kim Cheol-Eui , Jeong Jinhoon , Ryu Ho , Maeng Chanyoung , Kim Dongwook , Baik Mu-Hyun , Lee Phil Ho 
Published: December 2023

AbstractWe report a transition metal-catalyzed ring expansion of azulene that can be contrasted with C–H functionalization. This study represents the first example of the successful ring expansion of azulene using Cu(hfacac)2 (hfacac: hexafluoroacetylacetonate) with a diazo reagent. This result is notable for extending the Buchner reaction, previously limited to benzenoid aromatics, to nonbenzenoid compounds. The chemoselectivity of the reaction can be directed towards C–H functionalization by substituting the Cu catalyst with AgOTf. This approach does not require the addition of phosphine, NHC, or related ligands, and prefunctionalization of azulenes is unnecessary. Furthermore, the method exhibits excellent functional group tolerance, allowing for the synthesis of a wide range of 6,7-bicyclic compounds and C–H functionalized azulenes. We also present a theoretical study that explains the experimental observations, explaining why copper afford the ring expansion product while silver forms the C–H alkylation product.
SMARCB1 loss activates patient-specific distal oncogenic enhancers in malignant rhabdoid tumors
Authors: Liu Ning Qing , Paassen Irene , Custers Lars , Zeller Peter , Teunissen Hans , Ayyildiz Dilara , He Jiayou , Buhl Juliane Laura , Hoving Eelco Wieger , van Oudenaarden Alexander , de Wit Elzo , Drost Jarno 
Published: December 2023

AbstractMalignant rhabdoid tumor (MRT) is a highly malignant and often lethal childhood cancer. MRTs are genetically defined by bi-allelic inactivating mutations in SMARCB1, a member of the BRG1/BRM-associated factors (BAF) chromatin remodeling complex. Mutations in BAF complex members are common in human cancer, yet their contribution to tumorigenesis remains in many cases poorly understood. Here, we study derailed regulatory landscapes as a consequence of SMARCB1 loss in the context of MRT. Our multi-omics approach on patient-derived MRT organoids reveals a dramatic reshaping of the regulatory landscape upon SMARCB1 reconstitution. Chromosome conformation capture experiments subsequently reveal patient-specific looping of distal enhancer regions with the promoter of the MYC oncogene. This intertumoral heterogeneity in MYC enhancer utilization is also present in patient MRT tissues as shown by combined single-cell RNA-seq and ATAC-seq. We show that loss of SMARCB1 activates patient-specific epigenetic reprogramming underlying MRT tumorigenesis.
Higher Antarctic ice sheet accumulation and surface melt rates revealed at 2 km resolution
Authors: Noël Brice , van Wessem J. Melchior , Wouters Bert , Trusel Luke , Lhermitte Stef , van den Broeke Michiel R. 
Published: December 2023

AbstractAntarctic ice sheet (AIS) mass loss is predominantly driven by increased solid ice discharge, but its variability is governed by surface processes. Snowfall fluctuations control the surface mass balance (SMB) of the grounded AIS, while meltwater ponding can trigger ice shelf collapse potentially accelerating discharge. Surface processes are essential to quantify AIS mass change, but remain poorly represented in climate models typically running at 25-100 km resolution. Here we present SMB and surface melt products statistically downscaled to 2 km resolution for the contemporary climate (1979-2021) and low, moderate and high-end warming scenarios until 2100. We show that statistical downscaling modestly enhances contemporary SMB (3%), which is sufficient to reconcile modelled and satellite mass change. Furthermore, melt strongly increases (46%), notably near the grounding line, in better agreement with in-situ and satellite records. The melt increase persists by 2100 in all warming scenarios, revealing higher surface melt rates than previously estimated.
Bolometric detection of Josephson inductance in a highly resistive environment
Authors: Subero Diego , Maillet Olivier , Golubev Dmitry S. , Thomas George , Peltonen Joonas T. , Karimi Bayan , Marín-Suárez Marco , Yeyati Alfredo Levy , Sánchez Rafael , Park Sunghun , Pekola Jukka P. 
Published: December 2023

AbstractThe Josephson junction is a building block of quantum circuits. Its behavior, well understood when treated as an isolated entity, is strongly affected by coupling to an electromagnetic environment. In 1983, Schmid predicted that a Josephson junction shunted by a resistance exceeding the resistance quantum RQ = h/4e2 ≈ 6.45 kΩ for Cooper pairs would become insulating since the phase fluctuations would destroy the coherent Josephson coupling. However, recent microwave measurements have questioned this interpretation. Here, we insert a small Josephson junction in a Johnson-Nyquist-type setup where it is driven by weak current noise arising from thermal fluctuations. Our heat probe minimally perturbs the junction’s equilibrium, shedding light on features not visible in charge transport. We find that the Josephson critical current completely vanishes in DC charge transport measurement, and the junction demonstrates Coulomb blockade in agreement with the theory. Surprisingly, thermal transport measurements show that the Josephson junction acts as an inductor at high frequencies, unambiguously demonstrating that a supercurrent survives despite the Coulomb blockade observed in DC measurements.
Pyroptosis inhibiting nanobodies block Gasdermin D pore formation
Authors: Kopp Anja , Hagelueken Gregor , Jamitzky Isabell , Moecking Jonas , Schiffelers Lisa D. J. , Schmidt Florian I. , Geyer Matthias 
Published: December 2023

AbstractHuman Gasdermin D (GSDMD) is a key mediator of pyroptosis, a pro-inflammatory form of cell death occurring downstream of inflammasome activation as part of the innate immune defence. Upon cleavage by inflammatory caspases in the cytosol, the N-terminal domain of GSDMD forms pores in the plasma membrane resulting in cytokine release and eventually cell death. Targeting GSDMD is an attractive way to dampen inflammation. In this study, six GSDMD targeting nanobodies are characterized in terms of their binding affinity, stability, and effect on GSDMD pore formation. Three of the nanobodies inhibit GSDMD pore formation in a liposome leakage assay, although caspase cleavage was not perturbed. We determine the crystal structure of human GSDMD in complex with two nanobodies at 1.9 Å resolution, providing detailed insights into the GSDMD–nanobody interactions and epitope binding. The pore formation is sterically blocked by one of the nanobodies that binds to the oligomerization interface of the N-terminal domain in the multi-subunit pore assembly. Our biochemical and structural findings provide tools for studying inflammasome biology and build a framework for the design of GSDMD targeting drugs.
Enabling direct-growth route for highly efficient ethanol upgrading to long-chain alcohols in aqueous phase
Authors: Gu Juwen , Gong Wanbing , Zhang Qian , Long Ran , Ma Jun , Wang Xinyu , Li Jiawei , Li Jiayi , Fan Yujian , Zheng Xinqi , Qiu Songbai , Wang Tiejun , Xiong Yujie 
Published: December 2023

AbstractUpgrading ethanol to long-chain alcohols (LAS, C6+OH) offers an attractive and sustainable approach to carbon neutrality. Yet it remains a grand challenge to achieve efficient carbon chain propagation, particularly with noble metal-free catalysts in aqueous phase, toward LAS production. Here we report an unconventional but effective strategy for designing highly efficient catalysts for ethanol upgrading to LAS, in which Ni catalytic sites are controllably exposed on surface through sulfur modification. The optimal catalyst exhibits the performance well exceeding previous reports, achieving ultrahigh LAS selectivity (15.2% C6OH and 59.0% C8+OH) at nearly complete ethanol conversion (99.1%). Our in situ characterizations, together with theoretical simulation, reveal that the selectively exposed Ni sites which offer strong adsorption for aldehydes but are inert for side reactions can effectively stabilize and enrich aldehyde intermediates, dramatically improving direct-growth probability toward LAS production. This work opens a new paradigm for designing high-performance non-noble metal catalysts for upgrading aqueous EtOH to LAS.
Gate-tunable anomalous Hall effect in Bernal tetralayer graphene
Authors: Chen Hao , Arora Arpit , Song Justin C. W. , Loh Kian Ping 
Published: December 2023

AbstractLarge spin-orbit coupling is often thought to be critical in realizing magnetic order-locked charge transport such as the anomalous Hall effect (AHE). Recently, artificial stacks of two-dimensional materials, e.g., magic-angle twisted bilayer graphene on hexagonal boron-nitride heterostructures and dual-gated rhombohedral trilayer graphene, have become platforms for realizing AHE without spin-orbit coupling. However, these stacking arrangements are not energetically favorable, impeding experiments and further device engineering. Here we report an anomalous Hall effect in Bernal-stacked tetralayer graphene devices (BTG), the most stable configuration of four-layer graphene. BTG AHE is switched on by a displacement field and is most pronounced at low carrier densities. The onset of AHE occurs in tandem with a full metal to a broken isospin transition indicating an orbital origin of the itinerant ferromagnetism. At lowest densities, BTG exhibits an unconventional hysteresis with step-like anomalous Hall plateaus. Persisting to several tens of kelvin, AHE in BTG demonstrates the ubiquity and robustness of magnetic order in readily available and stable multilayer Bernal graphene stacks—a new venue for intrinsic non-reciprocal responses.
A multi-omics dataset for the analysis of frontotemporal dementia genetic subtypes
Authors: Menden Kevin , Francescatto Margherita , Nyima Tenzin , Blauwendraat Cornelis , Dhingra Ashutosh , Castillo-Lizardo Melissa , Fernandes Noémia , Kaurani Lalit , Kronenberg-Versteeg Deborah , Atasu Burcu , Sadikoglou Eldem , Borroni Barbara , Rodriguez-Nieto Salvador , Simon-Sanchez Javier , Fischer Andre , Craig David Wesley , Neumann Manuela , Bonn Stefan , Rizzu Patrizia , Heutink Peter 
Published: December 2023

AbstractUnderstanding the molecular mechanisms underlying frontotemporal dementia (FTD) is essential for the development of successful therapies. Systematic studies on human post-mortem brain tissue of patients with genetic subtypes of FTD are currently lacking. The Risk and Modyfing Factors of Frontotemporal Dementia (RiMod-FTD) consortium therefore has generated a multi-omics dataset for genetic subtypes of FTD to identify common and distinct molecular mechanisms disturbed in disease. Here, we present multi-omics datasets generated from the frontal lobe of post-mortem human brain tissue from patients with mutations in MAPT, GRN and C9orf72 and healthy controls. This data resource consists of four datasets generated with different technologies to capture the transcriptome by RNA-seq, small RNA-seq, CAGE-seq, and methylation profiling. We show concrete examples on how to use the resulting data and confirm current knowledge about FTD and identify new processes for further investigation. This extensive multi-omics dataset holds great value to reveal new research avenues for this devastating disease.
High-resolution grids of daily air temperature for Peru - the new PISCOt v1.2 dataset
Authors: Huerta Adrian , Aybar Cesar , Imfeld Noemi , Correa Kris , Felipe-Obando Oscar , Rau Pedro , Drenkhan Fabian , Lavado-Casimiro Waldo 
Published: December 2023

AbstractGridded high-resolution climate datasets are increasingly important for a wide range of modelling applications. Here we present PISCOt (v1.2), a novel high spatial resolution (0.01°) dataset of daily air temperature for entire Peru (1981–2020). The dataset development involves four main steps: (i) quality control; (ii) gap-filling; (iii) homogenisation of weather stations, and (iv) spatial interpolation using additional data, a revised calculation sequence and an enhanced version control. This improved methodological framework enables capturing complex spatial variability of maximum and minimum air temperature at a more accurate scale compared to other existing datasets (e.g. PISCOt v1.1, ERA5-Land, TerraClimate, CHIRTS). PISCOt performs well with mean absolute errors of 1.4 °C and 1.2 °C for maximum and minimum air temperature, respectively. For the first time, PISCOt v1.2 adequately captures complex climatology at high spatiotemporal resolution and therefore provides a substantial improvement for numerous applications at local-regional level. This is particularly useful in view of data scarcity and urgently needed model-based decision making for climate change, water balance and ecosystem assessment studies in Peru.
HALD, a human aging and longevity knowledge graph for precision gerontology and geroscience analyses
Authors: Wu Zexu , Feng Cong , Hu Yanshi , Zhou Yincong , Li Sida , Zhang Shilong , Hu Yueming , Chen Yuhao , Chao Haoyu , Ni Qingyang , Chen Ming 
Published: December 2023

AbstractHuman aging is a natural and inevitable biological process that leads to an increased risk of aging-related diseases. Developing anti-aging therapies for aging-related diseases requires a comprehensive understanding of the mechanisms and effects of aging and longevity from a multi-modal and multi-faceted perspective. However, most of the relevant knowledge is scattered in the biomedical literature, the volume of which reached 36 million in PubMed. Here, we presented HALD, a text mining-based human aging and longevity dataset of the biomedical knowledge graph from all published literature related to human aging and longevity in PubMed. HALD integrated multiple state-of-the-art natural language processing (NLP) techniques to improve the accuracy and coverage of the knowledge graph for precision gerontology and geroscience analyses. Up to September 2023, HALD had contained 12,227 entities in 10 types (gene, RNA, protein, carbohydrate, lipid, peptide, pharmaceutical preparations, toxin, mutation, and disease), 115,522 relations, 1,855 aging biomarkers, and 525 longevity biomarkers from 339,918 biomedical articles in PubMed. HALD is available at https://bis.zju.edu.cn/hald.
Assessment of the potential radiation hazards posed by Nubian sandstone, Egypt
Authors: Gawad Ahmed E. Abdel , Eliwa Hassan , Masoud Masoud S. , Khandaker Mayeen Uddin , Hanfi Mohamed Y. 
Published: December 2023

AbstractThe study found that the activity concentrations of the radionuclides 238U, 232Th and 40K in the sandstone are 32 ± 13, 29.6 ± 12.2, and 132.6 ± 86.4 Bq kg−1, respectively. These values are lower than the reported worldwide limits of 33, 45, and 412 Bq kg−1. According to the present study, the absorbed dose rate (Dair), the annual effective dose, and the excess life time cancer were all found to be below the worldwide mean. Pearson correlation, PCA, and HCA were used to analyze the data and identify patterns in the relationship between radionuclides and radiological hazards. A statistical analysis of the sandstones showed that the radioactive elements 238U, 232Th and 40K are the main contributors to the radioactive risk. The study suggests that the sandstone is safe to use. The levels of radioactivity are not high enough to pose a risk to human health.
The provenance of the stones in the Menga dolmen reveals one of the greatest engineering feats of the Neolithic
Authors: Rodríguez José Antonio Lozano , Sanjuán Leonardo García , Álvarez-Valero Antonio M. , Jiménez-Espejo Francisco , Arrieta Jesús María , Fraile-Nuez Eugenio , Artús Raquel Montero , Cultrone Giuseppe , Muñoz-Carballeda Fernando Alonso , Martínez-Sevilla Francisco 
Published: December 2023

AbstractThe technical and intellectual capabilities of past societies are reflected in the monuments they were able to build. Tracking the provenance of the stones utilised to build prehistoric megalithic monuments, through geological studies, is of utmost interest for interpreting ancient architectures as well as to contribute to their protection. According to the scarce information available, most stones used in European prehistoric megaliths originate from locations near the construction sites, which would have made transport easier. The Menga dolmen (Antequera, Malaga, Spain), listed in UNESCO World Heritage since July 2016, was designed and built with stones weighting up to nearly 150 tons, thus becoming the most colossal stone monument built in its time in Europe (c. 3800–3600 BC). Our study (based on high-resolution geological mapping as well as petrographic and stratigraphic analyses) reveals key geological and archaeological evidence to establish the precise provenance of the massive stones used in the construction of this monument. These stones are mostly calcarenites, a poorly cemented detrital sedimentary rock comparable to those known as 'soft stones' in modern civil engineering. They were quarried from a rocky outcrop located at a distance of approximately 1 km. In this study, it can be inferred the use of soft stone in Menga reveals the human application of new wood and stone technologies enabling the construction of a monument of unprecedented magnitude and complexity.