bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Quantified Galloway Ternary Diagram of Delta Morphology
Authors: Paniagua‐Arroyave Juan F. , Nienhuis Jaap H. 
Published: November 2024

AbstractWaves, rivers, and tides shape delta morphology. Recent studies have enabled predictions of their relative influence on deltas globally, but methods and associated uncertainties remain poorly known. Here, we address that gap and show how to quantify delta morphology within the Galloway ternary diagram of river, wave, and tidal sediment fluxes. We assess delta morphology predictions compared to observations for 31 deltas globally and find a median error of 4% (standard deviation of 11%) in the river, tide, or wave‐driven sediment fluxes. Relative uncertainties are greatest for mixed‐process deltas (e.g., Sinu, error of 49%) and tend to decrease for end‐member morphologies where either wave, tide, or river sediment fluxes dominate (e.g., Fly, error of 0.2%). Prediction uncertainties for delta morphologic metrics are more considerable: the delta shoreline protrusion angles set by wave influence have a median error of 45%, the delta channel widening from tides 25%, and the number of distributary channels 86%. Larger sources of prediction uncertainty are (a) delta morphology data, for example, delta slopes that modulate tidal fluxes, (b) data on river sediment flux distribution between individual delta river outlets, and (c) theoretical basis behind fluvial and tidal dominance. Broadly, these methods will help improve delta morphology predictions and assess how natural and anthropogenic forces affect morphologic change.
Emerging mechanisms of lipid peroxidation in regulated cell death and its physiological implications
Authors: Zheng Yongxin , Sun Junlu , Luo Zhiting , Li Yimin , Huang Yongbo 
Published: November 2024

AbstractRegulated cell death (RCD) refers to the form of cell death that can be regulated by various biomacromolecules. Each cell death modalities have their distinct morphological changes and molecular mechanisms. However, intense evidences suggest that lipid peroxidation can be the common feature that initiates and propagates the cell death. Excessive lipid peroxidation alters the property of membrane and further damage the proteins and nucleic acids, which is implicated in various human pathologies. Here, we firstly review the classical chain process of lipid peroxidation, and further clarify the current understanding of the myriad roles and molecular mechanisms of lipid peroxidation in various RCD types. We also discuss how lipid peroxidation involves in diseases and how such intimate association between lipid peroxidation-driven cell death and diseases can be leveraged to develop rational therapeutic strategies.
Microglial cannabinoid receptor type II stimulation improves cognitive impairment and neuroinflammation in Alzheimer’s disease mice by controlling astrocyte activation
Authors: Sobue Akira , Komine Okiru , Endo Fumito , Kakimi Chihiro , Miyoshi Yuka , Kawade Noe , Watanabe Seiji , Saito Yuko , Murayama Shigeo , Saido Takaomi C. , Saito Takashi , Yamanaka Koji 
Published: November 2024

AbstractAlzheimer’s disease (AD) is the most common form of dementia and is characterized by the accumulation of amyloid β (Aβ) and phosphorylated tau. Neuroinflammation, mainly mediated by glial activation, plays an important role in AD progression. Although there is growing evidence for the anti-neuroinflammatory and neuroprotective effects of the cannabinoid system modulation, the detailed mechanism remains unclear. To address these issues, we analyzed the expression levels of cannabinoid receptor type II (Cnr2/Cb2) in AppNL-G-F/NL-G-F mice and human AD precuneus, which is vulnerable to amyloid deposition in AD, and the effects of JWH 133, a selective CB2 agonist, on neuroinflammation in primary glial cells and neuroinflammation and cognitive impairment in AppNL-G-F/NL-G-F mice. The levels of Cnr2/Cb2 were upregulated in microglia isolated from the cerebral cortex of AppNL-G-F/NL-G-F mice. CNR2 expression was also increased in RNAs derived from human precuneus with advanced AD pathology. Chronic oral administration of JWH 133 significantly ameliorated the cognitive impairment of AppNL-G-F/NL-G-F mice without neuropsychiatric side effects. Microglia and astrocyte mRNAs were directly isolated from the mouse cerebral cortex by magnetic-activated cell sorting, and the gene expression was determined by quantitative PCR. JWH 133 administration significantly decreased reactive astrocyte markers and microglial C1q, an inducer for the reactive astrocytes in AppNL-G-F/NL-G-F mice. In addition, JWH133 administration inhibited the expression of p-STAT3 (signal transducer and activator of transcription 3) in astrocytes in AppNL-G-F/NL-G-F mice. Furthermore, JWH 133 administration suppressed dystrophic presynaptic terminals surrounding amyloid plaques. In conclusion, stimulation of microglial CB2 ameliorates cognitive dysfunction in AppNL-G-F/NL-G-F mice by controlling astrocyte activation and inducing beneficial neuroinflammation, and our study has implications that CB2 may represent an attractive therapeutic target for the treatment of AD and perhaps other neurodegenerative diseases involving neuroinflammation.
Structural mechanisms of human sodium-coupled high-affinity choline transporter CHT1
Authors: Xue Jing , Chen Hongwen , Wang Yong , Jiang Youxing 
Published: November 2024

AbstractMammalian sodium-coupled high-affinity choline transporter CHT1 uptakes choline in cholinergic neurons for acetylcholine synthesis and plays a critical role in cholinergic neurotransmission. Here, we present the high-resolution cryo-EM structures of human CHT1 in apo, substrate- and ion-bound, hemicholinium-3-inhibited, and ML352-inhibited states. These structures represent three distinct conformational states, elucidating the structural basis of the CHT1-mediated choline uptake mechanism. Three ion-binding sites, two for Na+ and one for Cl–, are unambiguously defined in the structures, demonstrating that both ions are indispensable cofactors for high-affinity choline-binding and are likely transported together with the substrate in a 2:1:1 stoichiometry. The two inhibitor-bound CHT1 structures reveal two distinct inhibitory mechanisms and provide a potential structural platform for designing therapeutic drugs to manipulate cholinergic neuron activity. Combined with the functional analysis, this study provides a comprehensive view of the structural mechanisms underlying substrate specificity, substrate/ion co-transport, and drug inhibition of a physiologically important symporter.
Multicentennial cycles in continental demography synchronous with solar activity and climate stability
Authors: Wirtz Kai W. , Antunes Nicolas , Diachenko Aleksandr , Laabs Julian , Lemmen Carsten , Lohmann Gerrit , McLaughlin Rowan , Zorita Eduardo , Gronenborn Detlef 
Published: November 2024

AbstractHuman population dynamics and their drivers are not well understood, especially over the long term and on large scales. Here, we estimate demographic growth trajectories from 9 to 3 ka BP across the entire globe by employing summed probability distributions of radiocarbon dates. Our reconstruction reveals multicentennial growth cycles on all six inhabited continents, which exhibited matching dominant frequencies and phase relations. These growth oscillations were often also synchronised with multicentennial variations in solar activity. The growth cycle for Europe, reconstructed based on >91,000 radiocarbon dates, was backed by archaeology-derived settlement data and showed only a weak correlation with mean climate states, but a strong correlation with the stability of these states. We therefore suggest a link between multicentennial variations in solar activity and climate stability. This stability provided more favourable conditions for human subsistence success, and seems to have induced synchrony between regional growth cycles worldwide.
Virus-modified paraspeckle-like condensates are hubs for viral RNA processing and their formation drives genomic instability
Authors: Harper Katherine L. , Harrington Elena M. , Hayward Connor , Anene Chinedu A. , Wongwiwat Wiyada , White Robert E. , Whitehouse Adrian 
Published: November 2024

AbstractThe nucleus is a highly organised yet dynamic environment containing distinct membraneless nuclear bodies. This spatial separation enables a subset of components to be concentrated within biomolecular condensates, allowing efficient and discrete processes to occur which regulate cellular function. One such nuclear body, paraspeckles, are comprised of multiple paraspeckle proteins (PSPs) built around the architectural RNA, NEAT1_2. Paraspeckle function is yet to be fully elucidated but has been implicated in a variety of developmental and disease scenarios. We demonstrate that Kaposi’s sarcoma-associated herpesvirus (KSHV) drives formation of structurally distinct paraspeckles with a dramatically increased size and altered protein composition that are required for productive lytic replication. We highlight these virus-modified paraspeckles form adjacent to virus replication centres, potentially functioning as RNA processing hubs for viral transcripts during infection. Notably, we reveal that PSP sequestration into virus-modified paraspeckles result in increased genome instability during both KSHV and Epstein Barr virus (EBV) infection, implicating their formation in virus-mediated tumourigenesis.
Neuronal diversity and stereotypy at multiple scales through whole brain morphometry
Authors: Liu Yufeng , Jiang Shengdian , Li Yingxin , Zhao Sujun , Yun Zhixi , Zhao Zuo-Han , Zhang Lingli , Wang Gaoyu , Chen Xin , Manubens-Gil Linus , Hang Yuning , Gong Qiaobo , Li Yuanyuan , Qian Penghao , Qu Lei , Garcia-Forn Marta , Wang Wei , De Rubeis Silvia , Wu Zhuhao , Osten Pavel , Gong Hui , Hawrylycz Michael , Mitra Partha , Dong Hongwei , Luo Qingming , Ascoli Giorgio A. , Zeng Hongkui , Liu Lijuan , Peng Hanchuan 
Published: November 2024

AbstractWe conducted a large-scale whole-brain morphometry study by analyzing 3.7 peta-voxels of mouse brain images at the single-cell resolution, producing one of the largest multi-morphometry databases of mammalian brains to date. We registered 204 mouse brains of three major imaging modalities to the Allen Common Coordinate Framework (CCF) atlas, annotated 182,497 neuronal cell bodies, modeled 15,441 dendritic microenvironments, characterized the full morphology of 1876 neurons along with their axonal motifs, and detected 2.63 million axonal varicosities that indicate potential synaptic sites. Our analyzed six levels of information related to neuronal populations, dendritic microenvironments, single-cell full morphology, dendritic and axonal arborization, axonal varicosities, and sub-neuronal structural motifs, along with a quantification of the diversity and stereotypy of patterns at each level. This integrative study provides key anatomical descriptions of neurons and their types across a multiple scales and features, contributing a substantial resource for understanding neuronal diversity in mammalian brains.
scRNA-seq revealed transcriptional signatures of human umbilical cord primitive stem cells and their germ lineage origin regulated by imprinted genes
Authors: Jarczak Justyna , Bujko Kamila , Ratajczak Mariusz Z. , Kucia Magdalena 
Published: November 2024

AbstractA population of CD133+lin-CD45- and CD34+lin-CD45- very small embryonic-like stem cells (VSELs) has been identified in postnatal human tissues, including bone marrow (BM), mobilized peripheral blood (mPB) and umbilical cord blood (UCB). Under appropriate conditions, VSELs in vitro and in vivo differentiate into tissue-committed stem cells for all three germ layers. Molecular analysis of adult murine BM-purified VSELs revealed that these rare cells deposited during development in adult tissues (i) express a similar transcriptome as embryonic stem cells, (ii) share several markers characteristic for epiblast and migratory primordial germ cells (PGCs), (iii) highly express a polycomb group protein enhancer of zeste drosophila homolog 2 (Ezh2) and finally (iv) display a unique pattern of imprinting at crucial paternally inherited genes that promotes their quiescence. Here, by employing single-cell RNA sequencing we demonstrate for the first time that purified from UCB human VSELs defined by expression of CD34 or CD133 antigens and lack of lineage markers, including CD45 antigen express similar molecular signature as murine BM-derived VSELs. Specifically, unsupervised clustering revealed numerous subpopulations of VSELs including ones i) annotated to germline compartments, ii) regulated by parental imprinting, iii) responding to early developmental fate decisions, iv) transcription factors involved in differentiation and development, including homeobox family of genes, and v) expressing innate immunity and purinergic signaling genes.
Synthesis, characterization, molecular docking, pharmacokinetics, and molecular dynamics of new bis-thiazoles based on bis-thiosemicarbazone as anti-coxsackievirus
Authors: Farghaly Thoraya A. , Abbas Eman M. H. , Abd-Elghaffar Heba S. , Elsayed Mohamed A. , Elnaggar Dina H. , El-Sayed Ahmed F. , Abd-Elshafy Dina N. , Mohamed Salwa F. 
Published: November 2024

AbstractIt was known that the majority of viral infections start off as cutaneous eruptions, which heal on their own in most cases. The prognosis is dependent on the state of immunologic surveillance, just like in other infectious disorders. Therefore, those who are immunosuppressed are more in danger. But recently it’s becoming increasingly clear that eruptions that were once thought to be benign diseases can really cause problems and even death, even in immunocompetent patients. Hence, in this article, our goal was to identify possible potential antiviral candidates. We have synthesized a series of bis-thiazole derivatives via the reaction of bis-thiosemicarbazone derivative 3 with hydrazonoyl chlorides and haloketones in an effort to examine their potential antiviral properties and interactions with the main protease of Coxsackievirus B. Spectroscopic methods and elemental analysis were used to corroborate the structures of the novel bis-thiazole derivatives. The most potent derivative, bis-thiazole derivative 7a, was found to have the strongest antiviral activity against Coxsackievirus B (Cox B). Further investigation into its mode of action indicated that compound 7a has a dual activity that inhibits viral adsorption and replication. The efficacy of many compounds against Coxsackievirus adenovirus targets was assessed using molecular docking. The findings revealed that compounds 7a, 7c, 11b and 11c have high binding energies, efficiently engaging the active sites of essential Cox B virus proteins such as the Coxsackievirus adenovirus receptor (CAR), 3C-protease, and RNA-dependent RNA polymerase (RdRp). These interactions involved a variety of chemical bonding types, indicating that these substances can inhibit enzyme activity while also exhibiting substantial antiviral effects involving viral replication and adsorption. Furthermore, the computational ADMET study of these compounds indicated conformance to Lipinski’s criteria, implying positive physicochemical properties. Furthermore, MD simulations demonstrated stable complexes of 7a and 11b with Coxsackievirus adenovirus receptor (CAR), 3C-protease, and RNA dependent RNA polymerase (RdRp) with RMSD (0.1–0.30, 0.20–0.30, and 0.20–0.35 nm), RMSF (0.1–0.5 nm), and SASA (80–105, 140–150, and 220–235). These outcomes further reinforce the potential of these compounds in current antiviral drug development endeavors. The collective findings underscore the potential of these compounds as candidates for antiviral therapies against Coxsackievirus adenovirus.
Optimal control of polar sea-ice near its tipping points
Authors: Kooloth Parvathi , Lu Jian , Bakker Craig , DeSantis Derek , Rupe Adam 
Published: November 2024

AbstractSeveral Earth system components are at a high risk of undergoing rapid, irreversible qualitative changes or “tipping” with increasing climate warming. It is therefore necessary to investigate the feasibility of arresting or even reversing the crossing of tipping thresholds. Here, we study feedback control of an idealized energy balance model (EBM) for Earth’s climate, which exhibits a “small icecap” instability responsible for a rapid transition to an ice-free climate under increasing greenhouse gas forcing. We develop an optimal control strategy for the EBM under different forcing scenarios to reverse sea-ice loss while minimizing costs. Control is achievable for this system, but the cost nearly quadruples once the system tips. While thermal inertia may delay tipping, leading to an overshoot of the critical forcing threshold, this leeway comes with a steep rise in requisite control once tipping occurs. Additionally, we find that the optimal control is localized in the polar region.
Septal wall synthesis is sufficient to change ameba-like cells into uniform oval-shaped cells in Escherichia coli L-forms
Authors: Hayashi Masafumi , Takaoka Chigusa , Higashi Koichi , Kurokawa Ken , Margolin William , Oshima Taku , Shiomi Daisuke 
Published: November 2024

AbstractA cell wall is required to control cell shape and size to maintain growth and division. However, some bacterial species maintain their morphology and size without a cell wall, calling into question the importance of the cell wall to maintain shape and size. It has been very difficult to examine the dispensability of cell wall synthesis in rod-shaped bacteria such as Escherichia coli for maintenance of their shape and size because they lyse without cell walls under normal culture conditions. Here, we show that wall-less E. coli L-form cells, which have a heterogeneous cell morphology, can be converted to a mostly uniform oval shape solely by FtsZ-dependent division, even in the absence of cylindrical cell wall synthesis. This FtsZ-dependent control of cell shape and size in the absence of a cell wall requires at least either the Min or nucleoid occlusion systems for positioning FtsZ at mid cell division sites.
A comprehensive construction of deep neural network‐based encoder–decoder framework for automatic image captioning systems
Authors: Rahman Md Mijanur , Uzzaman Ashik , Sami Sadia Islam , Khatun Fatema , Bhuiyan Md Al‐Amin 
Published: November 2024

AbstractThis study introduces a novel encoder–decoder framework based on deep neural networks and provides a thorough investigation into the field of automatic picture captioning systems. The suggested model uses a “long short‐term memory” decoder for word prediction and sentence construction, and a “convolutional neural network” as an encoder that is skilled at object recognition and spatial information retention. The long short‐term memory network functions as a sequence processor, generating a fixed‐length output vector for final predictions, while the VGG‐19 model is utilized as an image feature extractor. For both training and testing, the study uses a variety of photos from open‐access datasets, such as Flickr8k, Flickr30k, and MS COCO. The Python platform is used for implementation, with Keras and TensorFlow as backends. The experimental findings, which were assessed using the “bilingual evaluation understudy” metric, demonstrate the effectiveness of the suggested methodology in automatically captioning images. By addressing spatial relationships in images and producing logical, contextually relevant captions, the paper advances image captioning technology. Insightful ideas for future study directions are generated by the discussion of the difficulties faced during the experimentation phase. By establishing a strong neural network architecture for automatic picture captioning, this study creates opportunities for future advancement and improvement in the area.
Diffusive shock acceleration of dust grains at supernova remnants
Authors: Cristofari P. , Tatischeff V. , Chabot M. 
Published: November 2024

Context. Diffusive shock acceleration (DSA) is a prominent mechanism for energizing charged particles up to very large rigidities at astrophysical collisionless shocks. In addition to ions and electrons, it has been proposed that interstellar dust grains could also be accelerated through diffusive shock acceleration; for instance, at supernova remnants (SNRs).
Aims. Considering interstellar dust grains of various sizes and compositions, we investigate the possibility of grain acceleration at young SNR shocks (throughout the free expansion and Sedov-Taylor phases) and the maximum energies reached by the accelerated grains. We investigate the potential implications for the abundance of refractory species relative to volatile elements in the cosmic-ray composition.
Methods. We rely on semi-analytical descriptions of particle acceleration at strong shocks, and on self-similar solutions for the dynamics of SNR shock waves. For simplicity, type Ia thermonuclear SNRs expanding in a uniform interstellar medium are considered.
Results. We find that the acceleration of dust grains at relativistic speed is possible, up to a Lorentz factor of ∼102 and a kinetic energy of Ek/nuc ∼ 102 GeV/nuc for the smaller grains of size a ∼ 5 × 10−7 cm. We find that the subsequent sputtering of grains can produce nuclei with a sufficient rigidity to be injected in the process of diffusive shock acceleration. Such a scenario can help naturally account for the overabundance of refractory elements in the Galactic cosmic-ray composition, provided that a fraction, η ∼ 10−3 − 10−2, of dust grains swept up by an SNR are energized through DSA.
Chefsache Delirmanagement
Authors: Heeser Alexandra 
Published: November 2024

ZusammenfassungFast ein Drittel der Patienten erkrankt in der Klinik an einem Delir – viele haben bereits zuvor
Symptome. Prävention und Behandlung spielen eine immer größere Rolle. Das Thema in den Fokus zu nehmen
und passende Konzepte zu entwickeln ist auch Managementaufgabe.
Palliative treatment of malignant intestinal obstruction with EUS-guided ileosigmoidostomy – a case report
Authors: Zundler Sebastian , Wolff Kerstin , Leppkes Moritz , Gaza Anne , Haberkamp Sophie , Strobel Deike , Siebler Jürgen , Neurath Markus F. , Waldner Maximilian 
Published: November 2024

AbstractWe present the case of a 70-year-old patient of Caucasian origin under palliative chemotherapy for metastasized colorectal cancer, who presented with signs of complete small bowel obstruction six months after placement of a diverting ileostomy. Following previous tumor perforation, he was not considered a candidate for further surgical intervention.Thus, endoscopic ultrasound-guided enterocolostomy (i.e., ileosigmoidostomy) with a lumen-apposing metal stent was successfully performed in a coloenteric approach to restore the passage.Oral nutrition could be resumed the next day, and the patient could be discharged in substantially improved condition after three days.