bluuebunny/crossref_metadata_2025_split huggingface dataset:
The power of Drosophila genetics in studying insect toxicology and chemical ecology
Authors: Huang Jia , Lee Youngseok 
Published: November 2023

AbstractInsect toxicology and chemical ecology are inherently interconnected disciplines, both dedicated to unraveling the intricate relationships between insects and the diverse array of chemical compounds that pervade their surroundings. Drosophila melanogaster, owing to its genetic and physiological similarities to other insects, serves as a robust model system in the study of insect toxicology. Moreover, state-of-the-art techniques in Drosophila neurobiology have extensively probed the chemosensory system of insects, providing significant insights into their adaptation to chemical environments. In this review, we emphasize the advancements achieved through the application of Drosophila genetics in investigations spanning both of these fields, significantly enhancing our understanding of the mode of action and resistance mechanisms of insecticides, as well as unraveling the molecular and cellular mechanisms underlying insect chemosensation and associated behaviors. The profound insights derived through this tiny fly not only enrich our understanding of the broader world of insects but also hold the potential to develop more effective and sustainable strategies for pest management.
Darfur Model, Rwanda, and the ICTR: John Hagan’s Sociology of Genocide Continued
Authors: Savelsberg Joachim J. , Chambers Brooke B. 
Published: November 2023

AbstractCore contributions from John Hagan’s scholarship on genocide are at stake in this article. First, this article examines, for the Rwandan genocide, the applicability of Hagan and Wenona Rymond-Richmond’s multi-level causal model of genocide, developed in Darfur and the Crime of Genocide. Asking how causal factors and processes highlighted in that model play out in scholarship on the Rwandan genocide, it moves toward answering the question of external validity versus historical specificity. Second, the article examines, again with a focus on Rwanda, the relationship between social scientific explanation and judicial thought. While it highlights—in line with the first author’s previous work—how judicial narratives address or select out core factors highlighted in the Darfur model, the article focuses—in line with Hagan’s Justice in the Balkans—on the question of what knowledge social science can nevertheless gain from court proceedings. An analysis of a sample of cases processed by the International Criminal Tribunal for Rwanda identifies overlaps with social science analyses, but it also highlights distinctions.
NEW LIGHT ON THE ADDITAMENTVM ALDINVM (SILIUS ITALICUS, PVNICA 8.144–223)
Authors: Nagy Benjamin C. , Lee †Janice M. 
Published: November 2023

AbstractThe authenticity of the Additamentum Aldinum (Sil. Pun. 8.144–223) has long been a matter of debate. While many scholars have expressed doubts that it is by Silius and suggest rather that it is from the hands of a skilful humanist, it has not, up to this time, been possible to provide solid evidence to support their intuition. This paper not only re-examines the standard arguments for and against authenticity but brings the latest computational stylometric techniques to bear on the question. These analyses reveal that the style of the Additamentum differs in statistically significant terms from the rest of Silius’ Punica.1
Modeling the Evolution of Lunar Regolith: 2. Growth Rate and Spatial Distribution
Authors: Zhang Mingwei , Fa Wenzhe , Barnard Emily M. , Eke Vincent R. 
Published: November 2023

AbstractThe evolution of regolith thickness induced by continuous impact events on the lunar surface provides valuable information about lunar geology and the bombardment history of the inner Solar System. In this study, we develop a Lunar Topography and Regolith Evolution Model based on the production and distribution of lunar regolith resulting from individual impact craters. Considering the changing impact flux, evolving target properties, topographic degradation process, and crater superposition, our model simultaneously simulates both the spatial and temporal evolution of lunar cratered topography and regolith thickness. The modeled regolith thickness generally aligns with results estimated by in situ seismic experiments and measurements of small crater morphology. Through our simulations, we establish a novel quantitative relation between regolith growth rate and time, providing new constraints on the impact flux trend and buffering trend in the regolith growth process. By comparing this new relation with that predicted by our analytical regolith evolution model, we reveal the significant influences of evolving target properties and regolith distribution on the regolith growth rate. Our modeled results also show that the regional regolith thickness follows a characteristic long‐tailed distribution with substantial lateral variations. Both the root‐mean‐square fluctuation and correlation length of lunar regolith increase with lateral scale and the surface age, which are ∼4.7 and 18 m on the hectometer scale at 3.5 Ga. All these results contribute to a better understanding of the regolith evolution process and can provide valuable insights into the lunar surface dynamics.
Deubiquitinase USP1 enhances CCAAT/enhancer-binding protein beta (C/EBPβ) stability and accelerates adipogenesis and lipid accumulation
Authors: Kim Myung Sup , Baek Jung-Hwan , Lee JinAh , Sivaraman Aneesh , Lee Kyeong , Chun Kyung-Hee 
Published: November 2023

AbstractDysregulation of the ubiquitin-proteasome system has been implicated in the pathogenesis of several metabolic disorders, including obesity, diabetes, and non-alcoholic fatty liver disease; however, the mechanisms controlling pathogenic metabolic disorders remain unclear. Transcription factor CCAAT/enhancer binding protein beta (C/EBPβ) regulates adipogenic genes. The study showed that the expression level of C/EBPβ is post-translationally regulated by the deubiquitinase ubiquitin-specific protease 1 (USP1) and that USP1 expression is remarkably upregulated during adipocyte differentiation and in the adipose tissue of mice fed a high-fat diet (HFD). We found that USP1 directly interacts with C/EBPβ. Knock-down of USP1 decreased C/EBPβ protein stability and increased its ubiquitination. Overexpression of USP1 regulates its protein stability and ubiquitination, whereas catalytic mutant of USP1 had no effect on them. It suggests that USP1 directly deubiquitinases C/EBPβ and increases the protein expression, leading to adipogenesis and lipid accumulation. Notably, the USP1-specific inhibitor ML323—originally developed to sensitize cancer cells to DNA-damaging agents—decreased adipocyte differentiation and lipid accumulation in 3T3-L1 cells without cytotoxicity. Oral gavage of ML323 was administered to HFD-fed mice, which showed weight loss and improvement in insulin and glucose sensitivity. Both fat mass and adipocyte size in white adipose tissues were significantly reduced by ML323 treatment, which also reduced the expression of genes involved in adipogenesis and inflammatory responses. ML323 also reduced lipid accumulation, hepatic triglycerides, free fatty acids, and macrophage infiltration in the livers of HFD-fed mice. Taken together, we suggest that USP1 plays an important role in adipogenesis by regulating C/EBPβ ubiquitination, and USP1-specific inhibitor ML323 is a potential treatment option and further study by ML323 is needed for clinical application for metabolic disorders.
Engineered compact pan-neuronal promoter from Alphaherpesvirus LAP2 enhances target gene expression in the mouse brain and reduces tropism in the liver
Authors: Maturana Carola J. 
Published: November 2023

AbstractSmall promoters capable of driving potent neuron-restricted gene expression are required to support successful brain circuitry and clinical gene therapy studies. However, converting large promoters into functional MiniPromoters, which can be used in vectors with limited capacity, remains challenging. In this study, we describe the generation of a novel version of alphaherpesvirus latency-associated promoter 2 (LAP2), which facilitates precise transgene expression exclusively in the neurons of the mouse brain while minimizing undesired targeting in peripheral tissues. Additionally, we aimed to create a compact neural promoter to facilitate packaging of larger transgenes. Our results revealed that MiniLAP2 (278 bp) drives potent transgene expression in all neurons in the mouse brain, with little to no expression in glial cells. In contrast to the native promoter, MiniLAP2 reduced tropism in the spinal cord and liver. No expression was detected in the kidney or skeletal muscle. In summary, we developed a minimal pan-neuronal promoter that drives specific and robust transgene expression in the mouse brain when delivered intravenously via AAV-PHP.eB vector. The use of this novel MiniPromoter may broaden the range of deliverable therapeutics and improve their safety and efficacy by minimizing the potential for off-target effects.
Complex 33-beam simulated galactic cosmic radiation exposure impacts cognitive function and prefrontal cortex neurotransmitter networks in male mice
Authors: Desai Rajeev I. , Kangas Brian D. , Luc Oanh T. , Solakidou Eleana , Smith Evan C. , Dawes Monica H. , Ma Xiaoyu , Makriyannis Alexandros , Chatterjee Subhamoy , Dayeh Maher A. , Muñoz-Jaramillo Andrés , Desai Mihir I. , Limoli Charles L. 
Published: November 2023

AbstractAstronauts will encounter extended exposure to galactic cosmic radiation (GCR) during deep space exploration, which could impair brain function. Here, we report that in male mice, acute or chronic GCR exposure did not modify reward sensitivity but did adversely affect attentional processes and increased reaction times. Potassium (K+)-stimulation in the prefrontal cortex (PFC) elevated dopamine (DA) but abolished temporal DA responsiveness after acute and chronic GCR exposure. Unlike acute GCR, chronic GCR increased levels of all other neurotransmitters, with differences evident between groups after higher K+-stimulation. Correlational and machine learning analysis showed that acute and chronic GCR exposure differentially reorganized the connection strength and causation of DA and other PFC neurotransmitter networks compared to controls which may explain space radiation-induced neurocognitive deficits.
Synaptotagmin-7 outperforms synaptotagmin-1 to promote the formation of large, stable fusion pores via robust membrane penetration
Authors: Courtney Kevin C. , Mandal Taraknath , Mehta Nikunj , Wu Lanxi , Li Yueqi , Das Debasis , Cui Qiang , Chapman Edwin R. 
Published: November 2023

AbstractSynaptotagmin-1 and synaptotagmin-7 are two prominent calcium sensors that regulate exocytosis in neuronal and neuroendocrine cells. Upon binding calcium, both proteins partially penetrate lipid bilayers that bear anionic phospholipids, but the specific underlying mechanisms that enable them to trigger exocytosis remain controversial. Here, we examine the biophysical properties of these two synaptotagmin isoforms and compare their interactions with phospholipid membranes. We discover that synaptotagmin-1—membrane interactions are greatly influenced by membrane order; tight packing of phosphatidylserine inhibits binding due to impaired membrane penetration. In contrast, synaptotagmin-7 exhibits robust membrane binding and penetration activity regardless of phospholipid acyl chain structure. Thus, synaptotagmin-7 is a super-penetrator. We exploit these observations to specifically isolate and examine the role of membrane penetration in synaptotagmin function. Using nanodisc-black lipid membrane electrophysiology, we demonstrate that membrane penetration is a critical component that underlies how synaptotagmin proteins regulate reconstituted, exocytic fusion pores in response to calcium.
In situ observation of a stepwise [2 + 2] photocycloaddition process using fluorescence spectroscopy
Authors: Wang Meng-Fan , Deng Yun-Hu , Hong Yu-Xuan , Gu Jia-Hui , Cao Yong-Yong , Liu Qi , Braunstein Pierre , Lang Jian-Ping 
Published: November 2023

AbstractUsing highly sensitive and selective in situ techniques to investigate the dynamics of intermediates formation is key to better understand reaction mechanisms. However, investigating the early stages of solid-state reactions/transformations is still challenging. Here we introduce in situ fluorescence spectroscopy to observe the evolution of intermediates during a two-step [2 + 2] photocycloaddition process in a coordination polymer platform. The structural changes and kinetics of each step under ultraviolet light irradiation versus time are accompanied by the gradual increase-decrease of intensity and blue-shift of the fluorescence spectra from the crystals. Monitoring the fluorescence behavior using a laser scanning confocal microscope can directly visualize the inhomogeneity of the photocycloaddition reaction in a single crystal. Theoretical calculations allow us to rationalize the fluorescence behavior of these compounds. We provide a convenient strategy for visualizing the solid-state photocycloaddition dynamics using fluorescence spectroscopy and open an avenue for kinetic studies of a variety of fast reactions.
Fragment-sequencing unveils local tissue microenvironments at single-cell resolution
Authors: Handler Kristina , Bach Karsten , Borrelli Costanza , Piscuoglio Salvatore , Ficht Xenia , Acar Ilhan E. , Moor Andreas E. 
Published: November 2023

AbstractCells collectively determine biological functions by communicating with each other—both through direct physical contact and secreted factors. Consequently, the local microenvironment of a cell influences its behavior, gene expression, and cellular crosstalk. Disruption of this microenvironment causes reciprocal changes in those features, which can lead to the development and progression of diseases. Hence, assessing the cellular transcriptome while simultaneously capturing the spatial relationships of cells within a tissue provides highly valuable insights into how cells communicate in health and disease. Yet, methods to probe the transcriptome often fail to preserve native spatial relationships, lack single-cell resolution, or are highly limited in throughput, i.e. lack the capacity to assess multiple environments simultaneously. Here, we introduce fragment-sequencing (fragment-seq), a method that enables the characterization of single-cell transcriptomes within multiple spatially distinct tissue microenvironments. We apply fragment-seq to a murine model of the metastatic liver to study liver zonation and the metastatic niche. This analysis reveals zonated genes and ligand-receptor interactions enriched in specific hepatic microenvironments. Finally, we apply fragment-seq to other tissues and species, demonstrating the adaptability of our method.
Metagenomic profiles of archaea and bacteria within thermal and geochemical gradients of the Guaymas Basin deep subsurface
Authors: Mara Paraskevi , Geller-McGrath David , Edgcomb Virginia , Beaudoin David , Morono Yuki , Teske Andreas 
Published: November 2023

AbstractPrevious studies of microbial communities in subseafloor sediments reported that microbial abundance and diversity decrease with sediment depth and age, and microbes dominating at depth tend to be a subset of the local seafloor community. However, the existence of geographically widespread, subsurface-adapted specialists is also possible. Here, we use metagenomic and metatranscriptomic analyses of the hydrothermally heated, sediment layers of Guaymas Basin (Gulf of California, Mexico) to examine the distribution and activity patterns of bacteria and archaea along thermal, geochemical and cell count gradients. We find that the composition and distribution of metagenome-assembled genomes (MAGs), dominated by numerous lineages of Chloroflexota and Thermoproteota, correlate with biogeochemical parameters as long as temperatures remain moderate, but downcore increasing temperatures beyond ca. 45 ºC override other factors. Consistently, MAG size and diversity decrease with increasing temperature, indicating a downcore winnowing of the subsurface biosphere. By contrast, specific archaeal MAGs within the Thermoproteota and Hadarchaeota increase in relative abundance and in recruitment of transcriptome reads towards deeper, hotter sediments, marking the transition towards a specialized deep, hot biosphere.
A promising perovskite primary explosive
Authors: Feng Yongan , Zhang Jichuan , Cao Weiguo , Zhang Jiaheng , Shreeve Jean’ne M. 
Published: November 2023

AbstractA primary explosive is an ideal chemical substance for performing ignition in military and commercial applications. For over 150 years, nearly all of the developed primary explosives have suffered from various issues, such as troublesome syntheses, high toxicity, poor stability or/and weak ignition performance. Now we report an interesting example of a primary explosive with double perovskite framework, {(C6H14N2)2[Na(NH4)(IO4)6]}n (DPPE-1), which was synthesized using a simple green one-pot method in an aqueous solution at room temperature. DPPE-1 is free of heavy metals, toxic organic components, and doesn’t involve any explosive precursors. It exhibits good stability towards air, moisture, sunlight, and heat and has acceptable mechanical sensitivities. It affords ignition performance on par with the most powerful primary explosives reported to date. DPPE-1 promises to meet the challenges existing with current primary explosives, and this work could trigger more extensive applications of perovskite.
Ultra-durable cell-free bioactive hydrogel with fast shape memory and on-demand drug release for cartilage regeneration
Authors: Yang Yuxuan , Zhao Xiaodan , Wang Shuang , Zhang Yanfeng , Yang Aiming , Cheng Yilong , Chen Xuesi 
Published: November 2023

AbstractOsteoarthritis is a worldwide prevalent disease that imposes a significant socioeconomic burden on individuals and healthcare systems. Achieving cartilage regeneration in patients with osteoarthritis remains challenging clinically. In this work, we construct a multiple hydrogen-bond crosslinked hydrogel loaded with tannic acid and Kartogenin by polyaddition reaction as a cell-free scaffold for in vivo cartilage regeneration, which features ultra-durable mechanical properties and stage-dependent drug release behavior. We demonstrate that the hydrogel can withstand 28000 loading-unloading mechanical cycles and exhibits fast shape memory at body temperature (30 s) with the potential for minimally invasive surgery. We find that the hydrogel can also alleviate the inflammatory reaction and regulate oxidative stress in situ to establish a microenvironment conducive to healing. We show that the sequential release of tannic acid and Kartogenin can promote the migration of bone marrow mesenchymal stem cells into the hydrogel scaffold, followed by the induction of chondrocyte differentiation, thus leading to full-thickness cartilage regeneration in vivo. This work may provide a promising solution to address the problem of cartilage regeneration.
Anomalous efficiency elevation of quantum-dot light-emitting diodes induced by operational degradation
Authors: He Siyu , Tang Xiaoqi , Deng Yunzhou , Yin Ni , Jin Wangxiao , Lu Xiuyuan , Chen Desui , Wang Chenyang , Sun Tulai , Chen Qi , Jin Yizheng 
Published: November 2023

AbstractQuantum-dot light-emitting diodes promise a new generation of high-performance and solution-processed electroluminescent light sources. Understanding the operational degradation mechanisms of quantum-dot light-emitting diodes is crucial for their practical applications. Here, we show that quantum-dot light-emitting diodes may exhibit an anomalous degradation pattern characterized by a continuous increase in electroluminescent efficiency upon electrical stressing, which deviates from the typical decrease in electroluminescent efficiency observed in other light-emitting diodes. Various in-situ/operando characterizations were performed to investigate the evolutions of charge dynamics during the efficiency elevation, and the alterations in electric potential landscapes in the active devices. Furthermore, we carried out selective peel-off-and-rebuild experiments and depth-profiling analyses to pinpoint the critical degradation site and reveal the underlying microscopic mechanism. The results indicate that the operation-induced efficiency increase results from the degradation of electron-injection capability at the electron-transport layer/cathode interface, which in turn leads to gradually improved charge balance. Our work provides new insights into the degradation of red quantum-dot light-emitting diodes and has far-reaching implications for the design of charge-injection interfaces in solution-processed light-emitting diodes.
LipIDens: simulation assisted interpretation of lipid densities in cryo-EM structures of membrane proteins
Authors: Ansell T. Bertie , Song Wanling , Coupland Claire E. , Carrique Loic , Corey Robin A. , Duncan Anna L. , Cassidy C. Keith , Geurts Maxwell M. G. , Rasmussen Tim , Ward Andrew B. , Siebold Christian , Stansfeld Phillip J. , Sansom Mark S. P. 
Published: November 2023

AbstractCryo-electron microscopy (cryo-EM) enables the determination of membrane protein structures in native-like environments. Characterising how membrane proteins interact with the surrounding membrane lipid environment is assisted by resolution of lipid-like densities visible in cryo-EM maps. Nevertheless, establishing the molecular identity of putative lipid and/or detergent densities remains challenging. Here we present LipIDens, a pipeline for molecular dynamics (MD) simulation-assisted interpretation of lipid and lipid-like densities in cryo-EM structures. The pipeline integrates the implementation and analysis of multi-scale MD simulations for identification, ranking and refinement of lipid binding poses which superpose onto cryo-EM map densities. Thus, LipIDens enables direct integration of experimental and computational structural approaches to facilitate the interpretation of lipid-like cryo-EM densities and to reveal the molecular identities of protein-lipid interactions within a bilayer environment. We demonstrate this by application of our open-source LipIDens code to ten diverse membrane protein structures which exhibit lipid-like densities.
OVOL2 sustains postnatal thymic epithelial cell identity
Authors: Zhong Xue , Peddada Nagesh , Wang Jianhui , Moresco James J. , Zhan Xiaowei , Shelton John M. , SoRelle Jeffrey A. , Keller Katie , Lazaro Danielle Renee , Moresco Eva Marie Y. , Choi Jin Huk , Beutler Bruce 
Published: November 2023

AbstractDistinct pathways and molecules may support embryonic versus postnatal thymic epithelial cell (TEC) development and maintenance. Here, we identify a mechanism by which TEC numbers and function are maintained postnatally. A viable missense allele (C120Y) of Ovol2, expressed ubiquitously or specifically in TECs, results in lymphopenia, in which T cell development is compromised by loss of medullary TECs and dysfunction of cortical TECs. We show that the epithelial identity of TECs is aberrantly subverted towards a mesenchymal state in OVOL2-deficient mice. We demonstrate that OVOL2 inhibits the epigenetic regulatory BRAF-HDAC complex, specifically disrupting RCOR1-LSD1 interaction. This causes inhibition of LSD1-mediated H3K4me2 demethylation, resulting in chromatin accessibility and transcriptional activation of epithelial genes. Thus, OVOL2 controls the epigenetic landscape of TECs to enforce TEC identity. The identification of a non-redundant postnatal mechanism for TEC maintenance offers an entry point to understanding thymic involution, which normally begins in early adulthood.