bluuebunny/crossref_metadata_2025_split huggingface dataset:
The β-arrestin1/endothelin axis bolsters ovarian fibroblast-dependent invadosome activity and cancer cell metastatic potential
Authors: Del Rio Danila , Masi Ilenia , Caprara Valentina , Ottavi Flavia , Albertini Petroni Gabriele , Salvati Erica , Trisciuoglio Daniela , Giannitelli Sara Maria , Bagnato Anna , Mauri Emanuele , Spadaro Francesca , Rosanò Laura 
Published: May 2024

AbstractRecruitment of fibroblasts to tumors and their activation into cancer-associated fibroblasts (CAFs) is a strategy used by tumor cells to direct extracellular matrix (ECM) remodeling, invasion, and metastasis, highlighting the need to investigate the molecular mechanisms driving CAF function. Endothelin-1 (ET-1) regulates the communication between cancer and stroma and facilitates the progression of serous ovarian cancer (SOC). By binding to Endothelin A (ETA) and B (ETB) receptors, ET-1 enables the recruitment of β-arrestin1 (β-arr1) and the formation of signaling complexes that coordinate tumor progression. However, how ET-1 receptors might “educate” human ovarian fibroblasts (HOFs) to produce altered ECM and promote metastasis remains to be elucidated. This study identifies ET-1 as a pivotal factor in the activation of CAFs capable of proteolytic ECM remodeling and the generation of heterotypic spheroids containing cancer cells with a propensity to metastasize. An autocrine/paracrine ET-1/ETA/BR/β-arr1 loop enhances HOF proliferation, upregulates CAF marker expression, secretes pro-inflammatory cytokines, and increases collagen contractility, and cell motility. Furthermore, ET-1 facilitates ECM remodeling by promoting the lytic activity of invadosome and activation of integrin β1. In addition, ET-1 signaling supports the formation of heterotypic HOF/SOC spheroids with enhanced ability to migrate through the mesothelial monolayer, and invade, representing metastatic units. The blockade of ETA/BR or β-arr1 silencing prevents CAF activation, invadosome function, mesothelial clearance, and the invasive ability of heterotypic spheroids. In vivo, therapeutic inhibition of ETA/BR using bosentan (BOS) significantly reduces the metastatic potential of combined HOFs/SOC cells, associated with enhanced apoptotic effects on tumor cells and stromal components. These findings support a model in which ET-1/β-arr1 reinforces tumor/stroma interaction through CAF activation and fosters the survival and metastatic properties of SOC cells, which could be counteracted by ETA/BR antagonists.
Need for standardization of Influenza A virus-induced cell death in vivo to improve consistency of inter-laboratory research findings
Authors: Oltean Teodora , Maelfait Jonathan , Saelens Xavier , Vandenabeele Peter 
Published: May 2024

AbstractThe involvement of necroptosis in the control of influenza A virus (IAV) infection has been reported in multiple studies. Downstream of the nucleic acid sensor ZBP1, RIPK3 kinase activity is critically involved in the induction of necroptotic cell death by phosphorylating MLKL, while RIPK3 as a scaffold can induce apoptosis. Paradoxically, RIPK3-deficiency of mice may result in increased or decreased susceptibility to IAV infection. Here, we critically review the published reports on the involvement of RIPK3 in IAV infection susceptibility and try to identify differences in experimental settings that could explain seemingly conflicting outcomes. Analysis of the experimental reports revealed differences in the IAV challenge dose, the IAV inoculum preparation, IAV titer assessment, as well as the route of inoculation between studies. Furthermore, differences were noticed in the inclusion of littermate controls, which show high variance in viral sensitivity. Our evaluation argues for a standardized setup for IAV infection experiments including the preparation of the IAV virus, the use of different IAV infectious doses description and the proper experimental genetic controls of the mouse strains to increase inter-laboratory consistency in this field.
The role of plasmacytoid dendritic cells (pDCs) in immunity during viral infections and beyond
Authors: Ngo Clémence , Garrec Clémence , Tomasello Elena , Dalod Marc 
Published: May 2024

AbstractType I and III interferons (IFNs) are essential for antiviral immunity and act through two different but complimentary pathways. First, IFNs activate intracellular antimicrobial programs by triggering the upregulation of a broad repertoire of viral restriction factors. Second, IFNs activate innate and adaptive immunity. Dysregulation of IFN production can lead to severe immune system dysfunction. It is thus crucial to identify and characterize the cellular sources of IFNs, their effects, and their regulation to promote their beneficial effects and limit their detrimental effects, which can depend on the nature of the infected or diseased tissues, as we will discuss. Plasmacytoid dendritic cells (pDCs) can produce large amounts of all IFN subtypes during viral infection. pDCs are resistant to infection by many different viruses, thus inhibiting the immune evasion mechanisms of viruses that target IFN production or their downstream responses. Therefore, pDCs are considered essential for the control of viral infections and the establishment of protective immunity. A thorough bibliographical survey showed that, in most viral infections, despite being major IFN producers, pDCs are actually dispensable for host resistance, which is achieved by multiple IFN sources depending on the tissue. Moreover, primary innate and adaptive antiviral immune responses are only transiently affected in the absence of pDCs. More surprisingly, pDCs and their IFNs can be detrimental in some viral infections or autoimmune diseases. This makes the conservation of pDCs during vertebrate evolution an enigma and thus raises outstanding questions about their role not only in viral infections but also in other diseases and under physiological conditions.
Post-COVID conditions following COVID-19 vaccination: a retrospective matched cohort study of patients with SARS-CoV-2 infection
Authors: Malden Debbie E. , Liu In-Lu Amy , Qian Lei , Sy Lina S. , Lewin Bruno J. , Asamura Dawn T. , Ryan Denison S. , Bezi Cassandra , Williams Joshua T. B. , Kaiser Robyn , Daley Matthew F. , Nelson Jennifer C. , McClure David L. , Zerbo Ousseny , Henninger Michelle L. , Fuller Candace C. , Weintraub Eric S. , Saydah Sharon , Tartof Sara Y. 
Published: May 2024

AbstractCOVID-19 vaccinations protect against severe illness and death, but associations with post-COVID conditions (PCC) are less clear. We aimed to evaluate the association between prior COVID-19 vaccination and new-onset PCC among individuals with SARS-CoV-2 infection across eight large healthcare systems in the United States. This retrospective matched cohort study used electronic health records (EHR) from patients with SARS-CoV-2 positive tests during March 2021-February 2022. Vaccinated and unvaccinated COVID-19 cases were matched on location, test date, severity of acute infection, age, and sex. Vaccination status was ascertained using EHR and integrated data on externally administered vaccines. Adjusted relative risks (RRs) were obtained from Poisson regression. PCC was defined as a new diagnosis in one of 13 PCC categories 30 days to 6 months following a positive SARS-CoV-2 test. The study included 161,531 vaccinated COVID-19 cases and 161,531 matched unvaccinated cases. Compared to unvaccinated cases, vaccinated cases had a similar or lower risk of all PCC categories except mental health disorders (RR: 1.06, 95% CI: 1.02–1.10). Vaccination was associated with ≥10% lower risk of sensory (RR: 0.90, 0.86–0.95), circulatory (RR: 0.88, 0.83–0.94), blood and hematologic (RR: 0.79, 0.71–0.89), skin and subcutaneous (RR: 0.69, 0.66–0.72), and non-specific COVID-19 related disorders (RR: 0.53, 0.51–0.56). In general, associations were stronger at younger ages but mostly persisted regardless of SARS-CoV-2 variant period, receipt of ≥3 vs. 1–2 vaccine doses, or time since vaccination. Pre-infection vaccination was associated with reduced risk of several PCC outcomes and hence may decrease the long-term consequences of COVID-19.
A modular framework for multi-scale tissue imaging and neuronal segmentation
Authors: Cauzzo Simone , Bruno Ester , Boulet David , Nazac Paul , Basile Miriam , Callara Alejandro Luis , Tozzi Federico , Ahluwalia Arti , Magliaro Chiara , Danglot Lydia , Vanello Nicola 
Published: May 2024

AbstractThe development of robust tools for segmenting cellular and sub-cellular neuronal structures lags behind the massive production of high-resolution 3D images of neurons in brain tissue. The challenges are principally related to high neuronal density and low signal-to-noise characteristics in thick samples, as well as the heterogeneity of data acquired with different imaging methods. To address this issue, we design a framework which includes sample preparation for high resolution imaging and image analysis. Specifically, we set up a method for labeling thick samples and develop SENPAI, a scalable algorithm for segmenting neurons at cellular and sub-cellular scales in conventional and super-resolution STimulated Emission Depletion (STED) microscopy images of brain tissues. Further, we propose a validation paradigm for testing segmentation performance when a manual ground-truth may not exhaustively describe neuronal arborization. We show that SENPAI provides accurate multi-scale segmentation, from entire neurons down to spines, outperforming state-of-the-art tools. The framework will empower image processing of complex neuronal circuitries.
Hippocampal sharp-wave ripples correlate with periods of naturally occurring self-generated thoughts in humans
Authors: Iwata Takamitsu , Yanagisawa Takufumi , Ikegaya Yuji , Smallwood Jonathan , Fukuma Ryohei , Oshino Satoru , Tani Naoki , Khoo Hui Ming , Kishima Haruhiko 
Published: May 2024

AbstractCore features of human cognition highlight the importance of the capacity to focus on information distinct from events in the here and now, such as mind wandering. However, the brain mechanisms that underpin these self-generated states remain unclear. An emerging hypothesis is that self-generated states depend on the process of memory replay, which is linked to sharp-wave ripples (SWRs), which are transient high-frequency oscillations originating in the hippocampus. Local field potentials were recorded from the hippocampus of 10 patients with epilepsy for up to 15 days, and experience sampling was used to describe their association with ongoing thought patterns. The SWR rates were higher during extended periods of time when participants’ ongoing thoughts were more vivid, less desirable, had more imaginable properties, and exhibited fewer correlations with an external task. These data suggest a role for SWR in the patterns of ongoing thoughts that humans experience in daily life.
Abrupt onset of intensive human occupation 44,000 years ago on the threshold of Sahul
Authors: Shipton Ceri , Morley Mike W. , Kealy Shimona , Norman Kasih , Boulanger Clara , Hawkins Stuart , Litster Mirani , Withnell Caitlin , O’Connor Sue 
Published: May 2024

AbstractArchaeological evidence attests multiple early dispersals of Homo sapiens out of Africa, but genetic evidence points to the primacy of a single dispersal 70-40 ka. Laili in Timor-Leste is on the southern dispersal route between Eurasia and Australasia and has the earliest record of human occupation in the eastern Wallacean archipelago. New evidence from the site shows that, unusually in the region, sediment accumulated in the shelter without human occupation, in the window 59–54 ka. This was followed by an abrupt onset of intensive human habitation beginning ~44 ka. The initial occupation is distinctive from overlying layers in the aquatic focus of faunal exploitation, while it has similarities in material culture to other early Homo sapiens sites in Wallacea. We suggest that the intensive early occupation at Laili represents a colonisation phase, which may have overwhelmed previous human dispersals in this part of the world.
Cystine-knot peptide inhibitors of HTRA1 bind to a cryptic pocket within the active site region
Authors: Li Yanjie , Wei Yuehua , Ultsch Mark , Li Wei , Tang Wanjian , Tombling Benjamin , Gao Xinxin , Dimitrova Yoana , Gampe Christian , Fuhrmann Jakob , Zhang Yingnan , Hannoush Rami N. , Kirchhofer Daniel 
Published: May 2024

AbstractCystine-knot peptides (CKPs) are naturally occurring peptides that exhibit exceptional chemical and proteolytic stability. We leveraged the CKP carboxypeptidase A1 inhibitor as a scaffold to construct phage-displayed CKP libraries and subsequently screened these collections against HTRA1, a trimeric serine protease implicated in age-related macular degeneration and osteoarthritis. The initial hits were optimized by using affinity maturation strategies to yield highly selective and potent picomolar inhibitors of HTRA1. Crystal structures, coupled with biochemical studies, reveal that the CKPs do not interact in a substrate-like manner but bind to a cryptic pocket at the S1’ site region of HTRA1 and abolish catalysis by stabilizing a non-competent active site conformation. The opening and closing of this cryptic pocket is controlled by the gatekeeper residue V221, and its movement is facilitated by the absence of a constraining disulfide bond that is typically present in trypsin fold serine proteases, thereby explaining the remarkable selectivity of the CKPs. Our findings reveal an intriguing mechanism for modulating the activity of HTRA1, and highlight the utility of CKP-based phage display platforms in uncovering potent and selective inhibitors against challenging therapeutic targets.
Organocatalytic skeletal reorganization for enantioselective synthesis of S-stereogenic sulfinamides
Authors: Liu Zanjiao , Fang Siqiang , Li Haoze , Xiao Chunxiu , Xiao Kai , Su Zhishan , Wang Tianli 
Published: May 2024

AbstractThe enantioselective synthesis of S-stereogenic sulfinamides has garnered considerable attention due to their structural and physicochemical properties. However, catalytic asymmetric synthesis of sulfinamides still remains daunting challenges, impeding their broad application in drug discovery and development. Here, we present an approach for the synthesis of S-stereogenic sulfinamides through peptide-mimic phosphonium salt-catalyzed asymmetric skeletal reorganization of simple prochiral and/or racemic sulfoximines. This methodology allows for the facile access to a diverse array of substituted sulfinamides with excellent enantioselectivities, accommodating various substituent patterns through desymmetrization or parallel kinetic resolution process. Mechanistic experiments, coupled with density functional theory calculations, clarify a stepwise pathway involving ring-opening and ring-closing processes, with the ring-opening step identified as crucial for achieving stereoselective control. Given the prevalence of S-stereogenic centers in pharmaceuticals, we anticipate that this protocol will enhance the efficient and precise synthesis of relevant chiral molecules and their analogs, thereby contributing to advancements in drug discovery.
Intermolecular interactions probed by rotational dynamics in gas-phase clusters
Authors: Lu Chenxu , Xu Long , Zhou Lianrong , Shi Menghang , Lu Peifen , Li Wenxue , Dörner Reinhard , Lin Kang , Wu Jian 
Published: May 2024

AbstractThe rotational dynamics of a molecule is sensitive to neighboring atoms or molecules, which can be used to probe the intermolecular interactions in the gas phase. Here, we real-time track the laser-driven rotational dynamics of a single N2 molecule affected by neighboring Ar atoms using coincident Coulomb explosion imaging. We find that the alignment trace of N-N axis decays fast and only persists for a few picoseconds when an Ar atom is nearby. We show that the decay rate depends on the rotational geometry of whether the Ar atom stays in or out of the rotational plane of the N2 molecule. Additionally, the vibration of the van der Waals bond is found to be excited through coupling with the rotational N-N axis. The observations are well reproduced by solving the time-dependent Schrödinger equation after taking the interaction potential between the N2 and Ar into consideration. Our results demonstrate that environmental effects on a molecular level can be probed by directly visualizing the rotational dynamics.
Large-scale spatially explicit analysis of carbon capture at cellulosic biorefineries
Authors: O’Neill Eric G. , Geissler Caleb H. , Maravelias Christos T. 
Published: May 2024

AbstractThe large-scale production of cellulosic biofuels would involve spatially distributed systems including biomass fields, logistics networks and biorefineries. Better understanding of the interactions between landscape-related decisions and the design of biorefineries with carbon capture and storage (CCS) in a supply chain context is needed to enable efficient systems. Here we analyse the cost and greenhouse gas mitigation potential for cellulosic biofuel supply chains in the US Midwest using realistic spatially explicit land availability and crop productivity data and consider fuel conversion technologies with detailed CCS design for their associated CO2 streams. Optimization methods identify trade-offs and design strategies leading to systems with attractive environmental and economic performance. Strategic and operational decisions depend on underlying spatial features and are sensitive to biofuel demand and CCS incentives. US CCS incentives neglect to motivate greenhouse gas mitigation from all supply chain emission sources, which leverage spatial interactions between CCS, electricity prices and the biomass landscape.
De novo transcriptome assembly of a lipoxygenase knock-down strain in the diatom Pseudo-nitzschia arenysensis
Authors: Marotta Pina , Sabatino Valeria , Ambrosino Luca , Miralto Marco , Ferrante Maria Immacolata 
Published: May 2024

AbstractDiatoms are microalgae that live in marine and freshwater environments and are responsible for about 20% of the world’s carbon fixation. Population dynamics of these cells is finely regulated by intricate signal transduction systems, in which oxylipins are thought to play a relevant role. These are oxygenated fatty acids whose biosynthesis is initiated by a lipoxygenase enzyme (LOX) and are widely distributed in all phyla, including diatoms. Here, we present a de novo transcriptome obtained from the RNA-seq performed in the diatom species Pseudo-nitzschia arenysensis, using both a wild-type and a LOX-silenced strain, which will represent a reliable reference for comparative analyses within the Pseudo-nitzschia genus and at a broader taxonomic scale. Moreover, the RNA-seq data can be interrogated to go deeper into the oxylipins metabolic pathways.
A high-quality chromosome-level genome assembly of Ficus hirta
Authors: Huang Weicheng , Ding Yamei , Fan Songle , Liu Wanzhen , Chen Hongfeng , Segar Simon , Compton Stephen G. , Yu Hui 
Published: May 2024

AbstractFicus species (Moraceae) play pivotal roles in tropical and subtropical ecosystems. Thriving across diverse habitats, from rainforests to deserts, they harbor a multitude of mutualistic and antagonistic interactions with insects, nematodes, and pathogens. Despite their ecological significance, knowledge about the genomic background of Ficus remains limited. In this study, we report a chromosome-level reference genome of F. hirta, with a total size of 297.27 Mb, containing 28,625 protein-coding genes and 44.67% repeat sequences. These findings illuminate the genetic basis of Ficus responses to environmental challenges, offering valuable genomic resources for understanding genome size, adaptive evolution, and co-evolution with natural enemies and mutualists within the genus.
Welding-induced corrosion and protective measures for clad rebars in neutral chloride environments
Authors: Zhuang Zecheng , Lu Weiping , Zeng Lei , Tan Jianping , Qian Xuehai , Li Zhen , Jiang Wei , Xiang Yong 
Published: May 2024

AbstractCorrosion-resistant steel plays a vital role in marine steel structures. This study developed an SS304/HRB400 stainless-steel-clad rebar for application in a cross-sea bridge in Zhejiang Province. CO2 gas shielded welding was employed in the prefabricated steel structure, with SS304 steel as the welding wire. This study investigated the welding on the corrosion resistance of clad rebars and explored corrosion protection measures for welded joints.The results indicated that refined grains appeared in both stainless steel and carbon steel due to distinct dynamic recrystallization (DRX) during welding. The corrosion resistance, as determined by potentiodynamic polarization curve analysis of the material’s interaction with the solution ranked as follows: clad rebar (polished) > clad rebar welding (CRW) > painting the clad rebar after welding (PCRW) > clad rebar (unpolished) > carbon-steel welding (CSW) > carbon-steel bar > cold spraying zinc after clad rebar welding (ZCRW). However, an accelerated corrosion test with four samples for 600 s with a corrosion current of 0.8 A revealed minimal corrosion damage on zinc-coated surfaces. Hence, welding joints for clad steel structures are considered feasible and must be subject to cold zinc spraying after polishing to enhance their corrosion resistance.
A comprehensive study on changes in coastal hydrodynamics associated with cyclonic activity
Authors: Salama Nada M. , Tonbol Kareem M. , ElKut Ahmed , ElBessa Mohamed , Kotroni Vassiliki 
Published: May 2024

AbstractA Mediterranean cyclone is a weather phenomenon capable of producing extremely severe conditions, including heavy rainfall and strong winds. Between March 24 and 26, 2023, a cyclone passed along the western Egyptian Mediterranean coast, spanning three days. This paper aims to investigate the cyclone's impact on wave characteristics, focusing particularly on simulating changes in the energy transported from wind to waves during its passage, which constitutes the core objective of this study. The research methodology involved collecting meteorological and hydrodynamic data over five days from March 23 to 27, 2023, utilizing databases of the Bologna Limited Area Model (BOLAM) and the General Bathymetric Chart of the Oceans (GEBCO). This data, combined with field data for model calibration and validation, was analyzed using the Simulating the WAves Nearshore (SWAN) model packaged within the Delft 3D hydrodynamical model, integrated with other data manipulation tools. (SWAN) demonstrated the ability to simulate energy transport during extreme weather events along the coastal area with high resolution, up to 500 m. The results indicate a significant increase in significant wave height, reaching up to 2.5 m, and disturbances in wind direction, with velocities exceeding 10 m per second. These conditions pose risks to the infrastructure in some cities along the study area and have severe impacts on coastal communities. A notable finding from the simulations is the excess energy transport, which reached up to 12,000 watts per meter over the sea surface during the cyclone. Furthermore, calibration and validation results affirm the (SWAN) model's capability to accurately study wave characteristics.