bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatiotemporal Distribution of Shallow Tremors Along the Nankai Trough, Southwest Japan, as Determined From Waveform Amplitudes and Cross‐Correlations
Authors: Tamaribuchi Koji , Ogiso Masashi , Noda Akemi 
Published: August 2022

AbstractShallow slow earthquakes in subduction zones are related to spatiotemporal variations of stress on the plate boundary adjacent to a megathrust earthquake. A dense network (DONET) of cabled ocean‐bottom seismometers (OBSs) deployed in the Nankai Trough seismogenic zone, southwest Japan, has enabled real‐time monitoring of tremors. Because the amplitudes of tremor signals are very low, even when recorded by OBSs, we developed a hybrid method that simultaneously uses traveltimes based on cross‐correlations and amplitudes of waveforms to determine tremor hypocenters. We applied our method to waveforms observed during five years of continuous DONET recording from April 2016 to September 2021 to detect more than 6,500 tremors, including three major episodes in 2016, 2018, and 2020–2021. The tremors of each episode were distributed over distances of >100 km along the trench axis in two regions, southeast of the Kii Peninsula and off Cape Muroto. We also estimated seismic energy rates and found that for the three major tremor episodes, energy rates increased gradually with time. The 2018 and 2020–2021 episodes began near a subducted seamount and a subducted ridge, respectively, and were likely related to fluid movements controlled by the topography of the downgoing plate. We showed that the tremors were spatiotemporally synchronized with slow slip events, and their spatial variations of energy rate corresponded to stress heterogeneity on the shallow plate boundary. Future real‐time monitoring of shallow tremors will contribute to our understanding of changes of stress state due to slow earthquakes at the shallow plate boundary.
The Role of Turbulence in Fueling the Subsurface Chlorophyll Maximum in Tidally Dominated Shelf Seas
Authors: Becherer Johannes , Burchard Hans , Carpenter Jeffrey R. , Graewe Ulf , Merckelbach Lucas M. 
Published: August 2022

AbstractGlider observations show a subsurface chlorophyll maximum (SCM) at the base of the seasonal pycnocline in the North Sea during stable summer conditions. A colocated peak in the dissipation rate of turbulent kinetic energy suggests the presence of active turbulence that potentially generates a nutrient flux to fuel the SCM. A one‐dimensional turbulence closure model is used to investigate the dynamics behind this local maximum in turbulent dissipation at the base of the pycnocline (PCB) as well as its associated nutrient fluxes. Based on a number of increasingly idealized forcing setups of the model, we are able to draw the following conclusions: (a) only turbulence generated inside the stratified PCB is able to entrain a tracer (e.g., nutrients) from the bottom mixed layer into the SCM region; (b) surface wind forcing only plays a secondary role during stable summer conditions; (c) interfacial shear from the tide accounts for the majority of turbulence production at the PCB; (d) in stable summer conditions, the strength of the turbulent diapycnal fluxes at the PCB is set by the strength of the anticyclonic component of the tidal currents.
Ice Aggregation in Low‐Level Mixed‐Phase Clouds at a High Arctic Site: Enhanced by Dendritic Growth and Absent Close to the Melting Level
Authors: Chellini Giovanni , Gierens Rosa , Kneifel Stefan 
Published: August 2022

AbstractLow‐level mixed‐phase clouds (MPCs) occur extensively in the Arctic, and are known to play a key role for the energy budget. While their characteristic structure is nowadays well understood, the significance of different precipitation‐formation processes, such as aggregation and riming, is still unclear. Using a 3‐year data set of vertically pointing W‐band cloud radar and K‐band Micro Rain Radar (MRR) observations from Ny‐Ålesund, Svalbard, we statistically assess the relevance of aggregation in Arctic low‐level MPCs. Combining radar observations with thermodynamic profiling, we find that larger snowflakes (mass median diameter larger than 1 mm) are predominantly produced in low‐level MPCs whose mixed‐phase layer is at temperatures between −15 and −10°C. This coincides with the temperature regime known for favoring aggregation due to growth and subsequent mechanical entanglement of dendritic crystals. Doppler velocity information confirms that these signatures are likely due to enhanced ice particle growth by aggregation. Signatures indicative of enhanced aggregation are however not distributed uniformly across the cloud deck, and only observed in limited regions, suggesting a link with dynamical effects. Low Doppler velocity values further indicate that significant riming of large particles is unlikely at temperatures colder than −5°C. Surprisingly, we find no evidence of enhanced aggregation at temperatures warmer than −5°C, as is typically observed in deeper cloud systems. Possible reasons are discussed, likely connected to the ice habits that form at temperatures warmer than −10°C, increased riming, and lack of particle populations characterized by broader size distributions precipitating from higher altitudes.
Estimating Drivers and Pathways for Hydroelectric Reservoir Methane Emissions Using a New Mechanistic Model
Authors: Delwiche Kyle B. , Harrison John A. , Maasakkers Joannes D. , Sulprizio Melissa P. , Worden John , Jacob Daniel J. , Sunderland Elsie M. 
Published: August 2022

AbstractHydroelectric reservoirs can emit significant quantities of methane, particularly through degassing at turbine outlets. Improved understanding of processes affecting hydroelectric reservoir CH4 emissions is thus important as the world economy transitions to renewable forms of energy production. Here we develop and evaluate a new mechanistic model of CH4 emissions: ResME ([Res]ervoir [M]ethane [E]missions), which estimates carbon inputs and methanogenesis to predict CH4 release via ebullition and diffusion, plant emissions, and downstream emissions. ResME results demonstrate that the relative importance of allochthonous and autochthonous carbon input to methane emissions varies by latitude, with allochthonous carbon contributions typically being higher in tropical reservoirs. Results also demonstrate that total reservoir emissions are highly dependent on turbine intake depths, which are not typically reported. Potential maximum degassing emissions from existing hydroelectric reservoirs are estimated as 11 ± 4 Tg C/yr, if all reservoirs had deep turbine intakes and stratified for 5 months per year. In comparison, the estimated diffusive, ebullitive, and plant CH4 emissions are estimated to be 2.8 ± 0.2 Tg C/yr (where the true uncertainty is much higher than the model standard error). Future work should focus on improving estimates of reservoir carbon inputs and decomposition rates, as well as surveying turbine intake depths. Satellite measurements from missions such as TROPOMI may also help constrain hydropower methane emissions.
Development of a spontaneous pain indicator based on brain cellular calcium using deep learning
Authors: Yoon Heera , Bak Myeong Seong , Kim Seung Ha , Lee Ji Hwan , Chung Geehoon , Kim Sang Jeong , Kim Sun Kwang 
Published: August 2022

AbstractChronic pain remains an intractable condition in millions of patients worldwide. Spontaneous ongoing pain is a major clinical problem of chronic pain and is extremely challenging to diagnose and treat compared to stimulus-evoked pain. Although extensive efforts have been made in preclinical studies, there still exists a mismatch in pain type between the animal model and humans (i.e., evoked vs. spontaneous), which obstructs the translation of knowledge from preclinical animal models into objective diagnosis and effective new treatments. Here, we developed a deep learning algorithm, designated AI-bRNN (Average training, Individual test-bidirectional Recurrent Neural Network), to detect spontaneous pain information from brain cellular Ca2+ activity recorded by two-photon microscopy imaging in awake, head-fixed mice. AI-bRNN robustly determines the intensity and time points of spontaneous pain even in chronic pain models and evaluates the efficacy of analgesics in real time. Furthermore, AI-bRNN can be applied to various cell types (neurons and glia), brain areas (cerebral cortex and cerebellum) and forms of somatosensory input (itch and pain), proving its versatile performance. These results suggest that our approach offers a clinically relevant, quantitative, real-time preclinical evaluation platform for pain medicine, thereby accelerating the development of new methods for diagnosing and treating human patients with chronic pain.
Inhibiting peripheral and central MAO-B ameliorates joint inflammation and cognitive impairment in rheumatoid arthritis
Authors: Won Woojin , Choi Hyun-Ji , Yoo Ji-Young , Kim Daeun , Kim Tai Young , Ju YeonHa , Park Ki Duk , Lee Hyunbeom , Jung Sang Youn , Lee C. Justin 
Published: August 2022

AbstractRheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation and the destruction of joints and systemic organs. RA is commonly accompanied by neuropsychiatric complications, such as cognitive impairment and depression. However, the role of monoamine oxidase (MAO) and its inhibitors in controlling neurotransmitters associated with these complications in RA have not been clearly identified. Here, we report that peripheral and central MAO-B are highly associated with joint inflammation and cognitive impairment in RA, respectively. Ribonucleic acid (RNA) sequencing and protein expression quantification were used to show that MAO-B and related molecules, such as gamma aminobutyric acid (GABA), were elevated in the inflamed synovium of RA patients. In primary cultured fibroblast-like synoviocytes in the RA synovium, MAO-B expression was significantly increased by tumor necrosis factor (TNF)-α-induced autophagy, which produces putrescine, the polyamine substrate for GABA synthesis. We also observed that MAO-B-mediated aberrant astrocytic production of GABA was augmented by interleukin (IL)-1β and inhibited CA1-hippocampal pyramidal neurons, which are responsible for memory storage, in an animal model of RA. Moreover, a newly developed reversible inhibitor of MAO-B ameliorated joint inflammation by inhibiting cyclooxygenase (Cox)-2. Therefore, MAO-B can be an effective therapeutic target for joint inflammation and cognitive impairment in patients with RA.
FMRP modulates the Wnt signalling pathway in glioblastoma
Authors: Pedini Giorgia , Buccarelli Mariachiara , Bianchi Fabrizio , Pacini Laura , Cencelli Giulia , D’Alessandris Quintino Giorgio , Martini Maurizio , Giannetti Stefano , Sasso Franceschina , Melocchi Valentina , Farace Maria Giulia , Achsel Tilmann , Larocca Luigi M. , Ricci-Vitiani Lucia , Pallini Roberto , Bagni Claudia 
Published: August 2022

AbstractConverging evidence indicates that the Fragile X Messenger Ribonucleoprotein (FMRP), which absent or mutated in Fragile X Syndrome (FXS), plays a role in many types of cancers. However, while FMRP roles in brain development and function have been extensively studied, its involvement in the biology of brain tumors remains largely unexplored. Here we show, in human glioblastoma (GBM) biopsies, that increased expression of FMRP directly correlates with a worse patient outcome. In contrast, reductions in FMRP correlate with a diminished tumor growth and proliferation of human GBM stem-like cells (GSCs) in vitro in a cell culture model and in vivo in mouse brain GSC xenografts. Consistently, increased FMRP levels promote GSC proliferation. To characterize the mechanism(s) by which FMRP regulates GSC proliferation, we performed GSC transcriptome analyses in GSCs expressing high levels of FMRP, and in these GSCs after knockdown of FMRP. We show that the WNT signalling is the most significantly enriched among the published FMRP target genes and genes involved in ASD. Consistently, we find that reductions in FMRP downregulate both the canonical WNT/β-Catenin and the non-canonical WNT-ERK1/2 signalling pathways, reducing the stability of several key transcription factors (i.e. β-Catenin, CREB and ETS1) previously implicated in the modulation of malignant features of glioma cells. Our findings support a key role for FMRP in GBM cancer progression, acting via regulation of WNT signalling.
Novel 1-hydroxy phenothiazinium-based derivative protects against bacterial sepsis by inhibiting AAK1-mediated LPS internalization and caspase-11 signaling
Authors: Yuan Chuang , Ai Kelong , Xiang Menghua , Xie Chengliang , Zhao Mingyi , Wu Ming , Li Hongli , Wu Yueren , Cao Yueqing , Li Can , Zhong Yanjun , Pei Xiaomeng , Law Helen Ka Wai , Gao Liqian , Xiao Qicai , Yang Xinyu 
Published: August 2022

AbstractSepsis is a life-threatening syndrome with disturbed host responses to severe infections, accounting for the majority of death in hospitalized patients. However, effective medicines are currently scant in clinics due to the poor understanding of the exact underlying mechanism. We previously found that blocking caspase-11 pathway (human orthologs caspase-4/5) is effective to rescue coagulation-induced organ dysfunction and lethality in sepsis models. Herein, we screened our existing chemical pools established in our lab using bacterial outer membrane vesicle (OMV)-challenged macrophages, and found 7-(diethylamino)-1-hydroxy-phenothiazin-3-ylidene-diethylazanium chloride (PHZ-OH), a novel phenothiazinium-based derivative, was capable of robustly dampening caspase-11-dependent pyroptosis. The in-vitro study both in physics and physiology showed that PHZ-OH targeted AP2-associated protein kinase 1 (AAK1) and thus prevented AAK1-mediated LPS internalization for caspase-11 activation. By using a series of gene-modified mice, our in-vivo study further demonstrated that administration of PHZ-OH significantly protected mice against sepsis-associated coagulation, multiple organ dysfunction, and death. Besides, PHZ-OH showed additional protection on Nlrp3−/− and Casp1−/− mice but not on Casp11−/−, Casp1/11−/−, Msr1−/−, and AAK1 inhibitor-treated mice. These results suggest the critical role of AAK1 on caspase-11 signaling and may provide a new avenue that targeting AAK1-mediated LPS internalization would be a promising therapeutic strategy for sepsis. In particular, PHZ-OH may serve as a favorable molecule and an attractive scaffold in future medicine development for efficient treatment of bacterial sepsis.
Oral administration of Blautia wexlerae ameliorates obesity and type 2 diabetes via metabolic remodeling of the gut microbiota
Authors: Hosomi Koji , Saito Mayu , Park Jonguk , Murakami Haruka , Shibata Naoko , Ando Masahiro , Nagatake Takahiro , Konishi Kana , Ohno Harumi , Tanisawa Kumpei , Mohsen Attayeb , Chen Yi-An , Kawashima Hitoshi , Natsume-Kitatani Yayoi , Oka Yoshimasa , Shimizu Hidenori , Furuta Mari , Tojima Yoko , Sawane Kento , Saika Azusa , Kondo Saki , Yonejima Yasunori , Takeyama Haruko , Matsutani Akira , Mizuguchi Kenji , Miyachi Motohiko , Kunisawa Jun 
Published: August 2022

AbstractThe gut microbiome is an important determinant in various diseases. Here we perform a cross-sectional study of Japanese adults and identify the Blautia genus, especially B. wexlerae, as a commensal bacterium that is inversely correlated with obesity and type 2 diabetes mellitus. Oral administration of B. wexlerae to mice induce metabolic changes and anti-inflammatory effects that decrease both high-fat diet–induced obesity and diabetes. The beneficial effects of B. wexlerae are correlated with unique amino-acid metabolism to produce S-adenosylmethionine, acetylcholine, and l-ornithine and carbohydrate metabolism resulting in the accumulation of amylopectin and production of succinate, lactate, and acetate, with simultaneous modification of the gut bacterial composition. These findings reveal unique regulatory pathways of host and microbial metabolism that may provide novel strategies in preventive and therapeutic approaches for metabolic disorders.
SARS-CoV-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization
Authors: Mannar Dhiraj , Saville James W. , Sun Zehua , Zhu Xing , Marti Michelle M. , Srivastava Shanti S. , Berezuk Alison M. , Zhou Steven , Tuttle Katharine S. , Sobolewski Michele D. , Kim Andrew , Treat Benjamin R. , Da Silva Castanha Priscila Mayrelle , Jacobs Jana L. , Barratt-Boyes Simon M. , Mellors John W. , Dimitrov Dimiter S. , Li Wei , Subramaniam Sriram 
Published: August 2022

AbstractMutations in the spike glycoproteins of SARS-CoV-2 variants of concern have independently been shown to enhance aspects of spike protein fitness. Here, we describe an antibody fragment (VH ab6) that neutralizes all major variants including the recently emerged BA.1 and BA.2 Omicron subvariants, with a unique mode of binding revealed by cryo-EM studies. Further, we provide a comparative analysis of the mutational effects within previously emerged variant spikes and identify the structural role of mutations within the NTD and RBD in evading antibody neutralization. Our analysis shows that the highly mutated Gamma N-terminal domain exhibits considerable structural rearrangements, partially explaining its decreased neutralization by convalescent sera. Our results provide mechanistic insights into the structural, functional, and antigenic consequences of SARS-CoV-2 spike mutations and highlight a spike protein vulnerability that may be exploited to achieve broad protection against circulating variants.
SARS-CoV-2 antibodies and breakthrough infections in the Virus Watch cohort
Authors: Aldridge Robert W. , Yavlinsky Alexei , Nguyen Vincent , Eyre Max T. , Shrotri Madhumita , Navaratnam Annalan M. D. , Beale Sarah , Braithwaite Isobel , Byrne Thomas , Kovar Jana , Fragaszy Ellen , Fong Wing Lam Erica , Geismar Cyril , Patel Parth , Rodger Alison , Johnson Anne M. , Hayward Andrew 
Published: August 2022

AbstractA range of studies globally demonstrate that the effectiveness of SARS-CoV-2 vaccines wane over time, but the total effect of anti-S antibody levels on risk of SARS-CoV-2 infection and whether this varies by vaccine type is not well understood. Here we show that anti-S levels peak three to four weeks following the second dose of vaccine and the geometric mean of the samples is nine fold higher for BNT162b2 than ChAdOx1. Increasing anti-S levels are associated with a reduced risk of SARS-CoV-2 infection (Hazard Ratio 0.85; 95%CIs: 0.79-0.92). We do not find evidence that this antibody relationship with risk of infection varies by second dose vaccine type (BNT162b2 vs. ChAdOx1). In keeping with our anti-S antibody data, we find that people vaccinated with ChAdOx1 had 1.64 times the odds (95% confidence interval 1.45-1.85) of a breakthrough infection compared to BNT162b2. We anticipate our findings to be useful in the estimation of the protective effect of anti-S levels on risk of infection due to Delta. Our findings provide evidence about the relationship between antibody levels and protection for different vaccines and will support decisions on optimising the timing of booster vaccinations and identifying individuals who should be prioritised for booster vaccination, including those who are older, clinically extremely vulnerable, or received ChAdOx1 as their primary course. Our finding that risk of infection by anti-S level does not interact with vaccine type, but that individuals vaccinated with ChAdOx1 were at higher risk of infection, provides additional support for the use of using anti-S levels for estimating vaccine efficacy.
Sustained and intensified lacustrine methane cycling during Early Permian climate warming
Authors: Sun Funing , Hu Wenxuan , Cao Jian , Wang Xiaolin , Zhang Zhirong , Ramezani Jahandar , Shen Shuzhong 
Published: August 2022

AbstractLakes are a major emitter of the atmospheric greenhouse gas methane (CH4); however, their roles in past climate warming episodes remain poorly understood owing to a scarcity of geological records. Here we report the occurrence of sustained and intensified microbial CH4 cycling in paleo-Lake Junggar in northwestern China, one of the largest known Phanerozoic lakes, during Early Permian climate warming. High-precision U-Pb geochronology refines the age of the upper Lucaogou Formation to the Artinskian, which marks a major glacial-to-postglacial climate transition. The 13C-enriched authigenic dolomites indicate active methanogenesis in the anoxic lake sediments, and 13C-depleted hopanes suggest vigorous methanotrophy in the water column. The intensification of CH4 cycling coincided with increasing global temperature, as evidenced from elevated continental chemical weathering. Our results suggest that the lacustrine CH4 emissions acted as a positive feedback to global warming and contributed to the demise of the Late Paleozoic Ice Age.
Multiscale light-sheet organoid imaging framework
Authors: de Medeiros Gustavo , Ortiz Raphael , Strnad Petr , Boni Andrea , Moos Franziska , Repina Nicole , Challet Meylan Ludivine , Maurer Francisca , Liberali Prisca 
Published: August 2022

AbstractOrganoids provide an accessible in vitro system to mimic the dynamics of tissue regeneration and development. However, long-term live-imaging of organoids remains challenging. Here we present an experimental and image-processing framework capable of turning long-term light-sheet imaging of intestinal organoids into digital organoids. The framework combines specific imaging optimization combined with data processing via deep learning techniques to segment single organoids, their lumen, cells and nuclei in 3D over long periods of time. By linking lineage trees with corresponding 3D segmentation meshes for each organoid, the extracted information is visualized using a web-based “Digital Organoid Viewer” tool allowing combined understanding of the multivariate and multiscale data. We also show backtracking of cells of interest, providing detailed information about their history within entire organoid contexts. Furthermore, we show cytokinesis failure of regenerative cells and that these cells never reside in the intestinal crypt, hinting at a tissue scale control on cellular fidelity.
Cross-tissue analysis of blood and brain epigenome-wide association studies in Alzheimer’s disease
Authors: C. Silva Tiago , Young Juan I. , Zhang Lanyu , Gomez Lissette , Schmidt Michael A. , Varma Achintya , Chen X. Steven , Martin Eden R. , Wang Lily 
Published: August 2022

AbstractTo better understand DNA methylation in Alzheimer’s disease (AD) from both mechanistic and biomarker perspectives, we performed an epigenome-wide meta-analysis of blood DNA methylation in two large independent blood-based studies in AD, the ADNI and AIBL studies, and identified 5 CpGs, mapped to theSPIDR,CDH6genes, and intergenic regions, that are significantly associated with AD diagnosis. A cross-tissue analysis that combined these blood DNA methylation datasets with four brain methylation datasets prioritized 97 CpGs and 10 genomic regions that are significantly associated with both AD neuropathology and AD diagnosis. An out-of-sample validation using the AddNeuroMed dataset showed the best performing logistic regression model includes age, sex, immune cell type proportions, and methylation risk score based on prioritized CpGs in cross-tissue analysis (AUC = 0.696, 95% CI: 0.616 − 0.770,P-value = 2.78 × 10−5). Our study offers new insights into epigenetics in AD and provides a valuable resource for future AD biomarker discovery.