bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Impacts of Climate Change on Indian Riverine Thermal Regimes Using Hybrid Deep Learning Methods
Authors: Rehana S. , Rajesh M. 
Published: January 2023

AbstractUnderstanding the riverine thermal regimes is challenging due to sparse spatiotemporal data of river water temperatures (RWTs). The development of systematic models combined with machine learning models under data‐limited context has not been intensively studied for the prediction of RWT. The present study developed hybrid models using long short‐term memory (LSTM), integrated with (a) k‐nearest neighbor (k‐NN) bootstrap resampling algorithms (kNN‐LSTM) to address the data limitations of RWT prediction and (b) discrete wavelet transform (WT) approach (WT‐LSTM) to address the time–frequency localized features of RWT prediction. The study assessed the climate change impacts on RWT using an ensemble of National Aeronautics Space Administration Earth Exchange Global Daily Downscaled Projections of air temperature with Representative Concentration Pathway scenarios 4.5 and 8.5 for seven major polluted river catchments of India. The hybrid kNN‐LSTM has effectively predicted RWT at monthly time scales under data limitations and outperformed the standalone LSTM, WT‐LSTM, and hybrid three‐parameter version air2stream models. The RWT increase for Tunga‐Bhadra, Musi, Ganga, and Narmada basins is predicted as 3.0, 4.0, 4.6, and 4.7°C, respectively, for 2071–2100.
Version 2 of the TSIS‐1 Hybrid Solar Reference Spectrum and Extension to the Full Spectrum
Authors: Coddington O. M. , Richard E. C. , Harber D. , Pilewskie P. , Woods T. N. , Snow M. , Chance K. , Liu X. , Sun K. 
Published: January 2023

AbstractThis work describes two achievements to a key data set. First, we present version 2 of the Total and Spectral Solar Irradiance Sensor‐1 Hybrid Solar Reference Spectrum (TSIS‐1 HSRS), which has recently been recognized as a new solar irradiance reference standard (https://calvalportal.ceos.org/). Second, we present a new “full spectrum extension” of the TSIS‐1 HSRS. The TSIS‐1 HSRS observational composite solar irradiance reference spectrum spans 0.202–2.730 μm and encompasses more than 97% of the energy in the total solar irradiance (TSI). Version 2 is an incremental update that corrects the radiometric baseline between 0.202 and 0.210 μm and updates the solar lines at wavelengths longward of 0.743 μm to those listed in the most recent database. The full spectrum extension builds off version 2 of the TSIS‐1 HSRS and supports applications that require a solar spectrum encompassing nearly 100% of the energy in the TSI. It spans 0.115–200 μm and was developed by incorporating additional observations and theoretical knowledge where no direct observations currently exist.
The Phosphorus Budget of the Silicate Earth Based on an Updated Estimate of the P/Nd Ratio
Authors: Ma Chao , Tang Yanjie , Ying Jifeng , Zhang Hongfu 
Published: January 2023

AbstractCalculating the phosphorus (P) budget of the bulk silicate Earth (BSE) is necessary to understand the global P cycle and the origin and evolution of life. Covariations of P and neodymium (Nd) contents suggest that P is 1.1–1.4 times more incompatible than Nd during mantle melting and magmatic differentiation. As such, the P/Nd ratios of mantle sources can be estimated using inverse modeling, and the P budget of the BSE can be calculated from the P/Nd ratios of the continental crust, mid‐ocean ridge basalts (MORBs), and ocean island basalts (OIBs). The P/Nd ratios for the MORB and OIB mantle sources and continental crust are 62.5 ± 0.8 (2σm), 57.0 ± 0.5 (2σm), and 28.4 ± 12.0 (2σm), respectively. These reservoirs have different P/Nd ratios due to subduction, magmatic differentiation, and mineralogy. Subduction can significantly affect the global P and Nd cycles. Magmatic differentiation, especially in the continental crust, may redistribute P by changing the contents of garnet, apatite, and other minerals. The fractional contributions of these global reservoirs suggest the modern BSE has a P/Nd ratio of 57.7 ± 3.0 (2σm), equating to ∼3.1 × 1020 kg of P in the BSE.
Constraining Bedrock Groundwater Residence Times in a Mountain System With Environmental Tracer Observations and Bayesian Uncertainty Quantification
Authors: Thiros Nicholas E. , Siirila‐Woodburn Erica R. , Dennedy‐Frank P. James , Williams Kenneth H. , Gardner W. Payton 
Published: January 2023

AbstractGroundwater residence time distributions provide fundamental insights on the hydrological processes within watersheds. Yet, observations that can constrain groundwater residence times over broad timescales remain scarce in mountain catchment studies. We use environmental tracers (CFC‐12, SF6, 3H, and 4He) to investigate groundwater residence times along a hillslope in the East River Watershed, Colorado, USA. We develop a Bayesian inference framework that applies a Markov‐chain Monte Carlo (MCMC) approach to estimate noble gas recharge temperature, elevation, and excess‐air parameters and the resulting environmental tracer concentrations. MCMC is then used to propagate the environmental tracer uncertainties to estimates of groundwater mean residence times inferred with lumped parameter models. All samples contain 3H, CFC‐12, and SF6 in addition to terrigenic 4He, suggesting a mixture of water characterized by modern and premodern residence times. 4He exponential mean residence times range from hundreds of years at the upslope well to thousands of years at the toe‐slope well assuming average crustal production rates. We find that binary mixing residence time distributions with separate young and old mixing fractions are needed to predict the 4He, CFC‐12, SF6, and 3H observations, supporting the importance of flow path mixing in this bedrock system. Our findings that the fractured bedrock hosts groundwater with a mixture of residence times ranging from decades to millennia suggest variable recharge dynamics and flow path mixing along the hillslope and highlight the importance of characterizing groundwater systems with observations that are sensitive to transport over a broad range of residence times.
Deoxyguanosine kinase mutation F180S is associated with a lean phenotype in mice
Authors: Borreguero Cédric Francis , Wueest Stephan , Hantel Constanze , Schneider Holger , Konrad Daniel , Beuschlein Felix , Spyroglou Ariadni 
Published: January 2023

Abstract
Background
Deoxyguanosine kinase (DGUOK) deficiency is one of the genetic causes of mitochondrial DNA depletion syndrome (MDDS) in humans, leading to the hepatocerebral or the isolated hepatic form of MDDS. Mouse models are helpful tools for the improvement of understanding of the pathophysiology of diseases and offer the opportunity to examine new therapeutic options.

Methods
Herein, we describe the generation and metabolic characterization of a mouse line carrying a homozygous DguokF180S/F180S mutation derived from an N-ethyl-N-nitrosourea-mutagenesis screen. Energy expenditure (EE), oxygen consumption (VO2) and carbon dioxide production (VCO2) were assessed in metabolic cages. LC-MS/MS was used to quantify plasma adrenal steroids. Plasma insulin and leptin levels were quantified with commercially available assay kits.

Results
Mutant animals displayed significantly lower body weights and reduced inguinal fat pad mass, in comparison to unaffected littermates. Biochemically, they were characterized by significantly lower blood glucose levels, accompanied by significantly lower insulin, total cholesterol, high density lipoprotein and triglyceride levels. They also displayed an almost 2-fold increase in transaminases. Moreover, absolute EE was comparable in mutant and control mice, but EE in mutants was uncoupled from their body weights. Histological examination of inguinal white adipose tissue (WAT) revealed adipocytes with multilocular fat droplets reminiscent of WAT browning. In addition, mRNA and protein expression of Ucp1 was increased. Mutant mice also presented differing mitochondrial DNA content in various tissues and altered metabolic activity in mitochondria, but no further phenotypical or behavioral abnormalities. Preliminary data imply normal survival of DguokF180S/F180S mutant animals.

Conclusion
Taken together, DGUOK mutation F180S leads to a lean phenotype, with lower glucose, insulin, and lipid levels rendering this mouse model not only useful for the study of MDDS forms but also for deciphering mechanisms resulting in a lean phenotype.
The histone demethylase JMJD2C constitutes a novel NFE2 target gene that is required for the survival of JAK2V617F mutated cells
Authors: Staehle Anne Marie , Peeken Jan Caspar , Vladimirov Georg , Hoeness Mirjam Elisabeth , Bojtine Kovacs Sarolta , Karantzelis Nikolaos , Gruender Albert , Koellerer Christoph , Jutzi Jonas Samuel , Pahl Heike Luise , Staehle Hans Felix 
Published: January 2023

AbstractThe transcription factor NFE2 is overexpressed in most patients with myeloproliferative neoplasms (MPN). Moreover, mutations in NFE2, found in a subset of MPN patients, strongly predispose for transformation to acute leukemia. Transgenic mice overexpressing NFE2 as well as mice harboring NFE2 mutations display an MPN phenotype and spontaneously develop leukemia. However, the molecular mechanisms effecting NFE2-driven leukemic transformation remain incompletely understood. Here we show that the pro-leukemic histone demethylase JMJD2C constitutes a novel NFE2 target gene. JMJD2C expression is elevated in MPN patients as well as in NFE2 transgenic mice. Moreover, we show that loss of JMJD2C selectively impairs proliferation of JAK2V617F mutated cells. Our data suggest that JMJD2C represents a promising drug target in MPN and provide a rationale for further investigation in preclinical and clinical settings.
Interleukin-18-primed human umbilical cord-mesenchymal stem cells achieve superior therapeutic efficacy for severe viral pneumonia via enhancing T-cell immunosuppression
Authors: Liao Yan , Fu Zeqin , Huang Yinfu , Wu Shiduo , Wang Zhen , Ye Shaotang , Zeng Weijie , Zeng Guifang , Li Duanduan , Yang Yulin , Pei Ke , Yang Jian , Hu Zhiwei , Liang Xiao , Hu Junyuan , Liu Muyun , Jin Juan , Cai Cheguo 
Published: January 2023

AbstractCoronavirus disease 2019 (COVID-19) treatments are still urgently needed for critically and severely ill patients. Human umbilical cord-mesenchymal stem cells (hUC-MSCs) infusion has therapeutic benefits in COVID-19 patients; however, uncertain therapeutic efficacy has been reported in severe patients. In this study, we selected an appropriate cytokine, IL-18, based on the special cytokine expression profile in severe pneumonia of mice induced by H1N1virus to prime hUC-MSCs in vitro and improve the therapeutic effect of hUC-MSCs in vivo. In vitro, we demonstrated that IL-18-primed hUC-MSCs (IL18-hUCMSC) have higher proliferative ability than non-primed hUC-MSCs (hUCMSCcon). In addition, VCAM-1, MMP-1, TGF-β1, and some chemokines (CCL2 and CXCL12 cytokines) are more highly expressed in IL18-hUCMSCs. We found that IL18-hUCMSC significantly enhanced the immunosuppressive effect on CD3+ T-cells. In vivo, we demonstrated that IL18-hUCMSC infusion could reduce the body weight loss caused by a viral infection and significantly improve the survival rate. Of note, IL18-hUCMSC can also significantly attenuate certain clinical symptoms, including reduced activity, ruffled fur, hunched backs, and lung injuries. Pathologically, IL18-hUCMSC transplantation significantly enhanced the inhibition of inflammation, viral load, fibrosis, and cell apoptosis in acute lung injuries. Notably, IL18-hUCMSC treatment has a superior inhibitory effect on T-cell exudation and proinflammatory cytokine secretion in bronchoalveolar lavage fluid (BALF). Altogether, IL-18 is a promising cytokine that can prime hUC-MSCs to improve the efficacy of precision therapy against viral-induced pneumonia, such as COVID-19.
A first-in-class HBO1 inhibitor WM-3835 inhibits castration-resistant prostate cancer cell growth in vitro and in vivo
Authors: Mi Yuan-yuan , Ji Yu , Zhang Lifeng , Sun Chuan-yu , Wei Bing-bing , Yang Dong-jie , Wan Hong-yuan , Qi Xiao-wei , Wu Sheng , Zhu Li-jie 
Published: January 2023

AbstractThe prognosis and overall survival of castration-resistant prostate cancer (CRPC) patients are poor. The search for novel and efficient anti-CRPC agents is therefore extremely important. WM-3835 is a cell-permeable, potent and first-in-class HBO1 (KAT7 or MYST2) inhibitor. Here in primary human prostate cancer cells-derived from CRPC patients, WM-3835 potently inhibited cell viability, proliferation, cell cycle progression and in vitro cell migration. The HBO1 inhibitor provoked apoptosis in the prostate cancer cells. It failed to induce significant cytotoxicity and apoptosis in primary human prostate epithelial cells. shRNA-induced silencing of HBO1 resulted in robust anti-prostate cancer cell activity as well, and adding WM-3835 failed to induce further cytotoxicity in the primary prostate cancer cells. Conversely, ectopic overexpression of HBO1 further augmented primary prostate cancer cell proliferation and migration. WM-3835 inhibited H3-H4 acetylation and downregulated several pro-cancerous genes (CCR2, MYLK, VEGFR2, and OCIAD2) in primary CRPC cells. Importantly, HBO1 mRNA and protein levels are significantly elevated in CRPC tissues and cells. In vivo, daily intraperitoneal injection of WM-3835 potently inhibited pPC-1 xenograft growth in nude mice, and no apparent toxicities detected. Moreover, intratumoral injection of HBO1 shRNA adeno-associated virus (AAV) suppressed the growth of primary prostate cancer xenografts in nude mice. H3-H4 histone acetylation and HBO1-dependent genes (CCR2, MYLK, VEGFR2, and OCIAD2) were remarkably decreased in WM-3835-treated or HBO1-silenced xenograft tissues. Together, targeting HBO1 by WM-3835 robustly inhibits CRPC cell growth.
Metamorphism in TDP-43 prion-like domain determines chaperone recognition
Authors: Carrasco Jaime , Antón Rosa , Valbuena Alejandro , Pantoja-Uceda David , Mukhi Mayur , Hervás Rubén , Laurents Douglas V. , Gasset María , Oroz Javier 
Published: January 2023

AbstractThe RNA binding protein TDP-43 forms cytoplasmic inclusions via its C-terminal prion-like domain in several neurodegenerative diseases. Aberrant TDP-43 aggregation arises upon phase de-mixing and transitions from liquid to solid states, following still unknown structural conversions which are primed by oxidative stress and chaperone inhibition. Despite the well-established protective roles for molecular chaperones against protein aggregation pathologies, knowledge on the determinants of chaperone recognition in disease-related prions is scarce. Here we show that chaperones and co-chaperones primarily recognize the structured elements in TDP-43´s prion-like domain. Significantly, while HSP70 and HSP90 chaperones promote TDP-43 phase separation, co-chaperones from the three classes of the large human HSP40 family (namely DNAJA2, DNAJB1, DNAJB4 and DNAJC7) show strikingly different effects on TDP-43 de-mixing. Dismantling of the second helical element in TDP-43 prion-like domain by methionine sulfoxidation impacts phase separation and amyloid formation, abrogates chaperone recognition and alters phosphorylation by casein kinase-1δ. Our results show that metamorphism in the post-translationally modified TDP-43 prion-like domain encodes determinants that command mechanisms with major relevance in disease.
Concerted roles of LRRTM1 and SynCAM 1 in organizing prefrontal cortex synapses and cognitive functions
Authors: de Arce Karen Perez , Ribic Adema , Chowdhury Dhrubajyoti , Watters Katherine , Thompson Garth J. , Sanganahalli Basavaraju G. , Lippard Elizabeth T. C. , Rohlmann Astrid , Strittmatter Stephen M. , Missler Markus , Hyder Fahmeed , Biederer Thomas 
Published: January 2023

AbstractMultiple trans-synaptic complexes organize synapse development, yet their roles in the mature brain and cooperation remain unclear. We analyzed the postsynaptic adhesion protein LRRTM1 in the prefrontal cortex (PFC), a region relevant to cognition and disorders. LRRTM1 knockout (KO) mice had fewer synapses, and we asked whether other synapse organizers counteract further loss. This determined that the immunoglobulin family member SynCAM 1 controls synapse number in PFC and was upregulated upon LRRTM1 loss. Combined LRRTM1 and SynCAM 1 deletion substantially lowered dendritic spine number in PFC, but not hippocampus, more than the sum of single KO impairments. Their cooperation extended presynaptically, and puncta of Neurexins, LRRTM1 partners, were less abundant in double KO (DKO) PFC. Electrophysiology and fMRI demonstrated aberrant neuronal activity in DKO mice. Further, DKO mice were impaired in social interactions and cognitive tasks. Our results reveal concerted roles of LRRTM1 and SynCAM 1 across synaptic, network, and behavioral domains.
Sub-10 fJ/bit radiation-hard nanoelectromechanical non-volatile memory
Authors: Lee Yong-Bok , Kang Min-Ho , Choi Pan-Kyu , Kim Su-Hyun , Kim Tae-Soo , Lee So-Young , Yoon Jun-Bo 
Published: January 2023

AbstractWith the exponential growth of the semiconductor industry, radiation-hardness has become an indispensable property of memory devices. However, implementation of radiation-hardened semiconductor memory devices inevitably requires various radiation-hardening technologies from the layout level to the system level, and such technologies incur a significant energy overhead. Thus, there is a growing demand for emerging memory devices that are energy-efficient and intrinsically radiation-hard. Here, we report a nanoelectromechanical non-volatile memory (NEM-NVM) with an ultra-low energy consumption and radiation-hardness. To achieve an ultra-low operating energy of less than 10$${{{{{{\rm{fJ\; bit}}}}}}}^{-1}$$fJ bit−1, we introduce an out-of-plane electrode configuration and electrothermal erase operation. These approaches enable the NEM-NVM to be programmed with an ultra-low energy of 2.83$${{{{{{\rm{fJ\; bit}}}}}}}^{-1}$$fJ bit−1. Furthermore, due to its mechanically operating mechanisms and radiation-robust structural material, the NEM-NVM retains its superb characteristics without radiation-induced degradation such as increased leakage current, threshold voltage shift, and unintended bit-flip even after 1 Mrad irradiation.
Synaptic vesicle proteins and ATG9A self-organize in distinct vesicle phases within synapsin condensates
Authors: Park Daehun , Wu Yumei , Wang Xinbo , Gowrishankar Swetha , Baublis Aaron , De Camilli Pietro 
Published: January 2023

AbstractEctopic expression in fibroblasts of synapsin 1 and synaptophysin is sufficient to generate condensates of vesicles highly reminiscent of synaptic vesicle (SV) clusters and with liquid-like properties. Here we show that unlike synaptophysin, other major integral SV membrane proteins fail to form condensates with synapsin, but co-assemble into the clusters formed by synaptophysin and synapsin in this ectopic expression system. Another vesicle membrane protein, ATG9A, undergoes activity-dependent exo-endocytosis at synapses, raising questions about the relation of ATG9A traffic to the traffic of SVs. We find that both in fibroblasts and in nerve terminals ATG9A does not co-assemble into synaptophysin-positive vesicle condensates but localizes on a distinct class of vesicles that also assembles with synapsin but into a distinct phase. Our findings suggest that ATG9A undergoes differential sorting relative to SV proteins and also point to a dual role of synapsin in controlling clustering at synapses of SVs and ATG9A vesicles.
Glycolysis regulates KRAS plasma membrane localization and function through defined glycosphingolipids
Authors: Liu Junchen , van der Hoeven Ransome , Kattan Walaa E. , Chang Jeffrey T. , Montufar-Solis Dina , Chen Wei , Wong Maurice , Zhou Yong , Lebrilla Carlito B. , Hancock John F. 
Published: January 2023

AbstractOncogenic KRAS expression generates a metabolic dependency on aerobic glycolysis, known as the Warburg effect. We report an effect of increased glycolytic flux that feeds into glycosphingolipid biosynthesis and is directly linked to KRAS oncogenic function. High resolution imaging and genetic approaches show that a defined subset of outer leaflet glycosphingolipids, including GM3 and SM4, is required to maintain KRAS plasma membrane localization, with GM3 engaging in cross-bilayer coupling to maintain inner leaflet phosphatidylserine content. Thus, glycolysis is critical for KRAS plasma membrane localization and nanoscale spatial organization. Reciprocally oncogenic KRAS selectively upregulates cellular content of these same glycosphingolipids, whose depletion in turn abrogates KRAS oncogenesis in pancreatic cancer models. Our findings expand the role of the Warburg effect beyond ATP generation and biomass building to high-level regulation of KRAS function. The positive feedforward loop between oncogenic KRAS signaling and glycosphingolipid synthesis represents a vulnerability with therapeutic potential.
Hydrogel oxygen reservoirs increase functional integration of neural stem cell grafts by meeting metabolic demands
Authors: Wang Y. , Zoneff E. R. , Thomas J. W. , Hong N. , Tan L. L. , McGillivray D. J. , Perriman A. W. , Law K. C. L. , Thompson L. H. , Moriarty N. , Parish C. L. , Williams R. J. , Jackson C. J. , Nisbet D. R. 
Published: January 2023

AbstractInjectable biomimetic hydrogels have great potential for use in regenerative medicine as cellular delivery vectors. However, they can suffer from issues relating to hypoxia, including poor cell survival, differentiation, and functional integration owing to the lack of an established vascular network. Here we engineer a hybrid myoglobin:peptide hydrogel that can concomitantly deliver stem cells and oxygen to the brain to support engraftment until vascularisation can occur naturally. We show that this hybrid hydrogel can modulate cell fate specification within progenitor cell grafts, resulting in a significant increase in neuronal differentiation. We find that the addition of myoglobin to the hydrogel results in more extensive innervation within the host tissue from the grafted cells, which is essential for neuronal replacement strategies to ensure functional synaptic connectivity. This approach could result in greater functional integration of stem cell-derived grafts for the treatment of neural injuries and diseases affecting the central and peripheral nervous systems.
The function and evolution of a genetic switch controlling sexually dimorphic eye differentiation in honeybees
Authors: Netschitailo Oksana , Wang Yidong , Wagner Anna , Sommer Vivien , Verhulst Eveline C. , Beye Martin 
Published: January 2023

AbstractAnimals develop sex-specific morphological structures that are diverse between organisms. However, understanding the developmental and evolutionary mechanisms governing these traits is still limited and largely restricted to DM domain genes, which are conserved, sex-specific developmental regulators identified in genetic models. Here, we report a sex-specific developmental regulator gene, glubschauge (glu) that selectively regulates sexually dimorphic eye differentiation in honeybees. We found that the sex determination gene feminizer (fem) controls sex-specific splicing of glu transcripts, establishing a genetic switch in which Glu proteins with a zinc finger (ZnF) domain are only expressed in females. We showed that female coding sequence was essential and sufficient for partial feminization. Comparative sequence and functional studies revealed that the evolutionary origination of the genetic switch was followed by the mutational origin of the essential ZnF domain. Our results demonstrate that glu is a newly evolved sex-specific genetic switch for region-specific regulation of a dimorphic character.