bluuebunny/crossref_metadata_2025_split huggingface dataset:
Snow Avalanches as a Driver of Large Wood Dynamics in Mountain Streams
Authors: Kemper John T. , Scamardo Julianne 
Published: December 2023

AbstractSnow avalanches are thought to influence large wood dynamics within mountain streams, but studies that explicitly quantify their impact are minimal. In three headwater catchments of the Frying Pan River, Colorado, USA, we found that wood loads in stream reaches intersected by avalanche pathways ranged from 220 to 8,500 m3/ha and were significantly greater than in non‐avalanched reaches. Inter‐catchment differences in the number of avalanche occurrences were not reflected in control reach wood loads, suggesting that elevated loads may be restricted to the general vicinity of the avalanche pathway. However, the sizable wood volumes in avalanche reaches generated notable geomorphic impacts, indicating that avalanches can create hotspots of in‐stream geomorphic complexity and influence the overall habitat mosaic of the stream ecosystem. Loads in avalanche reaches were moreover significantly greater than literature values for similar streams and recruitment processes, emphasizing the importance of snow avalanches as a wood recruitment mechanism.
Nitrogen‐Containing Functional Groups Dominate the Molecular Absorption of Water‐Soluble Humic‐Like Substances in Air From Nanjing, China Revealed by the Machine Learning Combined FT‐ICR‐MS Technique
Authors: Hong Yihang , Zhang Yan‐Lin , Bao Mengying , Fan Mei‐Yi , Lin Yu‐Chi , Xu Rongshuang , Shu Zhiyang , Wu Ji‐Yan , Cao Fang , Jiang Hongxing , Cheng Zhineng , Li Jun , Zhang Gan 
Published: December 2023

AbstractThe light absorption capacity of water‐soluble humic‐like substances (HULISWS) at the molecular level is crucial for reducing the uncertainties in modeling the radiative forcing. This study proposed a machine learning approach to allocate the light absorption coefficient at 365 nm (Abs365) of HULISWS into 8084 Fourier transform‐ion cyclotron resonance mass spectrometry (FT‐ICR‐MS) detached molecular markers and their potential functional groups. The ML model showed an acceptable uncertainty (<5%) to the whole Abs365 value based on the prediction errors. The results showed that five critical light‐absorbing molecules (C4H6O4NS, C8H6O4NS, C11H15O3N2, C12H15O3N2, and C19H21O6) could explain 74% (±3%) of the variation of Abs365 in the winter, whereas no crucial light‐absorbing molecules were found in the summer. Besides, the nitrogen‐containing functional groups were found to dominate (61% ± 8%) the molecular absorption near the 365 nm of the spectrum. This work illustrated how functional groups affect the absorption of HULISWS, providing critical information for future research of HULISWS on the molecular level.
The Missing Craters and Basin Rings Beneath the Lunar Maria
Authors: Liang Weigang , Andrews‐Hanna Jeffrey C. , Evans Alexander J. 
Published: December 2023

AbstractEvidence for a population of craters buried beneath the nearside lunar maria has been found in the gravity data returned from the Gravity Recovery and Interior Laboratory mission. Although the total population of buried and visible craters within maria is comparable to the crater population in non‐mare regions at large diameters, a deficit was observed for craters less than ∼90 km in diameter. This deficit is surprising because the data can resolve craters down to 10 km in diameter. Similarly, the Imbrium basin only has a partially exposed ring system, with individual ring widths of up to ∼100 km, but where those rings should be buried beneath the mare surface, we find the gravitational signature mostly non‐existent. In this study, we test a series of mechanisms and scenarios that may explain the observed deficits in the buried crater populations by comparing localized Bouguer gravity power spectra and recovered crater size‐frequency distributions from models of a simulated volcanically flooded cratered surface to the observed data. Our results indicate that the observed crater deficit and missing rings of Imbrium are best explained by a smoothing of the pre‐mare surface. We represent this smoothing as a diffusional process, as might occur with thermomechanical erosion during the earliest stages of the mare eruptions. The removal of the missing craters and Imbrium rings was a massive and unprecedented event that sheds light on the early evolution of the mare region, possibly supporting high temperature voluminous floods of lava early during mare formation.
Integrating the Spatial Configurations of Green and Gray Infrastructure in Urban Stormwater Networks
Authors: Chen Xiating , Davitt‐Liu Indigo , Erickson Andrew J. , Feng Xue 
Published: December 2023

AbstractGreen infrastructure (GI) practices improve stormwater quality and reduce urban flooding, but as urban hydrology is highly controlled by its associated gray infrastructure (e.g., stormwater pipe network), GI's watershed‐scale performance depends on its siting within its associated watershed. Although many stormwater practitioners have begun considering GI's spatial configuration within a larger watershed, few approaches allow for flexible scenario exploration, which can untangle GI's interaction with gray infrastructure network and assess its effects on watershed hydrology. To address the gap in integrated gray‐green infrastructure planning, we used an exploratory model to examine gray‐green infrastructure performance using synthetic stormwater networks with varying degrees of flow path meandering, informed by analysis on stormwater networks from the Minneapolis‐St. Paul Metropolitan Area, MN, USA. Superimposed with different coverage and placements of GI (e.g., bioretention cells), these gray‐green stormwater networks are then subjected to different rainfall intensities within Environmental Protection Agency's Storm Water Management Model to simulate their hydrological benefits (e.g., peak flow reduction, flood reduction). Although only limited choices of green and gray infrastructure were explored, the results show that the gray infrastructure's spatial configuration can introduce tradeoffs between increased peak flow and increased flooding, and further interacts with GI coverage and placement to reduce peak flow and flooding at low rainfall intensity. However, as rainfall intensifies, GI ceases to reduce peak flow. For integrated gray‐green infrastructure planning, our results suggest that physical constraints of the stormwater networks and the range of rainfall intensities must be considered when implementing GI.
Exploring the Critical Zone Heterogeneity and the Hydrological Diversity Using an Integrated Ecohydrological Model in Three Contrasted Long‐Term Observatories
Authors: Ackerer J. , Kuppel S. , Braud I. , Pasquet S. , Fovet O. , Probst A. , Pierret M. C. , Ruiz L. , Tallec T. , Lesparre N. , Weill S. , Flechard C. , Probst J. L. , Marçais J. , Riviere A. , Habets F. , Anquetin S. , Gaillardet J. 
Published: December 2023

AbstractAn integrated ecohydrological modeling approach was deployed in three long‐term critical zone (CZ) observatories of the French CZ network (CZ Observatories—Application and Research) to better understand how the CZ heterogeneity modulates the water cycle within territories. Ecohydrological simulations with the physically based model EcH2O‐iso constrained by a wide range of observations crossing several disciplines (meteorology, hydrology, geomorphology, geophysics, soil sciences, and satellite imagery) are able to capture stream water discharges, evapotranspiration fluxes, and piezometric levels in the Naizin, Auradé, and Strengbach watersheds. In Naizin, an agricultural watershed in northwestern France with a schist bedrock underlying deep weathered materials (5–15 m) along gentle slopes, modeling results reveal a deep aquifer with a large total water storage (1,080–1,150 mm), an important fraction of inactive water storage (94%), and relatively long stream water transit times (0.5–2.5 years). In the Auradé watershed, representative of agricultural landscapes of the southwestern France developed on molasse, a relatively shallow regolith (1–8 m) is observed along hilly slopes. Simulations indicate a shallow aquifer with moderate total water storage (590–630 mm), an important fraction of inactive water storage (91%), and shorter stream water transit times (0.1–1.3 years). In the Strengbach watershed, typical of mid‐mountain forested landscapes developed on granite, CZ evolution implies a shallow regolith (1–5 m) along steep slopes. Modeling results infer a shallow aquifer with the smallest total water storage (475–575 mm), the shortest stream water transit times (0.1–0.7 years), but also the highest fraction of active water storage (18%).
Molecular mapping of a core transcriptional signature of microglia-specific genes in schizophrenia
Authors: Fiorito Anna M. , Fakra Eric , Sescousse Guillaume , Ibrahim El Chérif , Rey Romain 
Published: December 2023

AbstractBesides playing a central role in neuroinflammation, microglia regulate synaptic development and is involved in plasticity. Converging lines of evidence suggest that these different processes play a critical role in schizophrenia. Furthermore, previous studies reported altered transcription of microglia genes in schizophrenia, while microglia itself seems to be involved in the etiopathology of the disease. However, the regional specificity of these brain transcriptional abnormalities remains unclear. Moreover, it is unknown whether brain and peripheral expression of microglia genes are related. Thus, we investigated the expression of a pre-registered list of 10 genes from a core signature of human microglia both at brain and peripheral levels. We included 9 independent Gene Expression Omnibus datasets (764 samples obtained from 266 individuals with schizophrenia and 237 healthy controls) from 8 different brain regions and 3 peripheral tissues. We report evidence of a widespread transcriptional alteration of microglia genes both in brain tissues (we observed a decreased expression in the cerebellum, associative striatum, hippocampus, and parietal cortex of individuals with schizophrenia compared with healthy controls) and whole blood (characterized by a mixed altered expression pattern). Our results suggest that brain underexpression of microglia genes may represent a candidate transcriptional signature for schizophrenia. Moreover, the dual brain-whole blood transcriptional alterations of microglia/macrophage genes identified support the model of schizophrenia as a whole-body disorder and lend weight to the use of blood samples as a potential source of biological peripheral biomarkers.
Spatiotemporal expression patterns of anxiety disorder-associated genes
Authors: Karunakaran Kalyani B. , Amemori Ken-ichi 
Published: December 2023

AbstractAnxiety disorders (ADs) are the most common form of mental disorder that affects millions of individuals worldwide. Although physiological studies have revealed the neural circuits related to AD symptoms, how AD-associated genes are spatiotemporally expressed in the human brain still remains unclear. In this study, we integrated genome-wide association studies of four human AD subtypes—generalized anxiety disorder, social anxiety disorder, panic disorder, and obsessive-compulsive disorder—with spatial gene expression patterns. Our investigation uncovered a novel division among AD-associated genes, marked by significant and distinct expression enrichments in the cerebral nuclei, limbic, and midbrain regions. Each gene cluster was associated with specific anxiety-related behaviors, signaling pathways, region-specific gene networks, and cell types. Notably, we observed a significant negative correlation in the temporal expression patterns of these gene clusters during various developmental stages. Moreover, the specific brain regions enriched in each gene group aligned with neural circuits previously associated with negative decision-making and anxious temperament. These results suggest that the two distinct gene clusters may underlie separate neural systems involved in anxiety. As a result, our findings bridge the gap between genes and neural circuitry, shedding light on the mechanisms underlying AD-associated behaviors.
Elovanoid-N34 modulates TXNRD1 key in protection against oxidative stress-related diseases
Authors: Calandria Jorgelina M. , Bhattacharjee Surjyadipta , Kala-Bhattacharjee Sayantani , Mukherjee Pranab K. , Feng Yuehan , Vowinckel Jakob , Treiber Tobias , Bazan Nicolas G. 
Published: December 2023

AbstractThe thioredoxin (TXN) system is an NADPH + H+/FAD redox-triggered effector that sustains homeostasis, bioenergetics, detoxifying drug networks, and cell survival in oxidative stress-related diseases. Elovanoid (ELV)-N34 is an endogenously formed lipid mediator in neural cells from omega-3 fatty acid precursors that modulate neuroinflammation and senescence gene programming when reduction-oxidation (redox) homeostasis is disrupted, enhancing cell survival. Limited proteolysis (LiP) screening of human retinal pigment epithelial (RPE) cells identified TXNRD1 isoforms 2, 3, or 5, the reductase of the TXN system, as an intracellular target of ELV-N34. TXNRD1 silencing confirmed that the ELV-N34 target was isoform 2 or 3. This lipid mediator induces TXNRD1 structure changes that modify the FAD interface domain, leading to its activity modulation. The addition of ELV-N34 decreased membrane and cytosolic TXNRD1 activity, suggesting localizations for the targeted reductase. These results show for the first time that the lipid mediator ELV-N34 directly modulates TXNRD1 activity, underling its protection in several pathologies when uncompensated oxidative stress (UOS) evolves.
N6-methyladenosine demethylase FTO regulates synaptic and cognitive impairment by destabilizing PTEN mRNA in hypoxic-ischemic neonatal rats
Authors: Deng Jianhui , Liao Yanling , Chen Jianghu , Chen Andi , Wu Shuyan , Huang Yongxin , Qian Haitao , Gao Fei , Wu Guixi , Chen Yisheng , Chen Xiaohui , Zheng Xiaochun 
Published: December 2023

AbstractHypoxic-ischemic brain damage (HIBD) can result in significant global rates of neonatal death or permanent neurological disability. N6-methyladenosine (m6A) modification of RNA influences fundamental aspects of RNA metabolism, and m6A dysregulation is implicated in various neurological diseases. However, the biological roles and clinical significance of m6A in HIBD remain unclear. We currently evaluated the effect of HIBD on cerebral m6A methylation in RNAs in neonatal rats. The m6A dot blot assay showed a global augmentation in RNA m6A methylation post-HI. Herein, we also report on demethylase FTO, which is markedly downregulated in the hippocampus and is the main factor involved with aberrant m6A modification following HI. By conducting a comprehensive analysis of RNA-seq data and m6A microarray results, we found that transcripts with m6A modifications were more highly expressed overall than transcripts without m6A modifications. The overexpression of FTO resulted in the promotion of Akt/mTOR pathway hyperactivation, while simultaneously inhibiting autophagic function. This is carried out by the demethylation activity of FTO, which selectively demethylates transcripts of phosphatase and tensin homolog (PTEN), thus promoting its degradation and reduced protein expression after HI. Moreover, the synaptic and neurocognitive disorders induced by HI were effectively reversed through the overexpression of FTO in the hippocampus. Cumulatively, these findings demonstrate the functional importance of FTO-dependent hippocampal m6A methylome in cognitive function and provides novel mechanistic insights into the therapeutic potentials of FTO in neonatal HIBD.
The TRIM21-FOXD1-BCL-2 axis underlies hyperglycaemic cell death and diabetic tissue damage
Authors: Cheng Wenwen , Cai Cifeng , Xu Yifan , Xiao Xueqi , Shi Tiantian , Liao Yueling , Wang Xiaoyi , Chen Shasha , Zhou Meiliang , Liao Zhiyong 
Published: December 2023

AbstractChronic hyperglycaemia is a devastating factor that causes diabetes-induced damage to the retina and kidney. However, the precise mechanism by which hyperglycaemia drives apoptotic cell death is incompletely known. Herein, we found that FOXD1, a FOX family transcription factor specifically expressed in the retina and kidney, regulated the transcription of BCL-2, a master regulator of cell survival. Intriguingly, the protein level of FOXD1, which responded negatively to hyperglycaemic conditions, was controlled by the TRIM21-mediated K48-linked polyubiquitination and subsequent proteasomal degradation. The TRIM21-FOXD1-BCL-2 signalling axis was notably active during diabetes-induced damage to murine retinal and renal tissues. Furthermore, we found that tartary buckwheat flavonoids effectively reversed the downregulation of FOXD1 protein expression and thus restored BCL-2 expression and facilitated the survival of retinal and renal tissues. In summary, we identified a transcription factor responsible for BCL-2 expression, a signalling axis (TRM21-FOXD1-BCL-2) underlying hyperglycaemia-triggered apoptosis, and a potential treatment for deleterious diabetic complications.
Jagged1 intracellular domain/SMAD3 complex transcriptionally regulates TWIST1 to drive glioma invasion
Authors: Kim Jung Yun , Hong Nayoung , Park Sehyeon , Ham Seok Won , Kim Eun-Jung , Kim Sung-Ok , Jang Junseok , Kim Yoonji , Kim Jun-Kyum , Kim Sung-Chan , Park Jong-Whi , Kim Hyunggee 
Published: December 2023

AbstractJagged1 (JAG1) is a Notch ligand that correlates with tumor progression. Not limited to its function as a ligand, JAG1 can be cleaved, and its intracellular domain translocates to the nucleus, where it functions as a transcriptional cofactor. Previously, we showed that JAG1 intracellular domain (JICD1) forms a protein complex with DDX17/SMAD3/TGIF2. However, the molecular mechanisms underlying JICD1-mediated tumor aggressiveness remains unclear. Here, we demonstrate that JICD1 enhances the invasive phenotypes of glioblastoma cells by transcriptionally activating epithelial-to-mesenchymal transition (EMT)-related genes, especially TWIST1. The inhibition of TWIST1 reduced JICD1-driven tumor aggressiveness. Although SMAD3 is an important component of transforming growth factor (TGF)-β signaling, the JICD1/SMAD3 transcriptional complex was shown to govern brain tumor invasion independent of TGF-β signaling. Moreover, JICD1-TWIST1-MMP2 and MMP9 axes were significantly correlated with clinical outcome of glioblastoma patients. Collectively, we identified the JICD1/SMAD3-TWIST1 axis as a novel inducer of invasive phenotypes in cancer cells.
Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma
Authors: Nomura Miyuki , Ohuchi Mai , Sakamoto Yoshimi , Kudo Kei , Yaku Keisuke , Soga Tomoyoshi , Sugiura Yuki , Morita Mami , Hayashi Kayoko , Miyahara Shuko , Sato Taku , Yamashita Yoji , Ito Shigemi , Kikuchi Naohiko , Sato Ikuro , Saito Rintaro , Yaegashi Nobuo , Fukuhara Tatsuro , Yamada Hidekazu , Shima Hiroshi , Nakayama Keiichi I. , Hirao Atsushi , Kawasaki Kenta , Arai Yoichi , Akamatsu Shusuke , Tanuma Sei-ichi , Sato Toshiro , Nakagawa Takashi , Tanuma Nobuhiro 
Published: December 2023

AbstractNicotinamide phosphoribosyltransferase (NAMPT) plays a major role in NAD biosynthesis in many cancers and is an attractive potential cancer target. However, factors dictating therapeutic efficacy of NAMPT inhibitors (NAMPTi) are unclear. We report that neuroendocrine phenotypes predict lung and prostate carcinoma vulnerability to NAMPTi, and that NAMPTi therapy against those cancers is enhanced by dietary modification. Neuroendocrine differentiation of tumor cells is associated with down-regulation of genes relevant to quinolinate phosphoribosyltransferase-dependent de novo NAD synthesis, promoting NAMPTi susceptibility in vitro. We also report that circulating nicotinic acid riboside (NAR), a non-canonical niacin absent in culture media, antagonizes NAMPTi efficacy as it fuels NAMPT-independent but nicotinamide riboside kinase 1-dependent NAD synthesis in tumors. In mouse transplantation models, depleting blood NAR by nutritional or genetic manipulations is synthetic lethal to tumors when combined with NAMPTi. Our findings provide a rationale for simultaneous targeting of NAR metabolism and NAMPT therapeutically in neuroendocrine carcinoma.
Enhanced SREBP2-driven cholesterol biosynthesis by PKCλ/ι deficiency in intestinal epithelial cells promotes aggressive serrated tumorigenesis
Authors: Muta Yu , Linares Juan F. , Martinez-Ordoñez Anxo , Duran Angeles , Cid-Diaz Tania , Kinoshita Hiroto , Zhang Xiao , Han Qixiu , Nakanishi Yuki , Nakanishi Naoko , Cordes Thekla , Arora Gurpreet K. , Ruiz-Martinez Marc , Reina-Campos Miguel , Kasashima Hiroaki , Yashiro Masakazu , Maeda Kiyoshi , Albaladejo-Gonzalez Ana , Torres-Moreno Daniel , García-Solano José , Conesa-Zamora Pablo , Inghirami Giorgio , Metallo Christian M. , Osborne Timothy F. , Diaz-Meco Maria T. , Moscat Jorge 
Published: December 2023

AbstractThe metabolic and signaling pathways regulating aggressive mesenchymal colorectal cancer (CRC) initiation and progression through the serrated route are largely unknown. Although relatively well characterized as BRAF mutant cancers, their poor response to current targeted therapy, difficult preneoplastic detection, and challenging endoscopic resection make the identification of their metabolic requirements a priority. Here, we demonstrate that the phosphorylation of SCAP by the atypical PKC (aPKC), PKCλ/ι promotes its degradation and inhibits the processing and activation of SREBP2, the master regulator of cholesterol biosynthesis. We show that the upregulation of SREBP2 and cholesterol by reduced aPKC levels is essential for controlling metaplasia and generating the most aggressive cell subpopulation in serrated tumors in mice and humans. Since these alterations are also detected prior to neoplastic transformation, together with the sensitivity of these tumors to cholesterol metabolism inhibitors, our data indicate that targeting cholesterol biosynthesis is a potential mechanism for serrated chemoprevention.
Anti-VEGFR2 F(ab′)2 drug conjugate promotes renal accumulation and glomerular repair in diabetic nephropathy
Authors: Liu Di , Song Yanling , Chen Hui , You Yuchan , Zhu Luwen , Zhang Jucong , Xu Xinyi , Hu Jiahao , Huang Xiajie , Wu Xiaochuan , Xu Xiaoling , Jiang Saiping , Du Yongzhong 
Published: December 2023

AbstractPoor renal distribution of antibody-based drugs is the key factor contributing to low treatment efficiency for renal diseases and side effects. Here, we prepare F(ab′)2 fragmented vascular endothelial growth factor receptor 2 antibody (anti-VEGFR2 (F(ab′)2) to block VEGFR2 overactivation in diabetic nephropathy (DN). We find that the anti-VEGFR2 F(ab′)2 has a higher accumulation in DN male mice kidneys than the intact VEGFR2 antibody, and simultaneously preserves the binding ability to VEGFR2. Furthermore, we develop an antibody fragment drug conjugate, anti-VEGFR2 F(ab′)2-SS31, comprising the anti-VEGFR2 F(ab′)2 fragment linked to the mitochondria-targeted antioxidant peptide SS31. We find that introduction of SS31 potentiates the efficacy of anti-VEGFR2 F(ab′)2. These findings provide proof of concept for the premise that antibody fragment drug conjugate improves renal distribution and merits drug validation in renal disease therapy.