bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thickness of the Seasonal Deposits at the Martian North Polar Region From Shadow Variations of Fallen Ice Blocks
Authors: Xiao Haifeng , Xiao Yuchi , Su Shu , Schmidt Frédéric , Lara Luisa M. , Gutierrez Pedro J. 
Published: April 2024

AbstractThe seasonal deposition and sublimation of CO2 constitute a major element in the Martian volatile cycle. Here, we propose to use the shadow variations of the ice blocks at the foot of the steep scarps of the North Polar Layered Deposits (NPLD) to infer the vertical evolution of the seasonal deposits. We conduct an experiment at a steep scarp centered at (85.0°N, 151.5°E). We assume that no snowfall remains on top of the selected ice blocks, the frost ice layer is homogeneous around the ice blocks and their surroundings, and no significant moating is present. We show that the average thickness of the seasonal deposits due to snowfalls in Mars Year 31 is 0.97 ± 0.13 m at Ls = 350.7° in late winter. The large depth measured makes us wonder if snowfalls are more frequent and violent than previously thought. Meanwhile, we show that the average frost thickness in Mars Year 31 reaches 0.64 ± 0.18 m at Ls = 350.7° in late winter. Combined, the total thickness of the seasonal cover in Mars Year 31 reaches 1.63 ± 0.22 m at Ls = 350.7° in late winter, continuously decreases to 0.45 ± 0.06 m at Ls = 42.8° in middle spring and 0.06 ± 0.05 m at Ls = 69.6° in late spring. These estimates are up to 0.8 m lower than the existing Mars Orbiter Laser Altimeter results during the spring. Meanwhile, we observe that snow in the very early spring of Mars Year 36 can be 0.36 ± 0.13 m thicker than that in Mars Year 31. This study demonstrates the dynamics of the Martian climate and emphasizes the importance of its long‐term monitoring.
Spatial, Seasonal, and Diel Controls of Nitrogen‐Carbon‐Oxygen Cycling During Lake‐Water Infiltration to an Aquifer
Authors: Smith Richard L. , Repert Deborah A. , Underwood Jennifer C. , Böhlke J. K. , LeBlanc Denis R. , Hull Robert B. , Kent Douglas B. , Reed Ariel P. , Mroczkowski Stanley J. 
Published: April 2024

AbstractMany freshwater lakes are groundwater flow‐through systems. Although lakes commonly are considered to be sinks for nitrogen inputs, relatively little is known about carbon and nitrogen export from lakes to groundwater. The current study focused on lake‐bottom biogeochemical processes accompanying the transport of nitrogen, dissolved oxygen (O2), and dissolved organic carbon (DOC) during lake‐water recharge from a groundwater flow‐through lake. Lake‐water and porewater (15–100 cm below lakebed) samples were collected along transects within the lake downwelling zone. Infiltrating porewater O2and DOC concentrations decreased with depth while nitrate (NO3−) concentrations increased, indicating nitrification of organic matter within the profiles. The depth of NO3−production and transport was seasonally dependent. In winter, NO3−and O2were exported beyond 100‐cm depth; whereas in summer, shallow nitrification zones were underlain by deeper NO3−reduction zones, and diel patterns of O2and NO3−penetration depths were observed. Microbial community compositions and stable isotope profiles (δ15N[NO3−], δ18O[NO3−], δ18O[O2]) were consistent with apparent C–N–O reaction stoichiometries indicating O2reduction and nitrification in shallower porewater, followed by varying NO3−reduction at depth. Maximum porewater NO3−concentrations (∼10–20 μM) were limited by infiltrating O2concentrations and C/N ratios of reacting organic matter. Lake‐water level variations caused changes in shoreline position and porewater velocities, while variations in lake‐water temperature, DOC, and O2contributed to changes in reaction rates and depth of O2and NO3−penetration into the lakebed. The quality of groundwater recharged by lake water reflected temporally and spatially varying physical and biogeochemical processes in the sediment porewater.
Toward More Accurate Modeling of Canopy Radiative Transfer and Leaf Electron Transport in Land Surface Modeling
Authors: Wang Yujie , Frankenberg Christian 
Published: April 2024

AbstractModeling leaf photosynthesis is essential for quantifying the carbon, water, and energy fluxes of the terrestrial biosphere. However, due to the lack of simultaneous measurements of leaf light absorption and gas exchange, canopy radiative transfer (RT) and photosynthesis modeling often rely on simplified assumptions about light absorption and electron transport. These assumptions ignore variations in leaf biophysical traits and environmental conditions. In this study, we utilized a next‐generation land surface model (LSM)—CliMA Land, which incorporates hyperspectral canopy RT and provides a more accurate representation of trait variations. We evaluated the potential bias in electron transport estimates introduced by the broadband RT schemes used in traditional LSMs. Additionally, we explored the impact of different leaf electron transport parameterization schemes on global‐scale photosynthesis and fluorescence modeling. We showed that (a) traditional LSMs that disregard the impacts of leaf temperature and leaf traits on electron transport tend to overestimate electron transport rates. (b) Photosynthesis and fluorescence within a grid can exhibit biases exceeding 20%, with these biases demonstrating contrasting seasonality. (c) Global estimates of integrated photosynthesis and fluorescence differ by 8.1% and 8.8%, respectively. These results underscore the importance of adopting more sophisticated and accurate modeling schemes, such as hyperspectral canopy RT, in future LSMs and Earth system modeling to enhance the reliability of modeling outcomes.
The Loss of Starlink Satellites in February 2022: How Moderate Geomagnetic Storms Can Adversely Affect Assets in Low‐Earth Orbit
Authors: Baruah Yoshita , Roy Souvik , Sinha Suvadip , Palmerio Erika , Pal Sanchita , Oliveira Denny M. , Nandy Dibyendu 
Published: April 2024

AbstractOn 3 February 2022, SpaceX launched 49 Starlink satellites, 38 of which unexpectedly de‐orbited. Although this event was attributed to space weather, definitive causality remained elusive because space weather conditions were not extreme. In this study, we identify solar sources of the interplanetary coronal mass ejections that were responsible for the geomagnetic storms around the time of launch of the Starlink satellites and for the first time, investigate their impact on Earth's magnetosphere using magnetohydrodynamic modeling. The model results demonstrate that the satellites were launched into an already disturbed space environment that persisted over several days. However, on performing comparative satellite orbital decay analyses, we find that space weather alone was not responsible but conspired together with a low‐altitude insertion and low satellite mass‐to‐area ratio to precipitate this unusual loss. Our work bridges space weather causality across the Sun–Earth system—with relevance for space‐based human technologies.
Switching Between Whistler‐Mode Waves on Inhomogeneities of the Plasma Density and Magnetic Field
Authors: Nejad Salman A. , Streltsov Anatoly V. 
Published: April 2024

AbstractWe present results from the investigation of a transition between two whistler‐mode waves with the same frequency and the parallel wavelength but different perpendicular wavenumbers in the inhomogeneous media consisting of the plasma density and the background magnetic field. We consider transverse inhomogeneities of these quantities. We demonstrate that there are critical values of the plasma density and the magnetic field (which depend on the wave frequency and the parallel wavelength) and the switching between two whistler‐mode waves occurs in the vicinity of these values. We analyze this problem assuming that these critical values are reached inside the finite‐size transition layer between two regions where all the background quantities are homogeneous. We found analytical criteria for the mode switching and we confirmed our results with time‐dependent simulations of the electron‐MHD equations describing whistler‐mode waves in the magnetospheric plasma. We also investigate numerically the dependency of various parameters of the wave switching on the size of the transition region containing critical values of the plasma density and the magnetic field.
The selective D3Receptor antagonist VK4-116 reverses loss of insight caused by self-administration of cocaine in rats
Authors: Panayi Marios C. , Shetty Shohan , Porod Micaela , Bahena Lisette , Xi Zheng-Xiong , Newman Amy Hauck , Schoenbaum Geoffrey 
Published: April 2024

AbstractChronic psychostimulant use causes long-lasting changes to neural and cognitive function that persist after long periods of abstinence. As cocaine users transition from drug use to abstinence, a parallel transition from hyperactivity to hypoactivity has been found in orbitofrontal-striatal glucose metabolism and striatal D2/D3-receptor activity. Targeting these changes pharmacologically, using highly selective dopamine D3-receptor (D3R) antagonists and partial agonists, has shown promise in reducing drug-taking, and attenuating relapse in animal models of cocaine and opioid use disorder. However, much less attention has been paid to treating the loss of insight, operationalized as the inability to infer likely outcomes, associated with chronic psychostimulant use. Here we tested the selective D3R antagonist VK4-116 as a treatment for this loss in rats with a prior history of cocaine use. Male and female rats were first trained to self-administer cocaine or a sucrose liquid for 2 weeks. After 4 weeks of abstinence, performance was assessed using a sensory preconditioning (SPC) learning paradigm. Rats were given VK4-116 (15 mg/kg, i.p.) or vehicle 30 min prior to each SPC training session, thus creating four drug-treatment groups: sucrose-vehicle, sucrose-VK4-116, cocaine-vehicle, cocaine-VK4-116. The control groups (sucrose-vehicle, sucrose-VK4-116) showed normal sensory preconditioning, whereas cocaine use (cocaine-vehicle) selectively disrupted responding to the preconditioned cue, an effect that was reversed in the cocaine-VK4-116 group, which demonstrating responding to the preconditioned cue at levels comparable to controls. These preclinical findings demonstrate that highly selective dopamine D3R antagonists, particularly VK4-116, can reverse the long-term negative behavioral consequences of cocaine use.
The prognostic value of MEK pathway–associated estrogen receptor signaling activity for female cancers
Authors: Ng Chun Wai , Tsang Yvonne T. M. , Gershenson David M. , Wong Kwong-Kwok 
Published: April 2024

Abstract
Background
Other than for breast cancer, endocrine therapy has not been highly effective for gynecologic cancers. Endocrine therapy resistance in estrogen receptor positive gynecologic cancers is still poorly understood. In this retrospective study, we examined the estrogen receptor (ER) signaling pathway activities of breast, ovarian, endometrial, and cervical cancers to identify those that may predict endocrine therapy responsiveness.

Methods
Clinical and genomic data of women with breast and gynecological cancers were downloaded from cBioPortal for Cancer Genomics. Estrogen receptor alpha (ESR1) expression level and sample-level pathway enrichment scores (EERES) were calculated to classify patients into four groups (low/high ESR1 and low/high EERES). Correlation between ESR1/EERES score and survival was further validated with RNAseq data from low-grade serous ovarian cancer. Pathway analyses were performed among different ESR1/EERES groups to identify genes that correlate with endocrine resistance, which are validated using Cancer Cell Line Encyclopedia gene expression and Genomics of Drug Sensitivity in Cancer data.

Results
We identified a novel combined prognostic value of ESR1 expression and the corresponding estrogen response signaling (EERES score) for breast cancer. The combined prognostic value (ESR1/EERES) may be applicable to other gynecologic cancers. More importantly, we discovered that ER signaling can cross-regulate MEK pathway activation. We identified downstream genes in the MEK pathway (EPHA2, INAVA, MALL, MPZL2, PCDH1, and TNFRSF21) that are potential endocrine therapy response biomarkers.

Conclusion
This study demonstrated that targeting both the ER and the ER signaling activity related MEK pathway may aid the development of endocrine therapy strategies for personalized medicine.
A novel inhibitory BAK antibody enables assessment of non-activated BAK in cancer cells
Authors: Subas Satish Hema Preethi , Iyer Sweta , Shi Melissa X. , Wong Agnes W. , Fischer Karla C. , Wardak Ahmad Z. , Lio Daisy , Brouwer Jason M. , Uren Rachel T. , Czabotar Peter E. , Miller Michelle S. , Kluck Ruth M. 
Published: April 2024

AbstractBAX and BAK are pro-apoptotic members of the BCL2 family that are required to permeabilize the mitochondrial outer membrane. The proteins can adopt a non-activated monomeric conformation, or an activated conformation in which the exposed BH3 domain facilitates binding either to a prosurvival protein or to another activated BAK or BAX protein to promote pore formation. Certain cancer cells are proposed to have high levels of activated BAK sequestered by MCL1 or BCLXL, thus priming these cells to undergo apoptosis in response to BH3 mimetic compounds that target MCL1 or BCLXL. Here we report the first antibody, 14G6, that is specific for the non-activated BAK conformer. A crystal structure of 14G6 Fab bound to BAK revealed a binding site encompassing both the α1 helix and α5-α6 hinge regions of BAK, two sites involved in the unfolding of BAK during its activation. In mitochondrial experiments, 14G6 inhibited BAK unfolding triggered by three diverse BAK activators, supporting crucial roles for both α1 dissociation and separation of the core (α2-α5) and latch (α6-α9) regions in BAK activation. 14G6 bound the majority of BAK in several leukaemia cell lines, and binding decreased following treatment with BH3 mimetics, indicating only minor levels of constitutively activated BAK in those cells. In summary, 14G6 provides a new means of assessing BAK status in response to anti-cancer treatments.
Inhibition of acyl-CoA binding protein (ACBP) by means of a GABAARγ2-derived peptide
Authors: Anagnostopoulos Gerasimos , Saavedra Ester , Lambertucci Flavia , Motiño Omar , Dimitrov Jordan , Roiz-Valle David , Quesada Victor , Alvarez-Valadez Karla , Chen Hui , Sauvat Allan , Rong Yan , Nogueira-Recalde Uxía , Li Sijing , Montégut Léa , Djavaheri-Mergny Mojgan , Castedo Maria , Lopez-Otin Carlos , Maiuri Maria Chiara , Martins Isabelle , Kroemer Guido 
Published: April 2024

AbstractAcyl-CoA binding protein (ACBP) encoded by diazepam binding inhibitor (DBI) is an extracellular inhibitor of autophagy acting on the gamma-aminobutyric acid A receptor (GABAAR) γ2 subunit (GABAARγ2). Here, we show that lipoanabolic diets cause an upregulation of GABAARγ2 protein in liver hepatocytes but not in other major organs. ACBP/DBI inhibition by systemically injected antibodies has been demonstrated to mediate anorexigenic and organ-protective, autophagy-dependent effects. Here, we set out to develop a new strategy for developing ACBP/DBI antagonists. For this, we built a molecular model of the interaction of ACBP/DBI with peptides derived from GABAARγ2. We then validated the interaction between recombinant and native ACBP/DBI protein and a GABAARγ2-derived eicosapeptide (but not its F77I mutant) by pull down experiments or surface plasmon resonance. The GABAARγ2-derived eicosapeptide inhibited the metabolic activation of hepatocytes by recombinant ACBP/DBI protein in vitro. Moreover, the GABAARγ2-derived eicosapeptide (but not its F77I-mutated control) blocked appetite stimulation by recombinant ACBP/DBI in vivo, induced autophagy in the liver, and protected mice against the hepatotoxin concanavalin A. We conclude that peptidomimetics disrupting the interaction between ACBP/DBI and GABAARγ2 might be used as ACBP/DBI antagonists. This strategy might lead to the future development of clinically relevant small molecules of the ACBP/DBI system.
Paternal dietary macronutrient balance and energy intake drive metabolic and behavioral differences among offspring
Authors: Crean Angela Jane , Senior Alistair McNair , Freire Therese , Clark Thomas Daniel , Mackay Flora , Austin Gracie , Pulpitel Tamara Jayne , Nobrega Marcelo Aguiar , Barrès Romain , Simpson Stephen James 
Published: April 2024

AbstractPaternal diet can influence the phenotype of the next generation, yet, the dietary components inducing specific responses in the offspring are not identified. Here, we use the Nutritional Geometry Framework to determine the effects of pre-conception paternal dietary macronutrient balance on offspring metabolic and behavioral traits in mice. Ten isocaloric diets varying in the relative proportion of protein, fats, and carbohydrates are fed to male mice prior to mating. Dams and offspring are fed standard chow and never exposed to treatment diets. Body fat in female offspring is positively associated with the paternal consumption of fat, while in male offspring, an anxiety-like phenotype is associated to paternal diets low in protein and high in carbohydrates. Our study uncovers that the nature and the magnitude of paternal effects are driven by interactions between macronutrient balance and energy intake and are not solely the result of over- or undernutrition.
Tumor-activated in situ synthesis of single-atom catalysts for O2-independent photodynamic therapy based on water-splitting
Authors: Yin Yiyan , Ge Xiyang , Ouyang Jin , Na Na 
Published: April 2024

AbstractSingle-atom catalysts (SACs) have attracted interest in photodynamic therapy (PDT), while they are normally limited by the side effects on normal tissues and the interference from the Tumor Microenvironment (TME). Here we show a TME-activated in situ synthesis of SACs for efficient tumor-specific water-based PDT. Upon reduction by upregulated GSH in TME, C3N4-Mn SACs are obtained in TME with Mn atomically coordinated into the cavity of C3N4 nanosheets. This in situ synthesis overcomes toxicity from random distribution and catalyst release in healthy tissues. Based on the Ligand-to-Metal charge transfer (LMCT) process, C3N4-Mn SACs exhibit enhanced absorption in the red-light region. Thereby, a water-splitting process is induced by C3N4-Mn SACs under 660 nm irradiation, which initiates the O2-independent generation of highly toxic hydroxyl radical (·OH) for cancer-specific PDT. Subsequently, the ·OH-initiated lipid peroxidation process is demonstrated to devote effective cancer cell death. The in situ synthesized SACs facilitate the precise cancer-specific conversion of inert H2O to reactive ·OH, which facilitates efficient cancer therapy in female mice. This strategy achieves efficient and precise cancer therapy, not only avoiding the side effects on normal tissues but also overcoming tumor hypoxia.
Phage-specific immunity impairs efficacy of bacteriophage targeting Vancomycin Resistant Enterococcus in a murine model
Authors: Berkson Julia D. , Wate Claire E. , Allen Garrison B. , Schubert Alyxandria M. , Dunbar Kristin E. , Coryell Michael P. , Sava Rosa L. , Gao Yamei , Hastie Jessica L. , Smith Emily M. , Kenneally Charlotte R. , Zimmermann Sally K. , Carlson Paul E. 
Published: April 2024

AbstractBacteriophage therapy is a promising approach to address antimicrobial infections though questions remain regarding the impact of the immune response on clinical effectiveness. Here, we develop a mouse model to assess phage treatment using a cocktail of five phages from the Myoviridae and Siphoviridae families that target Vancomycin-Resistant Enterococcus gut colonization. Phage treatment significantly reduces fecal bacterial loads of Vancomycin-Resistant Enterococcus. We also characterize immune responses elicited following administration of the phage cocktail. While minimal innate responses are observed after phage administration, two rounds of treatment induces phage-specific neutralizing antibodies and accelerate phage clearance from tissues. Interestingly, the myophages in our cocktail induce a more robust neutralizing antibody response than the siphophages. This anti-phage immunity reduces the effectiveness of the phage cocktail in our murine model. Collectively, this study shows phage-specific immune responses may be an important consideration in the development of phage cocktails for therapeutic use.
The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation
Authors: Kang Eun-Jung , Kim Jae-Hoon , Kim Young Eun , Lee Hana , Jung Kwang Bo , Chang Dong-Ho , Lee Youngjin , Park Shinhye , Lee Eun-Young , Lee Eun-Ji , Kang Ho Bum , Rhyoo Moon-Young , Seo Seungwoo , Park Sohee , Huh Yubin , Go Jun , Choi Jung Hyeon , Choi Young-Keun , Lee In-Bok , Choi Dong-Hee , Seo Yun Jeong , Noh Jung-Ran , Kim Kyoung-Shim , Hwang Jung Hwan , Jeong Ji-Seon , Kwon Ha-Jeong , Yoo Hee Min , Son Mi-Young , Kim Yeon-Gu , Lee Dae-Hee , Kim Tae-Young , Kwon Hyo-Jung , Kim Myung Hee , Kim Byoung-Chan , Kim Yong-Hoon , Kang Dukjin , Lee Chul-Ho 
Published: April 2024

AbstractAkkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/β-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/β-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.