bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct Comparison Between a Non‐Orographic Gravity Wave Drag Scheme and Constant Level Balloons
Authors: Lott F. , Rani R. , Podglajen A. , Codron F. , Guez L. , Hertzog A. , Plougonven R. 
Published: February 2023

AbstractThe parameterization scheme that represents gravity waves due to convection in LMDz‐6A, the atmospheric components of the IPSL coupled climate model (IPSLCM6), is directly compared to Strateole‐2 balloon observations made in the lower tropical stratosphere from November 2019 to February 2020. The input meteorological fields necessary to run the parameterization offline are extracted from the ERA5 reanalysis and correspond to the instantaneous meteorological conditions found underneath the balloons. In general, we find a fair agreement between measurements of the momentum fluxes due to waves with periods less than 1 hr and the parameterization. The correlation of the daily values between the observations and the results of the parameterization is around 0.4, which is statistically elevated considering that we analyze around 600 days of data and surprisingly good considering that the parameterization has not been tuned: the scheme is just the standard one that helps producing a quasi‐biennial oscillation (QBO) in the IPSLCM6 model. Online simulations also show that the measured values of momentum fluxes are well representative of the zonally and averaged values of momentum fluxes needed in LMDz‐6A to simulate a QBO. The observations also show that longer waves with periods smaller than a day carry about twice as much flux as waves with periods smaller than an hour, which is a challenge since the low period waves that make the difference are potentially in the “gray zone” of most climate models.
Optimizing the Isoprene Emission Model MEGAN With Satellite and Ground‐Based Observational Constraints
Authors: DiMaria Christian A. , Jones Dylan B. A. , Worden Helen , Bloom A. Anthony , Bowman Kevin , Stavrakou Trissevgeni , Miyazaki Kazuyuki , Worden John , Guenther Alex , Sarkar Chinmoy , Seco Roger , Park Jeong‐Hoo , Tota Julio , Alves Eliane Gomes , Ferracci Valerio 
Published: February 2023

AbstractIsoprene is a hydrocarbon emitted in large quantities by terrestrial vegetation. It is a precursor to several air quality and climate pollutants including ozone. Emission rates vary with plant species and environmental conditions. This variability can be modeled using the Model of Emissions of Gases and Aerosols from Nature (MEGAN). MEGAN parameterizes isoprene emission rates as a vegetation‐specific standard rate which is modulated by scaling factors that depend on meteorological and environmental driving variables. Recent experiments have identified large uncertainties in the MEGAN temperature response parameterization, while the emission rates under standard conditions are poorly constrained in some regions due to a lack of representative measurements and uncertainties in landcover. In this study, we use Bayesian model‐data fusion to optimize the MEGAN temperature response and standard emission rates using satellite‐ and ground‐based observational constraints. Optimization of the standard emission rate with satellite constraints reduced model biases but was highly sensitive to model input errors and drought stress and was found to be inconsistent with ground‐based constraints at an Amazonian field site, reflecting large uncertainties in the satellite‐based emissions. Optimization of the temperature response with ground‐based constraints increased the temperature sensitivity of the model by a factor of five at an Amazonian field site but had no impact at a UK field site, demonstrating significant ecosystem‐dependent variability of the isoprene emission temperature sensitivity. Ground‐based measurements of isoprene across a wide range of ecosystems will be key for obtaining an accurate representation of isoprene emission temperature sensitivity in global biogeochemical models.
Visuomotor anomalies in achiasmatic mice expressing a transfer-defective Vax1 mutant
Authors: Min Kwang Wook , Kim Namsuk , Lee Jae Hoon , Sung Younghoon , Kim Museong , Lee Eun Jung , Kim Jong-Myeong , Kim Jae-Hyun , Lee Jaeyoung , Cho Wonjin , Yang Jee Myung , Kim Nury , Kim Jaehoon , Lee C. Justin , Park Young-Gyun , Lee Seung-Hee , Lee Han-Woong , Kim Jin Woo 
Published: February 2023

AbstractIn binocular animals that exhibit stereoscopic visual responses, the axons of retinal ganglion cells (RGCs) connect to brain areas bilaterally by forming a commissure called the optic chiasm (OC). Ventral anterior homeobox 1 (Vax1) contributes to the formation of the OC, acting endogenously in optic pathway cells and exogenously in growing RGC axons. Here, we generated Vax1AA/AA mice expressing the Vax1AA mutant, which is incapable of intercellular transfer. We found that RGC axons cannot take up Vax1AA protein from the Vax1AA/AA mouse optic stalk (OS) and grow slowly to arrive at the hypothalamus at a late stage. The RGC axons of Vax1AA/AA mice connect exclusively to ipsilateral brain areas after failing to access the midline, resulting in reduced visual acuity and abnormal oculomotor responses. Overall, our study provides physiological evidence for the necessity of intercellular transfer of Vax1 and the importance of the bilateral RGC axon projection in proper visuomotor responses.
Association of BMAL1 clock gene polymorphisms with fasting glucose in children
Authors: Yang Yi-De , Zeng Yuan , Li Jian , Zhou Jun-Hua , He Quan-Yuan , Zheng Chan-Juan , Reichetzeder Christoph , Krämer Bernhard K. , Hocher Berthold 
Published: February 2023

Abstract
Background
The brain and muscle Arnt-like protein-1 (BMAL1) gene is an important circadian clock gene and previous studies have found that certain polymorphisms are associated with type 2 diabetes in adults. However, it remains unknown if such polymorphisms can affect fasting glucose in children and if other factors modify the associations.

Methods
A school-based cross-sectional study with 947 Chinese children was conducted. A multivariable linear regression model was used to analyze the association between BMAL1 gene polymorphisms and fasting glucose level.

Results
After adjusting for age, sex, body mass index (BMI), physical activity, and unhealthy diet, GG genotype carriers of BMAL1 rs3789327 had higher fasting glucose than AA/GA genotype carriers (b = 0.101, SE = 0.050, P = 0.045). Adjusting for the same confounders, rs3816358 was shown to be significantly associated with fasting glucose (b = 0.060, SE = 0.028, P = 0.032). Furthermore, a significant interaction between rs3789327 and nutritional status on fasting glucose was identified (Pinteraction = 0.009); rs3789327 was associated with fasting glucose in the overweight/obese subgroup (b = 0.353, SE = 0.126, P = 0.006), but not in non-overweight/non-obese children.

Conclusions
BMAL1 polymorphisms were significantly associated with the fasting glucose level in children. Additionally, the observed interaction between nutritional status and BMAL1 supports promoting an optimal BMI in children genetically predisposed to higher glucose level.

Impact

Polymorphisms in the essential circadian clock gene BMAL1 were associated with fasting blood glucose levels in children. Additionally, there was a significant interaction between nutritional status and BMAL1 affecting fasting glucose levels.

BMAL1 rs3789327 was associated with fasting glucose only in overweight/obese children.

This finding could bring novel insights into mechanisms by which nutritional status influences fasting glucose in children.
Celastrol suppresses colorectal cancer via covalent targeting peroxiredoxin 1
Authors: Xu Heng , Zhao Hongfang , Ding Chunyong , Jiang Defang , Zhao Zijie , Li Yang , Ding Xiaoyu , Gao Jing , Zhou Hu , Luo Cheng , Chen Guoqiang , Zhang Ao , Xu Ying , Zhang Hao 
Published: February 2023

AbstractAs a terpenoids natural product isolated from the plant Thunder God Vine, Celastrol is widely studied for its pharmacological activities, including anti-tumor activities. The clinical application of Celastrol is strictly limited due to its severe side effects, whereas previously revealed targets and mechanism of Celastrol seldom reduce its in vivo toxicity via structural optimization. Target identification has a far-reaching influence on the development of innovative drugs, and omics data has been widely used for unbiased target prediction. However, it is difficult to enrich target of specific phenotype from thousands of genes or proteins, especially for natural products with broad promising activities. Here, we developed a text-mining-based web-server tool to enrich targets from omics data of inquired compounds. Then peroxiredoxin 1 (PRDX1) was identified as the ROS-manipulating target protein of Celastrol in colorectal cancer. Our solved high-resolution crystal structure revealed the unique covalent binding mode of Celastrol with PRDX1. New derivative compound 19-048 with improved potency against PRDX1 and selectivity towards PRDX2~PRDX6 were synthesized based on crystal structure analysis. Both Celastrol and 19-048 effectively suppressed the proliferation of colorectal cancer cells. The anti-tumor efficacy of Celastrol and 19-048 was significantly diminished on xenograft nude mice bearing PRDX1 knock-down colorectal cancer cells. Several downstream genes of p53 signaling pathway were dramatically up-regulated with Celastrol or 19-048 treatment. Our findings reveal that the side effects of Celastrol could be reduced via structural modification, and PRDX1 inhibition is promising for the treatment of colorectal cancer.
Circulating Th17 T cells at treatment onset predict autoimmune toxicity of PI3Kδ inhibitors
Authors: Gadi Deepti , Martindale Stephen P. , Chiu Pui Yan , Khalsa Jasneet , Chen Pei-Hsuan , Fernandes Stacey M. , Wang Zixu , Tyekucheva Svitlana , Machado John-Hanson , Fisher David C. , Armand Philippe , Davids Matthew S. , Rodig Scott , Sherry Barbara , Brown Jennifer R. 
Published: February 2023

AbstractPI3Kδ inhibitors are approved for the therapy of B cell malignancies, but their clinical use has been limited by unpredictable autoimmune toxicity, despite promising efficacy and evidence that toxicity is associated with improved clinical outcomes. Prior phenotypic evaluation by CyTOF has identified increases in activated CD8 T cells with activation of Th17 T cells, as well as decreases in Tregs, particularly in patients with toxicity. Here we sought to further understand the effects of idelalisib and duvelisib in vitro, and demonstrate that both idelalisib and duvelisib can inhibit T cell proliferation as well as Th1 and Treg differentiation in vitro, while promoting Th2 and Th17 differentiation. We further demonstrate directly using intracellular flow cytometry that autoimmune toxicity in patients is associated with higher absolute numbers of CD4 and CD8 T cells with Th17 differentiation in peripheral blood prior to therapy, and that gastrointestinal tissues from patients with active autoimmune complications of PI3Kδ inhibitors show infiltration with Th17+ T cells. These same tissues show depletion of Tregs as compared to CLL patients without toxicity, suggesting that loss of Tregs may be permissive for Th17 activation to lead to autoimmune toxicity. Clinical trials to restore this balance are warranted.
Non-canonical functions of spliceosome components in cancer progression
Authors: Ivanova Olga M. , Anufrieva Ksenia S. , Kazakova Anastasia N. , Malyants Irina K. , Shnaider Polina V. , Lukina Maria M. , Shender Victoria O. 
Published: February 2023

AbstractDysregulation of pre-mRNA splicing is a common hallmark of cancer cells and it is associated with altered expression, localization, and mutations of the components of the splicing machinery. In the last few years, it has been elucidated that spliceosome components can also influence cellular processes in a splicing-independent manner. Here, we analyze open source data to understand the effect of the knockdown of splicing factors in human cells on the expression and splicing of genes relevant to cell proliferation, migration, cell cycle regulation, DNA repair, and cell death. We supplement this information with a comprehensive literature review of non-canonical functions of splicing factors linked to cancer progression. We also specifically discuss the involvement of splicing factors in intercellular communication and known autoregulatory mechanisms in restoring their levels in cells. Finally, we discuss strategies to target components of the spliceosome machinery that are promising for anticancer therapy. Altogether, this review greatly expands understanding of the role of spliceosome proteins in cancer progression.
3-Carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) induces cell death through ferroptosis and acts as a trigger of apoptosis in kidney cells
Authors: Park Jung Sun , Kim Dong-Hyun , Choi Hoon-In , Kim Chang Seong , Bae Eun Hui , Ma Seong Kwon , Kim Soo Wan 
Published: February 2023

AbstractFerroptosis is a cell death mechanism characterized by intracellular iron accumulation and lipid peroxidation. Effects of uremic toxins on ferroptosis in the kidney are not well understood. We investigated whether protein-bound uremic toxins induce ferroptosis, resulting in cell death, using the bilateral ureteral obstruction (BUO) mouse model and kidney cells. In BUO mice, we observed elevated lipid peroxidation, increased iron concentration, and decreased glutathione peroxidase 4 (GPX4) expression. Levels of transferrin receptor 1 and system Xc-, which are involved in iron transport and storage, were also elevated, while those of ferritin heavy and light chains (FHC and FLC) were reduced. Treatment of HK-2 and NRK49F kidney cells with CMPF decreased GSH levels and the expression of GPX4, FHC, and FLC, and increased levels of ROS, lipid peroxidation, and intracellular iron concentration. CMPF-induced and erastin-induced decreases in GPX4 levels and increases in Bax and cytochrome C levels were counteracted by ferrostatin-1 pretreatment. However, GPX4 mRNA levels, protein abundance, or promoter activity were not restored by Z-VAD-FMK, a multi-caspase inhibitor. These results suggest that ferroptosis induced by CMPF treatment induces apoptosis, and inhibition of ferroptosis reduces apoptosis, suggesting that ferroptosis plays a role in triggering cell death by apoptosis.
Deletion of SNX9 alleviates CD8 T cell exhaustion for effective cellular cancer immunotherapy
Authors: Trefny Marcel P. , Kirchhammer Nicole , Auf der Maur Priska , Natoli Marina , Schmid Dominic , Germann Markus , Fernandez Rodriguez Laura , Herzig Petra , Lötscher Jonas , Akrami Maryam , Stinchcombe Jane C. , Stanczak Michal A. , Zingg Andreas , Buchi Melanie , Roux Julien , Marone Romina , Don Leyla , Lardinois Didier , Wiese Mark , Jeker Lukas T. , Bentires-Alj Mohamed , Rossy Jérémie , Thommen Daniela S. , Griffiths Gillian M. , Läubli Heinz , Hess Christoph , Zippelius Alfred 
Published: February 2023

AbstractTumor-specific T cells are frequently exhausted by chronic antigenic stimulation. We here report on a human antigen-specific ex vivo model to explore new therapeutic options for T cell immunotherapies. T cells generated with this model resemble tumor-infiltrating exhausted T cells on a phenotypic and transcriptional level. Using a targeted pooled CRISPR-Cas9 screen and individual gene knockout validation experiments, we uncover sorting nexin-9 (SNX9) as a mediator of T cell exhaustion. Upon TCR/CD28 stimulation, deletion of SNX9 in CD8 T cells decreases PLCγ1, Ca2+, and NFATc2-mediated T cell signaling and reduces expression of NR4A1/3 and TOX. SNX9 knockout enhances memory differentiation and IFNγ secretion of adoptively transferred T cells and results in improved anti-tumor efficacy of human chimeric antigen receptor T cells in vivo. Our findings highlight that targeting SNX9 is a strategy to prevent T cell exhaustion and enhance anti-tumor immunity.
Multi-area recordings and optogenetics in the awake, behaving marmoset
Authors: Jendritza Patrick , Klein Frederike J. , Fries Pascal 
Published: February 2023

AbstractThe common marmoset has emerged as a key model in neuroscience. Marmosets are small in size, show great potential for genetic modification and exhibit complex behaviors. Thus, it is necessary to develop technology that enables monitoring and manipulation of the underlying neural circuits. Here, we describe a novel approach to record and optogenetically manipulate neural activity in awake, behaving marmosets. Our design utilizes a light-weight, 3D printed titanium chamber that can house several high-density silicon probes for semi-chronic recordings, while enabling simultaneous optogenetic stimulation. We demonstrate the application of our method in male marmosets by recording multi- and single-unit data from areas V1 and V6 with 192 channels simultaneously, and show that optogenetic activation of excitatory neurons in area V6 can influence behavior in a detection task. This method may enable future studies to investigate the neural basis of perception and behavior in the marmoset.
Effects of exercise countermeasures on multisystem function in long duration spaceflight astronauts
Authors: Scott Jessica M. , Feiveson Alan H. , English Kirk L. , Spector Elisabeth R. , Sibonga Jean D. , Dillon E. Lichar , Ploutz-Snyder Lori , Everett Meghan E. 
Published: February 2023

AbstractExercise training is a key countermeasure used to offset spaceflight-induced multisystem deconditioning. Here, we evaluated the effects of exercise countermeasures on multisystem function in a large cohort (N = 46) of astronauts on long-duration spaceflight missions. We found that during 178 ± 48 d of spaceflight, ~600 min/wk of aerobic and resistance exercise did not fully protect against multisystem deconditioning. However, substantial inter-individual heterogeneity in multisystem response was apparent with changes from pre to postflight ranging from −30% to +5%. We estimated that up to 17% of astronauts would experience performance-limiting deconditioning if current exercise countermeasures were used on future spaceflight missions. These findings support the need for refinement of current countermeasures, adjunct interventions, or enhanced requirements for preflight physiologic and functional capacity for the protection of astronaut health and performance during exploration missions to the moon and beyond.
IFNγ binding to extracellular matrix prevents fatal systemic toxicity
Authors: Kemna Josephine , Gout Evelyne , Daniau Leon , Lao Jessica , Weißert Kristoffer , Ammann Sandra , Kühn Ralf , Richter Matthias , Molenda Christine , Sporbert Anje , Zocholl Dario , Klopfleisch Robert , Schütz Anja , Lortat-Jacob Hugues , Aichele Peter , Kammertoens Thomas , Blankenstein Thomas 
Published: February 2023

AbstractInterferon-γ (IFNγ) is an important mediator of cellular immune responses, but high systemic levels of this cytokine are associated with immunopathology. IFNγ binds to its receptor (IFNγR) and to extracellular matrix (ECM) via four positively charged C-terminal amino acids (KRKR), the ECM-binding domain (EBD). Across evolution, IFNγ is not well conserved, but the EBD is highly conserved, suggesting a critical function. Here, we show that IFNγ lacking the EBD (IFNγΔKRKR) does not bind to ECM but still binds to the IFNγR and retains bioactivity. Overexpression of IFNγΔKRKR in tumors reduced local ECM binding, increased systemic levels and induced sickness behavior, weight loss and toxicity. To analyze the function of the EBD during infection, we generated IFNγΔKRKR mice lacking the EBD by using CRISPR–Cas9. Infection with lymphocytic choriomeningitis virus resulted in higher systemic IFNγΔKRKR levels, enhanced sickness behavior, weight loss and fatal toxicity. We conclude that local retention of IFNγ is a pivotal mechanism to protect the organism from systemic toxicity during prolonged immune stimulation.
Understanding the role of natural and anthropogenic forcings in structuring the periphytic algal assemblages in a regulated river ecosystem
Authors: Sofi Mohd Sharjeel , Hamid Aadil , Bhat Sami Ullah , Rashid Irfan , Kuniyal Jagdish Chandra 
Published: February 2023

AbstractPeriphytic algal assemblages in the River Sindh of Kashmir Himalaya were studied in relation to environmental factors and anthropogenic alterations like flow regulation for Run-of-River hydropower plants to understand their ecology in a regulated river ecosystem. Sites were sampled from unregulated, regulated, and downstream reaches along the river on a seasonal basis from the year 2017 to 2019. A total of 48 species were identified, spread over 31 genera. Non-metric multidimensional analysis showed clear distinction in periphytic algal assemblage samples based on sites and potentially some more minor distinction based on seasons rendering the sites into two distinct groups (G1 and G2). The ADONIS test showed that the groups (G1 and G2 sites) do not significantly differ in terms of how communities differ from one another, but there is a difference in species compositions based on seasons. However, the betadisper test indicated that groups (G1 and G2 sites) and seasons present homogeneity among group dispersions (compositions vary similarly) while having significantly different compositions. Geo-physical factors (discharge and altitude) accounted for most variations, while the scraper community played a minor role. This study provides scientific insights related to the ecology of a regulated Himalayan river and may provide information relevant to managing the River Sindh sustainably.
Combining accelerometers and direct visual observations to detect sickness and pain in cows of different ages submitted to systemic inflammation
Authors: Ledoux Dorothée , Veissier Isabelle , Meunier Bruno , Gelin Valérie , Richard Christophe , Kiefer Hélène , Jammes Hélène , Foucras Gilles , de Boyer des Roches Alice 
Published: February 2023

AbstractCattle suffering from inflammatory infection display sickness and pain-related behaviours. As these behaviours may be transient and last only a few hours, one may miss them. The aim of this study was to assess the benefit of combining continuous monitoring of cow behaviour via collar-attached accelerometers with direct visual observations to detect sickness and pain-related behavioural responses after a systemic inflammatory challenge (intravenous lipopolysaccharide injection) in cows of two different ages, proven by clinical, physiological and blood parameters. Twelve cloned Holstein cows (six ‘old’ cows aged 10–15 years old and six ‘young’ cows aged 6 years old) were challenged and either directly observed at five time-points from just before the lipopolysaccharide injection up to 24 h post-injection (hpi) or continuously monitored using collar-attached accelerometers in either control or challenge situations. Direct observations identified specific sickness and pain behaviours (apathy, changes in facial expression and body posture, reduced motivation to feed) expressed partially at 3 hpi and fully at 6 hpi. These signs of sickness and pain behaviours then faded, and quicker for the young cows. Accelerometers detected changes in basic activities (low ingesting, low ruminating, high inactivity) and position (high time standing up) earlier and over a longer period of time than direct observations. The combination of sensors and direct observations improved the detection of behavioural signs of sickness and pain earlier on and over the whole study period, even when direct signs were weak especially in young cows. This system could provide great benefit for better earlier animal care.