bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing Ice Nucleating Particles Over the Southern Ocean Using Simultaneous Aircraft and Ship Observations
Authors: Moore Kathryn A. , Hill Thomas C. J. , McCluskey Christina S. , Twohy Cynthia H. , Rainwater Bryan , Toohey Darin W. , Sanchez Kevin J. , Kreidenweis Sonia M. , DeMott Paul J. 
Published: January 2024

AbstractSupercooled liquid clouds are ubiquitous over the Southern Ocean (SO), even to temperatures below −20°C, and comprise a large fraction of the marine boundary layer (MBL) clouds. Earth system models and reanalysis products have struggled to reproduce the observed cloud phase distribution and occurrence of cloud ice in the region. Recent simulations found the microphysical representation of ice nucleation and growth has a large impact on these properties, however, measurements of SO ice nucleating particles (INPs) to validate simulations are sparse. This study presents measurements of INPs from simultaneous aircraft and ship campaigns conducted over the SO in austral summer 2018, which include the first in situ observations in and above cloud in the region. Our results confirm recent observations that INP concentrations are uniformly lower than measurements made in the late 1960s. While INP concentrations below and above cloud are similar, higher ice nucleation efficiency above cloud supports model simulations that the dominant INP composition varies with height. Model parameterizations based solely on aerosol properties capture the mean relationship between INP concentration and temperature but not the observed variability, which is likely related to the only modest correlations observed between INPs and environmental or aerosol metrics. Including wind speed in addition to activation temperature in a marine INP parameterization reduces bias but does not explain the large range of observed INP concentrations. Direct and indirect inference of marine INP size suggests MBL INPs, at least during Austral summer, are dominated by particles with diameters smaller than 500 nm.
Prognostic utility of rhythmic components in 24-h ambulatory blood pressure monitoring for the risk stratification of chronic kidney disease patients with cardiovascular co-morbidity
Authors: El Jamal Nadim , Brooks Thomas G. , Cohen Jordana , Townsend Raymond R. , Sosa Giselle Rodriguez de , Shah Vallabh ,   Chronic Renal Insufficiency Cohort Study (CRIC) Consortium, Nelson Robert G. , Drawz Paul E. , Rao Panduranga , Bhat Zeenat , Chang Alexander , Yang Wei , FitzGerald Garret A. , Skarke Carsten 
Published: January 2024

AbstractChronic kidney disease (CKD) represents a significant global burden. Hypertension is a modifiable risk factor for rapid progression of CKD. We extend the risk stratification by introducing the non-parametric determination of rhythmic components in 24-h profiles of ambulatory blood pressure monitoring (ABPM) in the Chronic Renal Insufficiency Cohort (CRIC) and the African American Study for Kidney Disease and Hypertension (AASK) cohort using Cox proportional hazards models. We find that rhythmic profiling of BP through JTK_CYCLE analysis identifies subgroups of CRIC participants that were more likely to die due to cardiovascular causes. While our fully adjusted model shows a trend towards a significant association between absent cyclic components and cardiovascular death in the full CRIC cohort (HR: 1.71,95% CI: 0.99–2.97, p = 0.056), CRIC participants with a history of cardiovascular disease (CVD) and absent cyclic components in their BP profile had at any time a 3.4-times higher risk of cardiovascular death than CVD patients with cyclic components present in their BP profile (HR: 3.37, 95% CI: 1.45–7.87, p = 0.005). This increased risk was not explained by the dipping or non-dipping pattern in ABPM. Due to the large differences in patient characteristics, the results do not replicate in the AASK cohort. This study suggests rhythmic blood pressure components as a potential novel biomarker to unmask excess risk among CKD patients with prior cardiovascular disease.
Efficacy and safety of mineralocorticoid receptor antagonists for the treatment of low-renin hypertension: a systematic review and meta-analysis
Authors: Shah Sonali S. , Zhang Jinghong , Gwini Stella May , Young Morag J. , Fuller Peter J. , Yang Jun 
Published: January 2024

AbstractHypertension is the leading risk factor for premature death. The optimal treatment of low-renin hypertension (LRH), present in 30% of hypertensive individuals, is not known. LRH likely reflects a state of excess salt, expanded volume and/or mineralocorticoid receptor (MR) activation. Therefore, targeted treatment with MR antagonists (MRA) may be beneficial. The objective of this systematic review was to assess the efficacy of MRA therapy in LRH. MEDLINE, Embase and Cochrane databases were searched for randomised controlled trials of adults with LRH that compared the efficacy of MRA to placebo or other antihypertensive treatments. Risk of bias was assessed using the Cochrane risk of bias tool. A meta-analysis was performed using a random-effects model to estimate the difference in blood pressure and the certainty of evidence was assessed using the GRADE approach. The protocol is registered on PROSPERO (CRD42022318763). From the 1612 records identified, 17 studies met the inclusion criteria with a total sample size of 1043 participants. Seven studies (n = 345) were assessed as having a high risk of bias. Meta-analysis indicated that MRA reduced systolic blood pressure by −6.8 mmHg (95% confidence interval −9.6 to −4.1) and −4.8 mmHg (95% confidence interval −11.9 to 2.4) compared to angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) and diuretics. The certainty of the evidence was assessed as moderate and very low, respectively. The findings of this systematic review suggest that MRA is effective in lowering blood pressure in LRH and may be better than ACEi/ARB. Translation to clinical practice is limited by the uncertainty of evidence.
Amplitude-determined seizure-threshold, electric field modeling, and electroconvulsive therapy antidepressant and cognitive outcomes
Authors: Abbott Christopher C. , Miller Jeremy , Farrar Danielle , Argyelan Miklos , Lloyd Megan , Squillaci Taylor , Kimbrell Brian , Ryman Sephira , Jones Thomas R. , Upston Joel , Quinn Davin K. , Peterchev Angel V. , Erhardt Erik , Datta Abhishek , McClintock Shawn M. , Deng Zhi-De 
Published: January 2024

AbstractElectroconvulsive therapy (ECT) pulse amplitude, which dictates the induced electric field (E-field) magnitude in the brain, is presently fixed at 800 or 900 milliamperes (mA) without clinical or scientific rationale. We have previously demonstrated that increased E-field strength improves ECT’s antidepressant effect but worsens cognitive outcomes. Amplitude-determined seizure titration may reduce the E-field variability relative to fixed amplitude ECT. In this investigation, we assessed the relationships among amplitude-determined seizure-threshold (STa), E-field magnitude, and clinical outcomes in older adults (age range 50 to 80 years) with depression. Subjects received brain imaging, depression assessment, and neuropsychological assessment pre-, mid-, and post-ECT. STa was determined during the first treatment with a Soterix Medical 4×1 High Definition ECT Multi-channel Stimulation Interface (Investigation Device Exemption: G200123). Subsequent treatments were completed with right unilateral electrode placement (RUL) and 800 mA. We calculated Ebrain defined as the 90th percentile of E-field magnitude in the whole brain for RUL electrode placement. Twenty-nine subjects were included in the final analyses. Ebrain per unit electrode current, Ebrain/I, was associated with STa. STa was associated with antidepressant outcomes at the mid-ECT assessment and bitemporal electrode placement switch. Ebrain/I was associated with changes in category fluency with a large effect size. The relationship between STa and Ebrain/I extends work from preclinical models and provides a validation step for ECT E-field modeling. ECT with individualized amplitude based on E-field modeling or STa has the potential to enhance neuroscience-based ECT parameter selection and improve clinical outcomes.
Antidepressant-like effects of psychedelics in a chronic despair mouse model: is the 5-HT2A receptor the unique player?
Authors: Sekssaoui Mehdi , Bockaert Joël , Marin Philippe , Bécamel Carine 
Published: January 2024

AbstractMajor depressive disorder (MDD) is one of the most disabling psychiatric disorders in the world. First-line treatments such as selective serotonin reuptake inhibitors (SSRIs) still have many limitations, including a resistance to treatment in 30% of patients and a delayed clinical benefit that is observed only after several weeks of treatment. Increasing clinical evidence indicates that the acute administration of psychedelic agonists of the serotonin 5-HT2A receptor (5-HT2AR), such as psilocybin, to patients with MDD induce fast antidepressant effects, which persist up to five weeks after the treatment. However, the involvement of the 5-HT2AR in these antidepressant effects remains controversial. Furthermore, whether the hallucinogenic properties of 5-HT2AR agonists are mandatory to their antidepressant activity is still an open question. Here, we addressed these issues by investigating the effect of two psychedelics of different chemical families, DOI and psilocybin, and a non-hallucinogenic 5-HT2AR agonist, lisuride, in a chronic despair mouse model exhibiting a robust depressive-like phenotype. We show that a single injection of each drug to wild type mice induces anxiolytic- and antidepressant-like effects in the novelty-suppressed feeding, sucrose preference and forced swim tests, which last up to 15 days. DOI and lisuride administration did not produce antidepressant-like effects in 5-HT2A−/− mice, whereas psilocybin was still effective. Moreover, neither 5-HT1AR blockade nor dopamine D1 or D2 receptor blockade affected the antidepressant-like effects of psilocybin in 5-HT2A−/− mice. Collectively, these findings indicate that 5-HT2AR agonists can produce antidepressant-like effects independently of hallucinogenic properties through mechanisms involving or not involving the receptor.
Estradiol increases cortical and trabecular bone accrual and bone strength in an adolescent male-to-female mouse model of gender-affirming hormone therapy
Authors: Nie Tian , Venkatesh Varun S. , Golub Suzanne , Stok Kathryn S. , Hemmatian Haniyeh , Desai Reena , Handelsman David J. , Zajac Jeffrey D. , Grossmann Mathis , Davey Rachel A. 
Published: January 2024

AbstractThe effects of gender-affirming hormone therapy on the skeletal integrity and fracture risk in transitioning adolescent trans girls are unknown. To address this knowledge gap, we developed a mouse model to simulate male-to-female transition in human adolescents in whom puberty is first arrested by using gonadotrophin-releasing hormone analogs with subsequent estradiol treatment. Puberty was suppressed by orchidectomy in male mice at 5 weeks of age. At 3 weeks post-surgery, male-to-female mice were treated with a high dose of estradiol (~0.85 mg) by intraperitoneal silastic implantation for 12 weeks. Controls included intact and orchidectomized males at 3 weeks post-surgery, vehicle-treated intact males, intact females and orchidectomized males at 12 weeks post-treatment. Compared to male controls, orchidectomized males exhibited decreased peak bone mass accrual and a decreased maximal force the bone could withstand prior to fracture. Estradiol treatment in orchidectomized male-to-female mice compared to mice in all control groups was associated with an increased cortical thickness in the mid-diaphysis, while the periosteal circumference increased to a level that was intermediate between intact male and female controls, resulting in increased maximal force and stiffness. In trabecular bone, estradiol treatment increased newly formed trabeculae arising from the growth plate as well as mineralizing surface/bone surface and bone formation rate, consistent with the anabolic action of estradiol on osteoblast proliferation. These data support the concept that skeletal integrity can be preserved and that long-term fractures may be prevented in trans girls treated with GnRHa and a sufficiently high dose of GAHT. Further study is needed to identify an optimal dose of estradiol that protects the bone without adverse side effects.
The heterogeneity of signaling pathways and drug responses in intrahepatic cholangiocarcinoma with distinct genetic mutations
Authors: Feng Yangyang , Zhao Ming , Wang Lijian , Li Ling , Lei Josh Haipeng , Zhou Jingbo , Chen Jinghong , Wu Yumeng , Miao Kai , Deng Chu-Xia 
Published: January 2024

AbstractIntrahepatic cholangiocarcinoma (ICC) is the second most common malignancy among primary liver cancers, with an increasing overall incidence and poor prognosis. The intertumoral and intratumoral heterogeneity of ICC makes it difficult to find efficient drug therapies. Therefore, it is essential to identify tumor suppressor genes and oncogenes that induce ICC formation and progression. Here, we performed CRISPR/Cas9-mediated genome-wide screening in a liver-specific Smad4/Pten knockout mouse model (Smad4co/co;Ptenco/co;Alb-Cre, abbreviated as SPC), which normally generates ICC after 6 months, and detected that mutations in Trp53, Fbxw7, Inppl1, Tgfbr2, or Cul3 markedly accelerated ICC formation. To illustrate the potential mechanisms, we conducted transcriptome sequencing and found that multiple receptor tyrosine kinases were activated, which mainly upregulated the PI3K pathway to induce cell proliferation. Remarkably, the Cul3 mutation stimulated cancer progression mainly by altering the immune microenvironment, whereas other mutations promoted the cell cycle. Moreover, Fbxw7, Inppl1, Tgfbr2, and Trp53 also affect inflammatory responses, apelin signaling, mitotic spindles, ribosome biogenesis, and nucleocytoplasmic transport pathways, respectively. We further examined FDA-approved drugs for the treatment of liver cancer and performed high-throughput drug screening of the gene-mutant organoids. Different drug responses and promising drug therapies, including chemotherapy and targeted drugs, have been discovered for ICC.
FBXO5-mediated RNF183 degradation prevents endoplasmic reticulum stress-induced apoptosis and promotes colon cancer progression
Authors: Ji Jing , Jing Aixin , Ding Yuanyuan , Ma Xinhui , Qian Qilan , Geng Ting , Cheng Wenhao , Zhang Meiqi , Sun Qian , Ma Shaojie , Wang Xiujun , Yuan Qing , Xu Menghan , Qin Jingting , Ma Lin , Yang Jiayan , He Jingliang , Du Qianming , Xia Mengbei , Xu Yuting , Chen Ziyun , Zhu Lan , Liu Wei , Liu Shunfang , Liu Bin 
Published: January 2024

AbstractEndoplasmic reticulum (ER) stress induces the unfolded protein response (UPR), and prolonged ER stress leads to cell apoptosis. Despite increasing research in this area, the underlying molecular mechanisms remain unclear. Here, we discover that ER stress upregulates the UPR signaling pathway while downregulating E2F target gene expression and inhibiting the G2/M phase transition. Prolonged ER stress decreases the mRNA levels of E2F2, which specifically regulates the expression of F-Box Protein 5(FBXO5), an F-box protein that functions as an inhibitor of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase complex. Depletion of FBXO5 results in increased ER stress-induced apoptosis and decreased expression of proteins related to PERK/IRE1α/ATF6 signaling. Overexpression of FBXO5 wild-type (not its ΔF-box mutant) alleviates apoptosis and the expression of the C/EBP Homologous Protein (CHOP)/ATF. Mechanistically, we find that FBXO5 directly binds to and promotes the ubiquitin-dependent degradation of RNF183, which acts as a ubiquitin E3 ligase in regulating ER stress-induced apoptosis. Reversal of the apoptosis defects caused by FBXO5 deficiency in colorectal cancer cells can be achieved by knocking down RNF183 in FBXO5-deficient cells. Functionally, we observed significant upregulation of FBXO5 in colon cancer tissues, and its silencing suppresses tumor occurrence in vivo. Therefore, our study highlights the critical role of the FBXO5/RNF183 axis in ER stress regulation and identifies a potential therapeutic target for colon cancer treatment.
Field control of quasiparticle decay in a quantum antiferromagnet
Authors: Hasegawa Shunsuke , Kikuchi Hodaka , Asai Shinichiro , Wei Zijun , Winn Barry , Sala Gabriele , Itoh Shinichi , Masuda Takatsugu 
Published: January 2024

AbstractDynamics in a quantum material is described by quantized collective motion: a quasiparticle. The single-quasiparticle description is useful for a basic understanding of the system, whereas a phenomenon beyond the simple description such as quasiparticle decay which affects the current carried by the quasiparticle is an intriguing topic. The instability of the quasiparticle is phenomenologically determined by the magnitude of the repulsive interaction between a single quasiparticle and the two-quasiparticle continuum. Although the phenomenon has been studied in several materials, thermodynamic tuning of the quasiparticle decay in a single material has not yet been investigated. Here we show, by using neutron scattering, magnetic field control of the magnon decay in a quantum antiferromagnet RbFeCl3, where the interaction between the magnon and continuum is tuned by the field. At low fields where the interaction is small, the single magnon decay process is observed. In contrast, at high fields where the interaction exceeds a critical magnitude, the magnon is pushed downwards in energy and its lifetime increases. Our study demonstrates that field control of quasiparticle decay is possible in the system where the two-quasiparticle continuum covers wide momentum-energy space, and the phenomenon of the magnon avoiding decay is ubiquitous.
Structural basis of antiphage immunity generated by a prokaryotic Argonaute-associated SPARSA system
Authors: Zhen Xiangkai , Xu Xiaolong , Ye Le , Xie Song , Huang Zhijie , Yang Sheng , Wang Yanhui , Li Jinyu , Long Feng , Ouyang Songying 
Published: January 2024

AbstractArgonaute (Ago) proteins are ubiquitous across all kingdoms of life. Eukaryotic Agos (eAgos) use small RNAs to recognize transcripts for RNA silencing in eukaryotes. In contrast, the functions of prokaryotic counterparts (pAgo) are less well known. Recently, short pAgos in conjunction with the associated TIR or Sir2 (SPARTA or SPARSA) were found to serve as antiviral systems to combat phage infections. Herein, we present the cryo-EM structures of nicotinamide adenine dinucleotide (NAD+)-bound SPARSA with and without nucleic acids at resolutions of 3.1 Å and 3.6 Å, respectively. Our results reveal that the APAZ (Analogue of PAZ) domain and the short pAgo form a featured architecture similar to the long pAgo to accommodate nucleic acids. We further identified the key residues for NAD+ binding and elucidated the structural basis for guide RNA and target DNA recognition. Using structural comparisons, molecular dynamics simulations, and biochemical experiments, we proposed a putative mechanism for NAD+ hydrolysis in which an H186 loop mediates nucleophilic attack by catalytic water molecules. Overall, our study provides mechanistic insight into the antiphage role of the SPARSA system.
Diabetic sensory neuropathy and insulin resistance are induced by loss of UCHL1 in Drosophila
Authors: Lee Daewon , Yoon Eunju , Ham Su Jin , Lee Kunwoo , Jang Hansaem , Woo Daihn , Lee Da Hyun , Kim Sehyeon , Choi Sekyu , Chung Jongkyeong 
Published: January 2024

AbstractDiabetic sensory neuropathy (DSN) is one of the most common complications of type 2 diabetes (T2D), however the molecular mechanistic association between T2D and DSN remains elusive. Here we identify ubiquitin C-terminal hydrolase L1 (UCHL1), a deubiquitinase highly expressed in neurons, as a key molecule underlying T2D and DSN. Genetic ablation of UCHL1 leads to neuronal insulin resistance and T2D-related symptoms in Drosophila. Furthermore, loss of UCHL1 induces DSN-like phenotypes, including numbness to external noxious stimuli and axonal degeneration of sensory neurons in flies’ legs. Conversely, UCHL1 overexpression improves DSN-like defects of T2D model flies. UCHL1 governs insulin signaling by deubiquitinating insulin receptor substrate 1 (IRS1) and antagonizes an E3 ligase of IRS1, Cullin 1 (CUL1). Consistent with these results, genetic and pharmacological suppression of CUL1 activity rescues T2D- and DSN-associated phenotypes. Therefore, our findings suggest a complete set of genetic factors explaining T2D and DSN, together with potential remedies for the diseases.
Non-collinear magnetic atomic cluster expansion for iron
Authors: Rinaldi Matteo , Mrovec Matous , Bochkarev Anton , Lysogorskiy Yury , Drautz Ralf 
Published: January 2024

AbstractThe Atomic Cluster Expansion (ACE) provides a formally complete basis for the local atomic environment. ACE is not limited to representing energies as a function of atomic positions and chemical species, but can be generalized to vectorial or tensorial properties and to incorporate further degrees of freedom (DOF). This is crucial for magnetic materials with potential energy surfaces that depend on atomic positions and atomic magnetic moments simultaneously. In this work, we employ the ACE formalism to develop a non-collinear magnetic ACE parametrization for the prototypical magnetic element Fe. The model is trained on a broad range of collinear and non-collinear magnetic structures calculated using spin density functional theory. We demonstrate that the non-collinear magnetic ACE is able to reproduce not only ground state properties of various magnetic phases of Fe but also the magnetic and lattice excitations that are essential for a correct description of finite temperature behavior and properties of crystal defects.
Kagami Ogata syndrome: a small deletion refines critical region for imprinting
Authors: Kilich Gonench , Hassey Kelly , Behrens Edward M. , Falk Marni , Vanderver Adeline , Rader Daniel J. , Cahill Patrick J. , Raper Anna , Zhang Zhe , Westerfer Dawn , Jadhav Tanaya , Conlin Laura , Izumi Kosuke , Rajagopalan Ramakrishnan , Sullivan Kathleen E. ,   UDN Consortium
Published: January 2024

AbstractKagami–Ogata syndrome is a rare imprinting disorder and its phenotypic overlap with multiple different etiologies hampers diagnosis. Genetic etiologies include paternal uniparental isodisomy (upd(14)pat), maternal allele deletions of differentially methylated regions (DMR) in 14q32.2 or pure primary epimutations. We report a patient with Kagami–Ogata syndrome and an atypical diagnostic odyssey with several negative standard-of-care genetic tests followed by epigenetic testing using methylation microarray and a targeted analysis of whole-genome sequencing to reveal a 203 bp deletion involving theMEG3transcript andMEG3:TSS-DMR. Long-read sequencing enabled the simultaneous detection of the deletion, phasing, and biallelic hypermethylation of theMEG3:TSS-DMR region in a single assay. This case highlights the challenges in the sequential genetic testing paradigm, the utility of long-read sequencing as a single comprehensive diagnostic assay, and the smallest reported deletion causing Kagami–Ogata syndrome allowing important insights into the mechanism of imprinting effects at this locus.