bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depression and cognition are associated with lipid dysregulation in both a multigenerational study of depression and the National Health and Nutrition Examination Survey
Authors: Mehdi S. M. A. , Costa A. P. , Svob C. , Pan L. , Dartora W. J. , Talati A. , Gameroff M. J. , Wickramaratne P. J. , Weissman M. M. , McIntire L. B. J. 
Published: March 2024

AbstractChronic dysregulation of peripheral lipids has been found to be associated with depression and cognition, but their interaction has not been investigated. Growing evidence has highlighted the association between peripheral lipoprotein levels with depression and cognition with inconsistent results. We assessed the association between peripheral lipids, depression, and cognition while evaluating their potential interactions using robust clinically relevant predictors such as lipoprotein levels and chronic medical disorders that dysregulate lipoproteins. We report an association between peripheral lipids, depression, and cognition, suggesting a common underlying biological mechanism driven by lipid dysregulation in two independent studies. Analysis of a longitudinal study of a cohort at high or low familial risk for major depressive disorder (MDD) (n = 526) found metabolic diseases, including diabetes, hypertension, and other cardiovascular diseases, were associated with MDD and cognitive outcomes. Investigating a cross-sectional population survey of adults in the National Health and Nutrition Examination Survey 2011–2014 (NHANES) (n = 2377), depression was found to be associated with high density lipoprotein (HDL) and cognitive assessments. In the familial risk study, medical conditions were found to be associated with chronic lipid dysregulation and were significantly associated with MDD using the structural equation model. A positive association between chronic lipid dysregulation and cognitive scores was found in an exploratory analysis of the familial risk study. In a complementary study, analysis of NHANES revealed a positive association of HDL levels with cognition. Further analysis of the NHANES cohort indicated that depression status mediated the interaction between HDL levels and cognitive tests. Importantly, the protective effect of HDL on cognition was absent in those with depressive symptoms, which may ultimately result in worse outcomes leading to cognitive decline. These findings highlight the potential for the early predictive value of medical conditions with chronic lipid dyshomeostasis for the risk of depression and cognitive decline.
Roflumilast inhibits tumor growth and migration in STK11/LKB1 deficient pancreatic cancer
Authors: Zhang Shuman , Yun Duo , Yang Hao , Eckstein Markus , Elbait Gihan Daw , Zhou Yaxing , Lu Yanxi , Yang Hai , Zhang Jinping , Dörflein Isabella , Britzen-Laurent Nathalie , Pfeffer Susanne , Stemmler Marc P. , Dahl Andreas , Mukhopadhyay Debabrata , Chang David , He Hang , Zeng Siyuan , Lan Bin , Frey Benjamin , Hampel Chuanpit , Lentsch Eva , Gollavilli Paradesi Naidu , Büttner Christian , Ekici Arif B. , Biankin Andrew , Schneider-Stock Regine , Ceppi Paolo , Grützmann Robert , Pilarsky Christian 
Published: March 2024

AbstractPancreatic cancer is a malignant tumor of the digestive system. It is highly aggressive, easily metastasizes, and extremely difficult to treat. This study aimed to analyze the genes that might regulate pancreatic cancer migration to provide an essential basis for the prognostic assessment of pancreatic cancer and individualized treatment. A CRISPR knockout library directed against 915 murine genes was transfected into TB 32047 cell line to screen which gene loss promoted cell migration. Next-generation sequencing and PinAPL.py- analysis was performed to identify candidate genes. We then assessed the effect of serine/threonine kinase 11 (STK11) knockout on pancreatic cancer by wound-healing assay, chick agnosia (CAM) assay, and orthotopic mouse pancreatic cancer model. We performed RNA sequence and Western blotting for mechanistic studies to identify and verify the pathways. After accelerated Transwell migration screening, STK11 was identified as one of the top candidate genes. Further experiments showed that targeted knockout of STK11 promoted the cell migration and increased liver metastasis in mice. Mechanistic analyses revealed that STK11 knockout influences blood vessel morphogenesis and is closely associated with the enhanced expression of phosphodiesterases (PDEs), especially PDE4D, PDE4B, and PDE10A. PDE4 inhibitor Roflumilast inhibited STK11-KO cell migration and tumor size, further demonstrating that PDEs are essential for STK11-deficient cell migration. Our findings support the adoption of therapeutic strategies, including Roflumilast, for patients with STK11-mutated pancreatic cancer in order to improve treatment efficacy and ultimately prolong survival.
Novel meriolin derivatives activate the mitochondrial apoptosis pathway in the presence of antiapoptotic Bcl-2
Authors: Schmitt Laura , Lechtenberg Ilka , Drießen Daniel , Flores-Romero Hector , Skowron Margaretha A. , Sekeres Marlena , Hoppe Julia , Krings Karina S. , Llewellyn Tanya R. , Peter Christoph , Stork Björn , Qin Nan , Bhatia Sanil , Nettersheim Daniel , Fritz Gerhard , García-Sáez Ana J. , Müller Thomas J. J. , Wesselborg Sebastian 
Published: March 2024

AbstractMeriolin derivatives represent a new class of kinase inhibitors with a pronounced cytotoxic potential. Here, we investigated a newly synthesized meriolin derivative (termed meriolin 16) that displayed a strong apoptotic potential in Jurkat leukemia and Ramos lymphoma cells. Meriolin 16 induced apoptosis in rapid kinetics (within 2–3 h) and more potently (IC50: 50 nM) than the previously described derivatives meriolin 31 and 36 [1]. Exposure of Ramos cells to meriolin 16, 31, or 36 for 5 min was sufficient to trigger severe and irreversible cytotoxicity. Apoptosis induction by all three meriolin derivatives was independent of death receptor signaling but required caspase-9 and Apaf-1 as central mediators of the mitochondrial death pathway. Meriolin-induced mitochondrial toxicity was demonstrated by disruption of the mitochondrial membrane potential (ΔΨm), mitochondrial release of proapoptotic Smac, processing of the dynamin-like GTPase OPA1, and subsequent fragmentation of mitochondria. Remarkably, all meriolin derivatives were able to activate the mitochondrial death pathway in Jurkat cells, even in the presence of the antiapoptotic Bcl-2 protein. In addition, meriolins were capable of inducing cell death in imatinib-resistant K562 and KCL22 chronic myeloid leukemia cells as well as in cisplatin-resistant J82 urothelial carcinoma and 2102EP germ cell tumor cells. Given the frequent inactivation of the mitochondrial apoptosis pathway by tumor cells, such as through overexpression of antiapoptotic Bcl-2, meriolin derivatives emerge as promising therapeutic agents for overcoming treatment resistance.
New estimates indicate that males are not larger than females in most mammal species
Authors: Tombak Kaia J. , Hex Severine B. S. W. , Rubenstein Daniel I. 
Published: March 2024

AbstractSexual size dimorphism has motivated a large body of research on mammalian mating strategies and sexual selection. Despite some contrary evidence, the narrative that larger males are the norm in mammals—upheld since Darwin’sDescent of Man—still dominates today, supported by meta-analyses that use coarse measures of dimorphism and taxonomically-biased sampling. With newly-available datasets and primary sources reporting sex-segregated means and variances in adult body mass, we estimate statistically-determined rates of sexual size dimorphism in mammals, sampling taxa by their species richness at the family level. Our analyses of wild, non-provisioned populations representing >400 species indicate that although males tend to be larger than females when dimorphism occurs, males are not larger in most mammal species, suggesting a need to revisit other assumptions in sexual selection research.
Deep-sea hiatus record reveals orbital pacing by 2.4 Myr eccentricity grand cycles
Authors: Dutkiewicz Adriana , Boulila Slah , Dietmar Müller R. 
Published: March 2024

AbstractAstronomical forcing of Earth’s climate is embedded in the rhythms of stratigraphic records, most famously as short-period (104–105 year) Milankovitch cycles. Astronomical grand cycles with periods of millions of years also modulate climate variability but have been detected in relatively few proxy records. Here, we apply spectral analysis to a dataset of Cenozoic deep-sea hiatuses to reveal a ~2.4 Myr eccentricity signal, disrupted by episodes of major tectonic forcing. We propose that maxima in the hiatus cycles correspond to orbitally-forced intensification of deep-water circulation and erosive bottom current activity, linked to eccentricity maxima and peaks in insolation and seasonality. A prominent episode of cyclicity disturbance coincides with the Paleocene-Eocene Thermal Maximum (PETM) at ~56 Myr ago, and correlates with a chaotic orbital transition in the Solar System evident in several astronomical solutions. This hints at a potential intriguing coupling between the PETM and Solar System chaos.
Liquid metals for boosting stability of zeolite catalysts in the conversion of methanol to hydrocarbons
Authors: Zhou Yong , Santos Sara , Shamzhy Mariya , Marinova Maya , Blanchenet Anne-Marie , Kolyagin Yury G. , Simon Pardis , Trentesaux Martine , Sharna Sharmin , Ersen Ovidiu , Zholobenko Vladimir L. , Saeys Mark , Khodakov Andrei Y. , Ordomsky Vitaly V. 
Published: March 2024

AbstractMethanol-to-hydrocarbons (MTH) process has been considered one of the most practical approaches for producing value-added products from methanol. However, the commonly used zeolite catalysts suffer from rapid deactivation due to coke deposition and require regular regeneration treatments. We demonstrate that low-melting-point metals, such as Ga, can effectively promote more stable methanol conversion in the MTH process by slowing coke deposition and facilitating the desorption of carbonaceous species from the zeolite. The ZSM-5 zeolite physically mixed with liquid gallium exhibited an enhanced lifetime in the MTH reaction, which increased by a factor of up to ~14 as compared to the parent ZSM-5. These results suggest an alternative route to the design and preparation of deactivation-resistant zeolite catalysts.
Strategies for robust renovation of residential buildings in Switzerland
Authors: Galimshina Alina , Moustapha Maliki , Hollberg Alexander , Lasvaux Sébastien , Sudret Bruno , Habert Guillaume 
Published: March 2024

AbstractBuilding renovation is urgently required to reduce the environmental impact associated with the building stock. Typically, building renovation is performed by envelope insulation and/or changing the fossil-based heating system. The goal of this paper is to provide strategies for robust renovation considering uncertainties on the future evolution of climate, energy grid, and user behaviors, amongst others by applying life cycle assessment and life cycle cost analysis. The study includes identifying optimal renovation options for the envelope and heating systems for building representatives from all construction periods that are currently in need of renovation in Switzerland. The findings emphasize the paramount importance of heating system replacements across all construction periods. Notably, when incorporating bio-based insulation materials, a balance emerges between environmental impact reduction and low energy operation costs. This facilitates robust, equitable, and low-carbon transformations in Switzerland and similar Northern European contexts while avoiding a carbon spike due to the embodied carbon of the renovation.
Cell type signatures in cell-free DNA fragmentation profiles reveal disease biology
Authors: Stanley Kate E. , Jatsenko Tatjana , Tuveri Stefania , Sudhakaran Dhanya , Lannoo Lore , Van Calsteren Kristel , de Borre Marie , Van Parijs Ilse , Van Coillie Leen , Van Den Bogaert Kris , De Almeida Toledo Rodrigo , Lenaerts Liesbeth , Tejpar Sabine , Punie Kevin , Rengifo Laura Y. , Vandenberghe Peter , Thienpont Bernard , Vermeesch Joris Robert 
Published: March 2024

AbstractCirculating cell-free DNA (cfDNA) fragments have characteristics that are specific to the cell types that release them. Current methods for cfDNA deconvolution typically use disease tailored marker selection in a limited number of bulk tissues or cell lines. Here, we utilize single cell transcriptome data as a comprehensive cellular reference set for disease-agnostic cfDNA cell-of-origin analysis. We correlate cfDNA-inferred nucleosome spacing with gene expression to rank the relative contribution of over 490 cell types to plasma cfDNA. In 744 healthy individuals and patients, we uncover cell type signatures in support of emerging disease paradigms in oncology and prenatal care. We train predictive models that can differentiate patients with colorectal cancer (84.7%), early-stage breast cancer (90.1%), multiple myeloma (AUC 95.0%), and preeclampsia (88.3%) from matched controls. Importantly, our approach performs well in ultra-low coverage cfDNA datasets and can be readily transferred to diverse clinical settings for the expansion of liquid biopsy.
Completing the loop of the Late Jurassic–Early Cretaceous true polar wander event
Authors: Hou Yifei , Zhao Pan , Qin Huafeng , Mitchell Ross N. , Li Qiuli , Hao Wenxing , Zhang Min , Ward Peter D. , Yuan Jie , Deng Chenglong , Zhu Rixiang 
Published: March 2024

AbstractThe reorientation of Earth through rotation of its solid shell relative to its spin axis is known as True polar wander (TPW). It is well-documented at present, but the occurrence of TPW in the geologic past remains controversial. This is especially so for Late Jurassic TPW, where the veracity and dynamics of a particularly large shift remain debated. Here, we report three palaeomagnetic poles at 153, 147, and 141 million years (Myr) ago from the North China craton that document an ~ 12° southward shift in palaeolatitude from 155–147 Myr ago (~1.5° Myr−1), immediately followed by an ~ 10° northward displacement between 147–141 Myr ago (~1.6° Myr−1). Our data support a large round-trip TPW oscillation in the past 200 Myr and we suggest that the shifting back-and-forth of the continents may contribute to the biota evolution in East Asia and the global Jurassic–Cretaceous extinction and endemism.
Inhibition of urease-mediated ammonia production by 2-octynohydroxamic acid in hepatic encephalopathy
Authors: Evstafeva Diana , Ilievski Filip , Bao Yinyin , Luo Zhi , Abramovic Boris , Kang Sunghyun , Steuer Christian , Montanari Elita , Casalini Tommaso , Simicic Dunja , Sessa Dario , Mitrea Stefanita-Octavian , Pierzchala Katarzyna , Cudalbu Cristina , Armbruster Chelsie E. , Leroux Jean-Christophe 
Published: March 2024

AbstractHepatic encephalopathy is a neuropsychiatric complication of liver disease which is partly associated with elevated ammonemia. Urea hydrolysis by urease-producing bacteria in the colon is often mentioned as one of the main routes of ammonia production in the body, yet research on treatments targeting bacterial ureases in hepatic encephalopathy is limited. Herein we report a hydroxamate-based urease inhibitor, 2-octynohydroxamic acid, exhibiting improved in vitro potency compared to hydroxamic acids that were previously investigated for hepatic encephalopathy. 2-octynohydroxamic acid shows low cytotoxic and mutagenic potential within a micromolar concentration range as well as reduces ammonemia in rodent models of liver disease. Furthermore, 2-octynohydroxamic acid treatment decreases cerebellar glutamine, a product of ammonia metabolism, in male bile duct ligated rats. A prototype colonic formulation enables reduced systemic exposure to 2-octynohydroxamic acid in male dogs. Overall, this work suggests that urease inhibitors delivered to the colon by means of colonic formulations represent a prospective approach for the treatment of hepatic encephalopathy.
Neuropathogenesis-on-chips for neurodegenerative diseases
Authors: Amartumur Sarnai , Nguyen Huong , Huynh Thuy , Kim Testaverde S. , Woo Ran-Sook , Oh Eungseok , Kim Kyeong Kyu , Lee Luke P. , Heo Chaejeong 
Published: March 2024

AbstractDeveloping diagnostics and treatments for neurodegenerative diseases (NDs) is challenging due to multifactorial pathogenesis that progresses gradually. Advanced in vitro systems that recapitulate patient-like pathophysiology are emerging as alternatives to conventional animal-based models. In this review, we explore the interconnected pathogenic features of different types of ND, discuss the general strategy to modelling NDs using a microfluidic chip, and introduce the organoid-on-a-chip as the next advanced relevant model. Lastly, we overview how these models are being applied in academic and industrial drug development. The integration of microfluidic chips, stem cells, and biotechnological devices promises to provide valuable insights for biomedical research and developing diagnostic and therapeutic solutions for NDs.
ZNF827 is a single-stranded DNA binding protein that regulates the ATR-CHK1 DNA damage response pathway
Authors: Yang Sile F. , Nelson Christopher B. , Wells Jadon K. , Fernando Madushan , Lu Robert , Allen Joshua A. M. , Malloy Lisa , Lamm Noa , Murphy Vincent J. , Mackay Joel P. , Deans Andrew J. , Cesare Anthony J. , Sobinoff Alexander P. , Pickett Hilda A. 
Published: March 2024

AbstractThe ATR-CHK1 DNA damage response pathway becomes activated by the exposure of RPA-coated single-stranded DNA (ssDNA) that forms as an intermediate during DNA damage and repair, and as a part of the replication stress response. Here, we identify ZNF827 as a component of the ATR-CHK1 kinase pathway. We demonstrate that ZNF827 is a ssDNA binding protein that associates with RPA through concurrent binding to ssDNA intermediates. These interactions are dependent on two clusters of C2H2 zinc finger motifs within ZNF827. We find that ZNF827 accumulates at stalled forks and DNA damage sites, where it activates ATR and promotes the engagement of homologous recombination-mediated DNA repair. Additionally, we demonstrate that ZNF827 depletion inhibits replication initiation and sensitizes cancer cells to the topoisomerase inhibitor topotecan, revealing ZNF827 as a therapeutic target within the DNA damage response pathway.
Molecular sieving of iso-butene from C4 olefins with simultaneous high 1,3-butadiene and n-butene uptakes
Authors: Liu Junhui , Xiong Hanting , Shuai Hua , Liu Xing , Peng Yong , Wang Lingmin , Wang Pengxiang , Zhao Zhiwei , Deng Zhenning , Zhou Zhenyu , Chen Jingwen , Chen Shixia , Zeng Zheling , Deng Shuguang , Wang Jun 
Published: March 2024

AbstractIso-butene (iso-C4H8) is an important raw material in chemical industry, whereas its efficient separation remains challenging due to similar molecular properties of C4 olefins. The ideal adsorbent should possess simultaneous high uptakes for 1,3-butadiene (C4H6) and n-butene (n-C4H8) counterparts, endowing high efficiency for iso-C4H8 separation in adsorption columns. Herein, a sulfate-pillared adsorbent, SOFOUR-DPDS-Ni (DPDS = 4,4′-dipyridyldisulfide), is reported for the efficient iso-C4H8 separation from binary and ternary C4 olefin mixtures. The rigidity in pore sizes and shapes of SOFOUR-DPDS-Ni exerts the molecular sieving of iso-C4H8, while exhibiting high C4H6 and n-C4H8 uptakes. The benchmark Henry’s selectivity for C4H6/iso-C4H8 (2321.8) and n-C4H8/iso-C4H8 (233.5) outperforms most reported adsorbents. Computational simulations reveal the strong interactions for C4H6 and n-C4H8. Furthermore, dynamic breakthrough experiments demonstrate the direct production of high-purity iso-C4H8 (>99.9%) from C4H6/iso-C4H8 (50/50, v/v), n-C4H8/iso-C4H8 (50/50, v/v), and C4H6/n-C4H8/iso-C4H8 (50/15/35, v/v/v) gas-mixtures.
Cortical white matter microstructural alterations underlying the impaired gamma-band auditory steady-state response in schizophrenia
Authors: Koshiyama Daisuke , Nishimura Ryoichi , Usui Kaori , Fujioka Mao , Tada Mariko , Kirihara Kenji , Araki Tsuyoshi , Kawakami Shintaro , Okada Naohiro , Koike Shinsuke , Yamasue Hidenori , Abe Osamu , Kasai Kiyoto 
Published: March 2024

AbstractThe gamma-band auditory steady-state response (ASSR), primarily generated from the auditory cortex, has received substantial attention as a potential brain marker indicating the pathophysiology of schizophrenia. Previous studies have shown reduced gamma-band ASSR in patients with schizophrenia and demonstrated correlations with impaired neurocognition and psychosocial functioning. Recent studies in clinical and healthy populations have suggested that the neural substrates of reduced gamma-band ASSR may be distributed throughout the cortices surrounding the auditory cortex, especially in the right hemisphere. This study aimed to investigate associations between the gamma-band ASSR and white matter alterations in the bundles broadly connecting the right frontal, parietal and occipital cortices to clarify the networks underlying reduced gamma-band ASSR in patients with schizophrenia. We measured the 40 Hz ASSR using electroencephalography and diffusion tensor imaging in 42 patients with schizophrenia and 22 healthy comparison subjects. The results showed that the gamma-band ASSR was positively correlated with fractional anisotropy (an index of white matter integrity) in the regions connecting the right frontal, parietal and occipital cortices in healthy subjects (β = 0.41, corrected p = 0.075, uncorrected p = 0.038) but not in patients with schizophrenia (β = 0.17, corrected p = 0.46, uncorrected p = 0.23). These findings support our hypothesis that the generation of gamma-band ASSR is supported by white matter bundles that broadly connect the cortices and that these relationships may be disrupted in schizophrenia. Our study may help characterize and interpret reduced gamma-band ASSR as a useful brain marker of schizophrenia.
A biogeographical appraisal of the threatened South East Africa Montane Archipelago ecoregion
Authors: Bayliss Julian , Bittencourt-Silva Gabriela B. , Branch William R. , Bruessow Carl , Collins Steve , Congdon T. Colin E. , Conradie Werner , Curran Michael , Daniels Savel R. , Darbyshire Iain , Farooq Harith , Fishpool Lincoln , Grantham Geoffrey , Magombo Zacharia , Matimele Hermenegildo , Monadjem Ara , Monteiro Jose , Osborne Jo , Saunders Justin , Smith Paul , Spottiswoode Claire N. , Taylor Peter J. , Timberlake Jonathan , Tolley Krystal A. , Tovela Érica , Platts Philip J. 
Published: March 2024

AbstractRecent biological surveys of ancient inselbergs in southern Malawi and northern Mozambique have led to the discovery and description of many species new to science, and overlapping centres of endemism across multiple taxa. Combining these endemic taxa with data on geology and climate, we propose the ‘South East Africa Montane Archipelago’ (SEAMA) as a distinct ecoregion of global biological importance. The ecoregion encompasses 30 granitic inselbergs reaching > 1000 m above sea level, hosting the largest (Mt Mabu) and smallest (Mt Lico) mid-elevation rainforests in southern Africa, as well as biologically unique montane grasslands. Endemic taxa include 127 plants, 45 vertebrates (amphibians, reptiles, birds, mammals) and 45 invertebrate species (butterflies, freshwater crabs), and two endemic genera of plants and reptiles. Existing dated phylogenies of endemic animal lineages suggests this endemism arose from divergence events coinciding with repeated isolation of these mountains from the pan-African forests, together with the mountains’ great age and relative climatic stability. Since 2000, the SEAMA has lost 18% of its primary humid forest cover (up to 43% in some sites)—one of the highest deforestation rates in Africa. Urgently rectifying this situation, while addressing the resource needs of local communities, is a global priority for biodiversity conservation.