bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Faroe‐Shetland Channel Jet: Structure, Variability, and Driving Mechanisms
Authors: Chafik L. , Nilsson J. , Rossby T. , Kondetharayil Soman A. 
Published: April 2023

AbstractThe Faroe‐Bank Channel (FBC) is a key gateway through which dense overflow water of the Nordic Seas supplies the lower limb of the Atlantic Meridional Overturning Circulation. Most recently, it was discovered that a deep jet through the Faroe‐Shetland Channel carries the bulk of this overflow water, but numerous questions regarding its structure, seasonality, and interannual variability as well as its linkage to atmospheric forcing remain poorly understood. A realistic high‐resolution ocean reanalysis (GLORYS12; 1993–2018) is, therefore, employed to address these questions. We first confirm that the Faroe‐Shetland Channel Jet is a permanent feature in GLORYS12 as well as in an ensemble of low‐resolution reanalyses. On seasonal time scales, we find a strong transport covariability between this deep jet and the observed FBC overflow. On interannual time scales, the strength of this deep jet is governed by the wind‐forced circulation in the Nordic Seas. Due to the largely barotropic structure of these flows, they have a signature detectable in satellite sea‐surface heights. Further, we suggest that the structure of the deep jet is qualitatively consistent with a geostrophic dynamical model that accounts for along‐isobath density variations. This study indicates that GLORYS12 is a promising product to study the dense water pathways and dynamics in the Nordic Seas.
Nitrous Oxide Fluxes in Permafrost Peatlands Remain Negligible After Wildfire and Thermokarst Disturbance
Authors: Schulze Christopher , Sonnentag Oliver , Voigt Carolina , Thompson Lauren , van Delden Lona , Heffernan Liam , Hernandez‐Ramirez Guillermo , Kuhn McKenzie , Lin Sisi , Olefeldt David 
Published: April 2023

AbstractThe greenhouse gas (GHG) balance of boreal peatlands in permafrost regions will be affected by climate change through disturbances such as permafrost thaw and wildfire. Although the future GHG balance of boreal peatlands including ponds is dominated by the exchange of both carbon dioxide (CO2) and methane (CH4), disturbance impacts on fluxes of the potent GHG nitrous oxide (N2O) could contribute to shifts in the net radiative balance. Here, we measured monthly (April to October) fluxes of N2O, CH4, and CO2 from three sites located across the sporadic and discontinuous permafrost zones of western Canada. Undisturbed permafrost peat plateaus acted as N2O sinks (−0.025 mg N2O m−2 d−1), but N2O uptake was lower from burned plateaus (−0.003 mg N2O m−2 d−1) and higher following permafrost thaw in the thermokarst bogs (−0.054 mg N2O m−2 d−1). The thermokarst bogs had below‐ambient N2O soil gas concentrations, suggesting that denitrification consumed atmospheric N2O during reduction to dinitrogen. Atmospheric uptake of N2O in peat plateaus and thermokarst bogs increased with soil temperature and soil moisture, suggesting sensitivity of N2O consumption to further climate change. Four of five peatland ponds acted as N2O sinks (−0.018 mg N2O m−2 d−1), with no influence of thermokarst expansion. One pond with high nitrate concentrations had high N2O emissions (0.30 mg N2O m−2 d−1). Overall, our study suggests that the future net radiative balance of boreal peatlands will be dominated by impacts of wildfire and permafrost thaw on CH4 and CO2 fluxes, while the influence from N2O is minor.
Critical transition and reversion of tumorigenesis
Authors: Shin Dongkwan , Cho Kwang-Hyun 
Published: April 2023

AbstractCancer is caused by the accumulation of genetic alterations and therefore has been historically considered to be irreversible. Intriguingly, several studies have reported that cancer cells can be reversed to be normal cells under certain circumstances. Despite these experimental observations, conceptual and theoretical frameworks that explain these phenomena and enable their exploration in a systematic way are lacking. In this review, we provide an overview of cancer reversion studies and describe recent advancements in systems biological approaches based on attractor landscape analysis. We suggest that the critical transition in tumorigenesis is an important clue for achieving cancer reversion. During tumorigenesis, a critical transition may occur at a tipping point, where cells undergo abrupt changes and reach a new equilibrium state that is determined by complex intracellular regulatory events. We introduce a conceptual framework based on attractor landscapes through which we can investigate the critical transition in tumorigenesis and induce its reversion by combining intracellular molecular perturbation and extracellular signaling controls. Finally, we present a cancer reversion therapy approach that may be a paradigm-changing alternative to current cancer cell-killing therapies.
CCL12 induces trabecular bone loss by stimulating RANKL production in BMSCs during acute lung injury
Authors: Ma Chao , Gao Juan , Liang Jun , Wang Feizhen , Xu Long , Bu Jinhui , He Bo , Liu Guangpu , Niu Ru , Liu Guangwang 
Published: April 2023

AbstractIn the last three years, the capacity of health care systems and the public health policies of governments worldwide were challenged by the spread of SARS-CoV-2. Mortality due to SARS-CoV-2 mainly resulted from the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Moreover, millions of people who survived ALI/ARDS in SARS-CoV-2 infection suffer from multiple lung inflammation-induced complications that lead to disability and even death. The lung-bone axis refers to the relationship between lung inflammatory diseases (COPD, asthma, and cystic fibrosis) and bone diseases, including osteopenia/osteoporosis. Compared to chronic lung diseases, the influence of ALI on the skeleton has not been investigated until now. Therefore, we investigated the effect of ALI on bone phenotypes in mice to elucidate the underlying mechanisms. In vivo bone resorption enhancement and trabecular bone loss were observed in LPS-induced ALI mice. Moreover, chemokine (C-C motif) ligand 12 (CCL12) accumulated in the serum and bone marrow. In vivo global ablation of CCL12 or conditional ablation of CCR2 in bone marrow stromal cells (BMSCs) inhibited bone resorption and abrogated trabecular bone loss in ALI mice. Furthermore, we provided evidence that CCL12 promoted bone resorption by stimulating RANKL production in BMSCs, and the CCR2/Jak2/STAT4 axis played an essential role in this process. Our study provides information regarding the pathogenesis of ALI and lays the groundwork for future research to identify new targets to treat lung inflammation-induced bone loss.
LncRNA KIAA0087 suppresses the progression of osteosarcoma by mediating the SOCS1/JAK2/STAT3 signaling pathway
Authors: Gong Haoli , Tao Ye , Xiao Sheng , Li Xin , Fang Ke , Wen Jie , He Pan , Zeng Ming 
Published: April 2023

AbstractLong noncoding RNAs (lncRNAs), widely expressed in mammalian cells, play pivotal roles in osteosarcoma (OS) progression. Nevertheless, the detailed molecular mechanisms of lncRNA KIAA0087 in OS remain obscure. Here, the roles of KIAA0087 in OS tumorigenesis were investigated. KIAA0087 and miR-411-3p levels were detected by RT-qPCR. Malignant properties were assessed by CCK-8, colony formation, flow cytometry, wound healing, and transwell assays. SOCS1, EMT, and JAK2/STAT3 pathway-related protein levels were measured by western blotting. Direct binding between miR-411-3p and KIAA0087/SOCS1 was validated by a dual-luciferase reporter, RIP, and FISH assays. In vivo growth and lung metastasis were evaluated in nude mice. The expression levels of SOCS1, Ki-67, E-cadherin, and N-cadherin in tumor tissues were measured by immunohistochemical staining. Downregulation of KIAA0087 and SOCS1 and upregulation of miR-411-3p were found in OS tissues and cells. Low expression of KIAA0087 was associated with a poor survival rate. Forced expression of KIAA0087 or miR-411-3p inhibition repressed the growth, migration, invasion, EMT, and activation of the JAK2/STAT3 pathway and triggered apoptosis of OS cells. However, the opposite results were found with KIAA0087 knockdown or miR-411-3p overexpression. Mechanistic experiments indicated that KIAA0087 enhanced SOCS1 expression to inactivate the JAK2/STAT3 pathway by sponging miR-411-3p. Rescue experiments revealed that the antitumor effects of KIAA0087 overexpression or miR-411-3p suppression were counteracted by miR-411-3p mimics or SOCS1 inhibition, respectively. Finally, in vivo tumor growth and lung metastasis were inhibited in KIAA0087-overexpressing or miR-411-3p-inhibited OS cells. In summary, the downregulation of KIAA0087 promotes the growth, metastasis, and EMT of OS by targeting the miR-411-3p-mediated SOCS1/JAK2/STAT3 pathway.
Overlooked KCNQ4 variants augment the risk of hearing loss
Authors: Oh Kyung Seok , Roh Jae Won , Joo Sun Young , Ryu Kunhi , Kim Jung Ah , Kim Se Jin , Jang Seung Hyun , Koh Young Ik , Kim Da Hye , Kim Hye-Youn , Choi Murim , Jung Jinsei , Namkung Wan , Nam Joo Hyun , Choi Jae Young , Gee Heon Yung 
Published: April 2023

AbstractPathogenic variants of KCNQ4 cause symmetrical, late-onset, progressive, high-frequency-affected hearing loss, which eventually involves all frequencies with age. To understand the contribution of KCNQ4 variants to hearing loss, we analyzed whole-exome and genome sequencing data from patients with hearing loss and individuals whose hearing phenotypes were unknown. In KCNQ4, we identified seven missense variants and one deletion variant in 9 hearing loss patients and 14 missense variants in the Korean population with an unknown hearing loss phenotype. The p.R420W and p.R447W variants were found in both cohorts. To investigate the effects of these variants on KCNQ4 function, we performed whole-cell patch clamping and examined their expression levels. Except for p.G435Afs*61, all KCNQ4 variants exhibited normal expression patterns similar to those of wild-type KCNQ4. The p.R331Q, p.R331W, p.G435Afs*61, and p.S691G variants, which were identified in patients with hearing loss, showed a potassium (K+) current density lower than or similar to that of p.L47P, a previously reported pathogenic variant. The p.S185W and p.R216H variants shifted the activation voltage to hyperpolarized voltages. The channel activity of the p.S185W, p.R216H, p.V672M, and p.S691G KCNQ4 proteins was rescued by the KCNQ activators retigabine or zinc pyrithione, whereas p.G435Afs*61 KCNQ4 proteins were partially rescued by sodium butyrate, a chemical chaperone. Additionally, the structure of the variants predicted using AlphaFold2 showed impaired pore configurations, as did the patch-clamp data. Our findings suggest that KCNQ4 variants may be overlooked in hearing loss that starts in adulthood. Some of these variants are medically treatable; hence, genetic screening for KCNQ4 is important.
Comparative oncology: overcoming human cancer through companion animal studies
Authors: Oh Ji Hoon , Cho Je-Yoel 
Published: April 2023

AbstractComparative oncology is a field of study that has been recently adopted for studying cancer and developing cancer therapies. Companion animals such as dogs can be used to evaluate novel biomarkers or anticancer targets before clinical translation. Thus, the value of canine models is increasing, and numerous studies have been conducted to analyze similarities and differences between many types of spontaneously occurring cancers in canines and humans. A growing number of canine cancer models as well as research-grade reagents for these models are becoming available, leading to substantial growth in comparative oncology research spanning from basic science to clinical trials. In this review, we summarize comparative oncology studies that have been conducted on the molecular landscape of various canine cancers and highlight the importance of the integration of comparative biology into cancer research.
Glutathionylation on RNA-binding proteins: a regulator of liquid‒liquid phase separation in the pathogenesis of amyotrophic lateral sclerosis
Authors: Choi Hyun-Jun , Lee Ji Young , Kim Kiyoung 
Published: April 2023

AbstractRNA-binding proteins (RBPs) containing low-sequence complexity domains mediate the formation of cellular condensates and membrane-less organelles with biological functions via liquid‒liquid phase separation (LLPS). However, the abnormal phase transition of these proteins induces the formation of insoluble aggregates. Aggregates are pathological hallmarks of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). The molecular mechanisms underlying aggregate formation by ALS-associated RPBs remain largely unknown. This review highlights emerging studies on various posttranslational modifications (PTMs) related to protein aggregation. We begin with the introduction of several ALS-associated RBPs that form aggregates induced by phase separation. In addition, we highlight our recent discovery of a new PTM involved in the phase transition during the pathogenesis of fused-in-sarcoma (FUS)-associated ALS. We suggest a molecular mechanism through which LLPS mediates glutathionylation in FUS-linked ALS. This review aims to provide a detailed overview of the key molecular mechanisms of LLPS-mediated aggregate formation by PTMs, which will help further the understanding of the pathogenesis and development of ALS therapeutics.
Epicardioid single-cell genomics uncovers principles of human epicardium biology in heart development and disease
Authors: Meier Anna B. , Zawada Dorota , De Angelis Maria Teresa , Martens Laura D. , Santamaria Gianluca , Zengerle Sophie , Nowak-Imialek Monika , Kornherr Jessica , Zhang Fangfang , Tian Qinghai , Wolf Cordula M. , Kupatt Christian , Sahara Makoto , Lipp Peter , Theis Fabian J. , Gagneur Julien , Goedel Alexander , Laugwitz Karl-Ludwig , Dorn Tatjana , Moretti Alessandra 
Published: April 2023

AbstractThe epicardium, the mesothelial envelope of the vertebrate heart, is the source of multiple cardiac cell lineages during embryonic development and provides signals that are essential to myocardial growth and repair. Here we generate self-organizing human pluripotent stem cell-derived epicardioids that display retinoic acid-dependent morphological, molecular and functional patterning of the epicardium and myocardium typical of the left ventricular wall. By combining lineage tracing, single-cell transcriptomics and chromatin accessibility profiling, we describe the specification and differentiation process of different cell lineages in epicardioids and draw comparisons to human fetal development at the transcriptional and morphological levels. We then use epicardioids to investigate the functional cross-talk between cardiac cell types, gaining new insights into the role of IGF2/IGF1R and NRP2 signaling in human cardiogenesis. Finally, we show that epicardioids mimic the multicellular pathogenesis of congenital or stress-induced hypertrophy and fibrotic remodeling. As such, epicardioids offer a unique testing ground of epicardial activity in heart development, disease and regeneration.
Safety assessment of subchronic feeding of insect-resistant and herbicide-resistant transgenic soybeans to juvenile channel catfish (Ictalurus punctatus)
Authors: Xiang Dan , Luo Mingzhong , Jiang Fukun , Wen Zhengrong , Chen Xiaoyun , Wang Xiaofu , Xu Xiaoli , Wei Wei , Xu Junfeng 
Published: April 2023

AbstractTransgenic soybean is one of the most planted crops for human food and animal feed. The channel catfish (Ictalurus punctatus) is an important aquatic organism cultured worldwide. In this study, the effect of six different soybean diets containing: two transgenic soybeans expressing different types of cp4-epsps, Vip3Aa and pat genes (DBN9004 and DBN8002), their non-transgenic parent JACK, and three conventional soybean varieties (Dongsheng3, Dongsheng7, and Dongsheng9) was investigated in juvenile channel catfish for eight weeks, and a safety assessment was performed. During the experiment, no difference in survival rate was observed in six groups. The hepatosomatic index (HSI) and condition factor (CF) showed no significant difference. Moreover, comparable feed conversion (FC), feeding rate (FR), and feed conversion ratio (FCR) were found between transgenic soybean and JACK groups. Assessment of growth performance showed that the weight gain rate (WGR) and specific growth rate (SGR) of channel catfish were consistent. In addition, there were no changes in enzyme activity indexes (lactate dehydrogenase (LDH), total antioxidant capacity (T-AOC), aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) in channel catfish among treatments. The research provided an experimental basis for the aquaculture feed industry to employ transgenic soybean DBN9004 and DBN8002 for commercial purposes.
Comparative transcriptomics of aphid species that diverged > 22 MYA reveals genes that are important for the maintenance of their symbiosis
Authors: Argandona Jacob A. , Kim Dohyup , Hansen Allison K. 
Published: April 2023

AbstractMost plant-sap feeding insects have obligate relationships with maternally transmitted bacteria. Aphids require their nutritional endosymbiont, Buchnera aphidicola, for the production of essential amino acids. Such endosymbionts are harbored inside of specialized insect cells called bacteriocytes. Here, we use comparative transcriptomics of bacteriocytes between two recently diverged aphid species, Myzus persicae and Acyrthosiphon pisum, to identify key genes that are important for the maintenance of their nutritional mutualism. The majority of genes with conserved expression profiles in M. persicae and A. pisum are for orthologs previously identified in A. pisum to be important for the symbiosis. However, asparaginase which produces aspartate from asparagine was significantly up-regulated only in A. pisum bacteriocytes, potentially because Buchnera of M. persicae encodes its own asparaginase enzyme unlike Buchnera of A. pisum resulting in Buchnera of A. pisum to be dependent on its aphid host for aspartate. One-to-one orthologs that explained the most amount of variation for bacteriocyte specific mRNA expression for both species includes a collaborative gene for methionine biosynthesis, multiple transporters, a horizontally transmitted gene, and secreted proteins. Finally, we highlight species-specific gene clusters which may contribute to host adaptations and/or accommodations in gene regulation to changes in the symbiont or the symbiosis.
Longitudinal association of dietary habits and the risk of cardiovascular disease among Iranian population between 2001 and 2013: the Isfahan Cohort Study
Authors: Mohseni Maryam , Mohammadifard Noushin , Hassannejad Razieh , Aghabozorgi Mahnaz , Shirani Fatemeh , Sadeghi Masoumeh , Roohafza Hamidreza , Sarrafzadegan Nizal 
Published: April 2023

AbstractThere has been a steady rise in the incidence of cardiovascular disease (CVD) in the Iranian population. The aim of this study is to investigate the association between Global Dietary Index (GDI) and CVD risk among the Iranian adult population. This study was conducted based on Isfahan Cohort Study, a longitudinal study that collected data between 2001 and 2013 on 6405 adults. Dietary intakes were assessed by a validated food frequency questionnaire to calculate GDI. All participants were followed every two years by phone call to ask about death, any hospitalization, or cardiovascular events to examine CVD events. The Average age of participants was 50.70 ± 11.63 and the median of GDI score was 1 (IQR: 0.29). A total of 751 CVD events (1.4 incidence rate, per 100 person-year) occurred during 52,704 person-years of follow-up. One-unit GDI increase was associated with a higher risk of MI by 72% (HR: 1.72; 95% CI 1.04–2.84), stroke by 76% (HR: 1.76; 95% CI 1.09–2.85) and CVD by 30% (HR: 1.48; 95% CI 1.02–2.65). In addition, a one-unit GDI increase was associated with a higher risk of coronary heart disease more than 2 times (HR: 2.32; 95% CI 1.50–3.60) and CVD mortality and all-cause mortality over than 3 times [(HR: 3.65; 95% CI 1.90–7.01) and (HR: 3.10; 95% CI 1.90–5.06), respectively]. Higher GDI had a significant relationship with the increased risk of CVD events and all-cause mortality. Further epidemiological studies in other populations are suggested to confirm our findings.
The evaluation of tumorigenicity and characterization of colonies in a soft agar colony formation assay using polymerase chain reaction
Authors: Nakamura Daichi 
Published: April 2023

AbstractIn regenerative medicine, the tumorigenic potency of cells in cellular therapy products (CTPs) is a major concern for their application to patients. This study presents a method—the soft agar colony formation assay using polymerase chain reaction (PCR)—to evaluate tumorigenicity. MRC-5 cells, contaminated with HeLa cells, were cultured for up to 4 weeks in soft agar medium. Cell-proliferation-related mRNAs, Ki-67 and cyclin B, could be detected in 0.01% of HeLa cells after 5 days of culture, whereas cyclin-dependent kinase 1 (CDK1) could be detected after 2 weeks. On the other hand, CDK2, proliferating cell nuclear antigen (PCNA), and minichromosome maintenance protein 7 (MCM7) were not useful to detect HeLa cells even after 4 weeks of culture. The cancer stem cell (CSC) markers, aldehyde dehydrogenase 1 (ALDH1) and CD133 in 0.01% of HeLa cells, could be detected 2 and 4 weeks after culture, respectively. However, another CSC marker CD44 was not useful because its expression was also detected in MRC-5 cells alone. This study suggests that the application of the PCR method to the soft agar colony formation assay could evaluate not only the tumorigenic potency in the short-term but also characterize the colonies, eventually improving the safety of CTPs.
Studying pathogens degrades BLAST-based pathogen identification
Authors: Beal Jacob , Clore Adam , Manthey Jeff 
Published: April 2023

AbstractAs synthetic biology becomes increasingly capable and accessible, it is likewise increasingly critical to be able to make accurate biosecurity determinations regarding the pathogenicity or toxicity of particular nucleic acid or amino acid sequences. At present, this is typically done using the BLAST algorithm to determine the best match with sequences in the NCBI nucleic acid and protein databases. Neither BLAST nor any of the NCBI databases, however, are actually designed for biosafety determination. Critically, taxonomic errors or ambiguities in the NCBI nucleic acid and protein databases can also cause errors in BLAST-based taxonomic categorization. With heavily studied taxa and frequently used biotechnology tools, even low frequency taxonomic categorization issues can lead to high rates of errors in biosecurity decision-making. Here we focus on the implications for false positives, finding that BLAST against NCBI’s protein database will now incorrectly categorize a number of commonly used biotechnology tool sequences as the pathogens or toxins with which they have been used. Paradoxically, this implies that problems are expected to be most acute for the pathogens and toxins of highest interest and for the most widely used biotechnology tools. We thus conclude that biosecurity tools should shift away from BLAST against general purpose databases and towards new methods that are specifically tailored for biosafety purposes.