bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ocean Dynamics Causes the Equatorial Pacific SST Bias in CAS‐ESM2‐0
Authors: Si Wei , Liu Hailong , Zhang Minghua 
Published: November 2023

AbstractCoupled ocean‐atmosphere models still suffer from systematic biases in simulating the sea‐surface temperature (SST) in the equatorial Pacific. Like in many current generations of climate models, the Chinese Academy of Sciences (CAS) Earth System Model (CAS‐ESM2‐0) simulated warmer SST in the eastern Pacific and colder SST in the central to western Pacific at the equator. We analyzed the physical processes causing these biases. We find that model biases in surface heat flux are a consequence, not the cause, of the SST bias. Ocean currents are implicated as the cause. The biases in ocean currents come from both the ocean model itself and the bias in surface winds in the atmospheric model. We show that the bias of ocean currents in the standalone ocean model causes warming in the region of positive precipitation bias in the standalone atmospheric model. When the two models are coupled, the precipitation bias is greatly amplified. Anomalous equatorial winds as atmospheric Rossby‐gravity wave response to precipitation induce additional bias in ocean currents that transport heat in the upper ocean. The cold equatorial SST bias in the central and western Pacific is found to be due to temperature advection by the anomalous zonal currents, while the warm bias in the eastern Pacific is due to advection by the anomalous zonal and meridional currents as well as downwelling. Results from the analysis offer insights into the causes of the SST biases in coupled models in the equatorial Pacific.
Variable Salinity and Hydrogen Production in Europa's Ocean
Authors: Spiers E. M. , Schmidt B. E. 
Published: November 2023

AbstractEuropa's long‐term habitability depends on thermodynamics—modulated by tidal evolution—and geochemical pathways that define chemical and energy inventories for use by putative biology. Hydrogen produced from the reaction of water and rock during serpentinization is one potential source of metabolic energy. Here, we demonstrate how thermally modulated volumetric changes to Europa's ice shell, ocean, and fluid‐accessible rocky mantle influence oceanic salinity and serpentinization rates in Europa's interior. During periods of steady cooling, hydrogen flux into the ocean remains relatively constant because of the continuous propagation of thermal cracking into the rocky mantle regardless of ocean composition. However, during periods of fluctuating heat production driven by changes in orbital eccentricity, modulation of the ice shell volume, and consequently the salinity and water activity of the ocean, alters the serpentinization rate. In parallel, the extent of fracturing within the seafloor varies, changing the volume of reactable rock available. Our results show that the stability of serpentinization reactions on Europa over time highly depends on the thermal‐orbital evolution and oceanic salt content. The variability in the hydrogen production rate is significant across potential orbital histories, varying by up to 15 orders of magnitude for the lowest salinity and most kosmotropic ocean conditions, such as dilute MgSO4 compositions. We also show that this variability decreases with increasing ocean salinity and more chaotropic compositions, such as a concentrated NaCl ocean. These results suggest new ways that ocean composition and water activity are essential to stable habitable conditions in ocean worlds.
Signaling pathways and targeted therapies for psoriasis
Authors: Guo Jia , Zhang Hanyi , Lin Wenrui , Lu Lixia , Su Juan , Chen Xiang 
Published: November 2023

AbstractPsoriasis is a common, chronic, and inflammatory skin disease with a high burden on individuals, health systems, and society worldwide. With the immunological pathologies and pathogenesis of psoriasis becoming gradually revealed, the therapeutic approaches for this disease have gained revolutionary progress. Nevertheless, the mechanisms of less common forms of psoriasis remain elusive. Furthermore, severe adverse effects and the recurrence of disease upon treatment cessation should be noted and addressed during the treatment, which, however, has been rarely explored with the integration of preliminary findings. Therefore, it is crucial to have a comprehensive understanding of the mechanisms behind psoriasis pathogenesis, which might offer new insights for research and lead to more substantive progress in therapeutic approaches and expand clinical options for psoriasis treatment. In this review, we looked to briefly introduce the epidemiology, clinical subtypes, pathophysiology, and comorbidities of psoriasis and systematically discuss the signaling pathways involving extracellular cytokines and intracellular transmission, as well as the cross-talk between them. In the discussion, we also paid more attention to the potential metabolic and epigenetic mechanisms of psoriasis and the molecular mechanistic cascades related to its comorbidities. This review also outlined current treatment for psoriasis, especially targeted therapies and novel therapeutic strategies, as well as the potential mechanism of disease recurrence.
SRSF2 mutation reduces polycythemia and impairs hematopoietic progenitor functions in JAK2V617F-driven myeloproliferative neoplasm
Authors: Yang Yue , Abbas Salar , Sayem Mohammad A. , Dutta Avik , Mohi Golam 
Published: November 2023

AbstractSRSF2 mutations are found in association with JAK2V617F in myeloproliferative neoplasms (MPN), most frequently in myelofibrosis (MF). However, the contribution of SRSF2 mutation in JAK2V617F-driven MPN remains elusive. To investigate the consequences of SRSF2P95H and JAK2V617F mutations in MPN, we generated Cre-inducible Srsf2P95H/+Jak2V617F/+ knock-in mice. We show that co-expression of Srsf2P95H mutant reduced red blood cell, neutrophil, and platelet counts, attenuated splenomegaly but did not induce bone marrow fibrosis in Jak2V617F/+ mice. Furthermore, co-expression of Srsf2P95H diminished the competitiveness of Jak2V617F mutant hematopoietic stem/progenitor cells. We found that Srsf2P95H mutant reduced the TGF-β levels but increased the expression of S100A8 and S100A9 in Jak2V617F/+ mice. Furthermore, enforced expression of S100A9 in Jak2V617F/+ mice bone marrow significantly reduced the red blood cell, hemoglobin, and hematocrit levels. Overall, these data suggest that concurrent expression of Srsf2P95H and Jak2V617F mutants reduces erythropoiesis but does not promote the development of bone marrow fibrosis in mice.
Hypoxia-induced PLOD2 promotes clear cell renal cell carcinoma progression via modulating EGFR-dependent AKT pathway activation
Authors: Liu Tao , Xiang Wan , Chen Zhizhuang , Wang Gang , Cao Rui , Zhou Fenfang , Meng Zhe , Luo Yongwen , Chen Liang 
Published: November 2023

AbstractClear cell renal cell carcinoma (ccRCC) is a type of kidney cancer that is both common and aggressive, with a rising incidence in recent decades. Hypoxia is a key factor that plays a vital role in the tumorigenesis and metastasis of malignancy. However, the precise mechanisms of hypoxia driving ccRCC progression were not totally uncovered. Our study found that hypoxia level was elevated in ccRCC and might be an independent risk factor of prognosis in ccRCC patients. We identified a key protein PLOD2 was induced under hypoxic conditions and strongly associated with poor prognosis in ccRCC patients. When PLOD2 was depleted, the proliferation and migration of ccRCC cells were reduced in vitro and in vivo, while overexpression of PLOD2 had the opposite effect. Mechanically, the study further revealed that PLOD2 was transcriptionally activated by HIF1A, which binds to a specific promoter region of the PLOD2 gene. PLOD2 was also shown to interact with EGFR, leading to the phosphorylation of the receptor. Furthermore, PLOD2 was responsible for binding to the extracellular domain of EGFR, which ultimately activated the AKT signaling pathway, thus promoting the malignant progression of ccRCC. Treatment with the PLOD2 inhibitor Minoxidil significantly suppressed ccRCC progression by inactivating the EGFR/AKT signaling axis. In summary, the findings of this study shed light on the molecular mechanisms behind PLOD2 expression in ccRCC and suggest that it may serve as a potential predictor and therapeutic target for the clinical prognosis and treatment of ccRCC.
ΔNp63α facilitates proliferation and migration, and modulates the chromatin landscape in intrahepatic cholangiocarcinoma cells
Authors: Peng Anghui , Lin Xiaowen , Yang Quanli , Sun Yihao , Chen Ruiyan , Liu Bing , Yu Xinyang 
Published: November 2023

Abstractp63 plays a crucial role in epithelia-originating tumours; however, its role in intrahepatic cholangiocarcinoma (iCCA) has not been completely explored. Our study revealed the oncogenic properties of p63 in iCCA and identified the major expressed isoform as ΔNp63α. We collected iCCA clinical data from The Cancer Genome Atlas database and analyzed p63 expression in iCCA tissue samples. We further established genetically modified iCCA cell lines in which p63 was overexpressed or knocked down to study the protein function/function of p63 in iCCA. We found that cells overexpressing p63, but not p63 knockdown counterparts, displayed increased proliferation, migration, and invasion. Transcriptome analysis showed that p63 altered the iCCA transcriptome, particularly by affecting cell adhesion-related genes. Moreover, chromatin accessibility decreased at p63 target sites when p63 binding was lost and increased when p63 binding was gained. The majority of the p63 bound sites were located in the distal intergenic regions and showed strong enhancer marks; however, active histone modifications around the Transcription Start Site changed as p63 expression changed. We also detected an interaction between p63 and the chromatin structural protein YY1. Taken together, our results suggest an oncogenic role for p63 in iCCA.
Thermal sensitivity of field metabolic rate predicts differential futures for bluefin tuna juveniles across the Atlantic Ocean
Authors: Trueman Clive N. , Artetxe-Arrate Iraide , Kerr Lisa A. , Meijers Andrew J. S. , Rooker Jay R. , Sivankutty Rahul , Arrizabalaga Haritz , Belmonte Antonio , Deguara Simeon , Goñi Nicolas , Rodriguez-Marin Enrique , Dettman David L. , Santos Miguel Neves , Karakulak F. Saadet , Tinti Fausto , Tsukahara Yohei , Fraile Igaratza 
Published: November 2023

AbstractChanging environmental temperatures impact the physiological performance of fishes, and consequently their distributions. A mechanistic understanding of the linkages between experienced temperature and the physiological response expressed within complex natural environments is often lacking, hampering efforts to project impacts especially when future conditions exceed previous experience. In this study, we use natural chemical tracers to determine the individual experienced temperatures and expressed field metabolic rates of Atlantic bluefin tuna (Thunnus thynnus) during their first year of life. Our findings reveal that the tuna exhibit a preference for temperatures 2–4 °C lower than those that maximise field metabolic rates, thereby avoiding temperatures warm enough to limit metabolic performance. Based on current IPCC projections, our results indicate that historically-important spawning and nursery grounds for bluefin tuna will become thermally limiting due to warming within the next 50 years. However, limiting global warming to below 2 °C would preserve habitat conditions in the Mediterranean Sea for this species. Our approach, which is based on field observations, provides predictions of animal performance and behaviour that are not constrained by laboratory conditions, and can be extended to any marine teleost species for which otoliths are available.
Sis2 regulates yeast replicative lifespan in a dose-dependent manner
Authors: Ölmez Tolga T. , Moreno David F. , Liu Ping , Johnson Zane M. , McGinnis Madeline M. , Tu Benjamin P. , Hochstrasser Mark , Acar Murat 
Published: November 2023

AbstractApplication of microfluidic platforms facilitated high-precision measurements of yeast replicative lifespan (RLS); however, comparative quantification of lifespan across strain libraries has been missing. Here we microfluidically measure the RLS of 307 yeast strains, each deleted for a single gene. Despite previous reports of extended lifespan in these strains, we found that 56% of them did not actually live longer than the wild-type; while the remaining 44% showed extended lifespans, the degree of extension was often different from what was previously reported. Deletion ofSIS2gene led to the largest RLS increase observed. Sis2 regulated yeast lifespan in a dose-dependent manner, implying a role for the coenzyme A biosynthesis pathway in lifespan regulation. Introduction of the human PPCDC gene in thesis2Δbackground neutralized the lifespan extension. RNA-seq experiments revealed transcriptional increases in cell-cycle machinery components insis2Δbackground. High-precision lifespan measurement will be essential to elucidate the gene network governing lifespan.
Cortical reactivation of spatial and non-spatial features coordinates with hippocampus to form a memory dialogue
Authors: Chang HaoRan , Esteves Ingrid M. , Neumann Adam R. , Mohajerani Majid H. , McNaughton Bruce L. 
Published: November 2023

AbstractEpisodic memories comprise diverse attributes of experience distributed across neocortical areas. The hippocampus is integral to rapidly binding these diffuse representations, as they occur, to be later reinstated. However, the nature of the information exchanged during this hippocampal-cortical dialogue remains poorly understood. A recent study has shown that the secondary motor cortex carries two types of representations: place cell-like activity, which were impaired by hippocampal lesions, and responses tied to visuo-tactile cues, which became more pronounced following hippocampal lesions. Using two-photon Ca2+ imaging to record neuronal activities in the secondary motor cortex of male Thy1-GCaMP6s mice, we assessed the cortical retrieval of spatial and non-spatial attributes from previous explorations in a virtual environment. We show that, following navigation, spontaneous resting state reactivations convey varying degrees of spatial (trajectory sequences) and non-spatial (visuo-tactile attributes) information, while reactivations of non-spatial attributes tend to precede reactivations of spatial representations surrounding hippocampal sharp-wave ripples.
Persistent humoral immune response in youth throughout the COVID-19 pandemic: prospective school-based cohort study
Authors: Raineri Alessia , Radtke Thomas , Rueegg Sonja , Haile Sarah R. , Menges Dominik , Ballouz Tala , Ulyte Agne , Fehr Jan , Cornejo Daniel L. , Pantaleo Giuseppe , Pellaton Céline , Fenwick Craig , Puhan Milo A. , Kriemler Susi 
Published: November 2023

AbstractUnderstanding the development of humoral immune responses of children and adolescents to SARS-CoV-2 is essential for designing effective public health measures. Here we examine the changes of humoral immune response in school-aged children and adolescents during the COVID-19 pandemic (June 2020 to July 2022), with a specific interest in the Omicron variant (beginning of 2022). In our study “Ciao Corona”, we assess in each of the five testing rounds between 1874 and 2500 children and adolescents from 55 schools in the canton of Zurich with a particular focus on a longitudinal cohort (n=751). By July 2022, 96.9% (95% credible interval 95.3–98.1%) of children and adolescents have SARS-CoV-2 anti-spike IgG (S-IgG) antibodies. Those with hybrid immunity or vaccination have higher S-IgG titres and stronger neutralising responses against Wildtype, Delta and Omicron BA.1 variants compared to those infected but unvaccinated. S-IgG persist over 18 months in 93% of children and adolescents. During the study period one adolescent was hospitalised for less than 24 hours possibly related to an acute SARS-CoV-2 infection. These findings show that the Omicron wave and the rollout of vaccines boosted S-IgG titres and neutralising capacity. Trial registration number: NCT04448717. https://clinicaltrials.gov/ct2/show/NCT04448717.
Sequential vaccinations with divergent H1N1 influenza virus strains induce multi-H1 clade neutralizing antibodies in swine
Authors: Van Reeth Kristien , Parys Anna , Gracia José Carlos Mancera , Trus Ivan , Chiers Koen , Meade Philip , Liu Sean , Palese Peter , Krammer Florian , Vandoorn Elien 
Published: November 2023

AbstractVaccines that protect against any H1N1 influenza A virus strain would be advantageous for use in pigs and humans. Here, we try to induce a pan-H1N1 antibody response in pigs by sequential vaccination with antigenically divergent H1N1 strains. Adjuvanted whole inactivated vaccines are given intramuscularly in various two- and three-dose regimens. Three doses of heterologous monovalent H1N1 vaccine result in seroprotective neutralizing antibodies against 71% of a diverse panel of human and swine H1 strains, detectable antibodies against 88% of strains, and sterile cross-clade immunity against two heterologous challenge strains. This strategy outperforms any two-dose regimen and is as good or better than giving three doses of matched trivalent vaccine. Neutralizing antibodies are H1-specific, and the second heterologous booster enhances reactivity with conserved epitopes in the HA head. We show that even the most traditional influenza vaccines can offer surprisingly broad protection if they are administered in an alternative way.
Modular interneuron circuits control motion sensitivity in the mouse retina
Authors: Jo Andrew , Deniz Sercan , Cherian Suraj , Xu Jian , Futagi Daiki , DeVries Steven H. , Zhu Yongling 
Published: November 2023

AbstractNeural computations arise from highly precise connections between specific types of neurons. Retinal ganglion cells (RGCs) with similar stratification patterns are positioned to receive similar inputs but often display different response properties. In this study, we used intersectional mouse genetics to achieve single-cell type labeling and identified an object motion sensitive (OMS) AC type, COMS-AC(counter-OMS AC). Optogenetic stimulation revealed that COMS-AC makes glycinergic synapses with the OMS-insensitive HD2p-RGC, while chemogenetic inactivation showed that COMS-AC provides inhibitory control to HD2p-RGC during local motion. This local inhibition, combined with the inhibitory drive from TH2-AC during global motion, explains the OMS-insensitive feature of HD2p-RGC. In contrast, COMS-AC fails to make synapses with W3(UHD)-RGC, allowing it to exhibit OMS under the control of VGlut3-AC and TH2-AC. These findings reveal modular interneuron circuits that endow structurally similar RGC types with different responses and present a mechanism for redundancy-reduction in the retina to expand coding capacity.
A simeprevir-inducible molecular switch for the control of cell and gene therapies
Authors: Chin Stacey E. , Schindler Christina , Vinall Lisa , Dodd Roger B. , Bamber Lisa , Legg Sandrine , Sigurdardottir Anna , Rees D. Gareth , Malcolm Tim I. M. , Spratley Samantha J. , Granéli Cecilia , Sumner Jonathan , Tigue Natalie J. 
Published: November 2023

AbstractChemical inducer of dimerization (CID) modules can be used effectively as molecular switches to control biological processes, and thus there is significant interest within the synthetic biology community in identifying novel CID systems. To date, CID modules have been used primarily in engineering cells for in vitro applications. To broaden their utility to the clinical setting, including the potential to control cell and gene therapies, the identification of novel CID modules should consider factors such as the safety and pharmacokinetic profile of the small molecule inducer, and the orthogonality and immunogenicity of the protein components. Here we describe a CID module based on the orally available, approved, small molecule simeprevir and its target, the NS3/4A protease from hepatitis C virus. We demonstrate the utility of this CID module as a molecular switch to control biological processes such as gene expression and apoptosis in vitro, and show that the CID system can be used to rapidly induce apoptosis in tumor cells in a xenograft mouse model, leading to complete tumor regression.
scDREAMER for atlas-level integration of single-cell datasets using deep generative model paired with adversarial classifier
Authors: Shree Ajita , Pavan Musale Krushna , Zafar Hamim 
Published: November 2023

AbstractIntegration of heterogeneous single-cell sequencing datasets generated across multiple tissue locations, time, and conditions is essential for a comprehensive understanding of the cellular states and expression programs underlying complex biological systems. Here, we present scDREAMER (https://github.com/Zafar-Lab/scDREAMER), a data-integration framework that employs deep generative models and adversarial training for both unsupervised and supervised (scDREAMER-Sup) integration of multiple batches. Using six real benchmarking datasets, we demonstrate that scDREAMER can overcome critical challenges including skewed cell type distribution among batches, nested batch-effects, large number of batches and conservation of development trajectory across batches. Our experiments also show that scDREAMER and scDREAMER-Sup outperform state-of-the-art unsupervised and supervised integration methods respectively in batch-correction and conservation of biological variation. Using a 1 million cells dataset, we demonstrate that scDREAMER is scalable and can perform atlas-level cross-species (e.g., human and mouse) integration while being faster than other deep-learning-based methods.
The oxygen-tolerant reductive glycine pathway assimilates methanol, formate and CO2 in the yeast Komagataella phaffii
Authors: Mitic Bernd M. , Troyer Christina , Lutz Lisa , Baumschabl Michael , Hann Stephan , Mattanovich Diethard 
Published: November 2023

AbstractThe current climatic change is predominantly driven by excessive anthropogenic CO2 emissions. As industrial bioprocesses primarily depend on food-competing organic feedstocks or fossil raw materials, CO2 co-assimilation or the use of CO2-derived methanol or formate as carbon sources are considered pathbreaking contributions to solving this global problem. The number of industrially-relevant microorganisms that can use these two carbon sources is limited, and even fewer can concurrently co-assimilate CO2. Here, we search for alternative native methanol and formate assimilation pathways that co-assimilate CO2 in the industrially-relevant methylotrophic yeast Komagataella phaffii (Pichia pastoris). Using 13C-tracer-based metabolomic techniques and metabolic engineering approaches, we discover and confirm a growth supporting pathway based on native enzymes that can perform all three assimilations: namely, the oxygen-tolerant reductive glycine pathway. This finding paves the way towards metabolic engineering of formate and CO2 utilisation to produce proteins, biomass, or chemicals in yeast.