bluuebunny/crossref_metadata_2025_split huggingface dataset:
The SK4 channel allosteric blocker, BA6b9, reduces atrial fibrillation substrate in rats with reduced ejection fraction
Authors: Burg Shira , Levi Or , Elyagon Sigal , Shapiro Shir , Murninkas Michael , Etzion Sharon , Gradwohl Gideon , Makarovsky Daria , Lichtenstein Alexandra , Gordon Yaara , Attali Bernard , Etzion Yoram 
Published: May 2024

Abstract
Atrial fibrillation (AF), the most common cardiac arrhythmia, is strongly associated with several comorbidities including heart failure (HF). AF in general, and specifically in the context of HF, is progressive in nature and associated with poor clinical outcomes. Current therapies for AF are limited in number and efficacy and do not target the underlying causes of atrial remodeling such as inflammation or fibrosis. We previously identified the calcium-activated SK4 K+ channels, which are preferentially expressed in the atria relative to the ventricles in both rat and human hearts, as attractive druggable target for AF treatment. Here, we examined the ability of BA6b9, a novel allosteric inhibitor of SK4 channels that targets the specific calmodulin-PIP2 binding domain, to alter AF susceptibility and atrial remodeling in a systolic HF rat postmyocardial infarction (post-MI) model. Daily BA6b9 injection (20 mg/kg/day) for 3 weeks starting 1-week post-MI prolonged the atrial effective refractory period, reduced AF induction and duration, and dramatically prevented atrial structural remodeling. In the post-MI left atrium (LA), pronounced upregulation of the SK4 K+ channel was observed, with corresponding increases in collagen deposition, α-SMA levels, and NLRP3 inflammasome expression. Strikingly, BA6b9 treatment reversed these changes while also significantly reducing the lateralization of the atrial connexin Cx43 in the LA of post-MI rats. Our findings indicate that the blockade of SK4 K+ channels using BA6b9 not only favors rhythm control but also remarkably reduces atrial structural remodeling, a property that is highly desirable for novel AF therapies, particularly in patients with comorbid HF.
Towards verifications of Krylov complexity
Authors: Sasaki Ryu 
Published: May 2024

Abstract
Krylov complexity is considered to provide a measure of the growth of operators evolving under Hamiltonian dynamics. The main strategy is the analysis of the structure of Krylov subspace $\mathcal {K}_M(\mathcal {H},\eta )$ spanned by the multiple applications of the Liouville operator $\mathcal {L}$ defined by the commutator in terms of a Hamiltonian $\mathcal {H}$, $\mathcal {L}:=[\mathcal {H},\cdot ]$ acting on an operator η, $\mathcal {K}_M(\mathcal {H},\eta )=\text{span}\lbrace \eta ,\mathcal {L}\eta ,\ldots ,\mathcal {L}^{M-1}\eta \rbrace$. For a given inner product ( ·, ·) of the operators, the orthonormal basis $\lbrace \mathcal {O}_n\rbrace$ is constructed from $\mathcal {O}_0=\eta /\sqrt{(\eta ,\eta )}$ by Lanczos algorithm. The moments $\mu _m=(\mathcal {O}_0,\mathcal {L}^m\mathcal {O}_0)$ are closely related to the important data {bn} called Lanczos coefficients. I present the exact and explicit expressions of the moments {μm} for 16 quantum mechanical systems which are exactly solvable both in the Schrödinger and Heisenberg pictures. The operator η is the variable of the eigenpolynomials. Among them six systems show a clear sign of ‘non-complexity’ as vanishing higher Lanczos coefficients bm = 0, m ≥ 3.
The forced battle between peer-review and scientometric research assessment: Why the CoARA initiative is unsound
Authors: Abramo Giovanni 
Published: May 2024

Abstract
Endorsed by the European Research Area, a Coalition for Advancing Research Assessment (CoARA), primarily composed of research institutions and funders, was established in 2022. Its mission is to reform research assessment, emphasizing a shift towards qualitative judgment. This study examines the CoARA initiative from theoretical, practical, and applicative perspectives, exploring its implications. The manuscript questions a standardized way to evaluate research suitable in every context. Through empirical evidence and internal logical arguments, it challenges the supremacy of qualitative over quantitative methods in terms of robustness, accuracy, validity, functionality, and time and cost convenience in STEMM research assessment. The aim is to clear up common misunderstandings and offer insights to policymakers and decision-makers in charge of defining how research should be evaluated.
Beyond minimum wage: Broader employment policies can significantly affect food insecurity
Authors: Piekarz-Porter Elizabeth , Oddo Vanessa M , Stiehl Emily , Kim Sage J 
Published: May 2024

AbstractAlthough many have investigated the impacts of minimum wage on a broad array of health outcomes, innovative policies surrounding broader employment policies have largely not been studied. To that end, this paper contributes in three ways. First, it discusses the rise in precarious employment. Then, it turns to the current federal framework of employment policies, namely minimum wage. Finally, it explores what a broader definition of employment policies could include and how future studies could use state, county, and municipal policymaking in this space to investigate ways in which they might contribute to reducing food insecurity and in turn, improve health outcomes.
Heparan sulphate binding controlsin vivohalf-life of the HpARI protein family
Authors: Colomb Florent , Jamwal Abhishek , Ogunkanbi Adefunke , Frangova Tania , Savage Alice R. , Kelly Sarah , Wright Gavin J , Higgins Matthew K. , McSorley Henry J 
Published: May 2024

AbstractThe parasitic nematodeHeligmosomoides polygyrus bakerisecretes the HpARI family, which bind to IL-33, either suppressing (HpARI1 and HpARI2) or enhancing (HpARI3) responses to the cytokine. We previously showed that HpARI2 also bound to DNA via its first Complement Control Protein (CCP1) domain. Here, we find that HpARI1 can also bind DNA, while HpARI3 cannot. Through the production of HpARI2/HpARI3 CCP1 domain-swapped chimeras, DNA-binding ability can be transferred, and correlates with in vivo half-life of administered proteins. We found that HpARI1 and HpARI2 (but not HpARI3) also binds to the extracellular matrix component heparan sulphate (HS), and structural modelling showed a basic charged patch in the CCP1 domain of HpARI1 and HpARI2 (but not HpARI3) which could facilitate these interactions. Finally, a mutant of HpARI2 was produced which lacked DNA and HS binding, and was also shown to have a short half-life in vivo. Therefore, we propose that during infection the suppressive HpARI1 and HpARI2 proteins have long-lasting effects at the site of deposition due to DNA and/or extracellular matrix interactions, while HpARI3 has a shorter half-life due to a lack of these interactions.
Metastasis founder cells activate immunosuppression early in human melanoma metastatic colonization
Authors: Guetter Severin , König Courtney , Koerkel-Qu Huiqin , Markiewicz Aleksandra , Scheitler Sebastian , Katzer Marie , Berneburg Mark , Renner Philipp , Cucuruz Beatrix , Guttenberger Leonhard , Naimer Veronika , Weidele Kathrin , Treitschke Steffi , Werno Christian , Jaser Hanna , Bargmann Tonia , Braun Armin , Weber Florian , Rachel Reinhard , Baumann Felix , Schmidleithner Lisa , Schambeck Kathrin , Mohammadi Parvaneh , Ulmer Anja , Haferkamp Sebastian , Klein Christoph A. , Werner-Klein Melanie 
Published: May 2024

AbstractThe earliest steps of lethal metastasis in patients are incompletely understood. To dissect them, we prospectively searched for the earliest detectable disseminated cancer cells (DCC) in sentinel lymph node biopsies of 492 stage I-III patients. By visually-controlled, micromanipulator-assisted isolation and single cell transcriptome analysis of these extremely rare DCC, we identified MCSP+melanoma cells as strong candidates for metastasis founder cells (MFC) in lymph nodes. Based on a median follow-up time of 6 years, their detection was the strongest predictor of systemic metastasis and death upon multivariable analysis. During transition from single cells to metastasis-initiating clusters, melanoma DCC were exposed to CD8 T cell attack, activated the extracellular vesicular exosomal pathway, and expressed the immunomodulatory proteins CD155 and CD276, but rarely PD-L1. CD155 and CD276-positive extracellular vesicles from patient-derived DCC models exhibited an immunosuppressive activity on CD8 T cells. Our data indicate that either direct targeting of MFC employing MCSP or their immune escape mechanisms might be key for cure of early-stage melanoma.
Draft genome analysis ofDelftia tsuruhatensisIICT-RSP4, a strain with uricase potential isolated from soil
Authors: Anumalla Mahesh , Batchu Uma Rajeswari , Bhukya Bhima , Shetty Prakasham Reddy 
Published: May 2024

AbstractDelftia tsuruhatensisIICT-RSP4, an uricase producing bacterium was isolated usingi-chip method from soil and characterized. Here, we report the draft genome sequence ofD. tsuruhatensisIICT-RSP4. The genome data comprised of 6,627,718bp (6.6 MB) with a GC content of 66.6% with 7 protein encoding genes, 346 sub-systems with 6165 coding sequences and 112 RNAs. The genome revealed five functional secondary metabolite biosynthetic gene clusters viz. terpene, resorcinol, NRP+PKS, T2PKS, and RiPPS related to antimicrobial, anticancer and antimalarial functionality.In vitro, screening studies revealed the uricase potential of the strainD. tsuruhatensisIICT-RSP4. This is the first report on the whole genome sequence of an uricase-producingD. tsuruhatensisIICT-RSP4.
A New Species ofPachytritonfrom Anhui, China (Amphibia: Caudata: Salamandridae)
Authors: He Zhirong , Li Jiaqi , Wu Siyu , Wang Shanqing , Zhao Na , Ma Li , Jiang Jianping , Wu Xiaobing , Wang Supen 
Published: May 2024

AbstractA new species belonging to the genusPachytritonis delineated based on four specimens obtained from the Qingliangfeng Nature Reserve, Huangshan, Anhui, China. The identification of this distinct species within the Southeast Chinese Hilly Area enhances the recognized biodiversity ofPachytritonand signifies unresolved interrelations among species in southeastern China. This new species can be distinguished fromP. granulosusandP. feiithrough meticulous morphological and molecular examinations. The phylogenetic correlation was established utilizing the mitochondrial NADH dehydrogenase subunit 2 gene (ND2). The four recent specimens constitute a cohesive monophyletic clade with robust affirmation. The acknowledgment of this new species elevates the tally of documentedPachytritonspecies to 11.
Bayesian Estimation of Muscle Mechanisms and Therapeutic Targets Using Variational Autoencoders
Authors: Tune Travis , Kooiker Kristina B , Davis Jennifer , Daniel Thomas , Moussavi-Harami Farid 
Published: May 2024

ABSTRACTCardiomyopathies, often caused by mutations in genes encoding muscle proteins, are traditionally treated by phenotyping hearts and addressing symptoms post irreversible damage. With advancements in genotyping, early diagnosis is now possible, potentially introducing earlier treatment. However, the intricate structure of muscle and its myriad proteins make treatment predictions challenging. Here we approach the problem of estimating therapeutic targets for a mutation in mouse muscle using a spatially explicit half sarcomere muscle model. We selected 9 rate parameters in our model linked to both small molecules and cardiomyopathy-causing mutations. We then randomly varied these rate parameters and simulated an isometric twitch for each combination to generate a large training dataset. We used this dataset to train a Conditional Variational Autoencoder (CVAE), a technique used in Bayesian parameter estimation. Given simulated or experimental isometric twitches, this machine learning model is able to then predict the set of rate parameters which are most likely to yield that result. We then predict the set of rate parameters associated with twitches from control mice with the cardiac Troponin C (cTnC) I61Q variant and control twitches treated with the myosin activator Danicamtiv, as well as model parameters that recover the abnormal I61Q cTnC twitches.SIGNIFICANCEMachine learning techniques have potential to accelerate discoveries in biologically complex systems. However, they require large data sets and can be challenging in high dimensional systems such as cardiac muscle. In this study, we combined experimental measures of cardiac muscle twitch forces with mechanistic simulations and a newly developed mixture of Bayesian inference with neural networks (in autoencoders) to solve the inverse problem of determining the underlying kinetics for observed force generation by cardiac muscle. The autoencoders are trained on millions of simulations spanning parameter spaces that correspond to the mechanochemistry of cardiac sarcomeres. We apply the trained model to experimental data in order to infer parameters that can explain a diseased twitch and ways to recover it.
Plasmodesmal closure elicits stress responses
Authors: Tee Estee E. , Breakspear Andrew , Papp Diana , Thomas Hannah R. , Walker Catherine , Bellandi Annalisa , Faulkner Christine 
Published: May 2024

AbstractPlant cells are connected to their neighbors via plasmodesmata facilitating the exchange of nutrients and signaling molecules. During immune responses, plasmodesmata close, but how this contributes towards a full immune response is unknown. To investigate this, we developed two transgenic lines with which we could induce plasmodesmal closure independently of immune elicitors, using the over-active CALLOSE SYNTHASE3 alleleicals3mand the C-terminus of PDLP1 to drive callose deposition at plasmodesmata. Induction of plasmodesmal closure increased the expression of stress responsive genes, salicylic acid accumulation and resistance toPseudomonas syringaeDC3000. More homogeneous plasmodesmal closure usingicals3malso led to the accumulation of starch and sugars, decreased leaf growth, as well as hypersusceptibility toBotrytis cinerea. Based on the profile of responses, we conclude that plasmodesmal closure itself activates stress signaling, raising questions of what signals mediate this response and whether these responses occur in all circumstances when plasmodesmata close.
EMT-dependent cell-matrix interactions are linked to unjamming transitions in cancer spheroid invasion
Authors: van der Net Anouk , Rahman Zaid , Bordoloi Ankur D. , Muntz Iain , ten Dijke Peter , Boukany Pouyan E. , Koenderink Gijsje H. 
Published: May 2024

ABSTRACTThe plasticity of cancer cells allows them to switch between different migration modes, promoting their invasion into the extracellular matrix (ECM) and hence increasing the risks of metastasis. Epithelial-to-mesenchymal transitions (EMT) and unjamming transitions provide two distinct pathways for cancer cells to become invasive, but it is still unclear to what extent these pathways are connected. Here we addressed this question by performing 3D spheroid invasion assays of lung adenocarcinoma (A549, epithelial) and melanoma (MV3, mesenchymal-like) cancer cell lines in collagen-based hydrogels, where we varied both the invasive character of the cells (using Transforming Growth Factor (TGF)-βto promote EMT and matrix metalloprotease (MMP) inhibition to block cell-mediated matrix degradation) and the porosity of the matrix. Using a quantitative image analysis method to track spheroid invasion, we discovered that the onset time of invasion mostly depended on the matrix porosity and corresponded with vimentin levels, while the subsequent spheroid expansion rate mostly depended on metalloprotease MMP1 levels and thus cell-matrix interaction. Morphological analysis revealed that spheroids displayed solid-like (non-invasive) behavior in small-pore hydrogels and switched to fluid-like (strand-based) or gas-like (disseminating cells) phases in large-pore hydrogels and when cells were more mesenchymal-like. Our findings are consistent with unjamming transitions as a function of cell motility and matrix confinement predicted in recent models for cancer invasion, but show that cell motility and matrix confinement are coupled via EMT-dependent matrix degradation.
Oncogenic Ras-driven Dorsal/NF-κB signaling contributes to tumorigenesis in aDrosophilacarcinoma model
Authors: Dillard Caroline , Reis Jose Teles , Jain Ashish , Le Borgne Roland , Jasper Heinrich , Rusten Tor Erik 
Published: May 2024

AbstractCancer-driving mutations synergize with inflammatory stress signaling pathways during carcinogenesis.Drosophila melanogastertumour models are increasingly recognized as models to inform conserved molecular mechanisms of tumorigenesis with both local and systemic effects of cancer. Although initial discoveries of the Toll-NFκB signaling pathway in development and immunity was pioneered inDrosophila, limited information is available for its role in cancer progression. Using a well-studied cooperative RasV12-driven epithelial-derived tumour model, we here describe functions of Toll-NF-κB signaling in malignantRasV12, scrib-tumors. The extracellular Toll pathway components ModSP and PGRP-SA and intracellular signaling Kinase, Pelle/IRAK, are rate-limiting for tumor growth. The Toll pathway NFκB protein Dorsal, as well ascactus/IκB show elevated expression in tumors with highest expression in invasive cell populations. Oncogenic RasV12, and not loss ofscribble,confers increased expression and heterogenous distribution of two Dorsal isoforms, DorsalA and DorsalB in different tumour cell populations. Mechanistic analyses demonstrates that Dorsal drives growth and malignancy by suppressing differentiation, counteracting apoptosis and promoting invasion ofRasV12, scrib-tumors genetically dependent ontwistandsnail.
B cell-mediated antigen presentation promotes adverse cardiac remodeling in chronic heart failure
Authors: Lovell Jana P. , Duque Carolina , Rousseau Sylvie , Bhalodia Aashik , Bermea Kevin , Cohen Charles D. , Adamo Luigi 
Published: May 2024

AbstractCardiovascular disease remains the leading cause of death worldwide. A primary driver of cardiovascular mortality is ischemic heart failure, a form of cardiac dysfunction that can develop in patients who survive myocardial infarction. Acute cardiac damage triggers robust changes in the spleen with rapid migration of immune cells from the spleen to the heart. Activating this “cardio-splenic” axis contributes to progressive cardiac dysfunction. The cardio-splenic axis has, therefore, been identified as a promising therapeutic target to prevent or treat heart failure.However, our understanding of the precise mechanisms by which specific immune cells contribute to adverse cardiac remodeling within the cardio-splenic axis remains limited. Here, we show that splenic B cells contribute to the development of heart failure via MHC II-mediated antigen presentation. We found that the adoptive transfer of splenic B cells from mice with ischemic heart failure promoted adverse cardiac remodeling and splenic inflammatory changes in naïve recipient mice. Based on single-cell RNA sequencing analysis of splenic B cells from mice with ischemic heart failure, we hypothesized that B cells contributed to adverse cardiac remodeling through antigen presentation by MHC II molecules. This mechanism was confirmed using transgenic mice with B cell-specific MHC II deletion, and by analyzing circulating B cells from humans who experienced myocardial infarction. Our results broaden our understanding of B lymphocyte biology, reshape current models of immune activation in response to myocardial injury, and point towards MHC II-mediated signaling in B cells as a novel and specific therapeutic target in chronic heart failure.
PCIF1 is partly cytoplasmic, dynamically localizes to stress granules and binds mRNA coding regions upon oxidative stress
Authors: Tat Trinh T. , Raza Sabeen , Khan Shaheerah , Watson Tiara L. , Jung Sung Yun , Kiss Daniel L. 
Published: May 2024

AbstractPCIF1 (PhosphorylatedCTD-InteractingFactor1) is the mRNA (2’-O-methyladenosine-N(6)-)-methyltransferase that catalyzes the formation of cap-adjacent N6,2’-O-dimethyladenosine (m6Am) by methylating adenosines at the first transcribed position of capped mRNAs. While previous studies assumed that PCIF1 was nuclear, cell fractionation and immunofluorescence both show that a population of PCIF1 is localized to the cytoplasm. Further, PCIF1 redistributes to stress granules upon oxidative stress. Immunoprecipitation studies with stressed cells show that PCIF1 also physically interacts with G3BP and other stress granule components. In addition, PCIF1 behaves as a stress granule component as it disassociates from stress granules upon recovery from stress. Overexpressing full-length PCIF1 also inhibits stress granule formation, while knocking out PCIF1 slows stress granule disassembly. Next, our enhanced crosslinking and immunoprecipitation (eCLIP) data show that PCIF1 binds mRNAs in their coding sequences rather than cap-proximal regions. Further PCIF1’s association with mRNAs increased upon NaAsO2stress. In contrast to eCLIP data, ChIP-Seq experiments show that PCIF1 is predominantly associated with transcription start sites rather than gene bodies, indicating that PCIF1’s association with mature mRNA is not co-transcriptional. Collectively, our data suggest that PCIF1 has cytoplasmic RNA surveillance role(s) independent of transcription-associated cap-adjacent mRNA modification, particularly during the stress response.
SCO-pH: Microfluidic dynamic phenotyping platform for high-throughput screening of single cell acidification
Authors: Jeong Hyejoong , Porello Emilia A. Leyes , Rosario Jean Gabriel , Kuang Da , Han Syung Hun , Sul Jai-Yoon , Lim Bomyi , Lee Daeyeon , Kim Junhyong 
Published: May 2024

AbstractStudies on the dynamics of single cell phenotyping have been hampered by the lack of quantitative high-throughput metabolism assays. Extracellular acidification, a prominent phenotype, yields significant insights into cellular metabolism, including tumorigenicity. Here, we develop a versatile microfluidic system for single cell optical pH analysis (SCO-pH), which compartmentalizes single cells in 140-pL droplets and immobilizes approximately 40,000 droplets in a two-dimensional array for temporal extracellular pH analysis. SCO-pH distinguishes cells undergoing hyperglycolysis induced by oligomycin A from untreated cells by monitoring their extracellular acidification. To facilitate pH sensing in each droplet, we encapsulate a cell-impermeable pH probe whose fluorescence intensities are quantified. Using this approach, we can differentiate hyperglycolytic cells and concurrently observe single cell heterogeneity in extracellular acidification dynamics. This high-throughput system will be useful in applications that require dynamic phenotyping of single cells with significant heterogeneity.