bluuebunny/crossref_metadata_2025_split huggingface dataset:
Let’s Get Physical: On Observing Force Perturbations of Proliferating Glioblastomal Cells
Authors: Seto Jong , Chen Yong 
Published: January 2023

AbstractThe growth and proliferation of mutant astrocyte cells are widely known characteristics in high grade glioblastoma multiforme (GBM) neurological cancers. The infiltrative tumor processes during glioblastoma development follow predefined routes and patterns dictated by biochemical and physiological environments in the brain. Specifically, at the cellular-level the glioblastoma-related astrocytes cells typically are occluded along neural fissures, neurophysiological interfaces as well as along available blood vessel routes for sources of nutrients to drive overall tumor tissue growth and development. Additionally, each individual astrocyte cell maintains a predisposition to aggregate into a supracellular aggregate with organioid-like properties. Here in this work, we attempt to understand the physical processes involved at the single cell level in forming these pre-tumor states and investigate the environmental forces that may perturb the formation of intermediate cellular assemblies in order to ultimately perturb overall tumor growth and development processes.
Disrupted in Renal Carcinoma 3(DIRC3) impacts malignant phenotype and IGFBP5/IGF-1/Akt signaling axis in differentiated thyroid cancer
Authors: Wysocki Piotr T. , Czubak Karol , Marusiak Anna A. , Kolanowska Monika , Nowis Dominika 
Published: January 2023

ABSTRACTDifferentiated thyroid cancers (DTCs) are malignancies with ill-defined hereditary predisposition. Some germline variants influencing the risk of DTCs localize indisrupted in renal carcinoma 3(DIRC3), a poorly characterized long non-coding RNA (lncRNA) gene. Here, we characterized the function ofDIRC3in DTCs. We established thatDIRC3is downregulated in DTCs, and its high expression may reduce the risk of cancer recurrence in patients.DIRC3transcripts were enriched in cell nucleiin vitro, where they upregulatedinsulin-like growth factor binding protein 5(IGFBP5), a gene known to modulate the cellular response to insulin-like growth factor 1 (IGF-1). Silencing ofDIRC3in thyroid cancer cell lines produced a phenotypic dichotomy: it augmented cell migration and invasiveness, reduced apoptosis, but abrogated the MTT reduction rate. We demonstrated that the pro-migratory phenotype was produced by the downregulation ofIGFBP5. Transcriptomic profiling confirmed a functional redundancy in the activities ofDIRC3andIGFBP5. Moreover, downregulation ofDIRC3enhanced the susceptibility of cancer cells to IGF-1 stimulation and promoted Akt signaling. In conclusion,DIRC3expression alters the phenotype of thyroid cancer cells and modulates the activity of IGFBP5/IGF-1/Akt axis. We propose an interplay betweenDIRC3and IGF signaling as a mechanism that promotes thyroid carcinogenesis.
Importance of eDNA taphonomy and provenance for robust ecological inference: insights from interfacial geochemistry
Authors: Sand K.K. , Jelavić S. , Kjær K.H. , Prohaska A. 
Published: January 2023

ABSTRACTContext for and purposeRetrieval of modern and ancient environmental DNA (eDNA) from sediments has revolutionized our ability to reconstruct present and past ecosystems. Little emphasis has been placed, however, on the fundamentals of the DNA-sediment associations and, consequently, our understanding of taphonomy and provenance of eDNA in sediments remains extremely limited. If we are to be able to accurately infer community dynamics across time and space from eDNA data, we need to understand how depositional processes and sedimentary associations of DNA molecules in different settings influence our interpretation.Approach and methodsHere, we introduce interfacial geochemical principles to the field of eDNA and discuss current interpretational biases. We outline a way to increase the scope and resolution of ecological interpretations from eDNA by combining mineralogic composition with experimental adsorption data. We apply distribution coefficients to assess the relationship between the DNA fraction in water columns and DNA fraction sequestered by suspended sediment particles. We further evaluate the challenges with drawing ecological inference using eDNA from sedimentary systems that receive input from different ecosystem types as a consequence of sedimentary processes.Main results: We show thatThe retention of DNA in aqueous environments depends on the mineralogy of sediment particles and on the number of particles loaded in the water column.DNA attached to sediment particles from distal systems can be deposited in proximal systems and skew the interpretation of the proximal sediment samples.High particle loading in the water column can deplete suspended DNA and cause inaccurate interpretation of aqueous DNA samples.High particle loading in surface sediment pore waters enhances sequestration of DNA from benthic communities relative to that of water column communities, resulting in skewed estimates of species richness and abundance from sedimentary DNA.We discuss how to integrate taphonomy and provenance knowledge into the reconstruction of modern and past ecosystems, and ecosystem monitoring from eDNA data.Conclusions and the wider implicationsOur findings demonstrate that integrating information about eDNA taphonomy and provenance into modern and past ecosystem reconstruction from eDNA data can enhance the scope, resolution and accuracy of our interpretations.
Transpiration Responses to Potential Volatile Signals and Hydraulic Failure in Single Leaves ofVitis Vinifera(CV. Shiraz) andArabidopsis Thaliana(Col 0) Utilising Sensitive Liquid Flow and Simultaneous Gas Exchange
Authors: Balacey Suzanne L. , Capone Dimitra Liacopoulos , Sullivan Wendy , Tyerman Stephen D. 
Published: January 2023

AbstractVolatile organic compounds (VOCs) may communicate stress between plants. However little appears to be documented on how such VOCs affect transpiration. Changes in transpiration in response to some VOCs was examined by measurement of flow (Q) at high resolution into detached leaves ofVitis vinifera(cv. Shiraz) and Arabidopsis (Col 0). Sensors recorded arrival and decay of volatiles at the leaf lamina. Moderate xylem tensions were developed inV. viniferaleaves by incorporating a hydraulic resistance in the flow pathway. Simultaneous recording of leaf gas exchange (Assimilation,A, and Transpiration,E) for bothV. viniferaand Arabidopsis revealed that for ArabidopsisQwas stochastically restricted by the gas exchange cuvette but notEin the short term. Depending on the applied supply pressure cavitation could be controlled inV. viniferaevident from reducedQ, and leaf wilting. Stomatal closure occurred upon cavitation after a transitory increase inEandA, and after wilting began and was reversed by re-pressurization. VOCs were emitted from leaves corresponding to changes in flow rate, and light to dark transitions but not to cavitation. Volatile methanol but not ethanol or methyl salicylate induced a localised dose-dependent reversible stomatal closure in bothV. viniferaand Arabidopsis.
Cardiomyocyte apoptosis contributes to contractile dysfunction in stem cell model ofMYH7E848G hypertrophic cardiomyopathy
Authors: Loiben Alexander M. , Chien Wei-Ming , Friedman Clayton E. , Chao Leslie S-L. , Weber Gerhard , Goldstein Alex , Sniadecki Nathan , Murry Charles E. , Yang Kai-Chun 
Published: January 2023

AbstractMissense mutations in myosin heavy chain 7 (MYH7) are a common cause of hyper-trophic cardiomyopathy (HCM), but the molecular mechanisms underlyingMYH7-based HCM remain unclear. In this work, we generated cardiomyocytes derived from isogenic human induced pluripotent stem cells to model the heterozygous pathogenicMYH7missense variant, E848G, which is associated with left ventricular hypertrophy and adultonset systolic dysfunction.MYH7E848G/+increased cardiomyocyte size and reduced the maximum twitch forces of engineered heart tissue, consistent with the systolic dysfunction inMYH7E848G HCM patients. Interestingly,MYH7E848G/+cardiomyocytes more frequently underwent apoptosis that was associated with increased p53 activity relative to controls. However, genetic ablation ofTP53did not rescue cardiomyocyte survival or restore engineered heart tissue twitch force, indicatingMYH7E848G/+cardiomyocyte apoptosis and contractile dysfunction are p53-independent. Overall, our findings suggest that cardiomyocyte apoptosis plays an important role in theMYH7E848G/+HCM phenotypein vitroand that future efforts to target p53-independent cell death pathways may be beneficial for the treatment of HCM patients with systolic dysfunction.
DISCO: A deep learning ensemble for uncertainty-aware segmentation of acoustic signals
Authors: Colligan Thomas , Irish Kayla , Emlen Douglas J. , Wheeler Travis J. 
Published: January 2023

AbstractRecordings of animal sounds enable a wide range of observational inquiries into animal communication, behavior, and diversity. Automated labeling of sound events in such recordings can improve both throughput and reproducibility of analysis. Here, we describe our software package for labeling sound elements in recordings of animal sounds and demonstrate its utility on recordings of beetle courtships and whale songs. The software, DISCO, computes sensible confidence estimates and produces labels with high precision and accuracy. In addition to the core labeling software, it provides a simple tool for labeling training data, and a visual system for analysis of resulting labels. DISCO is open-source and easy to install, it works with standard file formats, and it presents a low barrier of entry to use.
The multilevel society of proboscis monkeys with a possible patrilineal basis
Authors: Matsuda Ikki , Murai Tadahiro , Grueter Cyril C. , Tuuga Augustine , Goossens Benoit , Bernard Henry , Yahya Nurhartini Kamalia , Orozco-terWengel Pablo , Salgado-Lynn Milena 
Published: January 2023

AbstractMultilevel societies (MLS), which are characterized by two or more levels of social organization, are among the most complex primate social systems. MLS have only been recorded in a limited number of primates, including humans. The aim of this study was to investigate whether proboscis monkeys (Nasalis larvatus) form MLS in Sabah, Malaysia, and to genetically characterize their dispersal patterns. Association data were obtained through direct observation (35 months) and kinship data through genetic analysis, based on feces collected from ∼200 individuals. The results strongly suggest that proboscis monkeys exhibit a form of MLS, with several core reproductive units and a bachelor group woven together into a higher-level band. Genetic analysis revealed that the females migrated randomly over short and long distances; however, the males tended to migrate relatively shorter distances than females. Furthermore, male-male dyads showed a slightly higher average relatedness than female-female dyads. Combined with the results of direct observations, we conclude that proboscis monkeys form a MLS with at least two layers and a patrilineal basis. Since patrilineal MLS have been identified as an important step in the evolution of human societies, their convergent appearance in proboscis monkeys may help us understand of the drivers of human social evolution.Significance StatementThe aim of this study was to determine the social organization of proboscis monkeys by direct observation and genetic analysis. The results revealed that their social system exhibited a form of multilevel society with a possible patrilineal basis. Since humans exhibit a similar constellation of social features, proboscis monkeys may offer insightful clues about human social evolution.
YersiniaType III-Secreted Effectors Evade the Caspase-4 Inflammasome in Human Cells
Authors: Zhang Jenna , Brodsky Igor E. , Shin Sunny 
Published: January 2023

AbstractYersiniaare gram-negative zoonotic bacteria that use a type III secretion system (T3SS) to injectYersiniaouter proteins (Yops) into the host cytosol to subvert essential components of innate immune signaling. However,Yersiniavirulence activities can elicit activation of inflammasomes, which lead to inflammatory cell death and cytokine release to contain infection.Yersiniaactivation and evasion of inflammasomes have been characterized in murine macrophages but remain poorly defined in human cells, particularly intestinal epithelial cells (IECs), a primary site of intestinalYersiniainfection. In contrast to murine macrophages, we find that in both human IECs and macrophages,Yersinia pseudotuberculosisT3SS effectors enable evasion of the caspase-4 inflammasome, which senses cytosolic lipopolysaccharide (LPS). The antiphagocytic YopE and YopH, as well as the translocation regulator YopK, were collectively responsible for evading inflammasome activation, in part by inhibitingYersiniainternalization mediated by YadA and β1-integrin signaling. These data provide insight into the mechanisms ofYersinia-mediated inflammasome activation and evasion in human cells, and reveal species-specific differences underlying regulation of inflammasome responses toYersinia.ImportanceYersiniaare responsible for significant disease burdens in humans, ranging from recurrent disease outbreaks (yersiniosis) to pandemics (Yersinia pestisplague). Together with rising antibiotic resistance rates, there is a critical need to better understandYersiniapathogenesis and host immune mechanisms, as this information will aid in developing improved immunomodulatory therapeutics. Inflammasome responses in human cells are less studied relative to murine models of infection, though recent studies have uncovered key differences in inflammasome responses between mice and humans. Here, we dissect human intestinal epithelial cell and macrophage inflammasome responses toYersinia pseudotuberculosis.Our findings provide insight into species- and cell type-specific differences in inflammasome responses toYersinia.
Overexpression of NIMA-related kinase suppresses cell proliferation and tip growth in a liverwortMarchantia polymorpha
Authors: Mase Hikari , Yoshitake Yoshihiro , Kohchi Takayuki , Takahashi Taku , Motose Hiroyasu 
Published: January 2023

AbstractNIMA-related kinases (NEKs) regulate a series of mitotic events in fungi and animals, whereas plant NEKs regulate growth direction of cells and organs. The liverwortMarchantia polymorphahas a single functional MpNEK1gene, whose knockout leads to twisted growth of rhizoids. MpNEK1is also expressed in the meristem of vegetative flat organ, thallus, while its function remains unknown. Here, we generated transgenic lines for the inducible expression of MpNEK1using an estrogen receptor mediated system. Estradiol treatment efficiently induced the accumulation of MpNEK1mRNA and MpNEK1-Citrine fusion protein throughout plant body. Overexpression of MpNEK1 severely suppressed growth of rhizoids and thalli, eventually causing the lethality of juvenile plants. The effect of estradiol was reversible until 3 days, whereas 7-days treatment resulted in irreversible suppression of growth. This severe effect was observed even at the nanomolar level of estradiol. EdU staining and microtubule imaging clearly indicated the suppression of cell proliferation by estradiol-induced MpNEK1. Unexpectedly, the overexpression of kinase-deficient MpNEK1 also suppressed thallus growth and rhizoid formation, despite their slightly mild effect than the full length MpNEK1, indicating phosphorylation-independent mechanism of growth suppression. In conclusion, overexpression of MpNEK1 suppresses cell division and elongation, leading to growth cessation and lethality. Our results imply that the expression of MpNEK1 is tightly regulated and plant NEKs might control cell division as in fungi and animals.
Long-term respiratory mucosal immune memory to SARS-CoV-2 after infection and vaccination
Authors: Mitsi Elena , Diniz Mariana O. , Reiné Jesús , Collins Andrea M. , Robinson Ryan , Hyder-Wright Angela , Farrar Madlen , Liatsikos Konstantinos , Hamilton Josh , Onyema Onyia , Urban Britta C. , Solorzano Carla , Lambe Teresa , Draper Simon J. , Weiskopf Daniela , Sette Alessandro , Maini Mala K. , Ferreira Daniela M. 
Published: January 2023

ABSTRACTRespiratory mucosal immunity induced by vaccination is vital for protection from coronavirus infection in animal models. In humans, SARS-CoV-2 immunity has been studied extensively in blood. However, the capacity of peripheral vaccination to generate sustained humoral and cellular immunity in the lung mucosa, and how this is influenced by prior SARS-CoV-2 infection, is unknown. Bronchoalveolar lavage samples obtained from vaccinated donors with or without prior infection revealed enrichment of spike-specific antibodies, class-switched memory B cells and T cells in the lung mucosa compared to the periphery in the setting of hybrid immunity, whereas in the context of vaccination alone, local anti-viral immunity was limited to antibody responses. Spike-specific T cells persisted in the lung mucosa for up to 5 months post-vaccination and multi-specific T cell responses were detected at least up to 11 months post-infection. Thus, durable lung mucosal immunity against SARS-CoV-2 seen after hybrid exposure cannot be achieved by peripheral vaccination alone, supporting the need for vaccines targeting the airways.
Comprehensive comparative assessment of theArabidopsis thalianaMLO2-calmodulin interaction by variousin vitroandin vivoprotein-protein interaction assays
Authors: von Bongartz Kira , Sabelleck Björn , Forero Anežka Baquero , Kuhn Hannah , Leissing Franz , Panstruga Ralph 
Published: January 2023

AbstractMildew resistance locus o (MLO) proteins are heptahelical integral membrane proteins of which some isoforms act as susceptibility factors for the fungal powdery mildew pathogen. In many angiosperm plant species, loss-of-functionmlomutants confer durable broad-spectrum resistance against the powdery mildew disease. Barley Mlo is known to interactviaa cytosolic carboxyl-terminal domain with the intracellular calcium sensor calmodulin (CAM) in a calcium-dependent manner. Site-directed mutagenesis has revealed key amino acid residues in the barley Mlo calcium-binding domain (CAMBD) that, when mutated, affect the MLO-CAM association. We here tested the respective interaction betweenArabidopsis thalianaMLO2 and CAM2 using seven different types ofin vitroandin vivoprotein-protein interaction assays. In each assay, we deployed a wild-type version of either the MLO2 carboxyl terminus (MLO2CT), harboring the CAMBD, or the MLO2 full-length protein and corresponding mutant variants in which two key residues within the CAMBD were substituted by non-functional amino acids. We focused in particular on the substitution of two hydrophobic amino acids (LW/RR mutant) and found in most protein-protein interaction experiments reduced binding of CAM2 to the corresponding MLO2/MLO2CTLW/RR mutant variants in comparison to the respective wild-type versions. However, the Ura3-based yeast split-ubiquitin system andin plantabimolecular fluorescence complementation (BiFC) assays failed to indicate reduced CAM2 binding to the mutated CAMBD. Our data shed further light on the interaction of MLO and CAM proteins and provide a comprehensive comparative assessment of different types of protein-protein interaction assays with wild-type and mutant versions of an integral membrane protein.
SIRT2 inhibition protects against cardiac hypertrophy and heart failure
Authors: Yang Xiaoyan , Chang Hsiang-Chun , Tatekoshi Yuki , Balibegloo Maryam , Wu Rongxue , Chen Chunlei , Sato Tatsuya , Shapiro Jason , Ardehali Hossein 
Published: January 2023

ABSTRACTSirtuins (SIRT) exhibit deacetylation or ADP-ribosyltransferase activity and regulate a wide range of cellular processes in the nucleus, mitochondria and cytoplasm. The role of the only sirtuin that resides in the cytoplasm, SIRT2, in the development of heart failure (HF) and cardiac hypertrophy is not known. In this paper, we show that the hearts of mice with deletion ofSirt2(Sirt2-/-) display improved cardiac function after ischemia-reperfusion (I/R) and pressure overload (PO), suggesting that SIRT2 exerts maladaptive effects in the heart in response to stress. Similar results were obtained in mice with cardiomyocyte-specificSirt2deletion. Mechanistic studies suggest that SIRT2 modulates cellular levels and activity of nuclear factor (erythroid-derived 2)-like 2 (NRF2), which results in reduced expression of antioxidant proteins. Deletion ofNrf2in the hearts ofSirt2-/-mice reversed protection after PO. Finally, treatment of mouse hearts with a specific SIRT2 inhibitors reduces cardiac size and attenuates cardiac hypertrophy in response to PO. These data indicate that SIRT2 has detrimental effects in the heart and plays a role in the progression of HF and cardiac hypertrophy, which makes this protein a unique member of the SIRT family. Additionally, our studies provide a novel approach for treatment of cardiac hypertrophy by targeting SIRT2 pharmacologically, providing a novel avenue for the treatment of this disorder.
Publication bias in meta-analyses of the therapeutic efficacy of remdesivir interventions for patients with COVID-19
Authors: Motahari-Nezhad Hossein , Sadeghdaghighi Aslan 
Published: January 2023

Purpose
No comprehensive statistical assessment of publication bias has been conducted in remdesivir-based intervention research for COVID-19 patients. This study aims to examine all meta-analyses of the efficacy of remdesivir interventions in COVID-19 patients and perform a statistical assessment of publication bias.

Design/methodology/approach
This is an analytic study conducted to assess the impact of publication bias on the results of meta-analyses of remdesivir-based interventions in patients infected with COVID-19. All English full-text meta-analyses published in peer-reviewed journals in 2019–2021 were included. A computerized search of PubMed and Web of Science electronic databases was performed on December 24, 2021. The trim-and-fill method calculated the number of missing studies and the adjusted cumulative effect sizes.

Findings
The final analysis comprised 21 studies with 88 outcomes. The investigation revealed missing studies in 46 outcomes (52%). Seventy-six missing studies were replaced in the outcomes using the trim-and-fill procedure. The adjusted recalculated effect sizes of the 27 outcomes increased by an average of 0.04. In comparison, the adjusted effect size of 18 outcomes fell by an average of 0.036. Only 14 out of 46 outcomes with publication bias were subjected to a gray literature search (30%). To discover related research, no gray literature search was conducted in most outcomes with publication bias (n = 32; 70%). In conclusion, the reported effect estimates regarding the effect of remdesivir in COVID-19 patients are only slightly affected by publication bias and can be considered authentic. Health-care decision-makers in COVID-19 should consider current research results when making clinical decisions.

Research limitations/implications
Most health decisions are based on the effect sizes revealed in meta-analyses. When deciding on remdesivir-based treatment for COVID-19 patients, therefore, the outcomes of this investigation may be of paramount importance to health policymakers, leading to better treatment strategies.

Practical implications
According to the results, no major publication bias and missing studies were detected on average. Therefore, the calculated effect sizes of remdesivir-based interventions on meta-analyses can be used as authentic and unbiased benchmarks by health-care decision-makers in treating patients with COVID-19.

Originality/value
This is the first study to examine the effect of publication bias and gray literature searches on the results of meta-analyses of treatment with COVID-19 (remdesivir).