bluuebunny/crossref_metadata_2025 huggingface dataset:
MYC promotes immune-suppression in triple-negative breast cancer via inhibition of interferon signaling
Authors: Zimmerli Dario , Brambillasca Chiara S. , Talens Francien , Bhin Jinhyuk , Linstra Renske , Romanens Lou , Bhattacharya Arkajyoti , Joosten Stacey E. P. , Da Silva Ana Moises , Padrao Nuno , Wellenstein Max D. , Kersten Kelly , de Boo Mart , Roorda Maurits , Henneman Linda , de Bruijn Roebi , Annunziato Stefano , van der Burg Eline , Drenth Anne Paulien , Lutz Catrin , Endres Theresa , van de Ven Marieke , Eilers Martin , Wessels Lodewyk , de Visser Karin E. , Zwart Wilbert , Fehrmann Rudolf S. N. , van Vugt Marcel A. T. M. , Jonkers Jos
Published: November 2022

The limited efficacy of immune checkpoint inhibitor treatment in triple-negative breast cancer (TNBC) patients is attributed to sparse or unresponsive tumor-infiltrating lymphocytes, but the mechanisms that lead to a therapy resistant tumor immune microenvironment are incompletely known. Here we show a strong correlation between MYC expression and loss of immune signatures in human TNBC. In mouse models of TNBC proficient or deficient of breast cancer type 1 susceptibility gene (BRCA1), MYC overexpression dramatically decreases lymphocyte infiltration in tumors, along with immune signature remodelling. MYC-mediated suppression of inflammatory signalling induced by BRCA1/2 inactivation is confirmed in human TNBC cell lines. Moreover, MYC overexpression prevents the recruitment and activation of lymphocytes in both human and mouse TNBC co-culture models. Chromatin-immunoprecipitation-sequencing reveals that MYC, together with its co-repressor MIZ1, directly binds promoters of multiple interferon-signalling genes, resulting in their downregulation. MYC overexpression thus counters tumor growth inhibition by a Stimulator of Interferon Genes (STING) agonist via suppressing induction of interferon signalling. Together, our data reveal that MYC suppresses innate immunity and facilitates tumor immune escape, explaining the poor immunogenicity of MYC-overexpressing TNBCs.
Uncertainty-informed deep learning models enable high-confidence predictions for digital histopathology
Authors: Dolezal James M. , Srisuwananukorn Andrew , Karpeyev Dmitry , Ramesh Siddhi , Kochanny Sara , Cody Brittany , Mansfield Aaron S. , Rakshit Sagar , Bansal Radhika , Bois Melanie C. , Bungum Aaron O. , Schulte Jefree J. , Vokes Everett E. , Garassino Marina Chiara , Husain Aliya N. , Pearson Alexander T.
Published: November 2022

A model’s ability to express its own predictive uncertainty is an essential attribute for maintaining clinical user confidence as computational biomarkers are deployed into real-world medical settings. In the domain of cancer digital histopathology, we describe a clinically-oriented approach to uncertainty quantification for whole-slide images, estimating uncertainty using dropout and calculating thresholds on training data to establish cutoffs for low- and high-confidence predictions. We train models to identify lung adenocarcinoma vs. squamous cell carcinoma and show that high-confidence predictions outperform predictions without uncertainty, in both cross-validation and testing on two large external datasets spanning multiple institutions. Our testing strategy closely approximates real-world application, with predictions generated on unsupervised, unannotated slides using predetermined thresholds. Furthermore, we show that uncertainty thresholding remains reliable in the setting of domain shift, with accurate high-confidence predictions of adenocarcinoma vs. squamous cell carcinoma for out-of-distribution, non-lung cancer cohorts.
Erratic and blood vessel-guided migration of astrocyte progenitors in the cerebral cortex
Authors: Tabata Hidenori , Sasaki Megumi , Agetsuma Masakazu , Sano Hitomi , Hirota Yuki , Miyajima Michio , Hayashi Kanehiro , Honda Takao , Nishikawa Masashi , Inaguma Yutaka , Ito Hidenori , Takebayashi Hirohide , Ema Masatsugu , Ikenaka Kazuhiro , Nabekura Junichi , Nagata Koh-ichi , Nakajima Kazunori
Published: November 2022

Astrocytes are one of the most abundant cell types in the mammalian brain. They play essential roles in synapse formation, maturation, and elimination. However, how astrocytes migrate into the gray matter to accomplish these processes is poorly understood. Here, we show that, by combinational analyses of in vitro and in vivo time-lapse observations and lineage traces, astrocyte progenitors move rapidly and irregularly within the developing cortex, which we call erratic migration. Astrocyte progenitors also adopt blood vessel-guided migration. These highly motile progenitors are generated in the restricted prenatal stages and differentiate into protoplasmic astrocytes in the gray matter, whereas postnatally generated progenitors do not move extensively and differentiate into fibrous astrocytes in the white matter. We found Cxcr4/7, and integrin β1 regulate the blood vessel-guided migration, and their functional blocking disrupts their positioning. This study provides insight into astrocyte development and may contribute to understanding the pathogenesis caused by their defects.
Network motifs shape distinct functioning of Earth’s moisture recycling hubs
Authors: Wunderling Nico , Wolf Frederik , Tuinenburg Obbe A. , Staal Arie
Published: November 2022

Earth’s hydrological cycle critically depends on the atmospheric moisture flows connecting evaporation to precipitation. Here we convert a decade of reanalysis-based moisture simulations into a high-resolution global directed network of spatial moisture provisions. We reveal global and local network structures that offer a new view of the global hydrological cycle. We identify four terrestrial moisture recycling hubs: the Amazon Basin, the Congo Rainforest, South Asia and the Indonesian Archipelago. Network motifs reveal contrasting functioning of these regions, where the Amazon strongly relies on directed connections (feed-forward loops) for moisture redistribution and the other hubs on reciprocal moisture connections (zero loops and neighboring loops). We conclude that Earth’s moisture recycling hubs are characterized by specific topologies shaping heterogeneous effects of land-use changes and climatic warming on precipitation patterns.
Strong band renormalization and emergent ferromagnetism induced by electron-antiferromagnetic-magnon coupling
Authors: Yu T. L. , Xu M. , Yang W. T. , Song Y. H. , Wen C. H. P. , Yao Q. , Lou X. , Zhang T. , Li W. , Wei X. Y. , Bao J. K. , Cao G. H. , Dudin P. , Denlinger J. D. , Strocov V. N. , Peng R. , Xu H. C. , Feng D. L.
Published: November 2022

The interactions between electrons and antiferromagnetic magnons (AFMMs) are important for a large class of correlated materials. For example, they are the most plausible pairing glues in high-temperature superconductors, such as cuprates and iron-based superconductors. However, unlike electron-phonon interactions (EPIs), clear-cut observations regarding how electron-AFMM interactions (EAIs) affect the band structure are still lacking. Consequently, critical information on the EAIs, such as its strength and doping dependence, remains elusive. Here we directly observe that EAIs induce a kink structure in the band dispersion of Ba1−xKxMn2As2, and subsequently unveil several key characteristics of EAIs. We found that the coupling constant of EAIs can be as large as 5.4, and it shows strong doping dependence and temperature dependence, all in stark contrast to the behaviors of EPIs. The colossal renormalization of electron bands by EAIs enhances the density of states at Fermi energy, which is likely driving the emergent ferromagnetic state in Ba1−xKxMn2As2 through a Stoner-like mechanism with mixed itinerant-local character. Our results expand the current knowledge of EAIs, which may facilitate the further understanding of many correlated materials where EAIs play a critical role.
Phosphorylation of 17β-hydroxysteroid dehydrogenase 13 at serine 33 attenuates nonalcoholic fatty liver disease in mice
Authors: Su Wen , Wu Sijin , Yang Yongliang , Guo Yanlin , Zhang Haibo , Su Jie , Chen Lei , Mao Zhuo , Lan Rongfeng , Cao Rong , Wang Chunjiong , Xu Hu , Zhang Cong , Li Sha , Gao Min , Chen Xiaocong , Zheng Zhiyou , Wang Bing , Liu Yi’ao , Liu Zuojun , Wang Zimei , Liu Baohua , Fan Xinmin , Zhang Xiaoyan , Guan Youfei
Published: November 2022

17β-hydroxysteroid dehydrogenase-13 is a hepatocyte-specific, lipid droplet-associated protein. A common loss-of-function variant ofHSD17B13(rs72613567: TA) protects patients against non-alcoholic fatty liver disease with underlying mechanism incompletely understood. In the present study, we identify the serine 33 of 17β-HSD13 as an evolutionally conserved PKA target site and its phosphorylation facilitates lipolysis by promoting its interaction with ATGL on lipid droplets. Targeted mutation of Ser33 to Ala (S33A) decreases ATGL-dependent lipolysis in cultured hepatocytes by reducing CGI-58-mediated ATGL activation. Importantly, a transgenic knock-in mouse strain carrying theHSD17B13S33A mutation (HSD17B1333A/A) spontaneously develops hepatic steatosis with reduced lipolysis and increased inflammation. Moreover,Hsd17B1333A/Amice are more susceptible to high-fat diet-induced nonalcoholic steatohepatitis. Finally, we find reproterol, a potential 17β-HSD13 modulator and FDA-approved drug, confers a protection against nonalcoholic steatohepatitis via PKA-mediated Ser33 phosphorylation of 17β-HSD13. Therefore, targeting the Ser33 phosphorylation site could represent a potential approach to treat NASH.
Self-mixing in microtubule-kinesin active fluid from nonuniform to uniform distribution of activity
Authors: Bate Teagan E. , Varney Megan E. , Taylor Ezra H. , Dickie Joshua H. , Chueh Chih-Che , Norton Michael M. , Wu Kun-Ta
Published: November 2022

Active fluids have applications in micromixing, but little is known about the mixing kinematics of systems with spatiotemporally-varying activity. To investigate, UV-activated caged ATP is used to activate controlled regions of microtubule-kinesin active fluid and the mixing process is observed with fluorescent tracers and molecular dyes. At low Péclet numbers (diffusive transport), the active-inactive interface progresses toward the inactive area in a diffusion-like manner that is described by a simple model combining diffusion with Michaelis-Menten kinetics. At high Péclet numbers (convective transport), the active-inactive interface progresses in a superdiffusion-like manner that is qualitatively captured by an active-fluid hydrodynamic model coupled to ATP transport. Results show that active fluid mixing involves complex coupling between distribution of active stress and active transport of ATP and reduces mixing time for suspended components with decreased impact of initial component distribution. This work will inform application of active fluids to promote micromixing in microfluidic devices.
Integrated analyses reveal evolutionarily conserved and specific injury response genes in dorsal root ganglion
Authors: Xu Lian , Chen Zhifeng , Li Xiaodi , Xu Hui , Zhang Yu , Yang Weiwei , Chen Jing , Zhang Shuqiang , Xu Lingchi , Zhou Songlin , Li Guicai , Yu Bin , Gu Xiaosong , Yang Jian
Published: November 2022

Rodent dorsal root ganglion (DRG) is widely used for studying axonal injury. Extensive studies have explored genome-wide profiles on rodent DRGs under peripheral nerve insults. However, systematic integration and exploration of these data still be limited. Herein, we re-analyzed 21 RNA-seq datasets and presented a web-based resource (DRGProfile). We identified 53 evolutionarily conserved injury response genes, including well-known injury genes (Atf3, Npy and Gal) and less-studied transcriptional factors (Arid5a, Csrnp1, Zfp367). Notably, we identified species-preference injury response candidates (e.g. Gpr151, Lipn, Anxa10 in mice; Crisp3, Csrp3, Vip, Hamp in rats). Temporal profile analysis reveals expression patterns of genes related to pre-regenerative and regenerating states. Finally, we found a large sex difference in response to sciatic nerve injury, and identified four male-specific markers (Uty, Eif2s3y, Kdm5d, Ddx3y) expressed in DRG. Our study provides a comprehensive integrated landscape for expression change in DRG upon injury which will greatly contribute to the neuroscience community.
Precise phase retrieval for propagation-based images using discrete mathematics
Authors: Pollock James A. , Morgan Kaye S. , Croton Linda C. P. , Croughan Michelle K. , Ruben Gary , Yagi Naoto , Sekiguchi Hiroshi , Kitchen Marcus J.
Published: November 2022

The ill-posed problem of phase retrieval in optics, using one or more intensity measurements, has a multitude of applications using electromagnetic or matter waves. Many phase retrieval algorithms are computed on pixel arrays using discrete Fourier transforms due to their high computational efficiency. However, the mathematics underpinning these algorithms is typically formulated using continuous mathematics, which can result in a loss of spatial resolution in the reconstructed images. Herein we investigate how phase retrieval algorithms for propagation-based phase-contrast X-ray imaging can be rederived using discrete mathematics and result in more precise retrieval for single- and multi-material objects and for spectral image decomposition. We validate this theory through experimental measurements of spatial resolution using computed tomography (CT) reconstructions of plastic phantoms and biological tissues, using detectors with a range of imaging system point spread functions (PSFs). We demonstrate that if the PSF substantially suppresses high spatial frequencies, the potential improvement from utilising the discrete derivation is limited. However, with detectors characterised by a single pixel PSF (e.g. direct, photon-counting X-ray detectors), a significant improvement in spatial resolution can be obtained, demonstrated here at up to 17%.
Pairwise and high-order dependencies in the cryptocurrency trading network
Authors: Scagliarini Tomas , Pappalardo Giuseppe , Biondo Alessio Emanuele , Pluchino Alessandro , Rapisarda Andrea , Stramaglia Sebastiano
Published: November 2022

In this paper we analyse the effects of information flows in cryptocurrency markets. We first define a cryptocurrency trading network, i.e. the network made using cryptocurrencies as nodes and the Granger causality among their weekly log returns as links, later we analyse its evolution over time. In particular, with reference to years 2020 and 2021, we study the logarithmic US dollar price returns of the cryptocurrency trading network using both pairwise and high-order statistical dependencies, quantified by Granger causality and O-information, respectively. With reference to the former, we find that it shows peaks in correspondence of important events, like e.g., Covid-19 pandemic turbulence or occasional sudden prices rise. The corresponding network structure is rather stable, across weekly time windows in the period considered and the coins are the most influential nodes in the network. In the pairwise description of the network, stable coins seem to play a marginal role whereas, turning high-order dependencies, they appear in the highest number of synergistic information circuits, thus proving that they play a major role for high order effects. With reference to redundancy and synergy with the time evolution of the total transactions in US dollars, we find that their large volume in the first semester of 2021 seems to have triggered a transition in the cryptocurrency network toward a more complex dynamical landscape. Our results show that pairwise and high-order descriptions of complex financial systems provide complementary information for cryptocurrency analysis.
Penalty feet positioning rule modification and laterality effect on soccer goalkeepers’ diving kinematics
Authors: Monteiro Rafael Luiz Martins , Bedo Bruno Luiz Souza , Monteiro Pedro Henrique Martins , de Andrade Felipe dos Santos Pinto , Moura Felipe Arruda , Cunha Sergio Augusto , Torres Ricardo da Silva , Memmert Daniel , Santiago Paulo Roberto Pereira
Published: November 2022

In 2019, a new rule was applied in soccer. It allows the goalkeeper to have only one foot or part of it on the goal line when the kicker hits the ball, unlike the previous rule that determined the goalkeeper should have both feet on the line. The purpose of the present study was to analyze how the change in the rule and the lower limbs laterality influences on the diving save kinematic performance in penalties. Six goalkeepers, two professionals and four amateurs, performed a total of 20 dives in the laboratory and had their force and impulse exerted by the lower limb and displacement/velocity data from the center of body mass collected through force plates and kinematic analysis. The side preference was collected through an inventory. The results showed that goalkeepers dive further (p < 0.001) and faster (p < 0.001) when diving according to the new rule. Dives for the non-dominant side presented higher values than the trials for the dominant side in mediolateral (p = 0.02) and resultant (p = 0.03) displacements. Concluding, the goalkeepers performed better with the new rule in the analyzed variables and the lower limb preference has influenced only the mediolateral and resultant displacement.
Detection of rare prostate cancer cells in human urine offers prospect of non-invasive diagnosis
Authors: Sayyadi Nima , Justiniano Irene , Wang Yan , Zheng Xianlin , Zhang Wei , Jiang Lianmei , Polikarpov Dmitry M. , Willows Robert D. , Gillatt David , Campbell Douglas , Walsh Bradley J. , Yuan Jingli , Lu Yiqing , Packer Nicolle H. , Wang Yuling , Piper James A.
Published: November 2022

Two molecular cytology approaches, (i) time-gated immunoluminescence assay (TGiA) and (ii) Raman-active immunolabeling assay (RiA), have been developed to detect prostate cancer (PCa) cells in urine from five prostate cancer patients. For TGiA, PCa cells stained by a biocompatible europium chelate antibody-conjugated probe were quantitated by automated time-gated microscopy (OSAM). For RiA, PCa cells labeled by antibody-conjugated Raman probe were detected by Raman spectrometer. TGiA and RiA were first optimized by the detection of PCa cultured cells (DU145) spiked into control urine, with TGiA-OSAM showing single-cell PCa detection sensitivity, while RiA had a limit of detection of 4–10 cells/mL. Blinded analysis of each patient urine sample, using MIL-38 antibody specific for PCa cells, was performed using both assays in parallel with control urine. Both assays detected very low abundance PCa cells in patient urine (3–20 PCa cells per mL by TGiA, 4–13 cells/mL by RiA). The normalized mean of the detected PCa cells per 1 ml of urine was plotted against the clinical data including prostate specific antigen (PSA) level and Clinical Risk Assessment for each patient. Both cell detection assays showed correlation with PSA in the high risk patients but aligned with the Clinical Assessment rather than with PSA levels of the low/intermediate risk patients. Despite the limited available urine samples of PCa patients, the data presented in this proof-of-principle work is promising for the development of highly sensitive diagnostic urine tests for PCa.
LncRNAs as biomarkers for predicting radioresistance and survival in cancer: a meta-analysis
Authors: Xie Yuxin , Han Jiaqi , Xie Keqi , Gou Qiheng
Published: November 2022

The effect of long noncoding RNAs (lncRNAs) on the radiotherapy response has been gradually revealed. This systematic review and meta-analysis aimed to evaluate the association between the function and underlying mechanism of lncRNAs in regulating the radiosensitivity and radioresistance of different tumors. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were calculated to estimate the effect of lncRNAs on cancer patient prognosis, including overall survival (OS), recurrence-free survival (RFS), disease-free survival (DFS) and progression-free survival (PFS). Collectively, 23 lncRNAs in 11 cancer types were enrolled. Of them, 13 lncRNAs were downregulated and related to radiosensitivity, 11 lncRNAs were upregulated and related to radioresistance, and 3 lncRNAs were upregulated and related to radiosensitivity in cancers. Furthermore, 17 microRNAs and 20 pathways were targeted by different lncRNAs and contributed to the cancer radiotherapy response in this meta-analysis. The individual pooled HRs (95% CIs) of downregulated radiation-resistant and upregulated radiation-resistant lncRNAs for OS were 0.49 (0.40–0.60) and 1.88 (1.26–2.79), respectively. Our results showed that lncRNAs could modulate tumor radioresistance or sensitivity by affecting radiation-related signaling pathways and serve as potential biomarkers to predict radiotherapy response.
Experimental evidence that shear bands in metallic glasses nucleate like cracks
Authors: Long Alan A. , Wright Wendelin J. , Gu Xiaojun , Thackray Anna , Nakib Mayisha , Uhl Jonathan T. , Dahmen Karin A.
Published: November 2022

Highly time-resolved mechanical measurements, modeling, and simulations show that large shear bands in bulk metallic glasses nucleate in a manner similar to cracks. When small slips reach a nucleation size, the dynamics changes and the shear band rapidly grows to span the entire sample. Smaller nucleation sizes imply lower ductility. Ductility can be increased by increasing the nucleation size relative to the maximum (“cutoff”) shear band size at the upper edge of the power law scaling range of their size distribution. This can be achieved in three ways: (1) by increasing the nucleation size beyond this cutoff size of the shear bands, (2) by keeping all shear bands smaller than the nucleation size, or (3) by choosing a sample size smaller than the nucleation size. The discussed methods can also be used to rapidly order metallic glasses according to ductility.
Selection of species specific panel of reference genes in peripheral blood mononuclear cells of native livestock species adapted to trans-Himalayan region of Leh-Ladakh
Authors: Tiwari Manish , Sodhi Monika , Verma Preeti , Vivek Prince , Kataria Ranjit S. , Niranjan Saket K. , Bharti Vijay K. , Masharing Nampher , Gujar Gayatri , Chanda Divya , Mukesh Manishi
Published: November 2022

The identification of appropriate references genes is an integral component of any gene expression-based study for getting accuracy and reliability in data interpretation. In this study, we evaluated the expression stability of 10 candidate reference genes (GAPDH, RPL4, EEF1A1, RPS9, HPRT1, UXT, RPS23, B2M, RPS15, ACTB) in peripheral blood mononuclear cells of livestock species that are adapted to high altitude hypoxia conditions of Leh-Ladakh. A total of 37 PBMCs samples from six native livestock species of Leh-Ladakh region such as Ladakhi cattle, Ladakhi yak, Ladakhi donkey, Chanthangi goat, Double hump cattle and Zanskar ponies were included in this study. The commonly used statistical algorithms such as geNorm, Normfinder, BestKeeper and RefFinder were employed to assess the stability of these RGs in all the livestock species. Our study has identified different panel of reference genes in each species; for example, EEF1A1, RPL4 in Ladakhi cattle; GAPDH, RPS9, ACTB in Ladakhi yak; HPRT1, B2M, ACTB in Ladakhi donkey; HPRT1, B2M, ACTB in Double hump camel, RPS9, HPRT1 in Changthangi goat, HPRT1 and ACTB in Zanskar ponies. To the best of our knowledge, this is the first systematic attempt to identify panel of RGs across different livestock species types adapted to high altitude hypoxia conditions. In future, the findings of the present study would be quite helpful in conducting any transcriptional studies to understand the molecular basis of high altitude adaptation of native livestock population of Leh-Ladakh.
Chemical composition of heartwood and sapwood of Tectona grandis characterized by CG/MS-PY
Authors: de Castro Vinícius Resende , Surdi Paula Gabriella , Fernandes Sergio Antonio , da Silva Berger Matheus , Vinha Zanuncio Antonio José , Zanuncio José Cola , de Oliveira Araujo Solange
Published: November 2022

Teak wood has chemical compounds that can be used for pharmaceutical and textile industries, in addition, this compounds are related to resistance to biodeterioration, color and modification processes. Heartwood and sapwood of T. grandis (teak), 15 years-old, were characterized by Py-CG/MS analysis and syringyl (S)/guaiacyl (G) ratio was evaluated. Heartwood and sapwood were pyrolyzed at 550 °C and 62 and 51 compounds were identified from them, respectively. The acetic acid (10%) and levoglucosan (26.65%) were the most abundant compound in the sapwood and heartwood, respectively. The high acetic acid content enhances the use of teak wood to production of artificial essences for perfumery, paints, dyes. While levoglucosan can be used in the manufacture of epoxy resins, antiparasitic and insecticides. The organic compounds identified include 2-methylanthraquinone as one of the main component responsible for the resistance of the teak wood to biological factors (fungi and termites). The syringyl (S)/guaiacyl (G) ratio of heartwood and sapwood was 0.51 and 0.50, respectively.
A sensitivity analysis of MHD nanofluid flow across an exponentially stretched surface with non-uniform heat flux by response surface methodology
Authors: Hussain Shahid , Rasheed Kianat , Ali Aamir , Vrinceanu Narcisa , Alshehri Ahmed , Shah Zahir
Published: November 2022

The current study investigates the MHD flow of nanofluid across an elongating surface while taking into account non-uniform heat flux. For this, we have considered the flow of a boundary layer over a stretched sheet containing (water-based) Al2O3 nanoparticles. The convective boundary conditions for temperature have been invoked. The flow created by a surface that is exponentially expanding in the presence of a magnetic field and a non-uniform heat flux has been mathematically formulated by using laws of conservation. Transformed non-dimensional systems of governing equations have been analyzed numerically by using Adam’s Bashforth predictor corrector approach. The effects of emerging parameters on the fluid velocity and temperature profiles have been further described by plotting graphs. An experimental design and a sensitivity analysis based on Response Surface Methodology (RSM) are used to examine the effects of various physical factors and the dependence of the response factors of interest on the change of the input parameter. To establish the model dependencies of the output response variables, which include the skin friction coefficient and the local Nusselt number, on the independent input parameters, which include the magnetic field parameter, the nanoparticle volume fraction, and the heat transfer Biot number, RSM is used. On the basis of statistical measures such as $$Q - Q$$

Q
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Q

residual plots, adjusted and hypothesis testing using p values, it is observed that both of our models for Skin Friction Coefficient (SFC) and the Local Nusselt Number (LNN) are best fitted. Further, it is concluded that the sensitivity of the SFC, as well as the LNN through heat transfer Biot number, is greater than that of nanoparticle volume fraction and magnetic field parameter. The SFC is sensitive to all combinations of the input parameters. At high levels of heat transfer Biot number, the LNN displays negative sensitivity via magnetic field parameters.
Synthesis of a new hydrophobic coating film from stearic acid of buffalo fat
Authors: Soliman Hanaa M. , Zahran Hamdy A.
Published: November 2022

This experiment involved the chemical conversion of pure stearic acid from buffalo adipose tissue to a waxy stearyl stearate, which was subsequently applied as a coating film to extend the shelf life of recently harvested fruits. Fat was extracted from minced adipose tissue using the dry rendering procedure, and it was then characterized. The extracted fat was hydrolyzed into a mixture of free fatty acids and glycerol. The supercritical CO2 extractor was used for stearic acid individual extraction in pure form from the free fatty acid mixture, and it was confirmed according to its melting point (69.2–70.0 °C), elemental analysis, GC–MS for esterified fatty acids. The isolated stearic acid was used for the synthesis of a new hydrophobic wax named stearyl stearate. The chemical structure of the prepared compound was established according to its elemental analysis and spectral data. The new hydrophobic wax was used as a coating film to enhance the shelf life of freshly harvested tomato fruits. Therefore, stearyl stearate solution (2.00% w/v diethyl ether) was used for tomato coating and compared to chitosan-coated tomatoes, where weight loss, pH, fruit firmness, ascorbic acid concentration, and total soluble solids were studied for a period of 15 days at 23 ± 1.0 °C and 65 ± 2.0% relative humidity. The results revealed that coating with stearyl stearate solution (2.00% w/v diethyl ether) could delay tomatoes’ ripening during the experiment condition. A sensory evaluation of the coated tomatoes was carried out and showed acceptable taste for the tomatoes that were coated with stearyl stearate. On the other hand, the acute oral toxicity of stearyl stearate using albino mice showed complete safety up to 25 g/kg mice weight.
Direct AKT activation in tumor-infiltrating lymphocytes markedly increases interferon-γ (IFN-γ) for the regression of tumors resistant to PD-1 checkpoint blockade
Authors: Santinon François , Ezzahra Bennani Fatima , Bachais Meriem , Sarabia Pacis Alain , Rudd Christopher E.
Published: November 2022

PD-1 immune checkpoint blockade against inhibitory receptors such as receptor programmed cell death-1 (PD-1), has revolutionized cancer treatment. Effective immune reactivity against tumour antigens requires the infiltration and activation of tumour-infiltrating T-cells (TILs). In this context, ligation of the antigen-receptor complex (TCR) in combination with the co-receptor CD28 activates the intracellular mediator AKT (or PKB, protein kinase B) and its downstream targets. PD-1 inhibits the activation of AKT/PKB. Given this, we assessed whether the direct activation of AKT might be effective in activating the immune system to limit the growth of tumors that are resistant to PD-1 checkpoint blockade. We found that the small molecule activator of AKT (SC79) limited growth of a B16 tumor and an EMT-6 syngeneic breast tumor model that are poorly responsive to PD-1 immunotherapy. In the case of B16 tumors, direct AKT activation induced (i) a reduction of suppressor regulatory (Treg) TILs and (ii) an increase in effector CD8+ TILs. SC79 in vivo therapy caused a major increase in the numbers of CD4+ and CD8+ TILs to express interferon-γ (IFN-γ). This effect on IFN-γ expression distinguished responsive from non-responsive anti-tumor responses and could be recapitulated ex vivo with human T-cells. In CD4+FoxP3+Treg TILs, AKT induced IFN-γ expression was accompanied by a loss of suppressor activity, the conversation to CD4+ helper Th1-like TILs and a marked reduction in phospho-SHP2. In CD8+ TILs, we observed an increase in the phospho-activation of PLC-γ. Further, the genetic deletion of the transcription factor T-bet (Tbx21) blocked the increased IFN-γ expression on all subsets while ablating the therapeutic benefits of SC79 on tumor growth. Our study shows that AKT activation therapy acts to induce IFN-γ on CD4 and CD8 TILs that is accompanied by the intra-tumoral conversation of suppressive Tregs into CD4+Th1-like T-cells and augmented CD8 responses.
Saliva metabolome alterations after acute stress
Authors: Morgan Liat , Birkler Rune Isak Dupont , Shaham-Niv Shira , Dong Yonghui , Wachsman Tal , Carmi Lior , Yakobson Boris , Adler-Abramovich Lihi , Cohen Hagit , Zohar Joseph , Bateson Melissa , Gazit Ehud
Published: November 2022

Major stress has systemic effects on the body that can have adverse consequences for physical and mental health. However, the molecular basis of these damaging effects remains incompletely understood. Here we use a longitudinal approach to characterise the acute systemic impact of major psychological stress in a pig model. We perform untargeted metabolomics on non-invasively obtained saliva samples from pigs before and 24 h after transfer to the novel physical and social environment of a slaughterhouse. The main molecular changes occurring include decreases in amino acids, B-vitamins, and amino acid-derived metabolites synthesized in B-vitamin-dependent reactions, as well as yet-unidentified metabolite features. Decreased levels of several of the identified metabolites are implicated in the pathology of human psychological disorders and neurodegenerative disease, suggesting a possible neuroprotective function. Our results provide a fingerprint of the acute effect of psychological stress on the metabolome and suggest candidate biomarkers with potential roles in stress-related disorders.
Study on crack evolutional behavior of rocks in triaxial compression based on colony growth dynamics model
Authors: Deng Naifu , Qiao Lan , Li Qingwen , Hao Jiawang , Wei Mengxi , Zhang Qinglong
Published: November 2022

The crack propagation behavior of rock during compression involves complex mechanisms. Describing the growth behavior of a large number of cracks with conventional mechanical models is a major challenge. Therefore, in this work, we propose a new method to describe crack growth behavior by considering crack bodies as free voxels that can expand and coalesce within a rock sample according to certain rules. Specifically, we first propose a crack growth model that quantitatively describes the crack growth ratio and crack growth rate, which are integrally related to the loading rate, internal friction angle, cohesion, initial porosity, and confining stress. Second, to avoid the complex analytical process of the traditional mechanical model in solving the propagation directions of multiple cracks, we introduce a method for determining the crack growth directions of shearing failure based on the colony growth assumption. This method defines the crack propagation direction as a synthetic vector of the inertial direction, the attractive direction, the Coulomb direction, and the edge direction. Moreover, a new mathematical description method of fracture energy and plastic energy is proposed to calculate the crack growth at each time step. The simulation results show that our crack growth model for shearing failure agrees well with the experimental results and explains the fracture behavior and transformation law of cracks to some extent.
MicroRNA-874 targets phosphomevalonate kinase and inhibits cancer cell growth via the mevalonate pathway
Authors: Aersilan Alimasi , Hashimoto Naoko , Yamagata Kazuyuki , Yokoyama Masataka , Nakayama Akitoshi , Shi Xiaoyan , Nagano Hidekazu , Sakuma Ikki , Nohata Nijiro , Kinoshita Takashi , Seki Naohiko , Rahmutulla Bahityar , Kaneda Atsushi , Zhahara Siti Nurul , Gong Yingbo , Nishimura Motoi , Kawauchi Shoichiro , Kawakami Eiryo , Tanaka Tomoaki
Published: November 2022

The microRNA (miR) miR-874, a potential tumour suppressor, causes cell death via target gene suppression in various cancer types. Mevalonate pathway inhibition also causes cell death in breast cancer. However, the relationship between the mevalonate pathway and miR-874-induced apoptosis or its association with the tumour suppressor p53 has not been elucidated. We identified phosphomevalonate kinase (PMVK), a key mevalonate pathway enzyme, and sterol regulatory element-binding factor 2 (SREBF2), the master cholesterol biosynthesis regulator, as direct miR‑874 targets. Next-generation sequencing analysis revealed a significant miR-874-mediated downregulation of PMVK and SREBF2 gene expression and p53 pathway enrichment. Luciferase reporter assays showed that miR-874 directly regulated PMVK and SREBF2. miR-874-induced apoptosis was p53 dependent, and single-cell RNA sequencing analysis demonstrated that miR-874 transfection resulted in apoptosis and p53 pathway activation. Downregulation of PMVK expression also caused cell cycle arrest and p53 pathway activation, which was rescued by geranylgeranyl pyrophosphate (GGPP) supplementation. Analysis of The Cancer Genome Atlas (TCGA) database indicated a negative correlation between miR-874 and PMVK expression and between miR-874 and SREBF2 expression. These findings suggest that miR-874 suppresses the mevalonate pathway by targeting SREBF2 and PMVK, resulting in GGPP depletion, which activates the p53 pathway and promotes cycle arrest or apoptosis.
Specimen mammography for intraoperative margin assessment in breast conserving surgery: a meta-analysis
Authors: Lin Chen , Wang Kai-yue , Chen Hai-lang , Xu Yu-hua , Pan Tao , Chen Yi-ding
Published: November 2022

In breast conserving surgery (BCS), specimen mammography is one of the most widely used intraoperative methods of assessing margin status. We performed a meta-analysis to evaluate the diagnostic accuracy of specimen mammography. Literature databases including PubMed, Cochrane Library, Web of Science, and EMBASE were searched prior to Jun 2022. A total of 1967 patients were included from 20 studies. A pooled analysis, heterogeneity testing, threshold effect testing, publication bias analysis, and subgroup analyses were performed from extracted data. The pooled weighted values were a sensitivity of 0.55 (95% confidence interval [CI], 0.47–0.63), a specificity of 0.85 (95% CI, 0.78–0.90), a diagnostic odds ratio of 7 (95% CI, 4–12), and a pooled positive likelihood ratio of 3.7 (95% CI 2.6–5.5). The area under the receiver operator characteristic curve was 0.75 (95% CI 0.71–0.78). In the subgroup analysis, the pooled specificity in the positive margin defined as tumor at margin subgroup was lower than the other positive margin definition subgroup (0.82 [95% CI: 0.71, 0.92] vs. 0.87 [95% CI: 0.80, 0.94], p = 0.01). Our findings indicated that specimen mammography was an accurate intraoperative imaging technique for margin assessment in BCS.
Overexpression of VEGF in dermal fibroblast cells accelerates the angiogenesis and wound healing function: in vitro and in vivo studies
Authors: Shams Forough , Moravvej Hamideh , Hosseinzadeh Simzar , Mostafavi Ebrahim , Bayat Hadi , Kazemi Bahram , Bandehpour Mojgan , Rostami Elnaz , Rahimpour Azam , Moosavian Hamidreza
Published: November 2022

Fibroblasts are the main cells of connective tissue and have pivotal roles in the proliferative and maturation phases of wound healing. These cells can secrete various cytokines, growth factors, and collagen. Vascular endothelial growth factor (VEGF) is a unique factor in the migration process of fibroblast cells through induces wound healing cascade components such as angiogenesis, collagen deposition, and epithelialization. This study aimed to create VEGF165 overexpressing fibroblast cells to evaluate angiogenesis function in wound healing. In vitro, a novel recombinant expression vector, pcDNA3.1(-)-VEGF, was produced and transfected into the fibroblast cells. Following selecting fibroblast cells with hygromycin, recombinant cells were investigated in terms of VEGF expression by quantifying and qualifying methods. Mechanical, physical, and survival properties of polyurethane-cellulose acetate (PU-CA) scaffold were investigated. Finally, in vivo, the angiogenic potential was evaluated in four groups containing control, PU-CA, PU-CA with fibroblast cells, and VEGF-expressing cells on days 0, 2, 5, 12 and 15. Wound biopsies were harvested and the healing process was histopathologically evaluated on different days. qRT-PCR showed VEGF overexpression (sevenfold) in genetically-manipulated cells compared to fibroblast cells. Recombinant VEGF expression was also confirmed by western blotting. Manipulated fibroblast cells represented more angiogenesis than other groups on the second day after surgery, which was also confirmed by the antiCD31 antibody. The percentage of wound closure area on day 5 in genetically-manipulated Hu02 and Hu02 groups showed a significant reduction of wound area compared to other groups. These findings indicate that overexpression of VEGF165 in fibroblast cells results in enhanced angiogenesis and formation of granulated tissue in the early stage of the healing process, which can show its therapeutic potential in patients with impaired wound healing and also provide functional support for gene therapy.
Integrative molecular analyses define correlates of high B7-H3 expression in metastatic castrate-resistant prostate cancer
Authors: Shi Xiaolei , Day Abderrahman , Bergom Hannah E. , Tape Sydney , Baca Sylvan C. , Sychev Zoi E. , Larson Gabrianne , Bozicevich Asha , Drake Justin M. , Zorko Nicholas , Wang Jinhua , Ryan Charles J. , Antonarakis Emmanuel S. , Hwang Justin
Published: November 2022

B7-H3 (CD276) is an immune checkpoint overexpressed in prostate cancer with minimal expression in normal tissues and associated with poor prognosis, making it an excellent therapy target. We interrogated B7-H3 expression and its regulation in metastatic castration-resistant prostate cancer (mCRPC). We found greater expression of B7-H3 transcript relative to other immunotherapy targets (CTLA-4, PD-L1/2), including in tumors that lacked expression of prostate-specific membrane antigen (PSMA). Enzalutamide-resistant mCRPC cells demonstrated increased amounts of B7-H3, and this was associated with resistance signaling pathways. Using a machine-learning algorithm, the gene network of B7-H3 was strongly correlated with androgen receptor (AR) and AR co-factor (HOXB13, FOXA1) networks. In mCRPC samples, the B7-H3 promoter and distal enhancer regions exhibited enhanced transcriptional activity and were directly bound by AR and its co-factors. Altogether, our study characterizes molecular profiles and epigenetic regulation of B7-H3-expressing mCRPC tumors, which informs optimal precision-oncology approaches for mCRPC patients.
Covid-19 vaccination and menstrual cycle length in the Apple Women’s Health Study
Authors: Gibson Elizabeth A. , Li Huichu , Fruh Victoria , Gabra Malaika , Asokan Gowtham , Jukic Anne Marie Z. , Baird Donna D. , Curry Christine L. , Fischer-Colbrie Tyler , Onnela Jukka-Pekka , Williams Michelle A. , Hauser Russ , Coull Brent A. , Mahalingaiah Shruthi
Published: November 2022

COVID-19 vaccination may be associated with change in menstrual cycle length following vaccination. We estimated covariate-adjusted differences in mean cycle length (MCL), measured in days, between pre-vaccination cycles, vaccination cycles, and post-vaccination cycles within vaccinated participants who met eligibility criteria in the Apple Women’s Health Study, a longitudinal mobile-application-based cohort of people in the U.S. with manually logged menstrual cycles. A total of 9652 participants (8486 vaccinated; 1166 unvaccinated) contributed 128,094 cycles (median = 10 cycles per participant; inter-quartile range: 4–22). Fifty-five percent of vaccinated participants received Pfizer-BioNTech’s mRNA vaccine, 37% received Moderna’s mRNA vaccine, and 8% received the Johnson & Johnson/Janssen (J&J) vaccine. COVID-19 vaccination was associated with a small increase in MCL for cycles in which participants received the first dose (0.50 days, 95% CI: 0.22, 0.78) and cycles in which participants received the second dose (0.39 days, 95% CI: 0.11, 0.67) of mRNA vaccines compared with pre-vaccination cycles. Cycles in which the single dose of J&J was administered were, on average, 1.26 days longer (95% CI: 0.45, 2.07) than pre-vaccination cycles. Post-vaccination cycles returned to average pre-vaccination length. Estimated follicular phase vaccination was associated with increased MCL in cycles in which participants received the first dose (0.97 days, 95% CI: 0.53, 1.42) or the second dose (1.43 days, 95% CI: 1.06, 1.80) of mRNA vaccines or the J&J dose (2.27 days, 95% CI: 1.04, 3.50), compared with pre-vaccination cycles. Menstrual cycle change following COVID-19 vaccination appears small and temporary and should not discourage individuals from becoming vaccinated.
Self-supervised machine learning for live cell imagery segmentation
Authors: Robitaille Michael C. , Byers Jeff M. , Christodoulides Joseph A. , Raphael Marc P.
Published: November 2022

Segmenting single cells is a necessary process for extracting quantitative data from biological microscopy imagery. The past decade has seen the advent of machine learning (ML) methods to aid in this process, the overwhelming majority of which fall under supervised learning (SL) which requires vast libraries of pre-processed, human-annotated labels to train the ML algorithms. Such SL pre-processing is labor intensive, can introduce bias, varies between end-users, and has yet to be shown capable of robust models to be effectively utilized throughout the greater cell biology community. Here, to address this pre-processing problem, we offer a self-supervised learning (SSL) approach that utilizes cellular motion between consecutive images to self-train a ML classifier, enabling cell and background segmentation without the need for adjustable parameters or curated imagery. By leveraging motion, we achieve accurate segmentation that trains itself directly on end-user data, is independent of optical modality, outperforms contemporary SL methods, and does so in a completely automated fashion—thus eliminating end-user variability and bias. To the best of our knowledge, this SSL algorithm represents a first of its kind effort and has appealing features that make it an ideal segmentation tool candidate for the broader cell biology research community.
Identification of a queen primer pheromone in higher termites
Authors: Dolejšová Klára , Křivánek Jan , Štáfková Jitka , Horáček Natan , Havlíčková Jana , Roy Virginie , Kalinová Blanka , Roy Amit , Kyjaková Pavlína , Hanus Robert
Published: November 2022

It is long established that queens of social insects, including termites, maintain their reproductive dominance with queen primer pheromones (QPPs). Yet, the QPP chemistry has only been elucidated in a single species of lower termites. By contrast, the most diversified termite family Termitidae (higher termites), comprising over 70% of termite species, has so far resisted all attempts at QPP identification. Here, we show that the queen- and egg-specific sesquiterpene (3R,6E)-nerolidol acts as the QPP in the higher termite Embiratermes neotenicus. This species has a polygynous breeding system, in which the primary queen is replaced by multiple neotenic queens of parthenogenetic origin. We demonstrate that (3R,6E)-nerolidol suppresses the development of these parthenogenetic queens and thus mimics the presence of mature queen(s). It acts as an airborne signal and may be used to optimize the number of queens, thus being the key regulatory element in the special breeding system of E. neotenicus.
Hidden magnetic texture in the pseudogap phase of high-Tc YBa2Cu3O6.6
Authors: Bounoua Dalila , Sidis Yvan , Loew Toshinao , Bourdarot Frédéric , Boehm Martin , Steffens Paul , Mangin-Thro Lucile , Balédent Victor , Bourges Philippe
Published: November 2022

Despite decades of intense research, the enigmatic pseudo-gap (PG) phase of superconducting cuprates remains unsolved. In the last 15 years, various symmetry breaking states were discovered in the PG phase, including an intra-unit cell (IUC) magnetism, which preserves the lattice translational (LT) symmetry but breaks the time-reversal and parity symmetries, and an additional incipient charge density wave breaking the LT symmetry. However, none of these states can (alone) account for the partial gapping of the Fermi surface. Here we report a hidden LT-breaking magnetism using polarized neutron diffraction. Our measurements reveal magnetic correlations, in two different underdoped YBa2Cu3O6.6 single crystals that set in at the PG onset temperature with (i) a planar propagation wave vector (π, 0) ≡ (0, π), yielding a doubling or quadrupling of the magnetic unit cell and (ii) magnetic moments mainly pointing perpendicular to the CuO2 layers. The LT-breaking magnetism is at short-range suggesting the formation of clusters of 5–6 unit cells. Together with the previously reported IUC magnetism, it yields a hidden magnetic texture of the CuO2 unit cells hosting loop currents, forming large supercells that may be helpful for elucidating the PG puzzle.