bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paladin, overexpressed in colon cancer, is required for actin polymerisation and liver metastasis dissemination
Authors: Rademaker Gilles , Costanza Brunella , Pyr dit Ruys Sébastien , Peiffer Raphaël , Agirman Ferman , Maloujahmoum Naïma , Vertommen Didier , Turtoi Andrei , Bellahcène Akeila , Castronovo Vincent , Peulen Olivier 
Published: July 2022

Abstract
Introduction
Colorectal cancer remains a public health issue and most colon cancer patients succumb to the development of metastases. Using a specific protocol of pressure-assisted interstitial fluid extrusion to recover soluble biomarkers, we identified paladin as a potential colon cancer liver metastases biomarker.

Methods
Using shRNA gene knockdown, we explored the biological function of paladin in colon cancer cells and investigated the phospho-proteome within colon cancer cells. We successively applied in vitro migration assays, in vivo metastasis models and co-immunoprecipitation experiments.

Results
We discovered that paladin is required for colon cancer cell migration and metastasis, and that paladin depletion altered the phospho-proteome within colon cancer cells. Data are available via ProteomeXchange with identifier PXD030803. Thanks to immunoprecipitation experiments, we demonstrated that paladin, was interacting with SSH1, a phosphatase involved in colon cancer metastasis. Finally, we showed that paladin depletion in cancer cells results in a less dynamic actin cytoskeleton.

Conclusions
Paladin is an undervalued protein in oncology. This study highlights for the first time that, paladin is participating in actin cytoskeleton remodelling and is required for efficient cancer cell migration.
Cross-reactivity of eight SARS-CoV-2 variants rationally predicts immunogenicity clustering in sarbecoviruses
Authors: Li Qianqian , Zhang Li , Liang Ziteng , Wang Nan , Liu Shuo , Li Tao , Yu Yuanling , Cui Qianqian , Wu Xi , Nie Jianhui , Wu Jiajing , Cui Zhimin , Lu Qiong , Wang Xiangxi , Huang Weijin , Wang Youchun 
Published: July 2022

AbstractA steep rise in Omicron reinfection cases suggests that this variant has increased immune evasion ability. To evaluate its antigenicity relationship with other variants, antisera from guinea pigs immunized with spike protein of SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) were cross-tested against pseudotyped variants. The neutralization activity against Omicron was markedly reduced when other VOCs or VOIs were used as immunogens, and Omicron (BA.1)-elicited sera did not efficiently neutralize the other variants. However, a Beta or Omicron booster, when administered as the 4th dose 3-months after the 3rd dose of any of the variants, could elicit broad neutralizing antibodies against all of the current variants including Omicron BA.1. Further analysis with 280 available antigen–antibody structures and quantification of immune escape from 715 reported neutralizing antibodies provide explanations for the observed differential immunogenicity. Three distinct clades predicted using an in silico algorithm for clustering of sarbecoviruses based on immune escape provide key information for rational design of vaccines.
Amino acid utilization allows intestinal dominance ofLactobacillus amylovorus
Authors: Jing Yujia , Mu Chunlong , Wang Huisong , Shen Junhua , Zoetendal Erwin G , Zhu Weiyun 
Published: July 2022

AbstractThe mammalian intestine harbors heterogeneous distribution of microbes among which specific taxa (e.g. Lactobacillus) dominate across mammals. Deterministic factors such as nutrient availability and utilization may affect microbial distributions. Due to physiological complexity, mechanisms linking nutrient utilization and the dominance of key taxa remain unclear. Lactobacillus amylovorus is a predominant species in the small intestine of pigs. Employing a pig model, we found that the small intestine was dominated by Lactobacillus and particularly L. amylovorus, and enriched with peptide-bound amino acids (PBAAs), all of which were further boosted after a peptide-rich diet. To investigate the bacterial growth dominance mechanism, a representative strain L. amylovorus S1 was isolated from the small intestine and anaerobically cultured in media with free amino acids or peptides as sole nitrogen sources. L. amylovorus S1 grew preferentially with peptide-rich rather than amino acid-rich substrates, as reflected by enhanced growth and PBAA utilization, and peptide transporter upregulations. Utilization of free amino acids (e.g. methionine, valine, lysine) and expressions of transporters and metabolic enzymes were enhanced simultaneously in peptide-rich substrate. Additionally, lactate was elevated in peptide-rich substrates while acetate in amino acid-rich substrates, indicating distinct metabolic patterns depending on substrate forms. These results suggest that an increased capability of utilizing PBAAs contributes to the dominance of L. amylovorus, indicating amino acid utilization as a deterministic factor affecting intestinal microbial distribution. These findings may provide new insights into the microbe-gut nutrition interplay and guidelines for dietary manipulations toward gut health especially small intestine health.
ARHGEF2/EDN1 pathway participates in ER stress-related drug resistance of hepatocellular carcinoma by promoting angiogenesis and malignant proliferation
Authors: Zhu Yue , Liu Weiwei , Wang Zishu , Wang Yanfei , Tan Chaisheng , Pan Zhipeng , Wang Anqi , Liu Jiatao , Sun Guoping 
Published: July 2022

AbstractEndoplasmic reticulum (ER) stress is widely involved in the drug resistance of hepatocellular carcinoma (HCC), but the mechanism of ER stress-induced drug resistance involves multiple signaling pathways that cannot be fully explained. Exploring genes associated with ER stress could yield a novel therapeutic target for ER stress-induced drug resistance. By analyzing RNA-sequencing, ATAC-sequencing, and Chip-sequencing data of Tunicamycin (TM)-treated or untreated HCC cells, we found that Rho guanine nucleotide exchange factor 2 (ARHGEF2) is upregulated in HCC cells with ER stress. ARHGEF2 plays an active role in tumor malignant progression. Notwithstanding, no research has been done on the link between ER stress and ARHGEF2. The function of ARHGEF2 as a novel downstream effector of ER stress in the angiogenesis and treatment resistance of HCC was revealed in this work. ARHGEF2 overexpression was linked to malignant development and a poor prognosis in HCC. ER stress stimulates the expression of ARHGEF2 through upregulation of ZNF263. Elevated ARHGEF2 accelerates HCC angiogenesis via the EDN1 pathway, enhances HCC cell proliferation and tumor growth both in vitro and in vivo, and contributes to ER stress-related treatment resistance. HCC cell growth was more inhibited when ARHGEF2 knockdown was paired with targeted medicines. Collectively, we uncovered a previously hidden mechanism where ARHGEF2/EDN1 pathway promotes angiogenesis and participates in ER stress-related drug resistance in HCC.
Emerging mechanisms of pyroptosis and its therapeutic strategy in cancer
Authors: Lu Liqing , Zhang Ye , Tan Xuemei , Merkher Yulia , Leonov Sergey , Zhu Li , Deng Yalan , zhang Huajun , Zhu Dandan , Tan Yuying , Fu Ying , Liu Ting , Chen Yongheng 
Published: July 2022

AbstractPyroptosis, a type of inflammatory programmed cell death, is triggered by caspase cleavage of gasdermin family proteins. Based on accumulating evidence, pyroptosis is closely associated with tumour development, but the molecular mechanism underlying pyroptosis activation and the signalling pathways regulated by pyroptosis remain unclear. In this review, we first briefly introduce the definition, morphological characteristics, and activation pathways of pyroptosis and the effect of pyroptosis on anticancer immunity. Then we review recent progress concerning the complex role of pyroptosis in various tumours. Importantly, we summarise various FDA-approved chemotherapy drugs or natural compounds that exerted antitumor properties by inducing pyroptosis of cancer cells. Moreover, we also focus on the current application of nanotechnology-induced pyroptosis in tumour therapy. In addition, some unsolved problems and potential future research directions are also raised.
Competing paradigms of obesity pathogenesis: energy balance versus carbohydrate-insulin models
Authors: Ludwig David S. , Apovian Caroline M. , Aronne Louis J. , Astrup Arne , Cantley Lewis C. , Ebbeling Cara B. , Heymsfield Steven B. , Johnson James D. , King Janet C. , Krauss Ronald M. , Taubes Gary , Volek Jeff S. , Westman Eric C. , Willett Walter C. , Yancy William S. , Friedman Mark I. 
Published: July 2022

AbstractThe obesity pandemic continues unabated despite a persistent public health campaign to decrease energy intake (“eat less”) and increase energy expenditure (“move more”). One explanation for this failure is that the current approach, based on the notion of energy balance, has not been adequately embraced by the public. Another possibility is that this approach rests on an erroneous paradigm. A new formulation of the energy balance model (EBM), like prior versions, considers overeating (energy intake > expenditure) the primary cause of obesity, incorporating an emphasis on “complex endocrine, metabolic, and nervous system signals” that control food intake below conscious level. This model attributes rising obesity prevalence to inexpensive, convenient, energy-dense, “ultra-processed” foods high in fat and sugar. An alternative view, the carbohydrate-insulin model (CIM), proposes that hormonal responses to highly processed carbohydrates shift energy partitioning toward deposition in adipose tissue, leaving fewer calories available for the body’s metabolic needs. Thus, increasing adiposity causes overeating to compensate for the sequestered calories. Here, we highlight robust contrasts in how the EBM and CIM view obesity pathophysiology and consider deficiencies in the EBM that impede paradigm testing and refinement. Rectifying these deficiencies should assume priority, as a constructive paradigm clash is needed to resolve long-standing scientific controversies and inform the design of new models to guide prevention and treatment. Nevertheless, public health action need not await resolution of this debate, as both models target processed carbohydrates as major drivers of obesity.
Win-win opportunities combining high yields with high multi-taxa biodiversity in tropical agroforestry
Authors: Wurz Annemarie , Tscharntke Teja , Martin Dominic Andreas , Osen Kristina , Rakotomalala Anjaharinony A. N. A. , Raveloaritiana Estelle , Andrianisaina Fanilo , Dröge Saskia , Fulgence Thio Rosin , Soazafy Marie Rolande , Andriafanomezantsoa Rouvah , Andrianarimisa Aristide , Babarezoto Fenohaja Soavita , Barkmann Jan , Hänke Hendrik , Hölscher Dirk , Kreft Holger , Rakouth Bakolimalala , Guerrero-Ramírez Nathaly R. , Ranarijaona Hery Lisy Tiana , Randriamanantena Romual , Ratsoavina Fanomezana Mihaja , Raveloson Ravaomanarivo Lala Harivelo , Grass Ingo 
Published: July 2022

AbstractResolving ecological-economic trade-offs between biodiversity and yields is a key challenge when addressing the biodiversity crisis in tropical agricultural landscapes. Here, we focused on the relation between seven different taxa (trees, herbaceous plants, birds, amphibians, reptiles, butterflies, and ants) and yields in vanilla agroforests in Madagascar. Agroforests established in forests supported overall 23% fewer species and 47% fewer endemic species than old-growth forests, and 14% fewer endemic species than forest fragments. In contrast, agroforests established on fallows had overall 12% more species and 38% more endemic species than fallows. While yields increased with vanilla vine density and length, non-yield related variables largely determined biodiversity. Nonetheless, trade-offs existed between yields and butterflies as well as reptiles. Vanilla yields were generally unrelated to richness of trees, herbaceous plants, birds, amphibians, reptiles, and ants, opening up possibilities for conservation outside of protected areas and restoring degraded land to benefit farmers and biodiversity alike.
Overload wave-memory induces amnesia of a self-propelled particle
Authors: Hubert Maxime , Perrard Stéphane , Vandewalle Nicolas , Labousse Matthieu 
Published: July 2022

AbstractInformation storage is a key element of autonomous, out-of-equilibrium dynamics, especially for biological and synthetic active matter. In synthetic active matter however, the implementation of internal memory in self-propelled systems is often absent, limiting our understanding of memory-driven dynamics. Recently, a system comprised of a droplet generating its guiding wavefield appeared as a prime candidate for such investigations. Indeed, the wavefield, propelling the droplet, encodes information about the droplet trajectory and the amount of information can be controlled by a single scalar experimental parameter. In this work, we show numerically and experimentally that the accumulation of information in the wavefield induces the loss of time correlations, where the dynamics can then be described by a memory-less process. We rationalize the resulting statistical behavior by defining an effective temperature for the particle dynamics where the wavefield acts as a thermostat of large dimensions, and by evidencing a minimization principle of the generated wavefield.
Reduction of primary graft dysfunction using cytokine adsorption during organ preservation and after lung transplantation
Authors: Ghaidan Haider , Stenlo Martin , Niroomand Anna , Mittendorfer Margareta , Hirdman Gabriel , Gvazava Nika , Edström Dag , Silva Iran A. N. , Broberg Ellen , Hallgren Oskar , Olm Franziska , Wagner Darcy E. , Pierre Leif , Hyllén Snejana , Lindstedt Sandra 
Published: July 2022

AbstractDespite improvements, lung transplantation remains hampered by both a scarcity of donor organs and by mortality following primary graft dysfunction (PGD). Since acute respiratory distress syndrome (ARDS) limits donor lungs utilization, we investigated cytokine adsorption as a means of treating ARDS donor lungs. We induced mild to moderate ARDS using lipopolysaccharide in 16 donor pigs. Lungs were then treated with or without cytokine adsorption during ex vivo lung perfusion (EVLP) and/or post-transplantation using extracorporeal hemoperfusion. The treatment significantly decreased cytokine levels during EVLP and decreased levels of immune cells post-transplantation. Histology demonstrated fewer signs of lung injury across both treatment periods and the incidence of PGD was significantly reduced among treated animals. Overall, cytokine adsorption was able to restore lung function and reduce PGD in lung transplantation. We suggest this treatment will increase the availability of donor lungs and increase the tolerability of donor lungs in the recipient.
Dirac-source diode with sub-unity ideality factor
Authors: Myeong Gyuho , Shin Wongil , Sung Kyunghwan , Kim Seungho , Lim Hongsik , Kim Boram , Jin Taehyeok , Park Jihoon , Lee Taehun , Fuhrer Michael S. , Watanabe Kenji , Taniguchi Takashi , Liu Fei , Cho Sungjae 
Published: July 2022

AbstractAn increase in power consumption necessitates a low-power circuit technology to extend Moore’s law. Low-power transistors, such as tunnel field-effect transistors (TFETs), negative-capacitance field-effect transistors (NC-FETs), and Dirac-source field-effect transistors (DS-FETs), have been realised to break the thermionic limit of the subthreshold swing (SS). However, a low-power rectifier, able to overcome the thermionic limit of an ideality factor (η) of 1 at room temperature, has not been proposed yet. In this study, we have realised a DS diode based on graphene/MoS2/graphite van der Waals heterostructures, which exhibits a steep-slope characteristic curve, by exploiting the linear density of states (DOSs) of graphene. For the developed DS diode, we obtained η < 1 for more than four decades of drain current (ηave_4dec < 1) with a minimum value of 0.8, and a rectifying ratio exceeding 108. The realisation of a DS diode represents an additional step towards the development of low-power electronic circuits.
Tracing the origin of lithium in Li-ion batteries using lithium isotopes
Authors: Desaulty Anne-Marie , Monfort Climent Daniel , Lefebvre Gaétan , Cristiano-Tassi Antonella , Peralta David , Perret Sébastien , Urban Anthony , Guerrot Catherine 
Published: July 2022

AbstractRechargeable lithium-ion batteries (LIB) play a key role in the energy transition towards clean energy, powering electric vehicles, storing energy on renewable grids, and helping to cut emissions from transportation and energy sectors. Lithium (Li) demand is estimated to increase considerably in the near future, due to the growing need for clean-energy technologies. The corollary is that consumer expectations will also grow in terms of guarantees on the origin of Li and the efforts made to reduce the environmental and social impact potentially associated with its extraction. Today, the LIB-industry supply chain is very complex, making it difficult for end users to ensure that Li comes from environmentally and responsible sources. Using an innovative geochemical approach based on the analysis of Li isotopes of raw and processed materials, we show that Li isotope ‘fingerprints’ are a useful tool for determining the origin of lithium in LIB. This sets the stage for a new method ensuring the certification of Li in LIB.
Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines
Authors: Wang Li , Kainulainen Markus H. , Jiang Nannan , Di Han , Bonenfant Gaston , Mills Lisa , Currier Michael , Shrivastava-Ranjan Punya , Calderon Brenda M. , Sheth Mili , Mann Brian R. , Hossain Jaber , Lin Xudong , Lester Sandra , Pusch Elizabeth A. , Jones Joyce , Cui Dan , Chatterjee Payel , Jenks M. Harley , Morantz Esther K. , Larson Gloria P. , Hatta Masato , Harcourt Jennifer L. , Tamin Azaibi , Li Yan , Tao Ying , Zhao Kun , Lacek Kristine , Burroughs Ashley , Wang Wei , Wilson Malania , Wong Terianne , Park So Hee , Tong Suxiang , Barnes John R. , Tenforde Mark W. , Self Wesley H. , Shapiro Nathan I. , Exline Matthew C. , Files D. Clark , Gibbs Kevin W. , Hager David N. , Patel Manish , Halpin Alison L. , McMullan Laura K. , Lee Justin S. , Xia Hongjie , Xie Xuping , Shi Pei-Yong , Davis C. Todd , Spiropoulou Christina F. , Thornburg Natalie J. , Oberste M. Steven , Dugan Vivien G. ,   SSEV Bioinformatics Working Group, Batra Dhwani , Beck Andrew S. , Caravas Jason , Chau Reina , Cintron-Moret Roxana , Cook Peter W. , Gerhart Jonathan , Gulvik Christopher A. , Hassell Norman , Howard Dakota , Knipe Kristen , Kondor Rebecca J. , Kovacs Nicholas A. , Moser Kara , Reddy-Nagilla Roopa , Paden Clinton R. , Rambo-Martin Benjamin , Mathew Sandra , Schmerer Matthew W. , Shepard Samuel S. , Shirk Philip , Stanton Richard A. , Stark Thomas J. , Sula Erisa , Tymeckia Kendall , Unoarumhi Yvette , Subbalakshmi Voleti , Zheng Xiao-yu , Wentworth David E. , Zhou Bin 
Published: July 2022

AbstractThe evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccine-mediated protection from disease. To ascertain and rank the risk of VOCs and VOIs, we analyze the ability of 14 variants (614G, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Eta, Theta, Iota, Kappa, Lambda, Mu, and Omicron) to escape from mRNA vaccine-induced antibodies. The variants show differential reductions in neutralization and replication by post-vaccination sera. Although the Omicron variant (BA.1, BA.1.1, and BA.2) shows the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retain moderate neutralizing activity against that variant. Therefore, vaccination remains an effective strategy during the COVID-19 pandemic.
Targeting de novo lipogenesis and the Lands cycle induces ferroptosis in KRAS-mutant lung cancer
Authors: Bartolacci Caterina , Andreani Cristina , Vale Gonçalo , Berto Stefano , Melegari Margherita , Crouch Anna Colleen , Baluya Dodge L. , Kemble George , Hodges Kurt , Starrett Jacqueline , Politi Katerina , Starnes Sandra L. , Lorenzini Daniele , Raso Maria Gabriela , Solis Soto Luisa M. , Behrens Carmen , Kadara Humam , Gao Boning , Wistuba Ignacio I. , Minna John D. , McDonald Jeffrey G. , Scaglioni Pier Paolo 
Published: July 2022

AbstractMutant KRAS (KM), the most common oncogene in lung cancer (LC), regulates fatty acid (FA) metabolism. However, the role of FA in LC tumorigenesis is still not sufficiently characterized. Here, we show that KMLC has a specific lipid profile, with high triacylglycerides and phosphatidylcholines (PC). We demonstrate that FASN, the rate-limiting enzyme in FA synthesis, while being dispensable in EGFR-mutant or wild-type KRAS LC, is required for the viability of KMLC cells. Integrating lipidomic, transcriptomic and functional analyses, we demonstrate that FASN provides saturated and monounsaturated FA to the Lands cycle, the process remodeling oxidized phospholipids, such as PC. Accordingly, blocking either FASN or the Lands cycle in KMLC, promotes ferroptosis, a reactive oxygen species (ROS)- and iron-dependent cell death, characterized by the intracellular accumulation of oxidation-prone PC. Our work indicates that KM dictates a dependency on newly synthesized FA to escape ferroptosis, establishing a targetable vulnerability in KMLC.
Thermodynamics-guided alloy and process design for additive manufacturing
Authors: Sun Zhongji , Ma Yan , Ponge Dirk , Zaefferer Stefan , Jägle Eric A. , Gault Baptiste , Rollett Anthony D. , Raabe Dierk 
Published: July 2022

AbstractIn conventional processing, metals go through multiple manufacturing steps including casting, plastic deformation, and heat treatment to achieve the desired property. In additive manufacturing (AM) the same target must be reached in one fabrication process, involving solidification and cyclic remelting. The thermodynamic and kinetic differences between the solid and liquid phases lead to constitutional undercooling, local variations in the solidification interval, and unexpected precipitation of secondary phases. These features may cause many undesired defects, one of which is the so-called hot cracking. The response of the thermodynamic and kinetic nature of these phenomena to high cooling rates provides access to the knowledge-based and tailored design of alloys for AM. Here, we illustrate such an approach by solving the hot cracking problem, using the commercially important IN738LC superalloy as a model material. The same approach could also be applied to adapt other hot-cracking susceptible alloy systems for AM.