bluuebunny/crossref_metadata_2025_split huggingface dataset:
A single-cell transcriptomic landscape of innate and adaptive intratumoral immunity in triple negative breast cancer during chemo- and immunotherapies
Authors: Carpen Laura , Falvo Paolo , Orecchioni Stefania , Mitola Giulia , Hillje Roman , Mazzara Saveria , Mancuso Patrizia , Pileri Stefano , Raveane Alessandro , Bertolini Francesco 
Published: March 2022

AbstractBreast cancer (BC) constitutes a major health problem worldwide, making it the most common malignancy in women. Current treatment options for BC depend primarily on histological type, molecular markers, clinical aggressiveness and stage of disease. Immunotherapy, such as αPD-1, have shown combinatorial clinical activity with chemotherapy in triple negative breast cancer (TNBC) delineating some therapeutic combinations as more effective than others. However, a clear overview of the main immune cell populations involved in these treatments has never been provided.Here, an assessment of the immune landscape in the tumor microenvironment (TME) of two TNBC mouse models has been performed using single-cell RNA sequencing technology. Specifically, immune cells were evaluated in untreated conditions and after treatments with chemotherapy or immunotherapy used as single agents or in combination. A decrease of Treg was found in treatments with in vivo efficacy as well as γδ T cells, which have a pro-tumoral activity in mice. Focusing on Cd8 T cells, across all the conditions, a general increase of exhausted-like Cd8 T cells was confirmed in pre-clinical treatments with low efficacy and an opposite trend was found for the proliferative Cd8 T cells. Regarding macrophages, M2-like cells were enriched in treatments with low efficacy while M1-like macrophages followed an opposite trend. For both models, similar proportions of B cells were detected with an increase of proliferative B cells in treatments involving cisplatin in combination with αPD-1. The fine-scale characterization of the immune TME in this work can lead to new insights on the diagnosis and treatment of TNBC.
A 2D material–based transparent hydrogel with engineerable interference colours
Authors: Ding Baofu , Zeng Pengyuan , Huang Ziyang , Dai Lixin , Lan Tianshu , Xu Hao , Pan Yikun , Luo Yuting , Yu Qiangmin , Cheng Hui-Ming , Liu Bilu 
Published: March 2022

AbstractTransparent hydrogels are key materials for many applications, such as contact lens, imperceptible soft robotics and invisible wearable devices. Introducing large and engineerable optical anisotropy offers great prospect for endowing them with extra birefringence-based functions and exploiting their applications in see-through flexible polarization optics. However, existing transparent hydrogels suffer from limitation of low and/or non-fine engineerable birefringence. Here, we invent a transparent magneto-birefringence hydrogel with large and finely engineerable optical anisotropy. The large optical anisotropy factor of the embedded magnetic two-dimensional material gives rise to the large magneto-birefringence of the hydrogel in the transparent condition of ultra-low concentration, which is several orders of magnitude larger than usual transparent magnetic hydrogels. High transparency, large and tunable optical anisotropy cooperatively permit the magnetic patterning of interference colours in the hydrogel. The hydrogel also shows mechanochromic and thermochromic property. Our finding provides an entry point for applying hydrogel in optical anisotropy and colour centred fields, with several proof-of-concept applications been demonstrated.
Kinetic model of GPCR-G protein interactions reveals allokairic modulation of signaling
Authors: Culhane Kelly J. , Gupte Tejas M. , Madhugiri Indrani , Gadgil Chetan J. , Sivaramakrishnan Sivaraj 
Published: March 2022

AbstractEstablished models of ternary complex formation between hormone, G protein coupled receptor (GPCR), and G protein assume that all interactions occur under equilibrium conditions. However, recent studies have established that the lifetimes of these interactions are comparable to the duration of hormone activated GPCR signaling. To simulate interactions during such non-equilibrium conditions, we propose a kinetic model wherein the receptor undergoes rate-limiting transitions between two hormone-bound active states. Simulations, using experimentally measured parameters, demonstrate transient states in ternary complex formation, and delineate the phenomenon of GPCR priming, wherein non-cognate G proteins substantially enhance cognate G protein signaling. Our model reveals that kinetic barriers of slow receptor interconversion can be overcome through allokairic modulation, a regulatory mechanism of ternary complex formation and downstream signaling.
Bacterial F-type ATP synthases follow a well-choreographed assembly pathway
Authors: Vu Huu Khanh , Zangl Rene , Hoffmann Jan , Just Alicia , Morgner Nina 
Published: March 2022

AbstractF-type ATP synthases are multiprotein complexes composed of two separate coupled motors (F1 and FO) generating adenosine triphosphate (ATP) as the universal major energy source in a variety of relevant biological processes in mitochondria, bacteria and chloroplasts. While the structure of many ATPases is solved today, the precise assembly pathway of F1FO-ATP synthases is still largely unclear. Here, we probe the assembly of the F1 complex from Acetobacterium woodii. Using laser induced liquid bead ion desorption (LILBID) mass spectrometry, we study the self-assembly of purified F1 subunits in different environments under non-denaturing conditions. We report assembly requirements and identify important assembly intermediates in vitro and in cellula. Our data provide evidence that nucleotide binding is crucial for in vitro F1 assembly, whereas ATP hydrolysis appears to be less critical. We correlate our results with activity measurements and propose a model for the assembly pathway of a functional F1 complex.
Spatial and temporal expansion of global wildland fire activity in response to climate change
Authors: Senande-Rivera Martín , Insua-Costa Damián , Miguez-Macho Gonzalo 
Published: March 2022

AbstractGlobal warming is expected to alter wildfire potential and fire season severity, but the magnitude and location of change is still unclear. Here, we show that climate largely determines present fire-prone regions and their fire season. We categorize these regions according to the climatic characteristics of their fire season into four classes, within general Boreal, Temperate, Tropical and Arid climate zones. Based on climate model projections, we assess the modification of the fire-prone regions in extent and fire season length at the end of the 21st century. We find that due to global warming, the global area with frequent fire-prone conditions would increase by 29%, mostly in Boreal (+111%) and Temperate (+25%) zones, where there may also be a significant lengthening of the potential fire season. Our estimates of the global expansion of fire-prone areas highlight the large but uneven impact of a warming climate on Earth’s environment.
MQuad enables clonal substructure discovery using single cell mitochondrial variants
Authors: Kwok Aaron Wing Cheung , Qiao Chen , Huang Rongting , Sham Mai-Har , Ho Joshua W. K. , Huang Yuanhua 
Published: March 2022

AbstractMitochondrial mutations are increasingly recognised as informative endogenous genetic markers that can be used to reconstruct cellular clonal structure using single-cell RNA or DNA sequencing data. However, identifying informative mtDNA variants in noisy and sparse single-cell sequencing data is still challenging with few computation methods available. Here we present an open source computational tool MQuad that accurately calls clonally informative mtDNA variants in a population of single cells, and an analysis suite for complete clonality inference, based on single cell RNA, DNA or ATAC sequencing data. Through a variety of simulated and experimental single cell sequencing data, we showed that MQuad can identify mitochondrial variants with both high sensitivity and specificity, outperforming existing methods by a large extent. Furthermore, we demonstrate its wide applicability in different single cell sequencing protocols, particularly in complementing single-nucleotide and copy-number variations to extract finer clonal resolution.
Differential recognition of canonical NF-κB dimers by Importin α3
Authors: Florio Tyler J. , Lokareddy Ravi K. , Yeggoni Daniel P. , Sankhala Rajeshwer S. , Ott Connor A. , Gillilan Richard E. , Cingolani Gino 
Published: March 2022

AbstractNuclear translocation of the p50/p65 heterodimer is essential for NF-κB signaling. In unstimulated cells, p50/p65 is retained by the inhibitor IκBα in the cytoplasm that masks the p65-nuclear localization sequence (NLS). Upon activation, p50/p65 is translocated into the nucleus by the adapter importin α3 and the receptor importin β. Here, we describe a bipartite NLS in p50/p65, analogous to nucleoplasmin NLS but exposed in trans. Importin α3 accommodates the p50- and p65-NLSs at the major and minor NLS-binding pockets, respectively. The p50-NLS is the predominant binding determinant, while the p65-NLS induces a conformational change in the Armadillo 7 of importin α3 that stabilizes a helical conformation of the p65-NLS. Neither conformational change was observed for importin α1, which makes fewer bonds with the p50/p65 NLSs, explaining the preference for α3. We propose that importin α3 discriminates between the transcriptionally active p50/p65 heterodimer and p50/p50 and p65/65 homodimers, ensuring fidelity in NF-κB signaling.
Cas9 exo-endonuclease eliminates chromosomal translocations during genome editing
Authors: Yin Jianhang , Lu Rusen , Xin Changchang , Wang Yuhong , Ling Xinyu , Li Dong , Zhang Weiwei , Liu Mengzhu , Xie Wutao , Kong Lingyun , Si Wen , Wei Ping , Xiao Bingbing , Lee Hsiang-Ying , Liu Tao , Hu Jiazhi 
Published: March 2022

AbstractThe mechanism underlying unwanted structural variations induced by CRISPR-Cas9 remains poorly understood, and no effective strategy is available to inhibit the generation of these byproducts. Here we find that the generation of a high level of translocations is dependent on repeated cleavage at the Cas9-targeting sites. Therefore, we employ a strategy in which Cas9 is fused with optimized TREX2 to generate Cas9TX, a Cas9 exo-endonuclease, which prevents perfect DNA repair and thereby avoids repeated cleavage. In comparison with CRISPR-Cas9, CRISPR-Cas9TX greatly suppressed translocation levels and enhanced the editing efficiency of single-site editing. The number of large deletions associated with Cas9TX was also reduced to very low level. The application of CRISPR-Cas9TX for multiplex gene editing in chimeric antigen receptor T cells nearly eliminated deleterious chromosomal translocations. We report the mechanism underlying translocations induced by Cas9, and propose a general strategy for reducing chromosomal abnormalities induced by CRISPR-RNA-guided endonucleases.
Liquid metal-tailored gluten network for protein-based e-skin
Authors: Chen Bin , Cao Yudong , Li Qiaoyu , Yan Zhuo , Liu Rui , Zhao Yunjiao , Zhang Xiang , Wu Minying , Qin Yixiu , Sun Chang , Yao Wei , Cao Ziyi , Ajayan Pulickel M. , Chee Mason Oliver Lam , Dong Pei , Li Zhaofen , Shen Jianfeng , Ye Mingxin 
Published: March 2022

AbstractDesigning electronic skin (e-skin) with proteins is a critical way to endow e-skin with biocompatibility, but engineering protein structures to achieve controllable mechanical properties and self-healing ability remains a challenge. Here, we develop a hybrid gluten network through the incorporation of a eutectic gallium indium alloy (EGaIn) to design a self-healable e-skin with improved mechanical properties. The intrinsic reversible disulfide bond/sulfhydryl group reconfiguration of gluten networks is explored as a driving force to introduce EGaIn as a chemical cross-linker, thus inducing secondary structure rearrangement of gluten to form additional β-sheets as physical cross-linkers. Remarkably, the obtained gluten-based material is self-healing, achieves synthetic material-like stretchability (>1600%) and possesses the ability to promote skin cell proliferation. The final e-skin is biocompatible and biodegradable and can sense strain changes from human motions of different scales. The protein network microregulation method paves the way for future skin-like protein-based e-skin.
In situ-formed tetrahedrally coordinated double-helical metal complexes for improved coordination-activated n-doping
Authors: Liu Ziyang , Li Xiao , Lu Yang , Zhang Chen , Zhang Yuewei , Huang Tianyu , Zhang Dongdong , Duan Lian 
Published: March 2022

AbstractIn situ coordination-activated n-doping by air-stable metals in electron-transport organic ligands has proven to be a viable method to achieve Ohmic electron injection for organic optoelectronics. However, the mutual exclusion of ligands with high nucleophilic quality and strong electron affinity limits the injection efficiency. Here, we propose meta-linkage diphenanthroline-type ligands, which not only possess high electron affinity and good electron transport ability but also favour the formation of tetrahedrally coordinated double-helical metal complexes to decrease the ionization energy of air-stable metals. An electron injection layer (EIL) compatible with various cathodes and electron transport materials is developed with silver as an n-dopant, and the injection efficiency outperforms conventional EILs such as lithium compounds. A deep-blue organic light-emitting diode with an optimized EIL achieves a high current efficiency calibrated by the y colour coordinate (0.045) of 237 cd A−1 and a superb LT95 of 104.1 h at 5000 cd m−2.
Regulation of protein secretion through chemical regulation of endoplasmic reticulum retention signal cleavage
Authors: Praznik Arne , Fink Tina , Franko Nik , Lonzarić Jan , Benčina Mojca , Jerala Nina , Plaper Tjaša , Roškar Samo , Jerala Roman 
Published: March 2022

AbstractSecreted proteins, such as hormones or cytokines, are key mediators in multicellular organisms. Response of protein secretion based on transcriptional control is rather slow, as it requires transcription, translation and transport from the endoplasmic reticulum (ER) to the plasma membrane via the conventional protein secretion (CPS) pathway. An alternative regulation to provide faster response would be valuable. Here we present two genetically encoded orthogonal regulatory secretion systems, which rely on the retention of pre-synthesized proteins on the ER membrane (membER, released by a cytosolic protease) or inside the ER lumen (lumER, released by an ER-luminal protease), respectively, and their release by the chemical signal-regulated proteolytic removal of an ER-retention signal, without triggering ER stress due to protein aggregates. Design of orthogonal chemically-regulated split proteases enables the combination of signals into logic functions. Its application was demonstrated on a chemically regulated therapeutic protein secretion and regulated membrane translocation of a chimeric antigen receptor (CAR) targeting cancer antigen. Regulation of the ER escape represents a platform for the design of fast-responsive and tightly-controlled modular and scalable protein secretion system for mammalian cells.
Tocilizumab overcomes chemotherapy resistance in mesenchymal stem-like breast cancer by negating autocrine IL-1A induction of IL-6
Authors: Chung Andrew W. , Kozielski Anthony J. , Qian Wei , Zhou Jianying , Anselme Ann C. , Chan Alfred A. , Pan Ping-Ying , Lee Delphine J. , Chang Jenny C. 
Published: March 2022

AbstractTriple-negative breast cancer (TNBC) patients with mesenchymal stem-like (MSL) subtype have responded poorly to chemotherapy whereas patients with basal-like 1 (BL1) subtype achieved the best clinical response. In order to gain insight into pathways that may contribute to the divergent sensitivity to chemotherapy, we compared the inflammatory profile of the two TNBC subtypes treated with docetaxel. Cellular signaling analysis determined that docetaxel activated MAPK pathway in MSL TNBCs but not BL1 TNBCs. The subsequent MAPK pathway activation in MSL TNBCs led to an IL-1A mediated cascade of autocrine inflammatory mediators including IL-6. Utilizing the humanized IL-6R antibody, tocilizumab, our in vitro and in vivo data show that MSL TNBCs treated with tocilizumab together with chemotherapy results in delayed tumor progression compared to MSL TNBCs treated with docetaxel alone. Our study highlights a molecular subset of TNBC that may be responsive to tocilizumab therapy for potential translational impact.
Assessment and diagnosis of chronic dyspnoea: a literature review
Authors: Sunjaya Anthony Paulo , Homaira Nusrat , Corcoran Kate , Martin Allison , Berend Norbert , Jenkins Christine 
Published: March 2022

AbstractDyspnoea or breathlessness is a common presenting symptom among patients attending primary care services. This review aimed to determine whether there are clinical tools that can be incorporated into a clinical decision support system for primary care for efficient and accurate diagnosis of causes of chronic dyspnoea. We searched MEDLINE, EMBASE and Google Scholar for all literature published between 1946 and 2020. Studies that evaluated a clinical algorithm for assessment of chronic dyspnoea in patients of any age group presenting to physicians with chronic dyspnoea were included. We identified 326 abstracts, 55 papers were reviewed, and eight included. A total 2026 patients aged between 20–80 years were included, 60% were women. The duration of dyspnoea was three weeks to 25 years. All studies undertook a stepwise or algorithmic approach to the assessment of dyspnoea. The results indicate that following history taking and physical examination, the first stage should include simply performed tests such as pulse oximetry, spirometry, and electrocardiography. If the patient remains undiagnosed, the second stage includes investigations such as chest x-ray, thyroid function tests, full blood count and NT-proBNP. In the third stage patients are referred for more advanced tests such as echocardiogram and thoracic CT. If dyspnoea remains unexplained, the fourth stage of assessment will require secondary care referral for more advanced diagnostic testing such as exercise tests. Utilising this proposed stepwise approach is expected to ascertain a cause for dyspnoea for 35% of the patients in stage 1, 83% by stage 3 and >90% of patients by stage 4.
Three doses of BNT162b2 vaccine confer neutralising antibody capacity against the SARS-CoV-2 Omicron variant
Authors: Ariën Kevin K. , Heyndrickx Leo , Michiels Johan , Vereecken Katleen , Van Lent Kurt , Coppens Sandra , Willems Betty , Pannus Pieter , Martens Geert A. , Van Esbroeck Marjan , Goossens Maria E. , Marchant Arnaud , Bartholomeeusen Koen , Desombere Isabelle 
Published: March 2022

AbstractWe report the levels of neutralising antibodies against Wuhan, Delta and Omicron variants in unimmunized infected (group 1), immunised and boosted (group 2) and infected immunised and boosted (group 3) adult individuals. Our observations support the rapid administration of a booster vaccine dose to prevent infection and disease caused by Omicron.
Portable real-time colorimetric LAMP-device for rapid quantitative detection of nucleic acids in crude samples
Authors: Papadakis G. , Pantazis A. K. , Fikas N. , Chatziioannidou S. , Tsiakalou V. , Michaelidou K. , Pogka V. , Megariti M. , Vardaki M. , Giarentis K. , Heaney J. , Nastouli E. , Karamitros T. , Mentis A. , Zafiropoulos A. , Sourvinos G. , Agelaki S. , Gizeli E. 
Published: March 2022

AbstractLoop-mediated isothermal amplification is known for its high sensitivity, specificity and tolerance to inhibiting-substances. In this work, we developed a device for performing real-time colorimetric LAMP combining the accuracy of lab-based quantitative analysis with the simplicity of point-of-care testing. The device innovation lies on the use of a plastic tube anchored vertically on a hot surface while the side walls are exposed to a mini camera able to take snapshots of the colour change in real time during LAMP amplification. Competitive features are the rapid analysis (< 30 min), quantification over 9 log-units, crude sample-compatibility (saliva, tissue, swabs), low detection limit (< 5 copies/reaction), smartphone-operation, fast prototyping (3D-printing) and ability to select the dye of interest (Phenol red, HNB). The device’s clinical utility is demonstrated in cancer mutations-analysis during the detection of 0.01% of BRAF-V600E-to-wild-type molecules from tissue samples and COVID-19 testing with 97% (Ct < 36.8) and 98% (Ct < 30) sensitivity when using extracted RNA and nasopharyngeal-swabs, respectively. The device high technology-readiness-level makes it a suitable platform for performing any colorimetric LAMP assay; moreover, its simple and inexpensive fabrication holds promise for fast deployment and application in global diagnostics.
Naïve-like pluripotency to pave the way for saving the northern white rhinoceros from extinction
Authors: Zywitza Vera , Rusha Ejona , Shaposhnikov Dmitry , Ruiz-Orera Jorge , Telugu Narasimha , Rishko Valentyna , Hayashi Masafumi , Michel Geert , Wittler Lars , Stejskal Jan , Holtze Susanne , Göritz Frank , Hermes Robert , Wang Jichang , Izsvák Zsuzsanna , Colleoni Silvia , Lazzari Giovanna , Galli Cesare , Hildebrandt Thomas B. , Hayashi Katsuhiko , Diecke Sebastian , Drukker Micha 
Published: March 2022

AbstractThe northern white rhinoceros (NWR) is probably the earth’s most endangered mammal. To rescue the functionally extinct species, we aim to employ induced pluripotent stem cells (iPSCs) to generate gametes and subsequently embryos in vitro. To elucidate the regulation of pluripotency and differentiation of NWR PSCs, we generated iPSCs from a deceased NWR female using episomal reprogramming, and observed surprising similarities to human PSCs. NWR iPSCs exhibit a broad differentiation potency into the three germ layers and trophoblast, and acquire a naïve-like state of pluripotency, which is pivotal to differentiate PSCs into primordial germ cells (PGCs). Naïve culturing conditions induced a similar expression profile of pluripotency related genes in NWR iPSCs and human ESCs. Furthermore, naïve-like NWR iPSCs displayed increased expression of naïve and PGC marker genes, and a higher integration propensity into developing mouse embryos. As the conversion process was aided by ectopic BCL2 expression, and we observed integration of reprogramming factors, the NWR iPSCs presented here are unsuitable for gamete production. However, the gained insights into the developmental potential of both primed and naïve-like NWR iPSCs are fundamental for in future PGC-specification in order to rescue the species from extinction using cryopreserved somatic cells.