bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell protein profiling in microchambers with barcoded beads
Authors: Armbrecht Lucas , Müller Rafael Sebastian , Nikoloff Jonas , Dittrich Petra Stephanie 
Published: November 2019

AbstractSingle-cell profiling provides insights into cellular behaviour that macroscale cell cultures and bulk measurements cannot reveal. In the context of personalized cancer treatment, the profiling of individual tumour cells may lead to higher success rates for therapies by rapidly selecting the most efficacious drugs. Currently, genomic analysis at the single-cell level is available through highly sensitive sequencing approaches. However, the identification and quantification of intracellular or secreted proteins or metabolites remains challenging. Here, we introduce a microfluidic method that facilitates capture, automated data acquisition and the multiplexed quantification of proteins from individual cells. The microfluidic platform comprises 1026 chambers with a volume of 152 pL each, in which single cells and barcoded beads are co-immobilized. We demonstrated multiplexed single-cell protein quantification with three different mammalian cell lines, including two model breast cancer cell lines. We established on-chip immunoassays for glyceraldehyde-3-phosphate dehydrogenase (GAPDH), galectin-3 (Gal-3) and galectin-3 binding protein (Gal-3bp) with detection limits as low as 7.0 × 104, 2.3 × 105 and 1.8 × 103 molecules per cell, respectively. The three investigated cell types had high cytosolic levels of GAPDH and could be clearly differentiated by their expression levels of Gal-3 and Gal-3bp, which are important factors that contribute to cancer metastasis. Because it employed commercially available barcoded beads for this study, our platform could be easily used for the single-cell protein profiling of several hundred different targets. Moreover, this versatile method is applicable to the analysis of bacteria, yeast and mammalian cells and nanometre-sized lipid vesicles.
Periodontal inflammation recruits distant metastatic breast cancer cells by increasing myeloid-derived suppressor cells
Authors: Cheng Ran , Billet Sandrine , Liu Chuanxia , Haldar Subhash , Choudhury Diptiman , Tripathi Manisha , Hav Monirath , Merchant Akil , Hu Tao , Huang Haiyun , Zhou Hongmei , Bhowmick Neil A. 
Published: November 2019

Abstract
Periodontal diseases can lead to chronic inflammation affecting the integrity of the tooth supporting tissues. Recently, a striking association has been made between periodontal diseases and primary cancers in the absence of a mechanistic understanding. Here we address the effect of periodontal inflammation (PI) on tumor progression, metastasis, and possible underlining mechanisms. We show that an experimental model of PI in mice can promote lymph node (LN) micrometastasis, as well as head and neck metastasis of 4T1 breast cancer cells, both in early and late stages of cancer progression. The cervical LNs had a greater tumor burden and infiltration of MDSC and M2 macrophages compared with LNs at other sites. Pyroptosis and the resultant IL-1β production were detected in patients with PI, mirrored in mouse models. Anakinra, IL-1 receptor antagonist, limited metastasis, and MDSC recruitment at early stages of tumor progression, but failed to reverse established metastatic tumors. PI and the resulting production of IL-1β was found to promote CCL5, CXCL12, CCL2, and CXCL5 expression. These chemokines recruit MDSC and macrophages, finally enabling the generation of a premetastatic niche in the inflammatory site. These findings support the idea that periodontal inflammation promotes metastasis of breast cancer by recruiting MDSC in part by pyroptosis-induced IL-1β generation and downstream CCL2, CCL5, and CXCL5 signaling in the early steps of metastasis. These studies define the role for IL-1β in the metastatic progression of breast cancer and highlight the need to control PI, a pervasive inflammatory condition in older patients.
DEPTOR is an in vivo tumor suppressor that inhibits prostate tumorigenesis via the inactivation of mTORC1/2 signals
Authors: Chen Xiaoyu , Xiong Xiufang , Cui Danrui , Yang Fei , Wei Dongping , Li Haomin , Shu Jianfeng , Bi Yanli , Dai Xiaoqing , Gong Longyuan , Sun Yi , Zhao Yongchao 
Published: November 2019

Abstract
The DEPTOR-mTORC1/2 axis has been shown to play an important, but a context dependent role in the regulation of proliferation and the survival of various cancer cells in cell culture settings. The in vivo role of DEPTOR in tumorigenesis remains elusive. Here we showed that the levels of both DEPTOR protein and mRNA were substantially decreased in human prostate cancer tissues, which positively correlated with disease progression. DEPTOR depletion accelerated proliferation and survival, migration, and invasion in human prostate cancer cells. Mechanistically, DEPTOR depletion not only activated both mTORC1 and mTORC2 signals to promote cell proliferation and survival, but also induced an AKT-dependent epithelial–mesenchymal transition (EMT) and β-catenin nuclear translocation to promote cell migration and invasion. Abrogation of mTOR or AKT activation rescued the biological consequences of DEPTOR depletion. Importantly, in a Deptor-KO mouse model, Deptor knockout accelerated prostate tumorigenesis triggered by Pten loss via the activation of mTOR signaling. Collectively, our study demonstrates that DEPTOR is a tumor suppressor in the prostate, and its depletion promotes tumorigenesis via the activation of mTORC1 and mTORC2 signals. Thus, DEPTOR reactivation via a variety of means would have therapeutic potential for the treatment of prostate cancer.
KCTD15 inhibits the Hedgehog pathway in Medulloblastoma cells by increasing protein levels of the oncosuppressor KCASH2
Authors: Spiombi Eleonora , Angrisani Annapaola , Fonte Simone , De Feudis Giuseppina , Fabretti Francesca , Cucchi Danilo , Izzo Mariapaola , Infante Paola , Miele Evelina , Po Agnese , Di Magno Laura , Magliozzi Roberto , Guardavaccaro Daniele , Maroder Marella , Canettieri Gianluca , Giannini Giuseppe , Ferretti Elisabetta , Gulino Alberto , Di Marcotullio Lucia , Moretti Marta , De Smaele Enrico 
Published: November 2019

AbstractMedulloblastoma (MB) is the most common malignant childhood brain tumor. About 30% of all MBs belong to the I molecular subgroup, characterized by constitutive activation of the Sonic Hedgehog (Hh) pathway. The Hh pathway is involved in several fundamental processes during embryogenesis and in adult life and its deregulation may lead to cerebellar tumorigenesis. Indeed, Hh activity must be maintained via a complex network of activating and repressor signals. One of these repressor signals is KCASH2, belonging to the KCASH family of protein, which acts as negative regulators of the Hedgehog signaling pathway during cerebellar development and differentiation. KCASH2 leads HDAC1 to degradation, allowing hyperacetylation and inhibition of transcriptional activity of Gli1, the main effector of the Hh pathway. In turn, the KCASH2 loss leads to persistent Hh activity and eventually tumorigenesis. In order to better characterize the physiologic role and modulation mechanisms of KCASH2, we have searched through a proteomic approach for new KCASH2 interactors, identifying Potassium Channel Tetramerization Domain Containing 15 (KCTD15). KCTD15 is able to directly interact with KCASH2, through its BTB/POZ domain. This interaction leads to increase KCASH2 stability which implies a reduction of the Hh pathway activity and a reduction of Hh-dependent MB cells proliferation. Here we report the identification of KCTD15 as a novel player in the complex network of regulatory proteins, which modulate Hh pathway, this could be a promising new target for therapeutic approach against MB.
The planktonic protist interactome: where do we stand after a century of research?
Authors: Bjorbækmo Marit F Markussen , Evenstad Andreas , Røsæg Line Lieblein , Krabberød Anders K , Logares Ramiro 
Published: November 2019

Abstract
Microbial interactions are crucial for Earth ecosystem function, but our knowledge about them is limited and has so far mainly existed as scattered records. Here, we have surveyed the literature involving planktonic protist interactions and gathered the information in a manually curated Protist Interaction DAtabase (PIDA). In total, we have registered ~2500 ecological interactions from ~500 publications, spanning the last 150 years. All major protistan lineages were involved in interactions as hosts, symbionts (mutualists and commensalists), parasites, predators, and/or prey. Predation was the most common interaction (39% of all records), followed by symbiosis (29%), parasitism (18%), and ‘unresolved interactions’ (14%, where it is uncertain whether the interaction is beneficial or antagonistic). Using bipartite networks, we found that protist predators seem to be ‘multivorous’ while parasite–host and symbiont–host interactions appear to have moderate degrees of specialization. The SAR supergroup (i.e., Stramenopiles, Alveolata, and Rhizaria) heavily dominated PIDA, and comparisons against a global-ocean molecular survey (TARA Oceans) indicated that several SAR lineages, which are abundant and diverse in the marine realm, were underrepresented among the recorded interactions. Despite historical biases, our work not only unveils large-scale eco-evolutionary trends in the protist interactome, but it also constitutes an expandable resource to investigate protist interactions and to test hypotheses deriving from omics tools.
Circadian clock helps cyanobacteria manage energy in coastal and high latitude ocean
Authors: Hellweger Ferdi L , Jabbur Maria Luísa , Johnson Carl Hirschie , van Sebille Erik , Sasaki Hideharu 
Published: November 2019

Abstract
The circadian clock coordinates cellular functions over the diel cycle in many organisms. The molecular mechanisms of the cyanobacterial clock are well characterized, but its ecological role remains a mystery. We present an agent-based model of Synechococcus (harboring a self-sustained, bona fide circadian clock) that explicitly represents genes (e.g., kaiABC), transcripts, proteins, and metabolites. The model is calibrated to data from laboratory experiments with wild type and no-clock mutant strains, and it successfully reproduces the main observed patterns of glycogen metabolism. Comparison of wild type and no-clock mutant strains suggests a main benefit of the clock is due to energy management. For example, it inhibits glycogen synthesis early in the day when it is not needed and energy is better used for making the photosynthesis apparatus. To explore the ecological role of the clock, we integrate the model into a dynamic, three-dimensional global circulation model that includes light variability due to seasonal and diel incident radiation and vertical extinction. Model output is compared with field data, including in situ gene transcript levels. We simulate cyanobaceria with and without a circadian clock, which allows us to quantify the fitness benefit of the clock. Interestingly, the benefit is weakest in the low latitude open ocean, where Prochlorococcus (lacking a self-sustained clock) dominates. However, our attempt to experimentally validate this testable prediction failed. Our study provides insights into the role of the clock and an example for how models can be used to integrate across multiple levels of biological organization.
Zfp422 promotes skeletal muscle differentiation by regulating EphA7 to induce appropriate myoblast apoptosis
Authors: Nie Yaping , Cai Shufang , Yuan Renqiang , Ding Suying , Zhang Xumeng , Chen Luxi , Chen Yaosheng , Mo Delin 
Published: November 2019

AbstractZinc finger protein 422 (Zfp422) is a widely expressed zinc finger protein that serves as a transcriptional factor to regulate downstream gene expression, but until now, little is known about its roles in myogenesis. We found here that Zfp422 plays a critical role in skeletal muscle development and regeneration. It highly expresses in mouse skeletal muscle during embryonic development. Specific knockout of Zfp422 in skeletal muscle impaired embryonic muscle formation. Satellite cell-specific Zfp422 deletion severely inhibited muscle regeneration. Myoblast differentiation and myotube formation were suppressed in Zfp422-deleted C2C12 cells, isolated primary myoblasts, and satellite cells. Chromatin Immunoprecipitation Sequencing (ChIP-Seq) revealed that Zfp422 regulated ephrin type-A receptor 7 (EphA7) expression by binding an upstream 169-bp DNA sequence, which was proved to be an enhancer ofEphA7. Knocking EphA7 down in C2C12 cells or deleting Zfp422 in myoblasts will inhibit cell apoptosis which is required for myoblast differentiation. These results indicate that Zfp422 is essential for skeletal muscle differentiation and fusion, through regulating EphA7 expression to maintain proper apoptosis.
ASPP2 inhibits tumor growth by repressing the mevalonate pathway in hepatocellular carcinoma
Authors: Liang Beibei , Chen Rui , Song Shaohua , Wang Hao , Sun Guowei , Yang Hao , Jing Wei , Zhou Xuyu , Fu Zhiren , Huang Gang , Zhao Jian 
Published: November 2019

AbstractCancer is, fundamentally, a disorder of cell growth and proliferation, which requires adequate supplies of energy and nutrients. In this study, we report that the haplo-insufficient tumor suppressor ASPP2, a p53 activator, negatively regulates the mevalonate pathway to mediate its inhibitory effect on tumor growth in hepatocellular carcinoma (HCC). Gene expression profile analysis revealed that the expression of key enzymes in the mevalonate pathway were increased when ASPP2 was downregulated. HCC cells gained higher cholesterol levels and enhanced tumor-initiating capability in response to the depletion of ASPP2. Simvastatin, a mevalonate pathway inhibitor, efficiently abrogated ASPP2 depletion-induced anchorage-independent cell proliferation, resistance to chemotherapy drugs in vitro, and tumor growth in xenografted nude mice. Mechanistically, ASPP2 interacts with SREBP-2 in the nucleus and restricts the transcriptional activity of SREBP-2 on its target genes, which include key enzymes involved in the mevalonate pathway. Moreover, clinical data revealed better prognosis in patients with high levels of ASPP2 and low levels of the mevalonate pathway enzyme HMGCR. Our findings provide functional and mechanistic insights into the critical role of ASPP2 in the regulation of the mevalonate pathway and the importance of this pathway in tumor initiation and tumor growth, which may provide a new therapeutic opportunity for HCC.
LncRNA RPPH1 promotes colorectal cancer metastasis by interacting with TUBB3 and by promoting exosomes-mediated macrophage M2 polarization
Authors: Liang Zhen-xing , Liu Hua-shan , Wang Feng-wei , Xiong Li , Zhou Chi , Hu Tuo , He Xiao-wen , Wu Xiao-jian , Xie Dan , Wu Xian-rui , Lan Ping 
Published: November 2019

AbstractMetastasis is a well-known poor prognostic factor in cancer. However, the mechanisms how long non-coding RNAs (lncRNAs) regulate metastasis in colorectal cancer (CRC) remain largely unknown. Besides, tumor-associated macrophages (TAMs) play an important role in tumor progression, yet the contribution of lncRNA-mediated crosstalk between TAMs and CRC cells to tumor progression is not well understood. In this study, we report that lncRNA RPPH1 was significantly upregulated in CRC tissues, and the RPPH1 overexpression was associated with advanced TNM stages and poor prognosis. RPPH1 was found to promote CRC metastasis in vitro and in vivo. Mechanistically, RPPH1 induced epithelial–mesenchymal transition (EMT) of CRC cells via interacting with β-III tubulin (TUBB3) to prevent its ubiquitination. Furthermore, CRC cell-derived exosomes transported RPPH1 into macrophages which mediate macrophage M2 polarization, thereby in turn promoting metastasis and proliferation of CRC cells. In addition, exosomal RPPH1 levels in blood plasma turned out to be higher in treatment-naive CRC patients but lower after tumor resection. Compared to CEA and CA199, exosomal RPPH1 in CRC plasma displayed a better diagnostic value (AUC = 0.86). Collectively, RPPH1 serves as a potential therapeutic and diagnostic target in CRC.
Inhibition of microRNA-711 limits angiopoietin-1 and Akt changes, tissue damage, and motor dysfunction after contusive spinal cord injury in mice
Authors: Sabirzhanov Boris , Matyas Jessica , Coll-Miro Marina , Yu Laina Lijia , Faden Alan I. , Stoica Bogdan A. , Wu Junfang 
Published: November 2019

AbstractSpinal cord injury (SCI) causes neuronal cell death and vascular damage, which contribute to neurological dysfunction. Given that many biochemical changes contribute to such secondary injury, treatment approaches have increasingly focused on combined therapies or use of multi-functional drugs. MicroRNAs (miRs) are small (20–23 nucleotide), non-protein-coding RNAs and can negatively regulate target gene expression at the post-transcriptional level. As individual miRs can potentially modulate expression of multiple relevant proteins after injury, they are attractive candidates as upstream regulators of the secondary SCI progression. In the present study we examined the role of miR-711 modulation after SCI. Levels of miR-711 were increased in injured spinal cord early after SCI, accompanied by rapid downregulation of its target angiopoietin-1 (Ang-1), an endothelial growth factor. Changes of miR-711 were also associated with downregulation of the pro-survival protein Akt (protein kinase B), another target of miR-711, with sequential activation of glycogen synthase kinase 3 and the pro-apoptotic BH3-only molecule PUMA. Central administration of a miR-711 hairpin inhibitor after SCI limited decreases of Ang-1/Akt expression and attenuated apoptotic pathways. Such treatment also reduced neuronal/axonal damage, protected microvasculature and improved motor dysfunction following SCI. In vitro, miR-711 levels were rapidly elevated by neuronal insults, but not by activated microglia and astrocytes. Together, our data suggest that post-traumatic miR-711 elevation contributes to neuronal cell death after SCI, in part by inhibiting Ang-1 and Akt pathways, and may serve as a novel therapeutic target.
Evaluation of leakage resistance improvement in transconjunctival sutureless vitrectomy sclerotomies closed with adhesives. an experimental study
Authors: López-Guajardo Lorenzo , Benítez-Herreros Javier , Donate-López Juan , Opazo-Toro Valeria 
Published: November 2019

Abstract

Background
The purpose of this paper is to study the utility of adhesives (artificial-cyanoacrylate and biological-fibrin glue) for improving transconjunctival sutureless vitrectomy (TSV) sclerotomy closure competency.

Methods
Experimental and observer-masked study in which after performing TSV in cadaveric pig eyes, different adhesives were tested on sclerotomy entrances in order to determine if they improved closure competency in face of progressive intraocular pressure increase. In 76 eyes cyanoacrylate-treated sclerotomies were compared with sclerotomies in which no additional manoeuvre to aid closing was performed; in 76 eyes fibrin glue with no manoeuvre; and in the last 76 eyes, cyanoacrylate-treated sclerotomies were compared with fibrin glue-treated sclerotomies.

Results
A total of 228 eyes had a 23-gauge TSV performed. Both cyanoacrylate and fibrin glue treated sclerotomies achieved higher mean opening pressures when compared with nontreated sclerotomies in the same eye (p < 0.002). When cyanoacrylate was compared with biological adhesive in the same eye, no statistically significant differences were obtained (p = 0.216).

Discussions
This experimental study provides support for the possible role of adhesives in improving TSV sclerotomy closure competency in clinical practice.
Membrane protein megahertz crystallography at the European XFEL
Authors: Gisriel Chris , Coe Jesse , Letrun Romain , Yefanov Oleksandr M. , Luna-Chavez Cesar , Stander Natasha E. , Lisova Stella , Mariani Valerio , Kuhn Manuela , Aplin Steve , Grant Thomas D. , Dörner Katerina , Sato Tokushi , Echelmeier Austin , Cruz Villarreal Jorvani , Hunter Mark S. , Wiedorn Max O. , Knoska Juraj , Mazalova Victoria , Roy-Chowdhury Shatabdi , Yang Jay-How , Jones Alex , Bean Richard , Bielecki Johan , Kim Yoonhee , Mills Grant , Weinhausen Britta , Meza Jose D. , Al-Qudami Nasser , Bajt Saša , Brehm Gerrit , Botha Sabine , Boukhelef Djelloul , Brockhauser Sandor , Bruce Barry D. , Coleman Matthew A. , Danilevski Cyril , Discianno Erin , Dobson Zachary , Fangohr Hans , Martin-Garcia Jose M. , Gevorkov Yaroslav , Hauf Steffen , Hosseinizadeh Ahmad , Januschek Friederike , Ketawala Gihan K. , Kupitz Christopher , Maia Luis , Manetti Maurizio , Messerschmidt Marc , Michelat Thomas , Mondal Jyotirmoy , Ourmazd Abbas , Previtali Gianpietro , Sarrou Iosifina , Schön Silvan , Schwander Peter , Shelby Megan L. , Silenzi Alessandro , Sztuk-Dambietz Jolanta , Szuba Janusz , Turcato Monica , White Thomas A. , Wrona Krzysztof , Xu Chen , Abdellatif Mohamed H. , Zook James D. , Spence John C. H. , Chapman Henry N. , Barty Anton , Kirian Richard A. , Frank Matthias , Ros Alexandra , Schmidt Marius , Fromme Raimund , Mancuso Adrian P. , Fromme Petra , Zatsepin Nadia A. 
Published: November 2019

AbstractThe world’s first superconducting megahertz repetition rate hard X-ray free-electron laser (XFEL), the European XFEL, began operation in 2017, featuring a unique pulse train structure with 886 ns between pulses. With its rapid pulse rate, the European XFEL may alleviate some of the increasing demand for XFEL beamtime, particularly for membrane protein serial femtosecond crystallography (SFX), leveraging orders-of-magnitude faster data collection. Here, we report the first membrane protein megahertz SFX experiment, where we determined a 2.9 Å-resolution SFX structure of the large membrane protein complex, Photosystem I, a > 1 MDa complex containing 36 protein subunits and 381 cofactors. We address challenges to megahertz SFX for membrane protein complexes, including growth of large quantities of crystals and the large molecular and unit cell size that influence data collection and analysis. The results imply that megahertz crystallography could have an important impact on structure determination of large protein complexes with XFELs.
Minimal biomass deposition in banded iron formations inferred from organic matter and clay relationships
Authors: Dodd Matthew S. , Papineau Dominic , Pirajno Franco , Wan Yusheng , Karhu Juha A. 
Published: November 2019

AbstractThe cycling of iron and organic matter (OM) is thought to have been a major biogeochemical cycle in the early ferruginous oceans which contributed to the deposition of banded iron formations (BIF). However, BIF are deficient in OM, which is postulated to be the result of near-complete oxidation of OM during iron reduction. We test this idea by documenting the prevalence of OM in clays within BIF and clays in shales associated with BIF. We find in shales >80% of OM occurs in clays, but <1% occurs in clays within BIF. Instead, in BIF OM occurs with 13C-depleted carbonate and apatite, implying OM oxidation occurred. Conversely, BIF which possess primary clays would be expected to preserve OM in clays, yet this is not seen. This implies OM deposition in silicate-bearing BIF would have been minimal, this consequently stifled iron-cycling and primary productivity through the retention of nutrients in the sediments.