bluuebunny/crossref_metadata_2025_split huggingface dataset:
CHIP-mediated CIB1 ubiquitination regulated epithelial–mesenchymal transition and tumor metastasis in lung adenocarcinoma
Authors: Liu Yuanqi , Zhou Yanwu , Zhang Pengfei , Li Xizhe , Duan Chaojun , Zhang Chunfang 
Published: October 2020

AbstractCIB1 is a homolog of calmodulin that regulates cell adhesion, migration, and differentiation. It has been considered as an oncogene in many tumor cells; however, its role in lung adenocarcinoma (LAC) has not been studied. In this study, the expression levels of CIB1 in LAC tissues and adjacent normal tissues were examined by immunohistochemistry, and the relationship between CIB1 expression and patient clinicopathological characteristics was analyzed. The effects of CIB1 on epithelial–mesenchymal transition (EMT), migration, and metastasis of LAC cells were determined in vitro and vivo. Proteins interacting with CIB1 were identified using electrospray mass spectrometry (LS-MS), and CHIP was selected in the following assays. Carboxyl-terminus of Hsp70-interacting protein (CHIP) is a ubiquitin E3 ligase. We show that CHIP can degrade CIB1 via promoting polyubiquitination of CIB1 and its subsequent proteasomal degradation. Besides, lysine residue 10 and 65 of CIB1 is the ubiquitinated site of CIB1. Furthermore, CHIP-mediated CIB1 downregulation is critical for the suppression of metastasis and migration of LAC. These results indicated that CHIP-mediated CIB1 ubiquitination could regulate epithelial–mesenchymal and tumor metastasis in LAC.
Consequences of Zmat3 loss in c-MYC- and mutant KRAS-driven tumorigenesis
Authors: Best Sarah A. , Vandenberg Cassandra J. , Abad Etna , Whitehead Lachlan , Guiu Laia , Ding Sheryl , Brennan Margs S. , Strasser Andreas , Herold Marco J. , Sutherland Kate D. , Janic Ana 
Published: October 2020

AbstractTP53 is a critical tumor suppressor that is mutated in approximately 50% of human cancers. Unveiling the downstream target genes of TP53 that fulfill its tumor suppressor function is an area of intense investigation. Zmat3 (also known as Wig-1 or PAG608) is one such downstream target of p53, whose loss in hemopoietic stem cells lacking the apoptosis and cell cycle regulators, Puma and p21, respectively, promotes the development of leukemia. The function of Zmat3 in tumorigenesis however remains unclear. Here, to investigate which oncogenic drivers co-operate with Zmat3 loss to promote neoplastic transformation, we utilized Zmat3 knockout mice in models of c-MYC-driven lymphomagenesis and KrasG12D-driven lung adenocarcinoma development. Interestingly, unlike loss of p53, Zmat3 germline loss had little impact on the rate of tumor development or severity of malignant disease upon either the c-MYC or KrasG12D oncogenic activation. Furthermore, loss of Zmat3 failed to rescue KrasG12D primary lung tumor cells from oncogene-induced senescence. Taken together, we conclude that in the context of c-MYC-driven lymphomagenesis or mutant KrasG12D-driven lung adenocarcinoma development, additional co-occurring mutations are required to resolve Zmat3 tumor suppressive activity.
EVI1 phosphorylation at S436 regulates interactions with CtBP1 and DNMT3A and promotes self-renewal
Authors: Paredes Roberto , Kelly James R. , Geary Bethany , Almarzouq Batool , Schneider Marion , Pearson Stella , Narayanan Prakrithi , Williamson Andrew , Lovell Simon C. , Wiseman Daniel H. , Chadwick John A. , Jones Nigel J. , Kustikova Olga , Schambach Axel , Garner Terence , Amaral Fabio M. R. , Pierce Andrew , Stevens Adam , Somervaille Tim C. P. , Whetton Anthony D. , Meyer Stefan 
Published: October 2020

AbstractThe transcriptional regulator EVI1 has an essential role in early development and haematopoiesis. However, acute myeloid leukaemia (AML) driven by aberrantly high EVI1 expression has very poor prognosis. To investigate the effects of post-translational modifications on EVI1 function, we carried out a mass spectrometry (MS) analysis of EVI1 in AML and detected dynamic phosphorylation at serine 436 (S436). Wild-type EVI1 (EVI1-WT) with S436 available for phosphorylation, but not non-phosphorylatable EVI1-S436A, conferred haematopoietic progenitor cell self-renewal and was associated with significantly higher organised transcriptional patterns. In silico modelling of EVI1-S436 phosphorylation showed reduced affinity to CtBP1, and CtBP1 showed reduced interaction with EVI1-WT compared with EVI1-S436A. The motif harbouring S436 is a target of CDK2 and CDK3 kinases, which interacted with EVI1-WT. The methyltransferase DNMT3A bound preferentially to EVI1-WT compared with EVI1-S436A, and a hypomethylated cell population associated by EVI1-WT expression in murine haematopoietic progenitors is not maintained with EVI1-S436A. These data point to EVI1-S436 phosphorylation directing functional protein interactions for haematopoietic self-renewal. Targeting EVI1-S436 phosphorylation may be of therapeutic benefit when treating EVI1-driven leukaemia.
Structure of the human gonadotropin-releasing hormone receptor GnRH1R reveals an unusual ligand binding mode
Authors: Yan Wei , Cheng Lin , Wang Wei , Wu Chao , Yang Xin , Du Xiaozhe , Ma Liang , Qi Shiqian , Wei Yuquan , Lu Zhiliang , Yang Shengyong , Shao Zhenhua 
Published: October 2020

AbstractGonadotrophin-releasing hormone (GnRH), also known as luteinizing hormone-releasing hormone, is the main regulator of the reproductive system, acting on gonadotropic cells by binding to the GnRH1 receptor (GnRH1R). The GnRH-GnRH1R system is a promising therapeutic target for maintaining reproductive function; to date, a number of ligands targeting GnRH1R for disease treatment are available on the market. Here, we report the crystal structure of GnRH1R bound to the small-molecule drug elagolix at 2.8 Å resolution. The structure reveals an interesting N-terminus that could co-occupy the enlarged orthosteric binding site together with elagolix. The unusual ligand binding mode was further investigated by structural analyses, functional assays and molecular docking studies. On the other hand, because of the unique characteristic of lacking a cytoplasmic C-terminal helix, GnRH1R exhibits different microswitch structural features from other class A GPCRs. In summary, this study provides insight into the ligand binding mode of GnRH1R and offers an atomic framework for rational drug design.
Molecular motor-functionalized porphyrin macrocycles
Authors: Gilissen Pieter J. , White Paul B. , Berrocal José Augusto , Vanthuyne Nicolas , Rutjes Floris P. J. T. , Feringa Ben L. , Elemans Johannes A. A. W. , Nolte Roeland J. M. 
Published: October 2020

AbstractMolecular motors and switches change conformation under the influence of an external stimulus, e.g. light. They can be incorporated into functional systems, allowing the construction of adaptive materials and switchable catalysts. Here, we present two molecular motor-functionalized porphyrin macrocycles for future photo-switchable catalysis. They display helical, planar and point chirality, and are diastereomers, which differ in the relative orientation of the motor and macrocyclic components. Fluorescence, UV-vis, and 1H NMR experiments reveal that the motor-functionalized macrocycles can bind and thread different variants of viologen guests, including a one-side blocked polymeric one of 30 repeat units. The latter feature indicates that the motor systems can find the open end of a polymer chain, thread on it, and move along the chain to eventually bind at the viologen trap, opening possibilities for catalytic writing on single polymer chains via chemical routes.
Exploring the synthetic biology potential of bacteriophages for engineering non-model bacteria
Authors: Lammens Eveline-Marie , Nikel Pablo Ivan , Lavigne Rob 
Published: October 2020

AbstractNon-model bacteria like Pseudomonas putida, Lactococcus lactis and other species have unique and versatile metabolisms, offering unique opportunities for Synthetic Biology (SynBio). However, key genome editing and recombineering tools require optimization and large-scale multiplexing to unlock the full SynBio potential of these bacteria. In addition, the limited availability of a set of characterized, species-specific biological parts hampers the construction of reliable genetic circuitry. Mining of currently available, diverse bacteriophages could complete the SynBio toolbox, as they constitute an unexplored treasure trove for fully adapted metabolic modulators and orthogonally-functioning parts, driven by the longstanding co-evolution between phage and host.
The tomato receptor CuRe1 senses a cell wall protein to identify Cuscuta as a pathogen
Authors: Hegenauer Volker , Slaby Peter , Körner Max , Bruckmüller Julien-Alexander , Burggraf Ronja , Albert Isabell , Kaiser Bettina , Löffelhardt Birgit , Droste-Borel Irina , Sklenar Jan , Menke Frank L. H. , Maček Boris , Ranjan Aashish , Sinha Neelima , Nürnberger Thorsten , Felix Georg , Krause Kirsten , Stahl Mark , Albert Markus 
Published: October 2020

AbstractParasitic plants of the genus Cuscuta penetrate shoots of host plants with haustoria and build a connection to the host vasculature to exhaust water, solutes and carbohydrates. Such infections usually stay unrecognized by the host and lead to harmful host plant damage. Here, we show a molecular mechanism of how plants can sense parasitic Cuscuta. We isolated an 11 kDa protein of the parasite cell wall and identified it as a glycine-rich protein (GRP). This GRP, as well as its minimal peptide epitope Crip21, serve as a pathogen-associated molecular pattern and specifically bind and activate a membrane-bound immune receptor of tomato, the Cuscuta Receptor 1 (CuRe1), leading to defense responses in resistant hosts. These findings provide the initial steps to understand the resistance mechanisms against parasitic plants and further offer great potential for protecting crops by engineering resistance against parasitic plants.
Nkx2-5 defines distinct scaffold and recruitment phases during formation of the murine cardiac Purkinje fiber network
Authors: Choquet Caroline , Kelly Robert G. , Miquerol Lucile 
Published: October 2020

AbstractThe ventricular conduction system coordinates heartbeats by rapid propagation of electrical activity through the Purkinje fiber (PF) network. PFs share common progenitors with contractile cardiomyocytes, yet the mechanisms of segregation and network morphogenesis are poorly understood. Here, we apply genetic fate mapping and temporal clonal analysis to identify murine cardiomyocytes committed to the PF lineage as early as E7.5. We find that a polyclonal PF network emerges by progressive recruitment of conductive precursors to this scaffold from a pool of bipotent progenitors. At late fetal stages, the segregation of conductive cells increases during a phase of rapid recruitment to build the definitive PF network through a non-cell autonomous mechanism. We also show that PF differentiation is impaired in Nkx2-5 haploinsufficient embryos leading to failure to extend the scaffold. In particular, late fetal recruitment fails, resulting in PF hypoplasia and persistence of bipotent progenitors. Our results identify how transcription factor dosage regulates cell fate divergence during distinct phases of PF network morphogenesis.
The essential inner membrane protein YejM is a metalloenzyme
Authors: Gabale Uma , Peña Palomino Perla Arianna , Kim HyunAh , Chen Wenya , Ressl Susanne 
Published: October 2020

AbstractRecent recurrent outbreaks of Gram-negative bacteria show the critical need to target essential bacterial mechanisms to fight the increase of antibiotic resistance. Pathogenic Gram-negative bacteria have developed several strategies to protect themselves against the host immune response and antibiotics. One such strategy is to remodel the outer membrane where several genes are involved.yejMwas discovered as an essential gene inE. coliandS. typhimuriumthat plays a critical role in their virulence by changing the outer membrane permeability. How the inner membrane protein YejM with its periplasmic domain changes membrane properties remains unknown. Despite overwhelming structural similarity between the periplasmic domains of two YejM homologues with hydrolases like arylsulfatases, no enzymatic activity has been previously reported for YejM. Our studies reveal an intact active site with bound metal ions in the structure of YejM periplasmic domain. Furthermore, we show that YejM has a phosphatase activity that is dependent on the presence of magnesium ions and is linked to its function of regulating outer membrane properties. Understanding the molecular mechanism by which YejM is involved in outer membrane remodeling will help to identify a new drug target in the fight against the increased antibiotic resistance.
Accurate population estimation of Caprinae using camera traps and distance sampling
Authors: Harris Grant M. , Butler Matthew J. , Stewart David R. , Rominger Eric M. , Ruhl Caitlin Q. 
Published: October 2020

AbstractWith most of the world’sCaprinaetaxa threatened with extinction, the IUCN appeals to the development of simple and affordable sampling methods that will produce credible abundance and distribution data for helping conserve these species inhabiting remote areas. Traditional sampling approaches, like aerial sampling or mark-capture-recapture, can generate bias by failing to meet sampling assumptions, or by incurring too much cost and logistical burden for most projects to address them. Therefore, we met the IUCN’s challenge by testing a sampling technique that leverages imagery from camera traps with conventional distance sampling, validating its operability in mountainous topography by comparing results to known abundances. Our project occurred within a captive facility housing a wild population of desert bighorn sheep (Ovis canadensis) in the Chihuahuan desert of New Mexico, which is censused yearly. True abundance was always within our 90% confidence bounds, and the mean abundance estimates were within 4.9 individuals (average) of the census values. By demonstrating the veracity of this straightforward and inexpensive sampling method, we provide confidence in its operability, urging its use to fill conservation voids forCaprinaeand other data-deficient species inhabiting rugged or heavily vegetated terrain.
LC–MS/MS and GC–MS profiling as well as the antimicrobial effect of leaves of selected Yucca species introduced to Egypt
Authors: El Sayed Abeer M. , Basam Samar M. , El-Naggar El-Moataz bellah A. , Marzouk Hanan S. , El-Hawary Seham 
Published: October 2020

AbstractFew studies thoroughly investigated different Yucca species introduced to Egypt. As a part of our ongoing investigation of the Yucca species; Yucca aloifolia and its variety Yucca aloifolia variegata, Yucca filamentosa, and Yucca elephantipes (Asparagaceae) were extensively subjected to phytochemical and antimicrobial investigation. Yucca species cultivated in Egypt showed no antimicrobial effect. GC/MS of the lipoid contents of Y. aloifolia variegata was carried out. Twenty-six fatty acids were identified. Saturated fatty acids established almost twice the unsaturated ones and constituted 64.64% of which palmitic acid and palmitoleic acid signifying 58.28% and 30.98%, respectively. Hydrocarbons were 21 constituting 39.64% of the unsaponifiable fraction. Only three sterols 42.36% were detected, major was γ-sitosterol. LC–MS/MS comparison of the 4 plant extracts imply that Y.aloifolia variegata L extract was the richest, which was apparent through its superior biological activity. LC–MS/MS analysis of the total alcoholic extract (Alc) of the leaves of Y.aloifolia variegata L. was performed using MS-techniques at different voltages; equal to 35 and 135 eV. Negative and positive-ion modes analyses at low fragmentation energy allowed the tentative identification of 41 and 34 compounds, respectively. The LC–ESI–MS/MS analysis in the positive mode proved to be better in the identification of saponins.
CDCA7 and HELLS suppress DNA:RNA hybrid-associated DNA damage at pericentromeric repeats
Authors: Unoki Motoko , Sharif Jafar , Saito Yuichiro , Velasco Guillaume , Francastel Claire , Koseki Haruhiko , Sasaki Hiroyuki 
Published: October 2020

AbstractImmunodeficiency, centromeric instability, facial anomalies (ICF) syndrome is a rare autosomal recessive disorder that is caused by mutations in either DNMT3B, ZBTB24, CDCA7, HELLS, or yet unidentified gene(s). Previously, we reported that the CDCA7/HELLS chromatin remodeling complex facilitates non-homologous end-joining. Here, we show that the same complex is required for the accumulation of proteins on nascent DNA, including the DNMT1/UHRF1 maintenance DNA methylation complex as well as proteins involved in the resolution or prevention of R-loops composed of DNA:RNA hybrids and ssDNA. Consistent with the hypomethylation state of pericentromeric repeats, the transcription and formation of aberrant DNA:RNA hybrids at the repeats were increased in ICF mutant cells. Furthermore, the ectopic expression of RNASEH1 reduced the accumulation of DNA damage at a broad range of genomic regions including pericentromeric repeats in these cells. Hence, we propose that hypomethylation due to inefficient DNMT1/UHRF1 recruitment at pericentromeric repeats by defects in the CDCA7/HELLS complex could induce pericentromeric instability, which may explain a part of the molecular pathogenesis of ICF syndrome.
Dependency of Queensland and the Great Barrier Reef’s tropical fisheries on reef-associated fish
Authors: Brown Christopher J. , Taylor William , Wabnitz Colette C. C. , Connolly Rod M. 
Published: October 2020

AbstractCoral reefs have been subject to mass coral bleaching, potentially causing rapid and widespread degradation of ecosystem services that depend on live coral cover, such as fisheries catch. Fisheries species in tropical waters associate with a wide range of habitats, so assessing the dependency of fisheries on coral reefs is important for guiding fishery responses to coral reef degradation. This study aimed to determine how fisheries catches associate with coral reefs in Queensland, Australia. Queensland’s largest fisheries did not target fish associated with reefs, but specific sectors, particularly aquarium fisheries and commercial fisheries in the mid to northern region had a high dependence on species that use coral reefs. Regions that had a greater relative area of coral reefs had higher catches of species that depend on live coral, suggesting that coral area could be used to predict the sensitivity of a jurisdiction’s fisheries to bleaching. Dynamic analysis of stock trends found that coral trout and red throat emperor, the two largest species by catch for the reef line fishery, were at risk of overfishing if habitat loss caused declines in stock productivity. Management of fisheries that are highly dependent on reefs may need to adapt to declining productivity, but further research to support ongoing reforms in Queensland’s fisheries is needed to quantitatively link reef degradation to stock production parameters is needed.
Improved hyperacuity estimation of spike timing from calcium imaging
Authors: Hoang Huu , Sato Masa-aki , Shinomoto Shigeru , Tsutsumi Shinichiro , Hashizume Miki , Ishikawa Tomoe , Kano Masanobu , Ikegaya Yuji , Kitamura Kazuo , Kawato Mitsuo , Toyama Keisuke 
Published: October 2020

AbstractTwo-photon imaging is a major recording technique used in neuroscience. However, it suffers from several limitations, including a low sampling rate, the nonlinearity of calcium responses, the slow dynamics of calcium dyes and a low SNR, all of which severely limit the potential of two-photon imaging to elucidate neuronal dynamics with high temporal resolution. We developed a hyperacuity algorithm (HA_time) based on an approach that combines a generative model and machine learning to improve spike detection and the precision of spike time inference. Bayesian inference was performed to estimate the calcium spike model, assuming constant spike shape and size. A support vector machine using this information and a jittering method maximizing the likelihood of estimated spike times enhanced spike time estimation precision approximately fourfold (range, 2–7; mean, 3.5–4.0; 2SEM, 0.1–0.25) compared to the sampling interval. Benchmark scores of HA_time for biological data from three different brain regions were among the best of the benchmark algorithms. Simulation of broader data conditions indicated that our algorithm performed better than others with high firing rate conditions. Furthermore, HA_time exhibited comparable performance for conditions with and without ground truths. Thus HA_time is a useful tool for spike reconstruction from two-photon imaging.
Neuroprotective effect of ACTH on collagenase-induced peri-intraventricular hemorrhage in newborn male rats
Authors: Martins Camila A. , Neves Laura Tartari , de Oliveira Marina M. B. P. , Bagatini Pamela Brambilla , Barboza Rafaela , Mestriner Régis Gemerasca , Xavier Léder Leal , Rasia-Filho Alberto A. 
Published: October 2020

AbstractPeri-intraventricular hemorrhage (PIVH) is a common and serious prematurity-related complication in neonates. Adrenocorticotropic hormone (ACTH) has neuroprotective actions and is a candidate to ameliorate brain damage following PIVH. Here, we tested the efficacy of ACTH1-24 on a collagenase-induced lesion of the germinal matrix (GM) in newborn male rats. Animals received microinjection of the vehicle (PBS, 2 µl) or collagenase type VII (0.3 IU) into the GM/periventricular tissue on postnatal day (PN) 2. Twelve hours later pups received microinjection of either the agonist ACTH1-24 (0.048 mg/kg), or the antagonist SHU9119 (antagonist of MCR3/MCR4 receptors, 0.01 mg/kg), or their combination. Morphological outcomes included striatal injury extension, neuronal and glial cells counting, and immunohistochemical expression of brain lesion biomarkers ipsilateral and contralateral to the hemorrhagic site. Data were evaluated on PN 8. Collagenase induced PIVH and severe ipsilateral striatal lesion. ACTH1-24 dampened the deleterious effects of collagenase-induced hemorrhage in significantly reducing the extension of the damaged area, the striatal neuronal and glial losses, and the immunoreactive expression of the GFAP, S100β, and NG2-glia biomarkers in the affected periventricular area. SHU9119 blocked the glial density rescuing effect of ACTH1-24. ACTH1-24 could be further evaluated to determine its suitability for preclinical models of PVH in premature infants.
Longitudinal plasma inflammatory proteome profiling during pregnancy in the Born into Life study
Authors: Hedman Anna M. , Lundholm Cecilia , Andolf Ellika , Pershagen Göran , Fall Tove , Almqvist Catarina 
Published: October 2020

AbstractThe maternal immune system is going through considerable changes during pregnancy. However, little is known about the determinants of the inflammatory proteome and its relation to pregnancy stages. Our aim was to investigate the plasma inflammatory proteome before, during and after pregnancy. In addition we wanted to test whether maternal and child outcomes were associated with the proteome. A cohort of 94 healthy women, enrolled in a longitudinal study with assessments at up to five time points around pregnancy, ninety-two inflammatory proteins were analysed in plasma with a multiplex Proximity Extension Assay. First, principal components analysis were applied and thereafter regression modelling while correcting for multiple testing. We found profound shifts in the overall inflammatory proteome associated with pregnancy stage after multiple testing (p < .001). Moreover, maternal body mass index (BMI) was associated with inflammatory proteome primarily driven by VEGFA, CCL3 and CSF-1 (p < .05). The levels of most inflammatory proteins changed substantially during pregnancy and some of these were related to biological processes such as regulation of immune response. Maternal BMI was significantly associated with higher levels of three inflammation proteins calling for more research in the interplay between pregnancy, inflammation and BMI.