bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of the yeastSaccharomycescerevisiae as a biosensor for the toxicity detection of toxic substances
Authors: Gong Linlin , Yang Guang , Yang Bo , Gu Jihui 
Published: January 2020

AbstractA whole-cell biosensor developed with yeastSaccharomycescerevisia to detect the toxicity of chlorothalonil has been developed. This biosensor relied on the inhibition effect for metabolism by toxicants to provide detection and the degree of toxicity to yeast cells. In order to further improve the toxic sensitivity of yeast cells biosensor, the effect of the action time, the initial pH value of the medium and the temperature on inhibiting cell growth were investigated. Response surface regression analysis was conducted to obtain optimal culture conditions. Th effects of treated yeast morphology, ROS, DNA, caspase 3 activity were analyzed. This optimized yeast as a biosensor was used to detect chlorothalonil and heavy metals. The results are as follows: at optimal culture conditions, EC50values of chlorothalonil to yeast biosensor determined at incubation time 4 h increased from 0.25 µg·mL-1in the control to 0.006 µg·mL-1, which increased by 41.67 times. Compared with the control yeast cells, the morphology of optimized yeast cells were more transparent, with significantly increased intracellular vesicle rate and cell membrane permeability, intracelluar ROS increased siginificantly, DNA bands extracted was ladder, and caspase 3 activity was stimulated. The yeast biosensor had a high sensitivity to heavy metals. After analysis, many treated cells were apoptosis which was the main reason for the increasing sensitivity to detect harmful substances. It was found that the method provides a new idea for the detection of harmful substances in the environment.Yeast cells biosensor could be used to detect harmful substances in the environment, sunch as chlorothalonil, heavy metals. Even through chemical analysis methods, such as ICP-MS and High Performance Liquid Choromatography (HPLC), have strengths in accuracy and limit of detection, it is impossible to evaluate the cytotoxicity and the biological effect of waste water by chemical result alone, and it is also expensive, prolix and complicated. However, the yeast cell biosensor is easy to operate, is sensitive to various toxicants, comparable to the other totxicity detection methods, is cheap in cost, and has. Therefore, the method which used yeast cells as biosensor will have great potential in the detection of the cytotoxicity of waste water in the future.
Interval between two sequential arrays determines their storage state in visual working memory
Authors: Li Ziyuan , Zhang Jiafeng , Liang Tengfei , Ye Chaoxiong , Liu Qiang 
Published: January 2020

AbstractThe visual information can be stored as either “active” representations in the active state or “activity-silent” representations in the passive state during the retention period in visual working memory (VWM). Catering to the dynamic nature of visual world, we explored how the temporally dynamic visual input was stored in VWM. In the current study, the memory arrays were presented sequentially, and the contralateral delay activity (CDA), an electrophysiological measure, was used to identify whether the memory representations were transferred into the passive state. Participants were instructed to encode two sequential arrays and retrieve them respectively, with two conditions of interval across the two arrays: 400ms and 800ms. These results provided strong evidence for the state-separated storage of two sequential arrays in different neural states if the interval between them was long enough, and the concurrent storage of them in the active state if the interval was relatively short. This conclusion was valid only when the participants encountered the task for the first time. Once participants have formed their mindset, they would apply the same storage mode to the subsequently extended or shortened interval condition.
Gene replacement therapy provides benefit in an adult mouse model of Leigh syndrome
Authors: Dulaurier Robin Reynaud , Benegiamo Giorgia , Marrocco Elena , Al-Tannir Racha , Surace Enrico Maria , Auwerx Johan , Decressac Michael 
Published: January 2020

AbstractMutations in nuclear-encoded mitochondrial genes are responsible for a broad spectrum of disorders among which Leigh syndrome (LS) is the most common in infancy. No effective therapies are available for this severe disease mainly because of the limited capabilities of the standard adeno-associated viral (AAV) vectors to transduce both peripheral organs and the central nervous system (CNS) when injected systemically in adults.Here, we used the brain-penetrating AAV-PHP.B vector to reinstate gene expression in theNdufs4KO mouse model of LS. Intravenous delivery of an AAV.PHP.B-Ndufs4 vector in 1-month old KO mice restored mitochondrial complex I activity in several organs including the CNS. This gene replacement strategy extended lifespan, rescued metabolic parameters, provided behavioral improvement, and corrected the pathological phenotype in the brain, retina, and heart ofNdufs4KO mice. These results provide a robust proof that gene therapy strategies targeting multiple organs can rescue fatal neurometabolic disorders with CNS involvement.
A Rainbow Reporter Tracks Single Cells and Reveals Heterogeneous Cellular Dynamics among Pluripotent Stem Cells and their Differentiated Derivatives
Authors: El-Nachef Danny , Shi Kevin , Beussman Kevin M. , Martinez Refugio , Regier Mary C. , Everett Guy W. , Murry Charles E. , Stevens Kelly R. , Young Jessica E. , Sniadecki Nathan J. , Davis Jennifer 
Published: January 2020

SummaryRecent single cell analyses have found molecular heterogeneities within populations of pluripotent stem cells (PSCs). A tool that tracks single cell lineages and their phenotypes longitudinally would reveal whether heterogeneity extends beyond molecular identity. Hence, we generated a stable Cre-inducible rainbow reporter human PSC line that provides up to 18 unique membrane-targeted fluorescent barcodes. These barcodes enable repeated assessments of single cells as they clonally expand, change morphology, and migrate. Owing to the cellular resolution of this reporter, we identified subsets of PSCs with enhanced clonal expansion, synchronized cell divisions, and persistent localization to colony edges. Reporter expression was stably maintained throughout directed differentiation into cardiac myocytes, cortical neurons, and hepatoblasts. Repeated examination of neural differentiation revealed self-assembled cortical tissues derive from clonally dominant progenitors. Collectively, these findings demonstrate the broad utility and easy implementation of this reporter line for tracking single cell behavior.
OvirusTdb: A Repository of Oncolytic Viruses used in Cancer Treatment
Authors: Lathwal Anjali , Kumar Rajesh , Raghava Gajendra P.S. 
Published: January 2020

AbstractOne of the emerging technologies to fight against cancer is oncolytic virus-based immunotherapy which directly lysis tumor cells. Recently, the FDA approved an oncolytic virus named T-vec for the treatment of melanoma; several hundred other viruses are in clinical trials. In order to facilitate the scientific community to fight against cancer, we build a repository of oncolytic viruses called OvirusTdb (https://webs.iiitd.edu.in/raghava/ovirustdb/). This is a manually curated repository where information is curated from research papers and patents. The current version of the repository maintains comprehensive information on therapeutically important oncolytic viruses with 5927 records where each record has 25 fields such as the virus species, cancer cell line, synergism with anti-cancer drugs, and many more. It stores information on 09 types of DNA and 15 types of RNA viruses; 300 recombinant and 09 wildtype viral strains; tested against 124 cancer types and 427 cancer cell lines. Approximately, 1047 records show improved anti-cancer response using combinatorial approach of chemotherapeutic agents with virus strains. Nearly, 3243 and 1506 records show cancer cell death via apoptosis induction and immune activation, respectively. In summary, a user-friendly web repository of oncolytic viruses for information retrieval and analysis have been developed to facilitate researchers in designing and discovering new oncolytic viruses for effective cancer treatment.
Molecular Mechanisms of Non-ionotropic NMDA Receptor Signaling
Authors: Stein Ivar S. , Park Deborah K. , Jahncke Jennifer N. , Flores Juan C. , Zito Karen 
Published: January 2020

AbstractStructural plasticity of dendritic spines is a key component of the refinement of synaptic connections during learning. Recent studies highlight a novel role for the NMDA receptor (NMDAR), independent of ion flow, in driving spine shrinkage and LTD. Yet little is known about the molecular mechanisms that link conformational changes in the NMDAR to changes in spine size and synaptic strength. Here, using two-photon glutamate uncaging to induce plasticity in hippocampal CA1 neurons from mice and rats, we demonstrate that p38 MAPK is required downstream of conformational NMDAR signaling to drive both spine shrinkage and LTD at individual dendritic spines. In a series of pharmacological and molecular genetic experiments, we identify key components of the non-ionotropic NMDAR signaling pathway driving dendritic spine shrinkage, including the interaction between NOS1AP and nNOS, nNOS enzymatic activity, activation of MK2 and cofilin, and signaling through CaMKII. Our results represent a large step forward in delineating the molecular mechanisms of non-ionotropic NMDAR signaling that drive the shrinkage and elimination of dendritic spines during synaptic plasticity.
Independent domestications shape the genetic pattern of a reproductive isolation system in rice
Authors: Xu Xun , Ge Song , Zhang Fu-Min 
Published: January 2020

AbstractSevere reproductive isolation (RI) exists between the two subspecies of rice,IndicaandJaponica, but in the wild ancestors no post-zygotic RI was found. The studies about the establishment of the interspecies RI of rice are still rear. A pair of rice hybrid sterility genes,DOPPELGANGER 1(DPL1) andDOPPELGANGER 2(DPL2), offers a convenient example to study the evolutionary history of RI genes. Either of the two loci has one non-functional allele (DPL1-andDPL2-). The hybrid pollen carrying bothDPL1-andDPL2-will be sterility.We collected 811 individuals:Oryza sativa(132), the two wild ancestorsO. nivara(296) andO. rufipogon(383) as well as 20DPL1and 34DPL2sequences ofO. sativafrom on-line databases. We analysed the genetic and geographic pattern ofDPLsin all three species to determine the origination regions ofDPL1-andDPL2-. The neutral test as well as the diversities of nucleotide and haplotype were used to detect if selection shaped the pattern ofDPLs.We found thatDPL1-andDPL2-of rice emerged from wild ancestor populations in South Asia and South China through two respective domestications. Comparing with the ancestral populations,DPL1-andDPL2-both showed reduce of diversities, however their frequencies increased in rice. We assume that the reduce of diversities due to the bottleneck effect of domestication while the loss of one copy was preferred by artificial selection for cost savings.
Catabolism of 3-hydroxypyridine byEnsifer adhaerensHP1: a novel four-component gene encoding 3-hydroxypyridine dehydrogenase HpdA catalyzes the first step of biodegradation
Authors: Wang Haixia , Wang Xiaoyu , Ren Hao , Wang Xuejun , Lu Zhenmei 
Published: January 2020

Abstract3-Hydroxypyridine (3HP) is an important natural pyridine derivative.Ensifer adhaerensHP1 can utilize 3HP as the sole source of carbon, nitrogen and energy to grow. However, the genes responsible for the degradation of 3HP remain unknown. In this study, we predicted that a gene cluster, designated3hpd, may be responsible for the degradation of 3HP. The initial hydroxylation of 3HP is catalyzed by a four-component dehydrogenase (HpdA1A2A3A4), leading to the formation of 2,5-dihydroxypyridine (2,5-DHP) inE. adhaerensHP1. In addition, the SRPBCC component in HpdA existed as a separate subunit, which is different from other SRPBCC-containing molybdohydroxylases acting on N-heterocyclic aromatic compounds. Our findings provide a better understanding of the microbial degradation of pyridine derivatives in nature. Additionally, research on the origin of the discovered four-component dehydrogenase with a separate SRPBCC domain may be of great significance.Importance3-Hydroxypyridine is an important building block for synthesizing drugs, herbicides and antibiotics. Although the microbial degradation of 3-hydroxypyridine has been studied for many years, the molecular mechanisms remain unclear. Here, we show that3hpdis responsible for the catabolism of 3-hydroxypyridine. The3hpdgene cluster was found to be widespread inActinobacteria,Rubrobacteria,Thermoleophilia, andAlpha-,Beta-, andGammaproteobacteria, and the genetic organization of the3hpdgene clusters in these bacteria showed high diversity. Our findings provide new insight into the catabolism of 3-hydroxypyridine in bacteria.
Tissue engineered model of hepatic breast cancer micrometastasis shows host-dependent colonization patterns and drug responses
Authors: Guller Anna , Rozova Vlada , Kuschnerus Inga , Khabir Zahra , Nadort Annemarie , Garcia-Bennett Alfonso , Liang Liuen , Qian Yi , Goldys Ewa M. , Zvyagin Andrei V. 
Published: January 2020

ABSTRACTEarly stages of colonization of distant organs by metastatic cancer cells (micrometastasis) remain almost inaccessible to study due to lack of relevant experimental approaches. Here, we show the first 3D tissue engineered model of hepatic micrometastasis of triple negative breast cancer (TNBC). It reproduces characteristic histopathological features of the disease and reveals that metastatic TNBC cells colonize liver parenchymal and stromal extracellular matrix with different speed and by different strategies. These engineered tumors induce the angiogenic switch when grafted in vivo, confirming their metastatic-specific behaviour. Furthermore, we proved feasibility and biological relevance of our model for drug and nanoparticle testing and found a down-regulatory effect of the liver microenvironment of the sensitivity of TNBC cells to chemotherapeutic drug doxorubicin in free and nanoformulated forms. The convenient and affordable methodology established here can be translated to other types of metastatic tumors for basic cancer biology research and adapted for high-throughput assays.
NAChRDB: A Web Resource of Structure-Function Annotations to Unravel the Allostery of Nicotinic Acetylcholine Receptors
Authors: Chareshneu Aliaksei , Pant Purbaj , José Tristão Ramos Ravi , Gökbel Tuğrul , Ionescu Crina-Maria , Koča Jaroslav 
Published: January 2020

AbstractSummaryDue to their paramount importance, near-ubiquitous presence, and complex nature, nicotinic acetylcholine receptors (nAChRs) have remained the focus of intensive research for over 50 years. The vast amount of knowledge accumulated on the topic has become extremely difficult to navigate. NAChRDB addresses this challenge by providing web-based, real-time access to curated residue-level functional annotations of neuromuscular nAChRs with interactive 3D visualization and sequence alignment. NAChRDB provides systematic access to experimental observations and predictions from computational studies reported in the literature or performed specifically to complement current knowledge, which allows new findings to be interpreted in a more holistic context, both from a structural and a functional perspective. NAChRDB aims to serve as an invaluable resource for identifying gaps in knowledge and for guiding discovery through structural and molecular biology experiments, especially when exploring the allosteric mechanisms underlying neuromuscular nAChR function and pathology.Availability and ImplementationNAChRDB is freely available online, with a self-explanatory interface and useful tool tips (https://crocodile.ncbr.muni.cz/Apps/NAChRDB/). No installation or user registration is required. NAChRDB content is stored in .json format, queried using Python, and rendered in browser using Javascript and WebGL (LiteMol). NAChRDB is highly responsive and accessible through any modern Internet browser on desktop and mobile devices.Contactjkoca@ceitec.czSupplementary informationSupplementary data are available online.
In vivocontrol of the ezrin/radixin/moesin protein ERM-1 inC. elegans
Authors: Ramalho João J. , Nicolle Ophélie , Michaux Grégoire , Boxem Mike 
Published: January 2020

AbstractERM proteins are conserved regulators of cortical membrane specialization, that function as membrane–actin linkers and molecular hubs. Activity of ERM proteins requires a conformational switch from an inactive cytoplasmic form into an active membrane- and actin-bound form, which is thought to be mediated by sequential PIP2-binding and phosphorylation of a conserved C-terminal threonine residue. Here, we use the singleC. elegansERM ortholog, ERM-1, to study the contribution of these regulatory events to ERM activity and tissue formationin vivo. Using CRISPR/Cas9-generatederm-1mutant alleles we demonstrate that PIP2-binding is critically required for ERM-1 function. In contrast, dynamic regulation of C-terminal T544 phosphorylation is not essential but modulates ERM-1 apical localization and dynamics in a tissue-specific manner, to control cortical actin organization and drive lumen formation in epithelial tubes. Our work highlights the dynamic nature of ERM protein regulation during tissue morphogenesis and the importance of C-terminal phosphorylation in fine-tuning ERM activity in a tissue-specific context.
Changes in the gene expression profile during spontaneous migraine attacks
Authors: Kogelman Lisette J.A. , Falkenberg Katrine , Buil Alfonso , Erola Pau , Courraud Julie , Laursen Susan Svane , Michoel Tom , Olesen Jes , Hansen Thomas F. 
Published: January 2020

AbstractObjectiveMigraine occurs in clearly defined attacks and thus lends itself to investigate changes during and outside attack. Gene expression fluctuates according to environmental and endogenous events and therefore is likely to reveal changes during a migraine attack. We examined the hypothesis that changes in RNA expression during and outside of a spontaneous migraine attack exist which are specific to the migraine attack.MethodsWe collected blood samples from 27 migraine patients during an attack, two hours after treatment with subcutaneous sumatriptan, on a headache-free day and after a cold pressor test. All patients were deeply phenotyped, including headache characteristics and treatment effect during the sampling. RNA-Sequencing, genotyping, and steroid profiling was performed on all samples. RNA-Sequences were analyzed at gene level (differential expression analysis) and at network level, and we integrated transcriptomic and genomic data.ResultsWe found 29 differentially expressed (DE) genes between ‘attack’ and ‘after treatment’, after subtracting non-migraine specific genes, i.e. genes related to a general pain/stress response. DE genes were functioning in fatty acid oxidation, signaling pathways and immune-related pathways. Network analysis revealed molecular mechanisms affected by change in gene interactions during the migraine attack, e.g. ‘ion transmembrane transport’ and ‘response to stress’. Integration of genomic and transcriptomic data revealed pathways related to sumatriptan treatment, i.e. ‘5HT1 type receptor mediated signaling pathway’.InterpretationUsing a paired-sample design, we uniquely investigated intra-individual changes in the gene expression during a migraine attack. We revealed both genes and pathway potentially involved in the pathophysiology of migraine.
A phospho-switch in the N-terminus of NRT2.1 affects nitrate uptake by controlling the interaction of NRT2.1 with NAR2.1
Authors: Li Zhi , Wu Xu Na , Jaquot Aurore , Lejay Larence , Schulze Waltraud X 
Published: January 2020

AbstractNRT2.1 can be phosphorylated at five different sites within N- and C-terminus. Here, we provide a systematic functional characterization of phosphorylation at S21 and S28 within the N-terminus of NRT2.1. We used existing phosphoproteomic data sets of nitrate starvation and nitrate resupply to construct a site-specific correlation network identifying kinase candidates to phosphorylate NRT2.1. By this approach, we identified NITRATEUPTAKEREGULATORYKINASE1 (AT5G49770) which itself was regulated by phosphorylation at S839 and S870 within its kinase domain. In the active state, when S839 was dephosphorylated and S870 was phosphorylated, NURK1 was found to interact with NRT2.1 at dephosphorylated S28. Upon that interaction, NURK1 can phosphorylate NRT2.1 at S21. Phosphorylation of NRT2.1 at S21 resulted in low interaction of NRT2.1 with its activator protein NAR2.1. By contrast, phosphorylation of NRT2.1 at S28 by a yet unknown kinase enhanced the interaction with NAR2.1, but inhibited the interaction with NURK1. We propose that serines S21 and S28 are involved in a phospho-switch mechanism and by which the interaction of NRT2.1 with its activator NAR2.1, and thus NRT2.1 activity, is modulated. NURK1 here was identified as the kinase affecting this phospho-switch through phosphorylation of NRT2.1 at S21 leading to inactivation of NRT2.1.
Crystal structure of calcium bound outer membrane phospholipase A (OmpLA) fromSalmonella typhiandin silicoanti-microbial screening
Authors: Perumal Perumal , Raina Rahul , Narayanan Sundara Baalaji , Arockiasamy Arulandu 
Published: January 2020

AbstractAntimicrobial resistance is widespread inSalmonellainfections that affect millions worldwide.Salmonella typhiand other Gram-negative bacterial pathogens encode an outer membrane phospholipase A (OmpLA), crucial for their membrane integrity. Further, OmpLA is implicated in pathogen internalization, haemolysis, acid tolerance, virulence and sustained infection in human hosts. OmpLA is an attractive drug target for developing novel anti-microbials that attenuate virulence, as the abrogation of OmpLA encodingpldAgene causes loss of virulence. Here, we present the crystal structure ofSalmonella typhiOmpLA in dimeric calcium bound activated state at 2.95 Å. Structure analysis suggests that OmpLA is a potential druggable target. Further, we have identified and shortlisted small molecules that bind at the dimer interface using structure basedin silicoscreening, docking and molecular dynamics. While it requires further experimental validation, anti-microbial discovery targeting OmpLA from gram-negative pathogens offers an advantage as OmpLA is required for virulence.