bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations of human lung and gut microbiome in non-small cell lung carcinomas and distant metastasis
Authors: Lu Hui , Gao Na L. , Wei Chunhua , Wang Jiaojiao , Tong Fan , Li Huanhuan , Zhang Ruiguang , Ma Hong , Yang Nong , Zhang Yongchang , Wang Ye , Liang Zhiwen , Zeng Hao , Chen Wei-Hua , Dong Xiaorong 
Published: January 2020

AbstractBackgroundNon-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Although dysbiosis of lung and gut microbiota have been associated with NSCLC, their relative contributions are unclear; in addition, their roles in distant metastasis (DM) are still illusive.ResultsWe surveyed the fecal and sputum (as a proxy for lung) microbiota in healthy controls and NSCLC patients of various stages, and found significant perturbations of gut- and sputum-microbiota in patients with NSCLC and DM. Machine-learning models combining both microbiota (mixed models) performed better than either dataset in patient stratification, with the highest area under the curve (AUC) value of 0.842. Sputum-microbiota contributed more than the gut in the mixed models; in addition, sputum-only models performed similarly to the mixed models in most cases. Several microbial-biomarkers were shared by both microbiota, indicating their similar roles at distinct body sites. Microbial-biomarkers of distinct disease stages were mostly shared, suggesting biomarkers for distant metastasis could be acquired early. Furthermore,Pseudomonas aeruginosa, a species previously associated with wound infections, was significantly more abundant in brain metastasis, indicating distinct types of DMs could have different microbial-biomarkers.ConclusionOur results indicate that alterations of sputum-microbiota have stronger relationships with NSCLC and distant metastasis than the gut, and strongly support the feasibility of metagenome-based non-invasive disease diagnosis and risk evaluation.
Late onset of Syt2a expression at synapses relevant to social behavior
Authors: Goode Collette , Voeun Mae , Ncube Denver , Eisen Judith , Washbourne Philip , Tallafuss Alexandra 
Published: January 2020

AbstractAs they form, synapses go through various stages of maturation and refinement. These steps are linked to significant changes in synaptic function, potentially resulting in changes in behavior. Here, we examined the distribution of the synaptic vesicle protein Synaptotagmin 2a (Syt2a) during development of the zebrafish nervous system. Syt2a is widely distributed throughout the midbrain and hindbrain early during larval development but very weakly expressed in the forebrain. Later in development, Syt2a expression levels increase, particularly in regions associated with social behavior, and most intriguingly, around the time social behavior becomes apparent. We provide evidence that Syt2a localizes to synapses on socially-relevant neurons in the ventral forebrain, co-localizing with tyrosine hydroxylase, a biosynthetic enzyme in the dopamine pathway. Our results suggest a maturation step for synapses in the forebrain that are spatiotemporally related to social behavior.
Differential proteomic analysis by SWATH-MS unravels the most dominant mechanisms underlying yeast adaptation to non-optimal temperatures under anaerobic conditions
Authors: Pinheiro Tânia , Lip Ka Ying Florence , García-Ríos Estéfani , Querol Amparo , Teixeira José , van Gulik Walter , Guillamón José Manuel , Domingues Lucília 
Published: January 2020

AbstractElucidation of temperature tolerance mechanisms in yeast is essential for enhancing cellular robustness of strains, providing more economically and sustainable processes. We investigated the differential responses of three distinctSaccharomyces cerevisiaestrains, an industrial wine strain, ADY5, a laboratory strain, CEN.PK113-7D and an industrial bioethanol strain, Ethanol Red, grown at sub- and supra-optimal temperatures under chemostat conditions. We employed anaerobic conditions, mimicking the industrial processes. The proteomic profile of these strains was performed by SWATH-MS, allowing the quantification of 997 proteins, data available via ProteomeXchange (PXD016567). Our analysis demonstrated that temperature responses differ between the strains; however, we also found some common responsive proteins, revealing that the response to temperature involves general stress and specific mechanisms. Overall, sub-optimal temperature conditions involved a higher remodeling of the proteome. The proteomic data evidenced that the cold response involves strong repression of translation-related proteins as well as induction of amino acid metabolism, together with components related to protein folding and degradation while, the high temperature response mainly recruits amino acid metabolism. Our study provides a global and thorough insight into how growth temperature affects the yeast proteome, which can be a step forward in the comprehension and improvement of yeast thermotolerance.
Correlation-based and feature-driven mutation signature analyses to identify genetic features associated with DNA mutagenic processes in cancer genomes
Authors: Jeong Hye Young , Yoo Jinseon , Kim Hyunwoo , Kim Tae-Min 
Published: January 2020

AbstractMutation signatures represent unique sequence footprints of somatic mutations resulting from specific DNA mutagenic and repair processes; however, their causal associations and potential utility for genome research remain largely unknown. In this study, we performed PanCancer-scale correlative analyses to identify the genomic features associated with tumor mutation burdens (TMB) and individual mutation signatures. We observed that TMB was correlated with tumor purity, ploidy, and the level of aneuploidy, as well as with the expression of cell proliferation-related genes representing genomic covariates in evaluating TMB. Correlative analyses of mutation signature levels with genes belonging to DNA damage-repair processes revealed that deficiencies ofNHEJ1andALKBH3may elevate TMB levels in cancer genomes accompanying APOBEC overactivity and DNA mismatch repair deficiency, respectively. We further employed a strategy to identify feature-driven,de novomutation signatures and demonstrated they can be reconstructed using known causal features such as APOBEC overexpression, MLH1 underexpression,POLEmutations, and the level of homologous recombination deficiency. We further demonstrated, that tumor hypoxia-related mutation signatures are similar to those associated with APOBEC suggesting that APOBEC-related mutagenic activity mediates hypoxia-related mutational consequences in cancer genomes, and also, that mutation signatures can be further used to predict hypoxic tumors. Taken together, our study advances mutation signature-level mechanistic insights in cancer genomes, extending categories of cancer-relevant mutation signatures and their potential biological implications.Author summaryMutation signature analysis is powerful in deciphering the causative mutagenic events and their contributions in individual cancer genomes, but the causal relationship of individual mutation signatures are still largely unknown. PanCancer-scaled correlative analysis revealed mutation resource candidates in cancer genomes such asNHEJ1andALKBH3deficiencies that may facilitate the accumulation of mutations in the setting of APOBEC overactivity and DNA mismatch repair deficiency, respectively. A feature-driven mutation discovery approach was employed to identify the mutation signatures representing homologous recombination deficiency and tumor hypoxia, the extent of which may serve as mutation-based phenotypic measures, previously estimated by DNA copy number alterations and mRNA expression signatures, respectively. Our study advances our understanding into the mechanistic insights of mutation signatures and proposes a method to utilize somatic mutations as a molecular proxy in terms of mutation signatures.
Multidrug resistance and high prevalence of class 1 integrons inEscherichia coliisolated from waters and vegetables in Nsukka and Enugu, Nigeria
Authors: Chigor Chinyere B. , Ibangha Ini-Abasi I. , Nweze Nkechinyere O. , Ozochi Chizoba A. , Onuora Valentino C. , Titilawo Yinka , Chernikova Tatyana N. , Golyshin Peter N. , Chigor Vincent N. 
Published: January 2020

AbstractIn spite of treated wastewater presenting itself as an attractive alternative to scarce quality water in the developing countries, the associated contamination of fresh produce by irrigation waters leading to outbreak of foodborne illnesses is on the rise. Horizontal transfer of integrons play important role in the spread and maintenance of antimicrobial resistance among strains ofEscherichia coli. This study assessed the effluents from the University of Nigeria, Nsukka Wastewater Treatment Plant (UNN-WWTP) as well as vegetables irrigated with the effluent, and vegetables sold in selected markets from Nsukka and Enugu cities for the presence ofE. coliand determined the prevalence integrons in multidrug-resistant isolates. Isolation ofE. coliwas done using eosin methylene blue agar and isolates subjected to Gram staining for identification of presumptive colonies. Confirmation ofE. coliwas achieved by polymerase chain reaction (PCR) technique, targeting beta-glucuronidase (uidA). Resistance to antibiotics was determined using the Bauer-Kirby disk diffusion assay and the Clinical and Laboratory Standard Institute criteria. Integrons were detected by multiplex PCR using primers specific for class 1 and 2 integrons. A total of 178E. coliisolates were obtained from WWTP effluent (41), and vegetables from greenhouse (46), farms (55) and market (36). Multi-drug resistance was detected in all the isolates, ranging from five-drug resistance in a single isolate to 16-drug resistance patterns in two different isolates. Of the total isolates, class 1 integrons were abundantly detected in 175 (98.3%) and class 2 in 5 (2.8%). All the class 2 integrons were found in isolates that were positive for class 1. The high detection ofE. coliin the studied effluent and vegetables pose potential public health hazards heightened by observed multidrug resistance in all the isolates and the high prevalence of class 1 integron. It is concluded that the vegetable samples are significant reservoirs for potentially pathogenicE. coli.Therefore, vegetable irrigation farming with unsafe water should be discontinued, while appropriate improvement strategies to ensure compliance should be facilitated without further delay.
The conserved herpesviral kinase ORF36 activates B2 retrotransposons during murine gammaherpesvirus infection
Authors: Schaller Aaron M. , Tucker Jessica , Willis Ian , Glaunsinger Britt A. 
Published: January 2020

ABSTRACTShort interspersed nuclear elements (SINEs) are RNA polymerase III (RNAPIII) transcribed, retrotransposable noncoding RNA (ncRNA) elements ubiquitously spread throughout mammalian genomes. While normally silenced in healthy somatic tissue, SINEs can be induced during infection with DNA viruses, including the model murine gammaherpesvirus MHV68. Here, we explored the mechanisms underlying MHV68 activation of SINE ncRNAs. We demonstrate that lytic MHV68 infection of B cells, macrophages and fibroblasts leads to robust activation of the B2 family of SINEs in a cell autonomous manner. B2 ncRNA induction requires neither host innate immune signaling factors nor involvement of the RNAPIII master regulator Maf1. However, we identify MHV68 ORF36, the conserved herpesviral kinase, as playing a key role in B2 induction during lytic infection. SINE activation is linked to ORF36 kinase activity and can also be induced by HDAC1/2 inhibition, which is one of the known ORF36 functions. Collectively, our data suggest that ORF36-mediated changes in chromatin modification contribute to B2 activation during MHV68 infection, and that this activity is conserved in other herpesviral protein kinase homologs.AUTHOR SUMMARYViral infection dramatically changes the levels of many types of RNA in a cell. In particular, certain oncogenic viruses activate expression of repetitive genes called retrotransposons, which are normally silenced due to their ability to copy and spread throughout the genome. Here, we established that infection with the gammaherpesvirus MHV68 leads to a dramatic induction of a class of noncoding retrotransposons called B2 SINEs in multiple cell types. We then explored how MHV68 activates B2 SINEs, revealing a role for the conserved herpesviral protein kinase ORF36. Both ORF36 kinase-dependent and kinase-independent functions contribute to B2 induction, perhaps through ORF36 targeting of proteins involved in controlling the accessibility of chromatin surrounding SINE loci. Understanding features underlying induction of these elements following MHV68 infection should provide insight into core elements of SINE regulation, as well as dis-regulation of SINE elements associated with disease.
Lipid-specific labeling of enveloped viruses with quantum dots for single-virus tracking
Authors: Zhang Li-Juan , Wang Shaobo , Xia Li , Lv Cheng , Tang Hong-Wu , Xiao Gengfu , Pang Dai-Wen 
Published: January 2020

AbstractQuantum dots (QDs) possess optical properties of superbright fluorescence, excellent photostability, narrow emission spectra, and optional colors. Labeled with QDs, single molecules/viruses can be rapidly and continuously imaged for a long time, providing more detailed information than labeled with other fluorophores. While they are widely used to label proteins in single-molecule tracking studies, QDs have rarely been used to study virus infection, mainly due to lack of accepted labeling strategies. Here, we report a general method to mildly and readily label enveloped viruses with QDs. Lipid-biotin conjugates were used to recognize and mark viral lipid membranes, and streptavidin (SA)-QD conjugates were used to light them up. Such a method allowed enveloped viruses to be labeled in 2 hours with specificity and efficiency up to 99% and 98%. The intact morphology and the native infectivity of viruses could be furthest preserved. With the aid of this QD labeling method, we lit wild-type (WT) and mutant Japanese encephalitis virus (JEV) up, tracked their infection in living Vero cells, and found that H144A and Q258A substitutions in the envelope (E) protein didn’t affect the virus intracellular trafficking. The lipid-specific QD labeling method described in this study provides a handy and practical tool to readily “see” the viruses and follow their infection, facilitating the widespread use of single-virus tracking and the uncovering of complex infection mechanisms.Author summaryVirus infection in host cells is a complex process comprising a large number of dynamic molecular events. Single-virus tracking is a versatile technique to study these events. To perform this technique, viruses must be fluorescently labeled to be visible to fluorescence microscopes. Quantum dot is a kind of fluorescent tags that has many unique optical properties. It has been widely used to label proteins in single-molecule tracking studies, but rarely used to study virus infection, mainly due to lack of accepted labeling method. In this study, we developed a lipid-specific method to readily, mildly, specifically, and efficiently label enveloped viruses with quantum dots by recognizing viral envelope lipids with lipid-biotin conjugates and recognizing these lipid-biotin conjugates with streptavidin-quantum dot conjugates. Such a method is superior to the commonly used DiD/DiO labeling and the other QD labeling methods. It is not only applicable to normal viruses, but also competent to label the key protein-mutated viruses and the inactivated high virulent viruses, providing a powerful tool for single-virus tracking.
Myosin X interaction with KIF13B, a crucial pathway for Netrin-1-induced axonal development
Authors: Yu Hua-Li , Peng Yun , Zhao Yang , Lan Yong-Sheng , Wang Bo , Zhao Lu , Sun Dong , Pan Jin-Xiu , Dong Zhao-Qi , Mei Lin , Ding Yu-Qiang , Zhu Xiao-Juan , Xiong Wen-Cheng 
Published: January 2020

ABSTRACTMyosin X (Myo X) transports cargos to the tip of filopodia for cell adhesion, migration, and neuronal axon guidance. Deleted in Colorectal Cancer (DCC) is one of Myo X cargos essential for Netrin-1-regulated axon pathfinding. Myo X’s function in axon development in vivo and the underlying mechanisms remain poorly understood. Here, we provide evidence for Myo X’s function in Netrin-1-DCC regulated axon development in mouse neocortex. Knocking-out (KO) or knocking-down (KD) Myo X in embryonic cortical neurons impairs axon initiation and contralateral branching/targeting. Similar axon deficits are detected in Netrin-1-KO or DCC-KD cortical neurons. Myo X interacts with KIF13B (a kinesin family motor protein), which is induced by Netrin-1. Netrin-1 promotes anterograde transportation of Myo X into axons in KIF13B dependent manner. KIF13B-KD cortical neurons exhibit similar axon deficits. These results suggest Myo X-KIF13B as a critical pathway for Netrin-1 promoted axon initiation and branching/targeting.
Resolving brain organoid heterogeneity by mapping single cell genomic data to a spatial reference
Authors: Fleck Jonas Simon , He Zhisong , Boyle Michael James , Camp J. Gray , Treutlein Barbara 
Published: January 2020

ABSTRACTSelf-organizing tissues resembling brain regions grown in vitro from human stem cells (so-called organoids or spheroids) offer exciting possibilities to study human brain development, disease, and evolution. Brain organoids or spheroids are complex and can contain cells at various stages of differentiation from different brain structures. Single-cell genomic methods provide powerful approaches to explore cell composition, differentiation trajectories, gene regulation, and genetic perturbations in brain organoid systems. However, it remains a major challenge to understand the cellular heterogeneity observed within and between individual organoids. Here, we have developed a computational approach (VoxHunt) to assess brain organoid patterning, developmental state, and cell composition through systematic comparisons to three-dimensionalin situhybridization data from the Allen Brain Atlas. Cellular transcriptomes as well as accessible chromatin landscapes can be compared to spatial transcript patterns in the developing mammalian brain, which enables characterization and visualization of organoid cell compositions. VoxHunt will be useful to assess novel organoid engineering protocols and to annotate cell fates that emerge in organoids during genetic and environmental perturbation experiments.
Structure and mechanism of human diacylglycerol acyltransferase 1
Authors: Wang Lie , Qian Hongwu , Nian Yin , Han Yimo , Ren Zhenning , Zhang Hanzhi , Hu Liya , Prasad B. V. Venkataram , Yan Nieng , Zhou Ming 
Published: January 2020

SummaryHuman diacylglycerol O-acyltransferase-1 (hDGAT1) synthesizes triacylglycerides and is required for dietary fat absorption and fat storage. The lack of 3-dimensional structure has limited our understanding of substrate recognition and mechanism of catalysis, and hampers rational targeting of hDGAT1 for therapeutic purposes. Here we present the structure of hDGAT1 in complex with a substrate oleoyl Coenzyme A at 3.1 Å resolution. hDGAT1 forms a homodimer and each protomer has nine transmembrane helices that carve out a hollow chamber in the lipid bilayer. The chamber encloses highly conserved catalytic residues and has separate entrances for the two substrates fatty acyl Coenzyme A and diacylglycerol. The N-terminus of hDGAT1 makes extensive interactions with the neighboring protomer, and is required for enzymatic activity.
Controlling brain state prior to stimulation of parietal cortex prevents deterioration of sustained attention
Authors: Edwards Grace , Contò Federica , Bucci Loryn K. , Battelli Lorella 
Published: January 2020

AbstractSustained attention is a limited resource which declines during daily tasks. Such decay is exacerbated in clinical and aging populations. Recent research has demonstrated that inhibition of the intraparietal sulcus (IPS) using low-frequency transcranial magnetic stimulation (LF-rTMS) can lead to an upregulation of functional communication within the attention network. Attributed to functional compensation for the inhibited node, this boost outlasts the stimulation for tens of minutes. Despite the neural change, no behavioral correlate has been found in healthy subjects, a necessary direct evidence of functional compensation. To understand the functional significance of neuromodulatory induced fluctuations on attention, we sought to boost the impact of LF-rTMS through controlling neural excitability prior to LF-rTMS, with the goal to impact behavior. Brain state was controlled using high-frequency transcranial random noise stimulation (HF-tRNS), shown to increase and stabilizes neuronal excitability. Using fMRI-guided stimulation protocols combining HF-tRNS and LF-rTMS, we tested the post-stimulation impact on sustained attention via a multiple object tracking task (MOT). Whilst attention deteriorated across time in the control conditions, HF-tRNS followed by LF-rTMS maintained attention performance up to 94 minutes, doubling the length of successful sustained attention. Multimethod stimulation was also more effective when targeting right IPS, supporting the notion of specialized attention processing in the right hemisphere. Used in a cognitive domain dependent on network-wide neural activity, this tool may be effective in causing lasting neural compensation important for clinical rehabilitation.
Soybean CHX protein GmSALT3 confers leaf Na+exclusion via a root derived mechanism, and Cl−exclusion via a shoot derived process
Authors: Qu Yue , Guan Rongxia , Bose Jayakumar , Henderson Sam W. , Wege Stefanie , Qiu Lijuan , Gilliham Matthew 
Published: January 2020

AbstractSoybean (Glycine max) yields are threatened by multiple stresses including soil salinity.GmSALT3confers net shoot exclusion for both Na+ and Cl−and improves salt tolerance of soybean; however, how the ER-localised GmSALT3 achieves this is unknown. Here, GmSALT3’s function was investigated in heterologous systems and near-isogenic lines that contained the full-lengthGmSALT3(NIL-T; salt-tolerant) or a truncated transcriptGmsalt3(NIL-S; salt-sensitive). GmSALT3 restored growth of K+-uptake-defectiveE. coliand contributed toward net influx and accumulation of Na+, K+, and Cl−inXenopus laevisoocytes, whileGmsalt3was non-functional. A time-course analysis of the NILs confirmed that shoot Cl−exclusion breaks down prior to Na+ exclusion, while grafting showed that shoot Na+exclusion occurs via a root xylem-based mechanism. In contrast, NIL-T plants exhibited significantly greater Cl−content in both the stem xylem and phloem sap compared to NIL-S, indicating that shoot Cl−exclusion likely depends upon novel phloem-based Cl−recirculation. NIL-T shoots grafted on NIL-S roots contained low shoot Cl−, which confirmed that Cl−recirculation is dependent on the presence of GmSALT3 in shoots. Overall, these findings provide new insights on GmSALT3’s impact on salinity tolerance and reveal a novel mechanism for shoot Cl– exclusion in plants.HighlightGmSALT3 improves soybean salt tolerance. Here, using heterologous expression, we found GmSALT3 is a functional ion transporter, and,in plantathat it confers shoot salt exclusion through root-based Na+xylem exclusion and shoot-based Cl−exclusion via phloem derived Cl-recirculation.