bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased FDG Uptake in a Giant Bone Island Mimicking Malignancy
Authors: Ran Pengcheng , Dong Aisheng , Wang Yang , Zhang Yu , Wu Shanshan 
Published: April 2018

Abstract
Histologically proven bone islands exhibiting increased FDG uptake have been rarely reported before. We present a case with active giant bone island in the left humerus showing increased FDG uptake with SUVmax of 3.8. The diagnosis was confirmed by open biopsy and follow-up. Increased osteoblastic activity, proliferating and active fibroblasts, and increased blood flow may contribute to the increased FDG uptake of this giant bone island. This case indicates bone island should be included in the differential diagnosis of abnormal FDG uptake in focal sclerotic bone lesions, especially in patients with known malignancy.
Incidental Detection of an Unusual Case of B-Cell Lymphoma of the Urachal Remnant on 18F-FDG PET/CT
Authors: Vadi Shelvin Kumar , Kumar Rajender , Mittal Bhagwant Rai , Singh Harmandeep , Bal Amanjit , Prakash Gaurav , Bhattacharya Anish 
Published: April 2018

Abstract
Neoplasms arising from the urachus are extremely rare. We present a case of a young woman with mild abdominal pain and a palpable swelling in the mid abdomen with incidental detection of a subumbilical mass. Repeated fine-needle aspiration cytology failed to reveal the true nature of the lesion. 18F-FDG PET/CT showed tracer uptake in the cranial end of urachal remnant lesion. Core biopsy from the site with maximal FDG uptake turned out to be lymphomatous involvement in urachus, which is extremely rare and previously unreported.
Pancreatic islet chromatin accessibility and conformation defines distal enhancer networks of type 2 diabetes risk
Authors: Greenwald William W , Chiou Joshua , Yan Jian , Qiu Yunjiang , Dai Ning , Wang Allen , Nariai Naoki , Aylward Anthony , Han Jee Yun , Kadakia Nikita , Barrufet Laura , Okino Mei-Lin , Drees Frauke , Vinckier Nicholas , Minichiello Liliana , Gorkin David , Avruch Joseph , Frazer Kelly , Sander Maike , Ren Bing , Gaulton Kyle J 
Published: April 2018

AbstractThe gene targets of enhancer activity in pancreatic islets are largely unknown, impeding discovery of islet regulatory networks involved in type 2 diabetes (T2D) risk. We mapped chromatin state, accessibility and conformation using ChIP-seq, ATAC-seq and Hi-C in human pancreatic islets, which we integrated with T2D genetic fine-mapping and islet expression QTL data. Active islet regulatory elements preferentially interacted with other active elements, often at distances over 1MB, and we identified target genes for thousands of distal islet enhancers. A third of T2D risk signals mapped in islet enhancers, and target genes regulated by these signals were specifically involved in processes related to protein transport and secretion. Among implicated target genes of T2D islet enhancer signals with no prior known role in islet function, we demonstrated that reduced IGF2BP2 activity in mouse islets leads to impaired glucose-stimulated insulin secretion. These results link distal islet enhancer regulation of protein secretion and transport to genetic risk of T2D, and highlight the utility of high-throughput chromatin conformation maps to uncover the gene regulatory networks of complex disease.
A novel approach to modeling transcriptional heterogeneity identifies the oncogene candidate CBX2 in invasive breast carcinoma
Authors: Piqué Daniel G. , Montagna Cristina , Greally John M. , Mar Jessica C. 
Published: April 2018

AbstractOncogenes promote the development of and serve as therapeutic targets against subsets of cancers. Here, a new statistical approach that captures transcriptional heterogeneity in tumor and adjacent normal (i.e. tumor-free) mRNA expression profiles was developed to identify oncogene candidates that were overexpressed in a subset of breast tumors. Intronic DNA methylation was strongly associated with the overexpression of chromobox 2 (CBX2), an oncogene candidate that was identified using our method but not through prior analytical approaches. CBX2 overexpression in breast tumors was associated with the upregulation of genes involved in cell cycle progression and is associated with poorer 5-year survival. The predicted function of CBX2 was confirmed in vitro providing the first experimental evidence that CBX2 promotes breast cancer cell growth. Modeling mRNA expression heterogeneity in tumors is a novel powerful approach with the potential to uncover therapeutic targets that benefit subsets of cancer patients.
SoupX removes ambient RNA contamination from droplet based single-cell RNA sequencing data
Authors: Young Matthew D , Behjati Sam 
Published: April 2018

AbstractBackgroundDroplet based single-cell RNA sequence analyses assume all acquired RNAs are endogenous to cells. However, any cell free RNAs contained within the input solution are also captured by these assays. This sequencing of cell free RNA constitutes a background contamination that confounds the biological interpretation of single-cell transcriptomic data.ResultsWe demonstrate that contamination from this ‘soup’ of cell free RNAs is ubiquitous, with experiment-specific variations in composition and magnitude. We present a method, SoupX, for quantifying the extent of the contamination and estimating ‘background corrected’ cell expression profiles that seamlessly integrate with existing downstream analysis tools. Applying this method to several datasets using multiple droplet sequencing technologies, we demonstrate that its application improves biological interpretation of otherwise misleading data, as well as improving quality control metrics.ConclusionsWe present ‘SoupX’, a tool for removing ambient RNA contamination from droplet based single cell RNA sequencing experiments. This tool has broad applicability and its application can improve the biological utility of existing and future data sets.Key PointsThe signal from droplet based single cell RNA sequencing is ubiquitously contaminated by capture of ambient mRNA.SoupX is a method to quantify the abundance of these ambient mRNAs and remove them.Correcting for ambient mRNA contamination improves biological interpretation.
Disruption of The Psychiatric Risk Gene Ankyrin 3 Enhances Microtubule Dynamics Through GSK3/CRMP2 Signaling
Authors: Garza Jacob C , Qi Xiaoli , Gjeluci Klaudio , Leussis Melanie P , Basu Himanish , Reis Surya A , Zhao Wen Ning , Piguel Nicolas H , Penzes Peter , Haggarty Stephen J , Martens Gerard J , Poelmans Geert , Petryshen Tracey L 
Published: April 2018

AbstractThe ankyrin 3 gene (ANK3) is a well-established risk gene for psychiatric illness, but the mechanisms underlying its pathophysiology remain elusive. We examined the molecular effects of disrupting brain-specificAnk3isoforms in mouse and neuronal model systems. RNA sequencing of hippocampus fromAnk3+/-andAnk3+/+mice identified altered expression of 282 genes that were enriched for microtubule-related functions. Results were supported by increased expression of microtubule end-binding protein 3 (EB3), an indicator of microtubule dynamics, inAnk3+/-mouse hippocampus. Live-cell imaging of EB3 movement in primary neurons fromAnk3+/-mice revealed impaired elongation of microtubules. Using a CRISPR-dCas9-KRAB transcriptional repressor in mouse neuro-2a cells, we determined that repression of brain-specificAnk3increased EB3 expression, decreased tubulin acetylation, and increased the soluble:polymerized tubulin ratio, indicating enhanced microtubule dynamics. These changes were rescued by inhibition of glycogen synthase kinase 3 (GSK3) with lithium or CHIR99021, a highly selective GSK3 inhibitor. Brain-specificAnk3repression in neuro-2a cells increased GSK3 activity (reduced inhibitory phosphorylation) and elevated collapsin response mediator protein 2 (CRMP2) phosphorylation, a known GSK3 substrate and microtubule-binding protein. Pharmacological inhibition of CRMP2 activity attenuated the rescue of EB3 expression and tubulin polymerization inAnk3repressed cells by lithium or CHIR99021, suggesting microtubule instability induced byAnk3repression is dependent on CRMP2 activity. Taken together, our data indicate that aNK3 functions in neuronal microtubule dynamics through GSK3 and its downstream substrate CRMP2. These findings reveal cellular and molecular mechanisms underlying brain-specific ANK3 disruption that may be related to its role in psychiatric illness.
SpeciFlex: A Protocol for Mining Binding Site Conformational Selectivity in Structure-Based Inhibitor Discovery
Authors: Tonero Matthew E. , Kuhn Leslie A. 
Published: April 2018

AbstractSelectivity for a target site is challenging when the site is conserved in homologous proteins. A novel protocol is presented for attaining selectivity by taking advantage of conformational population differences between homologs. Conformational ensembles of the targeted protein and the homolog are compared to identify pockets significantly populated in the target, but rarely or never sampled in the homolog. SLIDE screening then identifies molecules that fit the unique pocket and also interact well with an adjacent substrate pocket. The SpeciFlex protocol, demonstrated for a pair of pyrophosphokinases, yields ligand candidates with good interactions in both the substrate and unique pockets of the targetYersinia pestisprotein, while selecting against interactions with the homologous site inEscherichia coli.
Instantaneous midbrain control of saccade kinematics
Authors: Smalianchuk Ivan , Jagadisan Uday , Gandhi Neeraj J. 
Published: April 2018

AbstractThe ability to interact with our environment requires the brain to transform spatially-represented sensory signals into temporally-encoded motor commands for appropriate control of the relevant effectors. For visually-guided eye movements, or saccades, the superior colliculus (SC) is assumed to be the final stage of spatial representation, and instantaneous control of the movement is achieved through a rate code representation in the lower brain stem. We questioned this dogma and investigated whether SC activity also employs a dynamic rate code, in addition to the spatial representation. Noting that the kinematics of repeated movements exhibits trial-to-trial variability, we regressed instantaneous SC activity with instantaneous eye velocity and found a robust correlation throughout saccade duration. Peak correlation was tightly linked to time of peak velocity, and SC neurons with higher firing rates exhibited stronger correlations. Moreover, the strong correlative relationship was preserved when eye movement profiles were substantially altered by a blink-induced perturbation. These results indicate that the rate code of individual SC neurons can control instantaneous eye velocity, similar to how primary motor cortex controls hand movements, and argue against a serial process for transforming spatially encoded information into a rate code.
DivNet: Estimating diversity in networked communities
Authors: Willis Amy D , Martin Bryan D 
Published: April 2018

AbstractDiversity is a marker of ecosystem health in ecology, microbiology and immunology, with implications for disease diagnosis and infection resistance. However, accurately comparing diversity across environmental gradients is challenging, especially when number of different taxonomic groups in the community is large. Furthermore, existing approaches to estimating diversity do not perform well when the taxonomic groups in the community interact via an ecological network, such as by competing within their niche, or with mutualistic relationships. To address this, we propose DivNet, a method for estimating within- and between-community diversity in ecosystems where taxa interact via an ecological network. In particular, accounting for network structure permits more accurate estimates of alpha- and beta-diversity, even in settings with a large number of taxa and a small number of samples. DivNet is fast, accurate, precise, performs well with large numbers of taxa, and is robust to both weakly and strongly networked communities. We show that the advantages of incorporating taxon interactions into diversity estimation are especially clear in analyzing microbiomes and other high-diversity, strongly networked ecosystems. Therefore, to illustrate the method, we analyze the microbiome of seafloor basalts based on a 16S amplicon sequencing dataset with 1490 taxa and 13 samples.
Regulatory B cells contribute to the alleviation of colitis induced by Dextran Sulphate Sodium afterH.pyloriinfection
Authors: Li Xia , Tan Jiang , Zhang Feng , Xue Qian , Wang Ning , Cong Xu , Wang Jingtong 
Published: April 2018

BackgroundEpidemiological studies showed that there was an inverse relationship betweenHelicobacter pyloriinfection and the incidence of inflammatory bowel disease. Our previous research indicated that the regulatory immune responses induced byH.pyloriinfection were not limited to gastric mucosa, and the balance of intestinal mucosal immunity was influenced. In this study, we investigated the role of the regulatory B cells in the effects of theH.pyloriinfection on acute and chronic colitis induced by dextran sulphate sodium.MethodsMice were infected withH.pyloriand then colitis was induced by 3% DSS, the CD19+IL-10+Breg cells and CD4+CD25+Foxp3+Treg cells in blood、 spleen、 mesenteric lymph nodes (MLN)、 Peyer’s Patches (PP) and gastrointestinal mucosa were measured and examined. The anti– and pro-inflammatory cytokines were also detected at mRNA level.ResultsIn the acute and chronic colitis groups, DAI and colonic histological scores reduced significantly and colon length shorted less; the anti-inflammatory cytokines mRNA expression upregulated while the pro-inflammatory cytokines mRNA expression downregulated in colonic mucosa; and the percentages of CD19+IL-10+Breg cells in blood spleen MLN、 PP were higher in theH.pylori/DSS co-treated group compared with the DSS treated group.ConclusionH.pyloriinfection can alleviate the acute and chronic colitis induced by DSS. CD19+IL-10+Breg cells may play a critical role in the alleviation of acute and chronic colitis followingH.pyloriinfection.
CD161 mediates prenatal immune suppression of IFNγ-producing PLZF+T cells
Authors: Halkias Joanna , Rackaityte Elze , Aran Dvir , Mendoza Ventura F. , Eckalbar Walter L. , Burt Trevor 
Published: April 2018

SUMMARYWhile the fetal immune system defaults to a program of tolerance, there is concurrent need for protective immunity to meet the antigenic challenges after birth. Activation of fetal T cells is associated with fetal inflammation and the termination of pregnancy, yet which fetal T cells contribute to this process is poorly understood. Here we show a transcriptionally distinct population of pro-inflammatory T cells that predominates in the human fetal intestine. Activation of PLZF+T cells results in rapid production of Th1 cytokines and is inhibited upon ligation of surface CD161. This mechanism of fetal immune suppression may inform how immune dysregulation could result in fetal and neonatal inflammatory pathologies such as preterm birth. Our data support that human development of protective adaptive immunity originatesin uterowithin the specialized microenvironment of the fetal intestine.
A Freeloader?: The Highly Eroded Yet large Genome of theSerratia symbioticasymbiont ofCinara strobi
Authors: Manzano-Marín Alejandro , d’acier Armelle Coeur , Clamens Anne-Laure , Orvain Céline , Cruaud Corinne , Barbe Valérie , Jousselin Emmanuelle 
Published: April 2018

ABSTRACTGenome reduction is pervasive among maternally-inherited bacterial endosymbionts. This genome reduction can eventually lead to serious deterioration of essential metabolic pathways, thus rendering an obligate endosymbiont unable to provide essential nutrients to its host. This loss of essential pathways can lead to either symbiont complementation (sharing of the nutrient production with a novel co-obligate symbiont) or symbiont replacement (complete takeover of nutrient production by the novel symbiont). However, the process by which these two evolutionary events happen remains somewhat enigmatic by the lack of examples of intermediate stages of this process.Cinaraaphids (Hemiptera: Aphididae) typically harbour two obligate bacterial symbionts:BuchneraandSerratia symbiotica.However, the latter has been replaced by different bacterial taxa in specific lineages, and thus species within this aphid lineage could provide important clues into the process of symbiont replacement. In the present study, using 16S rRNA high-throughput amplicon sequencing, we determined that the aphidCinara strobiharbours not two, but three fixed bacterial symbionts:Buchnera aphidicola,aSodalissp., andS. symbiotica.Through genome assembly and genome-based metabolic inference, we have found that only the first two symbionts (BuchneraandSodalis) actually contribute to the hosts’ supply of essential nutrients whileS. symbioticahas become unable to contribute towards this task. We found thatS. symbioticahas a rather large and highly eroded genome which codes only for a few proteins and displays extensive pseudogenisation. Thus, we propose an ongoing symbiont replacement withinC. strobi,in which a once ‘‘competent”S. symbioticadoes no longer contribute towards the beneficial association. These results suggest that in dual symbiotic systems, when a substitute co-symbiont is available, genome deterioration can precede genome reduction and a symbiont can be maintained despite the apparent lack of benefit to its host.
Directional coupling of slow and fast hippocampal gamma with neocortical alpha/beta oscillations in human episodic memory
Authors: Griffiths Benjamin J. , Parish George , Roux Frederic , Michelmann Sebastian , van der Plas Mircea , Kolibius Luca D. , Chelvarajah Ramesh , Rollings David T. , Sawlani Vijay , Hamer Hajo , Gollwitzer Stephanie , Kreiselmeyer Gernot , Staresina Bernhard , Wimber Maria , Hanslmayr Simon 
Published: April 2018

AbstractEpisodic memories hinge upon our ability to process a wide range of multisensory information and bind this information into a coherent, memorable representation. On a neural level, these two processes are thought to be supported by neocortical alpha/beta desynchronisation and hippocampal theta/gamma synchronisation, respectively. Intuitively, these two processes should couple to successfully create and retrieve episodic memories, yet this hypothesis has not been tested empirically. We address this by analysing human intracranial EEG data recorded during two associative memory tasks. We find that neocortical alpha/beta (8-20Hz) power decreases reliably precede and predict hippocampal “fast” gamma (60-80Hz) power increases during episodic memory formation; during episodic memory retrieval however, hippocampal “slow” gamma (40-50Hz) power increases reliably precede and predict later neocortical alpha/beta power decreases. We speculate that this coupling reflects the flow of information from neocortex to hippocampus during memory formation, and hippocampal pattern completion inducing information reinstatement in the neocortex during memory retrieval.Significance StatementEpisodic memories detail our personally-experienced past. The formation and retrieval of these memories has long been thought to be supported by a division of labour between the neocortex and the hippocampus, where the former processes event-related information and the latter binds this information together. However, it remains unclear how the two regions interact. We uncover directional coupling between these regions, with power decreases in the neocortex that precede and predict power increases in the hippocampus during memory formation. Fascinatingly, this process reverses during memory retrieval, with hippocampal power increases preceding and predicting neocortical power decreases. These results suggest a bidirectional flow of information between the neocortex and hippocampus is fundamental to the formation and retrieval of episodic memories.
The closed form of Mad2 is bound to Mad1 and Cdc20 at unattached kinetochores
Authors: Zhang Gang , Nilsson Jakob 
Published: April 2018

ABSTRACTThe spindle assembly checkpoint (SAC) ensures accurate chromosome segregation by delaying anaphase onset in response to unattached kinetochores. Anaphase is delayed by the generation of the mitotic checkpoint complex (MCC) composed of the checkpoint proteins Mad2 and BubR1/Bub3 bound to the protein Cdc20. Current models assume that MCC production is catalyzed at unattached kinetochores and that the Mad1/Mad2 complex is instrumental in the conversion of Mad2 from an open form (O-Mad2) to a closed form (C-Mad2) that can bind to Cdc20. Importantly the levels of Mad2 at kinetochores correlate with SAC activity but whether C-Mad2 at kinetochores exclusively represents its complex with Mad1 is not fully established. Here we use a recently established C-Mad2 specific monoclonal antibody to show that Cdc20 and C-Mad2 levels correlate at kinetochores and that depletion of Cdc20 reduces Mad2 but not Mad1 kinetochore levels. Importantly reintroducing wild type Cdc20 but not Cdc20 R132A, a mutant form that cannot bind Mad2, restores Mad2 levels. In agreement with this live cell imaging of fluorescent tagged Mad2 reveals that Cdc20 depletion strongly reduces Mad2 localization to kinetochores. These results support the presence of Mad2-Cdc20 complexes at kinetochores in agreement with current models of the SAC but also argue that Mad2 levels at kinetochores cannot be used as a direct readout of Mad1 levels.
Comparison of two commercial ELISA kits for detection of rubella specific IgM and IgG antibodies
Authors: Viswanathan Rajlakshmi , George Suji , Murhekar Manoj V , Abraham Asha Mary , Singh Mini P , Jadhav Santoshkumar M , Nag Vijayalakshmi , Naik Sadanand , Raut Chandrashekhar , Ashok M , Gupta Minakshi , Jagtap Vishal , Kaduskar Ojas , Gupta Nivedita , Sapkal Gajanan N 
Published: April 2018

AbstractEnzyme linked immunosorbent assay (ELISA) plays an important role in laboratory confirmation of congenital rubella syndrome (CRS), postnatal rubella and seroprevalence studies in different populations. Variation of results are documented for samples tested by different commercial kits. The Enzygnost rubella ELISA, widely used in the WHO network, is expensive and not readily available. In the present study, performance of the Euroimmun ELISA was compared to the Enzygnost ELISA for detection of rubella specific IgM and IgG antibodies.Two hundred and eighty five serum samples collected from suspected CRS patients identified through a recently initiated surveillance for CRS at six sentinel hospitals and 435 serum samples from a serosurvey of pregnant women from these sites, were available for testing of rubella specific IgM and IgG antibodies respectively. Qualitative agreement (concordance percentage and Cohen’s Kappa coefficient -κ) was evaluated for both IgM and IgG assays. Bland – Altman plots were used to assess the difference in quantitative agreement for IgG titers.Good qualitative agreement between the two ELISA kits was observed for detection of both anti rubella IgM (94.7% agreement and k of 0.86) and IgG (96.3% agreement and k of 0.84). Sensitivity and specificity of Euroimmun assays compared to Enzygnost was 100% and 93.1% for IgM and 95.9% and 100% for IgG respectively. Bland – Altman analysis for paired quantitative results of rubella specific IgG yielded a mean difference of 0.781 IU/ml with majority of values (97.1%) within ± 2 SD of the mean difference. Euroimmun ELISA provided on an average, higher titers as compared to Enzygnost.Our study findings suggest that Euroimmun ELISA may be considered for detection of rubella specific IgM in suspected CRS cases and rubella specific IgG in surveillance studies.