bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrahepatic mass-forming cholangiocarcinoma growing in a giant hepatic hemangioma
Authors: Zhou Mengqi , Ling Wenwu , Luo Yan 
Published: July 2019

Abstract

Rationale:
Hepatic hemangioma (HH) is a common benign tumor with a high number of normal or abnormal blood vessels. Intrahepatic cholangiocarcinoma (ICC) is a relatively common malignant primary hepatic carcinoma (10%–15%) with high incidence rate and high fatality, yet low discovery rate in the early stages. Ultrasonography (US), computed tomography, and magnetic resonance imaging (MRI) are frequently used and indispensable imaging techniques for the diagnosis of hepatic lesions. It is possible to differentiate a liver lesion from HH with high accuracy owing to their different patterns and hemodynamic characteristics.

Patient concerns:
A 59-year-old Asian woman was referred to hospital for a hepatic mass, which was 9.0 × 6.5 cm in size, The patient was tested positive for hepatitis B antigen but negative for serum alpha-fetoprotein and carbohydrate antigen 199 and had a slightly elevated carcinoembryonic antigen level (3.56 ng/ml).

Diagnosis:
Liver US and MRI were performed. Grey-scale US revealed a huge heterogeneous mass on the right lobe with a point and line-like blood flow signal on Doppler US. Dynamic contrast-enhanced MRI showed heterogeneous annular nodular enhancement in the arterial phase. An initial diagnosis of HH was made based on the clinical history and imaging results; however, histopathologic examination of the liver lesions revealed modest to severe atypical hyperplasia of intrahepatic bile duct epithelium, cancerization, and mid to high differentiated mass-forming type cholangiocarcinoma combined with focal organized hemangioma.

Interventions:
The intrahepatic mass-forming cholangiocarcinoma (IMCC) lesion was considered a focal organization of hemangioma during operation and was surgically removed. No routine chemotherapy was performed after the operation.

Outcomes:
The IMCC recurred 23 months after surgery, with elevated serum CA19-9 and CA125. Liver damage was evident, and the patient developed jaundice. The patient was discharged without active treatment and died in 4 months.

Lessons:
Although preoperative imaging of focal hepatic lesions is indispensable, intraoperative frozen section analysis and histopathological examination remain essential for definitive diagnosis. This is particularly important for high-risk patients and those with suspected malignancy.
LncRNA GUARDIN suppresses cellular senescence through a LRP130-PGC1α-FOXO4-p21-dependent signaling axis
Authors: Sun Xuedan , FrancisThorne Rick , Zhang Xu Dong , He Miao , Feng Shanshan , Liu Xiaoying , Wu Mian 
Published: July 2019

AbstractThe long non-coding RNA GUARDIN functions to protect genome stability. Inhibiting GUARDIN expression can alter cell fate decisions towards senescence or apoptosis, but the underlying molecular signals are unknown. Here we show that GUARDIN is an essential component of a transcriptional repressor complex involving LRP130 and PGC1α which suppresses FOXO4 expression. GUARDIN acts as a scaffold to stabilize LRP130/PGC1α heterodimers and their occupancy at the FOXO4 promotor. Destabilizing this complex by silencing of GUARDIN, LRP130 or PGC1α leads to FOXO4-dependent upregulation of p21, thereby driving cells into senescence. We also found that GUARDIN expression was induced by rapamycin, a senolytic agent that suppresses cell senescence. FOS-Like Antigen 2 (FOSL2) acts as a transcriptional repressor of GUARDIN with increased levels in the presence of rapamycin resulting from downregulation of FOSL2. Together, these results demonstrate that GUARDIN inhibits p21-dependent senescence through a LRP130-PGC1α-FOXO4 signaling axis and moreover, GUARDIN contributes to the anti-senolytic activities of rapamycin.
TGFβ restricts T cell function and bacterial control within the tuberculous granuloma
Authors: Gern Benjamin H , Adams Kristin N , Plumlee Courtney R , Stoltzfus Caleb R , Shehata Laila , Busman-Sahay Kathleen , Hansen Scott G , Axthelm Michael K , Picker Louis J , Estes Jacob D , Urdahl Kevin B , Gerner Michael Y 
Published: July 2019

SUMMARYInterferon gamma (IFNγ) produced by CD4 T cells is required for immune containment ofMycobacterium tuberculosis(Mtb) infection. Despite this, IFNγ plays a minor role in CD4 T cell-mediated immunity within the lung. In this study, we use a recently-developed murine model of physiologic Mtb infection coupled with advanced quantitative imaging to demonstrate that IFNγ production by Mtb-specific T cells is rapidly extinguished within the granuloma, but not in unaffected areas of the lung. This is mediated via localized immunosuppression through cell-intrinsic TGFβ signaling in effector T helper 1 cells within the granuloma, and blockade of TGFβ signaling in T cells results in improved immune cell function and decreased pulmonary bacterial burden. These findings uncover a potent immunosuppressive mechanism associated with Mtb infection and provide potential targets for host-directed therapy.
Inference of selection from genetic time series using various parametric approximations to the Wright-Fisher model
Authors: Paris Cyriel , Servin Bertrand , Boitard Simon 
Published: July 2019

AbstractDetecting genomic regions under selection is an important objective of population genetics. Typical analyses for this goal are based on exploiting genetic diversity patterns in present time data but rapid advances in DNA sequencing have increased the availability of time series genomic data. A common approach to analyze such data is to model the temporal evolution of an allele frequency as a Markov chain. Based on this principle, several methods have been proposed to infer selection intensity. One of their differences lies in how they model the transition probabilities of the Markoiv chain. Using the Wright-Fisher model is a natural choice but its computational cost is prohibitive for large population sizes so approximations to this model based on parametric distributions have been proposed. Here, we compared the performance of some of these approximations with respect to their power to detect selection and estimation of the selection coefficient. We developped a new generic Hidden Markov Model likelihood calculator and applied it on genetic time series simulated under various evolutionary scenarios. The Beta-with-Spikes approximation, which combines discrete fixation probabilities with a continuous Beta distribution, was found to perform consistently better than the others. This distribution provides an almost perfect fit to the Wright-Fisher model in terms of selection inference, for a computational cost that does not increase with population size. We further evaluate this model for population sizes not accessible to the Wright-Fisher model and illustrate its performance on a dataset of two divergently selected chicken populations.
Structures of virus-like capsids formed by the Drosophila neuronal Arc proteins
Authors: Erlendsson Simon , Morado Dustin R. , Shepherd Jason D. , Briggs John A. G. 
Published: July 2019

AbstractThe neuronal protein Arc is a critical mediator of synaptic plasticity. Arc originated in tetrapods and flies through domestication of retrotransposon Gag genes. Recent studies have suggested that Arc mediates intercellular mRNA transfer and like Gag, can form capsid-like structures. Here we report that Drosophila proteins dArc1 and dArc2 assemble virus-like capsids. We determine the capsid structures to 2.8 Å and 3.7 Å resolution, respectively, finding similarity to capsids of retroviruses and retrotransposons. Differences between dArc1 and dArc2 capsids, including the presence of a structured zinc-finger pair in dArc1, are consistent with differential RNA-binding specificity. Our data support a model in which ancestral capsid-forming and RNA-binding properties of Arc remain under positive selection pressure and have been repurposed to function in neuronal signalling.
Dyslexic children show altered temporal structure of the nonlinear VEP
Authors: Crewther Sheila , Rutkowski Jacqueline , Crewther David 
Published: July 2019

AbstractThe neural basis of dyslexia remains unresolved, despite many theories relating dyslexia to dysfunction in visual magnocellular and auditory temporal processing, cerebellar dysfunction, attentional deficits, as well as excessive neural noise. Recent research identifies perceptual speed as a common factor, integrating several of these systems. Optimal perceptual speed invokes transient attention as a necessary component, and change detection in gap paradigm tasks is impaired in those with dyslexia. This research has also identified an overall better change detection for targets presented in the upper compared with lower visual fields. Despite the magnocellular visual pathway being implicated in the aetiology of dyslexia over 30 years ago, objective physiological measures have been lacking. Thus, we employed nonlinear visual evoked potential (VEP) techniques which generate second order kernel terms specific for magno and parvocellular processing as a means to assessing the physiological status of poor readers (PR, n=12) compared with good readers (GR, n=16) selected from children with a mean age of 10yr. The first and second order Wiener kernels using multifocal VEP were recorded from a 4° foveal stimulus patch as well as for upper and lower visual field peripheral arcs. Foveal responses showed little difference between GR and PR for low contrast stimulation, except for the second slice of the second order kernel where lower peak amplitudes were recorded for PR vs GR. At high contrast, there was a trend to smaller first order kernel amplitudes for short latency peaks of the PR vs GR. In addition, there were significant latency differences for the first negativity in the first two slices of the second order kernel. In terms of peripheral stimulation, lower visual field response amplitudes were larger compared with upper visual field responses, for both PR and GR. A trend to larger second/first order ratio for magnocellularly driven responses suggests the possibility of lesser neural efficiency in the periphery for the PR compared with the GR. Stronger lower field peripheral response may relate to better upper visual field change detection performance when target visibility is controlled through flicking masks. In conclusion, early cortical magnocellular processing at low contrast was normal in those with dyslexia, while cortical activity related to parvocellular afferents was reduced. In addition, the study demonstrated a physiological basis for upper versus lower visual field differences related to magnocellular function.
Detecting Transcriptomic Structural Variants in Heterogeneous Contexts via the Multiple Compatible Arrangements Problem
Authors: Qiu Yutong , Ma Cong , Xie Han , Kingsford Carl 
Published: July 2019

AbstractTranscriptomic structural variants (TSVs) — structural variants that affect expressed regions — are common, especially in cancer. Detecting TSVs is a challenging computational problem. Sample heterogeneity (including differences between alleles in diploid organisms) is a critical confounding factor when identifying TSVs. To improve TSV detection in heterogeneous RNA-seq samples, we introduce the MULTIPLECOMPATIBLEARRANGEMENTPROBLEM(MCAP), which seekskgenome rearrangements to maximize the number of reads that are concordant with at least one rearrangement. This directly models the situation of a heterogeneous or diploid sample. We prove that MCAP is NP-hard and provide a-approximation algorithm fork= 1 and a-approximation algorithm for the diploid case (k= 2) assuming an oracle fork= 1. Combining these, we obtain a-approximation algorithm for MCAP whenk= 2 (without an oracle). We also present an integer linear programming formulation for generalk. We completely characterize the graph structures that requirek> 1 to satisfy all edges and show such structures are prevalent in cancer samples. We evaluate our algorithms on 381 TCGA samples and 2 cancer cell lines and show improved performance compared to the state-of-the-art TSV-calling tool, SQUID.
Genomic analysis on broiler-associated Clostridium perfringens strains and caecal microbiome profiling reveals key factors linked to poultry Necrotic Enteritis
Authors: Kiu Raymond , Brown Joseph , Bedwell Harley , Leclaire Charlotte , Caim Shabhonam , Pickard Derek , Dougan Gordon , Dixon Ronald A , Hall Lindsay J 
Published: July 2019

AbstractBackgroundClostridium perfringens is a key pathogen in poultry-associated necrotic enteritis (NE). To date there are limited Whole Genome Sequencing based studies describing broiler-associated C. perfringens in healthy and diseased birds. Moreover, changes in the caecal microbiome during NE is currently not well characterised. Thus, the aim of this present study was to investigate C. perfringens virulence factors linked to health and diseased chickens, including identifying caecal microbiota signatures associated with NE.ResultsWe analysed 88 broiler chicken C. perfringens genomes (representing 66 publicly available genomes and 22 newly sequenced genomes) using different phylogenomics approaches and identified a potential hypervirulent and globally-distributed clone spanning 20-year time-frame (1993-2013). These isolates harbored a greater number of virulence genes (including toxin and collagen adhesin genes) when compared to other isolates. Further genomic analysis indicated exclusive and overabundant presence of important NE-linked toxin genes including netB and tpeL in NE-associated broiler isolates. Secondary virulence genes including pfoA, cpb2, and collagen adhesin genes cna, cnaA and cnaD were also enriched in the NE-linked C. perfringens genomes. Moreover, an environmental isolate obtained from farm animal feeds was found to encode netB, suggesting potential reservoirs of NetB-positive C. perfringens strains (toxinotype G). We also analysed caecal samples from a sub-set of 11 diseased and healthy broilers using 16S rRNA amplicon sequencing, which indicated a significant and positive correlation in genus Clostridium within the wider microbiota of those broilers diagnosed with NE, alongside reductions in beneficial microbiota members.ConclusionsThese data indicate a positive association of virulence genes including netB, pfoA, cpb2, tpeL and cna variants linked to NE-linked isolates. Potential global dissemination of specific hypervirulent lineage, coupled with distinctive microbiome profiles, highlights the need for further investigations, which will require a large worldwide sample collection from healthy and NE-associated birds.
64-Channel Carbon Fiber Electrode Arrays for Chronic Electrophysiology
Authors: Guitchounts Grigori , Cox David 
Published: July 2019

ABSTRACTA chief goal in neuroscience is to understand how neuronal activity relates to behavior, perception, and cognition. However, monitoring neuronal activity over long periods of time is technically challenging, and limited, in part, by the invasive nature of recording tools. While electrodes allow for recording in freely-behaving animals, they tend to be bulky and stiff, causing damage to the tissue they are implanted in. One solution to this invasiveness problem may be probes that are small enough to fly under the immune system’s radar. Carbon fiber (CF) electrodes are thinner and more flexible than typical metal or silicon electrodes, but the arrays described in previous reports had low channel counts and required time-consuming manual assembly. Here we report the design of an expanded-channel-count carbon fiber electrode array (CFEA) as well as a method for fast preparation of the recording sites using acid etching and electroplating with PEDOT-TFB, and demonstrate the ability of the 64-channel CFEA to record from rat visual cortex. We include designs for interfacing the system with micro-drives or flex-PCB cables for recording from multiple brain regions, as well as a facilitated method for coating CFs with the insulator Parylene-C. High-channel-count CFEAs may thus be an alternative to traditional microwire-based electrodes and a practical tool for exploring the neural code.
Classification of hospital and urban wastewater resistome and microbiota over time and their relationship to the eco-exposome
Authors: Buelow Elena , Rico Andreu , Gaschet Margaux , Lourenço José , Kennedy Sean P. , Wiest Laure , Ploy Marie-Cecile , Dagot Christophe 
Published: July 2019

AbstractWastewaters (WW) are important sources for the dissemination of antimicrobial resistance (AMR) into the environment. Hospital WW (HWW) contain higher loads of micro-pollutants and AMR markers than urban WW (UWW). Little is known about the long-term dynamics of H and U WW and the impact of their joined treatment on the general burden of AMR. Here, we characterized the resistome, microbiota and eco-exposome signature of 126 H and U WW samples treated separately for three years, and then mixed, over one year. Multi-variate analysis and machine learning revealed a robust signature for each WW with no significant variation over time before mixing, and once mixed, both WW closely resembled U signatures. We demonstrated a significant impact of pharmaceuticals and surfactants on the resistome and microbiota of H and U WW. Our results present considerable targets for AMR related risk assessment of WW.
Mozambican genetic variation provides new insights into the Bantu expansion
Authors: Semo Armando , Gayà-Vidal Magdalena , Fortes-Lima Cesar , Alard Bérénice , Oliveira Sandra , Almeida João , Prista António , Damasceno Albertino , Fehn Anne-Maria , Schlebusch Carina , Rocha Jorge 
Published: July 2019

AbstractThe Bantu expansion, which started in West Central Africa around 5,000 BP, constitutes a major migratory movement involving the joint spread of peoples and languages across sub-Saharan Africa. Despite the rich linguistic and archaeological evidence available, the genetic relationships between different Bantu-speaking populations and the migratory routes they followed during various phases of the expansion remain poorly understood. Here, we analyze the genetic profiles of southwestern and southeastern Bantu-speaking peoples located at the edges of the Bantu expansion by generating genome-wide data for 200 individuals from 12 Mozambican and 3 Angolan populations using ∼1.9 million autosomal single nucleotide polymorphisms. Incorporating a wide range of available genetic data, our analyses confirm previous results favoring a “late split” between West and East Bantu speakers, following a joint passage through the rainforest. In addition, we find that Bantu speakers from eastern Africa display genetic substructure, with Mozambican populations forming a gradient of relatedness along a North-South cline stretching from the coastal border between Kenya and Tanzania to South Africa. This gradient is further associated with a southward increase in genetic homogeneity, and involved minimum admixture with resident populations. Together, our results provide the first genetic evidence in support of a rapid North-South dispersal of Bantu peoples along the Indian Ocean Coast, as inferred from the distribution and antiquity of Early Iron Age assemblages associated with the Kwale archaeological tradition.
C. elegans LIN-28 controls temporal cell-fate progression by regulating LIN-46 expression via the 5’UTR of lin-46 mRNA
Authors: Ilbay Orkan , Nelson Charles , Ambros Victor 
Published: July 2019

ABSTRACTHuman Lin28 is a conserved RNA-binding protein that promotes proliferation and pluripotency and can be oncogenic. Lin28 and C. elegans LIN-28 bind to precursor RNAs of the conserved, cellular differentiation-promoting, microRNA let-7 and inhibits production of mature let-7 microRNA. Lin28/LIN-28 also binds to and regulates many mRNAs in various cell types. However, the determinants and consequences of these LIN-28-mRNA interactions are not well understood. Here, we report that LIN-28 in C. elegans represses the expression of LIN-46, a downstream protein in the heterochronic pathway, via the 5’ UTR of the lin-46 mRNA. We show that both LIN-28 and the 5’UTR of lin-46 are required to prevent LIN-46 expression in the L1 and L2 stages, and that precocious LIN-46 expression is sufficient to skip L2 stage proliferative cell-fates, resulting in heterochronic defects similar to the ones observed in lin-28(0) animals. We propose that the lin-46 5’UTR mediates LIN-28 binding to and repression of the lin-46 mRNA. Our results demonstrate that precocious LIN-46 expression alone can account for lin-28(0) phenotypes, demonstrating the biological importance of regulation of individual target mRNAs by LIN-28.
An analysis of respiratory function and mitochondrial morphology in Candida albicans
Authors: Duvenage Lucian , Pentland Daniel R. , Munro Carol A. , Gourlay Campbell W. 
Published: July 2019

AbstractRespiratory function and mitochondrial dynamics have been well characterised in a number of cell types, including the model yeast Saccharomyces cerevisiae, but remain under-researched in fungal pathogens such as Candida albicans. An understanding of mitochondrial activity and morphology is important if we are to understand the role that this organelle plays in adaption and response to stress. Here we examine the respiratory profiles of several prominent pathogenic Candida species and present a useful GFP probe for the study of mitochondrial morphology. We examine mitochondrial morphology under a variety of conditions that Candida species may encounter within the host, such as acidic pH, respiratory and oxidative stress. The GFP probe also allowed for the visualisation of mitochondria during hyphal development, during growth following macrophage engulfment and distribution within biofilms. These data demonstrate that the mitochondrial network of C. albicans is highly responsive to both environmental conditions and developmental cues, suggesting important roles for this organelle in environmental adaption.
Neurotensin receptor 1 deletion suppresses methamphetamine self-administration and the associated reduction in dopamine cell firing
Authors: Dominguez-Lopez Sergio , Sharma Ramaswamy , Beckstead Michael J. 
Published: July 2019

ABSTRACTWe previously reported that pharmacological blockade of neurotensin receptors in the ventral tegmental area (VTA) decreases methamphetamine (METH) self-administration in mice. Here we explored the consequences of genetic deletion of neurotensin receptor 1 (NtsR1) in METH self-administration and VTA dopamine neuron firing activity. We implanted mice with an indwelling jugular catheter and trained them to nose-poke for intravenous infusions of METH. Mice with NtsR1 deletion (KO) acquired selfadministration similar to wildtype (WT) and heterozygous (HET) littermates. However, in NtsR1 KO and HET mice, METH intake and motivated METH seeking decreased when the response requirement was increased to a fixed ratio 3 and when mice were tested on a progressive ratio protocol. After completion of METH self-administration, single cell in vivo extracellular recordings of dopamine firing activity in the VTA were obtained in anesthetized mice. In WT METH-experienced mice, dopamine cell firing frequency dramatically decreases compared to WT drug-naïve mice. NtsR1 KO and HET mice did not exhibit this decline of dopamine cell firing activity after prolonged METH selfadministration. We also observed an increase in population activity following METH selfadministration that was strongest in the WT group. Our results suggest a role for NtsR1 in METH-seeking behavior, and ablation of NtsR1 receptors prevents the detrimental effects of prolonged METH self-administration on VTA dopamine cell firing frequency.