bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential Use of 18F-THK5351 PET to Identify Wallerian Degeneration of the Pyramidal Tract Caused by Cerebral Infarction
Authors: Ishibashi Kenji , Kameyama Masashi , Tago Tetsuro , Toyohara Jun , Ishii Kenji 
Published: October 2017

Abstract
A 41-year-old man underwent 18F-THK5351 PET 2 years after a right middle cerebral artery infarction. 18F-THK5351 PET imaging revealed intense radioligand uptake along the ipsilateral pyramidal tract from the corona radiata to the medulla; intense uptake changed from the right side to the left side with descending axial sections at the level of the pyramidal decussation. 18F-THK5351 reportedly binds to monoamine oxidase B, which is highly expressed in astrocytes, suggesting that 18F-THK5351 concentrates in the lesion where gliosis occurs. Hence, in this case, 18F-THK5351 uptake may represent Wallerian degeneration accompanied with gliosis in the ipsilateral pyramidal tract.
Imaging Characteristics of Chemotherapy Related Adult-Onset Still Disease
Authors: Lu Yang , Chasen Beth A. , Macapinlac Homer A. 
Published: October 2017

Abstract
A 60-year-old man with lymphoma completed chemotherapy on October 21, 2016, with complete remission. He then received rituximab maintenance therapy. Since March 2017, he has had progressive fatigue, myalgias, rash, weight loss, diarrhea, and recurrent low-grade fever. Subsequent bone marrow biopsy and FDG PET/CT demonstrated no active lymphoma. An 111In–white blood cell scan showed abnormal tracer uptake on 20-hour postinjection, but not on 3-hour postinjection images, including innumerable skeleton muscle foci, multiple cutaneous foci, and persistent diffuse increased uptake in the lungs. Diagnosis of adult-onset Still disease was made accordingly. The patient's cytopenia was deemed a chemotherapy-related adverse effect.
Small Bowel Metastasis From Hepatocellular Carcinoma Detected by 18F-FDG PET/CT But Not by 11C-Acetate PET/CT
Authors: Yoo Su Woong , Kim Dong-Yeon , Lee Changho , Min Jung-Joon , Kwon Seong Young 
Published: October 2017

Abstract
Gastrointestinal tract is rarely a metastatic site of hepatocellular carcinoma (HCC). We present a 43-year-old woman with small bowel metastasis from HCC in which metastasis was detected using 18F-FDG PET/CT. However, the site of metastasis showed no significant uptake on 11C-acetate PET/CT. 11C-acetate PET/CT has a limited value in HCC patients with suspected extrahepatic metastasis, compared with 18F-FDG PET/CT.
Conservation of specificity in two low-specificity protein
Authors: Wheeler Lucas C. , Anderson Jeremy A. , Morrison Anneliese J. , Wong Caitlyn E. , Harms Michael J. 
Published: October 2017

AbstractS100 proteins bind linear peptide regions of target proteins and modulate their activity. The peptide binding interface, however, has remarkably low specificity and can interact with many target peptides. It is not clear if the interface discriminates targets in a biological context, or whether biological specificity is achieved exclusively through external factors such as subcellular localization. To discriminate these possibilities, we used an evolutionary biochemical approach to trace the evolution of paralogs S100A5 and S100A6. We first used isothermal titration calorimetry to study the binding of a collection of peptides with diverse sequence, hydrophobicity, and charge to human S100A5 and S100A6. These proteins bound distinct, but overlapping, sets of peptide targets. We then studied the peptide binding properties of S100A5 and S100A6 orthologs sampled from across five representative amniote species. We found that the pattern of binding specificity was conserved along all lineages, for the last 320 million years, despite the low specificity of each protein. We next used Ancestral Sequence Reconstruction to determine the binding specificity of the last common ancestor of the paralogs. We found the ancestor bound the whole set of peptides bound by modern S100A5 and S100A6 proteins, suggesting that paralog specificity evolved by subfunctionalization. To rule out the possibility that specificity is conserved because it is difficult to modify, we identified a single historical mutation that, when reverted in human S100A5, gave it the ability to bind an S100A6-specific peptide. These results indicate that there are strong evolutionary constraints on peptide binding specificity, and that, despite being able to bind a large number of targets, the specificity of S100 peptide interfaces is indeed important for the biology of these proteins.
Computational discovery of tissue morphology biomarkers in very long-term survivors with pancreatic ductal adenocarcinoma
Authors: Sarnecki Jacob S. , Wood Laura D. , Wolfgang Christopher L. , Hruban Ralph H. , Maitra Anirban , Wirtz Denis , Wu Pei-Hsun 
Published: October 2017

AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer, with an average 5-year survival rate of only 8%. Within PDAC patients, however, there is a small subset of patients who survive >10 years. Deciphering underlying reasons behind prolonged survival could potentially provide new opportunities to treat PDAC; however, no genomic, transcriptomic, proteomic, or clinical signatures have been found to robustly separate this subset of patients. Digital pathology, in combination with machine learning, provides an opportunity to computationally search for tissue morphology patterns associated with disease outcomes. Here, we developed a computational framework to analyze whole-slide images (WSI) of PDAC patient tissue and identify tissue-morphology signatures for very long term surviving patients. Our results indicate that less tissue morphology heterogeneity is significantly linked to better patient survival and that the extra-tumoral space encodes prognostic information for survival. Based on information from morphological heterogeneity in the tumor and its adjacent area, we established a machine learning model with an AUC of 0.94. Our analysis workflow highlighted a quantitative visual-based tissue phenotype analysis that also allows direct interaction with pathology. This study demonstrates a pathway to accelerate the discovery of undetermined tissue morphology associated with pathogenesis states and prognosis and diagnosis of patients by utilizing new computational approaches.
Modulation of theNeisseria gonorrhoeaedrug efflux conduit MtrE
Authors: Tamburrino Giulia , Llabrés Salomé , Vickery Owen N. , Pitt Samantha J. , Zachariae Ulrich 
Published: October 2017

ABSTRACTWidespread antibiotic resistance, especially of Gram-negative bacteria, has become a severe concern for human health. Tripartite efflux pumps are one of the major contributors to resistance in Gram-negative pathogens, by efficiently expelling a broad spectrum of antibiotics from the organism. InNeisseria gonorrhoeae, one of the first bacteria for which pan-resistance has been reported, the most expressed efflux complex is MtrCDE. Here we present the electrophysiological characterisation of the outer membrane component MtrE and the membrane fusion protein MtrC, obtained by a combination of planar lipid bilayer recordings andin silicotechniques. Ourin vitroresults show that MtrE can be regulated by periplasmic binding events and that the interaction between MtrE and MtrC is sufficient to stabilize this complex in an open state. In contrast to other efflux conduits, the open complex only displays a slight preference for cations. The maximum conductance we obtain in thein vitrorecordings is comparable to that seen in our computational electrophysiology simulations conducted on the MtrE crystal structure, indicating that this state may reflect a physiologically relevant open conformation of MtrE. Our results suggest that the MtrC/E binding interface is an important modulator of MtrE function, which could potentially be targeted by new efflux inhibitors.
Image-based methods for phenotyping growth dynamics and fitness components inArabidopsis thaliana
Authors: Vasseur François , Wang George , Bresson Justine , Schwab Rebecca , Weigel Detlef 
Published: October 2017

AbstractBackgroundThe model speciesArabidopsis thalianahas extensive resources to investigate intraspecific trait variability and the genetic bases of ecologically relevant traits. However, the cost of equipment and software required for high-throughput phenotyping is often a bottleneck for large-scale studies, such as mutant screening or quantitative genetics analyses. Simple tools are needed for the measurement of fitness-related traits, like relative growth rate and fruit production, without investment in expensive infrastructures. Here, we describe methods that enable the estimation of biomass accumulation and fruit number from the analysis of rosette and inflorescence images taken with a regular camera.ResultsWe developed two models to predict plant dry mass and fruit number from the parameters extracted with the analysis of rosette and inflorescence images. Predictive models were trained by sacrificing growing individuals for dry mass estimation, and manually measuring a fraction of individuals for fruit number at maturity. Using a cross-validation approach, we showed that quantitative parameters extracted from image analysis predicts more 90% of both plant dry mass and fruit number. When used on 451 natural accessions, the method allowed modelling growth dynamics, including relative growth rate, throughout the life cycle of various ecotypes. Estimated growth-related traits had high heritability (0.65 <H2< 0.93), as well as estimated fruit number (H2= 0.68). In addition, we validated the method for estimating fruit number withrev5, a mutant with increased flower abortion.ConclusionsThe method we propose here is based on the automated computerization of plant images with ImageJ, and subsequent statistical modelling in R. It allows plant biologists to measure growth dynamics and fruit number in hundreds of individuals with simple computing steps that can be repeated and adjusted to a wide range of laboratory conditions. It is thus a flexible toolkit for the measurement of fitness-related traits in large plant populations.
Early Detection of Apathetic Phenotypes in Huntington’s Disease Knock-in Mice Using Open Source Tools
Authors: Minnig Shawn , Bragg Robert M. , Tiwana Hardeep S. , Solem Wes T. , Hovander William S. , Vik Eva-Mari S. , Hamilton Madeline , Legg Samuel R. W. , Shuttleworth Dominic D. , Coffey Sydney R. , Cantle Jeffrey P. , Carroll Jeffrey B. 
Published: October 2017

AbstractApathy is one of the most prevalent and progressive psychiatric symptom in Huntington’s disease (HD) patients. However, preclinical work in HD mouse models tend to focus on molecular and motor, rather than affective, phenotypes. Measuring behavior in mice often produces noisy data and requires large cohorts to detect phenotypic rescue with appropriate power. The operant equipment necessary for measuring affective phenotypes is typically expensive, proprietary to commercial entities, and bulky which can render adequately sized mouse cohorts as cost-prohibitive. Thus, we describe here a home-built open-source alternative to commercial hardware that is reliable, scalable, and reproducible. Using off-the-shelf hardware, we adapted and built several of the rodent operant buckets (ROBucket) designed to test HttQ111/+ mice for attention deficits in fixed ratio (FR) and progressive ratio (PR) tasks. We find that, despite normal performance in reward attainment in the FR task, HttQ111/+ mice exhibit reduced PR performance at 9-11 months of age, suggesting motivational deficits. We replicated this in two independent cohorts, which demonstrates the reliability and utility of both the apathetic phenotype, and these ROBuckets, for preclinical HD studies.
Neuronal CCL2 expression drives inflammatory monocyte infiltration into the brain during acute virus infection
Authors: Howe Charles L , LaFrance-Corey Reghann G. , Goddery Emma N , Mirchia Kanish 
Published: October 2017

AbstractBackgroundViral encephalitis is a dangerous compromise between the need to robustly clear pathogen from the brain and the need to protect neurons from bystander injury. Theiler's murine encephalomyelitis virus (TMEV) infection of C57Bl/6 mice is a model of viral encephalitis in which the compromise results in hippocampal damage and permanent neurological sequelae. We previously identified brain infiltrating inflammatory monocytes as the primary driver of this hippocampal pathology, but the mechanisms involved in recruiting these cells to the brain were unclear.MethodsChemokine expression levels in the hippocampus were assessed by microarray, ELISA, RT-PCR, and immunofluorescence. Monocyte infiltration during acute TMEV infection was measured by flow cytometry. CCL2 levels were manipulated by immunodepletion and by specific removal from neurons in mice generated by crossing a line expressing the Cre recombinase behind the synapsin promoter to animals with floxed CCL2.ResultsInoculation of the brain with TMEV induced hippocampal production of the proinflammatory chemokine CCL2 that peaked at 6 hours postinfection, whereas inoculation with UV-inactivated TMEV did not elicit this response. Immunofluorescence revealed that hippocampal neurons expressed high levels of CCL2 at this timepoint. Genetic deletion of CCR2 and systemic immunodepletion of CCL2 abrogated or blunted the infiltration of inflammatory monocytes into the brain during acute infection. Specific genetic deletion of CCL2 from neurons reduced serum and hippocampal CCL2 levels and inhibited inflammatory monocyte infiltration into the brain.ConclusionsWe conclude that intracranial inoculation with infectious TMEV rapidly induces the expression of CCL2 in neurons, and this cellular source is necessary for CCR2-dependent infiltration of inflammatory monocytes into the brain during the most acute stage of encephalitis. These findings highlight a unique role for neuronal production of chemokines in the initiation of leukocytic infiltration into the infected central nervous system.
Defining the Transcriptional Landscape during Cytomegalovirus Latency with Single-Cell RNA Sequencing
Authors: Shnayder Miri , Nachshon Aharon , Krishna Benjamin , Poole Emma , Boshkov Alina , Binyamin Amit , Maza Itay , Sinclair John , Schwartz Michal , Stern-Ginossar Noam 
Published: October 2017

AbstractPrimary infection with human cytomegalovirus (HCMV) results in a lifelong infection due to its ability to establish latent infection, one characterized viral reservoir being hematopoietic cells. Although reactivation from latency causes serious disease in immunocompromised individuals, our molecular understanding of latency is limited. Here, we delineate viral gene expression during natural HCMV persistent infection by analyzing the massive RNA-seq atlas generated by the Genotype-Tissue Expression (GTEx) project. This systematic analysis reveals that HCMV persistencein-vivois prevalent in diverse tissues. Unexpectedly, we find only viral transcripts that resemble gene expression during stages of lytic infection with no evidence of any highly restricted latency-associated viral gene expression program. To further define the transcriptional landscape during HCMV latent infection, we also used single cell RNA-seq and a tractable experimental latency model. In contrast to current views on latency, we also find no evidence for a specific restricted latency-associated viral gene expression program. Instead, we reveal that latency-associated gene expression largely mirrors a late lytic viral program albeit at much lower levels of expression. Overall, our work has the potential to revolutionize our understanding of HCMV persistence and suggests that latency is governed mainly by quantitative changes, with a limited number of qualitative changes, in viral gene expression.
Birthweight, Type 2 Diabetes and Cardiovascular Disease: Addressing the Barker Hypothesis with Mendelian randomization
Authors: Zanetti Daniela , Tikkanen Emmi , Gustafsson Stefan , Priest James Rush , Burgess Stephen , Ingelsson Erik 
Published: October 2017

AbstractBackgroundLow birthweight (BW) has been associated with a higher risk of hypertension, type 2 diabetes (T2D) and cardiovascular disease (CVD) in epidemiological studies. The Barker hypothesis posits that intrauterine growth restriction resulting in lower BW is causal for these diseases, but causality and mechanisms are difficult to infer from observational studies. Mendelian randomization (MR) is a new tool to address this important question.MethodsWe performed regression analyses to assess associations of self-reported BW with CVD and T2D in 237,631 individuals from the UK Biobank, a large population-based cohort study aged 40-69 years recruited across UK in 2006-2010. Further, we assessed the causal relationship of such associations using the two- sample MR approach, estimating the causal effect by contrasting the SNP effects on the exposure with the SNP effects on the outcome using independent publicly available genome-wide association datasets.ResultsIn the observational analyses, BW showed strong inverse associations with systolic and diastolic blood pressure (β, −0.83 and −0.26; per raw unit in outcomes and SD change in BW; 95% CI, −0.90, −0.75 and −0.31, −0.22, respectively), T2D (odds ratio [OR], 0.83; 95% CI, 0.79, 0.87), lipid-lowering treatment (OR, 0.84; 95% CI, 0.81, 0.86) and CAD (hazard ratio [HR] 0.85; 95% CI, 0.78, 0.94); while the associations with adult body mass index (BMI) and body fat (β, 0.04 and 0.02; per SD change in outcomes and BW; 95% CI, 0.03, 0.04 and 0.01, 0.02, respectively) were positive. The MR analyses indicated inverse causal associations of BW with low density lipoprotein cholesterol, 2-hour glucose, CAD and T2D, and positive causal association with BMI; but no associations with blood pressure. Sensitivity analyses and robust MR methods provided consistent results and indicated no horizontal pleiotropy.ConclusionOur study indicates that lower BW is causally and directly related with increased susceptibility to CAD and T2D in adulthood. This causal relationship is not mediated by adult obesity or hypertension.
Massive Factorial Design Untangles Coding Sequences Determinants of Translation Efficacy
Authors: Cambray Guillaume , Guimaraes Joao C. , Arkin Adam Paul 
Published: October 2017

AbstractComparative analyses of natural sequences or variant libraries are often used to infer mechanisms of expression, activity and evolution. Contingent selective histories and small sample sizes can profoundly bias such approaches. Both limitations can be lifted using precise design of large-scale DNA synthesis. Here, we precisely design 5E. coligenomes worth of synthetic DNA to untangle the relative contributions of 8 interlaced sequence properties described independently as major determinants of translation inEscherichia coli. To expose hierarchical effects, we engineer an inducible translational coupling device enabling epigenetic disruption of mRNA secondary structures. We find that properties commonly believed to modulate translation generally explain less than a third of the variation in protein production. We describe dominant effects of mRNA structures over codon composition on both initiation and elongation, and previously uncharacterized relationships among factors controlling translation. These results advance our understanding of translation efficiency and expose critical design challenges.
Graph abstraction reconciles clustering with trajectory inference through a topology preserving map of single cells
Authors: Wolf F. Alexander , Hamey Fiona , Plass Mireya , Solana Jordi , Dahlin Joakim S. , Göttgens Berthold , Rajewsky Nikolaus , Simon Lukas , Theis Fabian J. 
Published: October 2017

AbstractSingle-cell RNA-seq quantifies biological heterogeneity across both discrete cell types and continuous cell transitions. Partition-based graph abstraction (PAGA) provides an interpretable graph-like map of the arising data manifold, based on estimating connectivity of manifold partitions (https://github.com/theislab/paga). PAGA maps provide interpretable discrete and continuous latent coordinates for both disconnected and continuous structure in data, preserve the global topology of data, allow analyzing data at different resolutions and result in much higher computational efficiency of the typical exploratory data analysis workflow — one million cells take on the order of a minute, a speedup of 130 times compared to UMAP. We demonstrate the method by inferring structure-rich cell maps with consistent topology across four hematopoietic datasets, confirm the reconstruction of lineage relations of adult planaria and the zebrafish embryo, benchmark computational performance on a neuronal dataset and detect a biological trajectory in one deep-learning processed image dataset.
Bundle sheath extensions affect leaf structural and physiological plasticity in response to irradiance
Authors: Barbosa Maria Antonia M. , Chitwood Daniel H. , Azevedo Aristéa A. , Araújo Wagner L. , Ribeiro Dimas M. , Peres Lázaro E. P. , Martins Samuel C. V. , Zsögön Agustin 
Published: October 2017

AbstractCoordination between structural and physiological traits is key to plants’ responses to environmental fluctuations. In heterobaric leaves, bundle sheath extensions (BSEs) increase photosynthetic performance (light-saturated rates of photosynthesis, Amax) and water transport capacity (leaf hydraulic conductance, Kleaf). However, it is not clear how BSEs affect these and other leaf developmental and physiological parameters in response to environmental conditions. The obscuravenosa (obv) mutation, found in many commercial tomato varieties, leads to absence of BSEs. We examined structural and physiological traits of tomato heterobaric and homobaric (obv) near-isogenic lines (NILs) grown at two different irradiance levels. Kleaf, minor vein density and stomatal pore area index decreased with shading in heterobaric but not in homobaric leaves, which show similarly lower values in both conditions. Homobaric plants, on the other hand, showed increased Amax, leaf intercellular air spaces and mesophyll surface area exposed to intercellular airspace (Smes) in comparison with heterobaric plants when both were grown in the shade. BSEs further affected carbon isotope discrimination, a proxy for long-term water-use efficiency. BSEs confer plasticity in traits related to leaf structure and function in response to irradiance levels and might act as a hub integrating leaf structure, photosynthetic function and water supply and demand.Summary statementThe presence of bundle sheath extension (BSEs) defines leaves as heterobaric, as opposed to homobaric leaves that lack them. Multiple functions have been proposed for BSEs, but their impact on different environmental conditions is still unclear. Here, we compared a tomato (Solanum lycopersicum) homobaric mutant lacking BSEs with its corresponding heterobaric wild-type, grown under two irradiance conditions. We show that the presence of BSEs differentially alters various physiological and anatomical parameters in response to growth irradiance. We propose that BSEs could act as hubs coordinating leaf plasticity in response to environmental factors.Article typeResearch article