bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved Visualization and Identification of the Right Adrenal Vein in 70-kVp Contrast-Enhanced Computed Tomography
Authors: Maruyama Koji , Sofue Keitaro , Horinouchi Hiroki , Okada Takuya , Ueshima Eisuke , Gentsu Tomoyuki , Sasaki Koji , Yamaguchi Masato , Sugimoto Koji , Murakami Takamichi 
Published: January 2020

Objective
The aim of this study was to assess the utility of 70-kilovoltage-peak (kVp) contrast-enhanced computed tomography (CECT) for visualization and identification of the right adrenal vein (RAV) in comparison with that of conventional 120-kVp CECT.

Methods
This retrospective study included patients who underwent adrenal venous sampling with concurrent biphasic 120-kVp (120-kVp group, n = 43) or 70-kVp (70-kVp group, n = 47) CECT. Signal-to-noise ratios, contrast-to-noise ratios, longitudinal lengths, conspicuity scores, RAV detection rates, and size-specific dose estimates were compared between the 2 groups.

Results
In comparison with the 120-kVp group, the 70-kVp group had significantly higher signal-to-noise and contrast-to-noise ratios (P < 0.001–P = 0.033), greater longitudinal lengths (P < 0.001–P = 0.002), superior conspicuity scores for the RAV (P < 0.001), higher RAV detection rates (P = 0.015–P = 0.033), and lower size-specific dose estimates (P < 0.001).

Conclusions
Seventy-kilovoltage-peak CECT has advantages over conventional 120-kVp CECT and is potentially useful for noninvasive assessment of the precise anatomy of the RAV.
Gastrointestinal Air Motion Artifact Which Can Be Mistaken for Active Gastrointestinal Bleeding in Multidetector Computed Tomography: Phantom and Clinical Study
Authors: Lee Jeong Sub , Kim Seung Hyoung , Kim Jeong Jae , Kim Bong Soo , Choi Guk Myung , Kim Doo Ri 
Published: January 2020

Objectives
We investigated the computed tomographic characteristics of gastrointestinal air motion artifact (GIAMA), which can be misinterpreted as active gastrointestinal bleeding.

Methods
We simulated GIAMA using 3 types of air-ball phantoms (air-ball in water, air-ball in oil, air–water-ball in oil) and a bovine intestine in oil phantom. We also performed a retrospective clinical review of precontrast abdominal computed tomography images of 76 patients to investigate the frequency, location, shape, and maximum density of hyperdense GIAMA.

Results
In phantom studies, air motion artifacts appeared as dark and bright streak artifacts at the borders of a moving air-ball and water or oil. In the clinical study, hyperdense GIAMA was visualized in 60 (79.0%) of 76 patients. The small intestine was most commonly affected (46.4%), and the intramural type had the highest frequency (58.0%).

Conclusion
Knowing the radiologic features of GIAMA can assists radiologists in identifying active gastrointestinal bleeding sites accurately.
Differential processing and localization of human Nocturnin controls metabolism of mRNA and nicotinamide dinucleotide metabolites
Authors: Abshire Elizabeth T. , Hughes Kelsey , Diao Rucheng , Pearce Sarah , Trievel Raymond C. , Rorbach Joanna , Freddolino Peter L. , Goldstrohm Aaron C. 
Published: January 2020

ABSTRACTNocturnin (NOCT) is a eukaryotic enzyme that belongs to a superfamily of exoribonucleases, endonucleases, and phosphatases. In this study, we analyze the expression, processing, localization, and cellular functions of human NOCT. We demonstrate that the NOCT protein is differentially expressed and processed in a cell and tissue type specific manner as a means to control its localization to the cytoplasm or mitochondria. Our studies also show that the N-terminus of NOCT is necessary and sufficient to confer mitochondrial localization. We then measured the impact of cytoplasmic NOCT on the transcriptome and report that it regulates the levels of hundreds of mRNAs that are enriched for components of signaling pathways, neurological functions, and regulators of osteoblast differentiation. Recent biochemical data indicate that NOCT dephosphorylates nicotinamide adenine dinucleotide (NAD) metabolites, and thus we measured the effect of NOCT on these cofactors in cells. We find that NOCT increases NAD(H) and decreases NADP(H) levels in a manner dependent on its intracellular localization. Collectively, our data indicate that NOCT can regulate levels of both mRNAs and NADP(H) cofactors in manner specified by its intracellular localization.
Within and cross species predictions of plant specialized metabolism genes using transfer learning
Authors: Moore Bethany M. , Wang Peipei , Fan Pengxiang , Lee Aaron , Leong Bryan , Lou Yann-Ru , Schenck Craig A. , Sugimoto Koichi , Last Robert , Lehti-Shiu Melissa D. , Barry Cornelius S. , Shiu Shin-Han 
Published: January 2020

AbstractPlant specialized metabolites mediate interactions between plants and the environment and have significant agronomical/pharmaceutical value. Most genes involved in specialized metabolism (SM) are unknown because of the large number of metabolites and the challenge in differentiating SM genes from general metabolism (GM) genes. Plant models likeArabidopsis thalianahave extensive, experimentally derived annotations, whereas many non-model species do not. Here we employed a machine learning strategy, transfer learning, where knowledge fromA. thalianais transferred to predict gene functions in cultivated tomato with fewer experimentally annotated genes. The first tomato SM/GM prediction model using only tomato data performs well (F-measure=0.74, compared with 0.5 for random and 1.0 for perfect predictions), but from manually curating 88 SM/GM genes, we found many mis-predicted entries were likely mis-annotated. When the SM/GM prediction models built withA. thalianadata were used to filter out genes where theA. thaliana-based model predictions disagreed with tomato annotations, the new tomato model trained with filtered data improved significantly (F-measure=0.92). Our study demonstrates that SM/GM genes can be better predicted by leveraging cross-species information. Additionally, our findings provide an example for transfer learning in genomics where knowledge can be transferred from an information-rich species to an information-poor one.
Microbial Source Tracking in the Love Creek Watershed, Delaware (USA)
Authors: Main Christopher R. , Tyler Robin , Lopez Karen , Heurta Serigo 
Published: January 2020

AbstractFecal contamination of waterways in Delaware pose an ongoing problem for environmental and public health. For monitoring efforts,Enterococcushas been widely adopted by the state to indicate the presence of fecal matter from warm-blooded animals and to establish Primary and Secondary Contact Recreation criteria. In this study, we examined sites within the Love Creek watershed, a tributary of the Rehoboth bay, using next-generation sequencing and SourceTracker to determine sources of potential fecal contamination and compared to bacterial communities to chemical and nutrient concentrations. Microbial community from fecal samples of 10 different types of animals and 1 human sample were used to generate a fecal library for community-based microbial source tracking. Orthophosphate and total dissolved solids were among the major factors associated with community composition. SourceTracker analysis of the monthly samples from the Love Creek watershed indicated the majority of the microbial community were attributed to “unknown” sources, i.e. wildlife. Those that attribute to known sources were primarily domestic animals, i.e. cat and dog. These results suggest that at the state level these methods are capable of giving the start for source tracking as a means to understanding bacterial contamination.
Antisense targeting of decoy exons can reduce intron retention and increase protein expression in human erythroblasts
Authors: Parra Marilyn , Zhang Weiguo , Vu Jonathan , DeWitt Mark , Conboy John G. 
Published: January 2020

AbstractThe decoy exon model has been proposed to regulate a subset of intron retention (IR) events involving predominantly larger introns (>1kb). Splicing reporter studies have shown that decoy splice sites are essential for activity, suggesting that decoys act by engaging intron-terminal splice sites and competing with cross-intron interactions required for intron excision. The decoy model predicts that antisense oligonucleotides blocking decoy splice sites in endogenous pre-mRNA should increase productive gene expression by reducing IR. Indeed, we now demonstrate that targeting a decoy 5′ splice site in the O-GlcNAc transferase (OGT) gene reduced IR from ∼80% to ∼20% in primary human erythroblasts, accompanied by increases in spliced OGT RNA and OGT protein expression. The remaining OGT IR was refractory to antisense treatment and might be mediated by independent mechanism(s). In contrast, other retained introns were strongly dependent on decoy function, since IR was nearly eliminated by antisense targeting of 5′ splice sites. Genes in the latter group encode the widely expressed splicing factor (SF3B1), and the erythroid-specific structural protein, alpha-spectrin (SPTA1). These results show that modulating decoy exon function can dramatically alter IR, and suggest that dynamic regulation of decoy exons could be a mechanism to fine tune gene expression post-transcriptionally in many cell types.
Multi valent DNA vaccine against group A human rotavirus: anin-silicoinvestigation
Authors: Dutta Kunal 
Published: January 2020

SummaryGastroenteritis due to single rotavirus causes huge economic loss annually. Severity of rotaviral diarrhoea among children is primarily manifested by different combinations of G and P types. Rotavirus surveillance studies resulted in two ambitious globally licensed vaccine namely, Rotarix and RotaTaq and a few other. However, post-vaccination surveillance studies indicate, vaccine failure and other complications such as intussusception, environmental enteric dysfunction,etc. Herein, we design a multivalent DNA vaccine against rotavirus and tested its efficiency by usingin silicotools. Two main neutralizing rotaviral antigensi.e, VP7 and VP8 were taken into account and respectively 390, 450 known sequences of different serogroup have been analyzed to obtain a consensus sequence for epitope prediction. Epitopes specific for MHC-I and -II were predicted using IEDB and chosen based on their best IC50value and CPR. A good binding profile with a monoclonal antibody specific for B-cell antigens is displayed by all epitopes they were found to be non-allergenic in the human host. Ethnic specificity of the epitopes is also within acceptable range except for South African and Central American populations. We use pBI-CMV1 bidirectional mammalian expression vector to design the DNA vaccine, where we stapled manually integrated epitopes for VP7 and VP8 at MCS1 and 2 respectively. In conclusion, this study provides a new set of data for a new DNA vaccine against rotavirus.
Structural Analysis of the PATZ1 BTB domain homodimer
Authors: Piepoli Sofia , Alt Aaron Oliver , Atilgan Canan , Mancini Erika J. , Erman Batu 
Published: January 2020

AbstractPATZ1 is a transcriptional repressor belonging to the ZBTB family that is functionally expressed in T-lymphocytes, as well as in a ubiquitous fashion. PATZ1 targets theCd8gene in lymphocyte development and interacts with the p53 protein to control genes important in proliferation and DNA damage response. PATZ1 exerts its activity through an N-terminal BTB domain that mediates dimerization and co-repressor interactions and a C-terminal zinc finger motif-containing domain that mediates DNA binding. Here, the crystal structures of the murine and zebrafish PATZ1 BTB domains are reported at 2.3 and 1.8 Å resolution respectively. The structures reveal that, like other ZBTB structures, the PATZ1 BTB domain forms a stable homodimer and likely binds co-repressors through a lateral surface groove that is formed upon dimerization. Analysis of the lateral groove reveals a large acidic patch in this region which contrasts previously resolved basic co-repressor binding interfaces in other ZBTB proteins. A large 30 amino acids glycine- and alanine-rich central loop, unique to mammalian PATZ1 amongst all ZBTB proteins, could not be resolved likely due to its flexibility. Modelling of this loop indicates that it can participate in the dimerization interface of BTB monomers.SynopsisThe crystal structures of the PATZ1 BTB domain in mammals and fish are homodimers. The core dimer conformation of these BTB proteins is dynamically stable, despite the presence of highly flexible regions in the dimerization interface.
A calibrated optogenetic toolbox of stable zebrafish opsin lines
Authors: Antinucci P , Dumitrescu AS , Deleuze C , Morley HJ , Leung K , Hagley T , Kubo F , Baier H , Bianco IH , Wyart C 
Published: January 2020

AbstractOptogenetic actuators with diverse spectral tuning, ion selectivity and kinetics are constantly being engineered providing powerful tools for controlling neural activity with subcellular resolution and millisecond precision. Achieving reliable and interpretablein vivooptogenetic manipulations requires reproducible actuator expression and calibration of photocurrents in target neurons. Here, we developed nine transgenic zebrafish lines for stable opsin expression and calibrated their efficacyin vivo. We first used high-throughput behavioural assays to compare opsin ability to elicit or silence neural activity. Next, we performedin vivowhole-cell electrophysiological recordings to quantify the amplitude and kinetics of photocurrents and test opsin ability to precisely control spiking. We observed substantial variation in efficacy, associated with differences in both opsin expression level and photocurrent characteristics, and identified conditions for optimal use of the most efficient opsins. Overall, our calibrated optogenetic toolkit will facilitate the design of controlled optogenetic circuit manipulations.
A multi-layered systems approach for renal cell carcinoma
Authors: Cooley Lindsay S. , Rudewicz Justine , Souleyreau Wilfried , Clarke Kim , Falciani Francesco , Dufies Maeva , Verbeke Stephanie , Emanuelli Andrea , Benzekry Sebastien , Taing Cécile , Ribot Emeline Julie , Miraux Sylvain , Lambrechts Diether , Modave Elodie , Pineau Raphael , Derieppe Marie-Alix , Ambrosetti Damien , Bernhard Jean-Christophe , Ravaud Alain , Négrier Sylvie , Ferrero Jean-Marc , Pagès Gilles , Nikolski Macha , Bikfalvi Andreas 
Published: January 2020

AbstractRenal cell carcinoma (RCC) still lacks prognostic and predictive biomarkers to monitor the disease and the response to therapy. The usual strategy in translational research is to start from human samples, to identify molecular markers and gene networks and then to functionally validate themin vitroand in animal models. We devised herein a completely opposite strategy from “mouse to man” by performing an aggressiveness screen and used functional genomics, imaging, clinical data and computational approaches in order to discover molecular pathways and players in renal cancer development and metastasis. Multiple cell lines for primary tumor growth, survival in the blood circulation and lung metastasis or metastatic spread from the primary tumor were generated and analyzed using a multi-layered approach which includes large-scale transcriptome, genome and methylome analyses. Transcriptome and methylome analyses demonstrated distinct clustering in three different groups. Remarkably, DNA sequencing did not show significant genomic variations in the different groups which indicates absence of clonal selection during thein vivoamplification process. Transcriptome analysis revealed distinct signatures of tumor aggressiveness which were validated in patient cohorts. Methylome analysis of full-length DNA allowed clustering of the same groups and revealed clinically relevant signatures. Furthermore, we identified SAA2 and CFB as soluble prognostic and predictive biomarkers of the therapeutic response. We also uncovered IL34 as another soluble prognostic biomarker and key regulator of renal cell carcinoma (RCC) progression. This was also functionally validatedin vivo,and a mathematical model of IL34-dependent primary tumor growth and metastasis development was provided. These results indicate that such multilayered analysis in a RCC animal model leads to meaningful results that are of translational significance.One Sentence SummaryAn aggressiveness screen with multilayer systems analysis to identify signatures and biomarkers for renal cell carcinoma aggressiveness.
A binary arginine methylation switch on histone H3 Arginine 2 regulates its interaction with WDR5
Authors: Lorton Benjamin M. , Harijan Rajesh K. , Burgos Emmanuel S. , Bonanno Jeffery B. , Almo Steven C. , Shechter David 
Published: January 2020

ABSTRACTHistone H3 arginine 2 (H3R2) is post-translationally modified in three different states by “writers” of the protein arginine methyltransferase (PRMT) family. H3R2 methylarginine isoforms include PRMT5-catalyzed mono- and symmetric di-methylation (me1, me2s), and PRMT6-catalyzed me1 and asymmetric dimethylation (me2a). WD-40 repeat-containing protein 5 (WDR5) is an epigenetic “reader” protein that interacts with H3R2 and is a subunit of numerous chromatin-modifying complexes, such as theMixedLineageLeukemia (MLL) H3 lysine 4 methyltransferase complex. Previous studies suggested that MLL recruitment to chromatin was specified by the high-affinity interaction between WDR5 and H3R2me2s. However, our prior biological data prompted the hypothesis that WDR5 may also interact with H3R2me1 to recruit MLL activity. Here, using highly accurate quantitative binding analysis combined with high-resolution crystal structures of WDR5 in complex with unmodified (me0) and me1/me2s L-Arginine amino acids and in complex with H3R2me1 peptide, we provide a rigorous biochemical study of this important biological interaction. Despite modest structural differences at the binding interface, our study supports an interaction model regulated by a binary arginine methylation switch: H3R2me2a prevents interaction with WDR5, whereas H3R2me0/me1/me2s are equally permissive.
Trait-environment relationships are predictive, but not general across species
Authors: Frances Dachin N. , Barber Amelia J. , Tucker Caroline M. 
Published: January 2020

AbstractUnderstanding the relationships between organisms and their environments is increasingly important given human impacts on global conditions. However, predicting how community diversity and composition will change in the future remains challenging (Mouquetet al2015). One recent approach is to use traits to mechanistically inform how environmental conditions affect performance (i.e., trait-environment relationships), under the assumptions that these measures relate to each other in predictive and general ways. Unfortunately, results have been inconsistent, ignore phenotypic plasticity, and rely heavily on observational data (Shipleyet al2016). We evaluated the predictability and generality of trait-environment relationships in a controlled experimental microcosm system of four daphniid species. We cultured each species along a stressful gradient (conspecific density), measuring performance (fecundity) and traits related to performance (body length, 2nd antenna length, eye diameter, relative growth rate, and age at first reproduction). Using structural equation models, we evaluated the role of traits in mediating changes in individual fecundity in response to conspecific density. We built models for each species separately considering within-species trait variation, and for all species together by considering all trait variation across the four species. Results from this controlled system highlight that the relationship between individual traits and the environment (conspecific density) is strong and predictive of performance (fecundity), both within- and across-species. However, the specific trait-environment relationships which predicted fecundity differed for each species and differed from the relationships observed in the interspecific model, suggesting a lack of generality. These results will inform and improve the use of traits as a tool for predicting how changing environments will impact species abundances and distributions.
Integrative analysis identifies candidate tumor microenvironment and intracellular signaling pathways that define tumor heterogeneity in NF1
Authors: Banerjee Jineta , Allaway Robert J , Taroni Jaclyn N , Baker Aaron , Zhang Xiaochun , Moon Chang In , Pratilas Christine A , Blakeley Jaishri O , Guinney Justin , Hirbe Angela , Greene Casey S , Gosline Sara JC 
Published: January 2020

AbstractNeurofibromatosis type 1 is a monogenic syndrome that gives rise to numerous symptoms including cognitive impairment, skeletal abnormalities, and growth of benign nerve sheath tumors. Nearly all NF1 patients develop cutaneous neurofibromas (cNFs), which occur on the skin surface, while 40-60% of patients develop plexiform neurofibromas (pNFs) which are deeply embedded in the peripheral nerves. Patients with pNFs have a ∼10% lifetime chance of these tumors becoming malignant peripheral nerve sheath tumors (MPNSTs). These tumors have a severe prognosis and few treatment options other than surgery. Given the lack of therapeutic options available to patients with these tumors, identification of druggable pathways or other key molecular features could aid ongoing therapeutic discovery studies. In this work, we used statistical and machine learning methods to analyze 77 NF1 tumors with genomic data to characterize key signaling pathways that distinguish these tumors and identify candidates for drug development. We identified subsets of latent gene expression variables that may be important in the identification and etiology of cNFs, pNFs, other neurofibromas, and MPNSTs. Furthermore, we characterized the association between these latent variables and genetic variants, immune deconvolution predictions, and protein activity predictions.
ATR Inhibitors as Potent Modulators of DNA End Resection Capacity
Authors: Dibitetto Diego , Sims Jennie R. , Ascenção Carolline F.R. , Feng Kevin , Freire Raimundo , Smolka Marcus B. 
Published: January 2020

AbstractDNA end resection is a key step in homologous recombination-mediated DNA repair. The ability to manipulate resection capacity is expected to be a powerful strategy to rationally modulate DNA repair outcomes in cancer cells and induce selective cell lethality. However, clinically compatible strategies to manipulate resection are not yet well established. Here we find that long-term inhibition of the ATR kinase has a drastic effect on DNA end resection. Inhibition of ATR over multiple cell division cycles depletes the pool of pro-resection factors and prevents RAD51 as well as RAD52-mediated DNA repair, leading to toxic end-joining and hypersensitivity to PARP inhibitors. The effect is markedly distinct from acute ATR inhibition, which blocks RAD51-mediated repair but not resection and RAD52-mediated repair. Our findings reveal a key pro-resection function for ATR and define how ATR inhibitors can be used for effective manipulation of DNA end resection capacity and DNA repair outcomes in cancer cells.