bluuebunny/crossref_metadata_2025_split huggingface dataset:
To Improve Protein Sequence Profile Prediction through Image Captioning on Pairwise Residue Distance Map
Authors: Chen Sheng , Sun Zhe , Liu Zifeng , Liu Xun , Chong Yutian , Lu Yutong , Zhao Huiying , Yang Yuedong 
Published: May 2019

ABSTRACTProtein sequence profile prediction aims to generate multiple sequences from structural information to advance the protein design. Protein sequence profile can be computationally predicted by energy-based method or fragment-based methods. By integrating these methods with neural networks, our previous method, SPIN2 has achieved a sequence recovery rate of 34%. However, SPIN2 employed only one dimensional (1D) structural properties that are not sufficient to represent 3D structures. In this study, we represented 3D structures by 2D maps of pairwise residue distances. and developed a new method (SPROF) to predict protein sequence profile based on an image captioning learning frame. To our best knowledge, this is the first method to employ 2D distance map for predicting protein properties. SPROF achieved 39.8% in sequence recovery of residues on the independent test set, representing a 5.2% improvement over SPIN2. We also found the sequence recovery increased with the number of their neighbored residues in 3D structural space, indicating that our method can effectively learn long range information from the 2D distance map. Thus, such network architecture using 2D distance map is expected to be useful for other 3D structure-based applications, such as binding site prediction, protein function prediction, and protein interaction prediction.
Controlling emulsification for organic solvent-based tissue clearing
Authors: Hou Bing , Liu Xinyi , Zhang Dan , Yang Zaifu , Hui Hui , Wang Peixin , Wang Jiarui , Qiu Zilong , Liu Yanyan , Yang Zhengyi , Jiang Tianzi 
Published: May 2019

AbstractOrganic solvent-based tissue clearing techniques are hampered by the quenching of fluorescent proteins, partially due to routine complete dehydration. Unexpectedly, we discovered that complete dehydration is unnecessary for organic solvents to clear tissues and that the hidden purpose has been to prevent emulsification. After controlling emulsification of organic solvent-cleared but incompletely dehydrated mouse brain, we achieved sufficient tissue transparency that allowed light-sheet imaging while well-preserving the fluorescence of fluorescent proteins.
Reduction ofBacillus cereusBiofilms on Stainless Steel Surfaces byPestalotiopsissp. Culture Crude Extract
Authors: De Jesus Rener S. , Dedeles Gina R. 
Published: May 2019

AbstractBacillus cereusis capable of forming biofilms on many types of substrata, including stainless steel surfaces. Thus, the presence ofB. cereusbiofilms in food production facilities is inevitable, and possible food contamination could occur, resulting in product spoilage and deterioration, which would eventually lead to product rejection and financial loss.Pestalotiopsisspp. have been shown to produce a wide range of novel secondary metabolites that have potential medicinal, industrial, and agricultural applications. In this study,B. cereusbiofilms were grown on milk pre-soiled stainless steel coupons (20 × 5 mm) for 48 hr at 30°C in nutrient-depleted medium. After incubation, the biofilms on the coupons were immersed for 15 min in different concentrations (25, 50, or 100 mg/mL) ofPestalotiopsissp. culture extract at 25°C or 50°C. The results showed that the 48-hr oldB. cereusbiofilms were significantly reduced (p < 0.05) following immersion in all concentrations of extract. Specifically, the 100-mg/mL concentration resulted in 0.18- to 2-log10and 0.48- to 2.28-log10reductions at 25°C and 50°C, respectively. Secondary metabolites were detected inPestalotiopsissp. culture crude extract using thin layer chromatography, indicating that these metabolites have antibiofilm activity. Additionally, fluorescence micrographs displayed decreasing light intensities emitted by the fluorescent dye ethidium bromide at 605 nm, as was also evident from the interactive 3-D surface plots generated using ImageJ 1.52a software, which indicated that the extracellular polymeric substances in the biofilms were disrupted. The current study concluded that secondary metabolites from the extract ofPestalotiopsissp. have antibiofilm activity and contain possible bioactive agents with activity against many varieties of microbial biofilms.
Performance comparison of reverse transcriptases for single-cell studies
Authors: Daniel Zucha , Peter Androvic , Mikael Kubista , Lukas Valihrach 
Published: May 2019

ABSTRACTBackgroundRecent technical advances allowing quantification of RNA from single cells are revolutionizing biology and medicine. Currently, almost all single-cell transcriptomic protocols rely on conversion of RNA to cDNA by reverse transcription (RT). However, RT is recognized as highly limiting step due to its inherent variability and suboptimal sensitivity, especially at minute amounts of RNA. Primary factor influencing RT outcome is reverse transcriptase (RTase). Recently, several new RTases with potential to decrease the loss of information during RT have been developed, but the thorough assessment of their performance is missing.MethodsWe have compared the performance of 11 RTases in RT-qPCR on single-cell and 100-cell bulk templates using two priming strategies: conventional mixture of random hexamers with oligo(dT)s and reduced concentration of oligo(dT)s mimicking common single-cell RNA-Seq library preparation protocols. Based on the performance, two RTases were further tested in high-throughput single-cell experiment.ResultsAll RTases tested reverse transcribed low-concentration templates with high accuracy (R2 > 0.9445) but variable reproducibility (median CVRT = 40.1 %). The most pronounced differences were found in the ability to capture rare transcripts (0 - 90% reaction positivity rate) as well as in the rate of RNA conversion to cDNA (7.3 - 124.5 % absolute yield). Finally, RTase performance and reproducibility across all tested parameters were compared using Z-scores and validity of obtained results was confirmed in a single-cell model experiment. The better performing RTase provided higher positive reaction rate and expression levels and improved resolution in clustering analysis.ConclusionsWe performed a comprehensive comparison of 11 RTases in low RNA concentration range and identified two best-performing enzymes (Maxima H-; SuperScript IV). We found that using better-performing enzyme (Maxima H-) over commonly-used below-average performer (SuperScript II) increases the sensitivity of single-cell experiment. Our results provide a reference for the improvement of current single-cell quantification protocols.
Discovery of tumoricidal DNA oligonucleotides by effect-directedin-vitroevolution
Authors: Mamet Noam , Amir Yaniv , Lavi Erez , Bassali Liron , Harari Gil , Rusinek Itai , Skalka Nir , Debby Elinor , Greenberg Mor , Zamir Adva , Paz Anastasia , Reiss Neria , Loewenthal Gil , Avivi Irit , Shimoni Avichai , Neev Guy , Abu-Horowitz Almogit , Bachelet Ido 
Published: May 2019

AbstractOur current model of drug discovery is challenged by the relative ineffectiveness of drugs against highly variable and rapidly evolving diseases and their relatively high incidence of adverse effects due to poor selectivity. Here we describe a robust and reproducible platform which could potentially address these limitations. The platform enables rapid,de-novodiscovery of DNA oligonucleotides evolvedin-vitroto exert specific biological effects on target cells. Unlike aptamers, which are selected by their ligand binding capacity, this platform is driven directly by therapeutic effect and selectivity towards target vs negative target cells. The process could, therefore, operate without anya-prioriknowledge (e.g. mutations, biomarker expression, or known drug resistance) of the target. We report the discovery of DNA oligonucleotides with direct and selective cytotoxicity towards several tumor cell lines as well as primary, patient-derived solid and hematological tumors, some with chemotherapy resistance. Oligonucleotides discovered by this platform exhibited favorable biodistribution in animals, persistence in target tumors up to 48 hours after injection, and safety in human blood. These oligonucleotides showed remarkable efficacyin-vivoas well asex-vivoin freshly obtained, 3D cultured human tumors resistant to multiple chemotherapies. With further improvement, these findings could lead to a drug discovery model which is target-tailored, mechanism-flexible, and nearly on-demand.
High-speed motility originates from cooperatively pushing and pulling flagella bundles in bilophotrichous bacteria
Authors: Bente Klaas , Mohammadinejad Sarah , Charsooghi Mohammad A. , Bachmann Felix , Codutti Agnese , Lefèvre Christopher T. , Klumpp Stefan , Faivre Damien 
Published: May 2019

AbstractBacteria propel and change direction by rotating long, helical filaments, called flagella. The number of flagella, their arrangement on the cell body and their sense of rotation hypothetically determine the locomotion characteristics of a species. The movement of the most rapid microorganisms has in particular remained unexplored because of additional experimental limitations. We show that magnetotactic cocci with two flagella bundles on one pole swim faster than 500 µm⋅s−1 along a double helical path, making them one of the fastest natural microswimmers. We additionally reveal that the cells reorient in less than 5 ms, an order of magnitude faster than reported so far for any other bacteria. Using hydrodynamic modeling, we demonstrate that a mode where a pushing and a pulling bundle cooperate is the only possibility to enable both helical tracks and fast reorientations. The advantage of sheathed flagella bundles is the high rigidity, making high swimming speeds possible.
An in vivo inflammatory loop potentiates KRAS blockade
Authors: Arendt Kristina A.M. , Ntaliarda Giannoula , Armenis Vasileios , Kati Danai , Henning Christin , Giotopoulou Georgia A. , Pepe Mario A.A. , Klotz Laura V. , Lamort Anne-Sophie , Hatz Rudolf A. , Kobold Sebastian , Stathopoulos Georgios T. 
Published: May 2019

ABSTRACTKRAS inhibitors perform inferior to other targeted drugs. To investigate a possible reason for this, we treated cancer cells with KRAS inhibitors deltarasin (targeting phosphodiesterase-δ), cysmethynil (targeting isoprenylcysteine carboxylmethyltransferase), and AA12 (targeting KRASG12C), and silenced/overexpressed mutant KRAS using custom vectors. We show that KRAS-mutant tumor cells exclusively respond to KRAS blockade in vivo, because the oncogene co-opts host myeloid cells via a C-C-motif chemokine ligand 2/interleukin-1β signaling loop for sustained tumorigenicity. Indeed, KRAS-mutant tumors did not respond to deltarasin in Ccr2 and Il1b gene-deficient mice, but were deltarasin-sensitive in wild-type and Ccr2-deficient mice adoptively transplanted with wild-type murine bone marrow. A KRAS-dependent pro-inflammatory transcriptome was prominent in human cancers with high KRAS mutation prevalence and predicted poor survival. Hence the findings support that in vitro systems are suboptimal for anti-KRAS drug screens, and suggest that interleukin-1β blockade might be specific for KRAS-mutant cancers.
Development of SGC-GAK-1 as an orally active in vivo probe for cyclin G associated kinase through cytochrome P450 inhibition
Authors: Asquith Christopher R. M. , Bennett James M. , Su Lianyong , Laitinen Tuomo , Elkins Jonathan M. , Pickett Julie E. , Wells Carrow I. , Li Zengbiao , Willson Timothy M. , Zuercher William J. 
Published: May 2019

AbstractSGC-GAK-1 (1), a potent, selective, cell-active chemical probe for cyclin G associated kinase (GAK), was rapidly metabolized in mouse liver microsomes by P450 mediated oxidation. 1 displayed rapid clearance in mice, limiting its utility for in vivo studies. All chemical modifications of 1 that improved metabolic stability led to a loss in GAK activity. However, pretreatment of liver microsomes with the irreversible cytochrome P450 inhibitor 1-aminobenzotriazole (ABT) decreased intrinsic clearance of 1. Coadministration of ABT also greatly improved plasma exposure of 1 in mice, supporting its use as a chemical probe to study the in vivo biology of GAK inhibition.
Determination of complete chromosomal haplotypes by bulk DNA sequencing
Authors: Tourdot Richard W. , Zhang Cheng-Zhong 
Published: May 2019

AbstractHaplotype phase represents the collective genetic variation between homologous chromosomes and is an essential feature of non-haploid genomes. Determining the haplotype phase requires knowledge of both the genotypes at variant sites and their linkage across each chromosome. Haplotype linkage can be either inferred statistically from a genotyped population, or determined by long-range sequencing of an individual genome. However, extending haplotype inference to the whole-chromosome scale remains challenging and usually requires special experimental techniques. Here we describe a general computational strategy to determine complete chromosomal haplotypes using a combination of bulk long-range sequencing and Hi-C sequencing. We demonstrate that this strategy can resolve the haplotypes of parental chromosomes in diploid human genomes at high precision (99%) and completeness (98%), and is further able to assemble the syntenic organization of aneuploid genomes (“digital karyotype”).
Concurrent Guidance of Attention by Multiple Working Memory Items: Behavioral and Computational Evidence
Authors: Zhou Cherie , Lorist Monicque M. , Mathôt Sebastiaan 
Published: May 2019

AbstractDuring visual search, task-relevant representations in visual working memory (VWM), known as attentional templates, are assumed to guide attention. A current debate concerns whether only one (Single-Item-Template hypothesis, or SIT) or multiple (Multiple-Item-Template hypothesis, or MIT) items can serve as attentional templates simultaneously. The current study was designed to test these two hypotheses. Participants memorized two colors, prior to a visual-search task in which the target and the distractor could match or not match the colors held in VWM. Robust attentional guidance was observed when one of the memory colors was presented as the target (reduced response times [RTs] on target-match trials) or the distractor (increased RTs on distractor-match trials). We constructed two drift-diffusion models that implemented the MIT and SIT hypotheses, which are similar in their predictions about overall RTs, but differ in their predictions about RTs on individual trials. Critically, simulated RT distributions and error rates revealed a better match of the MIT hypothesis to the observed data than the SIT hypothesis. Taken together, our findings provide behavioral and computational evidence for the concurrent guidance of attention by multiple items in VWM.Significance statementTheories differ in how many items within visual working memory can guide attention at the same time. This question is difficult to address, because multiple- and single-item-template theories make very similar predictions about average response times. Here we use drift-diffusion modeling in addition to behavioral data, to model response times at an individual level. Crucially, we find that our model of the multiple-item-template theory predicts human behavior much better than our model of the single-item-template theory; that is, modeling of behavioral data provides compelling evidence for multiple attentional templates that are simultaneously active.
Genome-wide 5-hydroxymethylcytosine (5hmC) emerges at early stage of in vitro hepatocyte differentiation
Authors: Rodríguez-Aguilera Jesús Rafael , Ecsedi Szilvia , Cros Marie-Pierre , Goldsmith Chloe , Domínguez-López Mariana , Guerrero-Celis Nuria , de Vaca Rebeca Pérez-Cabeza , Chemin Isabelle , Recillas-Targa Félix , de Sánchez Victoria Chagoya , Hernández-Vargas Héctor 
Published: May 2019

AbstractHow cells reach different fates despite using the same DNA template, is a basic question linked to differential patterns of gene expression. Since 5-hydroxymethylcytosine (5hmC) emerged as an intermediate metabolite in active DNA demethylation, there have been increasing efforts to elucidate its function as a stable modification of the genome, including a role in establishing such tissue-specific patterns of expression. Recently we described TET1-mediated enrichment of 5hmC on the promoter region of the master regulator of hepatocyte identity, HNF4A, which precedes differentiation of liver adult progenitor cells in vitro. Here we asked whether 5hmC is involved in hepatocyte differentiation. We found a genome-wide increase of 5hmC as well as a reduction of 5-methylcytosine at early hepatocyte differentiation, a time when the liver transcript program is already established. Furthermore, we suggest that modifying s-adenosylmethionine (SAM) levels through an adenosine derivative could decrease 5hmC enrichment, triggering an impaired acquisition of hepatic identity markers. These results suggest that 5hmC is a regulator of differentiation as well as an imprint related with cell identity. Furthermore, 5hmC modulation could be a useful biomarker in conditions associated with cell de-differentiation such as liver malignancies.Graphical AbstractIt has been suggested that 5-hydroxymethylcytosine (5hmC) is an imprint of cell identity. Here we show that commitment to a hepatocyte transcriptional program is characterized by a demethylation process and emergence of 5hmC at multiple genomic locations. Cells exposed to an adenosine derivative during differentiation did not reach such 5hmC levels, and this was associated with a lower expression of hepatocyte-markers. These results suggest that 5hmC enrichment is an important step on the road to hepatocyte cell fate.
Heterogenization of remaining biodiversity in fragmented tropical forests across agricultural landscapes
Authors: Vidal Cristina Yuri , Souza Bezerra Rocha Diogo , Ferreira de Siqueira Marinez , Rodrigues Ricardo Ribeiro , Siqueira Tadeu 
Published: May 2019

AbstractThe increasing worldwide interest on the conservation of tropical forests reflects the conversion of over 50% of their area into agricultural lands and other uses. Understanding the distribution of remaining biodiversity across agricultural landscapes is an essential task to guide future conservation strategies. To understand the long-term effects of fragmentation on biodiversity, we investigated whether forest fragments in southeastern Brazil are under a taxonomic homogenization or heterogenization process. We estimated pre-deforestation species richness and composition based on a Species Distribution Modelling approach, and compared them to the observed patterns of α- and β-diversity. In particular, we asked (i) if changes in β-diversity reveal convergence or divergence on species composition; (ii) if these changes are similar between forest fragments in Strictly Protected Areas (SPAs) (n=20) and within private lands (n=367) and in different regions of the state (West, Center, and Southeast). We detected steep reductions in observed local species richness in relation to our modeled predictions, and this was particularly true among forest fragments in non-protected private lands. The higher observed β diversity indicated an overall biotic heterogenization process, consistent with the idea that the originally diverse vegetation is now reduced to small and isolated patches, with unique disturbance histories and impoverished communities derived from a large regional species pool. Since conservation of biodiversity extends beyond the boundaries of strictly Protected Areas, we advocate forest fragments are valuable for conservation in agricultural landscapes, with particular relevance for private lands, which represent the most exposed and neglected share of what is left.
Deep Learning Approach to Identifying Breast Cancer Subtypes Using High-Dimensional Genomic Data
Authors: Chen Runpu , Yang Le , Goodison Steve , Sun Yijun 
Published: May 2019

AbstractMotivationCancer subtype classification has the potential to significantly improve disease prognosis and develop individualized patient management. Existing methods are limited by their ability to handle extremely high-dimensional data and by the influence of misleading, irrelevant factors, resulting in ambiguous and overlapping subtypes.ResultsTo address the above issues, we proposed a novel approach to disentangling and eliminating irrelevant factors by leveraging the power of deep learning. Specifically, we designed a deep learning framework, referred to as DeepType, that performs joint supervised classification, unsupervised clustering and dimensionality reduction to learn cancer-relevant data representation with cluster structure. We applied DeepType to the METABRIC breast cancer dataset and compared its performance to state-of-the-art methods. DeepType significantly outperformed the existing methods, identifying more robust subtypes while using fewer genes. The new approach provides a framework for the derivation of more accurate and robust molecular cancer subtypes by using increasingly complex, multi-source data.Availability and implementationAn open-source software package for the proposed method is freely available atwww.acsu.buffalo.edu/~yijunsun/lab/DeepType.html.
Hypoxia in cancer chemo- and immunotherapy: foe or friend?
Authors: Vitos Noemi , Chen Shannon , Mathur Shreya , Chamseddine Ibrahim , Rejniak Katarzyna A. 
Published: May 2019

AbstractHypoxia, a low level of oxygen in the tissue, is a feature of most solid tumors. It arises due to an imbalance between the oxygen supply from the abnormal vasculature and oxygen demand by the large number of tumor and stromal cells. Hypoxia has been implicated in the development of aggressive tumors and tumor resistance to various therapies. This makes hypoxia a negative marker of patients’ survival. However, recent advances in designing new hypoxia-activated pro-drugs and adoptive T cell therapies provide an opportunity for exploiting hypoxia in order to improve cancer treatment. We used novel mathematical models of micro-pharmacology and computational optimization techniques for determining the most effective treatment protocols that take advantage of heterogeneous and dynamically changing oxygenation in in vivo tumors. These models were applied to design schedules for a combination of three therapeutic compounds in pancreatic cancers and determine the most effective adoptive T cell therapy protocols in melanomas.