bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatiotemporal Feature Selection Improves Prediction Accuracy of Multi-Voxel Pattern Classification
Authors: Choupan Jeiran , Gal Yaniv , Douglas Pamela K. , Cohen Mark S. , Reutens David C. , Yang Zhengyi 
Published: August 2019

AbstractThe importance of spatiotemporal feature selection in fMRI decoding studies has not been studied exhaustively. Temporal embedding of features allows the incorporation of brain activity dynamics into multivariate pattern classification, and may provide enriched information about stimulus-specific response patterns and potentially improve prediction accuracy. This study investigates the possibility of enhancing the classification performance by exploring spatial and temporal (spatiotemporal) domain, to identify the optimum combination of the spatiotemporal features based on the classification performance. We investigated the importance of spatiotemporal feature selection using a slow event-related design adapted from the classic Haxby et al. (2001) study. Data were collected using a multiband fMRI sequence with temporal resolution of 0.568 seconds. A wide range of spatiotemporal observations was created as various combinations of spatiotemporal features. Using both random forest, and support vector machine, classifiers, prediction accuracies for these combinations were then compared with the single time-point spatial multivariate pattern approach that uses only a single temporal observation. The results showed that on average spatiotemporal feature selection improved prediction accuracy. Moreover, the random forest algorithm outperformed the support vector machine and benefitted from temporal information to a greater extent. As expected, the most influential temporal durations were found to be around the peak of the hemodynamic response function, a few seconds after the stimuli onset until ∼4 seconds after the peak of the hemodynamic response function. The superiority of spatiotemporal feature selection over single time-point spatial approaches invites future work to design systematic and optimal approaches to the incorporation of spatiotemporal dependencies into feature selection for decoding.HighlightsSpatiotemporal feature selection effect on MVPC was assessed in slow event-related fMRISpatiotemporal feature selection improved brain decoding accuracyFrom ∼2-11 seconds after stimuli onset were the most informative part of each trialRandom forest outperformed support vector machinesRandom forest benefited more from temporal changes compared with support vector machine
Close homologue of L1 sensitizes lung cancer cells to cisplatin and paclitaxel via inhibition Akt pathway
Authors: Cai Xiangdao , Hu Bang , Liu Sheng , Liu Maolin , Huang Yunhe , Lei Peng , Zhang Zhi , He Zhiwei , Zhang Linquan , Huang Rimao 
Published: August 2019

AbstractDrug resistance is a serious promble during chemotherapy in lung cancer, which may lead to tumor relapse and further progression. CHL1 was a tumor suppressor in most malignancies, and it was found downregulated in NSCLC cisplatin-resistant cells H460. Thus, in this study, we investigated the role and mechanism of chemoresistance by CHL1 in lung cancer. Human lung adenocarcinoma cell lines A549 and its cisplatin resistant cells (A549/DDP) and paclitaxel resistant cells (A549/PTX) were applied in this research. CHL1 was found obvious downregulation in A549/DDP and A549/PTX cells versus A549 cells. Suppression of CHL1 in A549 cells, promoted cell survival rate and clone formation, decreased cell apoptosis when treated with or without DDP and PTX, respectively. While excessive CHL1 expression in A549/DDP and A549/PTX cells, the results were opposite. Moreover, CHL1 knockdown mediating chemoresistance was reversed by Akt inhibitor SC66 in A549 cells. In summary, overexpression of CHL1 reversed chemoresistance to cisplatin and PTX via suppressing Akt pathway in lung cancer, it was suggested that CHL1 maybe as a potential target for overcome chemoresistance in lung cancer.
Abscisic acid is essential for rewiring of jasmonic acid-dependent defenses during herbivory
Authors: Vos Irene A , Verhage Adriaan , Watt Lewis G , Vlaardingerbroek Ido , Schuurink Robert C , Pieterse Corné MJ , Van Wees Saskia CM 
Published: August 2019

AbstractJasmonic acid (JA) is an important plant hormone in the regulation of defenses against chewing herbivores and necrotrophic pathogens. In Arabidopsis thaliana, the JA response pathway consists of two antagonistic branches that are regulated by MYC- and ERF-type transcription factors, respectively. The role of abscisic acid (ABA) and ethylene (ET) in the molecular regulation of the MYC/ERF antagonism during plant-insect interactions is still unclear. Here, we show that production of ABA induced in response to leaf-chewing Pieris rapae caterpillars is required for both the activation of the MYC-branch and the suppression of the ERF-branch during herbivory. Exogenous application of ABA suppressed ectopic ERF-mediated PDF1.2 expression in 35S::ORA59 plants. Moreover, the GCC-box promoter motif, which is required for JA/ET-induced activation of the ERF-branch genes ORA59 and PDF1.2, was targeted by ABA. Application of gaseous ET counteracted activation of the MYC-branch and repression of the ERF-branch by P. rapae, but infection with the ET-inducing necrotrophic pathogen Botrytis cinerea did not. Accordingly, P. rapae performed equally well on B. cinerea-infected and control plants, whereas activation of the MYC-branch resulted in reduced caterpillar performance. Together, these data indicate that upon feeding by P. rapae, ABA is essential for activating the MYC-branch and suppressing the ERF-branch of the JA pathway, which maximizes defense against caterpillars.
Type I fatty acid synthase (FAS) trapped in the octanoyl-bound state
Authors: Rittner Alexander , Paithankar Karthik S. , Himmler Aaron , Grininger Martin 
Published: August 2019

AbstractDe novofatty acid biosynthesis in humans is accomplished by a multidomain protein, the type I fatty acid synthase (FAS). Although ubiquitously expressed in all tissues, fatty acid synthesis is not essential in normal healthy cells due to sufficient supply with fatty acids by the diet. However, FAS is overexpressed in cancer cells and correlates with tumor malignancy, which makes FAS an attractive selective therapeutic target in tumorigenesis. Herein, we present a crystal structure of the condensing part of murine FAS, highly homologous to human FAS, with octanoyl moieties covalently bound to the transferase (MAT) and the condensation (KS) domain. The MAT domain binds the octanoyl moiety in a novel (unique) conformation, which reflects the pronounced conformational dynamics of the substrate binding site responsible for the MAT substrate promiscuity. In contrast, the KS binding pocket just subtly adapts to the octanoyl moiety upon substrate binding. Besides the rigid domain structure, we found a positive cooperative effect in the substrate binding of the KS domain by a comprehensive enzyme kinetic study. These structural and mechanistic findings contribute significantly to our understanding of the mode of action of FAS and may guide future rational inhibitor designs.HighlightsThe X-ray structure of the KS-MAT didomain of murine type I FAS is presented in an octanoyl-bound state.Multiple conformations of the MAT domain and a dynamic active site pocket explain substrate promiscuity.The rigid domain structure and minor structural changes upon acylation are in line with the strict substrate specificity of the KS domain.Enzyme kinetics reveals cooperativity in the KS-mediated transacylation step.
Reconstruction of nine thousand years of agriculture-based diet and impact on human genetic diversity in Asia
Authors: Raj Srilakshmi M. , Pei Allison , Foll Matthieu , Schlamp Florencia , Excoffier Laurent , Fuller Dorian Q. , Kivisild Toomas , Clark Andrew G. 
Published: August 2019

SUMMARYDomestication of crops and animals during the Holocene epoch played a critical role in shaping human culture, diet and genetic variation. This domestication process took place across a span of time and space, especially in Asia. We hypothesize that domestication of plants and animals around the world must have influenced the human genome differentially among human populations to a far greater degree than has been appreciated previously. The range of domesticated foods that were available in different regions can be expected to have created regionally distinct nutrient intake profiles and deficiencies. To capture this complexity, we used archaeobotanical evidence to construct two models of dietary nutrient composition over a 9000 year time span in Asia: one based on Larson et al. (2014) and measured through composition of 8 nutrients, and another taking into account a wider range of crops, cooking and lifestyle variation, and the dietary variables glycemic index and carbohydrate content. We hypothesize that the subtle dietary shifts through time and space have also influenced current human genetic variation among Asians. We used statistical methods BayeScEnv, BayeScan and Baypass, to examine the impact of our reconstructed long-term dietary habits on genome-wide genetic variation in 29 current-day Asian populations (Figure S1, Figure 1, Figure 2). Our results show that genetic variation in diet-related pathways is correlated with dietary differences among Asian populations. SNPs in five genes, GHR, LAMA1, SEMA3A, CAST and TCF7L2, involved in the gene ontologies ‘salivary gland morphogenesis’ and ‘negative regulation of type B pancreatic cell apoptotic process’ suggest that metabolism may have been primary targets of selection driven by dietary shifts. These shifts may have influenced biological pathways in ways that have a lasting impact on health. We present a case that archaeobotanical evidence can provide valuable insight for understanding how historical human niche construction might have influenced modern human genetic variation.
Developmental gene expression differences between humans and mammalian models
Authors: Cardoso-Moreira Margarida , Velten Britta , Mort Matthew , Cooper David N. , Huber Wolfgang , Kaessmann Henrik 
Published: August 2019

AbstractIdentifying the molecular programs underlying human organ development and how they differ from those in model species will advance our understanding of human health and disease. Developmental gene expression profiles provide a window into the genes underlying organ development as well as a direct means to compare them across species. We use a transcriptomic resource for mammalian organ development to characterize the temporal profiles of human genes associated with distinct disease classes and to determine, for each human gene, the similarity of its spatiotemporal expression with its orthologs in rhesus macaque, mouse, rat and rabbit. We find that half of human genes differ from their mouse orthologs in their temporal trajectories. These include more than 200 disease genes associated with brain, heart and liver disease, for which mouse models should undergo extra scrutiny. We provide a new resource that evaluates for every human gene its suitability to be modeled in different mammalian species.
Specific Regulation of TCP genes by miR319
Authors: Palatnik Javier F. , Weigel Detlef 
Published: August 2019

AbstractMicroRNAs (miRNAs) are major regulators of gene expression in multicellular organisms. Many of the evolutionarily conserved miRNAs in plants are encoded by small gene families. The miR159/miR319 family has six members of similar sequences sharing 17 nucleotides in Arabidopsis thaliana. The members of this miRNA family regulate genes encoding TCP (TEOSINTE BRANCHED1, CYCLOIDEA and PCF1/2) and MYB transcription factors. However, despite their sequence similarities, genetic evidence indicates that miR159 and miR319 fulfil different roles in vivo. Here, we confirm previous findings showing that TCP genes are not targeted by miR159. Thus, specific small sequence differences between the miRNAs allow for the specific regulation of TCP transcription factors by miR319 miRNAs.
Environmental pH impacts division assembly and cell size inEscherichia coli
Authors: Mueller Elizabeth A. , Westfall Corey S. , Levin Petra Anne 
Published: August 2019

ABSTRACTCell size is a complex trait, derived from both genetic and environmental factors. Environmental determinants of bacterial cell size identified to date primarily target assembly of cytosolic components of the cell division machinery. Whether certain environmental cues also impact cell size through changes in the assembly or activity of extracytoplasmic division proteins remains an open question. Here, we identify extracellular pH as a modulator of cell division and a key determinant of cell size across evolutionarily distant bacterial species. In the Gram-negative model organismEscherichia coli, our data indicate environmental pH impacts the length at which cells divide by altering the ability of the terminal cell division protein FtsN to localize to the cytokinetic machinery and activate division. Acidic environments lead to enrichment of FtsN at the septum and activation of division at a reduced cell length, while alkaline pH inhibits FtsN localization and suppress division activation. Altogether, our work reveals a previously unappreciated role for pH in bacterial cell size control.
Systematic identification of engineered methionines and oxaziridines for efficient, stable, and site-specific antibody bioconjugation
Authors: Elledge Susanna K. , Tran Hai L. , Christian Alec H. , Steri Veronica , Hann Byron , Dean Toste F. , Chang Christopher J. , Wells James A. 
Published: August 2019

AbstractChemical modification of antibodies is one of the most important bioconjugations utilized by biologists and biotechnology. To date, the field has been dominated by random modification of lysines or more site-specific labeling of cysteines, each with attendant challenges. Recently we have developed oxaziridine chemistry for highly selective and efficient sulfimide modification of methionine called redox-activated chemical tagging (ReACT). Here, we systematically scanned methionines throughout one of the most popular antibody scaffolds, trastuzumab, for antibody engineering and drug conjugation. We tested the expression, reactivities, and stabilities of 123 single engineered methionines distributed over the surface of the antibody when reacted with oxaziridine. We found uniformly high expression for these mutants and generally good reaction efficiencies with the panel of oxaziridines. Remarkably, the stability to hydrolysis of the sulfimide varied more than ten-fold depending on temperature and the site of the engineered methionine. Interestingly, the most stable and reactive sites were those that were partially buried, likely because of their reduced access to water. There was also a ten-fold variation in stability depending on the nature of the oxaziridine, which we determined was inversely correlated with the electrophilic nature of the sulfimide. Importantly, the stabilities of the best analogs and antibody drug conjugate potencies were comparable to those reported for cysteine-maleimide modifications of trastuzumab. We also found our antibody drug conjugates to be potent in a breast cancer mouse xenograft model. These studies provide a roadmap for broad application of ReACT for efficient, stable, and site-specific antibody and protein bioconjugation.
The Integrator complex cleaves nascent mRNAs to attenuate transcription
Authors: Tatomer Deirdre C. , Elrod Nathan D. , Liang Dongming , Xiao Mei-Sheng , Jiang Jeffrey Z. , Jonathan Michael , Huang Kai-Lieh , Wagner Eric J. , Cherry Sara , Wilusz Jeremy E. 
Published: August 2019

ABSTRACTCellular homeostasis requires transcriptional outputs to be coordinated, and many events post transcription initiation can dictate the levels and functions of mature transcripts. To systematically identify regulators of inducible gene expression, we performed high-throughput RNAi screening of the Drosophila Metallothionein A (MtnA) promoter. This revealed that the Integrator complex, which has a well-established role in 3’ end processing of small nuclear RNAs (snRNAs), attenuates MtnA transcription during copper stress. Integrator complex subunit 11 (IntS11) endonucleolytically cleaves MtnA transcripts, resulting in premature transcription termination and degradation of the nascent RNAs by the RNA exosome, a complex also identified in the screen. Using RNA-seq, we then identified >400 additional Drosophila protein-coding genes whose expression increases upon Integrator depletion. We focused on a subset of these genes and confirmed that Integrator is bound to their 5’ ends and negatively regulates their transcription via IntS11 endonuclease activity. Many non-catalytic Integrator subunits, which are largely dispensable for snRNA processing, also have regulatory roles at these protein-coding genes, possibly by controlling Integrator recruitment or RNA polymerase II dynamics. Altogether, our results suggest that attenuation via Integrator cleavage limits production of many full-length mRNAs, allowing precise control of transcription outputs.
The diagnostic chronic lymphocytic leukaemia genome by nanopore sequencing
Authors: Burns Adam , DiSalvo-Williams Daniella , Bruce David , Robbe Pauline , Timbs Adele , Stamatopoulos Basile , Clifford Ruth , Lopopolo Maria , Parkes Duncan , Ridout Kate , Schuh Anna 
Published: August 2019

AbstractChronic lymphocytic leukaemia (CLL) is characterised by considerable clinical and biological heterogeneity, with specific recurrent genomic alterations, includingTP53mutations, deletions of chromosome 17p, and IgHV mutational status, impacting on response to chemo-immunotherapy and targeted agents. Consequently, diagnostic screening for these predictive biomarkers is recommended in both national and international clinical guidelines. Current conventional methods, including fluorescentin-situhybridisation and Sanger sequencing, exhibit shortcomings in terms of cost, speed and sensitivity, and even second-generation sequencing methods encounter technical limitations imposed by short-read lengths and bio-informatics analysis. The MinION platform from Oxford Nanopore Technologies generates exceptionally long (1-100kbp) read lengths in a short period of time and at low cost, making it a good candidate for diagnostic testing. In this paper, we present a nanopore-based CLL-specific screening assay, to simultaneously screen for bothTP53mutations and del17p13.1, as well as determining the IgHV mutation status for a single patient in one sequencing run. We sequenced 11 CLL patients and were able to generate a full diagnostic dataset for all. We identified somatic SNVs and indels in the coding region ofTP53, and demonstrate that, following error correction of the data, we could accurately define the somatically hypermutated IgHV region in all patients. We also demonstrated the ability of the MinION platform to detect large-scale genomic deletions through low-coverage whole-genome sequencing. We conclude that nanopore sequencing has the potential to provide accurate, low-cost and rapid diagnostic information, which could be applied to other cancer types.
Detecting anomalies in financial statements using machine learning algorithm
Authors: Lokanan Mark , Tran Vincent , Vuong Nam Hoai 
Published: August 2019

Purpose
The purpose of this paper is to evaluate the possibility of rating the credit worthiness of a firm’s quarterly financial report using a dynamic anomaly detection method.

Design/methodology/approach
The study uses a data set containing financial statements from Quarter 1 – 2001 to Quarter 4 – 2016 of 937 Vietnamese listed firms. In sum, 24 fundamental financial indices are chosen as control variables. The study employs the Mahalanobis distance to measure the proximity of each data point from the centroid of the distribution to point out the extent of the anomaly.

Findings
The finding shows that the model is capable of ranking quarterly financial reports in terms of credit worthiness. The execution of the model on all observations also revealed that most financial statements of Vietnamese listed firms are trustworthy, while almost a quarter of them are highly anomalous and questionable.

Research limitations/implications
The study faces several limitations, including the availability of genuine accounting data from stock exchanges, the strong assumptions of a simple statistical distribution, the restricted timeframe of financial data and the sensitivity of the thresholds for anomaly levels.

Practical implications
The study opens an avenue for ordinary users of financial information to process the data and question the validity of the numbers presented by listed firms. Furthermore, if fraud information is available, similar research can be conducted to examine the tendency for companies with anomalous financial reports to commit fraud.

Originality/value
This is the first paper of its kind that attempts to build an anomaly detection model for Vietnamese listed companies.
Elaboration and validation of a checklist for the evaluation of good hygiene practices in food trucks
Authors: Dolberth Dardin Francine , Stangarlin-Fiori Lize , Olmedo Patrícia Vitório , Serafim Ana Lúcia , Opolski Medeiros Caroline 
Published: August 2019

Purpose
The purpose of this paper is to develop, validate the content and analyze the inter-rater reliability of a checklist of good hygiene practices in food trucks (GHPFT).

Design/methodology/approach
The study was carried out in Curitiba, Brazil, and divided into three stages: preparation of the evaluation checklist; validation of the checklist’s content; and reliability analysis. Content validation was carried out by six experts using the Content Validity Index (CVI). The reliability analysis was performed on five food trucks by four partners using the κ coefficient.

Findings
Prior to validation, the checklist contained 34 items divided into 9 categories; after, this number was changed to 30 items divided into 8 categories. The validated checklist presented a CVI=0.867 for each of the categories and κ between 0.636 and 0.759, indicating good reproducibility.

Research limitations/implications
The checklist considered the requirements of Brazilian laws, and may not reflect the good hygiene practices requirements specific to other countries.

Practical implications
The checklist proposed is an unprecedented tool, and may be used in the implementation of good hygiene practices and in inspections carried out by the Health Regulatory Agency for the street food segment.

Originality/value
The study was the first to describe the development, content validation and inter-rater reliability analysis of an evaluation checklist for GHPFT, and the results can be used by professionals working in the area.