bluuebunny/crossref_metadata_2025_split huggingface dataset:
The wide distribution and horizontal transfers of beta satellite DNA in eukaryotes
Authors: Yang Jiawen , Yuan Bin , Wu Yu , Li Meiyu , Li Jian , Xu Donglin , Gao Zeng-hong , Ma Guangwei , Zhou Yiting , Zuo Yachao , Wang Jin , Guo Yabin 
Published: September 2019

AbstractBeta satellite DNA (satDNA), also known as Sau3A sequences, are repeated DNA sequences reported in human and primate genomes. It is previously thought that beta satDNAs originated in old world monkeys and bursted in great apes. In this study, we searched 7,821 genome assemblies of 3,767 eukaryotic species and found that beta satDNAs are widely distributed across eukaryotes. The four major branches of eukaryotes, animals, fungi, plants and Harosa/SAR, all have multiple clades containing beta satDNAs. These results were also confirmed by searching whole genome sequencing data (SRA) and PCR assay. Beta satDNA sequences were found in all the primate clades, as well as in Dermoptera and Scandentia, indicating that the beta satDNAs in primates might originate in the common ancestor of Primatomorpha or Euarchonta. In contrast, the widely patchy distribution of beta satDNAs across eukaryotes presents a typical scenario of multiple horizontal transfers.One-sentence summaryBeta satDNAs in Opimoda could be result of HT from Diaphoretickes and those in primates might have originated in common ancestor of Primatomorpha.
Molecular correlates and therapeutic targets in T cell-inflamed versus non-T cell-inflamed tumors across cancer types
Authors: Bao Riyue , Luke Jason J. 
Published: September 2019

AbstractThe T cell-inflamed tumor microenvironment, characterized by CD8 T cells and type I/II interferon transcripts, is an important cancer immunotherapy biomarker. Tumor mutational profile may also dictate response with some oncogenes (i.e. WNT/β-catenin) known to mediate immuno-suppression. Building on these observations we performed a multi-omic analysis of human cancer correlating the T cell-inflamed gene expression signature with the somatic mutanome and transcriptome for different immune phenotypes, by tumor type and across cancers. Strong correlations were noted between mutations in oncogenes and non-T cell-inflamed tumors with examples including IDH1 and GNAQ as well as less well-known genes including KDM6A, CD11c and genes with unknown functions. Conversely, we observe many genes associating with the T cell-inflamed phenotype including VHL and PBRM1, among others. Analyzing gene expression patterns, we identify oncogenic mediators of immune exclusion broadly active across cancer types including HIF1A and MYC. Novel examples from specific tumors include sonic hedgehog signaling in ovarian cancer or hormone signaling and novel transcription factors across multiple tumors. Using network analysis, somatic and transcriptomic events were integrated, demonstrating that most non-T cell-inflamed tumors are influenced by multiple pathways. Validating these analyses, we observe significant inverse relationships between protein levels and the T cell-inflamed gene signature with examples including NRF2 in lung, ERBB2 in urothelial and choriogonadotropin in cervical cancer. Finally, we integrate available databases for drugs that might overcome or augment the identified mechanisms. These results nominate molecular targets and drugs potentially available for immediate translation into clinical trials for patients with cancer.
Loss of CHCHD2 and CHCHD10 activates OMA1 peptidase to disrupt mitochondrial cristae phenocopying patient mutations in vivo
Authors: Liu Yi-Ting , Huang Xiaoping , Nguyen Diana , Dombi Eszter , Springer Danielle A , Poulton Joanna , Sekine Shiori , Narendra Derek P 
Published: September 2019

AbstractDominant mutations in the mitochondrial paralogs CHCHD2 (C2) and CHCHD10 (C10) were recently identified as causing Parkinson’s disease and ALS/FTD/myopathy, respectively. Disruption of mitochondrial cristae has been observed in mutant C10 patient tissues and animal models, but the mechanism for this disruption remains controversial. Additionally, C10 patient mutant knock-in (KI) mice were recently reported to activate a mitochondrial integrated stress response (mt-ISR) and develop cardiomyopathy not seen in C10 knockout (KO) mice, calling into question whether mutant C10 pathogenesis is related to C2/C10 normal function or purely toxic gain of function. Here, using the first C2/10 double knockout (DKO) mice, we report that C10 pathogenesis and the normal function of C2/10 are intimately linked. Similar to patients with C10 mutations, we found that C2/10 DKO mice (but not either single KO mice) have disrupted mitochondrial cristae, due to cleavage of the mitochondrial shaping protein L-OPA1 by the stress-induced peptidase OMA1. OMA1 was found to be activated similarly in affected tissues of mutant C10 KI mice, demonstrating that L-OPA1 cleavage is a novel mechanism for cristae abnormalities due to both C10 mutation and C2/C10 loss, and that OMA1, a driver of neurodegeneration in other contexts, may be a therapeutic target. Finally, C2/10 DKO mice partially phenocopied mutant C10 KI mice with the development of cardiomyopathy and activation of the mt-ISR in affected tissues, tying mutant C10 pathogenesis to C2/C10 function.
The Hrq1 helicase stimulates Pso2 translesion nuclease activity to promote DNA inter-strand crosslink repair
Authors: Rogers Cody M. , Lee Chun-Ying , Parkins Samuel , Buehler Nicholas J. , Wenzel Sabine , Martínez-Márquez Francisco , Takagi Yuichiro , Myong Sua , Bochman Matthew L. 
Published: September 2019

AbstractDNA inter-strand crosslink (ICL) repair requires a complicated network of DNA damage response pathways. Removal of these lesions is vital as they are physical barriers to essential DNA processes that require the separation of duplex DNA, such as replication and transcription. The Fanconi anemia (FA) pathway is the principle mechanism for ICL repair in metazoans and is coupled to replication. InSaccharomyces cerevisiae, a degenerate FA pathway is present, but ICLs are predominantly repaired by a pathway involving the Pso2 nuclease that is hypothesized to digest through the lesion to provide access for translesion polymerases. However, Pso2 lacks translesion nuclease activityin vitro, and mechanistic details of this pathway are lacking, especially relative to FA. We recently identified the Hrq1 helicase, a homolog of the disease-linked RECQL4, as a novel component of Pso2- mediated ICL repair. Here, we show that Hrq1 stimulates the Pso2 nuclease in a mechanism that requires Hrq1 catalytic activity. Importantly, Hrq1 also stimulates Pso2 translesion nuclease activity through a site- specific ICLin vitro. Stimulation of Pso2 nuclease activity is specific to eukaryotic RecQ4 subfamily helicases, and Hrq1 likely interacts with Pso2 through their N-terminal domains. These results advance our understanding of FA-independent ICL repair and establish a role for the RecQ4 helicases in the repair of these dangerous lesions.
Structural organization of the C1a-e-c supercomplex within the ciliary central apparatus
Authors: Fu Gang , Zhao Lei , Dymek Erin , Hou Yuqing , Song Kangkang , Phan Nhan , Shang Zhiguo , Smith Elizabeth F. , Witman George B. , Nicastro Daniela 
Published: September 2019

AbstractNearly all motile cilia contain a central apparatus (CA) composed of two connected singlet-microtubules with attached projections that play crucial roles in regulating ciliary motility. Defects in CA assembly usually result in motility-impaired or paralyzed cilia, which in humans causes disease. Despite their importance, the protein composition and functions of the CA projections are largely unknown. Here, we integrated biochemical and genetic approaches with cryo-electron tomography to compare the CA of wild typeChlamydomonaswith CA mutants. We identified a large (>2 MDa) complex, the C1a-e-c supercomplex, that requires the PF16 protein for assembly and contains the CA components FAP76, FAP81, FAP92, and FAP216. We localized these subunits within the supercomplex using nanogold-labeling and show that loss of any one of them results in impaired ciliary motility. These data provide insight into the subunit organization and three-dimensional (3D) structure of the CA, which is a prerequisite for understanding the molecular mechanisms by which the CA regulates ciliary beating.SummaryFu et al. use a wild-type vs. mutant comparison and cryo-electron tomography ofChlamydomonasflagella to identify central apparatus (CA) subunits and visualize their location in the native 3D CA structure. The study provides a better understanding of the CA and how it regulates ciliary motility.
A framework for testing different imputation methods for tabular datasets
Authors: Kossen Tabea , Livne Michelle , Madai Vince I , Galinovic Ivana , Frey Dietmar , Fiebach Jochen B 
Published: September 2019

AbstractBackground and purposeHandling missing values is a prevalent challenge in the analysis of clinical data. The rise of data-driven models demands an efficient use of the available data. Methods to impute missing values are thus crucial. Here, we developed a publicly available framework to test different imputation methods and compared their impact in a typical stroke clinical dataset as a use case.MethodsA clinical dataset based on the 1000Plus stroke study with 380 completed-entries patients was used. 13 common clinical parameters including numerical and categorical values were selected. Missing values in a missing-at-random (MAR) and missing-completely-at-random (MCAR) fashion from 0% to 60% were simulated and consequently imputed using the mean, hot-deck, multiple imputation by chained equations, expectation maximization method and listwise deletion. The performance was assessed by the root mean squared error, the absolute bias and the performance of a linear model for discharge mRS prediction.ResultsListwise deletion was the worst performing method and started to be significantly worse than any imputation method from 2% (MAR) and 3% (MCAR) missing values on. The underlying missing value mechanism seemed to have a crucial influence on the identified best performing imputation method. Consequently no single imputation method outperformed all others. A significant performance drop of the linear model started from 11% (MAR+MCAR) and 18% (MCAR) missing values.ConclusionsIn the presented case study of a typical clinical stroke dataset we confirmed that listwise deletion should be avoided for dealing with missing values. Our findings indicate that the underlying missing value mechanism and other dataset characteristics strongly influence the best choice of imputation method. For future studies with similar data structure, we thus suggest to use the developed framework in this study to select the most suitable imputation method for a given dataset prior to analysis.
A CLN6-CLN8 complex recruits lysosomal enzymes at the ER for Golgi transfer
Authors: Bajaj Lakshya , di Ronza Alberto , Zheng Pengcheng , Eblimit Aiden , Pal Rituraj , Sharma Jaiprakash , Roman Dany , Collette John R. , Sifers Richard N. , Jung Sung Y. , Chen Rui , Schekman Randy W. , Sardiello Marco 
Published: September 2019

ABSTRACTLysosomal enzymes are synthesized in the endoplasmic reticulum (ER) and transferred to the Golgi complex by interaction with the Batten disease protein CLN8. Here we investigated the relationship of this pathway with CLN6, an ER-associated protein of unknown function that is defective in a different Batten disease subtype. Experiments focused on protein interaction and trafficking identified CLN6 as an obligate component of a CLN6-CLN8 complex (herein referred to as EGRESS:ER-to-Golgi relaying ofenzymes of the lysosomalsystem) which recruits lysosomal enzymes at the ER to promote their Golgi transfer. Simultaneous deficiency of CLN6 and CLN8 did not aggravate mouse pathology compared to the single deficiencies, indicating that the EGRESS complex works as a functional unit. Mutagenesis experiments showed that the second luminal loop of CLN6 is required for the interaction of CLN6 with the enzymes but dispensable for interaction with CLN8, and in vitro and in vivo studies showed that CLN6 deficiency results in inefficient ER export of lysosomal enzymes and diminished levels of the enzymes at the lysosome. These results identify CLN6 and the EGRESS complex as key players in lysosome biogenesis and shed light on the molecular etiology of Batten disease caused by defects in CLN6.
Deep Mutational Scan of a cardiac sodium channel voltage sensor
Authors: Glazer Andrew M. , Kroncke Brett M. , Matreyek Kenneth A. , Yang Tao , Wada Yuko , Shields Tiffany , Salem Joe-Elie , Fowler Douglas M. , Roden Dan M. 
Published: September 2019

AbstractVariants in ion channel genes have classically been studied in low-throughput by patch clamping. Deep Mutational Scanning (DMS) is a complementary approach that can simultaneously assess function of thousands of variants. We have developed and validated a method to perform a DMS of variants in SCN5A, which encodes the major voltage-gated sodium channel in the heart. We created a library of nearly all possible variants in a 36 base region of SCN5A in the S4 voltage sensor of domain IV and stably integrated the library into HEK293T cells. In preliminary experiments, challenge with three drugs (veratridine, brevetoxin, and ouabain) could discriminate wildtype channels from gain and loss of function pathogenic variants. High-throughput sequencing of the pre- and post-drug challenge pools was used to count the prevalence of each variant and identify variants with abnormal function. The DMS scores identified 40 putative gain of function and 33 putative loss of function variants. For 8/9 variants, patch clamping data was consistent with the scores. These experiments demonstrate the accuracy of a high-throughput in vitro scan of SCN5A variant function, which can be used to identify deleterious variants in SCN5A and other ion channel genes.
Plastid phylogenomics resolves ambiguous relationships within the orchid family and provides a solid timeframe for biogeography and macroevolution
Authors: Serna-Sánchez Maria Alejandra , Pérez-Escobar Oscar A. , Bogarín Diego , Torres María Fernanda , Alvarez-Yela Astrid Catalina , Arcila Juliana E. , Hall Climbie F. , de Barros Fábio , Pinheiro Fábio , Dodsworth Steven , Chase Mark W. , Antonelli Alexandre , Arias Tatiana 
Published: September 2019

ABSTRACTRecent phylogenomic analyses based on the maternally inherited plastid organelle have enlightened evolutionary relationships between the subfamilies of Orchidaceae and most of the tribes. However, uncertainty remains within several subtribes and genera for which phylogenetic relationships have not ever been tested in a phylogenomic context. To address these knowledge-gaps, we here provide the most extensively sampled analysis of the orchid family to date, based on 78 plastid coding genes representing 264 species, 117 genera, 18 tribes and 28 subtribes. Divergence times are also provided as inferred from strict and relaxed molecular clocks and birth-death tree models. Our taxon sampling includes 51 newly sequenced plastid genomes produced by a genome skimming approach. We focus our sampling efforts on previously unplaced clades within tribes Cymbidieae and Epidendreae. Our results confirmed phylogenetic relationships in Orchidaceae as recovered in previous studies, most of which were recovered with maximum support (209 of the 262 tree nodes). We provide for the first time a clear phylogenetic placement for Codonorchideae within subfamily Orchidoideae, and Podochilieae and Collabieae within subfamily Epidendroideae. We also identify relationships that have been persistently problematic across multiple studies, regardless of the different details of sampling and genomic datasets used for phylogenetic reconstructions. Our study provides an expanded, robust temporal phylogenomic framework of the Orchidaceae that paves the way for biogeographical and macroevolutionary studies.
The formation of research ethics for data sharing by biological scientists: an empirical analysis
Authors: Ju Boryung , Kim Youngseek 
Published: September 2019

PurposeThe purpose of this paper is to investigate how biological scientists form research ethics for data sharing, and what the major factors affecting biological scientists’ formation of research ethics for data sharing are.Design/methodology/approachA research model for data sharing was developed based on the consequential theorists’ perspective of ethics. An online survey of 577 participants was administered, and the proposed research model was validated with a structural equation modeling technique.FindingsThe results show that egoism factors (perceived reputation, perceived risk, perceived effort), utilitarianism factors (perceived community benefit and perceived reciprocity) and norm of practice factors (perceived pressure by funding agency, perceived pressure by journal and norm of data sharing) all contribute to the formation of research ethics for data sharing.Research limitations/implicationsThis research employed the consequentialist perspective of ethics for its research model development, and the proposed research model nicely explained how egoism, utilitarianism and norm of practice factors influence biological scientists’ research ethics for data sharing, which eventually leads to their data sharing intentions.Practical implicationsThis research provides important practical implications for examining scientists’ data sharing behaviors from the perspective of research ethics. This research suggests that scientists’ data sharing behaviors can be better facilitated by emphasizing their egoism, utilitarianism and normative factors involved in research ethics for data sharing.Originality/valueThe ethical perspectives in data sharing research has been under-studied; this research sheds light on biological scientists’ formation of research ethics for data sharing, which can be applied in promoting scientists’ data sharing behaviors across different disciplines.
May trust and solidarity defy food scares? The case of Parmigiano-Reggiano PDO sales in the aftermath of natural disaster
Authors: Menozzi Davide , Finardi Corrado 
Published: September 2019

Purpose
A major earthquake and aftershocks have hit the North-East part of Italy in May 2012, and caused 26 deaths and diffuse economic damage in the localised agri-food system (LAFS) of Parmigiano-Reggiano protected designation of origin (PDO), including several dairy warehouses. In the broad mobilization to help the stricken people, the LAFS actors played a primary role, giving rise to the sales of “Parmigiano-Reggiano damaged by the earthquake” (PR-T). The purpose of this paper is to investigate the main determinants of PR-T purchasing using the theory of planned behaviour (TPB).

Design/methodology/approach
A survey on 200 consumers was performed. Data were collected with face-to-face interviews in stores and markets where the PR-T has been sold, and analyzed by structural equation modelling.

Findings
The TPB model predictors accounted for 52 per cent of the variance of intentions to purchase PR-T in the future and 21 per cent of the variance of behaviour. Perceived behavioural control is the main predictor of intention and behaviour, indicating that making easier the access to key resources and increasing people’s capability seems a major aspect to reach the intended goals. Trust in producers and retailers communication, positive image of the PDO label, sense of belonging to the region of origin and socio-demographics, i.e. age and educational levels, are correlated with intention and behaviour. The food scare flare up in the media was not a reason impeding purchasing PR-T.

Originality/value
These findings show the solidarity aspects underlying the collective purchases of PR-T in the aftermath of the 2012 earthquake waves, and the importance of increasing people’s capability and trust to reach the goal of facing dreadful food scares effectively.
Brand co-creation through triadic stakeholder participation
Authors: Sarkar Sanmitra , Banerjee Saikat 
Published: September 2019

PurposeThe purpose of this paper is to find prior research work on brand co-creation and the role of different stakeholders in brand co-creation and to come up with a conceptual model that can be empirically validated.Design/methodology/approachA keyword approach has been used to find earlier published papers on co-creation and the role of different stakeholders in co-creation. The focus was more on brand co-creation. The inclusion criteria are empirical or conceptual research papers, books, conference papers, peer reviewed and published in English language journals. As the topic is encompassing various themes, a wide variety of academic resources were reviewed.FindingsThe history of literature brings forth the two major stakeholders consumers and organizations. The importance of third important stakeholder, i.e. suppliers has been mostly overlooked. However, previous studies show that appropriately managed supplier involvement can diminish product and brand development time and cost and it may provide access to newer technologies and better quality. Hence, for a successful brand co-creation one must not forget the importance of suppliers. Along with the motives and outcomes of brand co-creation from consumer and organization perspective this research aims to look into the supplier perspective of the brand co-creation framework.Originality/valueThis is the first academic literature review on brand co-creation from a triadic stakeholder perspective of consumers, organizations and suppliers. Also there is no comprehensive model that exists for brand co-creation looking at its input and its overall outcome. This review provides a bibliography of academic literature from 1959 to 2018 covering 150 journals.