bluuebunny/crossref_metadata_2025 huggingface dataset:
Does the Surgeon’s Caseload Affect the Outcome in Laparoscopic Cholecystectomy for Acute Cholecystitis?
Authors: Terho Petra , Sallinen Ville , Leppäniemi Ari , Mentula Panu
Published: July 2020

Background:

This study investigated how annual caseloads and the surgeon’s previous experience influence the outcome in laparoscopic cholecystectomy (LCC) for acute cholecystitis.

Methods:

A total of 892 patients treated in Helsinki University Hospital in 2013-2016 were retrospectively analyzed. Surgeons were compared regarding volume—over 5 LCCs for acute cholecystitis a year versus 5 or fewer LCCs a year, and experience—attendings versus residents.

Results:

High-volume surgeons (n=14) operated faster than low-volume surgeons (n=62) (91 vs. 108 min, P<0.001). Examining only procedures with an attending present, high-volume attendings (n=7) converted less (14.9% vs. 32.0%, P<0.001) and operated faster (95 vs. 110 min, P<0.001) compared with low-volume attendings (n=41). The results of residents did not significantly differ from the results of attendings.

Conclusions:

Attending surgeons, performing >5 LCCs for acute cholecystitis a year, have shorter operative times and lower conversion rates.
Not seeing the forest for the trees: a systematic review of comprehensive distress management programs and implementation strategies
Authors: McCarter Kristen , Fradgley Elizabeth A. , Britton Ben , Tait Jordan , Paul Christine
Published: July 2020

Purpose of review

Clinically significant distress is common in patients with cancer and if untreated can be associated with adverse outcomes. This article offers a review of current approaches to implementing and reporting the minimum components of distress screening and management interventions in cancer services.

Recent findings

Twenty-two relevant published articles were identified from January 2018 to February 2020. The reporting of recommended minimum components of distress screening and management interventions in these articles was not consistent. The majority of studies used validated tools to conduct initial screening. However, recommendations were either not reported or not followed regarding subsequent pathway components, secondary assessment, referral pathways linked to screening results and rescreening. The majority of studies did not include a description of the implementation of the distress screening program. A small number of studies described a comprehensive set of implementation strategies.

Distress screening and management interventions in cancer are an important component of comprehensive cancer care. To improve patient outcomes and guide researchers and services to identify effective models, studies must include and evaluate minimum recommended components and implementation strategies. Addressing these limitations with high-quality, robust interventions is vital for advancing the implementation of effective distress management.
Wenzhouxiangella limi sp. nov., isolated from a salt lake
Authors: Zhang Xiao-Yu , Zhang Rui , Wang Jia-Cheng , Zhang Ting , Du Zong-Jun
Published: July 2020

A novel Gram-stain-negative, strictly aerobic, gliding and rod-shaped bacterial strain, designated strain C33T, was isolated from Yuncheng Salt Lake, Shanxi, PR China. Strain C33T grows optimally at 37 °C, pH 7.5 and 5.0 % (w/v) NaCl. Cells of strain C33T are 0.3–0.5 µm wide and 1.0–2.0 µm long, catalase-positive and oxidase-positive. The major cellular fatty acids are iso-C15 : 0 and iso-C16 : 0. The sole respiratory quinone is Q-8. The major polar lipids include phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, one unidentified aminophospholipid, one unidentified glycolipid and four unidentified lipids. The results of phylogenetic analysis based on 16S rRNA gene sequences indicate that strain C33T has the highest similarities to

Wenzhouxiangella marina

KCTC 42284T (97.4 %),

Wenzhouxiangella sediminis

XDB06T (96.5 %) and ‘Wenzhouxiangella salilacus’ MCCC 1K03442T (95.2 %). The percentage of conserved proteins and average amino acid identity values between strain C33T and its close related species are higher than the threshold for dividing genera, the average nucleotide identity and digital DNA–DNA hybridization values are well below the threshold limits for species delineation. The genomic DNA G+C content is 63.7 mol%. Based on the results of phenotypic, chemotaxonomic and phylogenetic analyses, strain C33T is considered to represent a novel species of the genus

Wenzhouxiangella

, for which the name Wenzhouxiangella limi sp. nov. is proposed. The type strain is C33T (=MCCC 1H00413T=KCTC 72874T).
Improved treatment strategies can result in better outcomes following one-stage exchange surgery for MRSA periprosthetic joint infection
Authors: Ohlmeier Malte , Filitarin Sergei , Delgado Giorgio , Frings Jannik , Abdelaziz Hussein , Salber Jochen , Frommelt Lars , Gehrke Thorsten , Citak Mustafa
Published: July 2020

Introduction. Periprosthetic joint infections caused by methicillin-resistant

Staphylococcus aureus

(MRSA-PJIs) are rare, with only a few studies reporting the treatment outcomes and even fewer reporting outcomes with one-stage exchange.

Aim.
This study aims to analyse the outcomes of one-stage exchange in the management of MRSA-PJIs.

Methodology. Patients with MRSA-PJI of the hip and knee, who were treated with a one-stage exchange between 2001 and 2018 were enrolled in this study. The final cohort comprised of 29 patients, which included 23 hips and six knees. The mean follow-up was 5.3 years (1–9 years). Reinfection and complications rates after the one-stage exchange were analysed.

Results. Overall infection control could be achieved in 93.1 % (27 out of 29 patients). The overall revision rate was 31.0% (9 patients), with three patients requiring an in-hospital revision (10.3 %). Six patients had to be revised after hospital discharge (20.7 %). Of the two reinfections, one had a growth of MRSA while the other was of methicillin-sensitive Staphyloccocus epidermidis.

Conclusion. One-stage exchange surgery using current techniques could improve surgical outcomes with excellent results in the management of MRSA-PJIs.
Maternal blood lipidomics analyses link critical metabolic pathways associated with severe preeclampsia
Authors: Liu Yu , He Bing , Maurya Mano R , Benny Paula , Lassiter Cameron , Li Hui , Subraminiam Shankar , Garmire Lana X.
Published: July 2020

Preeclampsia is a pregnancy specific syndrome characterized by hypertension and proteinuria after 20 weeks of gestation. To reveal the relationship between lipids and preeclampsia, we conduct lipidomic profiling of maternal serums of 44 severe preeclamptic and 20 healthy pregnancies from a multi-ethnic cohort in Hawaii. Correlation network analysis shows that oxidized phospholipids (OxPLs) have increased inter-correlations and connections in preeclampsia, while other lipids, including triacylglycerols (TAGs), have reduced network correlations and connections. Thirty-one lipid species from various lipid classes demonstrate predominantly reductions and causal relationships with preeclampsia. They include phosphatidylglycerol (PG), TAG, diacylglycerol (DAG), phosphatidylcholine (PC), cholesterol esters (CE), phosphatidylethanolamine (PE), sphingomyelin (SM), ceramides (Cer-NS), hexosyl ceramides (HexCer-NS), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), and free fatty acid (FFA). Many of these lipids are also selected as important features by a linear discriminant analysis (LDA) classifier with high predictive accuracy (F-1 statistic 0.941 and balanced accuracy 0.88), indicating their potential to serve as biomarkers for severe preeclampsia. Our study supports the hypothesis of a phospholipid (PL) centered, dysregulated lipidomic metabolic atlas. That is, severe preeclampsia may be originated from hypoxia, which induces the accumulation of OxPLs through oxidative stress whereas reduces many other lipids (eg. reduced PCs, TAGs and ceramides). These molecular changes coherently lead to dysregulated biological functions, such as insulin signaling and inflammation/infections. Moreover, the lipid changes may also be responsible for the comorbidity between preeclampsia and gestational diabetes, a clinically known risk factor for preeclampsia.
Adaptor Template Oligo-Mediated Sequencing (ATOM-Seq): A versatile and ultra-sensitive UMI-based NGS library preparation technology, for use with cfDNA and cfRNA
Authors: Dunwell Thomas L. , Dailey Simon C. , Yu Jihang , Becker Philipp W. , Scaife Sarah , Richman Susan D. , Wood Henry M. , Slaney Hayley , Bottomley Daniel , Yang Xiangsheng , Xiao Hui , Ottestad Anine L. , Wahl Sissel G. F. , Grønberg Bjørn H. , Dai Hong Yan , Fu Guoliang
Published: July 2020

Liquid biopsy testing utilising Next Generation Sequencing (NGS) is rapidly moving towards clinical adoption for personalised oncology. However, before NGS can fulfil its potential any novel testing approach must identify ways of reducing errors, allowing for separating true low-frequency mutations from procedural artefacts, and be designed to improve upon current technologies while also avoiding their limitations. Popular NGS technologies typically utilise two approaches; PCR and ligation, which have known limitations and seem to have reached a development plateau with only small, stepwise improvements being made. To maximise the ultimate utility of liquid biopsy testing we have developed a highly versatile approach to NGS: Adaptor Template Oligo Mediated Sequencing (ATOM-Seq). ATOM-Seq’s strengths and versatility avoid the major limitations of both PCR- and ligation-based approaches. This technology is ligation free, simple, efficient, flexible, and streamlined, and offers novel advantages that make it perfectly suited for use on highly challenging clinical material. Using reference materials, we demonstrate detection of known SNVs at allele frequencies of 0.1% using as little as 20 ng of DNA, as well as the ability to detect fusions from RNA. We illustrate ATOM-Seq’s suitability for clinical testing by showing high concordance rates between paired cfDNA and FFPE clinical samples.
DNMT3A haploinsufficiency results in behavioral deficits and global epigenomic dysregulation shared across neurodevelopmental disorders
Authors: Christian Diana L. , Wu Dennis Y. , Martin Jenna R. , Moore J. Russell , Liu Yiran R. , Clemens Adam W. , Nettles Sabin A. , Kirkland Nicole M. , Hill Cheryl A. , Wozniak David F. , Dougherty Joseph D. , Gabel Harrison W.
Published: July 2020

Mutations in DNA methyltransferase 3A (DNMT3A) have been detected in autism and related disorders, but how these mutations disrupt nervous system function is unknown. Here we define the effects of neurodevelopmental disease-associated DNMT3A mutations. We show that diverse mutations affect different aspects of protein activity yet lead to shared deficiencies in neuronal DNA methylation. Heterozygous DNMT3A knockout mice mimicking DNMT3A disruption in disease display growth and behavioral alterations consistent with human phenotypes. Strikingly, in these mice we detect global disruption of neuron-enriched non-CG DNA methylation, a binding site for the Rett syndrome protein MeCP2. Loss of this methylation leads to enhancer and gene dysregulation that overlaps with models of Rett syndrome and autism. These findings define effects of DNMT3A haploinsufficiency in the brain and uncover disruption of the non-CG methylation pathway as a convergence point across neurodevelopmental disorders.
Geography is more important than life history in the recent diversification of the tiger salamander complex
Authors: Everson Kathryn M. , Gray Levi N. , Jones Angela G. , Lawrence Nicolette M. , Foley Mary E. , Sovacool Kelly L. , Kratovil Justin D. , Hotaling Scott , Hime Paul M. , Storfer Andrew , Parra-Olea Gabriela , Percino-Daniel Ruth , Aguilar-Miguel X. , O’Neill Eric M. , Zambrano Luis , Shaffer H. Bradley , Weisrock David W.
Published: July 2020

Abstract

The North American tiger salamander species complex, including its best-known species, the Mexican axolotl, has long been a source of biological fascination. The complex exhibits a wide range of variation in developmental life history strategies, including populations and individuals that undergo metamorphosis, those able to forego metamorphosis and retain a larval, aquatic lifestyle (i.e., paedomorphosis), and those that do both. This life history variation has been assumed to lead to reproductive isolation and speciation, but the degree to which it has shaped population- and species-level divergence is poorly understood. Using a large multi-locus dataset from hundreds of samples across North America, we identified genetic clusters across the geographic range of the tiger salamander complex. These clusters often contain a mixture of paedomorphic and metamorphic taxa, indicating that geographic isolation has played a larger role in lineage divergence than paedomorphosis in this system. This conclusion is bolstered by geography-informed analyses indicating no effect of life history strategy on population genetic differentiation and by model-based analyses demonstrating gene flow between adjacent metamorphic and paedomorphic populations. This fine-scale genetic perspective on life-history variation establishes a framework for understanding how plasticity, local adaptation, and gene flow contribute to lineage divergence. Many members of the tiger salamander complex are endangered, and the Mexican axolotl is an important model system in regenerative and biomedical research. Our results chart a course for more informed use of these taxa in experimental, ecological, and conservation research.

SignificanceStatement

Population structure and speciation are shaped by a combination of biotic and abiotic factors. The tiger salamander complex has been considered to be a key group where life history variation has led to a rapid rate of speciation, driven in large part by the evolution of obligate paedomorphosis–a condition where adults maintain an aquatic, larval phenotype. Using a large multi-locus dataset, we present evidence of gene flow between taxa with different life history strategies, suggesting that obligate paedomorphosis is not a strong driver of speciation in the tiger salamander complex. Many of these nominal taxa are listed as critically endangered, and our genetic results provide information and guidance that will be useful for their conservation.
SITH: an R package for visualizing and analyzing a spatial model of intratumor heterogeneity
Authors: Nicol Phillip B. , Barabási Dániel L. , Asiaee Amir , Coombes Kevin R.
Published: July 2020

Motivation

Cancer progression, including the development of intratumor heterogeneity, is inherently a spatial process. Mathematical models of tumor evolution can provide insights into patterns of heterogeneity that can emerge in the presence of spatial growth.

We develop SITH, an R package that implements a lattice-based stochastic model of tumor growth and mutation. SITH provides 3D interactive visualizations of the simulated tumor and highlights heavily mutated regions. SITH can produce synthetic bulk and single-cell sequencing data sets by sampling from the tumor. The streamlined API will make SITH a useful tool for investigating the relationship between spatial growth and intratumor heterogeneity.

Availability and Implementation

SITH is a part of CRAN and can thus be installed by runninginstall.packages(“SITH”)from the R console. Seehttps://CRAN.R-project.org/package=SITHfor the user manual and package vignette.
Normalizing single-cell RNA sequencing data with internal spike-in-like genes
Authors: Lin Li , Song Minfang , Jiang Yong , Zhao Xiaojing , Wang Haopeng , Zhang Liye
Published: July 2020

Normalization with respect to sequencing depth is a crucial step in single-cell RNA sequencing preprocessing. Most methods normalize data using the whole transcriptome based on the assumption that the majority of transcriptome remains constant and are unable to detect drastic changes of the transcriptome. Here, we develop an algorithm based on a small fraction of constantly expressed genes as internal spike-ins to normalize single cell RNA sequencing data. We demonstrate that the transcriptome of single cells may undergo drastic changes in several case study datasets and accounting for such heterogeneity by ISnorm improves the performance of downstream analyzes.
A novel hypoxia gene signature indicates prognosis and reveals the multi-omics molecular landscape of tumour tissue in patients with hepatocellular carcinoma
Authors: Zhang Qiangnu , Liao Juan , Qiao Lijun , Liu Quan , Liu Pengyu , Xia Mengting , Huang Xiaotao , Liu Liping
Published: July 2020

Background

Previous studies on the impact of hypoxia on hepatocellular carcinoma (HCC) mostly focused on in vitro and animal models. The clinical value of assessing the degree of hypoxia in in vivo tissues and hypoxia-related molecular landscapes in HCC remain poorly defined.

Methods

A novel hypoxia gene signature was extracted from hypoxia-treated HCC cells using microarray analysis and a robust rank aggregation algorithm and was verified using public data. Next, the relationships between the hypoxia gene signature and the clinical characteristics and prognoses of HCC patients were analysed. Based on the multi-omics data from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) and 10 independent HCC cohorts from the Gene Expression Omnibus (GEO), a comprehensive analysis was conducted using the hypoxia gene signature to describe hypoxia-associated multi-omic molecular landscapes and immune microenvironments in HCC tissues.

Results

A 21-gene hypoxia signature was constructed to effectively indicate the exposure of hypoxia in HCC tissues. This novel hypoxia signature and the hypoxia scores calculated based on this signature were closely correlated to some clinical characteristics of HCC patients and can be used to evaluate prognosis. HCC tissues with different hypoxia scores differed significantly in transcriptomic, genomic, epigenomic, and proteomic alterations and immune microenvironments, some of which were related to the clinical prognoses of patients.

Conclusion

The 21-gene signature can effectively estimate hypoxia exposure of HCC tissues and has clinical value in the assessment and prediction of the prognosis of HCC patients. Using this 21-gene signature, hypoxia-associated molecular landscapes were described at the tissue level. This comprehensive molecular-level understanding can help to further elucidate the mechanism of hypoxia in tumours and guide clinical cancer therapy. The assessment of the degree of hypoxia is strongly recommended in the personalized treatment of HCC patients to benefit specific patient groups.
Collateral Sensitivity Associated with Antibiotic Resistance Plasmids
Authors: Herencias Cristina , Rodríguez-Beltrán Jerónimo , León-Sampedro Ricardo , Alonso-del Valle Aida , Palkovičová Jana , Cantón Rafael , Millán Álvaro San
Published: July 2020

Collateral sensitivity (CS) is a promising alternative approach to counteract the rising problem of antibiotic resistance (ABR). CS occurs when the acquisition of resistance to one antibiotic produces increased susceptibility to a second antibiotic. For CS to be widely applicable in clinical practice, it would need to be effective against the different resistance mechanisms available to bacteria. Recent studies have focused on CS strategies designed against ABR mediated by chromosomal mutations. However, one of the main drivers of ABR in clinically relevant bacteria is the horizontal transfer of ABR genes mediated by plasmids. Here, we report the first analysis of CS associated with the acquisition of complete ABR plasmids, including the clinically important carbapenem-resistance conjugative plasmid pOXA-48. In addition, we describe the conservation of CS in clinicalE. coliisolates and its application to the selective elimination of plasmid-carrying bacteria. Our results provide new insights that establish the basis for developing CS-informed treatment strategies to combat plasmid-mediated ABR.
Template switching mechanism drives the tandem amplification of chromosome 20q11.21 in human pluripotent stem cells
Authors: Halliwell Jason A , Baker Duncan , Judge Kim , Quail Michael A , Oliver Karen , Betteridge Emma , Skelton Jason , Andrews Peter W , Barbaric Ivana
Published: July 2020

Copy number variants (CNVs) are genomic rearrangements implicated in numerous congenital and acquired diseases, including cancer. In human pluripotent stem cells (PSC), the appearance of culture-acquired CNVs prompted concerns for their use in regenerative medicine applications. A particularly common problem in PSC is the occurrence of CNVs in the q11.21 region of chromosome 20. However, the exact mechanisms of origin of this amplicon remains elusive due to the difficulty in delineating its sequence and breakpoints. Here, we used long-range Nanopore sequencing on two examples of this CNV, present as a duplication in one and a triplication in another line. The CNVs were arranged in a head-to-tail orientation in both lines, with sequences of microhomologies flanking or overlapping both the proximal and distal breakpoints. These breakpoint signatures point to a specific mechanism of template switching in CNV formation, with surroundingAlusequences likely contributing to the instability of this genomic region.
Bayesian Decoder Models with a Discriminative Observation Process
Authors: Rezaei Mohammad R. , Hadjinicolaou Alex E. , Cash Sydney S. , Eden Uri T. , Yousefi Ali
Published: July 2020

The Bayesian state-space neural encoder-decoder modeling framework is an established solution to reveal how changes in brain dynamics encode physiological covariates like movement or cognition. Although the framework is increasingly being applied to progress the field of neuroscience, its application to modeling high-dimensional neural data continues to be a challenge. Here, we propose a novel solution that avoids the complexity of encoder models that characterize high-dimensional data as a function of the underlying state processes. We build a discriminative model to estimate state processes as a function of current and previous observations of neural activity. We then develop the filter and parameter estimation solutions for this new class of state-space modeling framework called the “direct decoder” model. We applied the model to decode movement trajectories of a rat in a W-shaped maze from the ensemble spiking activity of place cells and achieve comparable performance to modern decoding solutions, without needing an encoding step in the model development. We further demonstrate how a dynamical auto-encoder can be built using the direct decoder model; where the underlying state process links the high-dimensional neural activity to the behavioral readout. We applied the dynamical auto-encoder model in estimating the intention to verbally communicate of an epileptic participant and their companions. The result shows that the dynamical auto-encoder can optimally estimate the low-dimensional dynamical manifold which represents the relationship between the brain and behavior.
PhageAI - Bacteriophage Life Cycle Recognition with Machine Learning and Natural Language Processing
Authors: Tynecki Piotr , Guziński Arkadiusz , Kazimierczak Joanna , Jadczuk Michał , Dastych Jarosław , Onisko Agnieszka
Published: July 2020

Background

As antibiotic resistance is becoming a major problem nowadays in a treatment of infections, bacteriophages (also known as phages) seem to be an alternative. However, to be used in a therapy, their life cycle should be strictly lytic. With the growing popularity of Next Generation Sequencing (NGS) technology, it is possible to gain such information from the genome sequence. A number of tools are available which help to define phage life cycle. However, there is still no unanimous way to deal with this problem, especially in the absence of well-defined open reading frames. To overcome this limitation, a new tool is definitely needed.

Results

We developed a novel tool, called PhageAI, that allows to access more than 10 000 publicly available bacteriophages and differentiate between their major types of life cycles: lytic and lysogenic. The tool included life cycle classifier which achieved 98.90% accuracy on a validation set and 97.18% average accuracy on a test set. We adopted nucleotide sequences embedding based on the Word2Vec with Ship-gram model and linear Support Vector Machine with 10-fold cross-validation for supervised classification. PhageAI is free of charge and it is available athttps://phage.ai/. PhageAI is a REST web service and available as Python package.

Conclusions

Machine learning and Natural Language Processing allows to extract information from bacteriophages nucleotide sequences for lifecycle prediction tasks. The PhageAI tool classifies phages into either virulent or temperate with a higher accuracy than any existing methods and shares interactive 3D visualization to help interpreting model classification results.
Independence of Cued and Contextual Components of Fear Conditioning is Gated by the Lateral Habenula
Authors: Sachella Tomas E. , Ihidoype Marina R. , Proulx Christophe D. , Pafundo Diego E. , Medina Jorge H. , Mendez Pablo , Piriz Joaquin
Published: July 2020

Fear is an extreme form of aversion that, if inappropriately generalized, initiates pathological conditions such as panic or anxiety. Fear conditioning (FC) is the best understood model of fear learning. During FC two independent associations link the cue and the training context to fear expression. The lateral habenula (LHb) is a general encoder of aversion. However, its role in fear learning has not been intensively studied. Here we studied the role of the LHb in FC using optogenetics and pharmacological tools in rats. Disrupting the neuronal activity of the LHb during training abolishes the expression of fear to isolated presentation of the training context or the cue, yet the recall of both associations when the cue is played in the training context reveals a conserved memory. Our results demonstrate that the LHb is required for the formation of independently expressible contextual and cued memories, a previously uncharacterized role in FC.
Chemoproteomics-Enabled Ligand Screening Yields Covalent RNF114-Based Degraders that Mimic Natural Product Function
Authors: Luo Mai , Spradlin Jessica N. , Brittain Scott M. , McKenna Jeffery M. , Tallarico John A. , Schirle Markus , Maimone Thomas J. , Nomura Daniel K.
Published: July 2020

The translation of natural product function to fully synthetic small molecules has remained an important process in medicinal chemistry for decades resulting in numerous FDA-approved medicines. We recently discovered that the terpene natural product nimbolide can be utilized as a covalent recruiter of the E3 ubiquitin ligase RNF114 for use in targeted protein degradation (TPD) – a powerful therapeutic modality within modern day drug discovery. Using activity-based protein profiling-enabled covalent ligand screening approaches, we herein report the discovery of fully synthetic RNF114-based recruiter molecules that can also be exploited for PROTAC applications, and demonstrate their utility in degrading therapeutically relevant targets such as BRD4 and BCR-ABL in cells. The identification of simple and easily manipulated drug-like scaffolds that can mimic the function of a complex natural product is beneficial in further expanding the toolbox of E3 ligase recruiters, an area of great importance in drug discovery and chemical biology.
Friendly regulates membrane depolarization induced mitophagy in Arabidopsis
Authors: Ma Juncai , Liang Zizhen , Zhao Jierui , Wang Pengfei , Ma Wenlong , Fernandez Andrade Juan A. , Zeng Yonglun , Grujic Nenad , Jiang Liwen , Dagdas Yasin , Kang Byung-Ho
Published: July 2020

The oxidative environment within the mitochondria makes them particularly vulnerable to proteotoxic stress. To maintain a healthy mitochondrial network, eukaryotes have evolved multi-tiered quality control pathways. If the stress cannot be alleviated, defective mitochondria are selectively removed by autophagy via a process termed mitophagy. Despite significant advances in metazoans and yeast, in plants, the molecular underpinnings of mitophagy are largely unknown. Here, using time-lapse imaging, electron tomography and biochemical assays, we show that uncoupler treatments cause loss of mitochondrial membrane potential and induce autophagy in Arabidopsis. The damaged mitochondria are selectively engulfed by autophagosomes that are ATG5 dependent and labelled by ATG8 proteins. Friendly, a member of the Clustered Mitochondria protein family, is recruited to the damaged mitochondria to mediate mitophagy. In addition to stress, mitophagy is also induced during de-etiolation, a major cellular transformation during photomorphogenesis that involves chloroplast biogenesis. De-etiolation triggered mitophagy regulates cotyledon greening, pointing towards an inter-organellar cross-talk mechanism. Altogether our results demonstrate how plants employ mitophagy to recycle damaged mitochondria during stress and development.
Validating molecular markers for barley leaf rust resistance genesRph20andRph24
Authors: Dracatos PM , Park RF , Singh D
Published: July 2020

Improving resistance to barley leaf rust (caused byPuccinia hordei) is an important breeding objective in most barley growing regions worldwide. The development and subsequent utilisation of high-throughput PCR-based co-dominant molecular markers remains an effective approach to select genotypes with multiple effective resistance genes, permitting efficient gene deployment and stewardship. The genesRph20andRph24confer widely effective adult plant resistance (APR) to leaf rust, are common in European and Australian barley germplasm (often in combination), and act interactively to confer high levels of resistance (Dracatos et al. 2015; Zeims et al. 2017; Singh et al. 2018). Here we report on the development and validation of co-dominant insertion-deletion (indel) based PCR markers that are highly predictive for theRph20andRph24resistances.
UGT76B1, a promiscuous hub of small molecule-based immune signaling, glucosylates N-hydroxypipecolic acid and controls basal pathogen defense
Authors: Bauer Sibylle , Mekonnen Dereje W. , Hartmann Michael , Janowski Robert , Lange Birgit , Geist Birgit , Zeier Jürgen , Schäffner Anton R.
Published: July 2020

Glucosylation modulates the biological activity of small molecules and frequently leads to their inactivation. TheArabidopsis thalianaglucosyltransferase UGT76B1 is involved in conjugating the stress hormone salicylic acid (SA) as well as isoleucic acid (ILA). Here, we show that UGT76B1 also glucosylates N-hydroxypipecolic acid (NHP), which is synthesized by FLAVIN-DEPENDENT MONOOXYGENASE 1 (FMO1) and activates systemic acquired resistance (SAR). Upon pathogen attack, Arabidopsis leaves accumulate two distinct NHP hexose conjugates, NHP-O-β-glucoside and NHP glucose ester, which are oppositely regulated by SA.ugt76b1mutants specifically fail to generate the NHP-O-β-glucoside, and recombinant UGT76B1 synthesizes NHP-O-β-glucosidein vitroin competition with SA and ILA. The loss ofUGT76B1elevates the endogenous levels of NHP in addition to SA and ILA and establishes a SAR-like, primed immune status without pathogen infestation. The introgression of thefmo1background lacking NHP biosynthesis intougt76b1abolishes the SAR-like resistance phenotype indicating an important function of UGT76B1-mediated NHP glucosylation in balancing the defense status. Our results further indicate that ILA promotes and SA finally executes the NHP-triggered immunity via the glucosyltransferase UGT76B1 as the common metabolic hub. Thus, UGT76B1 controls the levels of active NHP, SA, and ILA in concert to modulate plant immune signaling.
Costs and benefits of toxin production in a dinoflagellate
Authors: Ryderheim Fredrik , Selander Erik , Kiørboe Thomas
Published: July 2020

Many phytoplankton respond to chemical cues from grazers by upregulating defensive capabilities. Inducible defences like these are often assumed to come at a cost to the organism, but these trade-offs have not been experimentally established. A reason for this may be that costs only become evident under resource limiting conditions. Here, we exposed the toxin-producing dinoflagellateAlexandrium minutumto chemical cues from copepods under different levels of nitrogen limitation. Induced cells had higher cellular toxin content and a larger fraction of the cells were rejected by a copepod, demonstrating the clear benefits of toxin production. Induced cells also had a higher carbon and nitrogen content, despite an up to 25% reduction in cell size. Unexpectedly, induced cells seemed to grow faster than controls, likely owing to a higher nutrient affinity due to reduced size. We thus found no clear trade-offs, rather the opposite. However, we argue that indirect ecological costs that do not manifest under laboratory conditions are important and that the induction of toxins specific to particular defences prevents the cells from constantly synthesizing the large array of secondary metabolites that they are capable of producing.
ProtTrans: Towards Cracking the Language of Life’s Code Through Self-Supervised Learning
Authors: Elnaggar Ahmed , Heinzinger Michael , Dallago Christian , Rehawi Ghalia , Wang Yu , Jones Llion , Gibbs Tom , Feher Tamas , Angerer Christoph , Steinegger Martin , Bhowmik Debsindhu , Rost Burkhard
Published: July 2020

Computational biology and bioinformatics provide vast data gold-mines from protein sequences, ideal for Language Models taken from NLP. These LMs reach for new prediction frontiers at low inference costs. Here, we trained two auto-regressive models (Transformer-XL, XLNet) and four auto-encoder models (BERT, Albert, Electra, T5) on data from UniRef and BFD containing up to 393 billion amino acids. The LMs were trained on the Summit supercomputer using 5616 GPUs and TPU Pod up-to 1024 cores.

Dimensionality reduction revealed that the raw protein LM-embeddingsfrom unlabeled data captured some biophysical features of protein sequences. We validated the advantage of using theembeddingsas exclusive input for several subsequent tasks. The first was a per-residue prediction of protein secondary structure (3-state accuracy Q3=81%-87%); the second were per-protein predictions of protein sub-cellular localization (ten-state accuracy: Q10=81%) and membrane vs. water-soluble (2-state accuracy Q2=91%). For the per-residue predictions the transfer of the most informative embeddings (ProtT5) for the first time outperformed the state-of-the-art without using evolutionary information thereby bypassing expensive database searches. Taken together, the results implied that protein LMs learned some of thegrammarof thelanguage of life. To facilitate future work, we released our models athttps://github.com/agemagician/ProtTrans.
UKBCC: a cohort curation package for UK Biobank
Authors: Kiral Isabell , Willems Nathalie , Goudey Benjamin
Published: July 2020

The UK Biobank (UKB) has quickly become a critical resource for researchers conducting a wide-range of biomedical studies (Bycroftet al.,2018). The database is constructed from heterogeneous data sources, employs several different encoding schemes, and is disparately distributed throughout UKB servers. Consequently, querying these data remains complicated, making it difficult to quickly identify participants who meet a given set of criteria. We have developed UK Biobank Cohort Curator (UKBCC), a Python tool that allows researchers to rapidly construct cohorts based on a set of search terms. Here, we describe the UKBCC implementation, critical sub-modules and functions, and outline its usage through an example use case for replicable cohort creation.

Availability

UKBCC is available through PyPi (https://pypi.org/project/ukbcc) and as open source code on GitHub (https://github.com/tool-bin/ukbcc).

Contact

isa.kiral@gmail.com
SLC6A1 G443D associated with developmental delay and epilepsy
Authors: Devries Seth , Mulder Monica , Charron Jacob G. , Prokop Jeremy W. , Mark Paul R.
Published: July 2020

SLC6A1 is associated with an autosomal dominant early-onset seizure and epileptic encephalopathy associated with intellectual disability. We present a 2-yr-old girl with developmental delay and epilepsy, using a new computational filtering impact score to show the patient's variant ranks with other pathogenic variants. Genomic studies within the patient revealed a G443D variant of uncertain significance. Structural and evolutionary assessments establish this variant as a loss of function to the protein. Compiled metrics through our custom tools on sequence, structure, and protein dynamics combined with PolyPhen-2, PROVEAN, SIFT, and Align-GVGD reveal this variant to rank in the top functional outcome changes relative to gnomAD, TOPMed, and ClinVar variants known to date. The patient was resistant to multiple epileptic drugs, finally finding that valproic acid controls the seizures. This is consistent with additional groups studying SLC6A1 variants within patients.
An answer from Marxist economics to Weber's hypothesis about China: a concurrent discussion of the direction of rural reform in China
Authors: Yang Jiguo
Published: July 2020

Purpose

Weber's hypothesis about China is the hypothesis forwarded by Weber that why capitalist production did not appear in eastern countries such as China in the first place. Weber considered that the reason may be Chinese Confucianism and Taoism lack protestant ethic like Western countries.

Design/methodology/approach

The clarification has aroused wide discussion, meanwhile, East Asian capitalism belonging to the Chinese cultural circle has successfully refuted Weber's proposition. Chinese scholars have a broad debate around this topic while no agreement has been reached. This paper tries to explain Weber's hypothesis by Marx's theory of capital origin, which can be explained that the landlord economy caused by China's federal society under centralism leads to the result that the commodity of labor cannot exist in that environment.

Findings

The answer from Marxist economics has not only solved an enormous theoretical problem, but also it has vital practical significance. It easily clarifies the fact that the commodity of labor in full sense still cannot emerge in China nowadays, which is an important reason causing China to enter the New Normal and New Era.

Originality/value

Therefore, it leaves China the only way of the socialist road with Chinese characteristics and revitalizing China's rural economy, which means China can only promote rural industrialization and urbanization under the principle of adhering to rural collective ownership, while implementing various forms of integrated agricultural and industrial business models based on local conditions.
Police brutality and four other ways racism kills Black people
Authors: Holmes IV Oscar
Published: July 2020

Purpose

This article was written in response to the #BlackLivesMatter social justice protests that erupted around the world in response to the killings of George Floyd, Breonna Taylor and Ahmaud Arbery in 2020.

Design/methodology/approach

This article weaves personal experiences, published research and current events and social issues to build the case that there are many ways that racism kills Black people.

Findings

Although antiblack police brutality looms largely in people's minds of how racism kills Black people, less conspicuous ways that racism kills Black people are often overlooked.

Originality/value

In this article, the author highlights: (1) the perennial expectation that Black people cater to other people's needs and desires; (2) performative activism and allyship; (3) assigning Black people the responsibility for fixing racism and (4) thinking education, mentoring or wealth is the panacea for racism as these less conspicuous ways that racism kills Black people.
Reusable learning objects: a blended learning tool in teaching computer-aided design to engineering undergraduates
Authors: Onofrei George , Ferry Paul
Published: July 2020

Purpose

Blended learning is an emerging trend across many educational settings, adopting the purposeful integration of traditional face-to-face and online teaching to establishing an engaging learning experience for the students. Blended learning provides an ideal platform for the implementation of reusable learning objects (RLOs) as a pedagogical tool to support classroom instruction.

Design/methodology/approach

This study had conducted a quasi-experiment followed by semi-structured interviews to determine if a blended learning approach using RLOs can enhance students’ learning in an undergraduate engineering computer-aided design (CAD) module. This study involved learners studying engineering in two different academic years.

Findings

Students from the first year were taught using traditional face-to-face teaching approach. The cohort of students from the subsequent year adopted a blended learning approach: face to face and access to a series of RLOs. The analysis revealed statistical evidence that the use of blended learning had a significant impact on the students' end of term exam grades in the CAD module in comparison to the students who undertook traditional face-to-face teaching approach. The qualitative findings highlighted the positive impact of RLOs on students’ learning behaviour, engagement and knowledge retention.

Originality/value

This study provided empirical evidence of the benefits of using RLOs as a blended learning tool in engineering domain. From a theoretical perspective, the findings highlighted the importance of good instructional design and sound theoretical underpinning of the pedagogical strategy. From a practical point of view, this study informed academics on how to improve learner's academic achievement using RLOs.
Farmer groups, collective marketing and smallholder farm performance in rural Ghana
Authors: Abdul-Rahaman Awal , Abdulai Awudu
Published: July 2020

Purpose

Rapid transformation of agrifood value chains because of population growth, urbanization, rising consumer incomes and increased demand for food quality and safety has resulted in the need for smallholder farmers to coordinate horizontally through group formation and collective marketing to improve farm performance in developing countries. This paper aims to examine the factors that influence farmer group membership and collective marketing decisions and their impacts on smallholder farm performance in rural Ghana.

Design/methodology/approach

Using data from a recent survey of 447 rice farmers in rural Ghana, an endogenous switching regression model is employed to account for selection bias arising from both observable and unobservable farmer attributes.

Findings

The data reveal that group members and collective marketing participants obtained higher prices and also incurred lower input costs. The econometric estimates show that age, access to credit, mobile phone ownership, distance to market and road status are the main drivers of group membership and collective marketing decisions. The authors also find positive and significant impacts of farmer group membership and collective marketing on farm net revenues.

Research limitations/implications

The findings from this study suggest that government and donor support for the formation of farmer groups during implementation of agriculture and value chain interventions should as well incorporate strategies to facilitate collective marketing.

Originality/value

To the best of the authors’ knowledge, this study is the first to examine the role farmer groups and collective marketing play in improving smallholder farm performance.
New approach for target setting mechanism of course outcomes in higher education accreditation
Authors: P Dayananda , Latte Mrityunjaya V. , Raisinghani Mahesh S. , CN Sowmyarani
Published: July 2020

Purpose

Standard quality is very highly important parameter in the education sector. Accreditation is a process where standard quality of education is given and the process of continuous improvement is defined. Emphasizing quality of student education is achieved through outcome-based education system (OBE). Program outcomes signify the comprehension, skills and attitude the students should have at the end of the program. At the end of each course, course outcomes signify the knowledge acquired by the students. Course outcomes assessment is one of the key aspects of the OBE model. In this research, the following four factors: subject quality, number of times subject handled by faculty members, faculty experience and student quality with different weightage, are used for analysis of the target setting for individual courses, used for higher education accreditation. This new approach for target setting will improve the teaching and learning process.

Design/methodology/approach

Four factors: subject quality, number of times subject handled by faculty members, faculty experience and student quality with different weightage, are used for analysis of the target setting for individual courses, used for higher education accreditation.

Practical implications

Using proposed approach, higher targets can be achieved in teaching and learning.

Findings

New approach for target setting will improve the teaching and learning process.

Research limitations/implications

Proposed approach for target setting will improve the teaching and learning process; it should be implemented across all engineering colleges or universities.

Social implications

All engineering colleges will have impact on teaching and learning process.

Originality/value

The following four factors: subject quality, number of times subject handled by faculty members, faculty experience and student quality with different weightage, are used for analysis of the target setting for individual courses, used for higher education accreditation.
Impacts of capital structure: profitability of construction companies in Ethiopia
Authors: W. Fekadu Agmas
Published: July 2020

Purpose

Capital structure decisions are important decisions for any business activity because they have considerable influence on the worth and cost of companies. Most previous studies in Ethiopia were primarily focused on identifying and measuring problems in banking sectors and other sectors and paying little attention to the construction sector. The purpose of this study is mainly to fill the gap by examining the effects of capital structure on the profitability of construction firms in Ethiopia.

Design/methodology/approach

To test hypotheses of the study, time series secondary data were gathered from the sample of 30 grade one construction companies in Ethiopia during the 2011–2015 period. To examine the correlation among capital structures and its determinants, random effect multiple regression models were used.

Findings

From the regression outcomes, the study indicates that capital structure measured by debt to equity and long-term debt to total assets has a significant positive correlation with return on equity (ROE) and return on assets (ROA) of sampled construction companies. However, the capital structure measured by debt to assets has a significant negative correlation with ROE and ROA of sampled construction companies in Ethiopia.

Originality/value

This paper is the author’s original work and assures that the paper was not undertaken anywhere and is also not published in any journal before.