bluuebunny/crossref_metadata_2025_split huggingface dataset:
LTR_FINDER_parallel: parallelization of LTR_FINDER enabling rapid identification of long terminal repeat retrotransposons
Authors: Ou Shujun , Jiang Ning 
Published: August 2019

AbstractSummaryAnnotation of plant genomes is still a challenging task due to the abundance of repetitive sequences, especially long terminal repeat (LTR) retrotransposons. LTR_FINDER is a widely used program for identification of LTR retrotransposons but its application on large genomes is hindered by its single threaded processes. Here we report an accessory program that allows parallel operation of LTR_FINDER, resulting up to 8,500X faster identification of LTR elements. It takes only 72 minutes to process the 14.5 Gb bread wheat (Triticum aestivum) genome in comparison to 1.16 years required by the original sequential version.AvailabilityLTR_FINDER_parallel is freely available at https://github.com/oushujun/LTR_FINDER_parallel.Contactjiangn@msu.edu
genepanel.iobio - an easy to use web tool for generating disease- and phenotype-associated gene lists
Authors: Ekawade Aditya , Velinder Matt , Ward Alistair , DiSera Tonya , Marth Gabor 
Published: August 2019

AbstractA comprehensive list of candidate genes that succinctly describe the complete and objective phenotypic features of disease is critical when both ordering genetic testing and when triaging candidate variants in exome and genome sequencing studies. Great efforts have been made to curate gene:disease associations both in academic research and commercial gene testing settings. However, many of these valuable resources exist as islands and must be used independently, generating static, single-resource gene:disease association lists. To more effectively utilize these resources we created genepanel.iobio (https://genepanel.iobio.io), an easy to use, free and open-source web tool for generating disease- and phenotype-associated gene lists from multiple gene:disease association resources, including the NCBI Genetic Testing Registry (GTR), Phenolyzer, and the Human Phenotype Ontology (HPO). We demonstrate the utility of genepanel.iobio by applying it to complex, rare and undiagnosed disease cases which had reached a diagnostic conclusion. We find that genepanel.iobio is able to correctly prioritize the diagnostic variant in over half of these challenging cases. Importantly, each resource contributed diagnostic value, showing the benefits of this aggregate approach. We expect genepanel.iobio will improve the ease and diagnostic value of generating gene:disease association lists for genetic test ordering and whole genome or exome sequencing variant prioritization.
DeepC: Predicting chromatin interactions using megabase scaled deep neural networks and transfer learning
Authors: Schwessinger Ron , Gosden Matthew , Downes Damien , Brown Richard , Telenius Jelena , Teh Yee Whye , Lunter Gerton , Hughes Jim R. 
Published: August 2019

AbstractUnderstanding 3D genome structure requires high throughput, genome-wide approaches. However, assays for all vs. all chromatin interaction mapping are expensive and time consuming, which severely restricts their usage for large-scale mutagenesis screens or for mapping the impact of sequence variants. Computational models sophisticated enough to grasp the determinants of chromatin folding provide a unique window into the functional determinants of 3D genome structure as well as the effects of genome variation.A chromatin interaction predictor should work at the base pair level but also incorporate large-scale genomic context to simultaneously capture the large scale and intricate structures of chromatin architecture. Similarly, to be a flexible and generalisable approach it should also be applicable to data it has not been explicitly trained on. To develop a model with these properties, we designed a deep neuronal network (deepC) that utilizes transfer learning to accurately predict chromatin interactions from DNA sequence at megabase scale. The model generalizes well to unseen chromosomes and works across cell types, Hi-C data resolutions and a range of sequencing depths. DeepC integrates DNA sequence context on an unprecedented scale, bridging the different levels of resolution from base pairs to TADs. We demonstrate how this model allows us to investigate sequence determinants of chromatin folding at genome-wide scale and to predict the importance of regulatory elements and the impact of sequence variations.
Fronto-striatal oscillations predict vocal output in bats
Authors: Weineck Kristin , García-Rosales Francisco , Hechavarría Julio C. 
Published: August 2019

SummaryThe ability to vocalize is ubiquitous in vertebrates, but neural networks leading to vocalization production remain poorly understood. Here we performed simultaneous, large scale, neuronal recordings in the frontal cortex and dorsal striatum (caudate nucleus) during the production of echolocation and non-echolocation calls in bats. This approach allows to assess the general aspects underlying vocalization production in mammals and the unique evolutionary adaptations of bat echolocation. Our findings show that distinct intra-areal brain rhythms in the beta (12-30 Hz) and gamma (30-80 Hz) bands of the local field potential can be used to predict the bats’ vocal output and that phase locking between spikes and field potentials occurs prior vocalization production. Moreover, the fronto-striatal network is differentially coupled in the theta-band during the production of echolocation and non-echolocation calls. Overall, our results present evidence for fronto-striatal network oscillations in motor action prediction in mammals.
Comparative analysis of CreER transgenic mice for the study of brain macrophages – a case study
Authors: Chappell-Maor Louise , Kolesnikov Masha , Grozovski Jonathan , Kim Jung-Seok , Shemer Anat , Haimon Zhana , Boura-Halfon Sigalit , Masuda Takahiro , Prinz Marco , Jung Steffen 
Published: August 2019

AbstractConditional mutagenesis and fate mapping have contributed considerably to our understanding of physiology and pathology. Specifically, Cre recombinase-based approaches allow the definition of cell type-specific contributions to disease development and inter-cellular communication circuits in respective animals models. Here we compared Cx3cr1CreER and Sall1CreER transgenic mice and their use to decipher the brain macrophage compartment as a showcase to discuss recent technological advances. Specifically, we highlight the need to define the accuracy of Cre recombinase expression, as well as strengths and pitfalls of these particular systems that should be taken into consideration when applying these models.
Convolutional neural network model to predict causal risk factors that share complex regulatory features
Authors: Lee Taeyeop , Sung Min Kyung , Lee Seulkee , Yang Woojin , Oh Jaeho , Hwang Seongwon , Ban Hyo-Jeong , Choi Jung Kyoon 
Published: August 2019

ABSTRACTMajor progress in disease genetics has been made through genome-wide association studies (GWASs). One of the key tasks for post-GWAS analyses is to identify causal noncoding variants with regulatory function. Here, on the basis of > 2,000 functional features, we developed a convolutional neural network framework for combinatorial, nonlinear modeling of complex patterns shared by risk variants scattered among multiple associated loci. When applied for major psychiatric disorders and autoimmune diseases, neural and immune features, respectively, exhibited high explanatory power while reflecting the pathophysiology of the relevant disease. The predicted causal variants were concentrated in active regulatory regions of relevant cell types and tended to be in physical contact with transcription factors while residing in evolutionarily conserved regions and resulting in expression changes of genes related to the given disease. We demonstrate some examples of novel candidate causal variants and associated genes. Our method is expected to contribute to the identification and functional interpretation of causal noncoding variants in post-GWAS analyses.
Deep mutational scanning comprehensively maps how Zika envelope protein mutations affect viral growth and antibody escape
Authors: Sourisseau Marion , Lawrence Daniel J.P. , Schwarz Megan C. , Storrs Carina H. , Veit Ethan C. , Bloom Jesse D. , Evans Matthew J. 
Published: August 2019

AbstractFunctional constraints on viral proteins are often assessed by examining sequence conservation among natural strains, but this approach is relatively ineffective for Zika virus because all known sequences are highly similar. Here we take an alternative approach to map functional constraints on Zika virus’s envelope (E) protein by using deep mutational scanning to measure how all amino-acid mutations to the protein affect viral growth in cell culture. The resulting sequence-function map is consistent with existing knowledge about E protein structure and function, but also provides insight into mutation-level constraints in many regions of the protein that have not been well characterized in prior functional work. In addition, we extend our approach to completely map how mutations affect viral neutralization by two monoclonal antibodies, thereby precisely defining their functional epitopes. Overall, our study provides a valuable resource for understanding the effects of mutations to this important viral protein, and also offers a roadmap for future work to map functional and antigenic selection to Zika virus at high resolution.ImportanceZika virus has recently been shown to be associated with severe birth defects. The virus’s E protein mediates its ability to infect cells, and is also the primary target of the antibodies that are elicited by natural infection and vaccines that are being developed against the virus. Therefore, determining the effects of mutations to this protein is important for understanding its function, its susceptibility to vaccine-mediated immunity, and its potential for future evolution. We completely mapped how amino-acid mutations to E protein affected the virus’s ability to grow in cells in the lab and escape from several antibodies. The resulting maps relate changes in the E protein’s sequence to changes in viral function, and therefore provide a valuable complement to existing maps of the physical structure of the protein.
Neuronal-specific function of hTim8a in Complex IV assembly provides insight into the molecular mechanism underlying Mohr-Tranebjærg syndrome
Authors: Kang Yilin , Anderson Alexander J. , De Souza David P. , Palmer Catherine S. , Fujihara Kenji M. , Stait Tegan , Frazier Ann E , Clemons Nicholas J. , Tull Dedreia , Thorburn David R , McConville Malcolm J. , Ryan Michael T. , Stroud David A. , Stojanovski Diana 
Published: August 2019

AbstractHuman Tim8a is a member of an intermembrane space chaperone network, known as the small TIM family, which transport hydrophobic membrane proteins through this compartment. Mutations in TIMM8A cause a neurodegenerative disease, Mohr-Tranebjærg syndrome (MTS), which is characterised by sensorineural hearing loss, dystonia and blindness. Nothing is known about the function of hTim8a in neuronal cells and consequently how lack of hTim8a leads to a neurodegenerative disease. We identified a novel cell-specific function of hTim8a in the assembly of Complex IV, which is mediated through a transient interaction with the copper chaperone COX17. Complex IV assembly defects in cells lacking hTim8a leads to oxidative stress and changes to key apoptotic regulators, including cytochrome c and Bax, which primes cells for cell death. Alleviation of oxidative stress using Vitamin E rescues cells from apoptotic vulnerability. We hypothesis that enhanced sensitivity of neuronal cells to apoptosis is the underlying mechanism of MTS.
The results of biodiversity-ecosystem functioning experiments are realistic
Authors: Jochum Malte , Fischer Markus , Isbell Forest , Roscher Christiane , van der Plas Fons , Boch Steffen , Boenisch Gerhard , Buchmann Nina , Catford Jane A. , Cavender-Bares Jeannine , Ebeling Anne , Eisenhauer Nico , Gleixner Gerd , Hölzel Norbert , Kattge Jens , Klaus Valentin H. , Kleinebecker Till , Lange Markus , Le Provost Gaëtane , Meyer Sebastian T. , Molina-Venegas Rafael , Mommer Liesje , Oelmann Yvonne , Penone Caterina , Prati Daniel , Reich Peter B. , Rindisbacher Abiel , Schäfer Deborah , Scheu Stefan , Schmid Bernhard , Tilman David , Tscharntke Teja , Vogel Anja , Wagg Cameron , Weigelt Alexandra , Weisser Wolfgang W. , Wilcke Wolfgang , Manning Peter 
Published: August 2019

SummaryA large body of research shows that biodiversity loss can reduce ecosystem functioning, thus providing support for the conservation of biological diversity1–4. Much of the evidence for this relationship is drawn from biodiversity-ecosystem functioning experiments (hereafter: biodiversity experiments), in which biodiversity loss is simulated by randomly assembling communities of varying species diversity, and ecosystem functions are measured5–9. This random assembly has led some ecologists to question the relevance of biodiversity experiments to real-world ecosystems, where community assembly may often be non-random and influenced by external drivers, such as climate or land-use intensification10–18. Despite these repeated criticisms, there has been no comprehensive, quantitative assessment of how experimental and real-world plant communities really differ, and whether these differences invalidate the experimental results. Here, we compare data from two of the largest and longest-running grassland biodiversity experiments globally (Jena Experiment, Germany; BioDIV, USA) to related real-world grassland plant communities in terms of their taxonomic, functional, and phylogenetic diversity and functional-trait composition. We found that plant communities of biodiversity experiments have greater variance in these compositional features than their real-world counterparts, covering almost all of the variation of the real-world communities (82-96%) while also containing community types that are not currently observed in the real world. We then re-analysed a subset of experimental data that included only ecologically-realistic communities, i.e. those comparable to real-world communities. For ten out of twelve biodiversity-ecosystem functioning relationships, biodiversity effects did not differ significantly between the full dataset of biodiversity experiments and the ecologically-realistic subset of experimental communities. This demonstrates that the results of biodiversity experiments are largely insensitive to the inclusion/exclusion of unrealistic communities. By bridging the gap between experimental and real-world studies, these results demonstrate the validity of inferences from biodiversity experiments, a key step in translating their results into specific recommendations for real-world biodiversity management.
A dual foveal-peripheral visual processing model implements efficient saccade selection
Authors: Daucé Emmanuel , Albiges Pierre , Perrinet Laurent U 
Published: August 2019

AbstractWe develop a visuomotor model that implements visual search as a focal accuracy-seeking policy, with the target’s position and category drawn independently from a common generative process. Consistently with the anatomical separation between the ventral versus dorsal pathways, the model is composed of two pathways, that respectively infer what to see and where to look. The “What” network is a classical deep learning classifier, that only processes a small region around the center of fixation, providing a “foveal” accuracy. In contrast, the “Where” network processes the full visual field in a biomimetic fashion, using a log-polar retinotopic encoding, which is preserved up to the action selection level. The foveal accuracy is used to train the “Where” network. After training, the “Where” network provides an “accuracy map” that serves to guide the eye toward peripheral objects. The comparison of both networks accuracies amounts to either select a saccade or to keep the eye at the center to identify the target. We test this setup on a simple task of finding a digit in a large, cluttered image. Our simulation results demonstrate the effectiveness of this approach, increasing by one order of magnitude the radius of the visual field toward which the agent can detect and recognize a target, either through a single saccade or with multiple ones. Importantly, our log-polar treatment of the visual information exploits the strong compression rate performed at the sensory level, providing ways to implement visual search in a sub-linear fashion, in contrast with mainstream computer vision.
More Severe Loss-of-Function Sodium Channel induced by Compound SCN5A R965C and R1309H Mutants lead to Complex Familial Arrhythmia Syndrome
Authors: Lin Yubi , Qin Jiading , Shen Yuhui , Jiang Bin , Lin Xiufang 
Published: August 2019

[Abstract]ObjectiveA complex familial arrhythmia syndrome was identified in a Chinese Han family, characterized by sick sinus syndrome, progressive conduction block, atrial fibrillation, atrial standstill and Brugada syndrome. The underlying mechanism associated with the genetic mutation was investigated.MethodsGenetic analysis was conducted for probands in the coding and splicing regions of genes susceptible to cardiac arrhythmia diseases. The stable cell lines overexpressing wild-type (WT) or mutant SCN5A gene were generated in HEK293T cells and electrophysiological recordings were performed to evaluate the functional changes of mutant NaV1.5 channels.ResultsWe identified a rare double R965C and R1309H mutations in NaV1.5 channel, as a heterozygous and compound pattern, locating in the same chromosome. Compared to WT, a single mutation of R965C or R1309H, the compound mutations of R965C-R1309H most dramatically reduced the peak current of NaV1.5 channel with testing potentials ranging from −35 mV to 25 mV. Notably, the maximal peak current of NaV1.5 channel carrying R1309H only and R965C-R1309H mutations displayed significant decreases by 31.5% and 73.34%, respectively, compared to WT. Additionally, compared to single mutations of R965C or R1309H, the R965C-R1309H mutations resulted in more obviously depolarization-shifted activation and hyperpolarization-shifted inactivation, also caused most significantly changed time constant, V1/2 and slope factor of activation and inactivation.ConclusionsThe compound mutations of R965C-R1309H led to more dramatically reduced current density of Nav1.5 channel, as well as more depolarization-shifted activation and hyperpolarization-shifted inactivation than single mutation of R965C or R1309H, which may provide more understanding on the molecular mechanisms underlying the familial arrhythmia syndrome.Author summarySeveral limited types of research about the interaction of compound mutations and the mechanism of interaction remains controversial. Here we report a novel compound mutation R965C-R1309H in SCN5A gene.The compound mutations of R965C-R1309H markedly reduced the Na+ current density of Nav1.5 channel and caused significant depolarization-shifted activation and hyperpolarization-shifted inactivation, suggesting that R965C mutation aggravated the pore gating changes of sodium channel containing R1309H mutation. The R965C located in the S4-like region in the intracellular loop between DII and DIII, and the R1309H located in the S4 helix of DIII as voltage sensor, which thus potentially had synergistic and interacting effects on pore gating properties of the sodium channel. Additionally, the complex familial arrhythmia syndrome simultaneously complicated of early young onset of arrhythmia and harmful prognosis of recurrent ischemic cerebral stroke, even though effective Warfarin anticoagulation.
Symptoms expression of bakanae disease following seed treatment with phytohormone and metabolites
Authors: Quazi Shireen A. Jahan , Meon Sariah , Ahmad Zainal Abidin B.M. , Jaafar Hawa 
Published: August 2019

AbstractGibberellic acid (GA3) phytohormone responsible for bakanae disease development is well-known and identified. But a number of secondary metabolites along with GA3, produced by the causal pathogen in relation to bakanae symptoms expression were unknown. Therefore, the aims of this research were to evaluate the symptoms expression analysis of bakanae disease by pre-seed treatment with pure (synthetic) phytohormones and metabolites in susceptible rice variety MR 211. The typical bakanae symptoms were evaluated by applying pure GA3, FA and MON either singly or in mixtures. It was confirmed that higher concentration of GA3singly or with higher concentration of GA3and MON in mixtures, caused unusual elongation of internodes. Plants became stunted when high concentration of FA was applied. Browning of leaves and stems, crown rot, root necrosis occurred and root length was decreased when mixtures of higher concentration of FA *MON*GA3were used as pre-treatment. Similar observations were noted in plants inoculated withF. proliferatumat different score levels. The mechanisms of bakanae disease development through different symptoms expression in susceptible variety infected withF. proliferatumwere identified.
Megatek: “Do it right, do it yourself”
Authors: Garo Elona , Kume Vasilika 
Published: August 2019

Learning outcomes
The learning outcomes are as follows: examining the attributes and characteristics of successful entrepreneurs, understanding the biggest challenges entrepreneurs are facing in the process of developing their own business, understanding how to lead change and create competitive advantage in an emerging economy, identifying the challenges and pressuring the business in facing the retail industry and discussing and debating the challenge of diversification strategy and the risks associated with it.

Case overview/synopsis
It was year 2009 when the largest hypermarket in Albania, “Do it Yourself”, opened its doors to the public by bringing in Albania an important investment. This investment was significant for the country because it materialized in the midst of the world economic crisis. The company hired 500 employees, a big number for the size of the country. The 160,000 m2 area facility is strategically located 6 km from Tirana International Airport and 8 km from the center of Tirana, the capital city. The interior of the Hypermarket Retail Store occupies 20,000 m2 retail, 12,000 m2 wholesale and 2,600 m2 office space. The rest is green space and parking. Megatek carries a range of 51,000 products in different categories as homemade decorations, lighting and electrical, building materials, tools, gardening, heating and cooling, painting, wood and flooring. The products are available at a brick and mortar store and also online; the products are also home delivered. The company has been devoted to contribute to consumer education, quality service delivery and quality products at competitive prices. Armed with eight years of continuing success, Dionis was facing a critical decision. Should he expand or stand pat? Should he diversify the activity or maintain focus? Meanwhile, Megatek’s challenges on growing its business remain vivid. A couple of changes in the external environment ask for smart responses in the internal environment.

Complexity academic level
BA and Master level students.

Supplementary materials
Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS 11: Strategy