bluuebunny/crossref_metadata_2025 huggingface dataset:
Chlamydia trachomatisoutbreak: when the virulence-associated genome backbone imports a prevalence-associated major antigen signature
Authors: Borges Vítor , Cordeiro Dora , Salas Ana Isabel , Lodhia Zohra , Correia Cristina , Isidro Joana , Fernandes Cândida , Rodrigues Ana Maria , Azevedo Jacinta , Alves João , Roxo João , Rocha Miguel , Côrte-Real Rita , Vieira Luís , Borrego Maria José , Gomes João Paulo
Published: April 2019

Chlamydia trachomatisis the most prevalent sexually transmitted bacteria worldwide and the causative agent of blinding trachoma. Strains are classified based onompAgenotypes, which are strongly linked with differential tissue tropism and disease outcomes. A lymphogranuloma venereum (LGV) epidemics, characterized by ulcerative proctitis, has emerged in the last two decades (mainly L2b genotype), raising high concern especially due to its circulation among men who have sex with men (MSM). Here, we report an ongoing outbreak (mostly affecting HIV-positive MSM engaging in high-risk practices) caused by an L2b strain with a rather unique genome makeup that precluded the laboratory notification of this outbreak as LGV due to its non-LGVompAsignature. Homologous recombination mediated the transfer of a ~4.5Kbp fragment enrollingCT681/ompAand neighboring genes (CT677/rrf, CT678/pyrH, CT679/tsf, CT680/rpsB) from a serovar D/Da strain likely possessing the typical T1 clade genome backbone associated with most prevalent genotypes (E and F). The hybrid L2b/D-Da strain presents the adhesin and immunodominant antigen MOMP (coded byompA) with an epitope repertoire typical of non-invasive genital strains, while keeping the genome-dispersed virulence fingerprint of a classical LGV (L2b) strain. As previously reported for inter-cladeompAexchange among non-LGV clades, this unprecedentedC. trachomatisgenomic mosaic involving a contemporary epidemiologically and clinically relevant LGV strain may have implications on its transmission, tissue tropism and pathogenic capabilities. The emergence of such variants with epidemic and pathogenic potential highlights the need of more oriented surveillance strategies focused on capturing the C.trachomatisevolution in action.
Rapid, large-scale species discovery in hyperdiverse taxa using 1D MinION sequencing
Authors: Srivathsan Amrita , Hartop Emily , Puniamoorthy Jayanthi , Lee Wan Ting , Kutty Sujatha Narayanan , Kurina Olavi , Meier Rudolf
Published: April 2019

Background

More than 80% of all animal species remain unknown to science. Most of these species live in the tropics and belong to animal taxa that combine small body size with high specimen abundance and large species richness. For such clades, using morphology for species discovery is slow because large numbers of specimens must be sorted using detailed microscopic investigations. Fortunately, species discovery could be greatly accelerated if DNA sequences could be used for sorting specimens to species. Morphological verification of such “molecular Operational Taxonomic Units” (mOTUs) could then be based on dissection of a small subset of specimens. However, this approach requires cost-effective and low-tech DNA barcoding techniques because well equipped, well-funded molecular laboratories are not readily available in many biodiverse countries.

Results

We here document how MinION sequencing can be used for large-scale species discovery in a specimen- and species-rich taxon like the hyper-diverse fly family Phoridae (Diptera). We sequenced 7,059 specimens collected in a single Malaise trap in Kibale National Park, Uganda over the short period of eight weeks. We discovered >650 species which exceeded the number of phorid species currently described for the entire Afrotropical region. The barcodes were obtained using an improved low-cost MinION pipeline that increased the barcoding capacity sevenfold from 500 to 3,500 barcodes per flowcell. This was achieved by adopting 1D sequencing, re-sequencing weak amplicons on a used flowcell, and improving demultiplexing. Comparison with Illumina data revealed that the MinION barcodes were very accurate (99.99% accuracy, 0.46% Ns) and thus yielded very similar species units (match ratio: 0.991). Morphological examination of 100 mOTUs also confirmed good congruence with morphology (93% of mOTUs; >99% of specimens) and revealed that 90% of the putative species belong to a neglected, megadiverse genus (Megaselia). We demonstrate for oneMegaseliaspecies how the molecular data can guide the description of a new species (Megaselia sepsioidessp. nov.).

Conclusions

We document that one field site in Africa can be home to an estimated 1000 species of phorids and speculate that the Afrotropical diversity could exceed 100,000 species. We furthermore conclude that low-cost MinION sequencers are very suitable for reliable, rapid, and large-scale species discovery in hyperdiverse taxa. MinION sequencing could quickly reveal the extent of the unknown diversity and is especially suitable for biodiverse countries with limited access to capital-intensive sequencing facilities.
Transcriptional profiling of Impatiens walleriana genes through different stages of downy mildew infection reveals novel genes involved in disease susceptibility
Authors: Suarez Stephanie , Naveed Zunaira Afzal , Ali Gul Shad
Published: April 2019

Impatiens downy mildew is a highly destructive disease of Impatiens walleriana, and economically important bedding ornamental crop. This disease is caused by a recently emerged pathogen Plasmopara obducens. Since both the host and pathogen are relatively less studied, there are only a few genomic resources available for both I. walleriana and P. obducens. In this study, we have analyzed transcriptional changes in I. walleriana in response to P. obducens infection during different stages of disease development. Our main goal was to identify candidate genes that may be involved in I. walleriana susceptibility to P. obducens. Since the genome of I. walleriana is not available publicly, we constructed and optimized a de novo transcriptome assembly consisting of 73,022 transcripts. Differential expression analysis based on this optimized de novo transcriptome assembly revealed 3,000 to 4,500 differentially expressed transcripts (DETs) at 0 hr, 12 hr, 48 hr, 120 hr, and 240 hr time points after infection. Functional annotation of these DETs revealed that numerous plant stress responsive genes are activated and deactivated throughout the infection cycle. Genes in the calcium signaling pathways, receptor-like kinases (RLKs) including 10 disease resistance associated RLK transcripts, powdery mildew resistance genes (MLO), and many other plant stress related genes were predominantly differentially expressed in I. walleriana in response to P. obducens. Analyses reported here provides molecular insights into the disease susceptibility mechanism of the Impatiens downy mildew, and lays out a strong foundation for future studies aimed at improving downy mildew resistance in I. walleriana.
Neuromesodermal progenitors separate the axial stem zones while producing few single- and dual-fated descendants
Authors: Wood Timothy R. , Kyrsting Anders , Stegmaier Johannes , Kucinski Iwo , Kaminski Clemens F. , Mikut Ralf , Voiculescu Octavian
Published: April 2019

Most embryos and regenerating tissues grow by the action of stem zones. Two epithelial stem zones drive axial elongation in amniotes: the mature organizer generates mesoderm, the neuralised ectoderm around it extends the neuraxis. Bipotential progenitors were also shown to exist. How are these stem cell populations organised and what controls the cell fate of bipotential progenitors? We use direct, in vivo imaging of these stem cells in the chick. We find that progenitors of single and dual fates are mingled in a small region between the specialised stem zones. Divergent tissue movements surround this region. When transplanted downstream of these flows, cells from the region of mixed fates adopt the molecular identity and behaviour of the target stem zone, irrespective of their normal fate. Thus, multipotent cells serve to separate the specialized stem zones, instead of a classical boundary. We propose their fate is determined extrinsically by morphogenetic shearing.
CRZ1 regulator and calcium cooperatively modulate holocellulases gene expression in Trichoderma reesei QM6a
Authors: Martins-Santana Leonardo , de Paula Renato Graciano , Gomes Silva Adriano , Christian Borges Lopes Douglas , do Nascimento Silva Roberto , Silva-Rocha Rafael
Published: April 2019

Background

Trichoderma reesei is the main filamentous fungus used in industry to produce cellulases. Over the last decades, there have been a strong increase in the understanding of the regulatory network controlling cellulase-coding gene expression in response to a number of inducers and environmental signals. In this sense, the role of calcium and the Calcineurin-responsive protein (CRZ1) has been investigated in industrially relevant strains of T. reesei RUT-C30, but this system has not been investigated in wild-type reference strain of this fungus.

Results

Here, we investigated the role of CRZ1 and Ca2+ signaling in the fungus T. reesei QM6a. For this, we first searched for potential CRZ1 binding sites in promoter regions of key genes coding holocellulases, as well as transcriptional regulators and sugar and calcium transporters. Using a nearly constructed T. reesei Δcrzl strain, we demonstrated that most of the genes expected to be regulated by CRZ1 were affected in the mutant strain induced with sugarcane bagasse (SCB) and cellulose. In particular, our data demonstrate that Ca2+ acts synergistically with CRZ1 to modulate gene expression, but also exerts CRZ1-independent regulatory role in gene expression in T. reesei, suggesting the existence of additional Ca2+ sensing mechanisms in this fungus.

Conclusions

This work presents new evidence on the regulatory role of CRZ1 and Ca2+ sensing in the regulation of cellulolytic enzymes in T. reesei, evidencing significant and previously unknown function of this Ca2+ sensing system in the control key transcriptional regulators (XYR1 and CRE1) and on the expression of genes related to sugar and Ca2+ transport. Taken together, the data obtained here provide new evidence on the regulatory network of T. reesei related to plant biomass deconstruction.
Feature-Specific Neural Reactivation during Episodic Memory
Authors: Bone Michael B. , Ahmad Fahad , Buchsbaum Bradley R.
Published: April 2019

When recalling an experience of the past, many of the component features of the original episode may be, to a greater or lesser extent, reconstructed in the mind’s eye. There is strong evidence that the pattern of neural activity that occurred during an initial perceptual experience is recreated during episodic recall (neural reactivation), and that the degree of reactivation is correlated with the subjective vividness of the memory. However, while we know that reactivation occurs during episodic recall, we have lacked a way of precisely characterizing the contents—in terms of its featural constituents—of a reactivated memory. Here we present a novel approach, feature-specific informational connectivity (FSIC), that leverages hierarchical representations of image stimuli derived from a deep convolutional neural network to decode neural reactivation in fMRI data collected while participants performed an episodic recall task. We show that neural reactivation associated with low-level visual features (e.g. edges), high-level visual features (e.g. facial features), and semantic features (e.g. “terrier”) occur throughout the dorsal and ventral visual streams and extend into the frontal cortex. Moreover, we show that reactivation of both low- and high-level visual features correlate with the vividness of the memory, whereas only reactivation of low-level features correlates with recognition accuracy when the lure and target images are semantically similar. In addition to demonstrating the utility of FSIC for mapping feature-specific reactivation, these findings resolve the relative contributions of low- and high-level features to the vividness of visual memories, clarify the role of the frontal cortex during episodic recall, and challenge a strict interpretation the posterior-to-anterior visual hierarchy.
ThermoRawFileParser: modular, scalable and cross-platform RAW file conversion
Authors: Hulstaert Niels , Sachsenberg Timo , Walzer Mathias , Barsnes Harald , Martens Lennart , Perez-Riverol Yasset
Published: April 2019

The field of computational proteomics is approaching the big data age, driven both by a continuous growth in the number of samples analysed per experiment, as well as by the growing amount of data obtained in each analytical run. In order to process these large amounts of data, it is increasingly necessary to use elastic compute resources such as Linux-based cluster environments and cloud infrastructures. Unfortunately, the vast majority of cross-platform proteomics tools are not able to operate directly on the proprietary formats generated by the diverse mass spectrometers. Here, we presented ThermoRawFileParser, an open-source, crossplatform tool that converts Thermo RAW files into open file formats such as MGF and to the HUPO-PSI standard file format mzML. To ensure the broadest possible availability, and to increase integration capabilities with popular workflow systems such as Galaxy or Nextflow, we have also built Conda and BioContainers containers around ThermoRawFileParser. In addition, we implemented a user-friendly interface (ThermoRawFileParserGUI) for those users not familiar with command-line tools. Finally, we performed a benchmark of ThermoRawFileParser and msconvert to verify that the converted mzML files contain reliable quantitative results.
Genetic Architecture of Chilling Tolerance in Sorghum Dissected with a Nested Association Mapping Population
Authors: Marla Sandeep R. , Burow Gloria , Chopra Ratan , Hayes Chad , Olatoye Marcus O. , Felderhoff Terry , Hu Zhenbin , Raymundo Rubi , Perumal Ramasamy , Morris Geoffrey P.
Published: April 2019

Dissecting the genetic architecture of stress tolerance in crops is critical to understand and improve adaptation. In temperate climates, early planting of chilling-tolerant varieties could provide longer growing seasons and drought escape, but chilling tolerance (<15°) is generally lacking in tropical-origin crops. Here we developed a nested association mapping (NAM) population to dissect the genetic architecture of early-season chilling tolerance in the tropical-origin cereal sorghum(Sorghum bicolor[L.] Moench). The NAM resource, developed from reference line BTx623 and three chilling-tolerant Chinese lines, is comprised of 771 recombinant inbred lines genotyped by sequencing at 43,320 single nucleotide polymorphisms. We phenotyped the NAM population for emergence, seedling vigor, and agronomic traits (>75,000 data points from ∼16,000 plots) in multi-environment field trials in Kansas under natural chilling stress (sown 30–45 days early) and normal growing conditions. Joint linkage mapping with early-planted field phenotypes revealed an oligogenic architecture, with 5–10 chilling tolerance loci explaining 20–41% of variation. Surprisingly, several of the major chilling tolerance loci co-localize precisely with the classical grain tannin (Tan1andTan2) and dwarfing genes (Dw1andDw3) that were under strong directional selection in the US during the 20th century. These findings suggest that chilling sensitivity was inadvertently selected due to coinheritance with desired nontannin and dwarfing alleles. The characterization of genetic architecture with NAM reveals why past chilling tolerance breeding was stymied and provides a path for genomics-enabled breeding of chilling tolerance.

Article Summary

Chilling sensitivity limits productivity of tropical-origin crops in temperate climates, and remains poorly understood at a genetic level. We developed a nested association mapping resource in sorghum, a tropical-origin cereal, to understand the genetic architecture of chilling tolerance. Linkage mapping of growth traits from early-planted field trials revealed several major chilling tolerance loci, including some colocalized with genes that were selected in the origin of US grain sorghum. These findings suggest chilling sensitivity was inadvertently selected during 20th century breeding, but can be bypassed using a better understanding of the underlying genetic architecture.

Disclaimer

Mention of a trademark, warranty, proprietary product, or vendor does not constitute a guarantee by the USDA and does not imply approval or recommendation of the product to the exclusion of others that may be suitable. USDA is an equal opportunity provider and employer.
Multiple QTL mapping in autopolyploids: a random-effect model approach with application in a hexaploid sweetpotato full-sib population
Authors: Silva Pereira Guilherme da , Gemenet Dorcus C. , Mollinari Marcelo , Olukolu Bode A. , Wood Joshua C. , Diaz Federico , Mosquera Veronica , Gruneberg Wolfgang J. , Khan Awais , Buell C. Robin , Yencho G. Craig , Zeng Zhao-Bang
Published: April 2019

In developing countries, the sweetpotato,Ipomoea batatas(L.) Lam. (2n= 6x= 90), is an important autopolyploid species, both socially and economically. However, quantitative trait loci (QTL) mapping has remained limited due to its genetic complexity. Current fixed-effect models can only fit a single QTL and are generally hard to interpret. Here we report the use of a random-effect model approach to map multiple QTL based on score statistics in a sweetpotato bi-parental population (‘Beauregard’×‘Tanzania’) with 315 full-sibs. Phenotypic data were collected for eight yield component traits in six environments in Peru, and jointly predicted means were obtained using mixed-effect models. An integrated linkage map consisting of 30,684 markers distributed along 15 linkage groups (LGs) was used to obtain the genotype conditional probabilities of putative QTL at every cM position. Multiple interval mapping was performed using our R package QTLPOLY and detected a total of 41 QTL, ranging from one to ten QTL per trait. Some regions, such as those on LGs 3 and 15, were consistently detected among root number and yield traits and provided basis for candidate gene search. In addition, some QTL were found to affect commercial and noncommercial root traits distinctly. Further best linear unbiased predictions allowed us to characterize additive allele effects as well as to compute QTL-based breeding values for selection. Together with quantitative genotyping and its appropriate usage in linkage analyses, this QTL mapping methodology will facilitate the use of genomic tools in sweetpotato breeding as well as in other autopolyploids.
Interspecies interactions in bacterial colonies are determined by physiological traits and the environment
Authors: Booth Sean C. , Rice Scott A.
Published: April 2019

Interspecies interactions in bacterial biofilms have important impacts on the composition and function of communities in natural and engineered systems. To investigate these interactions, synthetic communities provide experimentally tractable systems. Agar-surface colonies are similar to biofilms and have been used for investigating the eco-evolutionary and biophysical forces that determine community composition and spatial distribution of bacteria. Prior work has focused on intraspecies interactions, using differently fluorescent tagged but identical or genetically modified strains of the same species. Here, we investigated how physiological differences determine the community composition and spatial distribution in synthetic communities of Pseudomonas aeruginosa, Pseudomonas protegens and Klebsiella pneumoniae. Using quantitative microscopic imaging, we found that interspecies interactions in multispecies colonies are influenced by type IV pilus mediated motility, extracellular matrix secretion, environmental parameters and the specific species involved. These results indicate that the patterns observable in mixed species colonies can be used to understand the mechanisms that drive interspecies interactions, which are dependent on the interplay between specific species’ physiology and environmental conditions.
Diverse conjugative elements silence natural transformation inLegionellaspecies
Authors: Durieux Isabelle , Ginevra Christophe , Attaiech Laetitia , Picq Kevin , Juan Pierre-Alexandre , Jarraud Sophie , Charpentier Xavier
Published: April 2019

Natural transformation,i.e.the uptake of DNA and its stable integration in the chromosome, is a major mechanism of horizontal gene transfer and is common in bacteria. The vast majority of bacterial genomes carry the specific genes involved in natural transformation, yet only a fraction of species are deemed naturally transformable. This is typically explained by the inability of standard laboratory conditions to induce this phenotypic trait. However, even when the inducing conditions are known, large intraspecific variations have been reported. In this study, we investigated the conservation and distribution of natural transformability in the human pathogenLegionella pneumophila. Using a panel of 113 clinical isolates, we found that natural transformability is relatively conserved but shows large variations inconsistent with the phylogeny. By conducting a genome-wide association study (GWAS) we identified the conjugative plasmid pLPL as a source of these intraspecific variations. We further show that the plasmid inhibits transformation by simultaneously silencing the genes required for DNA uptake and recombination,comEC, comEA, comFandcomM. We identified a plasmid-encoded small RNA (sRNA), RocRp, as solely responsible for the silencing of natural transformation. RocRp is homologous to the highly conserved and chromosome-encoded RocR which controls the transient expression of the DNA uptake system. We show that RocRp can take over the function of RocR, by acting as a substitute, ensuring that the bacterial host of the conjugative plasmid does not become naturally transformable. Distinct homologs of this plasmid-encoded sRNA are found in diverse conjugative elements in otherLegionellaspecies, suggesting that silencing natural transformation is beneficial to these genetic elements. We propose that transformation-interfering factors are frequent genetic cargo of mobile genetic elements, accounting for intraspecific variations in natural transformation but also responsible for the apparent non-transformability of some species.
A doublecortin-domain protein of Toxoplasma and its orthologues bind to and modify the structure and organization of tubulin polymers
Authors: Leung Jacqueline M. , Nagayasu Eiji , Hwang Yu-Chen , Liu Jun , Pierce Phillip G. , Phan Isabelle Q. , Prentice Robin A. , Murray John M. , Hu Ke
Published: April 2019

TgDCX is a doublecortin-domain protein associated with the conoid fibers, a set of strongly curved non-tubular tubulin-polymers in Toxoplasma. TgDCX deletion impairs conoid structure and parasite invasion. TgDCX contains two tubulin-binding domains: a partial P25-alpha and the DCX/doublecortin domain. Orthologues are found in apicomplexans and their free-living relatives Chromera and Vitrella. We report that isolated TgDCX-containing conoid fibers retain their pronounced curvature, but loss of TgDCX destabilizes the fibers. We crystallized and determined the 3D-structure of the DCX-domain, which is similar to those of human doublecortin and well-conserved among TgDCX orthologues. However, the orthologues vary widely in targeting to the conoid in Toxoplasma and in modulating microtubule organization in Xenopus cells. Several orthologues bind to microtubules in Xenopus cells, but only TgDCX generates short, strongly curved microtubule arcs. EM analysis shows microtubules decorated with TgDCX bundled into rafts, often bordered on one edge by a “C”-shaped incomplete tube. A Chromera orthologue closely mimics TgDCX targeting in Toxoplasma and binds to microtubules in Xenopus cells, but does not generate arcs or “C”-shaped tubes, and fails to rescue the defects of the TgDCX-knockout parasite. These observations suggest that species-specific features of TgDCX enable it to generate strongly curved tubulin-polymers to support efficient host-cell invasion.
Contrasting biogeographic patterns of bacterial and archaeal diversity in the top- and subsoils of temperate grasslands
Authors: Liu Nana , Hu Huifeng , Ma Wenhong , Deng Ye , Liu Yuqing , Hao Baihui , Zhang Xinying , Dimitrov Dimitar , Feng Xiaojuan , Wang Zhiheng
Published: April 2019

Biogeographic patterns and drivers of soil microbial diversity have been extensively studied in the past few decades. However, most research has focused on the topsoil while the subsoil is assumed to have similar microbial diversity patterns as the topsoil. Here we compare patterns and drivers of microbial diversity in the top- (0-10 cm) versus subsoils (30-50 cm) of temperate grasslands in Inner Mongolia of China along an aridity gradient covering a ~1500-km transect from arid to mesic ecosystems. Counter to the conventional assumption, we find contrasting biogeographic patterns of diversity and influencing factors for different bacterial and archaeal groups and between depths. While bacterial diversity increases with increasing aridity, archaeal diversity decreases. Microbial diversity in the topsoil is most strongly influenced by aboveground vegetation, but is most strongly influenced by historical temperature anomaly since the Last Glacial Maximum (LGM) in the subsoil. Moreover, the biogeographic patterns of top-subsoil diversity difference varies for different microbial groups and is overall most strongly influenced by soil fertility difference between depths and historical temperature anomaly. These findings suggest that diversity patterns observed in the topsoil may not be readily applied to the subsoil horizons. For the subsoil in particular, historical climate plays a vital role in the distribution of various microbial groups. Overall, our study provides novel information for understanding and predicting soil microbial diversity patterns at depth.

IMPORTANCE

Exploring the biogeographic patterns of soil microbial diversity is critical for understanding mechanisms underlying the response of soil processes to climate change. Using top- and subsoils from a ~1500-km temperature grassland transect, we find divergent patterns of microbial diversity and its determinants in the top-versus subsoils. Furthermore, we find important legacy effect of historical climate change on the microbial diversity of subsoil but not topsoil. Our findings challenge the conventional assumption of similar geographic patterns of soil microbial diversity along soil profiles and help to improve our understanding of how soil microbial communities may respond to future climate change in different regions with varied climate history.
Dynamics of adaptation in an anisotropic phenotype-fitness landscape
Authors: Hamel F. , Lavigne F. , Martin G. , Roques L.
Published: April 2019

We study the dynamics of adaptation of a large asexual population in a n-dimensional phenotypic space, under anisotropic mutation and selection effects. When n = 1 or under isotropy assumptions, the ‘replicator-mutator’ equation is a standard model to describe these dynamics. However, the n-dimensional anisotropic case remained largely unexplored.

We prove here that the equation admits a unique solution, which is interpreted as the phenotype distribution, and we propose a new and general framework to the study of the quantitative behavior of this solution. Our method builds upon a degenerate nonlocal parabolic equation satisfied by the distribution of the ‘fitness components’, and a nonlocal transport equation satisfied by the cumulant generating function of the joint distribution of these components. This last equation can be solved analytically and we then get a general formula for the trajectory of the mean fitness and all higher cumulants of the fitness distribution, over time. Such mean fitness trajectory is the typical outcome of empirical studies of adaptation by experimental evolution, and can thus be compared to empirical data.

In sharp contrast with the known results based on isotropic models, our results show that the trajectory of mean fitness may exhibit (n − 1) plateaus before it converges. It may thus appear ‘non-saturating’ for a transient but possibly long time, even though a phenotypic optimum exists. To illustrate the empirical relevance of these results, we show that the anisotropic model leads to a very good fit of Escherichia coli long-term evolution experiment, one of the most famous experimental dataset in experimental evolution. The two ‘evolutionary epochs’ that have been observed in this experiment have long puzzled the community: we propose that the pattern may simply stem form a climbing hill process, but in an anisotropic fitness landscape.
Extrinsic noise and heavy-tailed laws in gene expression
Authors: Ham Lucy , Brackston Rowan D. , Stumpf Michael P.H.
Published: April 2019

Noise in gene expression is one of the hallmarks of life at the molecular scale. Here we derive analytical solutions to a set of models describing the molecular mechanisms underlying transcription of DNA into RNA. Our Ansatz allows us to incorporate the effects of extrinsic noise – encompassing factors external to the transcription of the individual gene – and discuss the ramifications for heterogeneity in gene product abundance that has been widely observed in single cell data. Crucially, we are able to show that heavy-tailed distributions of RNA copy numbers cannot result from the intrinsic stochasticity in gene expression alone, but must instead reflect extrinsic sources of variability.
Parameter inference in dynamical systems with co-dimension 1 bifurcations
Authors: Roesch Elisabeth , Stumpf Michael P.H.
Published: April 2019

Dynamical systems with intricate behaviour are all-pervasive in biology. Many of the most interesting biological processes indicate the presence of bifurcations, i.e. phenomena where a small change in a system parameter causes qualitatively different behaviour. Bifurcation theory has become a rich field of research in its own right and evaluating the bifurcation behaviour of a given dynamical system can be challenging. An even greater challenge, however, is to learn the bifurcation structure of dynamical systems from data, where the precise model structure is not known. Here we study one aspects of this problem: the practical implications that the presence of bifurcations has on our ability to infer model parameters and initial conditions from empirical data; we focus on the canonical co-dimension 1 bifurcations and provide a comprehensive analysis of how dynamics, and our ability to infer kinetic parameters are linked. The picture thus emerging is surprisingly nuanced and suggests that identification of the qualitative dynamics — the bifurcation diagram — should precede any attempt at inferring kinetic parameters.
Within-population genome size variation is mediated by multiple genomic elements that segregate independently during meiosis
Authors: Stelzer Claus-Peter , Pichler Maria , Stadler Peter , Hatheuer Anita , Riss Simone
Published: April 2019

Within-species variation in genome size has been documented in many animals and plants. Despite its importance for understanding eukaryotic genome diversity, there is only sparse knowledge about how individual-level processes mediate genome size variation in populations. Here we study a natural population of the rotifer Brachionus asplanchnoidis whose members differ up to 1.9-fold in genome size, but were still able to interbreed and produce viable offspring. We show that genome size is highly heritable and can be artificially selected up or down, but not beyond a minimum diploid genome size. Analyses of segregation patterns in haploid males reveal that large genomic elements (several megabases in size) provide the substrate of genome size variation. These elements, and their segregation patterns, explain the generation of new genome size variants, the short-term evolutionary potential of genome size change in populations, and some seemingly paradoxical patterns, like an increase in genome size variation among highly inbred lines. Our study suggests that a conceptual model involving only two variables, (1) a minimum genome size of the population, and (2) a vector containing information on additional elements that may increase genome size in this population (size, number, and meiotic segregation behaviour), can effectively address most scenarios of short-term evolutionary change of genome size in a population.
Human rDNA Copy Number Is Unstable in Metastatic Breast Cancers
Authors: Valori Virginia , Tus Katalin , Laukaitis Christina , Harris David T. , LeBeau Lauren , Maggert Keith A.
Published: April 2019

Epigenetic silencing, including the formation of heterochromatin, silent chromosome territories, and repressed gene promoters, acts to stabilize patterns of gene regulation and the physical structure of the genome. Reduction of epigenetic silencing can result in genome rearrangements, particularly at intrinsically unstable regions of the genome such as transposons, satellite repeats, and repetitive gene clusters including the rRNA gene clusters (rDNA). It is thus expected that mutational or environmental conditions that compromise heterochromatin function might cause genome instability, and diseases associated with decreased epigenetic stability might exhibit genome changes as part of their etiology. We find support of this hypothesis in invasive ductal breast carcinoma, in which reduced epigenetic silencing has been previously described, by using a facile method to quantify rDNA copy number in biopsied breast tumors and pair-matched healthy tissue. We found that rDNA and satellite DNA sequences had significant copy number variation – both losses and gains of copies – compared to healthy tissue, arguing that these genome rearrangements are common in developing breast cancer. Thus, any proposed etiology onset or progression of breast cancer should consider alterations to the epigenome, but must also accommodate concomitant changes to genome sequence at heterochromatic loci.

Authors’ Statement

One of the common hallmarks of cancer is genome instability, including hypermutation and changes to chromosome structure. Using tumor tissues obtained from women with invasive ductal carcinoma, we find that a sensitive area of the genome – the ribosomal DNA gene repeat cluster – shows hypervariability in copy number. The patterns we observe as not consistent with an adaptive loss leading to increased tumor growth, but rather we conclude that copy number variation at repeat DNA is a general consequence of reduced heterochromatin function in cancer progression.
Isolated occurrences of membrane perturbation by mechanosensing from weakly aggregating silver nanoparticles
Authors: Perez Marcos Arribas , Moriones Oscar H. , Bastús Neus G. , Puntes Victor , Nelson Andrew , Beales Paul A.
Published: April 2019

Silver nanoparticles (AgNPs) have wide-ranging applications, including as additives in consumer products and in medical diagnostics and therapy. Therefore understanding how AgNPs interact with biological systems is important for ascertaining any potential health risks due to the likelihood of high levels of human exposure. Besides any severe, acute effects, it is desirable to understand more subtle interactions that could lead to milder, chronic health impacts. Nanoparticles are small enough to be able to enter biological cells and interfere with their internal biochemistry. The initial contact between nanoparticle and cell is at the plasma membrane. To gain fundamental mechanistic insight into AgNP-membrane interactions, we investigate these phenomena in minimal model systems using a wide-range of biophysical approaches applied to lipid vesicles. We find a strong dependence on the medium composition, where colloidally stable AgNPs in a glucose buffer have negligible effect on the membrane. However, at a physiological salt concentrations, the AgNPs start to weakly aggregate and sporadic but significant membrane perturbation events are observed. Under these latter conditions, transient poration and structural remodelling of some vesicle membranes is observed. We observe that the fluidity of giant vesicle membranes universally decreases by an average of 16% across all vesicles. However, we observe a small population of vesicles display a significant change in mechanical properties with lower bending rigidity and higher membrane tension. Therefore we argue that the isolated occurrences of membrane perturbation by AgNPs are due to low probability mechanosensing events of AgNP aggregation at the membrane.

GRAPHICAL ABSTRACT
Conformational Flexibility of p150Glued(1-191) Subunit of Dynactin Assembled with Microtubules
Authors: Guo C. , Williams J. C. , Polenova T.
Published: April 2019

Microtubule-associated proteins (MAPs) perform diverse functions in cells. These functions are dependent on their interactions with microtubules. Dynactin, a cofactor of dynein motor, assists the binding of dynein to various organelles and is crucial to the long-distance processivity of dynein-based complexes. The largest subunit of dynactin, the p150glued, contains a N-terminus segment that is responsible for the microtubule-binding interactions and long-range processivity of dynactin. We employed solution and magic angle spinning NMR spectroscopy to characterize the structure and dynamics of the p150glued N-terminal region, both free and in complex with polymerized microtubules. This 191-residue region encompasses the CAP-Gly domain, the basic domain and serine-proline-rich (SP-rich) domain. We demonstrate that the basic and SP-rich domains are intrinsically disordered in solution and significantly enhance the binding affinity to microtubules as these regions contain the second microtubule-binding site on the p150Glued subunit. The majority of the basic and SP-rich domains are predicted to be random-coil, while the segments S111–I116, A124–R132 and K144–T146 in the basic domain contain short α-helical or β-sheet structures. These three segments possibly encompass the microtubule binding site. Surprisingly, the protein retains high degree of flexibility upon binding to microtubules except for the regions that are directly involved in the binding interactions with microtubules. This conformational flexibility may be essential for the biological functions of the p150Glued subunit.

STATEMENT OF SIGNIFICANCE

Microtubule-associated proteins (MAPs) perform diverse functions in cells. Many of them comprises intrinsically disordered regions, whose structural flexibility are central to microtubule-based cellular functions of MAPs. We employed solution and magic angle spinning NMR spectroscopy to characterize the structure and dynamics of the p150glued N-terminal region encompassing the CAP-Gly domain, the basic domain and serine-proline-rich (SP-rich) domain, both free and in complex with polymerized microtubules. The results reveal that the basic and SP-rich domains are largely unstructured and retains high degree of flexibility upon binding to microtubules except for the regions that are possibly involved in the binding interactions with microtubules. This approach is informative for dynamics studies of intrinsically disordered MAPs and other disordered proteins in large biological assemblies.
Diverse accounting standards on disclosures of Islamic financial transactions
Authors: Ahmed Habib , Tajul Ariffin Faruq Arif , Karbhari Yusuf , Shafii Zurina
Published: April 2019

Purpose

Since International Financial Reporting Standards (IFRS) are not primarily meant for the accounting needs of Islamic banks, the Accounting and Auditing Organisation for Islamic Financial Institutions (AAOIFI) was established to develop specific accounting standards for Shari’ah compliance. The purpose of this paper is to assess the de jure harmonisation between the disclosure requirements of the IFRS-based Malaysian Accounting Standards (MAS) and those of the AAOIFI.

Design/methodology/approach

Using Malaysia as a case study, the paper examines the extent of the de jure congruence between the IFRS-based MAS and AAOIFI’s Financial Accounting Standard No 1 (FAS1), which is considered to be one of the key disclosure standards for Islamic banks. We employ leximetrics and content analysis to analyse these accounting standards and the additional guidelines introduced by the Malaysian Accounting Standards Board (MASB) and the Central Bank of Malaysia (Bank Negara Malaysia, BNM) to identify the gaps between different tiers of MAS and FAS1.

Findings

The study finds that de jure congruence between the IFRS-based MAS and AAOIFI standards has improved through the introduction of additional accounting guidelines by both the MASB and the banking regulator, BNM. However, some gaps remain between the two standards. These gaps may be difficult to completely eliminate due to differences in the fundamental principles underlying the development of both standards.

Originality/value

While some studies have explored the de facto congruence between AAOIFI accounting standards and others, this paper is the first, to the best of the authors’ knowledge, to examine the de jure congruence between those standards with the IFRS-based MAS.
Boundary element method for 3D conductive thin layer in eddy current problems
Authors: Issa Mohammad , Poirier Jean-René , Perrussel Ronan , Chadebec Olivier , Péron Victor
Published: April 2019

Purpose

Thin conducting sheets are used in many electric and electronic devices. Solving numerically the eddy current problems in presence of these thin conductive sheets requires a very fine mesh which leads to a large system of equations, and it becomes more problematic in case of higher frequencies. The purpose of this paper is to show the numerical pertinence of equivalent models for 3D eddy current problems with a conductive thin layer of small thickness e based on the replacement of the thin layer by its mid-surface with equivalent transmission conditions that satisfy the shielding purpose, and by using an efficient discretization using the boundary element method (BEM) to reduce the computational work.

Design/methodology/approach

These models are solved numerically using the BEM and some numerical experiments are performed to assess the accuracy of the proposed models. The results are validated by comparison with an analytical solution and a numerical solution by the commercial software Comsol.

Findings

The error between the equivalent models and analytical and numerical solutions confirms the theoretical approach. In addition to this accuracy, the computational work is reduced by considering a discretization method that requires only a surface mesh.

Originality/value

Based on a hybrid formulation, the authors present briefly a formal derivation of impedance transmission conditions for 3D thin layers in eddy current problems where non-conductive materials are considered in the interior and the exterior domain of the sheet. BEM is adopted to discretize the problem as there is no need for volume discretization.
Effect of eliminating mandatory reconciliation requirements for foreign issuers in the U.S.
Authors: Kumar Gaurav , Saini Jagjit S.
Published: April 2019

Purpose

The purpose of this paper is to examine the effect of choice of accounting standards on the value relevance and accrual quality of reported earnings and book values under International Financial Reporting Standards (IFRS) versus US Generally Accepted Accounting Principles (GAAP).

Design/methodology/approach

The authors examine the effect of choice of accounting standards on the value relevance and accrual quality of reported earnings and book values under IFRS versus US GAAP using 404 firms from 37 countries listed in the USA. They use the modified Jones (1991) model to measure accruals.

Findings

The authors find that value relevance of the book value of equity is increasing (significantly) when the sample firms use IFRS to prepare their financial statements. They also find some evidence in support of the mediating effect of the choice of accounting standards on the accrual quality of the sample firms. The results of this paper indicate that sample firms with lower accrual quality (larger discretionary accruals) experience higher returns during the fiscal year. However, the authors also find that the positive association between size of discretionary accruals and returns is decreasing in the use of IFRS by the sample firms.

Originality/value

This paper adds to prior literature on the harmonization of accounting standards and emphasizes the role of accounting standards in the quality of financial reporting. By using the financial data of all foreign registrants listed in the USA, the authors are able to provide deeper and more representative evidence.
‘Technologies of the self and other’: how self-tracking technologies also shape the other
Authors: Gabriels Katleen , Coeckelbergh Mark
Published: April 2019

Purpose

This paper aims to fill this gap (infra, originality) by providing a conceptual framework for discussing “technologies of the self and other,” by showing that, in most cases, self-tracking also involves other-tracking.

Design/methodology/approach

In so doing, we draw upon Foucault’s “technologies of the self” and present-day literature on self-tracking technologies. We elaborate on two cases and practical domains to illustrate and discuss this mutual process: first, the quantified workplace; and second, quantification by wearables in a non-clinical and self-initiated context.

Findings

The main conclusion is that these shapings are never (morally) neutral and have ethical implications, such as regarding “quantified otherness,” a notion we propose to point at the risk that the other could become an object of examination and competition.

Originality/value

Although there is ample literature on the quantified self, considerably less attention is given to how the relation with the other is being shaped by self-tracking technologies that allow data sharing (e.g. wearables or apps such as Strava or RunKeeper).
What influences the course major decision of accounting and non-accounting students?
Authors: Owusu Godfred Matthew Yaw , Bekoe Rita Amoah , Okyere Sarah Anobil , Welbeck Edem Emerald
Published: April 2019

Purpose

The purpose of this study is to investigate the factors that influence the course major decisions of accounting and non-accounting students.

Design/methodology/approach

A set of questionnaires was developed and administered to 550 undergraduate business students from the University of Ghana Business School. Statistical tests were conducted to examine the mean differences of students’ views on the factors that influence course major selection. Logistic regression analysis was employed to investigate the factors that influence the course major selection of students.

Findings

The results demonstrate that students’ confidence in their academic strength and abilities to manage academic work are good predictors of their course major decisions. Also, students who major in accounting are driven more by self-interest, while non-accounting students are largely motivated by extrinsic interest. Moreover, students’ academic performances were found to be influential on their course major decisions.

Research limitations/implications

This study relied on the views of students from only one university in Ghana, which, in some respect, limits the extent of generalization of the findings.

Practical implications

The paper provides some useful insights into the factors that inspire students to major in accounting. As a means of addressing the supply deficit of accountants globally, policymakers should find the results useful in developing the appropriate strategy that will attract students to the accounting field.

Originality/value

The study provides new insights into the course major selection discourse from a developing-country perspective.