bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptability and evolution of the cell polarization machinery in budding yeast
Authors: Brauns Fridtjof , Iñigo de la Cruz Leila M. , Daalman Werner K.-G. , de Bruin Ilse , Halatek Jacob , Laan Liedewij , Frey Erwin
Published: September 2020

How can a self-organized cellular function evolve, adapt to perturbations, and acquire new sub-functions? To make progress in answering these basic questions of evolutionary cell biology, we analyze, as a concrete example, the cell polarity machinery ofSaccharomyces cerevisiae. This cellular module exhibits an intriguing resilience: it remains operational under genetic perturbations and recovers quickly and reproducibly from the deletion of one of its key components. Using a combination of modeling, conceptual theory, and experiments, we show that multiple, redundant self-organization mechanisms coexist within the protein network underlying cell polarization and are responsible for the module’s resilience and adaptability. Based on our mechanistic understanding of polarity establishment, we hypothesize how scaffold proteins, by introducing new connections in the existing network, can increase the redundancy of mechanisms and thus increase the evolvability of other network components. Moreover, our work suggests how a complex, redundant cellular module could have evolved from a more rudimental ancestral form.
Neuronal Odor Coding in the Larval Sensory Cone ofAnopheles coluzzii: Complex Responses from a Simple System
Authors: Sun Huahua , Liu Feng , Baker Adam , Zwiebel Laurence J.
Published: September 2020

Anopheles mosquitoes are the sole vectors of malaria and other diseases that represent significant threats to global public health. While adult female mosquitoes are responsible for disease transmission, the pre-adult larval stages of the malaria vectorAnopheles coluzziiand other mosquitoes rely on a broad spectrum of sensory cues to navigate their aquatic habitats efficiently to avoid predators and search for food. Of these, mosquito larvae rely heavily on volatile chemical signals that directly activate their olfactory apparatus. Because most studies on mosquito olfaction focus on adults, a paucity of attention has been given to the larval olfactory system, in which the peripheral components are associated with the sensory cone of the larval antennae. To address this, we have investigated the electrophysiological response profile of the larval sensory cone in Anopheles mosquitoes. We found that the larval sensory cone is particularly tuned to alcohols, thiazoles and heterocyclics. Furthermore, these responses can be assigned to discrete groups of sensory cone neurons with distinctive, dose-dependent odorant-response profiles that also provide larvae with the ability to discriminate among compounds with similar chemical structures. A correlation analysis was conducted to determine the relationship between specific larval chemosensory receptors and the response profiles of sensory cone neuron groups. These studies reveal that the larval sensory cone is a highly sophisticated organ that is sensitive to a broad range of compounds and is capable of a remarkable degree of chemical discrimination. Taken together, this study presents critical insights into olfactory coding processes inAn. coluzziilarvae that further our understanding of larval chemical ecology and will contribute to the development of novel larval-based strategies and tools for mosquito control and the reduction of vector-borne disease transmission.
Quantification of Cas9 binding and cleavage across diverse guide sequences maps landscapes of target engagement
Authors: Boyle Evan A , Becker Winston R , Bai Hua B , Chen Janice S , Doudna Jennifer A , Greenleaf William J
Published: September 2020

The RNA-guided nuclease Cas9 has unlocked powerful methods for perturbing both the genome through targeted DNA cleavage and the regulome through targeted DNA binding, but limited biochemical data has hampered efforts to quantitatively model sequence perturbation of target binding and cleavage across diverse guide sequences. We present scalable, sequencing-based platforms for high-throughput filter binding and cleavage, then perform 62,444 quantitative binding and cleavage assays on 35,047 on- and off-target DNA sequences across 90 Cas9 ribonucleoproteins (RNPs) loaded with distinct guide RNAs. We observe that binding and cleavage efficacy, as well as specificity, vary substantially across RNPs; canonically studied guides often have atypically high specificity; sequence context surrounding the target significantly influences Cas9 on-rate; and Cas9 RNPs may sequester targets in nonproductive states that contribute to “proofreading” capability. Finally, we distill our findings into an interpretable biophysical model that predicts changes in binding and cleavage for diverse target sequence perturbations.
Phylotype-Level Characterization of Complex Lactobacilli Communities Using a High-Throughput, High-Resolution Phenylalanyl-tRNA Synthetase(pheS)Gene Amplicon Sequencing Approach
Authors: Silvaraju Shaktheeshwari , Menon Nandita , Fan Huan , Lim Kevin , Kittelmann Sandra
Published: September 2020

The ‘lactobacilli’ to date encompass more than 270 closely related species that were recently re-classified into 26 genera. Because of their relevance to industry, there is a need to distinguish between closely related, yet metabolically and regulatory distinct species, e.g., during monitoring of biotechnological processes or screening of samples of unknown composition. Current available methods, such as shotgun metagenomics or rRNA-based amplicon sequencing have significant limitations (high cost, low resolution, etc.). Here, we generated a lactobacilli phylogeny based on phenylalanyl-tRNA synthetase (pheS) genes and, from it, developed a high-resolution taxonomic framework which allows for comprehensive and confident characterization of lactobacilli community diversity and structure at the species-level. This framework is based on a total of 445pheSgene sequences, including sequences of 277 validly described species and subspecies (out of a total of 283, coverage of 98%). It allows differentiation between 263 lactobacilli species-level clades out of a total of 273 validly described species (including the proposed speciesL. timonensis) and a further two subspecies. The methodology was validated through next-generation sequencing of mock communities. At a sequencing depth of ∼30,000 sequences, the minimum level of detection was approximately 0.02 pg per μl DNA (equalling approximately 10 genome copies per µl template DNA). ThepheSapproach along with parallel sequencing of partial 16S rRNA genes revealed a considerable lactobacilli diversity and distinct community structures across a broad range of samples from different environmental niches. This novel complementary approach may be applicable to industry and academia alike.

IMPORTANCE

Species within the former generaLactobacillusandPediococcushave been studied extensively at the genomic level. To accommodate for their exceptional functional diversity, the over 270 species were recently re-classified into 26 distinct genera. Despite their relevance to both academia and industry, methods that allow detailed exploration of their ecology are still limited by low resolution, high cost or copy number variations. The approach described here makes use of a single copy marker gene which outperforms other markers with regards to species-level resolution and availability of reference sequences (98% coverage). The tool was validated against a mock community and used to address lactobacilli diversity and community structure in various environmental matrices. Such analyses can now be performed at broader scale to assess and monitor lactobacilli community assembly, structure and function at the species (in some cases even at sub-species) level across a wide range of academic and commercial applications.
Disruption of Zika virus xrRNA1-dependent sfRNA1 production results in tissue-specific attenuated viral replication
Authors: Sparks Hadrian , Monogue Brendan , Akiyama Benjamin , Kieft Jeffrey S. , Beckham J. David
Published: September 2020

Zika virus (ZIKV), like other flaviviruses, produces several species of sub-genomic RNAs (sfRNAs) during infection, corresponding to noncoding RNA fragments of different lengths derived from the viral 3’ untranslated region (UTR). Over the course of infection, these sfRNAs accumulate in the cell as a result of incomplete viral genome degradation of the 3’UTR by host 5’ to 3’ exoribonuclease (Xrn1). The halting of Xrn1 in the 3’UTR is due to two RNA pseudoknot structures in the 3’UTR termed exoribonuclease-resistant RNA1 and 2 (xrRNA1&2). Studies with related flaviviruses have shown that sfRNAs are important for pathogenicity and inhibiting both mosquito and mammalian host defense mechanisms. However, these investigations have not included ZIKV and there is very limited data addressing how sfRNAs impact infection in a whole animal model or specific tissues. In this study, we rescued a sfRNA1-deficient ZIKV (X1) by targeted mutation in the xrRNA1 3’ UTR structure. We found that virus which lacks the production of the largest ZIKV sfRNA species, sfRNA1. Using the X1 virus to infect adultIFNAR1-/-mice, we found that while the lack of sfRNA1 does not alter ZIKV replication in the spleen, there is a significant reduction of ZIKV genome replication in the brain and placenta compared to WT ZIKV infection. Despite thee attenuated phenotype of the X1 ZIKV, mice develop a robust neutralizing antibody response. We conclude that targeted disruption of xrRNA1 results in tissue-specific attenuation while still supporting robust neutralizing antibody responses. Future studies will need to investigate the tissue-specific mechanisms by which ZIKV sfRNAs influence infection and may utilize targeted xrRNA mutations to develop novel attenuated flavivirus vaccine approaches.
The chromosomal passenger complex establishes chromosome biorientation via two parallel localization pathways
Authors: Marsoner Theodor , Yedavalli Poornima , Masnovo Chiara , Schmitzer Katrin , Campbell Christopher S.
Published: September 2020

Chromosome biorientation is established by the four-member chromosomal passenger complex (CPC) through phosphorylation of incorrect kinetochore-microtubule attachments. During chromosome alignment, the CPC localizes to the inner centromere, the inner kinetochore and spindle microtubules. Here we show that a small region of the CPC subunit INCENP/Sli15 is required to target the complex to all three of these locations in budding yeast. This region, the SAH, is essential for phosphorylation of outer kinetochore substrates, chromosome segregation, and viability. By restoring the CPC to each of these three locations individually, we found that inner centromere localization is sufficient to establish chromosome biorientation and viability independently of the other two targeting mechanisms. Remarkably, although neither the inner kinetochore nor microtubule binding activities was able to rescue viability individually, they were able to do so when combined. We have therefore identified two parallel pathways by which the CPC can promote chromosome biorientation and proper completion of mitosis.
Human genetic variants disrupt RGS14 nuclear shuttling and regulation of LTP in hippocampal neurons
Authors: Squires Katherine E , Gerber Kyle J , Tillman Matthew C , Lustberg Daniel J , Montañez-Miranda Carolina , Zhao Meilan , Ramineni Suneela , Scharer Christopher D , Shu Feng-jue , Schroeder Jason P , Ortlund Eric A , Weinshenker David , Dudek Serena M , Hepler John R
Published: September 2020

The human genome contains vast genetic diversity in the form of naturally occurring coding variants, yet the impact of these variants on protein function and physiology is poorly understood. RGS14 is a multifunctional signaling protein that suppresses synaptic plasticity in dendritic spines of hippocampal neurons. RGS14 also is a nucleocytoplasmic shuttling protein, suggesting that balanced nuclear import/export and dendritic spine localization are essential for RGS14 functions. We identified genetic variants L505R (LR) and R507Q (RQ) located within the nuclear export sequence (NES) of humanRGS14. Here we report that RGS14 carrying LR or RQ profoundly impacts protein functions in hippocampal neurons and brain. Following nuclear import, RGS14 nuclear export is regulated by Exportin 1 (XPO1/CRM1). Remarkably, LR and RQ variants disrupt RGS14 binding to Gαi1-GDP and XPO1, nucleocytoplasmic equilibrium, and capacity to inhibit LTP. Variant LR accumulates irreversibly in the nucleus, preventing RGS14 binding to G proteins, localization to dendritic spines, and inhibitory actions on LTP induction, while variant RQ exhibits a mixed phenotype. When introduced into mice by CRISPR/Cas9, RGS14-LR protein expression was detected predominantly in the nuclei of neurons within hippocampus, central amygdala, piriform cortex, and striatum, brain regions associated with learning and synaptic plasticity. Whereas mice completely lacking RGS14 exhibit enhanced spatial learning, mice carrying variant LR exhibit normal spatial learning, suggesting that RGS14 may have distinct functions in the nucleus independent from those in dendrites and spines. These findings show that naturally occurring genetic variants can profoundly alter normal protein function, impacting physiology in unexpected ways.
CD8 T cell epitope generation toward the continually mutating SARS-CoV-2 spike protein in genetically diverse human population: Implications for disease control and prevention
Authors: Guo Elisa , Guo Hailong
Published: September 2020

The ongoing pandemic of SARS-CoV-2 has brought tremendous crisis on global health care systems and industrial operations that dramatically affect the economic and social life of numerous individuals worldwide. Understanding anti-SARS-CoV-2 immune responses in population with different genetic backgrounds and tracking the viral evolution are crucial for successful vaccine design. In this study, we reported the generation of CD8 T cell epitopes by a total of 80 alleles of three major class I HLAs using NetMHC 4.0 algorithm for the spike protein of SARS-CoV-2, a key antigen that is targeted by both B cells and T cells. We found diverse capacities of S protein specific epitope presentation by different HLA alleles with very limited number of predicted epitopes for HLA-B*2705, HLA-B*4402 and HLA-B*4403 and as high as 132 epitopes for HLA-A*6601. Our analysis of 1000 S protein sequences from field isolates collected globally over the past few months identified three recurrent point mutations including L5F, D614G and G1124V. Differential effects of these mutations on CD8 T cell epitope generation by corresponding HLA alleles were observed. Finally, our multiple alignment analysis indicated the absence of seasonal CoV induced cross-reactive CD8 T cells to drive these mutations. Our findings provided molecular explanations for the observation that individuals with certain HLA alleles such as B*44 are more prone to SARS-CoV-2 infection. Studying anti-S protein specific CD8 T cell immunity in diverse genetic background is critical for better control and prevention of the SARS-CoV-2 pandemic.
GABAergic inhibition in the human visual cortex relates to eye dominance
Authors: Ip I. Betina , Lunghi Claudia , Emir Uzay E. , Parker Andrew J. , Bridge Holly
Published: September 2020

Our binocular world is seamlessly assembled from two retinal images that remain segregated until the cerebral cortex. Despite the coherence of this input, there is often an imbalance between the strength of these connections in the brain. ‘Eye dominance’ provides a measure of the perceptual dominance of one eye over the other. Theoretical models suggest that eye dominance is related to reciprocal inhibition between monocular units in the primary visual cortex, the first location where the binocular input is combined. As the specific inhibitory interactions in the binocular visual system critically depend on the presence of visual input, we sought to test the role of inhibition by measuring the concentrations of inhibitory (GABA) neurotransmitters during monocular visual stimulation of the dominant and the non-dominant eye. GABA-levels were acquired in V1 using a combined functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) sequence on a 7-Tesla MRI scanner. Individuals with stronger eye dominance had a greater difference in GABAergic inhibition between the eyes. This relationship was present only when the visual system was actively processing sensory input and was not present at rest. We provide the first evidence that imbalances in GABA levels during ongoing sensory processing are related to eye dominance in the human visual cortex. This provides strong support to the view that intracortical inhibition underlies normal eye dominance.

SIGNIFICANCE STATEMENT

What we see is shaped by excitation and inhibition in our brain. We investigated how eye dominance, the perceptual preference of one eye’s input over the other, is related to levels of inhibitory neurotransmitter GABA during monocular visual stimulation. GABAergic inhibition is related to eye dominance, but only when the visual system is actively processing sensory input. This provides key support for the view that imbalances in visual competition that are observed in the normal visual system arise from an inability of GABA signalling to suppress the stronger sensory representation.
Structure of the Human Secretory Immunoglobulin M Core
Authors: Kumar Nikit , Arthur Christopher P. , Ciferri Claudio , Matsumoto Marissa L.
Published: September 2020

Immunoglobulins (Ig) A and M are the only human antibodies that form oligomers and undergo transcytosis to mucosal secretions via the polymeric Ig receptor (pIgR). When complexed with the J-chain (JC) and the secretory component (SC) of pIgR, secretory IgA and IgM (sIgA and sIgM) play critical roles in host-pathogen defense. Recently, we determined the structure of sIgA-Fc which elucidated the mechanism of polymeric IgA assembly and revealed an extensive binding interface between IgA-Fc, JC, and SC. Despite low sequence identity shared with IgA-Fc, IgM-Fc also undergoes JC-mediated assembly and binds pIgR. Here, we report the structure of sIgM-Fc and carryout a systematic comparison to sIgA-Fc. Our structural analysis reveals a remarkably conserved mechanism of JC-templated oligomerization and SC recognition of both IgM and IgA through highly a conserved network of interactions. These studies reveal the structurally conserved features of sIgM and sIgA required for function in mucosal immunity.
Evolution of research in biomedical sciences - a network-based characterization based on PubMed
Authors: Friedrichs Karla , Spranger Michael , Palaniappan Sucheendra K.
Published: September 2020

The rapid growth of scientific publications every year makes it infeasible to keep pace with and survey manually, even for a specific field. Keeping up with literature and gaining a birds-eye view in a timely manner is crucial to the pursuit of scientific discovery and innovation. To help gain a clearer understanding of the state and progress of science and the nature of discovery, one can encode key information from these publications and represent them as a network. Observations on the structural evolution of these graphs can offer valuable insights on the dynamics at play. This work describes the construction and analyses the temporal evolution of a knowledge network of keywords (specifically focusing on genes/proteins, diseases and chemicals) from publications in the biomedical sciences domain. We compare and contrast the representations and evolution of these keyword networks types and find significant differences in the network growth, largely corresponding to our intuition. Furthermore, we focus on the formation and evolution of new links, which we argue corresponds to new scientific discoveries. Our findings suggest that these links are progressively formed in short network distance, leading to clusters of extensively studied keywords. This strategy, however, seems to impede ground-breaking innovation, which could be beneficial for research progress.
Brain Connectivity Patterns in Children Linked to Neurocognitive Abilities
Authors: Sripada Chandra , Angstadt Mike , Rutherford Saige , Taxali Aman , Clark D. Angus , Greathouse Tristan , Weigard Alex , Hyde Luke , Heitzeg Mary
Published: September 2020

The development of objective brain-based measures of individual differences in psychological traits is a longstanding goal of clinical neuroscience. Here we show that reliable objective markers of children’s neurocognitive abilities can be built from measures of brain connectivity. The sample consists of 5,937 9- and 10-year-olds in the Adolescent Brain Cognitive Development multi-site study with high-quality functional connectomes that capture brain-wide connectivity. Using multivariate methods, we built predictive neuromarkers for a general factor of neurocognitive ability as well as for a number of specific cognitive abilities (e.g., spatial reasoning, working memory). Neuromarkers for the general neurocognitive factor successfully predicted scores for held-out participants at 19 out of 19 held-out sites, explaining over 14% of the variance in their scores. Neuromarkers for specific neurocognitive abilities also exhibited statistically reliable generalization to new participants. This study provides the strongest evidence to date that objective quantification of psychological traits is possible with functional neuroimaging.
FreshwaterChlorobiaexhibit metabolic specialization among cosmopolitan and endemic populations
Authors: Garcia Sarahi L. , Mehrshad Maliheh , Buck Moritz , Tsuji Jackson M. , Neufeld Josh D. , McMahon Katherine D. , Bertilsson Stefan , Greening Chris , Peura Sari
Published: September 2020

Photosynthetic bacteria from the classChlorobia(formerly phylumChlorobi) sustain carbon fixation in anoxic water columns. They harvest light at extremely low intensities and use various inorganic electron donors to fix carbon dioxide into biomass. Until now, most information on their functional ecology and local adaptations came from isolates and merely 26 sequenced genomes that are poor representatives of natural populations. To address these limitations, we analyzed global metagenomes to profile planktonicChlorobiacells from the oxyclines of 42 freshwater bodies, spanning subarctic to tropical regions and encompassing all four seasons. We assembled and compiled over 500 genomes, including metagenome-assembled genomes (MAGs), single-cell genomes (SAGs), and reference genomes from cultures, clustering them into 71 metagenomic operational taxonomic units (mOTUs) or “species”. Of the 71 mOTUs, 57 were classified as genusChlorobiumand these mOTUs varied in relative abundance up to ~60% of the microbial communities in the sampled anoxic waters. SeveralChlorobium-associated mOTUs were globally distributed whereas others were endemic to individual lakes. Although most clades encoded the ability to oxidize hydrogen, many were lacking genes for the oxidation of specific sulfur and iron substrates. Surprisingly, one globally distributed ScandinavianChlorobiumclade encoded the ability to oxidize hydrogen, sulfur, and iron, suggesting that metabolic versatility facilitated such widespread colonization. Overall, these findings provide new insights into the biogeography of theChlorobiaand the metabolic traits that facilitate niche specialization within lake ecosystems.

Importance

The reconstruction of genomes from metagenomes has enabled unprecedented insights into the ecology and evolution of environmental microbiomes. We applied this powerful approach to 274 metagenomes collected from diverse freshwater habitats that spanned oxic and anoxic zones, sampling seasons, and latitudes. We demonstrate widespread and abundant distributions of planktonicChlorobia-associated bacteria in hypolimnetic waters of stratified freshwater ecosystems and pinpoint nutrients that likely fuel their electron chains. Being photoautotrophs, theseChlorobiaorganisms also have the potential to serve as carbon sources that support metalimnetic and hypolimnetic food webs.
Frequency-resolved functional connectivity: Role of delay and the strength of connections
Authors: Ziaeemehr Abolfazl , Valizadeh Alireza
Published: September 2020

The brain functional network extracted from the BOLD signals reveals the correlated activity of the different brain regions, which is hypothesized to underlie the integration of the information across functionally specialized areas. Functional networks are not static and change over time and in different brain states, enabling the nervous system to engage and disengage different local areas in specific tasks on demand. Due to the low temporal resolution, however, BOLD signals do not allow the exploration of spectral properties of the brain dynamics over different frequency bands which are known to be important in cognitive processes. Recent studies using imaging tools with a high temporal resolution has made it possible to explore the correlation between the regions at multiple frequency bands. These studies introduce the frequency as a new dimension over which the functional networks change, enabling brain networks to transmit multiplex of information at any time. In this computational study, we explore the functional connectivity at different frequency ranges and highlight the role of the distance between the nodes in their correlation. We run the generalized Kuramoto model with delayed interactions on top of the brain’s connectome and show that how the transmission delay and the strength of the connections, affect the correlation between the pair of nodes over different frequency bands.
Reef Cover: a coral reef classification to guide global habitat mapping from remote sensing
Authors: Kennedy Emma , Roelfsema Chris , Lyons Mitchell , Kovacs Eva , Borrego-Acevedo Rodney , Roe Meredith , Phinn Stuart , Larsen Kirk , Murray Nicholas , Yuwono Doddy , Wolff Jeremy , Tudman Paul
Published: September 2020

Coral reef management and conservation stand to benefit from improved high-resolution global mapping. Yet classifications employed in large-scale reef mapping to date are typically poorly defined, not shared or region-specific. Here we presentReef Cover, a new coral reef geomorphic zone classification, developed to support global-scale coral reef habitat mapping in a transparent and version-based framework. We developed scalable classes by focusing on attributes that can be observed remotely, but whose membership rules also reflect knowledge of reef formation, growth and functioning. Bridging the divide between earth observation data and geo-ecological knowledge of reefs,Reef Covermaximises the trade-off between applicability at global scales, and relevance and accuracy at local scales. We use the Caroline and Mariana Island chains in the Pacific as a case study to demonstrate use of the classification scheme and its scientific and conservation applications. The primary application ofReef Cover is theAllen Coral Atlasglobal coral reef mapping project, but the system will support bespoke reef mapping conducted at a variety of spatial scales.
LIONirs: flexible Matlab toolbox for fNIRS data analysis
Authors: Tremblay Julie , Martínez-Montes Eduardo , Hüsser Alejandra , Caron-Desrochers Laura , Pouliot Philippe , Vannasing Phetsamone , Gallagher Anne
Published: September 2020

Background

Functional near-infrared spectroscopy (fNIRS) is a suitable tool for recording brain function in pediatric or challenging populations. As with other neuroimaging techniques, the scientific community is engaged in an evolving debate regarding the most adequate methods for performing fNIRS data analyses.

New method

We introduce LIONirs, a neuroinformatics toolbox for fNIRS data analysis, designed to follow two main goals: (1) flexibility, to explore several methods in parallel and verify results using 3D visualization; (2) simplicity, to apply a defined processing pipeline to a large dataset of subjects by using the MATLAB Batch System.

Results

Within the graphical user interfaces (DisplayGUI), the user can reject noisy intervals and correct artifacts, while visualizing the topographical projection of the data onto the 3D head representation. Data decomposition methods are available for the identification of relevant signatures, such as brain responses or artifacts. Multimodal data recorded simultaneously to fNIRS, such as physiology, electroencephalography or audio-video, can be visualized using the DisplayGUI. The toolbox includes several functions that allow one to read, preprocess, and analyze fNIRS data, including task-based and functional connectivity measures.

Comparison with existing methods

Several good neuroinformatics tools for fNIRS data analysis are currently available. None of them emphasize multimodal visualization of the data throughout the preprocessing steps and multidimensional decomposition, which are essential for understanding challenging data. Furthermore, LIONirs provides compatibility and complementarity with other existing tools by supporting common data format.

Conclusions

LIONirs offers a flexible platform for basic and advanced fNIRS data analysis, shown through real experimental examples.

Highlights

The LIONirs toolbox is designed for fNIRS data inspection and visualization.

Methods are integrated for isolation of relevant activity and correction of artifacts.

Multimodal auxiliary, EEG or audio-video are visualized alongside the fNIRS data.

Task-based and functional connectivity measure analysis tools are available.

The code structure allows to automated and standardized analysis of large data set.

Graphical abstract
A novel yeast hybrid modeling framework integrating Boolean and enzyme-constrained networks enables exploration of the interplay between signaling and metabolism
Authors: Österberg Linnea , Domenzain Iván , Münch Julia , Nielsen Jens , Hohmann Stefan , Cvijovic Marija
Published: September 2020

The interplay between nutrient-induced signaling and metabolism plays an important role in maintaining homeostasis and its malfunction has been implicated in many different human diseases such as obesity, type 2 diabetes, cancer and neurological disorders. Therefore, unravelling the role of nutrients as signaling molecules and metabolites as well as their interconnectivity may provide a deeper understanding of how these conditions occur. Both signalling and metabolism have been extensively studied using various systems biology approaches. However, they are mainly studied individually and in addition current models lack both the complexity of the dynamics and the effects of the crosstalk in the signaling system. To gain a better understanding of the interconnectivity between nutrient signaling and metabolism, we developed a hybrid model, combining Boolean model, describing the signalling layer and the enzyme constraint model accounting for metabolism using a regulatory network as a link. The model was capable of reproducing the regulatory effects that are associated with the Crabtree effect and glucose repression. We show that using this methodology one can investigat intrinsically different systems, such as signaling and metabolism, in the same model and gain insight into how the interplay between them can have non-trivial effects by showing a connection between Snf1 signaling and chronological lifespan by the regulation of NDE and NDI usage in respiring conditions. In addition, the model showed that during fermentation, enzyme utilization is the more important factor governing the protein allocation, while in low glucose conditions robustness and control is prioritized.

Author summary

Elucidating the complex relationship between nutrient-induced signaling and metabolism represents a key in understanding the onset of many different human diseases like obesity, type 3 diabetes, cancer and many neurological disorders. In this work we proposed a hybrid modeling approach, combining Boolean representation of singaling pathways, like Snf11, TORC1 and PKA with the enzyme constrained model of metabolism linking them via the regulatory network. This allowed us to improve individual model predictions and elucidate how single components in the dynamic signaling layer affect the steady-state metabolism. The model has been tested under respiration and fermentation, reveling novel connections and further reproducing the regulatory effects that are associated with the Crabtree effect and glucose repression. Finally, we show a connection between Snf1 signaling and chronological lifespan by the regulation of NDE and NDI usage in respiring conditions.
Striatal BOLD and midfrontal theta power express motivation for action
Authors: Algermissen Johannes , Swart Jennifer C. , Scheeringa René , Cools Roshan , den Ouden Hanneke E.M.
Published: September 2020

Action selection is biased by the valence of anticipated outcomes. To assess mechanisms by which these motivational biases are expressed and controlled, we measured simultaneous EEG-fMRI during a motivational Go/NoGo learning task (N=36), leveraging the temporal resolution of EEG and subcortical access of fMRI. VmPFC BOLD encoded cue valence, importantly predicting trial-by-trial valence-driven response speed differences and EEG theta power around cue onset. In contrast, striatal BOLD encoded selection of active Go responses and correlated with theta power around response time. Within trials, theta power ramped in the fashion of an evidence accumulation signal for the value of making a ‘Go’ response, capturing the faster responding to reward cues. Our findings reveal a dual nature of midfrontal theta power, with early components reflecting the vmPFC contribution to motivational biases, and late components reflecting their striatal translation into behavior, in line with influential recent “value of work” theories of striatal processing.
Numerical prediction of vortex trajectories and vortex–blade interaction on the CROR engine
Authors: Vinha Nuno , Vallespin David , Valero Eusebio , de Pablo Valentin , Cuesta-Lopez Santiago
Published: September 2020

Purpose

The exponential growth in computational capabilities and the increasing reliability of current simulation tools have fostered the use of computational fluid dynamics (CFD) in the design of pioneering aircraft engine architectures, such as the counter rotating open rotor (CROR) engine. Today, this design process is led by tight performance and noise constraints from a very early stage, thus requiring deep investigations of the aerodynamic and acoustic behaviour of the fluid flow. The purpose of this study is to track the trajectory of tip vortices, which is of critical importance to understand and prevent potential vortex–blade interactions with subsequent rows, as this condition strongly influences the aerodynamic and structural performance and acoustic footprints of the engine.

Design/methodology/approach

In this paper, a flow feature detection methodology is applied to a particular CROR test case with the goal of visualizing and tracking the development of these coherent structures from the tip of front rotating blades. The suitability and performance of four typical region-based methodologies and one line-based (LB) criteria are firstly evaluated. Then, two novel seeding methodologies are presented as an attempt to improve the performance of the LB algorithm previously investigated.

Findings

It was demonstrated that the new seeding algorithms increase the probability of the selected seeds to grow into a tip vortex line and reduce the user’s dependence upon the selection of candidate seeds, providing faster and more accurate answers during the design-to-noise iterative process.

Originality/value

Apart from the new vortex detection initialization methodologies, the paper also attempts to assist the user in the endeavour of extracting rotating structures from their own CFD simulations.
Heavy metal contamination in processed seafood and the associated health risk for Malaysian women
Authors: Jeevanaraj Pravina , Ahmad Foat Aliah , Tholib Halimah , Ahmad Nurul Izzah
Published: September 2020

Purpose

Malaysians are the highest seafood consumers in the region; be it fresh or processed. Environmental pollution has put the safety of seafood at stake, heavy metals among others. This study was done to assess the health risk associated with selected heavy metals ingestion from processed seafood.

Design/methodology/approach

The most preferred processed seafood type and the intake rates were determined from a cross-sectional survey among communities in Shah Alam, Selangor (n = 90). The processed seafood were then purchased from local traders (n = 81), underwent homogenization, acid digestion (0.5 g) in Multiwave 3,000 and heavy metal quantitation (Hg, Pb, Cd, As) using ICP-MS. Estimated weekly ingestion (EWI), hazard quotient (HQ), hazard index (HI), lifetime cancer risk (LCR), and target risk (TR) were used to estimate the risk associated with processed seafood consumption.

Findings

Arsenic was the highest metal detected, acetes topping the list (10.05 ± 0.02 mg/kg). Mercury was detected at significantly higher level in salted fourfinger threadfin (0.88 ± 0.09 mg/kg) while Pb and Cd in toli shad (2.67 ± 0.16 mg/kg; 0.32 ± 0.22 mg/kg). Non-cancer risk was estimated for consumption of dried/salted food types with hazard index (HI) anchoives (5.2) > salted fourfinger threadfin (1.8) > toli shad (1.7). Besides, an unacceptable cancer risk was estimated for all food types for continuous consumption (Total risk (TR) > 10–4), except the dried acetes.

Research limitations/implications

This study implies that although the concentration of most heavy metals were well below the permitted value, significant amount of risk present for consumption of several species. In addition, for selected heavy metals such as Hg and As, speciation analysis followed by risk assessment would provide a clearer picture.

Practical implications

There is a need to refer back to the local permissible level of heavy metals in processed seafood and formulate safe consumption guide.

Social implications

The food types are advised to be consumed with caution especially by the sensitive group.

Originality/value

This study estimated the risk of cancer and other non-cancer disease from processed seafood consumption among Malaysian women.
Automating Container Tracking System at Biginland Container Depot
Authors: Verma Sanjay
Published: September 2020

Ahmedabad Container Depot (ACD) was a fast growing inland container depot (ICD) in Ahmedabad. The area of the depot was 15 acres and it had a monthly turnover capacity of approximately 25,000 containers. The primary processes at the facility were imports, exports, and transshipments. ACD had been facing various challenges due to inefficient manual container tracking system at the facility. Due to good business, the company was able to reach 90–95% of its capacity which was also the main problem ACD had to deal with. The management wanted to increase efficiency by reducing the number of moves required to locate a container by implementing a technology solution. The Head IT of ACD, Bhavik, was examining proposals from vendors and had identified a few alternatives. He was also considering the options that other large container yards had used successfully. His dilemma was to determine the feasibility of the alternatives, particularly those which had not been tested by any other firms in the country. Also, implementing technology could cause a change in roles and responsibilities; dealing with that situation was another area of concern.
All Aboard the Metro Rail? LTMRHL's Campaign for Stakeholder Support
Authors: Kaul Asha , Chaudhri Vidhi
Published: September 2020

LTMRHL launched its Brand Ambassador campaign in Hyderabad on January 8, 2013 to bring about awareness and dispel negativity about the Metro Rail project. A two-year review in 2015 revealed that although many of the initial problems had been overcome, and negativity considerably reduced, the campaign had only achieved partial success. Based on the review, a decision had to be taken to continue or abandon the campaign after the scheduled commercial operations in July 2017. Will the current strategy be the gateway to success post commercial operations, mulled Sanjay Kapoor, General Manager & Head Corporate Communications (LTMRHL).
Understanding addiction, relapse and recovery amongst substance using offenders – a qualitative study informed by developmental psychological theories
Authors: Love Beverly , Vetere Arlene , Davis Paul
Published: September 2020

Purpose

Psychological developmental informed theories imply that addiction is not exclusively due to the addictive properties of the substance but that early psycho-social experiences are influential on later life. The purpose of this paper is to understand substance dependency, relapse and recovery amongst community-based substance using offenders in relation to their childhoods, relationships and significant life events, from their perspective. A key aim was to help better inform policy and practice.

Design/methodology/approach

A qualitative study (interpretative phenomenological analysis) was used to understand the impact of childhood, relationships and significant life events amongst (N = 17) adult ex/offenders with substance use dependency problems, (who were part of the UK Government rehabilitation programme), to understand their substance use and recovery from their own perspectives.

Findings

Four main superordinate themes were developed illustrating participants extremely adverse childhoods. Substance use was a means to cope with current and past trauma and crises and to help manage the emotions and mental health which could accompany these difficulties. Managing recovery was about learning to manage life itself, including emotions, mental health problems, trauma/responses, relationships and everyday life.

Originality/value

This group is under researched where qualitative methods have been used. The study focussed on early-psycho-social experiences and relationships and the influence of these throughout the life cycle, in relation to their substance use. The study was informed by theories often used in therapeutic settings but rarely in research, (Orford, 2008; Khantzian, 2012; Flores, 2012, Van Der Kolk, 2014).
Godrej properties: valuation using the capital cash flow technique
Authors: Rajhans Rajni Kant
Published: September 2020

Learning outcomes

The case is focused to meet the following learning objectives: the readers will be able to recall basic cash flow estimation concepts; and the readers will be able to explain various features of capital cash flow (CCF). The participants will be able to implement the CCF model in real estate firm valuation. The participants will be able to compare CCF and free cash flow to the firm (FCFF) models. The participants will be able to evaluate the benefits of CCF over FCFF. The readers will be able to construct the CCF valuation model for firm valuation.

Case overview/synopsis

On 19th April 2019, Mr Kai, an analyst tracking real estate firms was excited to present to his team a new robust technique of firm valuation suitable for real estate companies, namely, the CCF technique and was also keen to deliberate on its application. Though the investment scope using this technique could be located in Godrej properties (GP), a reputed brand and the largest listed real estate developer by sales in 2018, yet, he was concerned about the assumptions of growth of real estate industry in India, in general, and the GP in particular. Importantly, this was because the real estate market in India was undergoing many structural changes. For instance, the buyers’ preferences were changing and unsold inventory in the industry was at its peak. Under these market conditions, an announcement was made by GP about a target return on equity of 20% in 2018–2023 expecting a dominant place in the real estate market in India, which also carried the threat of jeopardizing the reputation of GP, if under any circumstance the target was not accomplished.

Complexity academic level

Masters program.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS: 11 Strategy.
P2P rooftop rentals in Barcelona: a descriptive analysis
Authors: Anguera-Torrell Oriol , Arcos-Pumarola Jordi , Cerdan Schwitzguébel Aurélie , Encinar-Prat Laia
Published: September 2020

Purpose

The purpose of this paper is to analyse the disruption potential on the daily life of Barcelona’s residents of HolaPlace, a new peer-to-peer (P2P) marketplace for terraces and rooftops. Specifically, it describes its listings’ characteristics and examines their geographical overlapping with signs of tourism-related disruption on residents’ quality of life.

Design/methodology/approach

Available data of the listings in this P2P platform has been scraped in November 2019. This data has been combined with two other sources of information that provide information on the tourism intensity in the different neighbourhoods of the city. The obtained information has been examined using quantitative and qualitative techniques.

Findings

P2P rooftops and terraces tend to be located in the same neighbourhoods that were already experiencing a high concentration of tourism activity. Moreover, the identified characteristics of the listings suggest that the rental of these terraces and rooftops might impact on the daily life of the residents.

Research limitations/implications

This study has only examined the offer of P2P terraces and rooftops in Barcelona. Further studies should also take into account how this business model affects other cities, and how it impacts on residents.

Social implications

The conducted analysis highlights the importance of a proactive regulation of this new P2P phenomenon that anticipates the potential socials costs on the daily life of residents.

Originality/value

The rental of terraces and rooftops in a P2P fashion is a novel phenomenon and, consequently, it has not been previously studied from an academic point of view.
Widened Price-Limits and Efficiency of Price Discovery over the Course of a Trading Day
Authors: Seon Junghoon
Published: September 2020

Korea Exchange has widen daily price limits from ±15% to ±30% of previous trading day’s closing price since June 15, 2015. In this paper, we examine how the event of widening price limits affect price discovery process over the course of trading day. In order to conduct this investigation, we compare price efficiency during such price discovery before and after the event. The changes that has occurred after the event can be summarized as follows: First, an analysis on full-sample indicates that price efficiency is maintained over the course of a trading, while it is aggravated temporary in two early intervals. Second, an analysis on sub-samples sorted by market capitalization, shares outstanding, or share price indicates that temporary aggravation of price efficiency in some mid-intervals is observed for shares outstanding lower group and share price top group. Overall, our results suggest that evidence supporting information hypothesis is found for the whole process of price discovery over the course of a trading day, though evidence supporting over-reaction hypothesis is found in some intervals or some types of stocks.