bluuebunny/crossref_metadata_2025 huggingface dataset:
KSTAR: An algorithm to predict patient-specific kinase activities from phosphoproteomic data
Authors: Crowl Sam , Jordan Benjamin , Ahmed Hamza , Ma Cynthia , Naegle Kristen M.
Published: July 2021

Kinase inhibitors are one of the largest classes of FDA-approved drugs and are major targets in oncology. Although kinase inhibitors have played an important role in improving cancer outcomes, major challenges still exist, including the development of resistance and failure to respond to treatments. Improvements for tumor profiling of kinase activity would be an important step in improving treatment outcomes and identifying effective kinase targets. Here, we present a graph- and statistics-based algorithm, called KSTAR, which harnesses the phosphoproteomic profiling of human cells and tissues by predicting kinase activity profiles from the observed phosphorylation of kinase substrates. The algorithm is based on the hypothesis that the more active a kinase is, the more of its substrates will be observed in a phosphoproteomic experiment. This method is error- and bias-aware in its approach, overcoming challenges presented by the variability of phosphoproteomic pipelines, limited information about kinase-substrate relationships, and limitations of global kinase-substrate predictions, such as training set bias and high overlap between predicted kinase networks. We demonstrate that the predicted kinase activities: 1) reproduce physiologically-relevant expectations and generates novel hypotheses within cell-specific experiments, 2) improve the ability to compare phosphoproteomic samples on the same tissues from different labs, and 3) identify tissue-specific kinase profiles. Global benchmarking and comparison to other algorithms demonstrates that KSTAR is particularly superior for predicting tyrosine kinase activities and, given its focus on utilizing more of the available phosphoproteomic data, significantly less sensitive to study bias. Finally, we apply the approach to complex human tissue biopsies in breast cancer, where we find that KSTAR activity predictions complement current clinical standards for identifying HER2-status – KSTAR can identify clinical false positives, patients who will fail to respond to inhibitor therapy, and clinically defined HER2-negative patients that might benefit from HER2-targeted therapy. KSTAR will be useful for both basic biological understanding of signaling networks and for improving clinical outcomes through improved clinical trial design, identification of new and/or combination therapies, and for identifying the failure to respond to targeted kinase therapies.
Straintables: An application that extracts sequences from genome assemblies and generates dissimilarity matrices
Authors: Araujo Gabriel Nogueira , Francis Richard W , Ferreira Cristina dos Santos , Rangel Alba Lucínia Peixoto
Published: July 2021

Background and Objectives

The dissimilarity matrix (DM) is an important component of phylogenetic analysis, and many software packages exist to build and show DMs. However, as the common input for this type of software are sequences in FASTA file format, the process of extracting and aligning each set of sequences to produce a big number of matrices can be laborious. Additionally, existing software do not facilitate the comparison of clusters of similarity across several DMs built for the same group of individuals, using different genomic regions. To address our requirements of such a tool, we designed Straintables to extract specific genomic region sequences from a group of intraspecies genomic assemblies, using extracted sequences to build dissimilarity matrices.

Methods

A Python module with executable scripts was developed for a study on genetic diversity across strains of Toxoplasma gondii, being a general purpose system for DM calculation and visualization for preliminary phylogenetic studies. For automatic region sequence extraction from genomic assemblies we assembled a system that designs virtual primers using reference sequences located at genomic annotations, then matches those primers on genome files by using regex patterns. Extracted sequences are then aligned using Clustal Omega and compared to generate matrices.

Results

Using this software saves the user from manual preparation and alignment of the sequences, a process that can be laborious when a large number of assemblies or regions are involved. The automatic sequence extraction process can be checked against BLAST results using extracted sequence as queries, where correct results were observed for same-species pools for various organisms. The package also contains a matrix visualization tool focused on cluster visualization, capable of drawing matrices into image files with custom settings, and features methods of reordering matrices to facilitate the comparison of clustering patterns across two or more matrices.

Conclusion

Straintables may replace and extend the functionality of existing matrix-oriented phylogenetic software, featuring automatic region extraction from genomic assemblies and enhanced matrix visualization capabilities emphasizing cluster identification. This module is open source, available at GitHub (https://github.com/Gab0/straintables) under a MIT license and also as a PIPY package.

Highlights

Simple in-silico protocol for generation, visualization and comparison of dissimilarity matrices.

Accurate automatic sequence extraction from multiple genomic assemblies by using virtual primers built from reference sequences in an annotation file.

Draws matrices as images, with enhanced cluster visualization and customized options.

Supports reordering of matrix indices to better visualize clustering pattern conservation across multiple regions.
Harmonic Passive Motion Paradigm
Authors: Tiseo Carlo , Charitos Sydney Rebecca , Mistry Michael
Published: July 2021

How humans robustly interact with external dynamics is not yet fully understood. This work presents a hierarchical architecture of semi-autonomous controllers that can control the redundant kinematics of the limbs during dynamic interaction, even with delays comparable to the nervous system. The postural optimisation is performed via a non-linear mapping of the system kineto-static properties, and it allows independent control of the end-effector trajectories and the arms stiffness. The proposed architecture is tested in a physical simulator in the absence of gravity, presence of gravity, and with gravity plus a viscous force field. The data indicate that the architecture can generalise motor strategies to different environmental conditions. The experiments also verify the existence of a deterministic solution to the task-separation principle. The architecture is also compatible with Optimal Feedback Control and the Passive Motion Paradigm. The existence of a deterministic mapping implies that this task could be encoded in neural networks capable of generalisation of motion strategies to affine tasks.
Rapid extraction and kinetic analysis of protein complexes from single cells
Authors: Sarıkaya Sena , Dickinson Daniel J.
Published: July 2021

Proteins contribute to cell biology by forming dynamic, regulated interactions, and measuring these interactions is a foundational approach in biochemistry. We present a rapid, quantitativein vivoassay for protein-protein interactions, based on optical cell lysis followed by time-resolved single-molecule analysis of protein complex binding to an antibody-coated substrate. We show that our approach has better reproducibility, higher dynamic range, and lower background than previous single-molecule pull-down assays. Furthermore, we demonstrate that by monitoring cellular protein complexes over time after cell lysis, we can measure the dissociation rate constant of a cellular protein complex, providing information about binding affinity and kinetics. Our dynamic single-cell, single-molecule pull-down method thus approaches the biochemical precision that is often sought fromin vitroassays, while being applicable to native protein complexes isolated from single cellsin vivo.
ArabidopsisTopless-related 1 mitigates physiological damage and growth penalties of induced immunity
Authors: Griebel Thomas , Lapin Dmitry , Locci Federica , Kracher Barbara , Bautor Jaqueline , Qiu Jingde , Concia Lorenzo , Benhamed Moussa , Parker Jane E.
Published: July 2021

Transcriptional corepressors of the Topless family are important regulators of plant hormone and immunity signaling. The lack of a genome-wide profile of their chromatin associations limits understanding of transcriptional regulation in plant immune responses. Chromatin immunoprecipitation with sequencing (ChIP-seq) was performed on GFP-tagged Topless-related 1 (TPR1) expressed inArabidopsis thalianalines with and without constitutive immunity dependent onEnhanced Disease Susceptibility 1(EDS1). RNA-seq profiling of pathogen-infectedtpl/tprmutants and assessments of growth and physiological parameters were employed to determine TPL/TPR roles in transcriptional immunity and defense homeostasis. TPR1 bound to promoter regions of ~1,400 genes and ~10% of the detected binding requiredEDS1immunity signaling. Atpr1 tpl tpr4(t3) mutant displayed mildly enhanced defense-related transcriptional reprogramming upon bacterial infection but not increased bacterial resistance. Bacteria or pep1 phytocytokine-challengedt3plants exhibited, respectively, photosystem II dysfunction and exacerbated root growth inhibition. Transgenic expression ofTPR1restored thet3physiological defects. We propose that TPR1 and TPL-family proteins function inArabidopsisto reduce detrimental effects associated with activated transcriptional immunity.
Structural-functional connectivity mapping of the insular cortex: A combined data-driven and meta-analytic topic mapping
Authors: Klugah-Brown Benjamin , Wang Pan , Jiang Yuan , Becker Benjamin , Hu Peng , Uddin Lucina Q. , Biswal Bharat
Published: July 2021

In this study, we examined structural and functional profiles of the insular cortex and mapped associations with well-described functional networks (FNs) throughout the brain using diffusion tensor imaging (DTI) and resting-state functional connectivity (RSFC) data. We used a data-driven method to independently estimate the structural-functional connectivity of the insular cortex. Data were obtained from the Human Connectome Project comprising 108 adult participants. Overall, we observed moderate to high associations between the structural and functional mapping scores of three different insular subregions: the posterior insula (associated with the sensorimotor network: RSFC, DTI = 50% and 72%, respectively), dorsal anterior insula (associated with ventral attention: RSFC, DTI = 83% and 83%, respectively), and ventral anterior insula (associated with the frontoparietal: RSFC, DTI = 42% and 89%, respectively). Further analyses utilized meta-analytic decoding maps to demonstrate specific cognitive and affective as well as gene expression profiles of the three subregions reflecting the core properties of the insular cortex. In summary, given the central role of the insular in the human brain, our results revealing correspondence between DTI and RSFC mappings provide a complementary approach and insight for clinical researchers to identify dysfunctional brain organization in various neurological disorders associated with insular pathology.
Feeding habits and the influence of pellet diameter on the feeding responses of the flathead grey mullet (Mugil cephalus) in captivity
Authors: Ramos-Júdez Sandra , Duncan Neil
Published: July 2021

The feeding habits and effect of the diameter of pelleted feeds on the feeding responses of wild juvenile and adult flathead grey mullet (Mugil cephalus) in captivity were examined. Optimal pellet size for feeding was defined according to the behavioural responses and ingestion of pellets with different diameters (2, 4, 6, 8 mm) that were dropped into the tank in a random sequence. Larger pellets (6 and 8 mm) were more attractive (lower reaction time, high percentage of capture), but the small to medium-sized pellets (2 and 4 mm) were consumed the most. The optimal size was the 2- and 4- mm pellet diameter for juvenile individuals (365.50 ± 36.90 g; 28.8 ± 0.84 cm) and the 4-mm diameter pellet for adults (937.49 ± 146.54 g; 40 ± 1.12 cm). The preferred feeding area of adult mullet was also studied to estimate preference in relation to pellet characteristics such as floating or sink. Two pellet types, floating or sinking, were offered simultaneously in the water column: at the surface, mid-water column and bottom of the tank. The flathead grey mullet had a preference to feed in the mid-water column and the bottom of the tanks indicating that sinking or slow-sinking pellets would be the optimal feed type in relation to mullet feeding behaviour.
Virtual meetings promise to eliminate the geographical and administrative barriers and increase accessibility, diversity, and inclusivity
Authors: Wu Juncheng , Rajesh Anushka , Huang Yu-Ning , Chhugani Karishma , Acharya Rajesh , Peng Kerui , Johnson Ruth D. , Fiscutean Andrada , Robles-Espinoza Carla Daniela , De La Vega Francisco M. , Bao Riyue , Mangul Serghei
Published: July 2021

The COVID-19 pandemic brought a new set of unprecedented challenges not only for healthcare, education, and everyday jobs but also in terms of academic conferences. In this study, we investigate the effect of the broad adoption of virtual platforms for academic conferences as a response to COVID-19 restrictions. We show that virtual platforms enable higher participation from underrepresented minority groups, increased inclusion, and broader geographic distribution. We also discuss emerging challenges associated with the virtual conference format resulting in a decreased engagement of social activities, limited possibilities of cross-fertilization between participants, and reduced peer-to-peer interactions. Lastly, we conclude that a novel comprehensive approach needs to be adopted by the conference organizers to ensure increased accessibility, diversity, and inclusivity of post-pandemic conferences. Our findings provide evidence favoring a hybrid format for future conferences, marrying the strength of both in-person and virtual platforms.
Genome binning of viral entities from bulk metagenomics data
Authors: Johansen Joachim , Plichta Damian , Nissen Jakob Nybo , Jespersen Marie Louise , Shah Shiraz A. , Deng Ling , Stokholm Jakob , Bisgaard Hans , Nielsen Dennis Sandris , Sørensen Søren , Rasmussen Simon
Published: July 2021

Despite the accelerating number of uncultivated virus sequences discovered in metagenomics and their apparent importance for health and disease, the human gut virome and its interactions with bacteria in the gastrointestinal are not well understood. In addition, a paucity of whole-virome datasets from subjects with gastrointestinal diseases is preventing a deeper understanding of the virome’s role in disease and in gastrointestinal ecology as a whole. By combining a deep-learning based metagenomics binning algorithm with paired metagenome and metavirome datasets we developed the Phages from Metagenomics Binning (PHAMB) approach for binning thousands of viral genomes directly from bulk metagenomics data. Simultaneously our methodology enables clustering of viral genomes into accurate taxonomic viral populations. We applied this methodology on the Human Microbiome Project 2 (HMP2) cohort and recovered 6,077 HQ genomes from 1,024 viral populations and explored viral-host interactions. We show that binning can be advantageously applied to existing and future metagenomes to illuminate viral ecological dynamics with other microbiome constituents.
The smooth transition from many-legged to bipedal locomotion - Gradual ground force reduction and its impact on total ground reaction forces, body dynamics and gait transitions
Authors: Weihmann Tom
Published: July 2021

Most terrestrial animals move with a specific number of propulsive legs, which differs between clades. The reasons for these differences are often unknown and rarely queried, despite the underlying mechanisms being indispensable for understanding the evolution of multilegged locomotor systems in the animal kingdom and the development of swiftly moving robots. Moreover, when speeding up, a range of species change their number of propulsive legs. The reasons for this behaviour have proven equally elusive. In animals and robots, the number of propulsive legs also has a decisive impact on the movement dynamics of the centre of mass. Here, I use the leg force interference model to elucidate these issues by introducing gradually declining ground reaction forces in locomotor apparatuses with varying numbers of leg pairs in a first numeric approach dealing with these measures’ impact on locomotion dynamics. The effects caused by the examined changes in ground reaction forces and timing thereof follow a continuum. However, the transition from quadrupedal to a bipedal locomotor system deviates from those between multilegged systems with different numbers of leg pairs. Only in quadrupeds do reduced ground reaction forces beneath one leg pair result in increased reliability of vertical body oscillations and therefore increased energy efficiency and dynamic stability of locomotion.

Significance statement

The model grants access to the effects of gradual ground force reduction on total ground reaction forces, body dynamics and gait transitions.
Adult medial habenula neurons require GDNF receptor GFRα1 for synaptic stability and function
Authors: Fernández-Suárez Diana , Krapacher Favio A. , Pietrajtis Katarzyna , Andersson Annika , Kisiswa Lilian , Diana Marco A. , Ibáñez Carlos F.
Published: July 2021

The medial habenula (mHb) is an understudied small brain nucleus linking forebrain and midbrain structures controlling anxiety and fear behaviors. The mechanisms that maintain the structural and functional integrity of mHb neurons and their synapses remain unknown. Using spatio-temporally controlled Cre-mediated recombination in adult mice, we found that the GDNF receptor alpha 1 (GFRα1) is required in adult mHb neurons for synaptic stability and function. mHb neurons express some of the highest levels of GFRα1 in the mouse brain, and acute ablation of GFRα1 results in loss of septo-habenular and habenulo-interpeduncular glutamatergic synapses, with the remaining synapses displaying reduced numbers of presynaptic vesicles. Chemo- and opto-genetic studies in mice lacking GFRα1 revealed impaired circuit connectivity, reduced AMPA receptor postsynaptic currents, and abnormally low rectification index of AMPARs, suggesting reduced Ca2+-permeability. Further biochemical and proximity ligation assay studies defined the presence of GluA1/GluA2 (Ca2+-impermeable) as well as GluA1/GluA4 (Ca2+-permeable) AMPAR complexes in mHb neurons, as well as clear differences in the levels and association of AMPAR subunits in mHb neurons lacking GFRα1. Finally, acute loss of GFRα1 in adult mHb neurons reduced anxiety-like behavior and potentiated context-based fear responses, phenocopying the effects of lesions to septal projections to the mHb. These results uncover an unexpected function for GFRα1 in the maintenance and function of adult glutamatergic synapses, and reveal a potential new mechanism for regulating synaptic plasticity in the septo-habenulo-interpeduncular pathway and attuning of anxiety and fear behaviors.
Characterization of the radiation desiccation response regulon of the radioresistant bacterium Deinococcus radiodurans by integrative genomic analyses
Authors: Eugénie Nicolas , Zivanovic Yvan , Lelandais Gaelle , Coste Geneviève , de la Tour Claire Bouthier , Bentchikou Esma , Servant Pascale , Confalonieri Fabrice
Published: July 2021

Numerous genes are overexpressed in the radioresistant bacterium Deinococcus radiodurans after exposure to radiation or prolonged desiccation. The DdrO and IrrE proteins play a major role in regulating the expression of approximately predicted twenty of these genes. The transcriptional repressor DdrO blocks the expression of these genes under normal growth conditions. After exposure to genotoxic agents, the IrrE metalloprotease cleaves DdrO and relieves gene repression. Bioinformatic analyzes showed that this mechanism seems to be conserved in several species of Deinococcus, but many questions remain as such the number of genes regulated by DdrO. Here, by RNA-seq and CHiP-seq assays performed at a genome-wide scale coupled with bioinformatic analyses, we show that, the DdrO regulon in D. radiodurans includes many other genes than those previously described. These results thus pave the way to better understand the radioresistance mechanisms encoded by this bacterium.

Author Summary

The main response pathway to genotoxic conditions in the radioresistant bacterium Deinococcus radiodurans is regulated by the constitutively expressed metalloprotease IrrE that cleaves the transcriptional repressor DdrO, leading to the expression of the genes repressed by DdrO. One of the major goals to better understand how pathways involved in radioresistance are coordinated into this fascinating bacterium is to highlight genes regulated by DdrO. In this study, we mapped in vivo the DdrO regulon in D. radiodurans by using two genome-scale approaches, ChIP-seq and RNA-seq analyses, coupled with bioinformatic analyses. As homologs of these two proteins are also found in many other bacteria, these results also pave the way to compare the stress-induced responses mediated by this couple of proteins in diverse bacteria.
All driven by energy demand? Integrative comparison of metabolism ofEnterococcus faecaliswildtype and a glutamine synthase mutant
Authors: Loghmani Seyed Babak , Zitzow Eric , Koh Gene Ching-Chiek , Ulmer Andreas , Veith Nadine , Großeholz Ruth , Rossnagel Madlen , Loesch Maren , Aebersold Ruedi , Kreikemeyer Bernd , Fiedler Tomas , Kummer Ursula
Published: July 2021

Lactic acid bacteria (LAB) play a significant role in biotechnology, e.g. food industry, but also in human health. Many LAB genera have developed a multidrug resistance in the past few years, becoming a serious problem in controlling hospital germs all around the world.Enterococcus faecalisaccounts for a large part of the human infections caused by LABs. Therefore, studying its adaptive metabolism under various environmental conditions is particularly important. In this study, we investigated the effect of glutamine auxotrophy (ΔglnAmutant) on metabolic and proteomic adaptations ofE. faecalisin response to a changing pH in its environment. Changing pH values are part of its natural environment in the human body, but also play a role in food industry. We compared the results to those of the wildtype. Our integrative method, using a genome-scale metabolic model, constrained by metabolic and proteomic data allows us to understand the bigger picture of adaptation strategies in this bacterium. The study showed that energy demand is the decisive factor in adapting to a new environmental pH. The energy demand of the mutant was higher at all conditions. It has been reported that ΔglnAmutants of bacteria are energetically less effective. With the aid of our data and model we are able to explain this phenomenon as a consequence of a failure to regulate glutamine uptake and the costs for the import of glutamine and the export of ammonium. Methodologically, it became apparent that taking into account the non-specificity of amino acid transporters is important for reproducing metabolic changes with genome-scale models since it affects energy balance.
A DEEP LEARNING APPROACH TO ESTIMATING INITIAL CONDITIONS OF BRAIN NETWORK MODELS IN REFERENCE TO MEASURED FMRI DATA
Authors: Kashyap Amrit , Plis Sergey , Schirner Michael , Ritter Petra , Keilholz Shella
Published: July 2021

1.

Brain Network Models (BNMs) are a family of dynamical systems that simulate whole brain activity using neural mass models to represent local activity in different brain regions that influence each other via a global structural network. Research has been interested in using these network models to explain measured whole brain activity measured via resting state functional magnetic resonance imaging (rs-fMRI). Properties computed over longer periods of simulated and measured data such as average functional connectivity (FC), have shown to be comparable with similar properties estimated from measured rs-fMRI data. While this shows that these network models have similar properties over the dynamical landscape, it is unclear how well simulated trajectories compare with empirical trajectories on a timepoint-by-timepoint basis. Previous studies have shown that BNMs are able to produce relevant features at shorter timescales, but analysis of short-term trajectories or transient dynamics as defined by synchronized predictions from BNM made at the same timescale as the collected data has not yet been conducted. Relevant neural processes exist in the time frame of measurements and are often used in task fMRI studies to understand neural responses to behavioral cues. Therefore, it is important to investigate how much of these dynamics are captured by our current brain simulations. To test the nature of BNMs short term trajectories against observed data, we utilize a deep learning technique known as Neural ODE that based on an observed sequence of fMRI measurements, estimates the initial conditions such that the BNM’s simulation is synchronized to produce the closest trajectory relative to the observed data. We test to see if the parameterization of a specific well studied BNM, the Firing Rate Model, calculated by maximizing its accuracy in reproducing observed short term trajectories matches with the parameterized model that produces the best average long-term metrics. Our results show that such an agreement between parameterization using long and short simulation analysis exists if also considering other factors such as the sensitivity in accuracy with relative to changes in structural connectivity. Therefore, we conclude that there is evidence that by solving for initial conditions, BNMs can be simulated in a meaningful way when comparing against measured data trajectories, although future studies are necessary to establish how BNM activity relate to behavioral variables or to faster neural processes during this time period.
H3K9me2 genome-wide distribution in the holocentric insect Spodoptera frugiperda (Lepidoptera: Noctuidae)
Authors: Nhim Sandra , Gimenez Sylvie , Nait-Saidi Rima , Severac Dany , Nam Kiwoong , d’Alençon Emmanuelle , Nègre Nicolas
Published: July 2021

Background

Eukaryotic genomes are packaged by Histone proteins in a structure called chromatin. There are different chromatin types. Euchromatin is typically associated with decondensed, transcriptionally active regions and heterochromatin to more condensed regions of the chromosomes. Methylation of Lysine 9 of Histone H3 (H3K9me) is a conserved biochemical marker of heterochromatin. In many organisms, heterochromatin is usually localized at telomeric as well as pericentromeric regions but can also be found at interstitial chromosomal loci. This distribution may vary in different species depending on their general chromosomal organization. Holocentric species such as Spodoptera frugiperda (Lepidoptera: Noctuidae) possess dispersed centromeres instead of a monocentric one and thus no observable pericentromeric compartment. To identify the localization of heterochromatin in such species we performed ChIP-Seq experiments and analyzed the distribution of the heterochromatin marker H3K9me2 in the Sf9 cell line and whole 4th instar larvae (L4) in relation to RNA-Seq data.

Results

In both samples we measured an enrichment of H3K9me2 at the (sub) telomeres, rDNA loci, and satellite DNA sequences, which could represent dispersed centromeric regions. We also observed that density of H3K9me2 is positively correlated with transposable elements and protein-coding genes. But contrary to most model organisms, H3K9me2 density is not correlated with transcriptional repression.

Conclusion

This is the first genome-wide ChIP-Seq analysis conducted in S. frugiperda for H3K9me2. Compared to model organisms, this mark is found in expected chromosomal compartments such as rDNA and telomeres. However, it is also localized at numerous dispersed regions, instead of the well described large pericentromeric domains, indicating that H3K9me2 might not represent a classical heterochromatin marker in Lepidoptera.
SufB intein splicing inMycobacterium tuberculosisis influenced by two remote conserved N-extein Histidines
Authors: Panda Sunita , Nanda Ananya , Sahu Nilanjan , Ojha Deepak , Pradhan Biswaranjan , Rai Anjali , Suryawanshi Amol R. , Banavali Nilesh , Nayak Sasmita
Published: July 2021

Inteins are auto-processing domains that implement a multi-step biochemical reaction termed protein splicing, marked by cleavage and formation of peptide bonds. They excise from a precursor protein, generating a functional protein via covalent bonding of flanking exteins. We report the kinetic study of splicing and cleavage reaction in [Fe-S] cluster assembly protein SufB fromMycobacterium tuberculosis. Although it follows a canonical intein splicing pathway, distinct features are added by extein residues present in the active site. Sequence analysis identified two conserved histidines in the N-extein region; His-5 and His-38. Kinetic analyses of His-5Ala and His-38Ala SufB mutants exhibited significant reductions in splicing and cleavage rates relative to the SufB wild-type precursor protein. Structural analysis and molecular dynamics simulations suggested thatMtuSufB displays a unique mechanism where two remote histidines work concurrently to facilitate N-terminal cleavage reaction. His-38 is stabilized by the solvent-exposed His-5, and can impact N-S acyl shift by direct interaction with the catalytic Cys1. Development of inteins as biotechnological tools or as pathogen specific novel antimicrobial targets requires a more complete understanding of such unexpected roles of conserved extein residues in protein splicing.
Spatially resolved transcriptomics reveals unique gene signatures associated with human temporal cortical architecture and Alzheimer’s pathology
Authors: Chen Shuo , Chang Yuzhou , Li Liangping , Acosta Diana , Morrison Cody , Wang Cankun , Julian Dominic , Hester Mark E. , Serrano Geidy E. , Beach Thomas G. , Ma Qin , Fu Hongjun
Published: July 2021

Alzheimer’s disease (AD) is pathologically characterized by amyloid beta (Aβ) plaques, neurofibrillary tangles (tau aggregates), and alterations in microglia, astrocytes and oligodendrocytes. The mesial temporal lobe is a vulnerable brain region in early AD; however, little is known about the transcriptome-scale gene expression in this region and its relation to AD pathology. Here we use the 10x Genomics Visium platform in combination with co-immunofluorescence staining of AD-associated pathological markers to define the spatial topography of gene expression in the middle temporal gyrus (MTG) from both early AD and age- and gender-matched control cases. We identify unique marker genes for six cortical layers and the adjacent white matter as well as gene expression patterns and alterations that showcase unique gene signatures and pathways associated with a range of AD pathology. Also, gene co-expression analyses of differentially expressed genes (DEGs) between AD and controls reveal four unique gene modules, which significantly change their co-expression patterns in the presence of variations of AD pathology. Furthermore, we validate the changes of key representative DEGs that are associated with AD pathology in neurons, microglia, astrocytes and oligodendrocytes using single-molecule fluorescent in situ hybridization. In summary, we provide a rich resource for the spatial transcriptomic profile of the human MTG, which will contribute to our understanding of the complex architecture and AD pathology of this vulnerable brain region.
Calpains are required for efficient microtubule detyrosination
Authors: Bär Julia , Popp Yannes , Koudelka Tomas , Tholey Andreas , Mikhaylova Marina
Published: July 2021

Detyrosination is a major post-translational modification of microtubules (MT), which has significant impact on MT function in cell division, differentiation, growth, migration, polarity, and intracellular trafficking. Detyrosination of α-tubulin occurs via the recently identified complex of vasohibin 1/2 (vash1/2) and small vasohibin binding protein (SVBP). However, there is still remaining detyrosinating activity in the absence of vash1/2/SVBP, and little is known about the regulation of detyrosination. Using cellular and cell-free assays we showed that the calcium-dependent proteases calpains 1 and 2 regulate MT detyrosination. We identified new calpain cleavage sites in the N-terminal disordered region of vash1 using in vitro proteolysis followed by mass spectrometry. However, this cleavage did not affect the detyrosination activity of vasohibin. In conclusion, the regulation of MT detyrosination by calpains occurs via another yet unknown tubulin carboxypeptidase. Importantly, calpains’ calcium dependency could allow a fine regulation of MT detyrosination. Thus, identifying the calpain-regulated pathway of MT detyrosination can be of major importance for several basic and clinical research and should be focused on in future studies.

Summary Statement

The conventional calpains 1 and 2 play an important role in the regulation of microtubule detyrosination in a vasohibin independent way. Thus, they possibly control another still unknown tubulin carboxypeptidase.
Transverse bunch-by-bunch feedback system for time-resolved experiments at PLS-II
Authors: Lee Jaeyu , Nakamura T. , Kobayashi K. , Kim D.-T. , Ha T. , Hahn G.-R. , Kim K.-J. , Shin S.
Published: July 2021

A description of the upgraded bunch-by-bunch feedback system for time-resolved experiments at Pohang Light Source II (PLS-II) is provided. The bunch-by-bunch feedback system has been upgraded to increase the single-bunch current in the hybrid fill pattern of the PLS-II facility. The project is part of the SPring-8 and PLS-II collaboration. The main features of the upgrade are to employ a single 500 MHz analog-to-digital converter (ADC) instead of the previous four 125 MHz interleaved ADCs for 500 MHz rate, to replace a single-loop two-dimensional feedback with two independent one-dimensional feedback loops, to implement the tune measurement function with a single bunch, and mainly to implement single-bunch and stretcher control. The realization of a 400 mA hybrid fill pattern including a 10 mA single bunch demonstrates the precision of the upgraded bunch-by-bunch feedback system.
Theoretical model proposal on direct calculation of wetted area and maximum lift-to-drag ratio
Authors: Durmus Seyhun
Published: July 2021

Purpose

As measuring flight performance by experimental methods requires a lot of effort and cost, theoretical models can bring new perspectives to aircraft design. This paper aims to propose a model on the direct calculation of wetted area and L/Dmax.

Design/methodology/approach

Model is based on idea that the wetted area is proportional to aircraft gross weight to the power of 2/3 (Wg2/3). Aerodynamic underpinning of this method is based on the square–cube law and the claim that parasitic drag is related to the Swet/Swing. The equation proposed by Raymer was used to find the L/Dmax estimate based on the calculated wetted area. The accuracy of the theoretical approach was measured by comparing the L/Dmax values found in the reference literature and the L/Dmax values predicted by the theoretical approach.

Findings

Proposed theoretical L/Dmax estimate matches with the actual L/Dmax data in different types of aircraft. Among the conventional tube-wing design, only the sailplanes have a very low Swet/Swing. The Swet/Swing of flying wings, blended wing bodies (BWBs) and large delta wings are lower than conventional tube-wing design. Lower relative wetted area (Swet/Swing) is the key design criterion in high L/Dmax targeted designs.

Originality/value

The proposed model could be used in wing sizing according to the targeted L/Dmax value in aircraft design. The approach can be used to estimate the effect of varying gross weight on L/Dmax. In addition, the model contributes to the L/Dmax estimation of unusual designs, such as variable-sweep wing, large delta wings, flying wings and BWBs. This study is valuable in that it reveals that L/Dmax value can be predicted only with aspect ratio, gross weight (Wg) and wing area (Swing) data.
Parental perspectives on support needs and availability of autism services in South and South-Eastern Europe
Authors: Vasilevska Petrovska Ivana , Giannakopoulou Anastasia C. , Tsecoura Vassiliki , Winstanley Angela , Miletto Roberto , Roşca Georgeta Constanţa , Ivanova Biserka , Kaisa Vasiliki , Trajkovski Vladimir
Published: July 2021

Purpose

Amid the expanding demand on the autism service delivery system, little knowledge is accumulated regarding access and availability of support and services in the region of Southern and South-Eastern Europe – critical for improvement of individual outcomes, as well as family quality of life. The purpose of this paper is to explore how service delivery systems are responding to the specific needs of autistic individuals with autism, as perceived by parents.

Design/methodology/approach

A qualitative exploratory descriptive method was used. Thematic analysis was used as a pragmatic method to report on the experiences of parents (92% mothers, n = 55) of children, youth and young autistic adults (76% male) across six South and South-Eastern European counties that participated in a survey involving a combination of qualitative and quantitative data collection.

Findings

Thematic analysis revealed three broad themes: challenging pathways to service utilization, insufficient service options and providers’ competences and lack of continuous and meaningful support across life span.

Originality/value

The findings from this study add to the small body of literature specific to South and South-Eastern Europe, by exposing problems related to meeting the needs of autistic children and youth and potential ways to strengthen services, as perceived by parents. The findings have potential policy ramifications for the region in which the research was conducted.
Why customers have the intention to reuse food delivery apps: evidence from China
Authors: Bao Zheshi , Zhu Yun
Published: July 2021

Purpose

Food delivery apps (FDA) have been widely adopted by customers in online-to-offline (O2O) catering businesses. This study aims to explore the mechanism regarding the stickiness of FDA and indicates why customers have the intention to reuse them.

Design/methodology/approach

A research model was developed based on the e-commerce system successful model (ECSS model) and social influence theory. Using the data collected from 312 customers who have FDA usage experience via an online survey, the established model was empirically assessed by partial least squares based structural equation model.

Findings

The results show that factors including information quality, ease of use, convenience and various choices perceived by FDA users are significant antecedents of customer satisfaction and perceived value, which in turn positively influence customers' intention to reuse. Besides, informational social influence and normative social influence play important roles in directly or indirectly affecting customers' intention to reuse.

Originality/value

This study extends the e-commerce system success model and enriches the literature regarding stickiness of FDA. Besides, the understanding of social influence in FDA usage has been deepened by addressing its role in the ECSS model based on the features and contexts of such apps.
Wecyclers roll out: Bilikiss Adebiyi-Abiola
Authors: Nwagwu Ijeoma Dhalia , Atanya Oreva , Onuzo Ngozi
Published: July 2021

Study level/applicability

This case is appropriate for the following courses in undergraduate, graduate or executive programs.

Subject area

Sustainability, strategy, inclusive business, environmental sustainability and women in leadership. Upon completion of the case study discussion successful students will be able to:

Case overview

Bilikiss Adebiyi-Abiola brought to life Wecyclers, an urban waste management company in Nigeria that started as an idea during her MBA programme at MIT. Bilikiss served as its CEO from 2012 and mobilized efforts to sign up thousands of individuals, corporate bodies and agents who turn in waste to recycle. While waste management already had a lot of private sector participants (PSPs), there was no recycling company with a focus on community engagement as at the time Wecyclers came on board. The company went through several iterations to arrive at business model, develop its peculiar infrastructure, build partnerships and raise funds. The case study documents Wecyclers roll-out under the leadership of Bilikiss, whose work with Wecyclers has been shaped by her evolution as a professional woman with a background, education and network that has enabled her excel in the face of social norms which emphasize men as leaders. The case dilemma involves strategy cross-roads Bilikiss faced in mid-2017 as Wecyclers considered expanding its operation, pushed beyond waste collection, pushed by infrastructural weaknesses in the landscape which forced the company to consider vertical integration of its inclusive business model as a way forward to meaningfully serving its stakeholders – from communities, corporates to agents.

Expected learning outcomes

• Explore the strategic contexts of doing business in emerging markets;• understand the challenges and opportunities in inclusive business model for solving a social problem such as waste management; and • Examine the growth and evolution of women’s leadership, possibilities and hurdles, in a range of contexts.

Supplementary materials

Teaching notes are available for educators only.

Social implications

In this way, the case study contributes to the limited body of knowledge about strategic and pragmatic facing social enterprises in emerging markets, including funding, community engagement, infrastructure, etc. It also gives us a view of inclusive business models and the evolution of women’s leadership.

Subject code

CSS 3: Entrepreneurship.
Discussing the potential of the institutional theory to leverage service-dominant logic advancements
Authors: Gonçalves Sara Martins , Silva Rui Vinhas
Published: July 2021

Purpose

Institutions play a central role in service-dominant logic. However, the discussion regarding how institutional theory supports service-dominant logic advancements is still insufficient. This paper aims to contribute to a discussion on the multiple service-dominant logic approaches to institutions.

Design/methodology/approach

This conceptual paper presents the characterization of the existing streams in the broad institutional literature, highlighting the differences among those streams and elaborates on how one of the discussed streams – neo-institutionalism – is suitable to support service-dominant researchers in understanding the role of institutions in markets and value co-creation.

Findings

The paper shows that the three institutional perspectives presented are used indistinctly by service-dominant logic and a greater fit between the service-dominant logic and the neo-institutionalism stands out.

Originality/value

The paper proposes that service-dominant researchers should look at the neo-institutional stream as a particularly fertile ground for furthering their research.
Exploring conflicts between stakeholders in tourism industry. Citizen attitude toward peer-to-peer accommodation platforms
Authors: Martín Martín José María , Prados-Castillo Juan F. , de Castro-Pardo Mónica , Jimenez Aguilera Juan De Dios
Published: July 2021

Purpose

The expansion of online platforms for renting tourist accommodations has given rise to a great deal of controversy in society. Likewise, the arrival of tourists in residential settings has led to a wide range of positive and negative impacts, resulting in conflicts between different stakeholders. The purpose of this paper is to analyze whether there is variation in the perception of the impacts associated with peer-to-peer accommodation platforms among different stakeholders? Additionally, it also seeks to investigate what kind of impacts generate the highest level of conflict among stakeholders?

Design/methodology/approach

Given the relative novelty of the problem, this paper proposes an exploratory study that sheds light on some of the main issues with the purpose of supporting further research in the future. The aim is to analyze which impacts are perceived as more positive or negative by each group and to create indexes of conflict for these groups regarding their perception of the impacts. This study is based on fieldwork carried out in April 2020, which consists of 600 online surveys of local residents in the city of Granada. This city, one of Spain’s main tourist spots, suffers the highest tourist pressure in the country.

Findings

The exploratory study suggests that the greatest consensus is generated in the assessment of economic impacts, either negative or positive. The greatest conflicts are related to the assessment of the effect of this activity on housing preservation. The group comprising accommodation owners of tourist flats is the one that shows a more dissenting opinion from the rest, confronting especially the group formed by citizens whose income depends on tourism.

Originality/value

There is a lack of studies on the perception of tourism impacts associated with online tourism rental platforms. This is the first study to analyze both, how the main stakeholders associated with this activity assess the different impacts derived from this form of tourist accommodation as a whole and the conflicts derived from such an assessment. An additional innovation is that the analysis investigates the potential fear of disease transmission caused by tourists. It would be interesting to continue this research by applying the same questionnaire in different environments, such as rural areas or societies with different structures from the one analyzed here. Likewise, future in-depth analysis of some of the conflicts is recommended so as to ascertain their origin.