bluuebunny/crossref_metadata_2025 huggingface dataset:
Lasting changes to circulating leukocytes in people with mild SARS-CoV-2 infections
Authors: Kennedy Allison E. , Cook Laura , Breznik Jessica A. , Cowbrough Braeden , Wallace Jessica G. , Huynh Angela , Smith James W , Son Kiho , Stacey Hannah , Ang Jann , McGeer Alison , Coleman Brenda L. , Larché Maggie , Larché Mark , Hambly Nathan , Nair Parameswaran , Ask Kjetil , Miller Matthew S. , Bramson Jonathan , Levings Megan K. , Nazy Ishac , Svenningsen Sarah , Mukherjee Manali , Bowdish Dawn M. E.
Published: September 2021

Survivors of severe SARS-CoV-2 infections frequently suffer from a range of post-infection sequelae. Whether survivors of mild or asymptomatic infections can expect any long-term health consequences is not yet known. Herein we investigated lasting changes to soluble inflammatory factors and cellular immune phenotype and function in individuals who had recovered from mild SARS-CoV-2 infections (n=22) compared to those that had recovered from other mild respiratory infections (n=11). Individuals who had mild SARS-CoV-2 infections had elevated levels of C-reactive protein 1-3 months after symptom onset, and changes in phenotype and function of circulating T cells that were not apparent in individuals 6-9 months post-symptom onset. Markers of monocyte activation and expression of adherence and chemokine receptors indicative of altered migratory capacity were also higher at 1-3 months post-infection in individuals who had mild SARS-CoV-2, but these were no longer elevated by 6-9 months post-infection. Perhaps most surprisingly, polyclonal activation of T cells was higher in individuals who had recently experienced a mild SARS-CoV-2 infection compared to individuals with other recent respiratory infections. These data are indicative of prolonged immune activation and systemic inflammation that persists for up to three months after mild or asymptomatic SARS-CoV-2 infections.
Simultaneous passive acoustic monitoring uncovers evidence of potentially overlooked temporal variation in an Amazonian bird community
Authors: Hopping W. Alexander , Sayers Christopher J. , Huaraca-Charca Noe Roger , Klinck Holger
Published: September 2021

The vocal activity and detectability of tropical birds are subject to high levels of temporal heterogeneity, but quantifying patterns of diel and day-to-day variation in complex systems is challenging with traditional point count methods. As a result, research concerning stochastic temporal effects on tropical avian assemblages is limited, typically offering only broad conclusions, e.g., overall activity is highest in the first few hours of the morning and some species are active at different times of the day. Passive acoustic monitoring introduces several advantages for studying temporal variation, particularly by enabling simultaneous and continuous data collection across adjacent sites. Here, we employed autonomous recording units to quantify temporal variation in avian vocal activity and observed species richness at an Amazonian reserve in Madre de Dios, Peru—a region featuring some of Earth’s richest, most complex avian assemblages. We manually annotated 18 dawn hour recordings, collected simultaneously from three separate days at the same six sites, which represent various microhabitats and avian community compositions. We documented significant and consistent temporal variation in avian vocal activity levels and observed species richness within the dawn hour and across days. We found that temporal effects were stronger for vocal activity than for observed species richness and that vocal activity patterns over the course of the dawn hour varied on a species-to-species basis. Our results indicate that overlooked temporal variation in Amazonian soundscapes may obfuscate the results of surveys that fail to sufficiently account for temporal variables with simultaneous monitoring. While manual analysis of large volumes of soundscape data remains challenging, such data should be collected as a supplement to traditional surveys whenever possible. Rapidly advancing research concerning the automated processing of acoustic data could lead to more efficient methods for reducing temporal bias and improving the calibration and accuracy of ornithological surveys in the tropics.
SARS-CoV-2 vaccines breakthrough infection hospitalizations after one dose in Libya: cohort study
Authors: Abdelhamid Mohamed Hadi Mohamed , Almsellati Iman A. , Annajar Badereddin B , Abdelhamid Alaa .H , Alemam Hafsa .A , Etikar Mohammed
Published: September 2021

SARS-CoV-2 infection is widely spread over people, from youth to the elderly. Vaccination against SARS-CoV-2 is an important preventive measurement to help end the SARS-CoV-2 pandemic. From 30 April to 15 July, we collected the number of people infected with SARS-COV-2 and the mortality rate from daily reports issued by the National Center for Disease Control of Libya (NCDC). Approximately 445000 doses have been administered in Libya since 10 April, and 5 thousand doses are now being administered during this period on a daily basis. To estimate the rate of breakthrough vaccine infection of the SARS-COV-2 in Libya. We found that one dose of the three different types of vaccines had decreased the virus transmission across people and mortality rate until 10 weeks after the first dose. This study highlights the dramatic success of the early months of the nation’s coronavirus vaccines rollout.
Transient dendritic cell activation diversifies the T cell response to acute infection
Authors: Hiam-Galvez Kamir J. , DeBarge Rachel , Lareau Caleb A. , Cho Nam Woo , Yee Jacqueline L. , Okholm Trine Line H. , Spitzer Matthew H.
Published: September 2021

The precise timing of T cell priming during infection remains unclear. Here, we mapped the cellular dynamics of all immune lineages during acute infection with Listeria monocytogenes (Lm). We identified highly transient DC activation 2 days post-infection that functions as a critical time window for priming effector T cells. Regulation of this transient state was mediated by DC extrinsic IFNγ provided by lymphocytes. Furthermore, antigen-specific T cells that arrive late to the site of priming and miss peak DC activation acquire only memory T cell fates. This temporal regulation of fate is recapitulated by CD8+ DCs ex vivo, suggesting that shifts in activation state of a single antigen presenting cell population alter T cell fates. These results uncover a novel mechanism for temporal regulation of T cell differentiation during a dynamic immune response to acute infection.

One-Sentence Summary

The immune system generates a balanced protective response through rapidly shifting activation states and recruitment of new cells into an ongoing inflammatory landscape.
Gene flow biases population genetic inference of recombination rate
Authors: Samuk K. , Noor M.A.F.
Published: September 2021

Accurate estimates of the rate of recombination are key to understanding a host of evolutionary processes as well as the evolution of recombination rate itself. Model-based population genetic methods that infer recombination rates from patterns of linkage disequilibrium (LD) in the genome have become a popular method to estimate rates of recombination. However, these LD-based methods make a variety of simplifying assumptions about the populations of interest that are often not met in natural populations. One such assumption is the absence of gene flow from other populations. Here, we use forward-time population genetic simulations of isolation-with-migration scenarios to explore how gene flow affects the accuracy of LD-based estimators of recombination rate. We find that moderate levels of gene flow can result in either the overestimation or underestimation of recombination rates by up to 20-50% depending on the timing of divergence. We also find that these biases can affect the detection of interpopulation differences in recombination rate, causing both false positive and false negatives depending on the scenario. We discuss future possibilities for mitigating these biases and recommend that investigators exercise caution and confirm that their study populations meet assumptions before deploying these methods.
Spatio-temporal, optogenetic control of gene expression in organoids
Authors: Legnini Ivano , Emmenegger Lisa , Zappulo Alessandra , Wurmus Ricardo , Martinez Anna Oliveras , Jara Cledi Cerda , Boltengagen Anastasiya , Hessler Talé , Mastrobuoni Guido , Rybak-Wolf Agnieszka , Kempa Stefan , Zinzen Robert , Woehler Andrew , Rajewsky Nikolaus
Published: September 2021

Organoids derived from stem cells become increasingly important to study human development and to model disease. However, methods are needed to control and study spatio-temporal patterns of gene expression in organoids. To this aim, we combined optogenetics and gene perturbation technologies to activate or knock-down RNA of target genes, at single-cell resolution and in programmable spatio-temporal patterns. To illustrate the usefulness of our approach, we locally activated Sonic Hedgehog (SHH) signaling in an organoid model for human neurodevelopment. High-resolution spatial transcriptomic and single-cell analyses showed that this local induction was sufficient to generate stereotypically patterned organoids in three dimensions and revealed new insights into SHH’s contribution to gene regulation in neurodevelopment.

With this study, we propose optogenetic perturbations in combination with spatial transcriptomics as a powerful technology to reprogram and study cell fates and tissue patterning in organoids.
Cytotoxic T-cell-based vaccine against SARS-CoV2: a hybrid immunoinformatic approach
Authors: Tîrziu Alexandru , Păunescu Virgil
Published: September 2021

This paper presents an alternative vaccination platform that provides long-term cellular immune protection mediated by cytotoxic T-cells. The immune response via cellular immunity creates superior resistance to viral mutations, which are currently the greatest threat to the global vaccination campaign. Furthermore, we also propose a safer, more facile and physiologically appropriate immunization method using either intra-nasal or oral administration. The underlying technology is an adaptation of synthetic long peptides (SLPs) previously used in cancer immunotherapy. SLPs comprising HLA class I and class II epitopes are used to stimulate antigen cross-presentation and canonical class II presentation by dendritic cells. The result is a cytotoxic T cell-mediated prompt and specific immune response against the virus-infected epithelia and a rapid and robust virus clearance. Peptides isolated from COVID-19 convalescent patients were screened for the best HLA population coverage and were tested for toxicity and allergenicity. 3D peptide folding followed by molecular docking studies provided positive results, suggesting a favourable antigen presentation.
Insight into Cross-Amyloid Interactions and Morphologies: Molecular Dynamics Simulations of Model Peptide Fragments of Amyloid-β (Aβ16-22) and Islet Amyloid Polypeptide (IAPP20-29)
Authors: Cramer N. , Kawecki G. , King K. M. , Bevan D. R. , Brown A.M.
Published: September 2021

Amyloid-beta (Aβ) and islet amyloid polypeptide (IAPP) are small peptides, classified as amyloids, that have the potential to self-assemble and form cytotoxic species, such as small soluble oligomers and large insoluble fibrils. The formation of Aβ aggregates facilitates the progression of Alzheimer’s disease (AD), while IAPP aggregates induce pancreatic β-cell apoptosis, leading to exacerbation of Type 2 diabetes (T2D). Cross-amyloid interactions between Aβ and IAPP have been described both in vivo and in vitro, implying the role of Aβ or IAPP as modulators of cytotoxic self-aggregation of each peptide, and suggesting that Aβ-IAPP interactions are a potential molecular link between AD and T2D. Using molecular dynamics simulations, “hot spot” regions of the two peptides were studied to understand the formation of hexamers in a heterogenous and homogenous peptide-containing environment. Systems of only Aβ(16-22) peptides formed antiparallel, β-barrel-like structures, while systems of only IAPP(20-29) peptides formed stacked, parallel beta strands and had relatively unstable aggregation structures after 2 μs of simulation time. Systems containing both Aβ and IAPP (1:1 ratio) hexamers showed antiparallel, β-barrel-like structures, with an interdigitated arrangement of Aβ(16-22) and IAPP(20-29). These β-barrel structures have features of cytotoxic amyloid species identified in previous literature. Ultimately, this work seeks to provide atomistic insight into both the mechanism behind cross-amyloid interactions and structural morphologies of these toxic amyloid species.

Statement of Significance

Molecular knowledge, biophysical characterization, structural morphologies, and formation pathways of amyloid oligomers - specifically low-molecular weight, cross-amyloid oligomers - remain preliminary and undefined. Characterizing interactions between homogenous and heterogenous amyloid oligomers is of great interest given that certain oligomer morphologies contribute to cytotoxicity, eventually resulting in comorbid diseases such as Alzheimer’s disease (AD) and Type 2 Diabetes Mellitus (T2DM). Utilizing model systems (e.g., fragments of full-length peptides) and molecular dynamics (MD) simulations to probe the biophysical underpinnings of cross-amyloid oligomer structures is the first step in understanding the dynamics, stability, and potential modes of cytotoxicity of these species, providing important insights into targetable biomolecular structures.
KLC4 shapes axon arbors during development and mediates adult behavior
Authors: Haynes Elizabeth M. , Burnett Korri H. , He Jiaye , Jean-Pierre Marcel , Jarzyna Martin , Eliceiri Kevin W. , Huisken Jan , Halloran Mary C.
Published: September 2021

Development of elaborate and polarized neuronal morphology requires precisely regulated transport of cellular cargos by motor proteins such as kinesin-1. Kinesin-1 has numerous cellular cargos which must be delivered to unique neuronal compartments. The process by which this motor selectively transports and delivers cargo to regulate neuronal morphogenesis is poorly understood, although the cargo-binding kinesin light chain (KLC) subunits contribute to specificity. Our work implicates one such subunit, KLC4, as an essential regulator of axon branching and arborization pattern of sensory neurons during development. Using live imaging approaches in klc4 mutant zebrafish, we show that KLC4 is required for stabilization of nascent axon branches, proper microtubule (MT) dynamics, and endosomal transport. Furthermore, KLC4 is required for proper tiling of peripheral axon arbors: in klc4 mutants, peripheral axons showed abnormal fasciculation, a behavior characteristic of central axons. This result suggests that KLC4 patterns axonal compartments and helps establish molecular differences between central and peripheral axons. Finally, we find that klc4 mutant larva are hypersensitive to touch and adults show anxiety-like behavior in a novel tank test, implicating klc4 as a new gene involved in stress response circuits.
How to model DNA replication in stochastic models of synthetic gene circuits (and why)
Authors: Clamons Samuel E. , Murray Richard M.
Published: September 2021

Biocircuit modeling sometimes requires explicit tracking of a self-replicating DNA species. The most obvious, straightforward way to model a replicating DNA is structurally unstable and leads to pathological model behavior. We describe a simple, stable replication mechanism with good model behavior and show how to derive it from a mechanistic model of ColE1 replication.
Different plasticity of bud outgrowth at cauline and rosette nodes in Arabidopsis thaliana
Authors: Fichtner Franziska , Barbier Francois F. , Kerr Stephanie C. , Dudley Caitlin , Cubas Pilar , Turnbull Colin , Brewer Philip B. , Beveridge Christine A.
Published: September 2021

Shoot branching is a complex mechanism in which secondary shoots grow from buds that are initiated from meristems established in leaf axils. The model plant Arabidopsis thaliana has a rosette leaf growth pattern in the vegetative stage. After flowering initiation, the main stem starts to elongate with the top leaf primordia developing into cauline leaves. Meristems in arabidopsis are initiated in the axils of rosette or cauline leaves, giving rise to rosette or cauline buds, respectively. Plasticity in the process of shoot branching is regulated by resource and nutrient availability as well as by plant hormones. However, few studies have attempted to test whether cauline and rosette branching are subject to the same plasticity. Here, we addressed this question by phenotyping cauline and rosette branching in three arabidopsis ecotypes and several arabidopsis mutants with varied shoot architectures. Our results show that there is no negative correlation between cauline and rosette branch numbers in arabidopsis, demonstrating that there is no trade-off between cauline and rosette bud outgrowth. Through investigation of the altered branching pattern of flowering pathway mutants and arabidopsis ecotypes grown in various photoperiods and light regimes, we further elucidated that the number of cauline branches is closely related to flowering time. The number or rosette branches has an enormous plasticity compared with cauline branches and is influenced by genetic background, flowering time, light intensity and temperature. Our data reveal different plasticity in the regulation of branching at rosette and cauline nodes and promote a framework for future branching analyses.

One sentence summary

Different plasticity of branching at cauline and rosette nodes of arabidopsis is revealed through detailed correlative analyses of branching under varied genetic and environmental contexts.
Elucidation of the molecular interactions that enable stable interaction between HIV protease inhibitor ritonavir and human DNA repair enzyme ALKBH2: a molecular dynamics simulation study
Authors: Mohan Monisha , Anindya Roy
Published: September 2021

The human DNA repair enzyme AlkB homologue-2 and 3 (ALKBH2 and ALKKBH3) repairs methyl adducts from genomic DNA. Overexpression of ALKBH2 and ALKBH3 has been implicated in both tumorigenesis and chemotherapy resistance in some cancers, including glioblastoma and renal cancer rendering it a potential therapeutic target and a diagnostic marker. However, no inhibitor is available against these important DNA repair proteins. Intending to repurpose a drug as an inhibitor of ALKBH2/ALKBH3, we performedin silicoevaluation of HIV protease inhibitors and identified Ritonavir as an ALKBH2-interacting molecule. Using molecular dynamics simulation, we elucidated the molecular details of Ritonavir-ALKBH2 interaction. The present work highlights that Ritonavir might be used to target the ALKBH2-mediated DNA alkylation repair.
The scratch-digging lifestyle of the Permian “microsaur”Batropetesas a model for the exaptative origin of jumping locomotion in frogs
Authors: Jansen Maren , Marjanović David
Published: September 2021

Recent studies have shown that the Triassic stem-frogTriadobatrachuslacked the ability to jump off, but nonetheless had the forelimb strength to withstand the impact of landing from a jump. We propose a hypothesis to resolve this pseudoparadox: the strengthened forelimbs are former adaptations to forelimb-based digging that later made jumping possible by exaptation.

Micro-CT data from a skeleton ofBatropetes palatinusreveal thin cortical bone, confirmingBatropetesas terrestrial. Combining adaptations to walking and digging, confirmed by statistical analyses,Batropetesis thought to have searched for food in leaf litter or topsoil. We interpretBatropetesas having used one forelimb at a time to shove leaf litter aside.Batropetesmay thus represent an analog or possibly a homolog of the digging stage that preceded the origin of Salientia.

We discuss the possibility of homology with the digging lifestyles of other “microsaurs” and other amphibians.
Bioorthogonally Cross-Linked Hyaluronan-Laminin Hydrogels for 3D Neuronal Cell Culture and Biofabrication
Authors: Jury Michael , Matthiesen Isabelle , Boroojeni Fatemeh Rasti , Ludwig Saskia L. , Civitelli Livia , Winkler Thomas E. , Selegård Robert , Herland Anna , Aili Daniel
Published: September 2021

Laminins (LNs) are key components in the extracellular matrix of neuronal tissues in the developing brain and neural stem cell niches. LN-presenting hydrogels can provide a biologically relevant matrix for the 3D culture of neurons towards development of advanced tissue models and cell-based therapies for the treatment of neurological disorders. Biologically derived hydrogels are rich in fragmented LN and are poorly defined concerning composition, which hampers clinical translation. Engineered hydrogels require elaborate and often cytotoxic chemistries for cross-linking and LN conjugation and provide limited possibilities to tailor the properties of the materials. Here we show a modular hydrogel system for neural 3D cell culture, based on hyaluronan (HA) and poly(ethylene glycol) (PEG), that is cross-linked and functionalized with human recombinant LN 521 using bioorthogonal copper-free click chemistry. Encapsulated human neuroblastoma cells demonstrate high viability and grow into spheroids. Neuroepithelial stem cells (lt-NES) cultured in the hydrogels can undergo spontaneous differentiation to neural fate and demonstrate significantly higher viability than cells cultured without LN. The hydrogels further support the structural integrity of 3D bioprinted structures and maintain high viability of syringe extruded lt-NES, which can facilitate the development of advanced neuronal tissue and disease models and translation of stem cell-based therapies.

The authors present an extracellular matrix mimicking hydrogel for 3D culture of neural cell models. Based on hyaluronic acid and poly(ethylene glycol), the hydrogel immobilizes recombinant laminin 521, associated with neuronal development. The study demonstrates support of neuroblastoma cell viability, spontaneous human neuroepithelial stem cell differentiation, and the protective effect of the hydrogels during bioprinting and syringe needle ejection.
Multiple types of genomic variation contribute to adaptive traits in the mustelid subfamily Guloninae
Authors: Derežanin Lorena , Blažytė Asta , Dobrynin Pavel , Duchêne David A. , Horacio Grau José , Jeon Sungwon , Kliver Sergei , Koepfli Klaus-Peter , Meneghini Dorina , Preick Michaela , Tomarovsky Andrey , Totikov Azamat , Fickel Jörns , Förster Daniel W.
Published: September 2021

Species of the mustelid subfamily Guloninae inhabit diverse habitats on multiple continents, and occupy a variety of ecological niches. They differ in feeding ecologies, reproductive strategies and morphological adaptations. To identify candidate loci associated with adaptations to their respective environments, we generated a de novo assembly of the tayra (Eira barbara), the earliest diverging species in the subfamily, and compared this with the genomes available for the wolverine (Gulo gulo) and the sable (Martes zibellina). Our comparative genomic analyses included searching for signs of positive selection, examining changes in gene family sizes, as well as searching for species-specific structural variants (SVs). Among candidate loci associated with phenotypic traits, we observed many related to diet, body condition and reproduction. For example, for the tayra, which has an atypical gulonine reproductive strategy of aseasonal breeding, we observe species-specific changes in many pregnancy-related genes. For the wolverine, a circumpolar hypercarnivore that must cope with seasonal food scarcity, we observed many changes in genes associated with diet and body condition. All types of genomic variation examined contributed substantially to the identification of candidate loci. This strongly argues for consideration of variation other than single nucleotide polymorphisms in comparative genomics studies aiming to identify loci of adaptive significance.
csdR, an R package for differential co-expression analysis
Authors: Pettersen Jakob P. , Almaas Eivind
Published: September 2021

Background

Differential co-expression network analysis has become an important tool to gain understanding of biological phenotypes and diseases. The CSD algorithm is a method to generate differential co-expression networks by comparing gene co-expressions from two different conditions. Each of the gene pairs is assigned conserved (C), specific (S) and differentiated (D) scores based on the co-expression of the gene pair between the two conditions. The result of the procedure is a network where the nodes are genes and the links are the gene pairs with the highest C-, S-, and D-scores. However, the existing CSD-implementations suffer from poor computational performance, difficult user procedures and lack of documentation.

Results

We created the R-package csdR aimed at reaching good performance together with ease of use, sufficient documentation, and with the ability to play well with other tools for data analysis. csdR was benchmarked on a realistic dataset with 20, 645 genes. After verifying that the chosen number of iterations gave sufficient robustness, we tested the performance against the two existing CSD implementations. csdR was superior in performance to one of the implementations, whereas the other did not run. Our implementation can utilize multiple processing cores. However, we were unable to achieve more than ∼ 2.7 parallel speedup with saturation reached at about 10 cores.

Conclusions

The results suggest that csdR is a useful tool for differential co-expression analysis and is able to generate robust results within a workday on datasets of realistic sizes when run on a workstation or compute server.
Engaging the ‘A’ Class Antibody: Variable-Heavy (VH) region influencing IgA1&2 engagement of FcαRI and superantigen proteins G, A, and L
Authors: Ling Wei-Li , Su Chinh Tran-To , Lua Wai-Heng , Yeo Joshua Yi , Poh Jun-Jie , Ng Yuen-Ling , Wipat Anil , Gan Samuel Ken-En
Published: September 2021

Interest in IgA as an alternative therapeutic and diagnostic antibody has increased over the years, yet much remains to be investigated especially given their importance in activating immune cells in blood and in mucosal immunity. Recent whole antibody-based investigations have shown significant distal effects between the variable (V) and constant (C)-regions that can be mitigated by the different hinge regions of the human IgA subtypes A1 and A2. Diving deeper into the mechanisms underlying this, systematic VH manipulations retaining the CDRs were performed on a panel of 28 IgA1s and A2s across the Trastuzumab and Pertuzumab models, revealed distal effects on FcαRI binding. Further insights from structural modelling showed these effects to also be mitigated by the differing glycosylation patterns in IgA1 and 2 to explain reversal of trends of IgA1s and 2s effected by slight changes in the CDRs. IgAs bound at the Fc showed similar trends but magnitudes better binding to Her2 with that bound by ppL, showing that ppL can sterically hinder Her2 antigen binding. Contrary to canonical knowledge, we found strong evidence of IgAs binding SpG that was narrowed to be at the CH2-3 region, and that the likely binding with SpA was beyond VH3 FWR and most likely at the CH1. VH1 was found to be the most suitable framework (FWRs) for CDR-grafting for both IgA1 and 2. With relevance to interactions with the microbiome at mucosal surfaces, mechanistic insight of how these IgAs can interact bacterial superantigens proteins G, A, and L are also discovered for potential future interventions.

One Sentence Summary

An insight into the mechanism of distal V-region effects on FCAR and superantigens proteins G, A, and L by both IgA1 and A2.
Fitness landscape analysis of a tRNA gene reveals that the wild type allele is sub-optimal, yet mutationally robust
Authors: Gabzi Tzahi , Pilpel Yitzhak , Friedlander Tamar
Published: September 2021

Fitness landscape mapping and the prediction of evolutionary trajectories on these landscapes are major tasks in evolutionary biology research. Evolutionary dynamics is tightly linked to the landscape topography, but this relation is not straightforward. Here, we analyze a fitness landscape of a yeast tRNA gene, previously measured under four different conditions. We find that the wild type allele is sub-optimal, and 8%-10% of its variants are fitter. We rule out the possibilities that the wild type is fittest on average on multiple conditions or located on a local fitness maximum. Instead, we find that the wild type is mutationally robust (‘flat’), while more fit variants are typically mutationally fragile. Similar observations of mutational robustness or flatness have been so far made in very few cases, predominantly in viral genomes.
scoMorphoFISH: A Deep-Learning enabled toolbox for single-cell single-mRNA quantification and correlative (ultra-)morphometry
Authors: Siegerist Florian , Hay Eleonora , Dikou Juan Saydou , Büscher Anja , Oh Jun , Ribback Silvia , Zimmermann Uwe , Bräsen Jan Hinrich , Lenoir Olivia , Endlich Karlhans , Tharaux Pierre-Louis , Endlich Nicole
Published: September 2021

Increasing the information depth of single kidney biopsies can improve diagnostic precision, personalized medicine and accelerate basic kidney research. Until now, information on mRNA abundance and morphologic analysis has been obtained from different samples, missing out on the spatial context and single-cell correlation of findings. Herein, we present scoMorphoFISH, a modular toolbox to get spatial single-cell single-mRNA expression data optimized for routinely generated kidney biopsies. Deep-Learning was used to virtually dissect tissue sections in tissue compartments and cell types to which single-cell expression data was assigned. Furthermore, we show correlative and spatial single-cell expression quantification with super-resolved podocyte foot process morphometry on the same histological section. In contrast to bulk analysis methods, this approach will help to identify local transcription changes even in less frequent kidney cell types on a spatial single-cell level with single-mRNA resolution. As this method performs well with standard formalin-fixed paraffin-embedded samples and we provide pretrained DL-networks embedded in a comprehensive image analysis workflow, this method can be applied immediately in a variety of settings.
Revealing Free Energy Landscape from MD Data via Conditional Angle Partition Tree
Authors: Jiang Hangjin , Li Han , Wong Wing Hung , Fan Xiaodan
Published: September 2021

Deciphering the free energy landscape of biomolecular structure space is crucial for understanding many complex molecular processes, such as protein-protein interaction, RNA folding, and protein folding. A major source of current dynamic structure data is Molecular Dynamics (MD) simulations. Several methods have been proposed to investigate the free energy landscape from MD data, but all of them rely on the assumption that kinetic similarity is associated with global geometric similarity, which may lead to unsatisfactory results. In this paper, we proposed a new method called Conditional Angle Partition Tree to reveal the hierarchical free energy landscape by correlating local geometric similarity with kinetic similarity. Its application on the benchmark alanine dipeptide MD data showed a much better performance than existing methods in exploring and understanding the free energy landscape. We also applied it to the MD data of Villin HP35. Our results are more reasonable on various aspects than those from other methods and very informative on the hierarchical structure of its energy landscape.
Validity and sensitivity of an inertial measurement unit-driven biomechanical model of motor variability for gait
Authors: Bailey Christopher A. , Uchida Thomas K. , Nantel Julie , Graham Ryan B.
Published: September 2021

Motor variability in gait is frequently linked to fall risk, yet field-based biomechanical joint evaluations are scarce. We evaluated the validity and sensitivity of an inertial measurement unit (IMU)-driven biomechanical model of joint angle variability for gait. Fourteen healthy young adults completed seven-minute trials of treadmill gait at several speeds and arm swing amplitudes. Joint kinematics were estimated by IMU- and optoelectronic-based models using OpenSim. We calculated range of motion (ROM), magnitude of variability (meanSD), local dynamic stability (λmax), persistence of ROM fluctuations (DFAα), and regularity (SaEn) of each angle over 200 continuous strides, and evaluated model accuracy (e.g., RMSD: root mean square difference), consistency (ICC2,1: intraclass correlation), biases, limits of agreement, and sensitivity to within-participant gait responses (effects of Speed and Swing). RMSDs of joint angles were 1.7–7.5° (pooled mean of 4.8°), excluding ankle inversion. ICCs were mostly good– excellent in the primary plane of motion for ROM and in all planes for meanSD and λmax, but were poor–moderate for DFAα and SaEn. Modeled Speed and Swing responses for ROM, meanSD, and λmax were similar. Results suggest that the IMU-driven model is valid and sensitive for field-based assessments of joint angles and several motor variability features.
Determination of intracellular protein–ligand binding affinity by competition binding in-cell NMR
Authors: Luchinat Enrico , Barbieri Letizia , Cremonini Matteo , Pennestri Matteo , Nocentini Alessio , Supuran Claudiu T. , Banci Lucia
Published: September 2021

Structure-based drug development suffers from high attrition rates due to the poor activity of lead compounds in cellular and animal models caused by low cell penetrance, off-target binding or changes in the conformation of the target protein in the cellular environment. The latter two effects cause a change in the apparent binding affinity of the compound, which is indirectly assessed by cellular activity assays. To date, direct measurement of the intracellular binding affinity remains a challenging task. In this work, in-cell NMR spectroscopy was applied to measure intracellular dissociation constants in the nanomolar range by means of protein-observed competition binding experiments. Competition binding curves relative to a reference compound could be retrieved either from a series of independent cell samples or from a single real-time NMR bioreactor run. The method was validated using a set of sulfonamide-based inhibitors of human carbonic anhydrase II with known activity in the subnanomolar to submicromolar range. The intracellular affinities were similar to those obtained in vitro, indicating that these compounds selectively bind to the intracellular target. In principle, the approach can be applied to any soluble intracellular target that gives rise to measurable chemical shift changes upon ligand binding.
Open social innovation for surplus food recovery and aid during COVID-19 crisis: the case of Fondazione Banco Alimentare Onlus
Authors: Penco Lara , Ciacci Andrea , Benevolo Clara , Torre Teresina
Published: September 2021

Purpose

The study analyses the role that open social innovation (OSI) perspective played for Fondazione Banco Alimentare Onlus (FBAO), a food bank in Italy, in responding to the COVID-19 crisis. It answers the following research question: how does a crisis, such as the COVID-19 pandemic, stimulate the adoption of OSI practices to revamp the activities of FBAO and facilitate appropriate solutions to carry out its social mission?

Design/methodology/approach

This study employs a qualitative approach. It is based on a single case study.

Findings

The study shows how COVID-19 has stimulated the adoption of OSI practices to continue to meet the social mission, creating innovative projects or finding new ways to do the same things.

Research limitations/implications

The study is based on a single case study.

Practical implications

The paper contributes insights into the literature on OSI, examining how inbound and outbound OSI mechanisms can modify business models and increase the adaptation capacity of food banks and their effectiveness. In addition, it provides a rich context in which the social value drivers provided by OSI are studied.

Originality/value

This paper applies the OSI to a food bank to evaluate what this action mode produces for the food bank during a health crisis. Specifically, this is the first paper that studies the COVID-19 crisis response of a food bank from the OSI perspective, focusing on the inbound and outbound OSI processes that characterized the entire network of relationships.
An optimized double-integral-sliding-mode-controller for a PV microgrid
Authors: Pradhan Swati Sucharita , Pradhan Raseswari , Subudhi Bidyadhar
Published: September 2021

Purpose

The dynamics of the PV microgrid (PVMG) system are highly nonlinear and uncertain in nature. It is encountered with parametric uncertainties and disturbances. This system cannot be controlled properly by conventional linear controllers. H− controller and sliding mode controller (SMC) may capable of controlling it with ease. Due to its inherent dynamics, SMC introduces unwanted chattering into the system output waveforms. This paper aims to propose a controller to reduce this chattering.

Design/methodology/approach

This paper presents redesign of the SMC by modifying its sliding surface and tuning its parameters by employing water-evaporation-optimization (WEO) based metaheuristic algorithm.

Findings

By using this proposed water-evaporation-optimization algorithm-double integral sliding mode controller (WEOA-DISMC), the chattering magnitude is diminished greatly. Further, to examine which controller between H8 controller and proposed WEOA-DISMC performs better in both normal and uncertain situations, a comparative analysis has been made in this paper. The considered comparison parameters are reference tracking, disturbance rejection and robust stability.

Originality/value

WEO tuned DISMC for PVMG system is the contribution.
The impact of corporate social responsibility (CSR) priming on consumers’ consumption and lifestyle choices with intertemporal tradeoffs
Authors: Fatemi Hajar , Dube Laurette
Published: September 2021

Purpose

This paper aims to study the unexplored possibility that priming firms’ corporate social responsibility (CSR) activity in consumers’ minds may impact consumers’ preference for non-firm related consumption and lifestyle choice options with intertemporal trade-offs.

Design/methodology/approach

Across four experimental studies, the authors looked at the impact of CSR priming on the preference of participants for later larger versus sooner smaller money (Study 1), saving versus spending (Study 2) and healthy versus unhealthy food choices (Studies 3 and 4). These choice options were not related to the focal firm that practiced CSR. The authors measured the changes in participants’ consideration of future consequences (CFC) as a potential mediator for the results.

Findings

The participants in the CSR condition showed a higher CFC and a higher preference for the options with long-term benefits and immediate costs over the ones with long-term costs and immediate benefits, i.e. later larger over sooner smaller money, saving over spending and healthy over unhealthy food. The authors documented a mediation role for CFC.

Research limitations/implications

All the participants in the studies were from the USA. Looking at the cultural differences can enrich the understanding of the impact of CSR on preference for the options with intertemporal trade-offs. Furthermore, this paper builds its theoretical justification based on the assumption of individuals’ acceptance of CSR activities. Nevertheless, consumers may have skepticism about these activities. Future studies may investigate the effect of CSR skepticism of individuals on the proposed effects. Additionally, investigating the moderating roles of individuals’ characteristics like their prosocial concern or their knowledge about choice options might be an avenue for future research.

Practical implications

The findings highlight the benefits of CSR priming on consumers’ welfare and normative behavior. Firms may use the findings to understand and manage the impact of other firms’ CSR communications on the evaluation of their own products.

Originality/value

This research is the first to highlight the impact of CSR priming on consumers’ non-firm-related consumption and lifestyle choices with intertemporal trade-offs. The results showed the positive effect of priming firms’ CSR activities on consumers’ CFC and the mediating role of CFC.
Towards competence-oriented higher education: a systematic literature review of the different perspectives on successful exit profiles
Authors: Brauer Sanna
Published: September 2021

Purpose

The twenty-first century education system seeks to meet the societal demands of economic effectiveness and the unique professional development needs of individuals. This paper aims to discuss the qualities of competence-oriented educational processes and the recent movement towards competence-based curricula in higher education.

Design/methodology/approach

This study follows a systematic literature review (SLR) methodology to explore the concept of competence within the context of educational science. The subsequent thematic synthesis analyses the findings of reviewed publications regarding graduate attributes in competence-oriented higher education and their perspectives and working-life expectations on exit profiles.

Findings

Interest in competence-oriented education, training and learning has grown in recent years, resulting in numerous theoretical and technical pedagogical applications in higher education. Nonetheless, ambiguous terminology presents a significant challenge, which is demonstrated by the inconsistent language of the study's results. Moreover, there is an obvious need for teachers' in-service training. The qualitative synthesis of this article will be useful for both educational and working life sectors to inform and promote different perspectives on competence-oriented educational processes. A clear articulation of competences is crucial for reforming higher education to meet students' interests and recognise their work-life needs.

Originality/value

The concept of competence has been under-investigated in higher education research and practices. This study offers novel insights and practical implications for competence-oriented learning concerning the paradigmatic change across higher education.
Business adversity during the COVID-19 crisis and beyond: the way forward for small and medium enterprises in India
Authors: Nair Saji Thazhungal Govindan
Published: September 2021

Purpose

The novel coronavirus (COVID-19) leaves Indian business teetering on the edge of survival. This paper aims to set out to assess the impact of the pandemic shocks on the small and medium business segments in India. The research also explores the strategies that potentially take the segments back to recovery and growth.

Design/methodology/approach

The findings draw on the perspectives of academic and business people, and the authors use linear and nonlinear regression modelling under three recovery scenarios to support our arguments.

Findings

Evidence suggests that the shocks to business are manifold and the severity of most of the issues will aggravate as the recovery prolongs.

Practical implications

The paper explains the rationale of realistic strategies and compares its effects across potent recoveries. The findings are useful for both academics and business and relates to the strategic decisions that would be taken by small and medium enterprises to expedite recovery from the crisis.

Originality/value

The research is unique in surveying the academics and entrepreneurs about the impact of COVID-19 on Indian business.
Mutual fund manager turnover: an empirical investigation of performance
Authors: Ghalke Avinash , Kulkarni Shripad
Published: September 2021

Purpose

When a fund manager leaves, the investment strategy of the fund changes or remains the same. The departing fund manager's resignation is either forced or voluntary. The study investigates the relationship between the portfolio manager's transition and the fund's investment strategy and how the change affects the mutual fund returns in the subsequent period.

Design/methodology/approach

The authors examine 148 fund manager changes in India between April 2005–March 2018 using three performance measures: abnormal return (fund return minus benchmark return), Jensen's alpha and Carhart four-factor alpha. The analysis includes an event study methodology, followed by a two-step Fama–MacBeth regression approach.

Findings

Contrary to the previous studies conducted in the developed markets, the authors find that fund performance improves irrespective of whether the fund manager change is forced or voluntary. The outperformance after the fund manager's exit is significant for funds belonging to the larger fund families.

Originality/value

In the context of investment management, the authors provide a conceptual framework to understand the effect of fund manager exit on mutual fund performance. The authors substantiate their arguments with empirical evidence. To the best of the authors' understanding, this is the first research to examine the effect of changing mutual fund managers in an emerging market setting.
FDI inflow, ICT and economic performance of India: an empirical investigation
Authors: Nayak Suryakanta , Sahoo Dukhabandhu
Published: September 2021

Purpose

The aim of this study is to examine the impact of foreign direct investment (FDI) inflow and information and communication technology (ICT) on the economic performance of India by analysing annual data from 1991 to 2019.

Design/methodology/approach

This study has used data collected from secondary sources. The variables considered for the analysis are based on the review of theoretical and empirical literature. Moreover, apart from the quantitative variables, two qualitative variables have also been considered through the use of dummy variables. The Cobb–Douglas, Transcendental logarithmic and Simultaneous equations models have been used for the study.

Findings

The result reveals that the partial elasticities of the per-capita gross domestic product (PCGDP) of India with respect to FDI, mobile density (MD) and internet density (ID) are 0.074, 0.024 and 0.036, respectively. The positive and significant coefficient of the interaction among FDI, MD and ID in the estimation of the transcendental logarithmic function indicates the importance of ICT infrastructure in extracting the best out of FDI (the coefficient is 0.011 for the model without any control variables and it is 0.005 with control variables).

Originality/value

The findings of this study are more reliable as the latest available data have been analysed through the appropriate econometric models. This study will be useful for the policymakers in the formulation of policies with regard to foreign capital and digitalisation.
Ensuring the halal integrity of the food supply chain through halal suppliers: a bibliometric review
Authors: Handayani Dwi Iryaning , Masudin Ilyas , Haris Abdul , Restuputri Dian Palupi
Published: September 2021

Purpose

This paper aims to provide a brief bibliometric review of previous literature reviews in understanding halal suppliers in the food supply chain to achieve halal standards from upstream to downstream.

Design/methodology/approach

The method used was a structured literature review sample of during 2008–2020 totalling 142 articles. The authors use the R-package bibliometric and VOSviewer to find out information about journals, articles, authors, citations, keywords and word hierarchy maps.

Findings

The analysis reveals five research clusters: halal supply chain, food supply chain, supply chain integration, halal lifestyle, halal logistics.

Research limitations/implications

This study focuses on articles that discuss halal suppliers in the food supply chain.

Originality/value

Bibliometric reviews related to suppliers in the halal food supply chain in this study will help explore halal suppliers and be useful for researchers and practitioners in their fields as well as assist supplier management in the halal food supply chain.