bluuebunny/crossref_metadata_2025 huggingface dataset:
The early dynamics of the SARS-CoV-2 epidemic in Portugal
Authors: Borges V , Isidro J , Trovão NS , Duarte S , Cortes-Martins H , Martiniano H , Gordo I , Leite R , Vieira L ,   Portuguese network for SARS-CoV-2 genomics (Consortium), Guiomar R , Gomes JP
Published: February 2021

Background

Genomic surveillance of SARS-CoV-2 in Portugal was rapidly implemented by the National Institute of Health in the early stages of the COVID-19 epidemic, in collaboration with more than 50 laboratories distributed nationwide. This unprecedented collaborative effort culminated in the generation of 1275 SARS-CoV-2 genome sequences, which represent 15.5% of all confirmed cases in March 2020, making Portugal one of the countries generating the highest volumes of SARS-CoV-2 genomic data during early COVID-19 pandemic.

Methods

We reconstructed and characterized the spatio-temporal dynamics of SARS-CoV-2 introductions and early dissemination in Portugal using recent phylodynamic models that allow integration of individual-based travel history, in order to obtain a more realistic reconstruction of the viral dynamics.

Results

We detected at least 277 independent SARS-CoV-2 introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy and Switzerland), which was broadly consistent with the available travel history data, as well as with the countries with most frequent connectivity and/or with the highest number of Portuguese immigrants. Although most introductions were estimated to have occurred during the last week of February and the first week of March 2020, it is likely that SARS-CoV-2 was silently circulating in Portugal several weeks before the first confirmed local cases on March 2, 2020.

Discussion and Conclusion

While the implemented preventive and early control measures seem to have been successful in mitigating community transmission from most independent introductions, our results suggest that their earlier implementation could have largely minimized the number of introductions and subsequent virus expansion. Here we lay the foundation for genomic epidemiology of SARS-CoV-2 in Portugal, and highlight the need for systematic, continuous and geographically-representative genomic surveillance to guide national and international public health authorities toward the characterization and control of SARS-CoV-2 circulating diversity.
Group IIA Secreted Phospholipase A2 Plays a Central Role in the Pathobiology of COVID-19
Authors: Snider Justin M. , You Jeehyun Karen , Wang Xia , Snider Ashley J , Hallmark Brian , Seeds Michael C. , Sergeant Susan , Johnstone Laurel , Wang Qiuming , Sprissler Ryan , Zhang Hao Helen , Luberto Chiara , Kew Richard R. , Hannun Yusuf A , McCall Charles E. , Yao Guang , Del Poeta Maurizio , Chilton Floyd H.
Published: February 2021

There is an urgent need to identify cellular and molecular mechanisms responsible for severe COVID-19 disease accompanied by multiple organ failure and high mortality rates. Here, we performed untargeted/targeted lipidomics and focused biochemistry on 127 patient plasma samples, and showed high levels of circulating, enzymatically active secreted phospholipase A2 Group IIA (sPLA2-IIA) in severe and fatal COVID-19 disease compared with uninfected patients or mild illness. Machine learning demonstrated that sPLA2-IIA effectively stratifies severe from fatal COVID-19 disease. We further introduce a PLA-BUN index that combines sPLA2-IIA and blood urea nitrogen (BUN) threshold levels as a critical risk factor for mitochondrial dysfunction, sustained inflammatory injury and lethal COVID-19. With the availability of clinically tested inhibitors of sPLA2-IIA, our study opens the door to a precision intervention using indices discovered here to reduce COVID-19 mortality.
Ketamine and attentional bias to threat: dynamic causal modeling of magnetoencephalographic connectivity in treatment-resistant depression
Authors: Gilbert Jessica R. , Galiano Christina S. , Nugent Allison C. , Zarate Carlos A.
Published: February 2021

The glutamatergic modulator ketamine rapidly reduces depressive symptoms in individuals with treatment-resistant major depressive disorder (MDD) and bipolar disorder. While its underlying mechanism of antidepressant action is not fully understood, modulating glutamatergically-mediated connectivity appears to be a critical component moderating antidepressant response. This double-blind, crossover, placebo-controlled study analyzed data from 19 drug-free individuals with MDD and 15 healthy volunteers who received a single intravenous infusion of ketamine hydrochloride (0.5 mg/kg) as well as an intravenous infusion of saline placebo. Magnetoencephalographic recordings were collected prior to the first infusion and six to nine hours after both drug and placebo infusions. During scanning, participants completed an attentional dot probe task that included emotional faces. Antidepressant response was measured across timepoints using the Montgomery-Asberg Depression Rating Scale (MADRS). Dynamic causal modeling (DCM) was used to measure changes in parameter estimates of connectivity via a biophysical model that included realistic local neuronal architecture and receptor channel signaling, modeling connectivity between the early visual cortex, fusiform cortex, amygdala, and inferior frontal gyrus. Clinically, ketamine administration significantly reduced depressive symptoms in MDD participants. Within the model, ketamine administration led to faster gamma aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA) transmission in the early visual cortex, faster NMDA transmission in the fusiform cortex, and slower NMDA transmission in the amygdala. Ketamine administration also led to direct and indirect changes in local inhibition in the early visual cortex and inferior frontal gyrus and to indirect increases in cortical excitability within the amygdala. Finally, reductions in depressive symptoms in MDD participants post-ketamine were associated with faster α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) transmission and increases in gain control of spiny stellate cells in the early visual cortex. These findings provide additional support for the GABA and NMDA inhibition and disinhibition hypotheses of depression and support the role of AMPA throughput in ketamine’s antidepressant effects.
TGF-β promotes microtube formation in glioblastoma through Thrombospondin 1
Authors: Joseph Justin V. , Magaut Capucine R. , Storevik Simon , Geraldo Luiz H. , Mathivet Thomas , Latif Md Abdul , Rudewicz Justine , Guyon Joris , Gambaretti Matteo , Haukas Frida , Trones Amalie , Rømo Ystaas Lars A. , Hossain Jubayer A. , Sandra Ninzima S , Zhou Wenjing , Tomar Tushar , Klink Barbara , Rane Lalit , Irving Bronwyn K. , Marrison Joanne , O’Toole Peter , Wurdak Heiko , Wang Jian , Di Zhang , Winkler Frank , Kruyt Frank A. E. , Bikfalvi Andreas , Bjerkvig Rolf , Daubon Thomas , Miletic Hrvoje
Published: February 2021

Microtubes (MTs), cytoplasmic extensions of glioma cells, are important cell communication structures promoting invasion and treatment resistance through network formation. MTs are abundant in chemoresistant gliomas, in particular glioblastomas (GBMs), while they are uncommon in chemosensitive IDH-mutant and 1p/19q co-deleted oligodendrogliomas. To identify potential signaling pathways involved in MT formation we performed a bioinformatics analysis of TCGA data showing that the TGF-β pathway is highly activated in GBMs compared to oligodendroglial tumors. In particular we observed that signaling pathways involved in extracellular matrix organization are differentially expressed between these tumor entities. Using patient-derived GBM stem cell lines, we demonstrated that TGF-β1 stimulation promotes enhanced MT formation and communication via Calcium signaling. Inhibition of the TGF-β pathway significantly reduced MT formation and its associated invasion in vitro and in vivo. Downstream of TGF-β, we identified thrombospondin 1 (TSP1) as a potential mediator of MT formation in GBM through SMAD activation. TSP1 was upregulated upon TGF-β stimulation and enhanced MT formation, which was inhibited by TSP1 shRNAs in vitro and in vivo. In conclusion, TGF-β and its downstream mediator TSP1 are important mediators of the MT network in GBM and blocking this pathway could potentially help to break the complex MT driven invasion/ resistance network.
Designing of multiepitope-based vaccine against Leptospirosis using Immuno-Informatics approaches
Authors: Abdullah Mohd , Kadivella Mohammad , Sharma Rolee , Faisal Syed M. , Azam Sarwar
Published: February 2021

Leptospirais a zoonotic pathogen causing significant morbidity and mortality both in animals and humans. Although several surface proteins have been identified as vaccine candidate, they failed to induce sterilizing immunity and cross protection against different serovars. Thus, identification of highly immunogenic antigens that are conserved among pathogenic serovars would be first step towards development of universal vaccine for Leptospirosis. Here we used reverse vaccinology pipeline to screen core genome of pathogenicLeptospiraspp.in order to identify suitable vaccine candidates. Based on properties like sub cellular localization, adhesin, homology to human proteins, antigenicity and allergenicity, 18 antigenic proteins were identified and were further investigated for immunological properties. Based on immunogenicity, Protegenicity, Antigenicity, B-cell and promiscuous T-cell epitopes, 6 Potential Vaccine Candidates (PVCs) were finally selected which covered most of the affected world population. For designing a Multi-Epitope Vaccine (MEV), 6 B-cell and 6 promiscuous MHC-I and MHC-II epitopes from each candidate were clustered with linkers in between and stitched along with a TLR4 adjuvant (APPHALS) at the N-terminal to form a construct of 361 amino acids. The physiochemical properties, secondary and tertiary structure analysis revealed that MEV was highly stable. Molecular docking analysis revealed the deep binding interactions of the MEV construct within the grooves of human TLR4 (4G8A). In-silico codon optimization and cloning of the vaccine construct assured good expression. Further, immune simulations have shown that MEV could induce strong and diverse B and T cell responses. Taken together our results indicate that the designed MEV could be a promising subunit vaccine candidate against Leptospirosis, however it requires experimental validation.
improv: A software platform for real-time and adaptive neuroscience experiments
Authors: Draelos Anne , Loring Matthew D. , Nikitchenko Maxim , Sriworarat Chaichontat , Gupta Pranjal , Sprague Daniel Y. , Pnevmatikakis Eftychios , Giovannucci Andrea , Benster Tyler , Deisseroth Karl , Pearson John M. , Naumann Eva A.
Published: February 2021

Current neuroscience research is often limited to testing predetermined hypotheses and post hoc analysis of already collected data. Adaptive experimental designs, in which modeling drives ongoing data collection and selects experimental manipulations, offer a promising alternative. Still, tight integration between models and data collection requires coordinating diverse hardware configurations and complex computations under real-time constraints. Here, we introduceimprov, a software platform that allows users to fully integrate custom modeling, analysis, and visualization with data collection and experimental control. We demonstrate bothin silicoandin vivohowimprovenables more efficient experimental designs for discovery and validation across various model organisms and data types.Improvcan orchestrate custom real-time behavioral analyses, rapid functional typing of neural responses from large populations via calcium microscopy, and optimal visual stimulus selection. We incorporate real-time machine learning methods for dimension reduction and predictive modeling of latent neural and behavioral features. Finally, we demonstrate howimprovcan perform model-driven interactive imaging and simultaneous optogenetic photostimulation of visually responsive neurons in the larval zebrafish brain expressing GCaMP6s and the red-shifted opsin rsChRmine. Together, these results demonstrate the power ofimprovto integrate modeling with data collection and experimental control to achieve next-generation adaptive experiments.
Astrocyte-derived TNF and glutamate critically modulate microglia reactivity by methamphetamine
Authors: Canedo Teresa , Portugal Camila Cabral , Socodato Renato , Bravo Joana , Almeida Tiago Oliveira , Magalhães João D. , Guerra-Gomes Sónia , Oliveira João Filipe , Sousa Nuno , Magalhães Ana , Relvas João Bettencourt , Summavielle Teresa
Published: February 2021

Methamphetamine (Meth) is a powerful illicit psychostimulant, widely used for recreational purposes. Besides disrupting the monoaminergic system and promoting oxidative brain damage, Meth also causes neuroinflammation that contributes to synaptic dysfunction and behavioral deficits. Aberrant activation of microglia, the largest myeloid cell population in the brain, is a common feature in neurological disorders linked to cognitive impairment and neuroinflammation. In this study, we investigated the mechanisms underlying the aberrant activation of microglia elicited by Meth in the adult mouse brain. We found that binge Meth exposure caused microgliosis and disrupted risk assessment behavior (a feature that usually occurs in human Meth abusers), both of which required astrocyte-to-microglia crosstalk. Mechanistically, Meth triggered a detrimental increase of glutamate exocytosis from astrocytes (in a manner dependent on TNF production and calcium mobilization), promoting microglial expansion and reactivity. Ablating TNF production or suppressing astrocytic calcium mobilization prevented microglia reactivity and abolished the behavioral phenotype elicited by Meth exposure. Overall, our data indicate that glial crosstalk is critical to relay behavioral alterations caused by acute Meth exposure.

One Sentence Summary

Glial crosstalk under methamphetamine exposure
The last battle of Anne of Brittany: solving mass grave through an interdisciplinary approach (paleopathology, anthropobiology, history, multiple isotopes and radiocarbon dating)
Authors: Colleter Rozenn , Bataille Clément , Dabernat Henri , Pichot Daniel , Hamon Philippe , Duchesne Sylvie , Labaune-Jean Françoise , Jean Stéphane , Cloirec Gaétan Le , Milano Stefania , Trost Manuel , Steinbrenner Sven , Marchal Marine , Guilbeau-Frugier Céline , Telmon Norbert , Crubézy Éric , Jaouen Klervia
Published: February 2021

Mass graves are usually key historical markers with strong incentive for archeological investigations. The identification of individuals buried in mass graves has long benefitted from traditional historical, archaeological, anthropological and paleopathological techniques. The addition of novel methods including genetic, genomic and isotopic geochemistry have renewed interest in solving unidentified mass graves. In this study, we demonstrate that the combined use of these techniques allows the identification of the individuals found in two Breton historical mass graves, where one method alone would not have revealed the importance of this discovery. The skeletons likely belong to soldiers from the two enemy armies who fought during a major event of Breton history: the siege of Rennes in 1491, which ended by the wedding of the Duchess of Brittany with the King of France and signaled the end of the independence of the region. Our study highlights the value of interdisciplinary approaches with a particular emphasis on increasingly accurate isotopic markers. The development of the sulfur isoscape and testing of the triple isotope geographic assignment are detailed in a companion paper [1].
How human runners regulate footsteps on uneven terrain
Authors: Dhawale Nihav , Venkadesan Madhusudhan
Published: February 2021

Running stably on uneven natural terrain takes skillful control and was critical for human evolution. Even as runners circumnavigate hazardous obstacles such as steep drops, they must contend with uneven ground that is gentler but still destabilizing. We do not know how footsteps are guided based on the uneven topography of the ground and how those choices influence stability. Therefore, we studied human runners on trail-like undulating uneven terrain and measured their energetics, kinematics, ground forces, and stepping patterns. We find that runners do not selectively step on more level ground areas. Instead, the body’s mechanical response, mediated by the control of leg compliance, helps maintain stability without requiring precise regulation of footsteps. Furthermore, their overall kinematics and energy consumption on uneven terrain showed little change from flat ground. These findings may explain how runners remain stable on natural terrain while devoting attention to tasks besides guiding footsteps.
The Optimum Cut-off Value of the Nelwan Score to Diagnose Typhoid Fever in Adults
Authors: Nelwan Erni Juwita , Paramita Luh Putu Listya , Sinto Robert , Hosea Fransiscus Nikodemus , Nugroho Pringgodigdo , Pohan Herdiman T.
Published: February 2021

Introduction

Typhoid fever can be challenging to diagnose since clinicians often depend merely on clinical presentation. Clinical scores are useful to provide more accurate diagnosis. Variables in Nelwan Score are derived from clinical signs and symptoms of suspected cases for typhoid. Diagnostic value of Nelwan Score based on a cut-off value has never been evaluated.

Methods

A cross sectional study was conducted between July 2017 and January 2018 in five hospitals and two Primary Health Centers in Jakarta and Tangerang. The inclusion criteria were patients with 3-14 days of fever and gastrointestinal symptoms between July 2017 and January 2018. Diagnosis are confirmed by blood culture, rectal swab culture, or PCR. Cut-off analysis was performed by using Receiver Operating Characteristic (ROC) curve and diagnostic value was analyzed to generate sensitivity, specificity, predictive value and likelihood ratio.

Result

From 233 subjects involved, 4.72% of them were confirmed to have typhoid fever. The optimal cut-off value of Nelwan Score is 10 with AUC 71.3%. This cut-off value has sensitivity 81.8%, specificity 60.8%, PPV 9.3%, NPV 98.5%, LR + 2.086, and LR – 0.299.

Conclusion

Nelwan Score with cut-off value of 10 provides a good diagnostic performance as a screening tool for patients with suspected typhoid fever clinical presentation.
ERICA: Emulated Retinal Image CApture - A tool for testing, training and validating retinal image processing methods
Authors: Young Laura K , Smithson Hannah E
Published: February 2021

High resolution retinal imaging systems, such as adaptive optics scanning laser ophthalmoscopes (AOSLO), are increasingly being used for clinical and fundamental studies in neuroscience. These systems offer unprecedented spatial and temporal resolution of retinal structuresin vivo. However, a major challenge is the development of robust and automated methods for processing and analysing these images. We present ERICA (Emulated Retinal Image CApture), a simulation tool that generates realistic synthetic images of the human cone mosaic, mimicking images that would be captured by an AOSLO, with specified image quality and with corresponding ground truth data. The simulation includes a self-organising mosaic of photoreceptors, the eye movements an observer might make during image capture, and data capture through a real system incorporating diffraction, residual optical aberrations and noise. The retinal photoreceptor mosaics generated by ERICA have a similar packing geometry to human retina, as determined by expert labelling of AOSLO images of real eyes. In the current implementation ERICA outputs convincingly realisticen faceimages of the cone photoreceptor mosaic but extensions to other imaging modalities and structures are also discussed. These images and associated ground-truth data can be used to develop, test and validate image processing and analysis algorithms or to train and validate machine learning approaches. The use of synthetic images has the advantage that neither access to an imaging system, nor to human participants is necessary for development.
Diffuse optical reconstructions of fNIRS data using Maximum Entropy on the Mean
Authors: Cai Zhengchen , Machado Alexis , Chowdhury Rasheda Arman , Spilkin Amanda , Vincent Thomas , Aydin Ümit , Pellegrino Giovanni , Lina Jean-Marc , Grova Christophe
Published: February 2021

Functional near-infrared spectroscopy (fNIRS) measures the hemoglobin concentration changes associated with neuronal activity. Diffuse optical tomography (DOT) consists of reconstructing the optical density changes measured from scalp channels to the oxy-/deoxy-hemoglobin (i.e., HbO/HbR) concentration changes within the cortical regions. In the present study, we adapted a nonlinear source localization method developed and validated in the context of Electro- and Magneto-Encephalography (EEG/MEG): the Maximum Entropy on the Mean (MEM), to solve the inverse problem of DOT reconstruction. We first introduced depth weighting strategy within the MEM framework for DOT reconstruction to avoid biasing the reconstruction results of DOT towards superficial regions. We also proposed a new initialization of the MEM model improving the temporal accuracy of the original MEM framework. To evaluate MEM performance and compare with widely used depth weighted Minimum Norm Estimate (MNE) inverse solution, we applied a realistic simulation scheme which contained 4000 simulations generated by 250 different seeds at different locations and 4 spatial extents ranging from 3 to 40cm2along the cortical surface. Our results showed that overall MEM provided more accurate DOT reconstructions than MNE. Moreover, we found that MEM was remained particularly robust in low signal-to-noise ratio (SNR) conditions. The proposed method was further illustrated by comparing to functional Magnetic Resonance Imaging (fMRI) activation maps, on real data involving finger tapping tasks with two different montages. The results showed that MEM provided more accurate HbO and HbR reconstructions in spatial agreement with the main fMRI cluster, when compared to MNE.

Highlights

We introduced a new fNIRS reconstruction method - Maximum Entropy on the Mean.

We implemented depth weighting strategy within the MEM framework.

We improved the temporal accuracy of the original MEM reconstruction.

Performances of MEM and MNE were evaluated with realistic simulations and real data.

MEM provided more accurate and robust reconstructions than MNE.
The amyloid concentric β-barrel hypothesis: models of Synuclein oligomers, annular protofibrils, lipoproteins, and transmembrane channels
Authors: Durell Stewart R. , Guy H. Robert
Published: February 2021

Amyloid beta (Aβ of Alzheimer’s disease) and α-synuclein (α-Syn of Parkinson’s disease) form large fibrils. Evidence is increasing however that much smaller oligomers are more toxic and that these oligomers can form transmembrane ion channels. We have proposed previously that Aβ42 oligomers, annular protofibrils, and ion channels adopt concentric β-barrel molecular structures. Here we extend that hypothesis to the superfamily of α, β, and γ-synucleins. Our models of numerous Synuclein oligomers, annular protofibrils, tubular protofibrils, lipoproteins, and ion channels were developed to be consistent with sizes, shapes, molecular weights, and secondary structures of assemblies as determined by EM and other studies. The models have the following features: 1) all subunits have identical structures and interactions; 2) they are consistent with conventional β-barrel theory; 3) the distance between walls of adjacent β-barrels is between 0.6 and 1.2 nm; 4) hydrogen bonds, salt bridges, interactions among aromatic side-chains, burial and tight packing of hydrophobic side-chains, and aqueous solvent exposure of hydrophilic side-chains are relatively optimal; and 5) residues that are identical among distantly related homologous proteins cluster in the interior of most oligomers whereas residues that are hypervariable are exposed on protein surfaces. Atomic scale models of some assemblies were developed.
Human immunocompetent Organ-on-Chip platforms allow safety profiling of tumor-targeted T-cell bispecific antibodies
Authors: Kerns S. Jordan , Belgur Chaitra , Petropolis Debora B. , Barrile Riccardo , Kanellias Marianne , Sam Johannes , Weinzierl Tina , Fauti Tanja , Freimoser-Grundschober Anne , Eckmann Jan , Hage Carina , Geiger Martina , Ng Patrick , Tien-Street William , Manatakis Dimitris V. , Micallef Virginie , Gerard Régine , Bscheider Michael , Breous-Nystrom Ekaterina , Schneider Anneliese , Giusti Anna-Maria , Bertinetti-Lapatki Cristina , Grant Heather S. , Roth Adrian B. , Hamilton Geraldine A. , Singer Thomas , Karalis Katia , Moisan Annie , Bruenker Peter , Klein Christian , Bacac Marina , Gjorevski Nikolce , Cabon Lauriane
Published: February 2021

Abstract

Traditional drug safety assessment often fails to predict complications in humans, especially when the drug targets the immune system. Here, we show the unprecedented capability of two Organs-on-Chips to evaluate the safety profile of T-cell bispecific antibodies (TCBs) targeting tumor antigens. Although promising for cancer immunotherapy, TCBs are associated with an on-target, off-tumor risk due to low levels of expression of tumor antigens in healthy tissues. We leveraged in vivo target expression and toxicity data of TCBs targeting folate receptor 1 (FOLR1) or carcinoembryonic antigen (CEA) to design and validate human immunocompetent Organs-on-Chips safety platforms. We discovered that the Lung-Chip and Intestine-Chip could reproduce and predict target-dependent TCB safety liabilities, based on sensitivity to key determinants thereof, such as target expression and antibody affinity. These novel tools broaden the research options available for mechanistic understandings of engineered therapeutic antibodies and assessing safety in tissues susceptible to adverse events.
Male mate choice unresolved in the mangrove rivulus
Authors: Gresham Jennifer D. , Bowman Sarah N. , Keck Chloe M.T. , Quertermous Haylee M. , Earley Ryan L.
Published: February 2021

Mate choice has the potential to drive phenotypic evolution because it can determine traits that increase an individual’s likelihood to reproduce (courtship behaviors, elaborate ornamentation). These traits, however, can also be detrimental for health or survival, often antagonizing the evolution of extreme phenotypes. Mangrove rivulus fish (Kryptolebias marmoratus) develop as self-fertilizing simultaneous hermaphrodites. Hermaphrodites overwhelmingly self-fertilize their eggs internally, but occasionally oviposit unfertilized eggs. Some individuals change sex to male after sexual maturity, essentially forgoing the reproductive assurance of selfing. In a continuing effort to understand how sex change to male is maintained this species, I designed an experiment to determine whether males act as choosers to increase their likelihood of finding unfertilized eggs for reproduction. I hypothesized that males would prefer to associate with younger hermaphrodites when given a dichotomous choice, as they lay a greater proportion of unfertilized eggs compared to older hermaphrodites. The males in this study did not show a preference for either the younger or older hermaphrodite but exhibited greater within individual variance across subtrials than among individual variation. I discuss alternative hypotheses concerning male mate choice in mangrove rivulus, which may illuminate hypotheses to be tested in this and other hermaphroditic species.
Surfactin stimulated by pectin molecular patterns and root exudates acts as a key driver ofBacillus-plant mutualistic interaction
Authors: Hoff Grégory , Arguelles-Arias Anthony , Boubsi Farah , Prsic Jelena , Meyer Thibault , Ibrahim Heba M. M. , Steels Sebastien , Luzuriaga Patricio , Legras Aurélien , Franzil Laurent , Lequart Michelle , Rayon Catherine , Osorio Victoria , de Pauw Edwin , Lara Yannick , Deboever Estelle , de Coninck Barbara , Jacques Philippe , Deleu Magali , Petit Emmanuel , Van Wuytswinkel Olivier , Ongena Marc
Published: February 2021

Bacillus velezensisis considered as model species belonging to the so-calledB. subtiliscomplex that typically evolved to dwell in the soil rhizosphere niche and establish intimate association with plant roots. This bacterium provides protection to its natural host against diseases and represents one of the most promising biocontrol agents. However, the molecular basis of the cross-talk that this bacterium establishes with its natural host has been poorly investigated. We show here that these plant-associated bacteria have evolved some polymer-sensing system to perceive their host and that in response, they increase the production of the surfactin-type lipopeptide. Furthermore, we demonstrate that surfactin synthesis is favoured upon growth on root exudates and that this lipopeptide is a key component used by the bacterium to optimize biofilm formation, motility and early root colonization. In this specific nutritional context, the bacterium also modulates qualitatively the pattern of surfactin homologues co-producedin plantaand mainly forms variants that are the most active at triggering plant immunity. Surfactin represents a shared good as it reinforces the defensive capacity of the host.

Importance

Within the plant-associated microbiome, some bacterial species are of particular interest due to the disease protective effect they provide via direct pathogen suppression and/or stimulation of host immunity. While these biocontrol mechanisms are quite well characterized, we still poorly understand the molecular basis of the cross talk these beneficial bacteria initiate with their host. Here we show that the model speciesBacillus velezensisstimulates production of the surfactin lipopeptide upon sensing pectin as cell surface molecular pattern and upon feeding on root exudates. Surfactin favors bacterial rhizosphere fitness on one hand and primes the plant immune system on the other hand. Our data therefore illustrate how both partners use this multifunctional compound as unique shared good to sustain mutualistic interaction.
NF-κB-repressed Sirt3 mediates testicular cholesterol metabolism and cytoskeleton assembly via P450scc/SOD2 deacetylation during spermatogenesis
Authors: Wang Mei , Zeng Ling , Xiong Yao , Wang Xiao-fei , Cheng Lin , Wang Fang , Su Ping , Zhang Yuan-zhen
Published: February 2021

Testicular homeostasis requires the balanced interplay between specific molecules in Sertoli cells, Leydig cells, germ cells. Loss of this coordination can lead to the disruption of spermatogenesis, even male infertility. By operating the upregulation and downregulation of Sirt3 in our male subfertility rats model and two testicular cells models, we indicated that Sirt3 overexpression and activator ameliorated cholesterol metabolism via P450scc deacetylation in Leydig cells, and cytoskeleton assembly via PDLIM1 with SOD2 deacetylation in Sertoli cells and elongating spermatids. In terms of the upstream regulator of Sirt3, the phosphorylation of NF-κB p65Ser536stimulated the nuclear translocation of NF-κB subunits (p50, p65, RelB), which bound to TFBS1 and TFBS2 synchronously in the promoter of Sirt3, repressing Sirt3 transcription. This study demonstrates that NF-κB-repressed SIRT3 acts directly on cholesterol metabolism of Leydig cells and cytoskeleton assembly of Sertoli cells via P450scc/SOD2 deacetylation to regulate sperm differentiation, influencing spermatogenesis, even male fertility.

Research organism: Rat, mouse
Single cell trajectory analysis of human pluripotent stem cells differentiating towards lung and hepatocyte progenitors
Authors: Ori Chaido , Ansari Meshal , Angelidis Ilias , Theis Fabian J. , Schiller Herbert B. , Drukker Micha
Published: February 2021

Understanding the development of human respiratory tissues is crucial for modeling and treating lung disorders. The molecular details for the specification of lung progenitors from human pluripotent stem cells (hPSCs) are unclear. Here, we use single cell RNA-sequencing with high temporal resolution along an optimized differentiation protocol to determine the transcriptional hierarchy of lung specification from human hPSCs and map out the underlying single cell trajectories. We show that Sonic hedgehog, TGF-βand Notch activation are required in anISL1/NKX2-1trajectory that gives rise to lung progenitors during the foregut endoderm stage. Induction ofHHEXmarks an alternative trajectory at the early definitive endoderm stage, which precedes the lung trajectory and generates a major hepatoblast population. Moreover, neither KDR+ nor mesendoderm progenitors are apparent intermediate states of lung and hepatic lineages. Our hierarchical multistep model predicts mechanisms leading to lung organogenesis, and creates a basis for studying early human lung development, as well as hPSC based disease and drug research.

Abstract Figure
Sphingolipid Control of Fibroblast Heterogeneity Revealed by Single-Cell Lipidomics
Authors: Capolupo Laura , Khven Irina , Mazzeo Luigi , Glousker Galina , Russo Francesco , Montoya Jonathan Paz , Ho Sylvia , Bhandari Dhaka R. , Bowman Andrew P. , Ellis Shane R. , Guiet Romain , Muthing Johannes , Spengler Bernhard , Heeren Ron M.A. , Dotto Gian Paolo , La Manno Gioele , D’Angelo Giovanni
Published: February 2021

Human cells produce thousands of lipids that impact a wide range of biological processes in ways we are only starting to characterize. The cellular composition in lipids changes during differentiation events and also varies across individual cells of the same type. Yet, the precise differences in lipid composition that directly affect cell phenotypes remain unknown. Here we have measured the lipidomes and transcriptomes of individual human dermal fibroblasts by coupling high-resolution mass spectrometry imaging to single-cell transcriptomics. We found that the cell-to-cell variation of specific lipid metabolic pathways contributes to the establishment of cell states involved in wound repair and in skin cancer growth. Sphingolipid composition defined fibroblast subpopulations while sphingolipid metabolic rewiring drove cell state transitions. These data uncover a role for cell-to-cell lipid heterogeneity in the determination of cell states and reveal a new regulatory component to the homeostasis and self-organization of multicellular systems.
Fluctuating environments maintain genetic diversity through neutral fitness effects and balancing selection
Authors: Abdul-Rahman Farah , Tranchina Daniel , Gresham David
Published: February 2021

Genetic variation is the raw material upon which selection acts. The majority of environmental conditions change over time and therefore may result in variable selective effects. How temporally fluctuating environments impact the distribution of fitness effects and in turn population diversity is an unresolved question in evolutionary biology. Here, we employed continuous culturing using chemostats to establish environments that switch periodically between different nutrient limitations and compared the dynamics of selection to static conditions. We used the pooledSaccharomyces cerevisiaehaploid gene deletion collection as a synthetic model for populations comprising thousands of unique genotypes. Using barcode sequencing (barseq), we find that static environments are uniquely characterized by a small number of high fitness genotypes that rapidly dominate the population leading to dramatic decreases in genetic diversity. By contrast, fluctuating environments are enriched in genotypes with neutral fitness effects and an absence of extreme fitness genotypes contributing to the maintenance of genetic diversity. We also identified a unique class of genotypes whose frequencies oscillate sinusoidally with a period matching the environmental fluctuation. Oscillatory behavior corresponds to large differences in short term fitness that are not observed across long timescales pointing to the importance of balancing selection in maintaining genetic diversity in fluctuating environments. Our results are consistent with a high degree of environmental specificity in the distribution of fitness effects and the combined effects of reduced and balancing selection in maintaining genetic diversity in the presence of variable selection.
What is behind grit? Developing stamina for your organization
Authors: Menéndez Blanco Juan Manuel
Published: February 2021

Purpose

This paper offers a practical conceptualization and understanding of grit, exploring what grit adds to the organizations and how to develop it at an individual and organizational level.

Design/methodology/approach

The article is based on Duckworth’s and colleagues’ research on grit and later developments, especially those related to the empirical check on the relationships between grit and individual accomplishment and company performance. It combines a literature review overview and conceptual developments with practical application.

Findings

Grit is a two-factor personality trait positively correlated to conscientiousness that promotes and predicts superior achievement and accomplishment. Developing a nurtured grit capacity requires promoting learning, coaching, executive intelligence, and positive interactions at work within a critical thinking environment.

Research limitations/implications

Following the conceptual model developed, further research is needed about the relationships between growth mindset, critical thinking, grit, grit and resilience, and how individual grit becomes organizational.

Practical implications

A superior accomplishment can be achieved by integrating and promoting grit employees within the company. Besides, grit is also a good predictor of happiness, rising above, hardiness, and other desirable attributes. Grit requires the development of a critical-thinking environment and executive intelligence workforce.

Social implications

Superior accomplishment through life helps to develop this goal in the workplace. The pandemic magnitude is partly due to a lack of critical thinking and grit.

Originality/value

This paper guides managers and professionals to implement a grit company strategy grounded on some reputation research without abstracted theoretical disquisitions.
Thanks, neighbor! Stock market experience around significant European tax cuts
Authors: Wang Huabing , Macy Anne
Published: February 2021

Purpose

This paper analyzes the effect of corporate tax cuts on the competitiveness of the tax-cutting countries and neighbor countries.

Design/methodology/approach

This study utilizes four significant corporate tax reforms among the OECD countries in Europe that offer a one-time tax cut of 6% or more. The short-term event study approach examines the stock index reactions for both the tax-cutting countries and the other countries. Multivariate fixed-effect regressions are employed to study the cross-sectional variations in the non-tax-cut countries.

Findings

This paper finds positive excess returns for Slovakia and Germany around the tax-cut passage. Multivariate analysis of stock market reactions of the non-tax-cutting countries reveals some evidence supporting both the positive spillover effect and the negative competitive loss effect. More advanced countries are more likely to experience higher abnormal returns, while higher tax countries are more likely to suffer lower abnormal returns. Other factors identified that might have influenced the effect of a foreign tax cut include the existing trade flows with the tax-cutting countries, whether the country has a common currency and the export orientation of the economy.

Research limitations/implications

The findings are subject to sample-size issues. The lack of results for the other two countries is due to complicating events, as suggested by the further investigation of concurrent news events around the event days.

Practical implications

The simultaneous analysis of the reform countries and the other countries in the region suggests that policymakers need to consider the relative positioning of their country vs the other countries in terms of economic development and current tax burdens when determining the optimal policy for their country or to respond to the tax policy changes in the other countries.

Originality/value

This study offers empirical evidence regarding the effect of corporate tax changes on competitiveness through the lens of stock markets' reactions, which depend on the net results of the spillover gain vs the competitive loss.
Blockchain in operations for food service distribution: steps before implementation
Authors: Vivaldini Mauro
Published: February 2021

Purpose

Considering the importance of a safe food chain for consumers and the advent of blockchain technology (BT), this research studies a food service (FS) distributor. The research aims to understand the implications related to the functional processes of distribution in FS in which it would be possible to use blockchain to achieve agility, transparency of information and improvements in food safety.

Design/methodology/approach

Firstly, theory regarding blockchain technology in the supply chain (BT-SC) and FS was analyzed to contextualize the theme conceptually. A single case study including 11 supply chain companies was applied in a BT implementation study in an FS distributor.

Findings

Investment in infrastructure is often identified as a barrier to adoption of BT-SC. This was, however, not found in this case. Furthermore, the validation of users was only necessary for those parties directly participating in the process or information input. Finally, findings differentiate between qualifying criteria and operational processes when considering BT projects in FS.

Research limitations/implications

The findings are restricted to this single case that provided an in-depth understanding of the topic. Statistical generalization is not possible at this stage of the research.

Practical implications

The study is a practical example and can provide several insights to anyone looking to implement BT in their SC.

Social implications

The social importance of the study lies in the importance of FS in the food sector, and by presenting ways that contribute to mitigating risks to consumers.

Originality/value

Real-life cases of application of BT-SC illustrate its functionalities in operational processes.
Impact of family control on information technology investment and information technology adoption in India
Authors: Mand Harvinder S. , Kaur Gaganpreet , Gill Amarjit , Mathur Neil
Published: February 2021

Purpose

This study tests the impact of family control on information technology (IT) investment and IT adoption in MSMEs in India.

Design/methodology/approach

This study employs a survey research design. Micro, small, and medium enterprise (MSME) owners in India were surveyed to test the impact of family control on IT investment and IT adoption.

Findings

Our empirical results show that family control — measured by family ownership, family member firm management, and/or family CEO duality — increases IT investment and IT adoption in India. Family ownership increases the chances of IT investment and IT adoption by 19.24% and 38.40%, respectively. Firm management by family members increases the chances of IT investment and IT adoption by 11.29% and 18.29%, respectively. CEO duality increases the chances of IT investment and IT adoption by 51.13% and 258%, respectively. Thus, CEO duality has a higher impact on IT investment and IT adoption than family ownership and firm management by family members.

Research limitations/implications

The empirical results may be generalized only to MSMEs similar to those surveyed in this study. Additionally, this study relied on the perceptions and judgments of MSME owners.

Originality/value

This study contributes to the literature on the impact of family control on IT investment and IT adoption in the developing economics. This study can help scholars to develop further studies in the family control area. Our findings may help MSME owners to increase family control to survive and prosper into the future. Additionally, MSME management consultants may find the empirical results useful to provide consulting services.
Deciding between cash-based and in-kind distributions during humanitarian emergencies
Authors: García Castillo Jorge
Published: February 2021

Purpose

The purpose of this paper is to provide an analytical model to decide between cash-based and in-kind distributions during emergency responses considering the needs of beneficiaries and market conditions. To allow the switch between modalities, a preparedness framework for humanitarian organizations (HOs) is provided.

Design/methodology/approach

A mathematical model is proposed to help humanitarian responders make quantitative decisions on the type of programs to implement in emergency responses. The model was applied to a field response by an international HO during the COVID-19 emergency in Colombia.

Findings

Cash-based and in-kind distributions are not mutually exclusive response modalities during emergencies, and the real needs of beneficiaries and market effects should be included in the modality selection decision to improve program effectiveness.

Research limitations/implications

The research is focused on short-term immediate response to emergencies; the proposed model assumes favorable market conditions and limits the aid options to direct in-kind and multipurpose cash assistance, excluding other types of cash transfers.

Practical implications

The research outlines practical preconditions to operationalize switching between programs during an emergency. The study provides evidence that HOs should consider dynamics decision tools to select aid modalities and evaluate their response depending on market conditions.

Social implications

Considering aid modality as a dynamic decision and including the needs from beneficiaries in the choice can have profound impact in the dignifying of humanitarian response to emergencies.

Originality/value

The quantitative model to decide between aid modalities is a novel approach to include beneficiaries' needs and market dynamics into humanitarian supply chain research. The preparedness framework closes the gap between the emergency preparedness literature and the operational constraints that organizations face for fast program implementation.