bluuebunny/crossref_metadata_2025 huggingface dataset:
Reweighting of molecular simulations with explicit-solvent SAXS restraints elucidates ion-dependent RNA ensembles
Authors: Bernetti Mattia , Hall Kathleen B , Bussi Giovanni
Published: May 2021

Small-angle X-ray scattering (SAXS) experiments are increasingly used to probe RNA structure. A number of forward models that relate measured SAXS intensities and structural features, and that are suitable to model either explicit-solvent effects or solute dynamics, have been proposed in the past years. Here, we introduce an approach that integrates atomistic molecular dynamics simulations and SAXS experiments to reconstruct RNA structural ensembles while simultaneously accounting for both RNA conformational dynamics and explicit-solvent effects. Our protocol exploits SAXS pure-solute forward models and enhanced sampling methods to sample an heterogenous ensemble of structures, with no information towards the experiments provided on-the-fly. The generated structural ensemble is then reweighted through the maximum entropy principle so as to match reference SAXS experimental data at multiple ionic conditions. Importantly, accurate explicit-solvent forward models are used at this reweighting stage. We apply this framework to the GTPase-associated center, a relevant RNA molecule involved in protein translation, in order to elucidate its ion-dependent conformational ensembles. We show that (a) both solvent and dynamics are crucial to reproduce experimental SAXS data and (b) the resulting dynamical ensembles contain an ion-dependent fraction of extended structures.
The aging slow wave: a shifting amalgam of distinct slow wave and spindle coupling subtypes define slow wave sleep across the human lifespan
Authors: McConnell Brice V , Kronberg Eugene , Teale Peter D , Sillau Stefan H , Fishback Grace M , Kaplan Rini I , Fought Angela J , Dhanasekaran A Ranjitha , Berman Brian D , Ramos Alberto R , McClure Rachel L , Bettcher Brianne M
Published: May 2021

Study Objectives

Slow wave and spindle coupling supports memory consolidation, and loss of coupling is linked with cognitive decline and neurodegeneration. Coupling is proposed to be a possible biomarker of neurological disease, yet little is known about the different subtypes of coupling that normally occur throughout human development and aging. Here we identify distinct subtypes of spindles within slow wave upstates and describe their relationships with sleep stage across the human lifespan.

Methods

Coupling within a cross-sectional cohort of 582 subjects was quantified from stages N2 and N3 sleep across ages 6–88 years old. Results were analyzed across the study population via mixed model regression. Within a subset of subjects, we further utilized coupling to identify discrete subtypes of slow waves by their coupled spindles.

Results

Two different subtypes of spindles were identified during the upstates of (distinct) slow waves: an “early-fast” spindle, more common in stage N2 sleep, and a “late-fast” spindle, more common in stage N3. We further found stages N2 and N3 sleep contain a mixture of discrete subtypes of slow waves, each identified by their unique coupled-spindle timing and frequency. The relative contribution of coupling subtypes shifts across the human lifespan, and a deeper sleep phenotype prevails with increasing age.

Conclusions

Distinct subtypes of slow waves and coupled spindles form the composite of slow wave sleep. Our findings support a model of sleep-dependent synaptic regulation via discrete slow wave/spindle coupling subtypes and advance a conceptual framework for the development of coupling-based biomarkers in age-associated neurological disease.
Study of the metabolic alterations in patulin-induced neoplastic transformation in normal intestinal cells
Authors: Singh Neha , Sharma Gaurav , Dev Indra , Shukla Sanjeev K , Ansari Kausar Mahmood
Published: May 2021

Several surveillance studies have reported significantly high level of patulin (PAT), mycotoxin in fruit juices suggesting the possible exposure to human. In vitro studies have showed that PAT can alter the permeability, ion transport and modulates tight junction of intestine. In real scenario, human can be exposed with low levels of PAT for longer duration through different fruits and their products. Hence, keeping this possibility in view, we conducted a study where normal intestinal cells were exposed with non-toxic levels of PAT for longer duration and found that PAT exposure causes cancer-like properties in normal intestinal cells. It is a well-known fact that cancer cells rewired their metabolism for cell growth and survival and metabolites closely depict the phenotypic properties of cells. Here, metabolomic study was performed in the PAT transformed and passage matched non-transformed cells using 1H HRMAS NMR. We have identified 12 significantly up-regulated metabolites, which, interestingly, were majorly amino acids, suggesting that PAT-induced pre-cancerous cells are involved in acquirement of nutrients for high protein turn-over. Furthermore, pathway analysis of metabolomics data indicated that aminoacyl tRNA biosynthesis, D-glutamate metabolism, glyoxylate and dicarboxylate metabolism and nitrogen metabolism were majorly hampered in PAT-induced pre-cancerous properties in normal intestinal cells.
Study on toxicological effect and the mechanism of cadmium in rice and inorganic cadmium on ICR mice
Authors: Yin Xiaoyao , Wu Qian , Song Wanying , Yang Qing , Wu Yongning , Fang Min , Gong Zhiyong
Published: May 2021

Cadmium (Cd) exposure may induce chronic intoxication, but the harm of cadmium in rice to human at chronic low-level Cd exposure remains unclear. This study employed a mouse model to investigate the toxicity and mechanism of cadmium in rice and CdCl2. After 8-week exposure to Cd (CdCl2 and Cd-contaminated rice), the biochemical indicators and oxidation indicators in the serum and liver of mice were determined, and used mRNA sequencing to investigate the mechanism of different forms of Cd. Results showed that the cadmium concentration of the liver in the CdCl2 + Rice-N group (CdCl2 mixed with feed and normal rice, 0.4mg/kg.bw) was higher than that in the Rice-H group (0.4mg/kg.bw). However, the cadmium concentration of the kidneys in the Rice-H group was higher than that in the CdCl2 + Rice-N group. Our study demonstrated that Cd-treated (Cd in rice and CdCl2) ICR mice generated obviously tissues injury, such as the increased biochemical studies, the activity of antioxidant enzymes debasement. Simultaneously, our data also indicated that there existed difference of the hepatic toxicity between Cd in rice and CdCl2. By means of transcriptomics, we discovered that CdCl2 and Cd in rice may affect different gene expression at the molecular level. We hope to provide some theoretical basis for the revision of food security standards.
Lessons From the Feasibility Testing of a Parent-Focused, Life Skills–Based Intervention to Prevent Obesity in Preschoolers From Underserved Families
Authors: Erinosho Temitope , Treadway Cayla , Wretman Christopher J. , Hales Derek , Blitstein Jonathan L. , Ward Dianne S.
Published: May 2021

This article describes lessons from the feasibility testing of a parent-focused, life skills–based intervention to promote healthy weight in 58 low-income children aged 2 to 5 years. This intervention was feasible and acceptable, with a potential to impact child weight and diet (calories) and parental quality of life (QOL). The group delivery approach through a partnering organization (Head Start) was a more efficient way to reach/engage parents. Compared with one-on-one sessions, the group could provide an avenue to enhance parental psychosocial well-being, given QOL improvements among parents in group sessions. Lessons will inform future research to test the effectiveness of life skills interventions.
Differences in the antinociceptive effects of serotonin–noradrenaline reuptake inhibitors via sodium channel blockade using the veratrine test in mice
Authors: Yoshizawa Kazumi , Suzuki Yukina , Nakamura Toka , Takahashi Yukino , Makino Kosho , Takahashi Hideyo
Published: May 2021

Antidepressants exert their analgesic effects by inhibiting the reuptake of noradrenaline. Several antidepressants have been shown to block the sodium channels, which might contribute to their analgesic potency. The aim of this study was to determine whether serotonin–noradrenaline reuptake inhibitors (SNRIs) could produce antinociceptive effects via sodium channel blockade using the veratrine test in mice. Furthermore, the effects of these agents on the veratrine test were examined to elucidate the effects of several antidepressants and tramadol on sodium channels. The administration of duloxetine (10 mg/kg) and venlafaxine (30 mg/kg) suppressed cuff-induced mechanical allodynia; however, these antinociceptive effects were only partially suppressed by atipamezole. Furthermore, duloxetine and venlafaxine demonstrated antinociceptive effects via sodium channel blockade, as assayed by the veratrine test. In addition, several antidepressants, including amitriptyline, paroxetine and mirtazapine, reduced veratrine-induced nociception. In contrast, milnacipran and tramadol did not alter the veratrine-induced nociception. These results indicated that, in addition to the primary action of SNRIs on monoamine transporters, sodium channel blockade might be involved in the antinociceptive activities of duloxetine and venlafaxine, but not milnacipran.
HnRNP F and hnRNP H1 regulate mRNA stability of amyloid precursor protein
Authors: Khan Muhammad I. , Zhang Juan , Liu Qiang
Published: May 2021

Amyloid precursor protein (APP) is a transmembrane protein that plays a crucial role in the production of amyloid-β peptides. Any disruption in APP protein production, its mRNA decay rate or processing may result in abnormal production of amyloid-β peptides and subsequent development of protein aggregation diseases. Therefore, the equilibrium is crucial for neuronal function. An association study of heterogeneous nuclear ribonucleoprotein (hnRNP)-F and hnRNP H1 with APP was carried out in Neuro-2a (N2a) cells. In the present study, we found that hnRNP F and hnRNP H1 were significantly upregulated in the hippocampus of APP/PS1 mice. The changes in APP expression were positively associated with hnRNP F and hnRNP H1 when hnRNP F and hnRNP H1 were depleted or increased in N2a cells. Importantly, cross-linked RNA immunoprecipitation demonstrated binding affinities of hnRNP F and hnRNP H1 for App mRNA. Mechanistically, mRNA stability assay revealed that overexpression of hnRNP F or hnRNP H1 increases the APP level by stabilizing App mRNA half-life, implying that levels of hnRNP F and hnRNP H1 can change the production of APP. Further understanding of the regulatory mechanism of APP expression in association with hnRNP F and hnRNP H1 would provide insights into the mechanism underlying the maintenance of brain health and cognition. This study provides a theoretical basis for the development of hnRNP-stabilizing compounds to regulate APP.
High mobility group box 1 is involved in the pathogenesis of passive transfer myasthenia gravis model
Authors: Maimaitiming Bibinu , Uzawa Akiyuki , Ozawa Yukiko , Yasuda Manato , Kojima Yuta , Kanai Tetsuya , Kuwabara Satoshi
Published: May 2021

Myasthenia gravis (MG) is an autoimmune disease with autoantibodies against the mainly nicotinic acetylcholine receptor (AChR). High mobility group box1 (HMGB1) acts as a danger signal and drives the pathogenesis of autoimmune-mediated diseases. However, the role of HMGB1 in the pathogenesis of MG is not fully understood. Therefore, in this study, we analyzed serum levels of HMGB1 and immunohistochemical HMGB1 staining of muscle tissues in the passive transfer MG model to investigate the role of HMGB1 in MG. As a result, serum HMGB1 levels tended to be higher and the quantitative score of muscle pathology showed greater HMGB1 deposition (P = 0.02) along with sparser AChR staining and more severe inflammation in the passive transfer MG rats (n = 6) than those in control rats (n = 6). These findings indicate that HMGB1 is an important mediator and biomarker for inflammation in the pathogenesis of MG and can be a therapeutic target in MG.
Difference in drug susceptibility distribution and clinical characteristics between Mycobacterium avium and Mycobacterium intracellulare lung diseases in Shanghai, China
Authors: Wang Weiping , Yang Jinghui , Wu Xiaocui , Wan Baoshan , Wang Hongxiu , Yu Fangyou , Guo Yinjuan
Published: May 2021

Introduction.

Mycobacterium avium

complex (MAC) has been reported as the most common aetiology of lung disease involving nontuberculous mycobacteria.

Hypothesis. Antimicrobial susceptibility and clinical characteristics may differ between

Mycobacterium avium

and

Mycobacterium intracellulare

.

Aim. We aimed to evaluate the differences in antimicrobial susceptibility profiles between two major MAC species (

Mycobacterium avium

and

Mycobacterium intracellulare

) from patients with pulmonary infections and to provide epidemiologic data with minimum inhibitory concentration (MIC) distributions.

Methodology. Between January 2019 and May 2020, 45

M. avium

and 242

M

.

intracellulare

isolates were obtained from Shanghai Pulmonary Hospital. The demographic and clinical characteristics of patients were obtained from their medical records. The MICs of 13 antimicrobials were determined for the MAC isolates using commercial Sensititre SLOWMYCO MIC plates and the broth microdilution method, as recommended by the Clinical and Laboratory Standards Institute (CLSI; Standards M24-A2). MIC50 and MIC90 values were derived from the MIC distributions.

Results.

M. intracellulare

had higher resistance rates than

M. avium

for most tested antimicrobials except clarithromycin, ethambutol, and ciprofloxacin. Clarithromycin was the most effective antimicrobial against both the

M. avium

(88.89 %) and

M. intracellulare

(91.32 %) isolates, with no significant difference between the species (P=0.601). The MIC90 of clarithromycin was higher for

M. avium

(32 µg ml−1) than

M. intracellulare

(8 µg ml−1). The MIC50 of rifabutin was more than four times higher for

M. intracellulare

(1 µg ml−1) than

M. avium

(≤0.25 µg ml−1). The percentages of patients aged >60 years and patients with sputum, cough, and cavitary lesions were significantly higher than among patients with

M. intracellulare

infection than

M. avium

infections.

Conclusions. The pulmonary disease caused by distinct MAC species had different antimicrobial susceptibility, symptoms, and radiographic findings.
Wilson Statistics: Derivation, Generalization, and Applications to Electron Cryomicroscopy
Authors: Singer Amit
Published: May 2021

The power spectrum of proteins at high frequencies is remarkably well described by the flat Wilson statistics. Wilson statistics therefore plays a significant role in X-ray crystallography and more recently in electron cryomicroscopy (cryo-EM). Specifically, modern computational methods for three-dimensional map sharpening and atomic modelling of macromolecules by single particle cryo-EM are based on Wilson statistics. Here we provide the first rigorous mathematical derivation of Wilson statistics. The derivation pinpoints the regime of validity of Wilson statistics in terms of the size of the macromolecule. Moreover, the analysis naturally leads to generalizations of the statistics to covariance and higher order spectra. These in turn provide theoretical foundation for assumptions underlying the widespread Bayesian inference framework for three-dimensional refinement and for explaining the limitations of autocorrelation based methods in cryo-EM.
The role of PI(4,5)P2 and synaptotagmin in membrane fusion - an in vitro study
Authors: Dietz Jörn , Oelkers Marieelen , Hubrich Raphael , Pérez-Lara Angel , Jahn Reinhard , Steinem Claudia , Janshoff Andreas
Published: May 2021

Synaptotagmin-1 (syt-1) is known to trigger fusion of neuronal synaptic vesicles with the presynaptic membrane by recognizing acidic membrane lipids. In particular, binding to PI(4,5)P2 is believed to be crucial for its function as a calcium sensor. We propose a mechanism for syt-1 to interact with anionic bilayers and promote fusion in the presence of SNARE proteins. We found that in the absence of Ca2+ the binding of syt-1 to membranes depends on the PI(4,5)P2 content. Addition of Ca2+ switches the interaction forces from weak to strong eventually exceeding the cohesion of the C2A domain, while the interaction between PI(4,5)P2 and the C2B domain was preserved even in the absence of Ca2+ or phosphatidylserine. Fusion of large unilamellar vesicles equipped with syt-1 and synaptobrevin with free-standing target membranes composed of PS/PI(4,5)P2 show an increased fusion speed, and by effective suppression of stalled intermediate states, a larger number of full fusion events. Fusion efficiency could be maximized when irreversible docking is additionally prevented by addition of multivalent anions. The picture that emerges is that syt-1 remodels the membrane in the presence of calcium and PIP2, thereby substantially increasing the efficiency of membrane fusion by avoiding stalled intermediate states.
Truncated Caveolin-3 Mutation In Familial Barrett’s Esophagus
Authors: Garman Katherine S. , Furstenberg Richard von , Fecteau Ryan , Becker Thomas C. , Purkayastha Biswa P. D. , Falk Gary W. , Dawson Dawn , Willis Joseph E. , McCall Shannon J. , Blum Andrew E. , Guda Kishore , Chak Amitabh
Published: May 2021

Objective

Barrett’s esophagus and esophageal adenocarcinoma demonstrate familial aggregation. The goal was to identify a segregating genetic variant in an large family and subsequently localize esophageal gene expression.

Methods

Whole exome sequencing of genomic DNA from affected members of a large family with Barrett’s esophagus and esophageal adenocarcinoma was analyzed to identify rare coding variants in genes segregating with disease. Histopathological assessment of archived formalin fixed esophageal human and porcine tissues to localize expression of identified genes in esophagus.

Results

A segregating nonsense mutation in the gene Caveolin-3 (CAV3) was identified. Esophageal CAV3 localized to myoepithelial cells around esophageal submucosal glands. Histologic examination of a formalin fixed paraffin embedded esophagectomy specimen from an individual carrying theCAV3null mutation revealed submucosal glands demonstrating atypical acinar metaplasia with absence of myoepithelial cells and no CAV3+ cells.

Conclusions

Submucosal glands contribute to healing of injured squamous esophagus. We theorize the truncating nonsenseCAV3mutation disrupts normal squamous healing and the organization of submucosal glands, making affected family members susceptible to the proliferation and development of metaplastic columnar Barrett’s esophagus.
Effective Computational Framework for Pre-Interventional Planning of Peripheral Arteriovenous Malformations with In Vivo and In Vitro Validation
Authors: Franzetti Gaia , Bonfanti Mirko , Tanade Cyrus , Lim Chung Sim , Tsui Janice , Hamilton George , Díaz-Zuccarini Vanessa , Balabani Stavroula
Published: May 2021

Purpose

Peripheral arteriovenous malformations (pAVMs) are congenital lesions characterised by abnormal high-flow, low-resistance vascular connections – constituting the so-called nidus – between arteries and veins. The mainstay treatment typically involves the embolisation of the nidus with embolic and sclerosant agents, however the complexity of AVMs often leads to uncertain outcomes. This study aims at developing a simple, yet effective computational framework to aid the clinical decision making around the treatment of pAVMs.

Methods

A computational model was developed to simulate the pre-, intra-, and post-intervention haemodynamics of an AVM. A porous medium of varying permeability was used to simulate the effect that the sclerosant has on the blood flow through the nidus. The computational model was informed by computed tomography (CT) scans and digital subtraction angiography (DSA) images, and the results were compared against clinical data and experimental results.

Results

The computational model was able to simulate the blood flow through the AVM throughout the intervention and predict (direct and indirect) haemodynamic changes due to the embolisation. The simulated transport of the dye in the AVM was compared against DSA time-series obtained at different intervention stages, providing confidence in the results. Moreover, experimental data obtained via a mock circulatory system involving a patient specific 3D printed phantom of the same AVM provided further validation of the simulation results.

Conclusion

We developed a simple computational framework to simulate AVM haemodynamics and predict the effects of the embolisation procedure. The developed model lays the foundation of a new, computationally driven treatment planning tool for AVM embolisation procedures.
BpOmpW Antigen Stimulates the Necessary Immune Correlates of Protection Against Melioidosis
Authors: Tomás-Cortázar Julen , Bossi Lorenzo , Quinn Conor , Reynolds Catherine , Butler David , Corcoran Niamh , Murchú Maitiú Ó , McMahon Eve , Singh Mahavir , Rongkard Patpong , Anguita Juan , Blanco Alfonso , Dunachie Susanna J. , Altmann Danny , Boyton Rosemary , Arnold Johan , Giltaire Severine , McClean Siobhán
Published: May 2021

SUMMMARY

Melioidosis is a fatal disease caused by Burkholderia pseudomallei Gram-negative bacteria. It is the causative of 89,000 deaths per year in endemic areas of Southeast Asia and Northern Australia. Diabetes mellitus is the most risk factor, increasing 12-fold the susceptibility for severe disease. IFN-γ responses from CD4 and CD8 T cells, but also from NK and NKT cells are necessary to eliminate the pathogen. Elucidating the immune correlates of protection of our previously described protective BpOmpW vaccine is an essential step of any vaccine before clinical trials. Thus, we immunized non-insulin resistant C57BL/6j mice and an insulin resistant C57BL/6j mouse model of Type 2 Diabetes (T2D) with BpOmpW using Sigma Adjuvant System (SAS) (treatment) or SAS only (control). Two weeks later bloods and spleens were collected and serological analysis & in vitro exposure of splenocytes to the antigen for 60 hours were performed in both controls and treatment groups to finally analyze the stained splenocytes by flow cytometry. BpOmpW induced strong antibody response, stimulated effector CD4+ and CD8+ T cells and CD4+ CD25+ Foxp3+regulatory T cells and produced higher IFN-γ responses in CD4+, CD8+, NK and NKT cells relative to the control group in non-insulin resistant mice. T cell responses of insulin resistant mice to BpOmpW were comparable to those in non-insulin resistant mice. In addition, as a precursor to its evaluation in human studies, humanised HLA-DR and HLA-DQ transgenic mice elicited IFN-γ recall responses in an ELISPoT-based study and PBMCs from donors that were in contact to BpOmpW for seven days experienced T cell proliferation. Finally, plasma from melioidosis survivors with diabetes recognized our BpOmpW vaccine antigen. Overall, these range of approaches used strongly indicate that BpOmpW elicits the required immune correlates of protection to combat melioidosis and bring the vaccine closer to clinical trials.
Monolayer graphene-on-polymer dressings promote healing and stabilize skin temperature on acute and chronic wound models
Authors: Le Gall Marion , Serantoni Vincent , Louche Hervé , Jourdan Franck , Sigaudo-Roussel Dominique , Bonod Christelle , Ferraro Sandra , Othmen Riadh , Bourrier Antoine , Dahri-Correia Latifa , Hurot Charlotte , Téot Luc , Bouchiat Vincent , Lacampagne Alain
Published: May 2021

Monolayer graphene presented on the wound bed is assessed for its healing properties using both in vitro and in vivo models. For in vivo study, a cutaneous excisional wound is created on the dorsal surface of healthy and type-1 diabetic mice to mimic acute and delayed wound healing, respectively. A pig model is also chosen for its resemblance to human skin. Photographic and histological assessment of the wound are coupled with thermographic data recorded with an infrared camera. Graphene monolayer accelerates early phases of wound healing in vivo in every tested model. Upon removal of the bandage, wounds coated with graphene are less prone to temperature drop compared to the control samples. We hypothesize that graphene may directly shorten the inflammatory phase and/or enhance angiogenesis and cell migration in proliferative phase as demonstrated in vitro. Thermographic assessment of wounds could be of particular interest to follow both phenomena in an objective, rapid and non-invasive manner.
pH-dependent 11° F1Fo ATP synthase sub-steps reveal insight into the Fo torque generating mechanism
Authors: Yanagisawa Seiga , Frasch Wayne D.
Published: May 2021

Most cellular ATP is made by rotary F1Fo ATP synthases using proton translocation-generated clockwise torque on the Fo c-ring rotor, while F1-ATP hydrolysis can force anticlockwise rotation and proton pumping. Although the interface of stator subunit-a containing the transmembrane half-channels and the c-ring is known from recent F1Fo structures, the torque generating mechanism remains elusive. Here, single-molecule studies reveal pH-dependent 11° rotational sub-steps in the ATP synthase direction of the E. coli c10-ring of F1Fo against the force of F1-ATPase-dependent rotation that result from H+ transfer events from Fo subunit-a groups with a low pKa to one c-subunit of the c-ring, and from an adjacent c-subunit to stator groups with a high pKa. Mutations of subunit-a residues in the proton translocation channels alter these pKa values, and the ability of synthase substeps to occur. Alternating 11° and 25° sub-steps then result in sustained ATP synthase rotation of the c10-ring.
Slow Cortical Waves through Cyclicity Analysis
Authors: Abraham Ivan , Shahsavarani Somayeh , Zimmerman Benjamin , Husain Fatima , Baryshnikov Yuliy
Published: May 2021

Fine-grained understanding of dynamics in cortical networks is crucial in unpacking brain function. Here, we introduce a novel analytical method to characterize the dynamic interaction between distant brain regions, and apply it to data from the Human Connectome Project.

Resting-state fMRI results in time series recordings of the activity of different brain regions, which are aperiodic and lacking a base frequency. Cyclicity Analysis, a novel technique robust with respect to time-reparametrizations, is effective in recovering temporal ordering of such time series along a circular trajectory without assuming any time-scale. Our analysis detected slow cortical waves of activity propagating across the brain with consistent lead-lag relationships between specific brain regions. We also observed short bursts of task-modulated strong temporal ordering that dominate overall lead-lag relationships between pairs of regions in the brain. Our results suggest the possible role played by slow waves of information transmission between brain regions that underlie emergent cognitive function.
Transcriptome analysis of the effect of AHR on productive and unproductive pathways of in vitro megakaryocytopoiesis
Authors: Mallo Léa , Sacramento Valentin Do , Gachet Christian , Lanza François , de la Salle Henri , Strassel Catherine
Published: May 2021

Human CD34+ progenitors can be differentiated in vitro into proplatelet-producing megakaryocytes (MKs) within 17 days. During this time, four cell populations emerge, phenotypically defined as CD34+CD41+ on day 7 (D7) and CD34+CD41+CD9- on D10 and D14 - qualified as “productive” because they can differentiate into proplatelet-forming cells during the D14-D17 period - and CD34-CD41+ or CD34+CD41+CD9+ on day 10 - qualified as “unproductive” because they are unable to form proplatelets later. Coculture with mesenchymal stem cells, or the presence of the AHR antagonist SR1, boosts the productive pathway in two ways: firstly, it increases the yield of D10 and D14 CD34+CD41+CD9- cells and secondly, it greatly increases their ability to generate proplatelets; in contrast, SR1 has no noticeable effect on the unproductive cell types. A transcriptome analysis was performed to decipher the genetic basis of these properties. This work represents the first extensive description of the genetic perturbations which accompany the differentiation of CD34+ progenitors into mature MKs at a subpopulation level. It highlights a wide variety of biological changes modulated in a time-dependent manner and allows anyone, according to his/her interests, to focus on specific biological processes accompanying MK differentiation. For example, the modulation of the expression of genes associated with cell proliferation, lipid and cholesterol synthesis, extracellular matrix components, intercellular interacting receptors and MK and platelet functions reflected the chronological development of the productive cells and pointed to unsuspected pathways. Surprisingly, SR1 only affected the gene expression profile of D10 CD34+CD41+CD9- cells; thus, as compared to these cells and those present on D14, the poorly productive D10 CD34+CD41+CD9- cells obtained in the absence of SR1 and the two unproductive populations present on D10 displayed an intermediate gene expression pattern. In other words, the ability to generate proplatelets between D10 and D14 appeared to be linked to the capacity of SR1 to delay MK differentiation, meanwhile avoiding intermediate and inappropriate genetic perturbations. Paradoxically, the D14 CD34+CD41+CD9- cells obtained under SR1- or SR1+ conditions were virtually identical, raising the question as to whether their strong differences in terms of proplatelet production, in the absence of SR1 and between D14 and D17, are mediated by miRNAs or by memory post-translational regulatory mechanisms.
Distinct roles for RSC and SWI/SNF chromatin remodelers in genomic excision repair
Authors: Bohm Kaitlynne A. , Hodges Amelia J. , Czaja Wioletta , Selvam Kathiresan , Smerdon Michael J. , Mao Peng , Wyrick John J.
Published: May 2021

Nucleosomes are a significant barrier to the repair of UV damage because they impede damage recognition by nucleotide excision repair (NER). The RSC and SWI/SNF chromatin remodelers function in cells to promote DNA access by moving or evicting nucleosomes, and both have been linked to NER in yeast. Here, we report genome-wide repair maps of UV-induced cyclobutane pyrimidine dimers (CPDs) in yeast cells lacking RSC or SWI/SNF activity. Our data indicate that SWI/SNF is not generally required for NER but instead promotes repair of CPD lesions at specific yeast genes. In contrast, mutation or depletion of RSC subunits causes a general defect in NER across the yeast genome. Our data indicate that RSC is required for repair not only in nucleosomal DNA but also in neighboring linker DNA and nucleosome-free regions (NFRs). Although depletion of the RSC catalytic subunit also affects base excision repair (BER) of N-methylpurine (NMP) lesions, RSC activity is less important for BER in linker DNA and NFRs. Furthermore, our data indicate that RSC plays a direct role in transcription-coupled NER (TC-NER) of transcribed DNA. These findings help to define the specific genomic and chromatin contexts in which each chromatin remodeler functions in DNA repair, and indicate that RSC plays a unique function in facilitating repair by both NER subpathways.
COVID-19 as an entrepreneurship, innovation, digitization and digitalization accelerator: Spanish Internet domains registration analysis
Authors: Gavrila Gavrila Sorin , de Lucas Ancillo Antonio
Published: May 2021

Purpose

The purpose of this study is to comprehend and determine the impact of the COVID-19 pandemic on business organizations and society, together with its relationship to entrepreneurship, innovation, digitization or digital transformation, by means of analysis of the Spanish Internet domains registration data set.

Design/methodology/approach

Following existing literature regarding time series analysis, the authors have designed a SARIMA methodology involving the forecasting of a non-COVID-19 data set from the available data and compared it to the existing COVID-19 data set in order to validate the formulated hypothesis.

Findings

The COVID-19 pandemic was found to be an unfortunate accelerator, regarding entrepreneurship and innovation as a digitization and digital transformation lever, with the results of the Internet domain registration analysis as a reliable indicator.

Originality/value

This research confirms the existence of new non-invasive approaches to complementary information, such as Internet domain registration analysis, that could serve as an early and quick indicator of innovation and entrepreneurship initiatives within business activities.
Managing inventory at GoUNESCO
Authors: Chejarla Kalyana C. , Chatterjee Sandeep
Published: May 2021

Learning outcomes

This case calls out the following inventory management learning objectives in a project context: to understand the project categories of inventories and their drivers for planning purposes, to learn how to manage different categories of inventory and to learn the importance of effective allocation of inventory at different project locations.

Case overview/synopsis

GoUNESCO is a start-up formed with the objective of providing a platform for laypersons to engage with places of heritage value. Among others, one of the key components of this platform is “go heritage runs,” in short GHR. In the past three years, the popularity of runs organized under the brand GHR has been increasing, both in terms of locations and the number of participants in each location in successive years. Inventory planning and management for projects is tricky. Different categories of inventory have different implications of shortages or excesses. The case dwells into inventory planning and management of t-shirts and medals, to drive home this point.

Complexity academic level

The case can be positioned in service operations management or supply chain management courses while covering inventory management topics for both Master of Business Administration (MBA) and executive MBA students.

Supplementary materials

Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS 11: Strategy.
Zolostays: competing in Indian co-living space
Authors: Ghosh Dastidar Surajit , Gupta Nitin , Raichandani Damini
Published: May 2021

Learning outcomes

The key learning objectives are mentioned as follows: to understand the attractiveness of the co-living sector using Michael Porter’s five forces model; to do competitive analysis of ZOLO by understanding its objectives, strengths and weaknesses; to understand various competitive strategies which ZOLO’s competitors could apply against it; and to understand application of various defense strategies, which ZOLO would follow to retain its market leader position.

Case overview/synopsis

ZoloStays (ZOLO) was an Indian real-tech start-up based in Bengaluru. It was in the business of co-living, i.e. providing affordable accommodation for students and young professionals who had to leave their home and temporarily settle in other cities in search for jobs or education. ZOLO had grown 300% and had served over 50,000 customers across 10 Indian cities, since its inception in 2015. It had claimed to be the largest co-living brand in India in FY 2019. Nikhil Sikri (Sikri), who was a Co-founder of ZOLO, had big plans of expanding the firm to a million beds in 5 years. However, increasing awareness of a huge untapped market in the co-living sector had led to entry of a flurry of competitors. Notable among them were Nestaway, Colive, StayAbode, CoHo and OYO Life. Facing such intense competition Sikri had the challenge to be able to sustain his company’s early momentum. How would he retain ZOLO’s market leadership position? What would be the best strategy to achieve further growth? Should ZOLO diversify into allied services or apply a more focused strategy? Sikri was facing all these challenging questions and had to quickly address them to continue to lead in this competitive race.

Complexity/academic level

The case can be taught in advanced undergraduate, MBA or executive-level programs dealing with marketing. This case study helps students in dealing with issues pertaining to a given market sector where a firm is operating, the strategies that could be used by the competitors and application of competitive strategies which the firm can apply.

Supplementary materials

Teaching Notes are available for educators only.

Subject code

CSS 8: Marketing
Do assurance and assurance providers enhance COVID-related disclosures in CSR reports? An examination in the UK context
Authors: Albitar Khaldoon , Al-Shaer Habiba , Elmarzouky Mahmoud
Published: May 2021

Purpose

The COVID-19 pandemic has been adding pressures on companies to commit to their social and ethical responsibilities. Corporate social responsibility (CSR) reporting is the main tool through which companies communicate their social behaviour and the need for credible information is censorious during the crisis. This paper aims to measure the level of COVID-19 disclosures in CSR reports by using an automated textual analysis technique based on a sample of UK companies and investigate whether the level of disclosure is enhanced for companies that subject their CSR reports to an assurance process.

Design/methodology/approach

The study sample consists of FTSE All-share non-financial listed companies. The authors use a computer-aided textual analysis, and we use a bag of words to capture COVID-related information in the CSR section of the firm’s annual reports.

Findings

The results suggest that the existence of independent external assurance is significantly and positively associated with the provision of COVID-19 information in CSR reports. The authors also find that when assurance is provided by Big 4 accountancy firms, the disclosure of COVID-related information is enhanced. Furthermore, large companies are more likely to disclose COVID-related information in their CSR reports that are externally assured from top-tier accountancy firms, suggesting that assurance could be a burden for smaller firms. Overall, the findings suggest that assurance on CSR reports provides an “insurance-like” protection that mitigates the risks and signals the management’s ethical behaviour during the pandemic.

Practical implications

The study approach helps to assess the level of corporate engagement with COVID-19 practices and the extent of related disclosures in CSR reports based on the COVID-19 Secure Guidelines published by the UK government. This helps to emphasise how companies engage and communicate COVID-19-related information to stakeholders through CSR reports and ensure a safe working environment during this pandemic. Managers will need to assess the costs and benefits of purchasing assurance on CSR disclosures, giving the ethical signal that assurance sends to the market and protection that it covers during the crisis.

Originality/value

This paper provides a shred of unique evidence of the impact of the existence of external assurance and the type of assurer on the disclosure of COVID-related information in CSR reports. To the best of authors’ knowledge, no study has yet investigated the corporate disclosure on an unforeseen event in CSR reports and the role of CSR assurance in this respect.
Events’ external stakeholders and their influence strategies in tourism: perspectives from Borneo
Authors: Tiew Fidella , Holmes Kirsten , de Bussy Nigel
Published: May 2021

Purpose

The purpose of this paper is to examine external event stakeholders’ strategic actions to advance their interests in tourism events, based on their resource relationships with the event. It takes the novel approach of examining stakeholder influence strategies from the external stakeholder perspective.

Design/methodology/approach

The study used a qualitative case study research design, with five government-owned tourism events in Sarawak, involving primary data from 37 interviews with external stakeholders.

Findings

The stakeholders perceived that they were not overly dependent on the events studied due to their short duration. Two types of resource relationships were found: event-dependent stakeholders and event non-dependent stakeholders. Stakeholders were found to be deploying various influence strategies, which were largely subtle, positive and collaborative in nature, regardless of whether they were event-dependent or event non-dependent stakeholders.

Research limitations/implications

The findings are limited to the context examined in this study. Going forward, stronger public–private partnerships and formalised resource relationships are needed to ensure continuity of resource supplies and greater event innovation.

Originality/value

The study adds to the knowledge of how event external stakeholders exert their influence in accordance with their interests and resource dependency relationship with government-owned tourism events in the context of Sarawak, Borneo.
Striving for balance: women entrepreneurs in Brazil, their multiple gendered roles and Covid-19
Authors: Ayatakshi-Endow Sukanya , Steele Jiselle
Published: May 2021

Purpose

This paper aims to explore how women entrepreneurs in Brazil are managing their businesses and gendered role expectations at home in the context of Covid-19. Using the lenses of business-family interface theoretical construct, the paper seeks to explain how women are navigating the business and family commitments in the pandemic context.

Design/methodology/approach

This paper adopts the interpretivist approach using Gioia methodology and 13 individual semi-structured interviews with women entrepreneurs in Rio De Janeiro, Brazil.

Findings

The findings demonstrate that women implement numerous strategies including reliance on social relationships within the family, and externally, to manage the home-business expectations. The findings also reveal entrepreneurial resilience and adaptability in the face of a crisis that marks how women entrepreneurs navigate challenges in their entrepreneurial journeys.

Originality/value

This paper contributes to the gender and entrepreneurship literature by giving greater visibility to women entrepreneurs in developing society in the context of the pandemic. This paper also demonstrates how negotiating gender roles can empower women entrepreneurs to challenge gendered norms.
Application of the constitutional principle of generality in Spanish companies’ taxation. A compared study to Portugal
Authors: Rodrigues Aldeia Susana Cristina
Published: May 2021

Purpose

This paper aims to analyse how constitutional law and corporate income tax (CIT) law, in the Iberian Peninsula, addresses the tax justice principle of generality. Also, it has as an intention to understand the dimension of tax exemptions predicted in the CIT law of both countries.

Design/methodology/approach

It analyses several data sources from Spain and Portugal, between them constitutions laws, CIT laws, general tax laws and some constitutional court cases. Furthermore, it uses the content analysis method to identify the level of exemptions and tax benefits present in the CIT law.

Findings

The results show that constitutional laws reserve a section to regulate tax issues, that it can present major or minor development. The Spanish article 31 explains the tax system and the Portuguese articles of 103 and 104 explain not only the tax system but also gives instructions about how must occur income, property and consumption taxation. Both jurisdictions, do not refer expressly to the generality principle, nevertheless, it has an implicit presence in the Supreme law and the same happen in the CIT law. They predict that all legal entities, public and private ones, have to contribute to financing the public expenditure. Furthermore, the respect to generality principle implies that tax income exemptions have to be justified, otherwise it can configure a break of the researched fundamental. In researched cases, the Spanish CIT have present more tax exemptions than Portugal, which can lead to consider a relation between the level of corporate contribution to income tax revenues collection and the tax exemptions predicted in the CIT law.

Originality/value

It allows understanding the difference between tax jurisdictions in the tax principles domain.
Blockchain technology development and implementation for global logistics operations: a reference model perspective
Authors: Kamran Rukshanda , Khan Nasreen , Sundarakani Balan
Published: May 2021

Purpose

Blockchain technology offers a lot of potential benefits in supply chain management. However, there is a need of a reference model which addresses the gaps in existing frameworks. This paper aims to propose a blockchain technology-based reference model which can be applied to global logistics operations.

Design/methodology/approach

The researchers have integrated the fit-for-purpose theoretical framework and prototyping methodology to design the reference model, a blockchain-based logistics, tracking and traceability system (BLTTS). The researchers demonstrated the application of the reference model through a health-care supply chain case study. The proposed BLTTS can be implemented across global logistics operations for business performance improvement.

Findings

The research provides a framework and recommendations for global companies to consider when adopting the blockchain technology for implementation. The researchers found that the Ethereum blockchain technology improves security of the data shared within the block through the secure hashing algorithm 1. The hash algorithm ensures anonymity of the involved parties. The model integrates blockchain with supply chain thus creating transparent process, efficiency and real-time communication.

Research limitations/implications

The reference model will offer a better solution to global logistics operations challenges. It provides recommendations to key stakeholders involved in logistics operations segment of the logistics industry while adopting blockchain technology. Apart from the methodological limitation of the study, the system compatibility and the layer configuration aspects might be posing potential challenges while upscaling the implementation.

Originality/value

The proposed reference model overcomes the drawbacks of existing models as it integrates Ethereum technology. In addition, the researchers have applied the model to demonstrate its functioning in real-time environment, which could guide for future research.