bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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.
Wilson Statistics: Derivation, Generalization, and Applications to Electron Cryomicroscopy
Authors: Singer Amit 
Published: May 2021

AbstractThe 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

ABSTRACTSynaptotagmin-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

ABSTRACTObjectiveBarrett’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.MethodsWhole 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.ResultsA 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.ConclusionsSubmucosal 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

AbstractPurposePeripheral 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.MethodsA 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.ResultsThe 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.ConclusionWe 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

SUMMMARYMelioidosis 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

ABSTRACTMonolayer 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

AbstractMost 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

AbstractFine-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

ABSTRACTHuman 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.
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

PurposeThe 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/approachFollowing 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.FindingsThe 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/valueThis 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