bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Alpha‐2‐Macroglobulins from Swine and Humans and their Copper Binding
Authors: Garcia Alejandra , Ramos Danny , Marzvaan Cameron , Vileno Bertrand , Faller Peter , Linder Maria C
Published: June 2021

Alpha‐2‐macroglobulin (a2M) is a member of the macroglobulin family of blood plasma proteins. It has a variety of functions, ranging from trapping proteases and transporting zinc to binding and transporting inflammatory and anti‐inflammatory cytokines and, growth factors and the small peptide regulating iron metabolism (hepcidin)[1]. a2M is the main form found in most mammals, while the alpha1‐inhibitor3 form dominates in the plasma of rodents. Some years ago, we determined in rats that a large plasma protein we named transcuprein was involved in transporting copper to the liver (exchanging copper with albumin), and upon purification found it was alpha1‐inhibitor3[2]. We then showed that human a2M also bound Cu(II) tightly, and that this copper was readily delivered by a2M to cultured human cells[3]. As we have been studying aspects of copper metabolism in pigs, we decided to also investigate the structure and copper binding of pig a2M to compare it to that of human a2M. Pig and human a2M were purified from heparinized Yorkshire pig plasma and from the heparinized plasma of human volunteers (under an approved university IRB protocol), using the established procedure for human a2M that uses a combination of PEG 8000 fractionation and Zn(II)‐immobilized metal affinity chromatography. The resulting samples were separated in large pore size exclusion chromatography on Sephacryl S300. Human a2M eluted had one large peak eluting with an Mr of ~900 kDa, and a much smaller peak of about 400 kDa. By SDS‐PAGE, both peaks showed the expected 180 kDa band, indicating that most of the human a2M was a tetramer, with a very small portion as a dimer. In the case of the pig, There was not tetrameric a2M; it was all in dimer form, and the subunits seen in SDS‐PAGE were two bands that together added up to ~180 kDa (120 + 60 kDa). Non‐denaturing PAGE gave single bands indicating that the smaller subunits of the pig a2M were combining into one structure. The copper content of the human a2M was 4 Cu atoms per tetramer (not taking into account potential non‐specific binding), but was 2 Cu atoms per tetramer when copper was first removed and added back in the presence of human or rat albumin. The Cu content of the pig a2M was 4 Cu atoms per dimer. Preliminary data obtained by EPR gave similar but not identical profiles and indicated there were two binding sites, the main one with Cu(II) atoms most likely bound to three Ns and one O. These findings indicate that in some species, a2M forms a dimer, while in others a tetramer; they bind Cu(II) in similar but not identical fashion; and that the subunits of pig a2M may have a vulnerable peptide bond that cleaves the 180 kDa unit into two pieces.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Renal Expression of Adhesion GPCR Gpr116 (ADGRF5) Contributes to Urinary Concentration in Mice
Authors: Zaidman Nathan , Pluznick Jennifer
Published: June 2021

G‐protein coupled receptors (GPCR) are a large and diverse family of integral membrane proteins that recognize a tremendous assortment of extracellular molecules including neurotransmitters, hormones, light and odors. They are a common target of pharmaceutical drug development, and uncovering the function of novel GPCRs in the kidney represents a wealth of untapped therapeutic potential. We previously performed an mRNA screen for novel GPCRs in the kidney to identify promising yet overlooked renal GPCRs. This screen revealed that Gpr116, an adhesion‐class GPCR, is highly expressed in the kidney. To understand the role of Gpr116 in renal physiology, we have taken a multidisciplinary approach. Using transfected HEK293 cells expressing cloned Gpr116, we validated a monoclonal antibody for Gpr116. In murine kidney, this antibody localizes Gpr116 to the apical membrane of intercalated cells in the collecting duct of mouse kidneys. This staining is absent in kidneys from targeted knockout (KO) of Gpr116 in renal tubules (Gpr116flox/flox, ksp‐Cre). Additionally, kidney‐specific KO animals have significantly reduced spot urine osmolality (1552±71 mOsm/kg, N=11) compared to wild‐type (WT) (2097±76, N=10, p<0.0001) and heterozygous (2423±86, N=6, p<0.0001) littermates. Furthermore, following 24‐hours of dehydration plasma vasopressin is not significantly upregulated from baseline in KO animals, but is in WT littermates. However, osmolality of 24‐hour urine collections from metabolic cages are not significantly different between the WT and KO groups. Overall, these results suggest a role for Gpr116 in the urinary concentrating mechanisms in the murine kidney. This study establishes a physiologic role of the previously understudied Gpr116 in the murine kidney and demonstrates the scientific potential of future investigations into novel GPCRs.

Support or Funding Information

Research was funded by NIH F32DK116499 (N.A.Z.) and NIH R01DK107726 (J.L.P.).

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Advanced Stages of Duchenne Muscular Dystrophy Exhibit Mitochondrial Bioenergetic Impairments Linked Specifically to Creatine‐Dependent Energy Exchange
Authors: Hughes Meghan C , Ramos Sofhia V , Turnbull Patrick C , Perry Christopher G R
Published: June 2021

Rationale

Our recent findings demonstrate that left ventricle and diaphragm from 4 week old D2.mdx mice with Duchenne Muscular Dystrophy (DMD) exhibit impaired mitochondrial oxidative phosphorylation and elevated H2O2 (mH2O2) emission. The present investigation sought to determine the degree of these deficits in advanced stages of DMD.

Methods

ADP‐dependent mH2O2 emission and respiration were assessed in permeabilized muscle fibre bundles from heart and diaphragm muscle of D2.mdx mice (52 weeks). Mitochondrial assessments were performed in the presence of 20mM creatine (+Cr) to maximally activate mitochondrial creatine kinase (mtCK)‐dependent shuttling of phosphate to the cytoplasm as phosphocreatine, which accelerates matrix ADP/ATP cycling, as well as in the absence of creatine (−Cr) to force mitochondria to rely solely on slower ATP/ADP diffusion.

Results

State II mH2O2 emission (0 mM ADP, maximal mH2O2 emission) was unchanged in DMD heart and lower in DMD diaphragm in both +Cr (96.0 pmol/sec/mg dry wt in DMD vs 498.0 pmol/sec/mg dry wt in WT, p<0.05) and –Cr (50.2 vs 312.9, p<0.05). 25 mM ADP was added to evaluate the ability of ADP to lower mH2O2 emission (state III). ADP's ability to lower mH2O2 emission was impaired in +Cr (heart: 69% of state II mH2O2 in DMD vs 61% in WT, p=0.06; diaphragm: 75% vs 54%, p<0.05) but improved in −Cr in the heart (69% vs 98%, p<0.05), and unchanged in diaphragm. State III respiration was also evaluated using 25 mM ADP. +Cr, respiration was impaired in the heart (48.0 pmol/sec/mg wet wt in DMD vs 75.6 pmol/sec/mg wet wt in WT, p<0.05) and diaphragm (43.4 vs 47.8, p<0.05). −Cr, respiration was improved in DMD heart (60.0 vs 29.8 pmol/sec/mg wet wt, p<0.05) and unchanged in diaphragm. The greater mH2O2 due to impaired mtCK did not alter heart glutathione in reduced or oxidized forms, total glutathione or GSH/GSSG, but did increase diaphragm glutathione in oxidized, reduced and total forms (117–204%, p<0.001).

Conclusion

These findings demonstrate that mitochondrial dysfunctions during advanced stages in DMD are attributed specifically to an impaired ability of creatine to enhance ADP's control of respiration and mH2O2 emission. A partial compensation in creatine‐independent control of ADP was observed which may prevent even further detriments to cellular energy and redox homeostasis. These findings suggest that restoration of normal mtCK activity and mitochondrial creatine‐dependent phosphate shuttling may be an effective approach at restoring mitochondrial bioenergetics and countering muscle‐specific weakness in DMD.

Support or Funding Information

NSERC Discovery Grant, The James H. Cummings Foundation, Canadian Foundation for Innovation, Ontario Research Fund

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Allicin Reverses Diabetes‐Induced Dysfunction of Human Coronary Artery Endothelial Cells
Authors: Horuzsko Daniel , LaCavera Margeaux , Ma Handong , Wu Yan , Zhu Shu , White Richard
Published: June 2021

Cardiovascular disease (CVD) is the leading cause of death in the United States, and is the major source of morbidity and mortality associated with diabetes mellitus. Because the incidence of diabetes continues to increase, reducing the risk of CVD in diabetes will continue to be a major focus of cardiovascular research. An early manifestation of diabetes‐induced CVD is dysfunction of the vascular endothelium, as indicated by depressed production of NO. Our findings now demonstrate depressed activity of endothelial nitric oxide synthase (eNOS) in diabetes, and suggest that treating human coronary artery endothelial cells with allicin, the major bioactive organosulfur component in garlic extract, can restore NO production in these cells. Coronary artery endothelial cells (Lonza) were obtained from control (HCAEC) or diabetic (DHCAEC) donors, and NO production was measured by fluorescence microscopy via 4,5‐diaminofluorescein diacetate. On average, NO production was depressed by 12.9% in DHCAEC compared to controls. Treating these cells for 20 minutes with 4 μM allicin restored NO production by 32.9%. Further, immunoblot studies revealed that diabetes decreased expression of eNOS protein by 20.3%; however, allicin was able to reverse this effect of diabetes. On average, eNOS expression was increased by 26% by overnight exposure to 5 μM allicin. Taken together, these data indicate that allicin improves endothelium‐dependent NO production in diabetes by enhancing the expression and/or activity of eNOS in human coronary artery endothelial cells. These studies further suggest that this improved endothelial function likely contributes to the established health benefits of garlic consumption (e.g., lowering blood pressure), and also suggests a natural means of reducing the devastating consequences of diabetes on CVD. Future experiments are needed to identify the mechanism of allicin action on eNOS and in vascular endothelial cells.

Support or Funding Information

Supported by the Division of Research, PCOM.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Anticancer mechanisms determination of N‐(o‐carboxybenzoyl)‐derived compounds of L‐amino acids serie on MDA‐MB‐231 cell line of TNBC
Authors: MARTINEZ DORIS CRUZ , PERCINO TERESA MANCILLA , JIMÉNEZ ELVIA MERA
Published: June 2021

Breast cancer is ranked as the second most frequent neoplasm worldwide [1], of which approximately 15% is subclassified as triple negative breast cancer (TNBC), characterized by absence of estrogen, progesterone and HER2/neu receptors. TNBC has been identified as one of the most aggressive cancers, due to its null response to endocrine therapies and trastuzumab [2]. Breast cancer is a pathology associated with aging and unhealthy lifestyles, which has been proven through studies that demonstrate MDA‐MB‐231 TNBC cells overexpress HDAC8 as a consequence of epigenetic dysregulation mechanisms linked to the high level proliferative capacity, resulting into high risk of recurrence and low survival [3]. Because all above our work group has focused in the design by Docking technique and synthesis of new HDAC inhibitor (HDACi) compounds as a therapeutic target for the TNBC. In this investigation, N‐(o‐carboxybenzoyl) derived compounds of L‐amino acids were used to determine their cytotoxicity by inhibiting the proliferation and viability of the cell line MDA‐MB‐231, as well as elucidate the possible mechanisms of cell death induced by the compounds BisLys, GlutEt and I1.

Methods

To evaluate overall cellular toxicity of BisLys, GlutEt and I1 compounds, MDA‐MB‐231 cells were seeded and incubated at 37°C in a 5% CO2, DMEM F12 medium supplemented with FBS. Compounds were added in 8 different concentrations, DMEM F12 medium was used as a negative control and SAHA as a positive control. The proliferation and viability of TNBC cells was quantified by the colorimetric for 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. Type of cell death whether it was necrosis or apoptosis was determined using Annexine V and propidium iodide by flow cytometry. Finally, the blocked cell cycle progression by those compounds was determined using Cayman 10009349 Kit by flow cytometry.

Results

The compounds BisLys and Glut Et decreased cell proliferation via apoptosis after 24h of treatment and blocked cell cycle progression at G1 phase with a concurrent decrease in S and G2/M phase. On the other hand, compound I1 did not significantly decrease cell proliferation after 24 hours of treatment. However, it shared the blocked cell cycle progression at G1 phase in the same way as the BisLys and Glut Et compounds.

Conclusion

Compounds BisLys and Glut Et were able to inhibit the proliferation of the MDA‐MB‐231 cell line and induced blocked cell cycle and cell death mainly by apoptosis, so they could be considered as potentially therapeutic compounds.

Support or Funding Information

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
RETINAL MICROVASCULAR CHANGES IN UVEAL MELANOMA FOLLOWING CONBERCEPT INJECTION AFTER PLAQUE RADIOTHERAPY AS DETECTED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Authors: Yang Jing Yan , Wang Qian , Chen Meng Xi , Yan Yan Ni , Zhou Wen Jia , Liu Yue Ming , Wei Wen Bin
Published: June 2021

Purpose:

To investigate macular microvascular characteristics imaged by optical coherence tomography angiography in patients with uveal melanoma following conbercept injections after plaque radiotherapy.

Methods:

Prospective comparative analysis comprising 15 patients with uveal melanoma with conbercept injections and 30 patients without conbercept injections after plaque radiotherapy by optical coherence tomography angiography. The conbercept group received intravitreal conbercept injections at the time of plaque removal, 1 month, 3 months, 6 months , 9 months and 12 months after plaque removal (total, 6 injections). The control group had no intravitreal conbercept injection.

Results:

After initiation of conbercept injections, superficial retinal vascular density in the whole image and parafoveal region were significantly higher at 6 months, whereas there was no significant difference at 9 months and 12 months. In analysis of variance analysis, superficial retinal vascular density in the whole image remained stable after conbercept injections (P = 0.069), whereas the superficial retinal vascular density decreased significantly after plaque radiotherapy in the control group (P = 0.011). In multivariable linear regression, a higher superficial retinal vascular density in the whole image region at 6 months was significantly associated with intravitreal conbercept injection (P = 0.018), wider tumor base (P = 0.026), and thinner tumor thickness (P = 0.04).

Conclusion:

Optical coherence tomography angiography can provide a quantitative evaluation of early retinal microvascular changes after radiotherapy. Intravitreal conbercept treatment could partly relieve the retinal vascular damage in response to radiation therapy at early stage in patients with uveal melanoma; however, it may not be able to provide long-term positive functional outcomes.
Assessing the (anti)-inflammatory potential of diets
Authors: Bahr Lina Samira , Franz Kristina , Mähler Anja
Published: June 2021

Purpose of review

It is accepted that several chronic diseases are associated with inflammation. Dietary habits and the consumption of certain nutrients have been shown to influence inflammation, reflected by inflammatory cytokines. In this narrative review, we discuss currently developed tools to assess the inflammatory potential of diets and compare them with established tools.

Recent findings

Four new indices were recently developed. The Inflammatory Score of the Diet is a modified version of the established Dietary Inflammatory Index. The novel Empirical Dietary Inflammatory Index works without previous dietary intake assessment and the Anti-Inflammatory Diet Index was specifically developed in a northern European population. The Dietary and Lifestyle Inflammation Scores addresses additional confounders. The informative value of dietary indices relies on the accuracy and completeness of dietary intake assessment.

Dietary inflammatory indices are important tools to assess, compare and validate the inflammatory potential of diets across populations without the need for biomarker assessments. They allow to investigate associations between an (anti)-inflammatory diet with disease risk and course. Although the Dietary Inflammatory Index remains the most used index worldwide, currently developed indices allow more flexibility, have a different focus or simplify assessment. Additional foods, that were recently shown to modulate inflammation, but are not (fully) considered yet, may deserve more attention in the future.
David Herman MacLennan. 3 July 1937—24 June 2020
Authors: Reithmeier Reinhart
Published: June 2021

David Herman MacLennan, one of Canada's foremost biomedical scientists, was known internationally for his research on the molecular mechanism of muscle contraction in human health and disease. David was born on 3 July 1937 in Swan River, Manitoba, and grew up in farm country. After obtaining a BS (Agriculture) in plant science from the University of Manitoba in 1959, David completed his MSc (1961) and PhD (1963) in biology at Purdue. A post-doctoral fellowship at the Enzyme Institute at the University of Wisconsin followed, where he was appointed as an assistant professor (1964–1968). At Wisconsin David published a series of elegant papers on the isolation and characterization of the mitochondrial ATPase and protein components of the electron transfer system. In 1969 he was recruited back to Canada as an associate professor in the Banting and Best Department of Medical Research at the University of Toronto, where he spent the rest of his illustrious career. Here, David shifted his focus to determine how calcium regulates muscle contraction, with a focus on the role of the sarcoplasmic reticulum (SR). David was a scientist who knew where a field was going and he often got there first, incorporating new technologies along the way. His early discovery of the Ca
2+
ATPase pump that controls calcium uptake into the SR was the key to muscle relaxation. His lab systematically characterized the components of the SR, including the ryanodine receptor which acts as a calcium release channel to allow muscle contraction. David's discoveries of these molecular mechanisms and their application to debilitating muscle disease are an inspiring scientific legacy. Although David published hundreds of papers, many cited hundreds of times, gave hundreds of invited seminars and won many prestigious awards, including Fellow of the Royal Society of London in 1994, his greatest legacy is the people he trained, many of whom went on to leadership positions in research and at universities around the world.
Lord Robert May of Oxford OM. 8 January 1936—28 April 2020
Authors: Krebs Lord (John) , Hassell Michael , Godfray Sir Charles
Published: June 2021

Robert May was the leading theoretical ecologist of his generation. He started his career as a theoretical physicist and began the transition to ecology soon after completing a post-doctoral fellowship at Harvard. His mathematical analysis of the stability of ecological communities challenged orthodox views and spawned a new research agenda. He demonstrated that many different patterns of population fluctuations, including chaotic behaviour, could arise from simple mathematical models. Together with R. M. Anderson, he transformed the mathematical modelling of infectious diseases. All of his work was characterized by his remarkable ability to reduce complex problems to their essential simplicities. His achievements were recognized by the award of numerous major international prizes. May also served as the UK government's chief scientific advisor between 1995 and 2000, and as President of the Royal Society between 2000 and 2005.
Genomic epidemiology of the first epidemic wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Palestine
Authors: Qutob Nouar , Salah Zaidoun , Richard Damien , Darwish Hisham , Sallam Husam , Shtayeh Issa , Najjar Osama , Ruzayqat Mahmoud , Najjar Dana , Balloux François , van Dorp Lucy
Published: June 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus responsible for the COVID-19 pandemic, continues to cause a significant public-health burden and disruption globally. Genomic epidemiology approaches point to most countries in the world having experienced many independent introductions of SARS-CoV-2 during the early stages of the pandemic. However, this situation may change with local lockdown policies and restrictions on travel, leading to the emergence of more geographically structured viral populations and lineages transmitting locally. Here, we report the first SARS-CoV-2 genomes from Palestine sampled from early March 2020, when the first cases were observed, through to August of 2020. SARS-CoV-2 genomes from Palestine fall across the diversity of the global phylogeny, consistent with at least nine independent introductions into the region. We identify one locally predominant lineage in circulation represented by 50 Palestinian SARS-CoV-2, grouping with genomes generated from Israel and the UK. We estimate the age of introduction of this lineage to 05/02/2020 (16/01/2020–19/02/2020), suggesting SARS-CoV-2 was already in circulation in Palestine predating its first detection in Bethlehem in early March. Our work highlights the value of ongoing genomic surveillance and monitoring to reconstruct the epidemiology of COVID-19 at both local and global scales.
Modeling the waves of Covid-19
Authors: Cherednik Ivan
Published: June 2021

Abstract

The challenges with modeling the spread of Covid-19 are its power-type growth during the middle stages with the exponents depending on time, and the saturations mainly due to the protective measures, though weakening and partial destruction of the virus due to mutations is a consideration too. The two-phase solution we propose for the total number of detected cases of Covid-19 describes the actual curves in many countries almost with the accuracy of physics laws. Bessel functions play the key role in our approach. The differential equations we obtain are of universal type; they describe momentum risk-management in behavioral psychology, transient processes in invasion ecology, etc. Due to a very small number of parameters, namely, the initial transmission rate and the intensity of the hard and soft measures, we obtain a convincing explanation of the surprising uniformity of the spread in many different areas. This theory can be used for forecasting the epidemic spread, evaluating the efficiency of the protective measures and the vaccinations. For instance, the early projection for the 3rd wave in the USA was very exact. The data until summer 2021 for India, South Africa and UK are discussed.
Nasogastric tube in critical care setting: combining ETCO2 and pH measuring to confirm correct placement
Authors: Ceruti S. , Dell’Era S. , Ruggiero F. , Bona G. , Glotta A. , Biggiogero M. , Tasciotti E. , Kronenberg C. , Saporito A.
Published: June 2021

Introduction

nasogastric tube (NGT) placement is a common procedure performed in critical care setting. Chest X-Ray is the diagnostic gold-standard to confirm correct placement, with the downsides of both the need for critical care patients’ mobilization and intrinsic actinic risk. Other potential methods to confirm NGT placement have shown lower accuracy compared to chest X-ray; ETCO2 and pH analysis have singularly yet investigated as an alternative to the gold standard. Aim of this study was to determine thresholds in combine measurements of ETCO2 and pH values, at which correct NGT positioning can be confirmed with the highest accuracy.

Material & Methods

a prospective, multicenter, observational trial; a continuous cohort of eligible patients was allocated to two arms, to identify clear cut-off threshold able to detect correct NGT tip positioning with the maximal accuracy. Patients underwent general anesthesia and orotracheal intubation; in the first group difference between tracheal and esophageal ETCO2 values were assessed. In the second group difference between esophageal and gastric pH values were determined.

Results

from November 2020 to March 2021, 85 consecutive patients were enrolled: 40 in the ETCO2 group and 45 in the pH group. The ETCO2 ROC analysis for predicting NGT tracheal misplacement demonstrate an optimal ETCO2 cutoff value of 25.5 mmHg, where both sensitivity than specificity reach 1.0 (AUC 1.0, p < 0.001). The pH ROC analysis for predicting NGT correct gastric placement demonstrated the optimal pH cutoff value at 4.25, with a mild diagnostic accuracy (AUC 0.79, p < 0.001).

Discussion

A device capable of combining the presence of a negative marker with a positive marker could be accurate enough in identifying the correct NGTs positioning. Further studies are required to validate the reproducibility of these results by a specific device, whose accuracy also ought to be compared with standard chest X-ray.

Trial number: NCT03934515 (www.clinicaltrials.gov)
COVID in Post Vaccinated individuals- Beacon of Light
Authors: Sashindran VK , Rajesh K , Nigam Ankur , Mohakuda Sourya Sourabh , Bhati Navin , Mohapatra D
Published: June 2021

Introduction

COVISHIELD and COVAXIN have been introduced post rapid approval as COVID vaccines in India, which has the second most COVID cases across countries. These vaccines are being administered in a two-dose schedule from 16 Jan 2021. This study deals with the clinical profile of individuals who developed COVID infection post-COVID vaccination.

This is the first study of similar nature in India.

Methodology

The study population comprised of individuals who were detected to be COVID positive 04 weeks post-vaccination and were compared with individuals detected positive within the first 04 weeks of vaccination. Data was collected in a digital questionnaire format and analyzed with SPSS v-23 software. Clinical features were profiled in detail. Chi-square analysis was done to find out the association of various demographic features with the severity of the disease.

Results

In the study population, fever was the commonest symptom (75.1%) followed by anosmia (72.1%), and shortness of breath (16.3%). There was a lower incidence of fever, cough, dyspnea, and requirement of hospitalization in the study population as compared to the control group and previous epidemiological data. The time required for complete recovery and disease severity was favorable in our study population. There was a significant correlation in the rate of hospitalization among the study group and the comparative group (p=0.0001) and between the number of dosage of COVID vaccine with the lowest SpO2 recorded (p=0.001).

Conclusion

This study will boost the ongoing initiative of having a maximal vaccinated population countrywide and emphasize the need for two doses of vaccination.
Artemisinin-based hybrids produce intracellular proteasome inhibitors that overcome resistance in Plasmodium falciparum
Authors: Zhan Wenhu , Liu Yi Jing , Yang Changmei , Zhang Hao , Harris Jacob C. , Wang Rong , Zhu Songbiao , Sherman Julian , Sukenick George , Rodriguez Ana , Deng Haiteng , Nathan Carl F. , Kirkman Laura A. , Lin Gang
Published: June 2021

Artemisinin resistant Plasmodium falciparum (Pf) is spreading despite combination chemotherapy (ACT). Here we report the design of artezomibs, single-molecule hybrids of an artemisinin and a Pf-selective proteasome inhibitor. Artezomibs exert a novel mode of action inside the malaria parasites. The artemisinin component covalently modifies parasite proteins, which become substrates of the Pf proteasome. The proteasomal degradation products that bear the proteasome inhibitor component of the hybrid then inhibit Pf proteasomes, including those with mutations that reduce binding affinity of the proteasome inhibitor component on its own. We demonstrated that artezomibs circumvent both artemisinin resistance conferred by Kelch13 polymorphism and resistance to the proteasome inhibitor associated with mutations in Pf proteasomes. This mode of action may enable the use of a single molecule with one pharmacokinetic profile to prevent the emergence of resistance.
An evolutionarily conserved odontode gene regulatory network underlies head armor formation in suckermouth armored catfish
Authors: Mori Shunsuke , Nakamura Tetsuya
Published: June 2021

Odontodes, i.e., teeth and tooth-like structures, consist of a pulp cavity and dentine covered by a mineralized cap. These structures first appeared on the outer surface of vertebrate ancestors and were repeatedly lost and gained across vertebrate clades; yet, the underlying genetic mechanisms and trajectories of this recurrent evolution remain long-standing mysteries. Here, we established suckermouth armored catfish (Ancistrus sp.; Loricariidae), which have uniquely evolved dermal odontodes (dermal denticles) all over most of their body surface, as an experimental model animal amenable to genetic manipulation for studying odontode development. Our histological analysis showed that suckermouth armored catfish develop dermal denticles through the previously defined odontode developmental stages.De novotranscriptomic profiling identified the conserved odontode genetic regulatory network (oGRN) as well as unique expression ofpaired like homeodomain 2(pitx2), previously characterized as an early regulator of oGRN in teeth, in developing dermal denticles. Knockdown ofpitx2perturbed formation of the epithelial placode of dermal denticles and altered expression oGRN genes. By comprehensively identifying the genetic program for dermal odontode development in suckermouth armored catfish, this work illuminates how dermal odontodes independently evolved and diverged in distinct teleost lineages.

Summary statement

Cranial dermal denticles in suckermouth armored catfish develop via an evolutionarily conserved and unique odontode genetic regulatory network.
Mucosal immunization with DTaP confers protection against Bordetella pertussis infection and cough in Sprague-Dawley rats
Authors: Hall Jesse M. , Bitzer Graham J. , DeJong Megan A. , Kang Jason , Wong Ting Y. , Wolf M. Allison , Bevere Justin R , Barbier Mariette , Damron F. Heath
Published: June 2021

Pertussis is a respiratory disease caused by the Gram-negative pathogen, Bordetella pertussis (Bp). The transition from a whole cell pertussis vaccine (wP; DTP) to an acellular pertussis vaccine (aP; DTaP; Tdap) correlates with an increase in pertussis cases, despite widespread vaccine implementation and coverage, and it is now appreciated that the protection provided by aP rapidly wanes. To recapitulate the localized immunity observed from natural infection, mucosal vaccination with aP was explored using the coughing rat model of pertussis. Immunity induced by both oral gavage (OG) and intranasal (IN) vaccination of aP in Bp challenged rats over a nine-day infection was compared to intramuscular (IM)-wP and IM-aP immunized rats that were used as positive controls as IM immunization is the current route for wP and aP vaccination. Our data demonstrate that both IN and OG immunization of aP resulted in production of anti-Bp IgG antibody titers similar to IM-wP and IM-aP vaccinated controls post-challenge. IN-aP also induced anti-Bp IgA antibodies in the nasal cavity. Immunization with IM-wP, IM-aP, IN-aP, and OG-aP immunization protected against Bp induced cough, while OG-aP immunization did not protect against respiratory distress. Mucosal immunization (IN-aP and OG-aP) also protected against acute inflammation and decreased bacterial burden in the lung compared to mock vaccinated challenge (MVC) rats. The data presented in this study suggests that mucosal vaccination with aP can induce a mucosal immune response and provide protection against Bp challenge.
Numerical study on trajectory of released store with manipulation of grid connections
Authors: Razzaghi Mohammad Mehdi
Published: June 2021

Purpose

This study aims to present a moving grid method based on the manipulation of connections.

Design/methodology/approach

In this study, the grid’s connections were manipulated to simulate a released store’s displacement. The selected model in this research is the EGLIN test case. In the introduced method, connections are modified in specific nodes of the grid. Governing flow equations were solved with the finite volume method. The major characteristic of this technique is using the averaging method for calculating the flux of cells.

Findings

This method maintains the grid’s quality even in large displacements of the released store. The three-dimensional simulation was carried out in transonic and supersonic regimes. Comparison of the results with experimental data were highly satisfactory.

Research limitations/implications

Using this moving grid method is recommended for simulating other models.

Practical implications

Prediction of store trajectory released from air vehicles is one of the most critical issues under study especially in the design of new stores.

Originality/value

The most prominent advantage of this method is maintaining the grid quality simultaneous with large displacements of the released store.
Candibod: building an online fitness brand through Instagram communities in the southern hemisphere
Authors: Chohan Raeesah , Reyneke Mignon , Barnardo Claire
Published: June 2021

Study level/applicability

The primary target audience for this teaching case is postgraduate business students, especially students of digital marketing, strategy and e-commerce, social media marketing, entrepreneurship and sports marketing. This teaching case is intended to be used as a case study in postgraduate business programmes such as Master of Business Administration, a specialist masters programme such as MM (entrepreneurship), postgraduate diploma in management, as well as selected executive education programmes.

Subject area

This case can be used in the subject areas of digital marketing, strategy and e-commerce, social media marketing, entrepreneurship and sports marketing.

Case overview

This case looks at South African fitness Instapreneur Candice Bodington and how her business trajectory unfolded at the same time of the successful Australian Kayla Itsines. The case begins with Bodington considering options for her brand in January 2020. Following her business, Candibod’s, fast initial growth via Instagram, the case tracks its development while also glancing at the enormous success of Itsines and her Sweat with Kayla app. However, as Bodington faces her own health care, the future and next steps of a brand built on social media becomes less certain. The case ends just a few months later with the unfolding effects of Covid-19 and a whole new host of uncertainties, especially in the fitness industry and Bodington having to reconsider her brand’s options.

Expected learning outcomes

The learning outcome of this paper is as follows: to understand the challenges of building an online brand. To evaluate the effect of brand communities as a growth strategy. To analyse the impact of social media platforms as a brand-building tool. To critically assess the effect of changing industry dynamics and technology on consumer behaviour. To evaluate how brands can navigate the negative implications of social media. To understand brand differentiation. To understand the strategic decisions associated with brand repositioning.

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 8: Marketing.

Keywords

Digital marketing, Brand building, Social media marketing, Strategic marketing
Collaboration strategy selection in BIM-enabled construction projects: a perspective through typical collaboration profiles
Authors: Chen Guangchong , Chen Jiayu , Tang Yuchun , Ning Yan , Li Qiming
Published: June 2021

Purpose

Collaboration is essential to BIM-enabled construction projects (BECPs). To facilitate collaboration, various strategies have been proposed. Usually, project team adopts single collaboration strategy for convenience. However, BIM-based collaboration is rather dynamic and exposed to a lot of barriers and risks, which easily changes collaboration conditions among partners. Therefore, better understanding of collaboration conditions in BECPs is crucial to develop flexible and suitable strategies. To fill in the gap, this study intends to identify typical collaboration profiles in BECPs and develop a profile-oriented strategy selection framework.

Design/methodology/approach

This study establishes a six-dimensional collaborative behavior matric based on a comprehensive literature review to profile collaboration. Then a questionnaire survey is conducted to collect the collaboration data from 162 BECPs in China. Finally, latent profile analysis (LPA) is utilized to identify the typical collaboration profiles in BECPs.

Findings

Through LPA, four profiles are identified, including restricted collaboration profile, smarmy collaboration profile, intuitive collaboration profile, and modest collaboration profile. A profile-oriented strategy selection framework is also established to match strategies with collaboration profiles. Two major categories of strategies are proposed to promote these collaboration profiles including trust building and elevating strategies and collaborative behaviors facilitating strategies.

Research limitations/implications

These identified profiles can provide an insightful understanding on the diversified collaboration conditions in BECPs.

Practical implications

The profile-oriented strategy selection framework will help managers develop strategies flexibly to promote collaboration in BECPs.

Originality/value

This study validates four typical collaboration profiles in BECPs. Moreover, a profile-oriented strategy selection framework is also established for collaboration facilitation in BECPs.
African leadership university: implementation strategies for innovative mass higher education
Authors: Mzyece Mjumo , Soumonni Ogundiran , Townsend Stephanie Althea
Published: June 2021

Learning outcomes

After studying this case, students should be able to: explain how strategic management relates to the areas of innovation, operations, technology, entrepreneurship and emerging markets; analyse strategy implementation and execution at the operational level, in contrast to strategy formulation at the strategic mission, values and vision level; discuss innovation, entrepreneurship and new technologies in emerging markets; and assess the impact of technology-driven entrepreneurship on significant socio-economic change that is on transformational entrepreneurship, in emerging markets.

Case overview/synopsis

This case outlines key global challenges facing higher education in the African context. It discusses the African Leadership University (ALU) as an innovative higher education institution, including its origins, establishment, strategy and purpose, curriculum, technology and operations, student support network and funding. It also describes ALU’s ongoing challenges and future prospects. ALU was launched in 2015 by Fred Swaniker, founder and chief executive officer and Khurram Masood, co-founder and chief operating officer. ALU’s vision was to transform Africa by developing and connecting three million high-calibre, ethical and entrepreneurial leaders by 2035. In August 2019, Swaniker and Masood considered how to ensure ALU’s sustainability and its vision. They had already changed ALU’s operational strategy by establishing micro-campuses instead of universities to scale rapidly and avoid regulatory barriers. However, would that be enough to uphold ALU’s vision for 2035?

Complexity academic level

This case is appropriate for postgraduate-level academic programmes and executive education programmes in management.

Supplementary materials

Teaching Notes are available for educators only.

Subject code

CSS 11: Strategy.
Robot vs human: expectations, performances and gaps in off-premise restaurant service modes
Authors: Byrd Karen , Fan Alei , Her EunSol , Liu Yiran , Almanza Barbara , Leitch Stephen
Published: June 2021

Purpose

Off-premise restaurant service has a new addition – food delivery robots. This new technology and off-premise service, in general, has received little research attention, despite continued year-over-year sales growth for both carry-out and delivery. Therefore, this study aims to analyze off-premise service modes, including food delivery robots, for service quality gaps between consumer expectations and actual performance and among the various modes.

Design/methodology/approach

Performance of three off-premise restaurant service modes (robot-delivery, human-delivery and carry-out) were evaluated using a mixed-methods approach. Consumer expectations were ascertained about food- and service-related performance factors using a survey, and a field observation study was conducted to obtain actual performance data for these factors. Findings from both approaches were compared to identify gaps and differences.

Findings

For food-related performance, consumers reported lower expectations for food safety and food quality from robot- and human-delivered food; however, no differences were observed among the three modes in the field study. Consumers also expected lower service-related performance from robot-delivery for service efficiency and ease of use (than human-delivery and carry-out) and monetary value (than carry-out). Consumers deemed robots the most sustainable and human-delivery the most convenient compared to other modes – however, not all service-related expectations aligned with actual performances.

Originality/value

This study was the first to comparatively examine off-premise restaurant service. Identification of a missing link in service gap analysis was among the theoretical contributions of this study. Managerially, this study provides previously unavailable insights into opportunities for improvement for off-premise service and use of delivery robots.
Does meaningful work encompass support towards supervisory, worker and engagement relationship?
Authors: Ahmed Umair , Yong Irene Seok-Ching , Pahi Munwar Hussain , Dakhan Sarfraz Ahmed
Published: June 2021

Purpose

This study aimed at examining the influence of two important elements of social supports, namely supervisor support and coworker support, on work engagement among employees in the university setting. The study also further examined the mediating potentials of meaningful work on the relationships between the former and the latter.

Design/methodology/approach

The sample study comprised academic and managerial staff members from a public-sector university in Malaysia. Out of the 420 distributed questionnaires, 216 were received back from which 177 were found useable and hence were taken further for final data analysis. Statistical software of SPSS and Smart PLS 2.0 M3 were used to perform data analysis.

Findings

Supervisor support and coworker support were found to be significant predictors of work engagement. Further, meaningful work was found mediating these relationships.

Originality/value

The findings enrich literature of social support, work engagement, and meaningful work. The study is one of the foremost empirical works examining the mediating potential of meaningful work on the relationships between two social resources (supervisor support and coworker support) and work engagement. The issue of work engagement is evident in several mainstream work sectors alongside the education sector. Hence, the research findings are worthy to help understand work engagement issues and how to tackle it in the education setting.
Beyond monetary motivation: the moderation of Hofstede's cultural dimensions
Authors: Tetteh Stephen , Dei Mensah Rebecca , Opata Christian Narh , Agyapong Gloria Nana Yaa Asirifua
Published: June 2021

Purpose

This study explicitly examines how Hofstede's cultural dimensions moderate the relationship between nonmonetary motivation factors and performance.

Design/methodology/approach

Through the simple random sampling technique, the hypotheses were tested with a sample of 604 employees from a mobile telecommunication company operating in both China and Ghana, two countries that represent two same and opposite cultural poles on Hofstede's cultural dimensions.

Findings

The results point that employee motives such as relationship, supervision, challenging work and achievement are moderated by cultural values. Whilst employees with high power distance cultural values are highly motivated by high supervision, those with low individualistic cultural values are highly motivated by high relationship. The results also depict that whilst the interaction effects between supervision and power distance and relationship and individualism on performance were marginal for both China and Ghana samples, the interaction effect of achievement and masculinity as well as challenging work and uncertainty avoidance on performance had great differences due to the different cultural values for the two countries.

Practical implications

This study implies that, as organizations are devising strategies to lower personnel costs in a recessionary period, there is the need to redesign motivation factors that go beyond monetary means and based on the cultural background of an employee in order to improve performance.

Originality/value

This is one of the few studies that focused on nonmonetary motives from a cultural management perspective with samples from emerging economies.
Contextual influences on marketing and consumerism: an East Asian perspective
Authors: Zhou Wenkai , Yang Zhilin , Hyman Michael R.
Published: June 2021

Purpose

This study aims to summarize the important contextual influences East Asian philosophy may have on marketing strategy and consumerism.

Design/methodology/approach

A qualitative approach is used to deconstruct (1) the literature on marketing as a contextual discipline, (2) East Asian philosophical underpinnings and their personal and institutional manifestations in East Asian marketing contexts, and (3) the implications for non-East Asian marketers. This essay includes a brief introduction to the manuscripts in this special issue.

Findings

Ancient philosophical wisdom shared by East Asian societies can shed light on how marketing activities and consumer behavior intertwine within East Asia and beyond. Three ancient philosophies (i.e. Confucianism, Taoism, Buddhism) heavily influence East Asian societies through personal and institutional-level cultural manifestations in marketing contexts.

Research limitations/implications

Although the three discussed East Asian philosophical schools are not exhaustive, they lay a foundation for future discussions about how alternative marketing-related theories and frameworks may complement ones grounded in western historical and cultural contexts.

Originality/value

This essay initiates an overdue academic discussion about relying on non-western historical and cultural contexts to globalize the marketing discipline further.