bluuebunny/crossref_metadata_2025 huggingface dataset:
VALIDATION OF AN INSTRUMENTED MOUTHGUARD
Authors: Jones Christopher M. , Brown M Rowan.
Published: March 2022

The purpose of this study was to determine the validity of an raw and filtered acceleration time-series data from an instrumented mouthguard system against an anthropometric testing device. Testing was conducted in a laboratory using a standard impact protocol utilising the head-form of reference system and the mouthguard system. Testing occurred at 5 impact locations: facemask, front, oblique, side and back, and at four velocities (3.6, 5.5, 7.4, and 9.3 m/s) to attain a total of 55 impacts. A 160 Hz Low-pass 4th order Butterworth filter was applied to the time-series data, and was reported as raw and filtered. Peak linear acceleration, peak rotational velocity and peak rotational acceleration was statistically compared to the reference measurement system. Total concordance correlation coefficient was 90.7% and 96.9%, for raw and filtered data set. Raw and filtered had intraclass correlation coefficients of 0.85 and 0.95 for peak linear acceleration, 0.99 and 0.99 for peak rotational velocity and 0.94 and 0.95 peak rotational acceleration respectively. The instrumented mouthguard displayed high accuracy when measuring head impact kinematics in a laboratory setting. The results presented in this study provide the basis on which the instrumented mouthguard can be further developed for deployment and application within sport quantify head impact collision dynamics in order to optimise performance and brain health.
Low Haemoglobin Levels are Associated with Reduced Psychomotor and Language Abilities in Young Ugandan Children
Authors: Nampijja Margaret , Mutua Agnes M , Elliott Alison M , Muriuki John Muthii , Abubakar Amina , Webb Emily L , Atkinson Sarah H
Published: March 2022

Children living in Sub-Saharan Africa are vulnerable to developmental delay, particularly in the critical first five years due to various adverse exposures including disease and nutritional deficiencies. Anaemia and iron deficiency (ID) are highly prevalent in pregnant mothers and young children and are implicated in abnormal brain development. However, available evidence on the association between anaemia, ID and neurodevelopment in Sub-Saharan Africa is limited. Using data from the Entebbe Mother and Baby Study prospective birth cohort, we examined the effect of maternal and child haemoglobin (Hb) levels and child iron status on developmental scores in 933 and 530 pre-school Ugandan children respectively. Associations between Hb levels, iron status and developmental scores were assessed using regression analyses adjusting for potential confounders. Lower maternal and child Hb levels were associated with reduced psychomotor scores at 15 months, while only lower Hb levels in infancy were associated with reduced language scores. We found no evidence that anaemia or ID was associated with cognitive or motor scores at five years. This study emphasizes the importance of managing anaemia in pregnancy and infancy and highlights the need for further studies on the effects of anaemia and ID in children living in Sub-Saharan Africa.
Profiling the plasmid conjugation potential of urinary E. coli
Authors: Hernandez Cesar Montelongo , Putonti Catherine , Wolfe Alan J.
Published: March 2022

Escherichia coli is often associated with urinary tract infection (UTI). Antibiotic resistance in E. coli is an ongoing challenge in managing UTI. Extrachromosomal elements – plasmids – are vectors for clinically relevant traits, such as antibiotic resistance, with conjugation being one of the main methods for horizontal propagation of plasmids in bacterial populations. Targeting of conjugation components has been proposed as a strategy to curb spread of plasmid-borne antibiotic resistance. Understanding the types of conjugative systems present in urinary E. coli isolates is fundamental to assessing the viability of these strategies. In this study, we profile the two well studied conjugation systems (F-type and P-type) in the draft genomes of 65 urinary isolates of E. coli obtained from bladder urine of adult women with and without UTI-like symptoms. Most of these isolates contained plasmids and we found that conjugation genes are abundant/ubiquitous, diverse, and often associated with IncF plasmids. To validate conjugation of these urinary plasmids, we conjugated the plasmids from two urinary isolates, UMB1223 (predicted to have F-type genes) and UMB1284 (predicted to have P-type genes), into the K-12 E. coli strain MG1655. Overall, the findings of this study support the notion that care should be taken in targeting any individual component of a urinary E. coli isolate’s conjugation system, given the inherent mechanistic redundancy, gene diversity, and different types of conjugation systems in this population.
Gene Expression and Tracer-Based Metabolic Flux Analysis Reveals Tissue-Specific Metabolic Scaling in vitro, ex vivo, and in vivo
Authors: Akingbesote Ngozi D. , Leitner Brooks P. , Jovin Daniel G. , Desrouleaux Reina , Zhu Wanling , Li Zongyu , Pollak Michael N. , Perry Rachel J.
Published: March 2022

Metabolic scaling, the inverse correlation of metabolic rates to body mass, has been appreciated for more than 80 years. Studies of metabolic scaling have almost exclusively been restricted to mathematical modeling of oxygen consumption. The possibility that other metabolic processes scale with body size has not been studied. To address this gap in knowledge, we employed a systems approach spanning from transcriptomics to in vitro and in vivo tracer-based flux. Gene expression in livers of five species spanning a 30,000-fold range in mass revealed differential expression of genes related to cytosolic and mitochondrial metabolic processes, in addition to detoxication of oxidative damage. This suggests that transcriptional scaling of damage control mechanisms accommodates increased oxidative metabolism in smaller species. To determine whether flux through key implicated metabolic pathways scaled, we applied stable isotope tracer methodology to study multiple cellular compartments, tissues, and species. Comparing mice and rats, we demonstrate that while scaling of metabolic fluxes is not observed in the cell-autonomous setting, it is present in liver slices and in vivo. Together, these data reveal that metabolic scaling extends beyond oxygen consumption to numerous other metabolic pathways, and is likely regulated at the level of gene expression and substrate supply.
Focal adhesion-based cell migration is differentially regulated in vivo versus in vitro by Paxillin phosphorylation
Authors: Xue Qian , Varady Sophia R. S. , Alaka’i Waddell Trinity Q , Carrington James , Roh-Johnson Minna
Published: March 2022

Focal adhesions are important subcellular structures that physically link the cell to the extracellular matrix (ECM), thus facilitating efficient cell migration. Although in vitro cell culture studies have provided a wealth of information regarding focal adhesion biology, it is critical to understand how focal adhesions are dynamically regulated in their native environment. We developed a zebrafish transplantation system in which we could efficiently visualize focal adhesion structures during single cell migration in vivo with high-resolution live cell imaging. By comparing focal adhesions between this in vivo system and the traditional in vitro cell culture model, we show differential regulation of a core focal adhesion protein, Paxillin. We find that a key site of phosphoregulation on Paxillin, tyrosine 118 (Y118), exhibits reduced phosphorylation in migrating cells in vivo in both zebrafish and mouse melanoma models, contrary to the pivotal role for this phosphorylation event in cell culture studies. Furthermore, direct modulation of this residue by site directed mutagenesis leads to opposite cell migration phenotypes in vivo versus in vitro in both migrating cancer cells and macrophages. Unexpectedly, expression of a non-phosphorylatable version of Y118-Paxillin promotes cell migration in vivo, despite inhibiting cell migration in the in vitro cell culture conditions. To further understand the mechanism of this regulation, we find that the upstream kinase, focal adhesion kinase (FAK), is downregulated in cells in vivo, and that cells expressing non-phosphorylatable Y118-Paxillin exhibit increased interactions between Paxillin and CRKII, an adaptor protein known to promote cell migration signaling. Collectively, our findings provide significant new insight into how focal adhesions are regulated in cells migrating in their native environment.
Regulation associated modules reflect 3D genome modularity associated with chromatin activity
Authors: Zheng Lina , Wang Wei
Published: March 2022

The 3D genome has been shown to be organized into modules including topologically associating domains (TADs) and compartments that are primarily defined by spatial contacts from Hi-C or other experiments. There exists a gap to investigate whether and how the spatial modularity of the chromatin is related to the functional modularity resulting from the chromatin activity. Increasing evidence shows a tight interplay between histone modifications and 3D chromatin organization. As the histone modifications reflect the chromatin activity, it is tempting to infer the spatial modularity of the genome directly from the histone modification patterns, which would establish the connection between the spatial and functional modularity of the genome. However, uncovering the 3D genomic modules using histone modifications has not been well explored. Here, we report that the histone modifications show a modular pattern (referred to as regulation associated modules, RAMs) that reflects the spatial modularity of the chromatin structure. We found that enhancer-promoter interactions and extrachromosomal DNAs (ecDNAs) occur more often within the same RAMs than within the same TADs, indicating stronger insulation of the RAM boundaries and a modularization of the 3D genome at a scale better aligned with the chromatin activity. Consistently, compared to the TAD boundaries, in silico predictions showed that deletions of RAM boundaries perturb the chromatin structure more severely and somatic variants in the cancer samples are more enriched in the RAM boundaries. These observations suggest that RAMs reflect a modular organization of the 3D genome at a scale better aligned with chromatin activity, providing a bridge connecting the structural and functional modularity of the genome.
Inhibition is a prevalent mode of activity in the neocortex around awake hippocampal ripples
Authors: Abadchi Javad Karimi , Rezaei Zahra , Knöpfel Thomas , McNaughton Bruce L. , Mohajerani Majid H.
Published: March 2022

Coordinated peri-ripple activity in the hippocampal-neocortical network is essential for mnemonic information processing in the brain. Hippocampal ripples likely serve different functions in sleep and awake states. Thus, the corresponding neocortical activity patterns may differ in important ways. We addressed this possibility by conducting voltage and glutamate wide-field imaging of the neocortex with concurrent hippocampal electrophysiology in awake mice. Contrary to our previously published sleep results, deactivation and activation were dominant in post-ripple neocortical voltage and glutamate activity, respectively, especially in the agranular retrosplenial cortex (aRSC). Additionally, the spiking activity of aRSC neurons, estimated by two-photon calcium imaging, revealed the existence of two subpopulations of excitatory neurons with opposite peri-ripple modulation patterns: one increases and the other decreases firing rate. These differences in peri-ripple spatiotemporal patterns of neocortical activity in sleep versus awake states might underlie the reported differences in the function of sleep versus awake ripples.
Morpho-functional analysis of the head glands in three Auchenorrhyncha species and their possible biological significance
Authors: Sevarika Milos , Di Giulio Andrea , Rondoni Gabriele , Conti Eric , Romani Roberto
Published: March 2022

The CicadomorphaPhilaenus spumarius, Neophilaenus campestrisandCicadella viridisare known transmitters of the bacteriumXylella fastidiosa. Here, we studied the ultrastructural organization of their cephalic glands. Our investigations with scanning, transmission, FIB-SEM electron microscope and light microscope revealed for the first time in Auchenorrhyncha the presence of two types of cephalic glands. Both belonged to the class III epidermal glands, according to Noirot and Quennedey classification. Type I glands were the most common, being mainly located around antennae, lorum and gena. Moreover, these glands were observed also on the abdomen and thorax, always in association with sensilla trichoidea. The second type of glands were located exclusively at the apical part of the postclypeus inP. spumariusandN. campestris.The ultrastructural organization was similar in both types, being composed of a secretory cell and a conducting canal. Differences were observed in the width of the cuticular opening, being smaller in the type II glands. In addition, we have recorded the presence of a maxillary sensory pit in all species and described sensilla trichoidea ultrastructural organization. Finally, we discussed the ultrastructural organization of the glands and their potential biological role.
EEG Responses to Auditory Figure-Ground Perception
Authors: Guo Xiaoxuan , Dheerendra Pradeep , Benzaquén Ester , Sedley William , Griffiths Timothy D
Published: March 2022

Speech-in-noise difficulty is commonly reported among hearing-impaired individuals. Recent work has established generic behavioural measures of sound segregation and grouping that are related to speech-in-noise processing but do not require language. In this study, we assessed potential clinical electroencephalographic (EEG) measures of central auditory grouping (stochastic figure-ground test) and speech-in-noise perception (speech-in-babble test) with and without relevant tasks. Auditory targets were presented within background noise (16 talker-babble or randomly generated pure-tones) in 50% of the trials and composed either a figure (pure-tone frequency chords repeating over time) or speech (English names). EEG was recorded while participants were presented with the target stimuli (figure or speech) under different attentional states (relevant task or visual-distractor task). EEG time-domain analysis demonstrated enhanced negative responses during detection of both types of auditory targets within the time window 650-850 ms but only figure detection produced significantly enhanced responses under the distracted condition. Further single-channel analysis showed that simple vertex-to-mastoid acquisition defines a very similar response to more complex arrays based on multiple channels. Evoked-potentials to the generic figure-ground task therefore represent a potential clinical measure of grouping relevant to real-world listening that can be assessed irrespective of language knowledge and expertise even without a relevant task.
Aeration Strategy at Birth Does Not Impact Carotid Haemodynamics in Preterm Lambs
Authors: Dahm Sophia I , Kenna Kelly R , Stewart David , Pereira-Fantini Prudence M , McCall Karen E , Perkins Liz , Sourial Magdy , Tingay David G
Published: March 2022

Background

The impact of different respiratory strategies at birth on the preterm lung is well understood, however, concerns have been raised that lung recruitment may impede cerebral haemodynamics. This study aims to examine the effect of three different ventilation strategies on cerebral haemodynamics and oxygenation.

Methods

124-127 day gestation apnoeic intubated preterm lambs (n=68) being studied as part of a larger program primarily assessing lung injury were randomised to positive pressure ventilation with positive end-expiratory pressure (PEEP) 8 cmH2O (No-RM; n=12), sustained inflation (SI; n=15) or dynamic PEEP strategy (DynPEEP; maximum PEEP 14 or 20 cmH2O, n=41) at birth, followed by 90 minutes of standardised ventilation. Haemodynamic data was continuously recorded, with intermittent arterial blood gas analysis. Main outcome measures for this study included carotid blood flow, carotid artery oxygen content and carotid oxygen delivery.

Results

Overall carotid blood flow measures were comparable between strategies, with the exception of mean carotid blood flow which was significantly lower for the SI group compared to the No-RM and DynPEEP groups respectively over the first 3 minutes (p<0.0001, mixed-effects model). Carotid oxygen content and oxygen delivery were similar between strategies. Maximum PEEP did not alter cerebral haemodynamic measures.

Conclusion

Although there were some short-term variations in cerebral haemodynamics between different PEEP strategies and SI, these were not sustained.

Impact

Different pressure strategies to facilitate lung aeration at birth in preterm infants have been proposed. There is minimal information on the effect of lung recruitment on cerebral haemodynamics.

This is the first study that compares the effect of sustained lung inflation, and dynamic and static positive end-expiratory pressure on cerebral haemodynamics.

We found that the different ventilation strategies did not alter carotid blood flow, carotid oxygen content or carotid oxygen delivery.

This preclinical study provides some reassurance that respiratory strategies designed to focus on lung aeration at birth may not impact cerebral haemodynamics in preterm neonates.
Effect of larval diet on adult immune function is contingent upon selection history and host sex inDrosophila melanogaster
Authors: Singh Aparajita , Basu Aabeer Kumar , Bansal Nitin , Shit Biswajit , Hegde Tejashwini , Prasad Nagaraj Guru
Published: March 2022

Mounting an immune response requires a considerable energy investment by the host. This makes expression of immune phenotypes susceptible to changes in availability of resources. There is ample evidence in scientific literature to suggest that hosts become more vulnerable to infection by pathogens and parasites when access to nutrition is limited. Using populations ofDrosophila melanogasterexperimentally evolved to better survive bacterial infections, we explore if host selection history influences host response to resource deprivation in terms of immune function. We find that when reared on a suboptimal diet (both in larval and adult stages), adult flies from evolved populations are still more immune to infections compared to flies from control populations. Furthermore, we observe a sex-dependent effect of interaction between selection history and diet on immune function. We thus conclude that immune function of hosts adapted to pathogen challenge is less affected by resource limitation compared to non-adapted hosts.
A Genome-Scale Metabolic Model for the Smut-FungusUstilago maydis
Authors: Liebal Ulf W. , Ullmann Lena , Lieven Christian , Kohl Philipp , Wibberg Daniel , Zambanini Thiemo , Blank Lars M.
Published: March 2022

Ustilago maydisis an important plant pathogen causing corn-smut disease and an effective biotechnological production host. The lack of a comprehensive metabolic overview hinders a full understanding of environmental adaptation and a full use of the organism’s metabolic potential. Here, we report the first genome scale metabolic model (GSMM) ofUstilago maydis(iUma22) for the simulation of metabolic activities. iUma22 was reconstructed from sequencing and annotation using PathwayTools, the biomass equation was derived from literature values and from the codon composition. The final model contains over 25% of annotated genes in the sequenced genome. Substrate utilization was corrected by Biolog-Phenotype arrays and exponential batch cultivations were used to test growth predictions. A pan-genome of four differentU. maydisstrains revealed missing metabolic pathways in iUma22. The majority of metabolic differences between iUma22 and the pangenome occurs in the inositol, purine and starch metabolic pathways. The new model allows studies of metabolic adaptations to different environmental niches as well as for biotechnological applications.
PtRNAdb: A web resource of Plant tRNA genes from a wide range of plant species
Authors: Das Durdam , Zahra Shafaque , Singh Ajeet , Kumar Shailesh
Published: March 2022

tRNA, as well as their derived products such as short interspersed nuclear elements (SINEs), pseudogenes and transfer-RNA, derived fragments (tRFs) has now been shown to be vital for cellular life, functioning and adaptation during different stress conditions in all diverse life forms. In this study, we have developed PtRNAdb (www.nipgr.ac.in/PtRNAdb), a plant exclusive tRNA database containing 113849 tRNA gene sequences from phylogenetically diverse plant species. We have analysed a total of 106 nuclear, 89 plastidial and 38 mitochondrial genomes of plants by tRNAscan-SE software package, and after careful curation of the output data, we developed this database and integrated the data. The information about the tRNA gene sequences obtained, were further enriched with consensus sequence based study of tRNA genes based on their isoacceptors and isodecoders. We have also built covariance models based on the isoacceptors and isodecoders of all the tRNA sequences using infernal tool. The user can also perform BLAST not only against PtRNAdb entries but also against all the tRNA sequences stored in PlantRNA databases; and annotated tRNA genes across the plant kingdom available at NCBI. For the users’ ease, we have also incorporated the tRNAscan-SE tool for tRNA gene prediction, and ViennaRNA package for structural analysis on the home page of PtRNAdb. This resource is believed to be of high utility for plant researchers as well as molecular biologists to carry out further exploration of plant tRNAome on a wider spectrum, as well as for performing comparative and evolutionary studies related to tRNAs and their derivatives across all domains of life.

Database URL

http://www.nipgr.ac.in/PtRNAdb/
Life history trade-offs in glucocorticoid-mediated habitat selection
Authors: Newediuk Levi , Mastromonaco Gabriela F. , Eric Vander Wal
Published: March 2022

The cort-adaptation and cort-fitness hypotheses both propose glucocorticoids produced by parents mediate trade-offs between their own survival and that of their offspring. The contribution of glucocorticoids to offspring provisioning can quantify these trade-offs because provisioning poses a risk to parents. However, attributing provisioning behaviour to glucocorticoids is difficult because glucocorticoids often drive foraging behaviours to store energy for later provisioning. We compared the effects of glucocorticoids on habitat selection before and after calving to test for the trade-offs female elk make when provisioning offspring. Despite finding that female elk with elevated glucocorticoids selected more strongly for high-risk, high-forage cropland, we found no difference in glucocorticoid production nor a significant change in the effect of glucocorticoids on cropland selection at calving time when lactating elk required the more energy. However, we found a gradual increase in the effect of glucocorticoids on cropland selection by female elk as their calves grew, suggesting the growing energy requirements of calves encouraged more risky habitat selection behaviours by their parents over time. We suggest trade-offs in investment between parents and offspring across life history stages can be tested by integrating glucocorticoids into habitat selection models. Ultimately, this integration will help elucidate the adaptive function of glucocorticoids.
SUMOylation of ABCD3 restricts bile acid synthesis and regulates metabolic homeostasis
Authors: Goyon Vanessa , Besse-Patin Aurèle , Zunino Rodolfo , Nguyen Mai , Coyaud Étienne , Lee Jonathan M. , Nguyen Bich N. , Raught Brian , McBride Heidi M.
Published: March 2022

Mitochondrial anchored protein ligase (MAPL) has been shown to function as both a SUMO and ubiquitin ligase with multiple roles in mitochondrial quality control, cell death pathways and inflammation. To examine the global function of MAPL we generated a knock-out mouse model and sought functional insight through unbiased BioID, transcriptomics and metabolic analysis. MAPL KO mice are lean and highly insulin sensitive, ultimately developing fully penetrant, spontaneous hepatocellular carcinoma after 18 months. BioID revealed the peroxisomal bile acid transporter ABCD3 as a primary MAPL interacting partner, which we show is SUMOylated in a MAPL-dependent manner. MAPL KO animals showed increased bile acid secretion in vivo and in isolated primary hepatocytes, along with robust compensatory changes in the expression of enzymes synthesizing and detoxifying bile acid. In addition, MAPL KO livers showed signs of ER stress and secreted high levels of Fgf21, the starvation hormone known to drive the reduction of white fat stores and promote insulin sensitivity. Lastly, during aging all MAPL KO mice developed hepatocellular carcinomas. These data reveal a major function for MAPL in the regulation of bile acid synthesis leading to profound changes in whole body metabolism and the ultimate generation of liver cancer when MAPL is lost.
Bioluminescent zebrafish transplantation model for drug discovery
Authors: Hason Martina , Jovicic Jovana , Vonkova Ivana , Bojic Milan , Simon-Vermot Theresa , White Richard M. , Bartunek Petr
Published: March 2022

In the last decade, zebrafish have accompanied the mouse as a robust animal model for cancer research. The possibility of screening small-molecule inhibitors in a large number of zebrafish embryos makes this model particularly valuable. However, the dynamic visualization of fluorescently labeled tumor cells needs to be complemented by a more sensitive, easy, and rapid mode for evaluating tumor growthin vivoto enable high-throughput screening of clinically relevant drugs. In this study we proposed and validated a pre-clinical screening model for drug discovery by utilizing bioluminescence as our readout for the determination of transplanted cancer cell growth and inhibition in zebrafish embryos. For this purpose, we used NanoLuc luciferase, which ensured rapid cancer cell growth quantificationin vivowith high sensitivity and low background when compared to conventional fluorescence measurements. This allowed us large-scale evaluation ofin vivodrug responses of 180 kinase inhibitors in zebrafish. Our bioluminescent screening platform could facilitate identification of new small-molecules for targeted cancer therapy as well as for drug repurposing.
Using machine learning to understand microgeographic determinants of the Zika vector, Aedes aegypti
Authors: Alexander Jagger , Bruno Wilke André Barreto , Mantero Alejandro , Vasquez Chalmers , Petrie William , Kumar Naresh , Beier John
Published: March 2022

There are limited data on why the 2016 Zika outbreak in Miami-Dade County, Florida was confined to certain neighborhoods. In this research, Aedes aegypti, the primary vector of Zika virus, are studied to examine neighborhood-level differences in their population dynamics and underlying processes. Weekly mosquito data were acquired from the Miami-Dade County Mosquito Control Division from 2016 to 2020 from 172 traps deployed around Miami-Dade County. Using Random Forest, a machine learning method, predictive models of spatiotemporal dynamics of Ae. aegypti in response to meteorological conditions and neighborhood-specific socio-demographic and physical characteristics, such as land-use and land-cover type and income level, were created. The study area was divided into two groups: areas affected by local transmission of Zika during the 2016 outbreak and unaffected areas. Aedes aegypti populations in areas affected by Zika were more strongly influenced by 14- and 21-day lagged weather conditions. In the unaffected areas, mosquito populations were more strongly influenced by land-use and day-of-collection weather conditions. There are neighborhood-scale differences in Ae. aegypti population dynamics. These differences in turn influence vector-borne disease diffusion in a region. These results have implications for vector control experts to lead neighborhood-specific vector control strategies and for epidemiologists to guide vector-borne disease risk preparations, especially for containing the spread of vector-borne disease in response to ongoing climate change.
Development of a Method Combining Peptidiscs and Proteomics to Identify, Stabilize and Purify a Detergent-Sensitive Membrane Protein Assembly
Authors: Young John William , Wason Irvinder Singh , Zhao Zhiyu , Kim Sunyoung , Aoki Hiroyuki , Phanse Sadhna , Rattray David G , Foster Leonard J. , Babu Mohan , van Hoa Franck Duong
Published: March 2022

The peptidisc membrane mimetic enables global reconstitution of the bacterial membrane proteome into water-soluble detergent-free particles, termed peptidisc libraries. We present here a method that combines peptidisc libraries and chromosomal-level gene tagging technology with affinity purification and mass spectrometry (AP/MS) to stabilize and identify fragile membrane protein complexes that exist at native expression levels. This method circumvents common artifacts caused by bait protein overproduction and protein complex dissociation due to lengthy exposure to detergents during protein isolation. Using the E. coli Sec system as a case study, we identify an expanded version of the translocon, termed the HMD complex, consisting of 9 different integral membrane subunits. This complex is stable in peptidiscs but dissociates in detergent. Guided by this native-level proteomic information, we design and validate a procedure that enables purification of the HMD complex with minimal protein dissociation. These results highlight the utility of peptidiscs and AP/MS to discover and stabilize fragile membrane protein assemblies.
Gut microbe Lactiplantiballus plantarum undergoes different evolutionary trajectories between insects and mammals
Authors: Maritan Elisa , Gallo Marialaura , Srutkova Dagmar , Jelinkova Anna , Benada Oldrich , Kofronova Olga , Silva-Soares Nuno F. , Hudcovic Tomas , Gifford Isaac , Barrick Jeffrey E. , Schwarzer Martin , Martino Maria Elena
Published: March 2022

Animals form complex symbiotic associations with their gut microbes, whose evolution is determined by an intricate network of host and environmental factors. In many insects, such as Drosophila melanogaster, the microbiome is flexible, environmentally determined and less diverse than in mammals. In contrast, mammals maintain complex multispecies consortia that are able to colonize and persist in the gastrointestinal tract. Understanding the evolutionary and ecological dynamics of gut microbes in different hosts is challenging. This requires disentangling the ecological factors of selection, determining the timescales over which evolution occurs, and elucidating the architecture of such evolutionary patterns. Here, we employ experimental evolution to track the pace of the evolution of a common gut commensal, Lactiplantibacillus plantarum, within invertebrate (Drosophila melanogaster) and vertebrate (Mus musculus) hosts and their respective diets. While the symbiosis between Drosophila and L. plantarum is mainly determined by host diet, with the host influencing the fitness of its gut microbes only over short timescales, bacterial evolution within the mammalian host follows a divergent evolutionary path. Here, the host and its intrinsic factors play a critical role in selection and influence both the phenotypic and genomic evolution of its gut microbes, as well as the outcome of their symbiosis.
Chimeric mRNA based COVID-19 vaccine induces protective immunity against Omicron and Delta
Authors: Hu Qidong , Zhao Ying , Shaabani Namir , Lyu Xiaoxuan , Sun Haotian , Cruz Vincent , Kao Yi , Xu Jia , Fossier Amber , Stegman Karen , Wang Zhihao , Wang Zhenping , Hu Yue , Zheng Yi , Kyaw Lilian , Zuluaga Cipriano , Wang Hua , Pei Hong , Powers Colin , Allen Robert , Xie Hui , Ji Henry , Chen Runqiang
Published: March 2022

The emerging SARS-CoV-2 variants of concern (VOCs) exhibit enhanced transmission and immune escape, reducing the efficacy and effectiveness of the two FDA-approved mRNA vaccines. Here, we explored various strategies to develop novel mRNAs vaccines to achieve safer and wider coverage of VOCs. Firstly, we constructed a cohort of mRNAs that feature a furin cleavage mutation in the spike (S) protein of predominant VOCs, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2). Not present in the mRNA vaccines currently in use, the mutation abolished the cleavage between the S1 and S2 subunits, potentially enhancing the safety profile of the immunogen. Secondly, we systematically evaluated the induction of neutralizing antibodies (nAb) in vaccinated mice, and discovered that individual VOC mRNAs elicited strong neutralizing activity in a VOC-specific manner. Thirdly, the IgG produced in mice immunized with Beta-Furin and Washington (WA)-Furin mRNAs showed potent cross-reactivity with other VOCs, which was further corroborated by challenging vaccinated mice with the live virus of VOCs. However, neither WA-Furin nor Beta-Furin mRNA elicited strong neutralizing activity against the Omicron variant. Hence, we further developed an Omicron-specific mRNA vaccine that restored protection against the original and the sublineages of Omicron variant. Finally, to broaden the protection spectrum of the new Omicron mRNA vaccine, we tested the concept of bivalent immunogen. Instead of just fusing two RBDs head-to-tail, we for the first time constructed an mRNA-based chimeric immunogen by introducing the RBD of Delta variant into the entire S antigen of Omicron. The resultant chimeric mRNA was capable of inducing potent and broadly acting nAb against Omicron (both BA.1 and BA.2) and Delta, which paves the way to develop new vaccine candidate to target emerging variants in the future.
Cilia regulate meiotic recombination in zebrafish
Authors: Xie Haibo , Wang Xiaosi , Jin Minjun , Li Lanqin , Zhu Junwen , Kang Yunsi , Chen Zhe , Sun Yonghua , Zhao Chengtian
Published: March 2022

Meiosis is essential for evolution and genetic diversity in almost all sexual eukaryotic organisms. The mechanisms of meiotic recombination, such as synapsis, have been extensively investigated. However, it is still unclear whether signals from the cytoplasm or even outside of the cell can regulate the meiosis process. Cilia are microtubule-based structures that protrude from cell surface and function as signaling hubs to sense extracellular signals. Here, we reported an unexpected and critical role of cilia during meiotic recombination. During gametogenesis of zebrafish, cilia were specifically present in the prophase stages of both spermatocytes and primary oocytes. By developing a novel germ cell-specific CRISPR/Cas9 system, we demonstrated that germ cell-specific depletion of ciliary genes resulted in compromised double strand break repair, reduced crossover formation, and increased germ cell apoptosis. Our study reveals a previously undiscovered role for cilia during meiosis and suggests that extracellular signals may regulate meiotic recombination via this particular organelle.
iPheGWAS: an intelligent computational framework to integrate and visualise genome-phenome wide association results
Authors: George Gittu , Huang Yu , Gan Sushrima , Nar Aditya S. , Ha Jason , Venkatesan Radha , Mohan Viswanathan , Wang Huan , Brown Andrew , Palmer Colin N. A. , Doney Alex S. F.
Published: March 2022

Estimating the genetic correlations by LDSC is computationally demanding and visualising multiple GWAS results along with their genetic relationships is restricted. This study developed iPheGWAS, a novel approach which applied hierarchical clustering to GWAS summary statistics to (i) calculate their genetic relatedness, and (ii) enable three-dimensional visualisation of multiple ordered GWAS plots. Simulation and real-world data analysis demonstrated that when investigating genetic relationships among multiple phenotypes, iPheGWAS can deliver comparable results with LDSC but with 8 times faster computational speed. It can also provide novel findings in studying genetically-correlated comorbidities, such as mental illness and rheumatoid arthritis.
Molecular mechanisms underlying Warburgia salutaris effects on oxidative stress and apoptotic parameters in Human Hepatoma Cells
Authors: Maruma Lebogang N. , Somboro Anou M. , Amoako Daniel G. , Khumalo Hezekiel M. , Khan Rene B.
Published: March 2022

This study aims to determine the molecular effects of Warburgia salutaris extract in HepG2 cells and elucidate the possible mechanisms. The MTT assay was employed to determine cell viability and the half maximal inhibitory concentration (IC50) of Warburgia salutaris-treated in HepG2 cells (0-5mg/ml). Extracellular lactate dehydrogenase and ATP were also quantified as a measure of cell viability. The production of reactive oxygen species (ROS) was assessed by quantifying lipid peroxidation and oxidative DNA damage, and reactive nitrogen species (RNS) in treated HepG2 cells. The cells response to free radicals was assessed by measuring GSH. Stress response antioxidant and apoptotic markers were detected using western blotting and /or qPCR. Cell death parameters assayed included annexin V, caspase activity and necrosis. Single-cell gel electrophoresis (SCGE) was used to visualise DNA damage in the HepG2 cells and confirmed with DNA fragmentation assay. The Hoechst assay allowed the visualisation of the nucleus to assess cell growth and apoptosis. Decreased cell viability was associated with a decreased level of ATP. The presence of oxidative stress was suggested by increased HSP70 and Nrf2 protein expression and confirmed by increase ROS, RNS, GPx and catalase; and a corresponding decrease of SOD2 and glutathione. Caspase 8 showed no significant difference between treatment concentrations, caspase 9 was decreased and caspase 3/7 increased. A reduction in p53 correlated with chromatin changes, increase in comet lengths and DNA fragmentation. NFκB protein was significantly decreased at the IC50, along with decreased cMyc protein expression. Our findings shows that Warburgia salutaris promotes apoptosis by inducing oxidative stress in HepG2 cells and may be a potential anti-cancer agent that would serve as an alternative to conventional therapeutic agents.
A molecular dynamic investigation of Human Rhinovirus 3C Protease Drug Target: Insights towards the design of potential Inhibitors
Authors: Buthelezi Ndumiso M , Amoako Daniel G. , Somboro Anou M. , Khan Rene B. , Kumalo Hezekiel M.
Published: March 2022

The 3C protease is distinguished from most proteases due to the presence of cysteine nucleophile that plays an essential role in viral replication. This peculiar structure encompassed with its role in viral replication has promoted 3C protease as an interesting target for therapeutic agents in the treatment of diseases caused by human rhinovirus (HRV). Herein we present a comprehensive molecular dynamics study of the comparison of two potent inhibitors, sg85 and rupintrivir complexed with HRV-3C protease. The binding free energy studies revealed a higher binding affinity for sg85 −58.853 kcal/mol than for rupintrivir −54.0873 kcal/mol and this was found to be in correlation with the experimental data. The energy decomposition analysis showed that, residues Leu 127, Thr 142, Ser 144, Gly 145, Tyr 146, Cys 147, His 161, Val 162, Gly 163, Gly 164, Asn 165, Phe 170 largely contributed to the binding of sg85, whereas His 40, Leu 127 and Gly 163 impacted the binding of rupintrivir. It further showed that His 40, Glu 71, Leu 127, Cys 147 Gly 163 and Gyl 164 are crucial residues that play a key role in ligand-enzyme binding; amongst these residues are residues of the conserved active site (His 40, Glu 71 and Cys 147). These findings provide a comprehensive understanding of the dynamics and structural features and will serve as guidance in the design and development of potent novel inhibitors of HRV.

Graphical Abstract
Factors influencing parasocial relationship in the virtual reality shopping environment: the moderating role of celebrity endorser dynamism
Authors: Yuan Chunlin , Wang Shuman , Liu Yue , Ma Jenny Weichen
Published: March 2022

Purpose

This paper explores the driving factors of parasocial relationship (PSR) in the virtual reality (VR) shopping environment, and how this relationship affects brand equity. The study also investigates the moderating role of the celebrity endorser dynamism (CED) in the relationship between PSR and its antecedents.

Design/methodology/approach

The primary data collection tool is a survey administered to Chinese consumers (n = 531) who have experienced the products of UNIQLO brand on Taobao Buy + platform, and who had a PSR with the endorser in their VR shopping process. Structural equation modeling is employed to examine the hypothesized relationships among all variables.

Findings

The findings show that VR shopping factors (i.e. physical attractiveness, social presence and technology novelty) perceived by consumers to affect PSR, and this relationship and brand equity are positively associated, while CED moderates the relationship between PSR and its antecedents.

Originality/value

This study sheds light on how PSR in the VR shopping environment can improve brand equity. It contributes to the theory of PSR and persuasion as well as marketing strategies. From a managerial perspective, guidelines are provided for firms to implement value communication activities using VR, and to increase their brand equity.
Stressful eating indulgence by generation Z: a cognitive conceptual framework of new age consumers’ obesity
Authors: Priporas Constantinos-Vasilios , Vellore-Nagarajan Durga , Kamenidou Irene (Eirini)
Published: March 2022

Purpose

This study aims to delineate the phenomenon of stressful eating within generation Z due to the times they are living in and to extract propositions which elucidate phases of stressful eating within Zers.

Design/methodology/approach

Based on relevant literature on consumer obesity, theories of pure impulse buying and reasoned action, cognitive constructs eminent for reasoned conditioned behaviour are extracted. Followed by extraction of the reasoned conditioned behaviour and its cognitive constructs within Zers. Thereafter, a conceptual framework is developed with propositions of stressful eating within Zers.

Findings

Zers indulge in reasoned conditioned behaviour initially owing to their healthy understanding insights, and the activations of cognitive capacities within them due to the law of effect. The law of effect is cyclical after the first reasoned consumption among Zers, leading to obesity and constricting self-controlling behaviour.

Originality/value

To the best of the authors’ knowledge, this is the first study that provides a deep understanding of the cognitive mechanism orienting generation Z’s stressful eating indulgence even though they have higher healthy lifestyle understandings.
Analysing scientific publications in the field of mobile information systems using bibliometric analysis
Authors: Zhang Guijie , Wei Fangfang , Guo Chunyan , Wang Yanfang
Published: March 2022

Purpose

This paper aims to present a longitudinal and visualising study using bibliometric approaches to depict the emerging trends and research hotspots within the mobile information system domain.

Design/methodology/approach

Publications included in the Web of Science (WoS) database for 2001–2021 are reviewed and analysed on various aspects through coauthorship, cocitation and co-occurrence analysis. The analyses are conducted using VOSViewer, a scientific visualisation software program.

Findings

Academic publications related to mobile information systems fluctuated at a low level during the initial part of the 21st century and have grown rapidly in number in the past decade. The USA and China are the leading contributors to these publications and hold dominant positions in the obtained collaboration network. Computer science, engineering and telecommunications are the top three research areas in which mainstream mobile information system research occurs. Moreover, medical informatics and health-care science services have gradually become new research hotspots.

Originality/value

This study provides a systematic and holistic account of the developmental landscape of the mobile information system domain. This study provides a good basis for analysing the evolution of research in mobile information systems and may serve as a potential foundation for future research.
State of the art of university social responsibility: a standardized model and compared self-diagnosis in Latin America
Authors: Vallaeys François , Oliveira M.L.S. , Crissien Tito , Solano David , Suarez Andres
Published: March 2022

Purpose

This paper aims to provide information about the state of the art of University Social Responsibility (USR) from a regional perspective, based on a theoretical and practical development proposed by a wide net of Latin-American higher education institutions (HEIs): the USR Union of Latin America (URSULA).

Design/methodology/approach

The state of the art was performed through a two-year measurement process (2018–2019) conducted in 80 HEI from 12 Latin-American countries. The state of the art was constructed through a self-reported diagnosis concerning four HEI scopes of action, twelve goals, and sixty-six indicators to measure the accomplishment of USR goals.

Findings

The study's primary results were twofold: first, the verification of a dynamic model for USR consensual management and second, the understanding of USR's challenging nature for standard practices in HEIs.

Practical implications

This study's results contribute to creating a practical framework for USR measurement based on a regional context (Latin America). Moreover, this research underlines the discrepancy between HEIs' social performance and the need to commit to the 2030 UN sustainable development goals.

Originality/value

This is the first study to examine the state of USR in a region such a Latin America.
Internationalization of Guanxi from China to Africa
Authors: Ado Abdoulkadre
Published: March 2022

Purpose

This study focuses on the use of guanxi by African returnees from China in Africa. It explains how returnees understood and leveraged guanxi to collaborate with Chinese partners.

Design/methodology/approach

This study uses semi-structured interviews to document how guanxi is increasingly extending beyond Chinese borders. It focuses on Ethiopia, Kenya and Tanzania and analyzes the returnees' mobilization of guanxi in Sino–African business contexts.

Findings

African returnees play an increasingly important role in guanxi internationalization in Africa. Returnees' understanding of guanxi is shaped by their African traditions and their Chinese experiences, creating their new cultural capital and a dynamic Sino–African business mindset.

Originality/value

This paper reveals an emerging shift in the business mindset among African returnees once initiated in guanxi. In addition, guanxi is increasingly practiced by African organizations.