bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell culture model system utilizing engineered A549 cells to express high levels of ACE2 and TMPRSS2 for investigating SARS-CoV-2 infection and antivirals
Authors: Chang Ching-Wen , Parsi Krishna Mohan , Somasundaran Mohan , Vanderleeden Emma , Cruz John , Cousineau Alyssa , Liu Ping , Li Qi , Wang Yang , Maehr Rene , Wang Jennifer P. , Finberg Robert W.
Published: January 2022

Novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose an imminent global threat since its initial outbreak in December 2019. A simple in vitro model system using cell lines highly susceptible to SARS-CoV-2 infection are critical to facilitate the study of the virus cycle and to discover effective antivirals against the virus. Human lung alveolar A549 cells are regarded as a useful and valuable model for respiratory virus infection. However, SARS-CoV-2 uses the ACE2 as receptor for viral entry and the TMPRSS2 to prime the Spike protein, both of which are negligibly expressed in A549 cells. Here, we report the generation of a robust human lung epithelial cell-based model by transducing ACE2 and TMPRSS2 into A549 cells and show that the ACE2 enriched A549ACE2/TMPRSS2 cells (ACE2plus) and its single-cell-derived subclone (ACE2plusC3) are highly susceptible to SARS-CoV-2 infection. These engineered ACE2plus showed higher ACE2 and TMPRSS2 mRNA expression levels than currently used Calu3 and commercial A549ACE2/TMPRSS2 cells. ACE2 and TMPRSS2 proteins were also highly and ubiquitously expressed in ACE2plusC3 cells. Additionally, antiviral drugs like Camostat mesylate, EIDD-1931, and Remdesivir strongly inhibited SARS-CoV-2 replication. Notably, multinucleated syncytia, a clinical feature commonly observed in severe COVID-19 patients was induced in ACE2plusC3 cells either by virus infection or by overexpressing the Spike proteins of different variants of SARS-CoV-2. Syncytial process was effectively blocked by the furin protease inhibitor, Decanoyl-RVKR-CMK. Taken together, we have developed a robust human A549 lung epithelial cell-based model that can be applied to probe SARS-CoV-2 replication and to facilitate the discovery of SARS-CoV-2 inhibitors.
RG203KR mutations in SARS-CoV-2 Nucleocapsid: Assessing the impact using Virus-like particle model system
Authors: Raheja Harsha , Das Soma , Banerjee Anindita , Dikshaya P , Deepika C , Mukhopadhyay Debanjan , Ramachandra Subbaraya G , Das Saumitra
Published: January 2022

The emergence and evolution of SARS-CoV-2 is characterized by the occurrence of diverse sets of mutations that affect virus characteristics, including transmissibility and antigenicity. Recent studies have focused mostly on Spike protein mutations; however, SARS-CoV-2 variants of interest (VoI) or concern (VoC) contain significant mutations in the nucleocapsid protein as well. To study the relevance of the mutations at the virion level, recombinant baculovirus expression system based VLPs were generated for the prototype Wuhan sequence along with Spike mutants like D614G, G1124V and the significant RG203KR mutation in Nucleocapsid. All the four structural proteins assembled in a particle wherein the morphology and size of the particle confirmed by TEM closely resembles the native virion. The VLP harbouring RG203KR mutations in nucleocapsid exhibited augmentation of humoral immune responses and enhanced neutralization by the immunized mice sera. Results demonstrate a non-infectious platform to quickly assess the implication of mutations in structural proteins of the emerging variant.
The common H202D variant in GDF-15 does not affect its bioactivity but can significantly interfere with measurement of its circulating levels
Authors: Karusheva Y , Ratcliff M , Melvin A , Mörseburg A , Sattar N , Barker P , Burling K , Backmark A , Roth R , Jermutus L , Guiu-Jurado E , Blüher M , Welsh P , Hyvönen M , O’Rahilly S
Published: January 2022

Genetic variants in proteins can interfere with measurement of their circulating concentrations. Given the growing biomedical importance of GDF-15, we wished to establish whether a common histidine to aspartate variant present in position 6 of the mature GDF-15 protein (H202D variant) interfered with its measurement by two commonly used immunoassays. We first examined the detectability of recombinant monomers, homodimers and heterodimers of GDF-15 by assays and/or reagents used in two widely used immunoassays (Roche Elecsys® GDF-15 and the R&D antibody combinations used in their Quantikine® and DuoSet® ELISA’s). The Roche assay detected the H and D containing peptides similarly but the assays based on the R&D reagents consistently underreported concentrations of the D-containing variant peptide. Measurements of plasma concentrations of GDF-15 in genotyped human participants showed that the R&D reagents reported values in heterozygotes were ∼25% lower, and in homozygotes, 50% lower than the Roche assay. We finally studied the activation of the GDF-15 receptor, GFRAL-Ret, in a cell based assay and found that the activities of the HH and DD containing GDF-15 peptide were indistinguishable. These results have implications for the interpretation of genetic epidemiological studies which have used the R&D reagents to measure GDF-15, and for the emerging clinical use of GDF-15 as a diagnostic and prognostic biomarker. We provide correction equations, which may be of utility for the analysis of data generated with the R&D reagents where the genotype of the participants is known.
Construct a variable-length fragment library forde novoprotein structure prediction
Authors: Feng Qiongqiong , Hou Minghua , Liu Jun , Zhao Kailong , Zhang Guijun
Published: January 2022

Although remarkable achievements, such as AlphaFold2, have been made in end-to-end structure prediction, fragment libraries remain essential forde novoprotein structure prediction, which can help explore and understand the protein-folding mechanism. In this work, we developed a variable-length fragment library (VFlib). In VFlib, a master structure database was first constructed from the Protein Data Bank through sequence clustering. The Hidden Markov Model (HMM) profile of each protein in the master structure database was generated by HHsuite, and the secondary structure of each protein was calculated by DSSP. For the query sequence, the HMM-profile was first constructed. Then, variable-length fragments were retrieved from the master structure database through dynamically variable-length profile-profile comparison. A complete method for chopping the query HMM-profile during this process was proposed to obtain fragments with increased diversity. Finally, secondary structure information was used to further screen the retrieved fragments to generate the final fragment library of specific query sequence. The experimental results obtained with a set of 120 nonredundant proteins showed that the global precision and coverage of the fragment library generated by VFlib were 55.04% and 94.95% at the RMSD cutoff of 1.5 Å, respectively. Compared to the benchmark method of NNMake, the global precision of our fragment library had increased by 62.89% with equivalent coverage. Furthermore, the fragments generated by VFlib and NNMake were used to predict structure models through fragment assembly. Controlled experimental results demonstrated that the average TM-score of VFlib was 16.00% higher than that of NNMake.
Mito-FUNCAT-FACS reveals cellular heterogeneity in mitochondrial translation
Authors: Kimura Yusuke , Saito Hironori , Osaki Tatsuya , Ikegami Yasuhiro , Wakigawa Taisei , Ikeuchi Yoshiho , Iwasaki Shintaro
Published: January 2022

Mitochondria possess their own genome that encodes components of oxidative phosphorylation (OXPHOS) complexes, and mitochondrial ribosomes within the organelle translate the mRNAs expressed from mitochondrial genome. Given the differential OXPHOS activity observed in diverse cell types, cell growth conditions, and other circumstances, cellular heterogeneity in mitochondrial translation can be expected. Although individual protein products translated in mitochondria have been monitored, the lack of techniques that address the variation in overall mitochondrial protein synthesis in cell populations poses analytic challenges. Here, we adapted mitochondrial-specific fluorescent noncanonical amino acid tagging (FUNCAT) for use with fluorescence-activated cell sorting (FACS) and developed mito-FUNCAT-FACS. The click chemistry-compatible methionine analog L-homopropargylglycine (HPG) enabled the metabolic labeling of newly synthesized proteins. In the presence of cytosolic translation inhibitors, HPG was selectively incorporated into mitochondrial nascent proteins and conjugated to fluorophores via the click reaction (mito-FUNCAT). The application ofin situmito-FUNCAT to flow cytometry allowed us to disentangle changes in net mitochondrial translation activity from those of the organelle mass and detect variations in mitochondrial translation in cancer cells. Our approach provides a useful methodology for examining mitochondrial protein synthesis in individual cells.
Lipoate protein ligase B primarily recognizes the C8-phosphopantetheine arm of its donor substrate, and weakly binds the acyl carrier protein
Authors: Dhembla Chetna , Yadav Usha , Kundu Suman , Sundd Monica
Published: January 2022

Lipoic acid is a sulfur containing cofactor, indispensable for the function of several metabolic enzymes. In microorganisms, lipoic acid can be salvaged from the surroundings by Lipoate protein ligase A (LplA), an ATP-dependent enzyme. Alternatively, it can be synthesized by the sequential action of Lipoate protein ligase B (LipB) and Lipoyl synthase (LipA), in a two-step reaction. LipB uptakes octanoyl-chain from C8-acyl carrier protein (C8-ACP), a byproduct of the type II fatty acid synthesis pathway, and transfers it to a conserved lysine of the lipoyl domain of a dehydrogenase. The molecular basis of substrate recognition by LipB is still not fully understood. Using E. coli LipB as a prototype, we show that the enzyme mainly recognizes the 4’-phosphopantetheine tethered acyl-chain of its donor substrate, and weakly binds the apo-acyl carrier protein. It can accept octanoate-from its own ACP, noncognate ACPs, as well as C8-CoA. Further, our NMR studies demonstrate the presence of an adenine and phosphate binding site in LipB, akin to LplA. A loop containing 71RGG73 sequence, analogous to the lipoate binding loop of LplA is also conserved. Collectively, our studies highlight commonalities between LipB and LplA in their mechanism of substrate recognition. This knowledge might be of significance in the treatment of mitochondrial fatty acid synthesis related disorders.
Dual fates of exogenous tau seeds: lysosomal clearance vs. cytoplasmic amplification
Authors: Kolay Sourav , Vega Anthony R. , Dodd Dana A. , Perez Valerie A. , Kashmer Omar M. , White Charles L. , Diamond Marc I.
Published: January 2022

Tau assembly propagation from the extracellular to intracellular space of a cell may underlie neurodegenerative tauopathies. The first step involves tau binding to heparan sulfate proteoglycans on the cell surface, followed by macropinocytosis. Pathological tau assemblies are thought to exit the vesicular compartment as “seeds” for replication in the cytoplasm. Tau uptake is highly efficient, but only ∼1-10% of cells that take up aggregates exhibit seeding. To investigate the basis for this observation, we used fluorescently tagged full-length (FL) tau fibrils added to native U2OS cells, and “biosensor” cells expressing FL tau or repeat domain fused to mClover (Clo). FL tau-Clo bound tubulin, but seeds triggered its aggregation in multiple locations simultaneously in the cytoplasm, generally independent of visible exogenous aggregates. Most exogenous tau trafficked to the lysosome, but imaging revealed a small percentage that slowly and steadily accumulated in the cytosol. Intracellular expression of Gal3-mRuby, which binds intravesicular galactosides and forms puncta upon vesicle rupture, revealed no evidence of vesicle damage following tau exposure. In fact, most seeded cells had no evidence of lysosome rupture. However, live cell imaging indicated that cells with pre-existing Gal3-positive puncta exhibited seeding at a slightly higher rate than the general population, indicating a potential role for vesicle instability as a predisposing factor. Clearance of tau seeds occurred rapidly in both vesicular and cytosolic fractions. Bafilomycin inhibited vesicular clearance, whereas MG132 inhibited cytosolic clearance. Tau seeds that enter the cell thus have at least two fates: lysosomal clearance that degrades most tau, and entry into the cytosol, where seeds replicate, and are cleared by the proteasome.
Revealing genomic changes responsible for cannabinoid receptor loss in parrots: mechanism and functional effects
Authors: Divín Daniel , Samblas Mercedes Goméz , Veetil Nithya Kuttiyarthu , Voukali Eleni , Świderska Zuzana , Krajzingrová Tereza , Tĕšický Martin , Beneš Vladimír , Elleder Daniel , Bartoš Oldřich , Vinkler Michal
Published: January 2022

In vertebrates, an ancient duplication in the genes for cannabinoid receptors (CNRs) allowed the evolution of specialised endocannabinoid receptors expressed in the brain (CNR1) and the periphery (CNR2). While dominantly conserved throughout vertebrate phylogeny, our comparative genomic analysis suggests that certain taxa may have lost either the CNR1 regulator of neural processes or, more frequently, the CNR2 involved in immune regulation. Focussing on conspicuousCNR2pseudogenization in parrots (Psittaciformes), a diversified crown lineage of cognitively-advanced birds, we highlight possible functional effects of such a loss. Parrots appear to have lost theCNR2gene at at least two separate occasions due to chromosomal rearrangement. Using gene expression data from the brain and periphery of birds with experimentally-induced sterile inflammation, we compareCNRand inflammatory marker (interleukin 1 beta,IL1B) expression patterns inCNR2-deficient parrots (represented by the budgerigar,Melopsittacus undulatusand five other parrot species) withCNR2-intact passerines (represented by the zebra finch,Taeniopygia guttata). Though no significant changes inCNRexpression were observed in either parrots or passerines during inflammation of the brain or periphery, we detected a significant up-regulation ofIL1Bexpression in the brain after stimulation with lipopolysaccharide (LPS) only in parrots. As our analysis failed to show evidence for selection on alteredCNR1functionality in parrots, compared to other birds,CNR1is unlikely to be involved in compensation forCNR2loss in modulation of the neuroimmune interaction. Thus, our results provide evidence for the functional importance ofCNR2pseudogenization for regulation of neuroinflammation.
Keeping time and rhythm by replaying a sensory-motor engram
Authors: de Lafuente Victor , Jazayeri Mehrdad , Merchant Hugo , Gracía-Garibay Otto , Cadena-Valencia Jaime , Malagón Ana M.
Published: January 2022

Imagine practicing a piece of music, or a speech, solely within the mind, without any sensory input or motor output. Our ability to implement dynamic internal representations is key for successful behavior, yet how the brain achieves this is not fully understood1–4. Here we trained primates to perceive, and internally maintain, rhythms of different tempos and performed large-scale recordings of neuronal activity across multiple areas spanning the sensory-motor processing hierarchy. Results show that perceiving and maintaining rhythms engage multiple brain areas, including visual, parietal, premotor, prefrontal, and hippocampal regions. Each area displayed oscillatory activity that reflected the temporal and spatial characteristics of an internal metronome which flexibly encoded fast, medium, and slow tempos on a trial-by-trial basis. The presence of widespread metronome-related activity across the brain, in the absence of stimuli and overt actions, is consistent with the idea that time and rhythm are maintained by a mechanism that internally replays the stimuli and actions that define well-timed behavior.
Effects of diversifying the planting period of maize on herbivorous and their natural enemies
Authors: Clemente-Orta Gemma , Alvarez Hugo Alejandro , Madeira Filipe , Albajes Ramon
Published: January 2022

Knowledge of the specific insect densities during crop development is necessary to perform appropriate measures for the control of insect pests and to minimize yield losses. In a previous study, both spatial and temporal approaches were adopted to analyse the influence of landscape structure and field variables on herbivore and predatory insects on maize. Both types of variables influenced insect abundance, but the highest effect was found with maize phenology. Given that the field planting date could modulate the influence produced by the structure of the landscape on herbivores and predatory insects, analyses of population dynamics must be performed at both the local and landscape levels. The anterior prompted us to study these aspects in the two common planting periods (early and late) in northern Spain. The present study tests the hypothesis that the period of maize planting could have a higher effect than phenology or interannual variation on the abundance of natural enemies and herbivores on maize. Our results showed that only the abundances of ‘other herbivore thrips’ and Syrphidae were significantly different between the two planting periods. Moreover, we found significant effects of planting period when we performed yearly analysis in 2015 for Coccinellidae and Chrysopidae and in 2016 and 2017 for Aeolothrips sp. Most of the taxa had abundance peaks in earlier growth stages, which are related to pollination (before or during), while only Stethorus punctillum and Syrphidae increased later in the season. Furthermore, Frankliniella occidentalis, aphids, Syrphidae and Coccinellidae registered higher abundances in fields sown in the late planting period than in the rest of the insect species. The results of the present study highlight the effects of sowing dates on insect dynamics in maize.

Highlights

Herbivorous and natural enemy abundance peaks in earlier growth stages.

Abundance of thrip and Syrphidae were different between the two planting periods.

Abundance of Coccinellidae, Chrysopidae and Aeolothrips sp. was different when performed yearly analysis.
Duplication and overexpression of the genes encoding a beta 1,3-glucan synthase confer the intrinsic resistance to echinocandin in Mucor circinelloides
Authors: Garcia Alexis , Huh Eun Young , Lee Soo Chan
Published: January 2022

Procedures such as solid organ transplants and cancer treatments can leave many patients in an immunocompromised state resulting in an increased susceptibility to opportunistic diseases including fungal infections. Mucormycosis infections are continually emerging and pose a serious threat to immunocompromised patients. Currently there has been a sharp increase in mucormycosis cases as a secondary infection in patients battling SARS-CoV-2 infections. Mucorales fungi are notorious for presenting resistance to most antifungal drugs. The absence of effective means to treat these infections results in mortality rates approaching 100% in cases of disseminated infection. One of the most effective antifungal drug classes currently available are echinocandins. Echinocandins seem to be efficacious in treatment of many other fungal infections. Unfortunately, susceptibility testing has found that echinocandins have no to little effect on Mucorales. In this study, we found that the model Mucorales Mucor circinelloides genome carries three copies of the genes encoding for the echinocandin β-(1,3)-D-glucan synthase (fksA, fksB, and fksC). Interestingly, we revealed that exposing M. circinelloides to micafungin significantly increased the expression of the fksA and fksB genes when compared to an untreated control. We further uncovered that the serine/threonine phosphatase calcineurin is responsible for the overexpression of fksA and fksB as deletion of calcineurin results in a decrease in expression of all three fks genes and a lower minimal inhibitory concentration (MIC) to micafungin. Taken together, this study demonstrates that the fks gene duplication and overexpression by calcineurin contribute to the intrinsic resistance to echinocandins in Mucor.

IMPORTANCE

The recent emergence of mucormycosis cases in immunocompromised patients has become a more prevalent issue. The Mucorales fungi that cause these infections are known to be highly drug resistant, thus treatment options are limited and the mortalities of these types of infections remain unacceptably high. Echinocandins are one of the latest antifungal drugs developed to successfully treat fungal infections, but it remains unclear why Mucorales fungi are resistant to these treatments. In our study, we uncovered three copies of the genes (fks) encoding the drug target for echinocandins. Furthermore, we discovered that the serine-threonine phosphatase calcineurin is regulating the over-expression of these genes, which confers resistance. By inhibiting calcineurin we found that the expression of these drug targets decreases resulting in an increase in susceptibility to echinocandins both in vitro and in vivo
Low vision impairs implicit sensorimotor adaptation in response to small errors, but not large errors
Authors: Tsay Jonathan S. , Tan Steven , Chu Marlena , Ivry Richard B. , Cooper Emily A.
Published: January 2022

Successful goal-directed actions require constant fine-tuning of the motor system. This fine-tuning is thought to rely on an implicit adaptation process that is driven by sensory prediction errors (i.e., where you see your hand after reaching versus where you expected it to be). Individuals with low vision experience challenges with visuomotor control, but whether they also experience challenges with implicit adaptation is unknown. To explore this question, we assessed individuals with low vision and matched controls with normal vision on a visuomotor task designed to isolate implicit adaptation. We found that low vision was associated with attenuated implicit adaptation only for small visual errors, but not large visual errors. This result not only underscores an unappreciated motor learning impairment associated with low vision, but also highlights an important constraint on how low-fidelity visual information is processed by the nervous system to enable successful implicit adaptation.

New and Noteworthy

Whether implicit adaptation is also impacted by visual uncertainty intrinsic to the nervous system remains unknown. To test this, we examined 20 people who live with visual uncertainty in daily life due to low vision on a visuomotor task that isolates implicit adaptation. We found that low vision attenuates adaptation in response to small errors only, paving the way for new developments in rehabilitation and assistive devices for individuals with sensory impairments.
Symmetry breaking organizes the brain's resting state manifold
Authors: Fousek Jan , Rabuffo Giovanni , Gudibanda Kashyap , Sheheitli Hiba , Jirsa Viktor , Petkoski Spase
Published: January 2022

Spontaneously fluctuating brain activity patterns that emerge at rest have been linked to brain's health and cognition. Despite detailed descriptions of the spatio-temporal brain patterns, our understanding of their generative mechanism is still incomplete. Using a combination of computational modeling and dynamical systems analysis we provide a mechanistic description of the formation of a resting state manifold via the network connectivity. We demonstrate that the symmetry breaking by the connectivity creates a characteristic flow on the manifold, which produces the major data features across scales and imaging modalities. These include spontaneous high amplitude co-activations, neuronal cascades, spectral cortical gradients, multistability and characteristic functional connectivity dynamics. When aggregated across cortical hierarchies, these match the profiles from empirical data. The understanding of the brain's resting state manifold is fundamental for the construction of task-specific flows and manifolds used in theories of brain function such as predictive coding. In addition, it shifts the focus from the single recordings towards brain's capacity to generate certain dynamics characteristic of health and pathology.
One-step pipetting of barcoded planar microparticles into compact monolayer assembling chip for efficient readout of multiplexed immunoassay
Authors: Bae Sangwook , Lee Daewon , Na Hunjong , Jang Jisung , Kwon Sunghoon
Published: January 2022

Barcoded planar microparticles have many qualities suitable for developing cost-efficient multiplexed immunoassays. But at the translational research level, there are a number of technical aspects yet remain to be addressed which includes robustness and efficiency of the assay readout process. Assay readout process involves automated barcode identification and signal intensity values from each planar microparticle. For this, each microparticle has to be correctly aligned for correct barcode readout while being, ideally, compactly assembled for maximum microparticle imaging efficiency. To simultaneously achieve such alignment and assembly of microparticles but in a straightforward manner, we designed a microfluidic microparticle assembling chip that only requires a single pipetting step. Our design utilizes capillary flow based guided particle assembly, which allows maximum microparticle-based immunoassay readout efficiency. With the aid of image processing algorithms, we obtained good multiplex immunoassay readout accuracy similar to conventional imaging platforms. Our approach is applicable to both soft elastomer materials (e.g. PDMS) and rigid materials (e.g. polystyrene), the latter of which is frequently used for injection molding based mass production. We anticipate our device could help developing facile and user-friendly platform technologies based on barcoded planar microparticles.
The 2009 pandemic H1N1 hemagglutinin stalk remained antigenically stable after circulating in humans for a decade
Authors: Christensen Shannon R. , Martin Emily T. , Petrie Joshua G. , Monto Arnold S. , Hensley Scott E.
Published: January 2022

An H1N1 influenza virus caused a pandemic in 2009 and descendants of this virus continue to circulate seasonally in humans. Upon infection with the 2009 H1N1 pandemic strain (pH1N1), many humans produced antibodies against epitopes in the hemagglutinin (HA) stalk. HA stalk-focused antibody responses were common among pH1N1-infected individuals because HA stalk epitopes were conserved between the pH1N1 strain and previously circulating H1N1 strains. Here, we completed a series of experiments to determine if the pH1N1 HA stalk has acquired substitutions since 2009 that prevent the binding of human antibodies. We identified several amino acid substitutions that have accrued in the pH1N1 HA stalk from 2009-2019. We completed enzyme-linked immunosorbent assays, absorption-based binding assays, and surface plasmon resonance experiments to determine if these substitutions affect antibody binding. Using sera collected from 230 humans (aged 21-80 years), we found that pH1N1 HA stalk substitutions that have emerged since 2009 do not affect antibody binding. Our data suggest that the HA stalk domain of pH1N1 viruses remained antigenically stable after circulating in humans for a decade.

Importance

In 2009, a new pandemic H1N1 (pH1N1) virus began circulating in humans. Many individuals mounted hemagglutinin (HA) stalk-focused antibody responses upon infection with the 2009 pH1N1, since the HA stalk of this virus was relatively conserved with other seasonal H1N1 strains. Here, we completed a series of studies to determine if the 2009 pH1N1 strain has undergone antigenic drift in the HA stalk domain over the past decade. We found that serum antibodies from 230 humans could not antigenically distinguish the 2009 and 2019 HA stalk. These data suggest that the HA stalk of pH1N1 has remained antigenically stable, despite the presence of high levels of HA stalk antibodies within the human population.
randtip, a generalized framework to expand incomplete phylogenies using non-molecular phylogenetic information
Authors: Ramos-Gutiérrez Ignacio , Lima Herlander , Molina-Venegas Rafael
Published: January 2022

The increasing availability of molecular information has lifted our understanding of species evolutionary relationships to unprecedent levels. However, current estimates of the world’s biodiversity suggest that about a fifth of all extant species are yet to be described, and we still lack molecular information for many of the known species. Hence, evolutionary biologists will have to tackle phylogenetic uncertainty for a long time to come.

This prospect has urged the development of software to expand phylogenies based on non-molecular phylogenetic information, and while the available tools provide some valuable features, major drawbacks persist and some of the proposed solutions are hardly generalizable to any group of organisms.

Here, we present a completely generalized and flexible framework to expand incomplete molecular phylogenies. The framework is implemented in the R package ‘randtip’, a toolkit of functions that was designed to randomly bind phylogenetically uncertain taxa in backbone phylogenies through a fully customizable and automatic procedure that uses taxonomic ranks as a major source of phylogenetic information.

Although randtip is capable of automatically generating fully operative phylogenies for any group of organisms using just a list of species and a backbone tree, we stress that the ‘blind’ expansion of phylogenies (using randtip or any other available software) often leads to suboptimal solutions. Thus, we discuss a variety of circumstances that may require customizing simulation parameters beyond default settings to optimally expand the trees, including a detailed step-by-step workflow.

Phylogenetic uncertainty should be tackled with caution, assessing potential pitfalls and opportunities to optimize parameter space prior to launch any simulation. Used judiciously, our framework will help evolutionary biologists to efficiently expand incomplete molecular phylogenies and thereby account for phylogenetic uncertainty in quantitative analyses.
Fasting Induces a Highly Resilient Deep Quiescent State in Muscle Stem Cells via Ketone Body Signaling
Authors: Benjamin Daniel I. , Both Pieter , Benjamin Joel S. , Nutter Christopher W. , Tan Jenna H. , Kang Jengmin , Machado Leo A. , Klein Julian D. D. , de Morree Antoine , Kim Soochi , Liu Ling , Dulay Hunter , Feraboli Ludovica , Louie Sharon M , Nomura Daniel K , Rando Thomas A.
Published: January 2022

Short-term fasting is beneficial for the regeneration of multiple tissue types. However, the effects of fasting on muscle regeneration are largely unknown. Here we report that fasting slows muscle repair both immediately after the conclusion of fasting as well as after multiple days of refeeding. We show that ketosis, either endogenously produced during fasting or a ketogenic diet, or exogenously administered, promotes a deep quiescent state in muscle stem cells (MuSCs). Although deep quiescent MuSCs are less poised to activate, slowing muscle regeneration, they have markedly improved survival when facing sources of cellular stress. Further, we show that ketone bodies, specifically β-hydroxybutyrate, directly promote MuSC deep quiescence via a non-metabolic mechanism. We show that β-hydroxybutyrate functions as an HDAC inhibitor within MuSCs leading to acetylation and activation of an HDAC1 target protein p53. Finally, we demonstrate that p53 activation contributes to the deep quiescence and enhanced resilience observed during fasting.
Modelling the resilience of start-ups during COVID-19 pandemic
Authors: Sreenivasan Aswathy , Suresh M. , Tuesta Panduro Juan Alfredo
Published: January 2022

Purpose

Resilience, the ability of start-ups to deal with anticipated instabilities and probable disruptions, is becoming an important success element during coronavirus disease 2019 (Covid-19). To survive in this pandemic situation, resilience is an important concept for start-ups. The present paper aims to “identify”, “analyse” and “categorize” the resilience factors for start-ups during the Covid-19 pandemic using total interpretive structural modelling (TISM).

Design/methodology/approach

The resilience elements of start-ups during Covid-19 were identified and shortlisted during the first phase, which included literature analysis and extensive interaction with experts. TISM was used in the second phase to investigate or to determine how the factors interplayed between the resilience factors of start-ups during Covid-19. The Matrice d'impacts Croises Multiplication Appliquee a un Classment (MICMAC) method is used to rank and categorize the factors. Closed-ended questionnaire with the scheduled interview was conducted to collect the data.

Findings

The first part of the study found ten resilience elements in total. The TISM digraph was constructed in the second step to show why one resilience component led to another. The MICMAC analysis divided these factors into four groups: autonomous, linkage, dependent and independent. These groups represented resilience variables based on their driving and dependent power, which assist executives and managers in proactively addressing them while using the TISM digraph as a guide.

Research limitations/implications

During the Covid-19 epidemic, this study focused primarily on resilience characteristics for Indian start-ups.

Practical implications

This study will help key stakeholders and scholars to better understand the elements that contribute to start-up's resilience.

Originality/value

The TISM method for start-up's resilience is suggested in this paper, which is a novel attempt in the field of resilience in this industry.
Quantitative visualization of physical barriers for vulnerable pedestrians based on photogrammetry
Authors: Taniguchi Koki , Kubota Satoshi , Yasumuro Yoshihiro
Published: January 2022

Purpose

The purpose of this study is to propose a method for vulnerable pedestrians to visualize potential obstacles on sidewalks. In recent years, the number of vulnerable pedestrians has been increasing as Japanese society has aged. The number of wheelchair users is also expected to increase in the future. Currently, barrier-free maps and street-view applications can be used by wheelchair users to check possible routes and the surroundings of their destinations in advance. However, identifying physical barriers that pose a threat to vulnerable pedestrians en route is often difficult.

Design/methodology/approach

This study uses photogrammetry to create a digital twin of the three-dimensional (3D) geometry of the existing walking space by collecting photographic images taken on sidewalks. This approach allows for the creation of high-resolution digital elevation models of the entire physical sidewalk surface from which physical barriers such as local gradients and height differences can be detected by uniform image filtering. The method can be used with a Web-based data visualization tool in a geographical information system, permitting first-person views of the ground and accurate geolocation of the barriers on the map.

Findings

The findings of this study showed that capturing the road surface with a small wide-angle camera while walking is sufficient for recording subtle 3D undulations in the road surface. The method used for capturing data and the precision of the 3D restoration results are described.

Originality/value

The proposed approach demonstrates the significant benefits of creating a digital twin of walking space using photogrammetry as a cost-effective means of balancing the acquisition of 3D data that is sufficiently accurate to show the detailed geometric features needed to navigate a walking space safely. Further, the findings showed how information can be provided directly to users through two-dimensional (2D) and 3D Web-based visualizations.
Design and lumped parameter magnetic network model of hybrid excited consequent pole flux switching machine
Authors: Ullah Basharat , Khan Faisal , Khan Bakhtiar , Yousuf Muhammad
Published: January 2022

Purpose

The purpose of this paper is to analyze electromagnetic performance and develop an analytical approach to find the suitable coil combination and no-load flux linkage of the proposed hybrid excited consequent pole flux switching machine (HECPFSM) while minimizing the drive storage and computational time which is the main problem in finite element analysis (FEA) tools.

Design/methodology/approach

First, a new HECPFSM based on conventional consequent pole flux switching permanent machine (FSPM) is proposed, and lumped parameter magnetic network model (LPMNM) is developed for the initial analysis like coil combination and no-load flux linkage. In LPMNM, all the parts of one-third machine are modeled which helps in reduction of drive storage, computational complexity and computational time without affecting the accuracy. Second, self and mutual inductance are calculated in the stator, and dq-axis inductance is calculated using park transformation in the rotor of the proposed machine. Furthermore, on-load performance analysis, like average torque, torque density and efficiency, is done by FEA.

Findings

The developed LPMNM is validated by FEA via JMAG v. 19.1. The results obtained show good agreement with an accuracy of 96.89%.

Practical implications

The proposed HECPFSM is developed for high-speed brushless AC applications like electric vehicle (EV)/hybrid electric vehicle (HEV).

Originality/value

The proposed HECPFSM offers better flux regulation capability with enhanced electromagnetic performance as compared to conventional consequent pole FSPM. Moreover, the developed LPMNM reduces drive storage and computational time by modeling one-third of the machine.
Experimental investigation and comparative study of signal processing techniques dedicated for the diagnosis of rotor failures in the induction motors
Authors: Dehina Wissam , Boumehraz Mohamed , Dehina Wissam , Kratz Frédéric
Published: January 2022

Purpose

The purpose of this paper is to propose applications of advanced signal-processing techniques for the diagnosis and detection of rotor fault in an induction machine. Two techniques are used: spectral analysis techniques and time frequency techniques for the diagnosis of an electrical machine. One is based on the power spectral density estimation techniques, such as periodogram and Welch periodogram. The second method is based on Hilbert transform (HT) to extract the envelope for the stator current. Then, this signal is processed via discrete wavelet transform (DWT) for determining the faulty components in the spectrum of the stator current envelope and identifying the eigenvalues of energies (HDWT).

Design/methodology/approach

First, this paper focused on theoretical development and a comparative study of these signal-processing techniques, which are based on the periodogram, Welch periodogram, HT and the DWT to extract the envelope for the stator current; it is used to compute the energy stored in each decomposition level obtained by the stator current envelope (HDWT). Moreover, the Welch periodogram is applied to obtain the envelope spectrum.

Findings

The simulation obtained and the experimental validation results of the proposed methods through MATLAB environment show the effectiveness of the proposed approaches with a good accuracy by power spectral density estimation techniques (periodogram and Welch periodogram). Moreover, the faults are manifested through the appearance of new frequencies components, as well as the envelope for the stator current (HT and DWT). This approach is effective for non-stationary and stationary signal to extract useful information for the detection of broken bar fault.

Originality/value

The current paper proposes a new diagnosis method for the detection and characterization of broken rotor bars defects early; it is founded primarily on theoretical development, and the comparison is based on the power spectral density technique (periodogram and Welch periodogram) and the computation of the energy stored in each decomposition level (precisely the HT and DWT). Moreover, the Welch periodogram is applied to obtain the envelope spectrum. The main advantages of the proposed techniques increase their reliability and availability.
Searching for hedging and safe haven assets for Indian equity market – a comparison between gold, cryptocurrency and commodities
Authors: Bandhu Majumder Sayantan
Published: January 2022

Purpose

This paper aims to evaluate the hedging and safe haven properties of gold, cryptocurrency and commodities against the Indian equity market.

Design/methodology/approach

First, the authors estimate the hedging and safe haven abilities of gold, cryptocurrency and commodities for the Indian stock market and further verify whether such properties vary across the broad stock market indices and over the different degrees of market volatility. Second, the authors use the multivariate GARCH framework to calculate the dynamic hedge ratios and hedging efficiencies to compare the hedging properties of the alternative asset classes. Third, the authors verify the robustness of the general findings during the recent crisis emanating from the outbreak of the COVID-19 pandemic.

Findings

Gold, cryptocurrency and most commodities have significant hedging abilities. Only natural gas, crude oil and aluminum, on the other hand, have safe haven property. Neither gold nor cryptocurrency qualifies as a safe haven asset. On the other hand, the financialization of the Indian commodities market provides a significant dividend to investors in terms of hedging and safe haven capabilities. The authors find the least negative hedge ratio and the highest positive hedging effectiveness for the stock-crude oil and stock-natural gas portfolios. The central observations of the paper remain immune to the COVID crisis.

Originality/value

Focusing on the Indian equity market, the paper compares the diversification abilities of traditional assets like gold with those of the modern class of assets, including cryptocurrency and other commodities.
Consumer intentions, reactance and the marketing implications of policy induced mergers and acquisitions in financial services
Authors: Mensah Kobby , Madichie Nnamdi O. , Mensah Gilbert Kofi , Awini Gideon
Published: January 2022

Purpose

The purpose of this study is to establish, drawing upon the indirect effects of customer reactance from an emerging economy perspective, the marketing implications of policy induced Mergers and Acquisitions (M&A) in Financial Services.

Design/methodology/approach

The study employed a quantitative research approach, relying on data from 517 customers of M&A banks in Ghana. Purposive sampling technique was used in selecting respondents for the study. Hypotheses were tested using a structural equation modelling.

Findings

A positive and significant relationship between immersive marketing communication and consumer intention is revealed in the study. The presence of consumer reactance highly influenced the relationship. As a public policy tool, forced mergers and acquisitions was found to increase customer reactance. However, when customers are frequently engaged with relevant and consistent marketing communications through appropriate channels, such reactance would only be partial.

Research limitations/implications

Although some of the information were collected, they were not the main focus of our analysis. We acknowledge, from the sample demographics perspective, the study did not consider certain other confounding factors that could influence customers' decisions to remain or switch such as customers' level of banking, type of account, income level, banking experiences in relation to service fees, online banking etc., as these could also potentially influence customers' reactance. Perhaps these may have to be considered in future studies.

Social implications

When timely and relevant marketing communications are targeted at the customers who are directly impacted by the M&A process, they would experience reactance, but only partially. This has a range of marketing implications for policy-induced M&A and its impact on consumer intention, reactance and attitudes towards the new entity.

Originality/value

The marketing of financial services literature has been silent on the implications of M&A from a policy induced perspective. This study, therefore, contributes to theory by highlighting that the “destruction” of brand value of the affected firms is relatively high in a policy induced M&A and thus increases the level of customer reactance. This is because a regulator enforced M&A, as public policy, usually generates high public interest and public discourse, leading to a heightened customer reactance. However, when immersive marketing communications are targeted at the customers directly impacted by the M&A, they would experience reactance, but only partially.
The causative relationship between natural resource rent and economic growth: evidence from Ghana’s crude oil resource extraction
Authors: Adabor Opoku , Buabeng Emmanuel , Fosua Dunyo Juliet
Published: January 2022

Purpose

While the relationship between natural resource rent and economic growth is well documented in the literature, not much robust analysis has been done to estimate the causative relationship between oil resource rent and economic growth in Ghana. This might be due to the fact that commercial production of crude oil started not long ago in Ghana. This paper aims to examine the causal relationship between oil resource rent and economic growth for the period of 2011 to 2020 in Ghana.

Design/methodology/approach

The study incorporates economic growth as a function of oil resource rent, non-oil revenue, foreign direct investment, capital and interest rate in a Cobb–Douglass production function/model. The study used four different estimation strategies including the autoregressive distributed lags model, Toda–Yamamoto test approach, nonlinear autoregressive distributed lags model and nonlinear Granger causality.

Findings

The main finding revealed that 1% increase in oil resource rent generates 0.84% increase in economic growth of Ghana in the long run. Contrary, the authors find an insignificant positive effect of oil resource rent on economic growth of Ghana in the short run for the period under study. The result from the Toda–Yamamoto test approach also showed a unidirectional causality running from oil resource rent to economic growth of Ghana, providing evidence in support of the resource blessing hypothesis in Ghana. The results are robust to two different alternative estimation strategies.

Originality/value

The causal relationship between crude oil resource rent and economic growth is examined.