bluuebunny/crossref_metadata_2025 huggingface dataset:
Peptide-based epitope design on non-structural proteins of SARS-CoV-2
Authors: Swathika R S , Vimal S , Bhagyashree E , Elumalai Elakkiya , Gupta Krishna Kant
Published: December 2021

The SARS-CoV-2 virus has caused the severe pandemic, COVID19 and since then its been critical to produce a potent vaccine to prevent the quick transmission and also to avoid alarming deaths. Among all type of vaccines peptide based epitope design tend to outshine with respect to low cost production and more efficacy. Therefore, we started with obtaining the necessary protein sequences from NCBI database of SARS-CoV-2 virus and filtered with respect to antigenicity, virulency, pathogenicity and non-homologous nature with human proteome using different available online tools and servers. The promising proteins was checked for containing common B and T-cell epitopes. The structure for these proteins were modeled from I-TASSER server followed by its refinement and validation. The predicted common epitopes were mapped on modeled structures of proteins by using Pepitope server. The surface exposed epitopes were docked with the most common allele DRB1*0101 using the GalaxyPepDock server. The epitopes, ELEGIQYGRS from Leader protein (NSP1), YGPFVDRQTA from 3c-like proteinase (nsp5), DLKWARFPKS from NSP9 and YQDVNCTEVP from Surface glycoprotein (spike protein) are the epitopes which has more hydrogen bonds. Hence these four epitopes could be considered as a more promising epitopes and these epitopes can be used for future studies.
SARS-CoV-2 seroprevalence in Delhi, India - September-October 2021 – a population based seroepidemiological study
Authors: Sharma Pragya , Basu Saurav , Mishra Suruchi , Gupta Ekta , Aggarwal Reshu , Kale Pratibha , Mundeja Nutan , Charan B S , Singh Gautam Kumar , Singh Mongjam Meghachandra
Published: December 2021

Background

We conducted a repeat serosurvey in Delhi, India to estimate the seroprevalence of SARS-CoV-2 in the general population and compare the antibody prevalence in the vaccinated and non-vaccinated groups.

Methods

This cross-sectional study was conducted from September 24 to October 14 2021 in 280 wards of Delhi among 27811 participants selected through a multistage sampling technique with housing settlement based stratification. The SARS-CoV-2 immunoglobulin (IgG) antibodies were screened with the VITROS® (Ortho Clinical Diagnostics, Raritan, NJ, USA) assay (90% sensitivity, 100% specificity).

Results

A total of 24895 (89.5%) samples were seropositive. The crude seroprevalence was 87.99% (95% CI 89.1, 89.8), weighted for age and sex was 88% (95% CI 87.6, 88.4), and after adjustment of assay performance was estimated as 97.5% (95% CI 97.0, 98.0). The weighted seroprevalence in the 11 districts ranged from 84.9% (South-West district) to 90.8% (East district) Females in all the age-groups (<18, 18-49 and ≥50) had significantly higher odds of seropositivity (p<0.001). On adjusted analysis, the odds of seroconversion in the participants vaccinated with at-least one dose of either Covid-19 vaccine (Covishield/Covaxin) was more than four times compared to the unvaccinated (aRR 4.2 (3.8, 4.6)). The seroprevalence was also comparable among the complete and partially vaccinated subgroups for both vaccines (Table 4). Most (86.8%) seropositive individuals had a SARS-CoV-2 signal/cut-off ≥4.0 except in children

Conclusions

We observed IgG antibodies against SARS-CoV-2 in most of the general population of Delhi with likely higher antibody titres in the vaccinated compared to the unvaccinated groups.
Safety and immunogenicity of BNT162b2 mRNA COVID-19 vaccine in Japanese patients after allogeneic stem cell transplantation
Authors: Watanabe Marika , Yakushijin Kimikazu , Funakoshi Yohei , Ohji Goh , Sakai Hironori , Hojo Wataru , Saeki Miki , Hirakawa Yuri , Matsumoto Sakuya , Sakai Rina , Nagao Shigeki , Kitao Akihito , Miyata Yoshiharu , Koyama Taiji , Saito Yasuyuki , Kawamoto Shinichiro , Ito Mitsuhiro , Murayama Tohru , Matsuoka Hiroshi , Minami Hironobu
Published: December 2021

Patients who have undergone hematopoietic stem cell transplantation (HSCT) for hematological disease experience high mortality when infected by coronavirus disease 2019 (COVID-19). However, the safety and efficacy of COVID-19 vaccine in HSCT patients remains to be investigated. We prospectively evaluated the safety and immunogenicity of BNT162b2 mRNA COVID-19 vaccine (Pfizer BioNTech) in 25 Japanese allogeneic HSCT patients in comparison with 19 healthy volunteers. While anti-S1 antibody titers in almost all healthy volunteers after the second dose were higher than the cut-off value reported previously, levels in HSCT patients after the second dose were diverse. Nineteen patients (76%) got seroconversion of anti-S1 IgG. Median optical density of antibody levels in HSCT patients with low IgG levels (< 600 mg/dL), steroid treatment, or low lymphocytes (< 1000 /μL) was significantly lower than that in the other HSCT patients. There were no serious adverse events (> Grade 3), no new development or exacerbation of graft-versus-host disease after vaccination. We concluded BNT162b2 mRNA vaccine is safe and effective in Japanese allogeneic HSCT patients.
Single Nuclei Transcriptome Reveals Perturbed Brain Vascular Molecules in Alzheimer’s Disease
Authors: İş Özkan , Wang Xue , Patel Tulsi A. , Quicksall Zachary S. , Heckman Michael G. , White Launia J. , Lewis-Tuffin Laura J. , Deniz Kaancan , Tutor-New Frederick Q. , Carnwath Troy P. , Min Yuhao , Oatman Stephanie R. , Reddy Joseph S. , Carrasquillo Minerva M. , Nguyen Thuy T. , Ho Charlotte C. G. , Malphrus Kimberly G. , Nho Kwangsik , Saykin Andrew J. , Murray Melissa E. , Dickson Dennis W. , Allen Mariet , Ertekin-Taner Nilüfer
Published: December 2021

Blood-brain barrier (BBB) dysfunction is well-known in Alzheimer’s disease (AD), but the precise molecular changes contributing to its pathophysiology are unclear. To understand the transcriptional changes in brain vascular cells, we performed single nucleus RNA sequencing (snRNAseq) of temporal cortex tissue in 24 AD and control brains resulting in 79,751 nuclei, 4,604 of which formed three distinct vascular clusters characterized as activated pericytes, endothelia and resting pericytes. We identified differentially expressed genes (DEGs) and their enriched pathways in these clusters and detected the most transcriptional changes within activated pericytes. Using our data and a knowledge-based predictive algorithm, we discovered and prioritized molecular interactions between vascular and astrocyte clusters, the main cell types of the gliovascular unit (GVU) of the BBB. Vascular targets predicted to interact with astrocytic ligands have biological functions in signalling, angiogenesis, amyloid ß metabolism and cytoskeletal structure. Top astrocytic and vascular interacting molecules include both novel and known AD risk genes such asAPOE,APPandECE1. Our findings provide information on transcriptional changes in predicted vascular-astrocytic partners at the GVU, bringing insights to the molecular mechanisms of BBB breakdown in AD.

Graphical Abstract

Pericytes (yellow), endothelia (salmon) and astrocytes (purple) that form the gliovascular unit (GVU) at the blood brain barrier (BBB) were interrogated for their differentially expressed genes (DEG) and vascular cell (pericyte or endothelia) to astrocyte interactions using single nucleus RNA sequencing (RNAseq) transcriptome obtained from brains of Alzheimer’s disease (AD) patients and controls. We identified many upregulated (red) or downregulated (blue) DEGs in AD brains in these cell types. These genes have known biological functions in amyloid ß (Aß) clearance, immune modulation, astrogliosis and neuronal death. Novel predicted interactions were identified between vascular cells and astrocytic DEGs. Collectively, our findings highlight the vast transcriptome changes that occur at the GVU and provide mechanistic insights into BBB dysfunction in AD. This figure was created with Biorender.com.
Inside-out Signalling From Aminopeptidase N (CD13) To Complement Receptor 3 (CR3, CD11b/CD18)
Authors: Díaz-Alvarez Laura , Martínez-Sánchez Mariana Esther , Gray Eleanor , Ortega Enrique
Published: December 2021

Upon ligand engagement, certain receptors can activate an integrin through a mechanism called inside-out signalling. This phenomenon prepares the cell for the next steps of the process it will perform. CR3 (Complement receptor 3), the most abundant β2 integrin in monocytes and macrophages, and CD13 (aminopeptidase N) are two immune receptors with overlapping activities: adhesion, phagocytosis of opsonized particles, and respiratory burst induction. They can be found together in functional signalling microdomains, or lipid rafts, on the surface of human leukocytes. Thus, given their common functions, shared physical location and the fact that some phagocytic and adhesion receptors activate a selection of integrins, we hypothesized that CD13 could activate CR3 through an inside-out signalling mechanism. To test this hypothesis, we first ascertained the activation of CR3 after CD13 crosslinking in human monocyte-derived macrophages. We used an integrated analysis of bioinformatics and experimental data to suggest two possible signalling cascades that could explain the phenomenon. Finally, we show that the non-receptor tyrosine kinase Syk is a key attenuator of this pathway. Our results demonstrated that, even in the absence of canonical signalling motifs, and despite having a noticeably short cytoplasmic tail (7-10 amino acids), CD13 was capable of triggering an inside-out signalling cascade, adding a new function to those already known for this moonlighting protein.

One Sentence Summary

Stimulation of CD13 activated the integrin CR3 via an inside-out signalling pathway, a mechanistic model is proposed.
Reconstitution of the S. aureus agr quorum sensing pathway reveals a direct role for the integral membrane protease MroQ in pheromone biosynthesis
Authors: Zhao Aishan , Bodine Steven P. , Xie Qian , Wang Boyuan , Ram Geeta , Novick Richard P. , Muir Tom W.
Published: December 2021

In Staphylococcus aureus, virulence is under the control of a quorum sensing (QS) circuit encoded in the accessory gene regulator (agr) genomic locus. Key to this pathogenic behavior is the production and signaling activity of a secreted pheromone, the autoinducing peptide (AIP), generated following the ribosomal synthesis and post-translational modification of a precursor polypeptide, AgrD, through two discrete cleavage steps. The integral membrane protease AgrB is known to catalyze the first processing event, generating the AIP biosynthetic intermediate, AgrD (1-32) thiolactone. However, the identity of the second protease in this biosynthetic pathway, which removes an N-terminal leader sequence, has remained ambiguous. Here, we show that MroQ, an integral membrane protease recently implicated in the agr response, is directly involved in AIP production. Genetic complementation and biochemical experiments reveal that MroQ proteolytic activity is required for AIP biosynthesis in agr specifiy groups -I and -II, but not group-III. Notably, as part of this effort, the biosynthesis and AIP-sensing arms of the QS circuit were reconstituted together in vitro. Our experiments also reveal the molecular features guiding MroQ cleavage activity, a critical factor in defining agr specificity group identity. Collectively, our study adds to the molecular understanding of the agr response and Staphylococcus aureus virulence.
Differences in running performance of single- and group-housed mice
Authors: Plenz Uma T. , Kanold Patrick O.
Published: December 2021

Mice are one of several common animal models in neuroscience and mouse behavior is becoming increasingly relevant. Mice are housed either in groups or alone in standard cages during which they show a variety of different behaviors. Moreover, housing conditions might alter the behavior of the mice as do social interactions. When given access to running wheels as an environmental enrichment, mice tend to run long distances preferentially during their dark cycle. However, it is currently not well understood whether and how mice utilize running wheels when single-housed or group-housed. Here we developed a low-cost running wheel data acquisition system to study running in adult C57BL/6 mice at high temporal resolution under different social conditions. As expected, adult C57BL/6 mice prefer to run in stretches during the dark cycle and mostly rest during the light cycle. When single-housed, running bouts occur independent from each other as indicated by an exponential decaying autocorrelation. In contrast, mice run ∼50% less when housed in groups of n = 3 and their temporal pattern of running exhibits a power law decay in the autocorrelation indicative of potential social interactions. Our results demonstrate that running wheels are a limited resource for which mice compete for when they are group-housed, thereby reducing their overall running activity.

Significance Statement

Voluntary cage wheel running is an important environmental enrichment for mice housed either alone or in groups. We show that this resource is considerably restricted for group-housed mice.
A spatially resolved stochastic model reveals the role of supercoiling in transcription regulation
Authors: Geng Yuncong , Bohrer Christopher H. , Yehya Nicolás , Hendrix Hunter , Shachaf Lior , Liu Jian , Xiao Jie , Roberts Elijah
Published: December 2021

InEscherichia coli, translocation of RNA polymerase (RNAP) during transcription introduces supercoiling to DNA, which influences the initiation and elongation behaviors of RNAP. To quantify the role of supercoiling in transcription regulation, we develop a spatially resolved supercoiling model of transcription, describing RNAP-supercoiling interactions, topoisomerase activities, stochastic topological domain formation, and supercoiling diffusion in all transcription stages. This model establishes that transcription-induced supercoiling mediates the cooperation of co-transcribing RNAP molecules in highly expressed genes. It reveals that supercoiling transmits RNAP-accessible information through DNA and enables different RNAP molecules to communicate within and between genes. It thus predicts that a topological domain could serve as a transcription regulator, generating substantial transcription bursting and coordinating communications between adjacent genes in the domain. The model provides a quantitative platform for further theoretical and experimental investigations of how genome organization impacts transcription.

Author Summary

DNA mechanics and transcription dynamics are intimately coupled. During transcription, the translocation of RNA polymerase overwinds the DNA ahead and underwinds the DNA behind, rendering the DNA supercoiled. The supercoiled DNA could, in return, influences the behavior of the RNA polymerase, and consequently the amount of mRNA product it makes. Furthermore, supercoils could propagate on the DNA over thousands of base pairs, impacting RNA polymerase molecules at faraway sites. These complicated interplays between supercoiling and RNA polymerase makes supercoiling an important transcription regulator. To quantitatively investigate the role of supercoiling in transcription, we build a spatially resolved model that links transcription with the generation, propagation, and dissipation of supercoiling. Our model reveals that supercoiling mediates transcription at multiple length scales. At a single-gene scale, we show that supercoiling gives rise to the collective motion of co-transcribing RNA polymerase molecules, supporting recent experimental observations. Additionally, large variations in mRNA production of a gene can arise from the constraints of supercoiling diffusion in a topological domain. At a multi-gene scale, we show that supercoiling dynamics allow two adjacent genes influence each other’s transcription kinetics, thus serving as a transcription regulator.
mRNA-1273 and Ad26.COV2.S vaccines protect against the B.1.621 variant of SARS-CoV-2
Authors: Darling Tamarand L. , Ying Baoling , Whitener Bradley , VanBlargan Laura A. , Bricker Traci L. , Liang Chieh-Yu , Joshi Astha , Bamunuarachchi Gayan , Seehra Kuljeet , Schmitz Aaron J. , Halfmann Peter J. , Kawoaka Yoshihiro , Elbashir Sayda M. , Edwards Darin K. , Thackray Larissa B. , Diamond Michael S. , Boon Adrianus C. M.
Published: December 2021

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019, viral variants with greater transmissibility or immune evasion properties have arisen, which could jeopardize recently deployed vaccine and antibody-based countermeasures. Here, we evaluated in mice and hamsters the efficacy of preclinical non-GMP Moderna mRNA vaccine (mRNA-1273) and the Johnson & Johnson recombinant adenoviral-vectored vaccine (Ad26.COV2.S) against the B.1.621 (Mu) South American variant of SARS-CoV-2, which contains spike mutations T95I, Y144S, Y145N, R346K, E484K, N501Y, D614G, P681H, and D950N. Immunization of 129S2 and K18-human ACE2 transgenic mice with mRNA-1273 vaccine protected against weight loss, lung infection, and lung pathology after challenge with B.1.621 or WA1/2020 N501Y/D614G SARS-CoV-2 strain. Similarly, immunization of 129S2 mice and Syrian hamsters with a high dose of Ad26.COV2.S reduced lung infection after B.1.621 virus challenge. Thus, immunity induced by mRNA-1273 or Ad26.COV2.S vaccines can protect against the B.1.621 variant of SARS-CoV-2 in multiple animal models.
Geminiviral βC1 orchestrates organellar genomic instability to augment viral infection by hijacking host RecA
Authors: Nair Ashwin , Harshith C.Y. , Anushree N. , Shivaprasad P. V.
Published: December 2021

Chloroplast is the site for transforming light energy to chemical energy. It also acts as a production unit for a variety of defense-related molecules. These defense moieties are necessary to mount a successful counter defence against pathogens including viruses. Geminiviruses disrupt chloroplast homeostasis as a basic strategy for their successful infection inducing vein-clearing, mosaics and chlorosis in infected plants. Here we show that a geminiviral pathogenicity determinant protein βC1 directly interferes with plastid homeostasis. βC1 was capable of inducing organelle-specific nuclease to degrade plastid genome as well as diverted functions of RecA1 protein, a major player in plastid genome maintenance. βC1 interacted with RecA1 in plants and its homolog in bacteria to reduce the ability of host cells to maintain genomic integrity under stresses. Further, reduction in the coding capacity of plastids severely affected retrograde signalling necessary for viral perception and activation of defense. Induction of chloroplast-specific nuclease by βC1 is similar to phosphate starvation-response in which nucleotides are recycled to augment synthesis of new, potentially viral, DNA. These results indicate the presence of a novel strategy in which a viral protein alters host defence by targeting regulators of chloroplast DNA. We predict that the mechanism identified here might have similarities in other plant-pathogen interactions.

One line summary

βC1 alters plastid genome metabolism.
Natural history of nonhuman primates after conjunctival exposure to Ebola virus
Authors: Cross Robert W. , Prasad Abhishek N. , Woolsey Courtney B. , Agans Krystle N. , Borisevich Viktoriya , Dobias Natalie S. , Comer Jason E. , Deer Daniel J. , Geisbert Joan B. , Rasmussen Angela L. , Lipkin W. Ian , Fenton Karla A. , Geisbert Thomas W.
Published: December 2021

Transmission of Ebola virus (EBOV) primarily occurs via contact exposure of mucosal surfaces with infected body fluids. Historically, nonhuman primate (NHP) challenge studies have employed intramuscular or small particle aerosol exposure, which are uniformly lethal routes of infection, but mimic worst-case scenarios such as a needlestick. When exposed by more likely routes of natural infection, limited NHP studies have shown delayed onset of disease and reduced mortality. Here we performed a series of systematic natural history studies in cynomolgus macaques with a range of conjunctival exposure doses. Challenge with 10,000 plaque forming units (PFU) of EBOV was uniformly lethal, whereas 5/6 subjects survived low and moderate dose challenges (100 or 500 PFU). Conjunctival challenge resulted in a protracted time-to death. Asymptomatic disease was observed in survivors with limited detection of EBOV replication. Inconsistent seropositivity in survivors may suggest physical or natural immunological barriers are sufficient to prevent widespread viral dissemination.
Rheology of crossbridge ensembles
Authors: Nguyen Khoi D. , Venkadesan Madhusudhan
Published: December 2021

How skeletal muscle responds to mechanical perturbations, its rheology, is important for animal movement control. The molecular machinery of myosin II-actin crossbridge cycling is a crucial part of muscle’s rheological properties, and multiple models have been proposed for this mechanochemical process. But current understanding of the scale-connection from individual molecular motors to ensemble rheology is limited. Here we present computational and mathematical analyses of several different hypotheses of crossbridge dynamics, from 2-state to 5-state myosin II motor models, and show that an ensemble of actomyosin crossbridges exhibits surprisingly simple rheological behavior in all cases. The ensemble rheology is captured by a sum of at most three linear viscoelastic sub-processes, and as few as one for some crossbridge models. This simplification lends itself to computationally efficient phenomenological muscle models with experimentally measurable parameters, while still remaining grounded in crossbridge theory. However, the collapse of the ensemble behavior to few linear sub-processes identifies major limitations of crossbridge models that cannot be resolved by adding complexity to the crossbridge cycle and point to the roles of inter-crossbridge interactions and non-crossbridge elements.
Retrovirus-derived acquired genes, RTL5 and RTL6, are novel constituents of the innate immune system in the eutherian brain
Authors: Irie Masahito , Itoh Johbu , Matuszawa Ayumi , Ikawa Masahito , Suzuki Toru , Hiraoka Yuichi , Ishino Fumitoshi , Kaneko-Ishino Tomoko
Published: December 2021

Retrotransposon Gag-like 5 (RTL5, also known as sushi-ichi-related retrotransposon homolog 8 (SIRH8)) and RTL6 (aka SIRH3) are eutherian-specific genes presumably derived from a retrovirus and phylogenetically related to each other. RTL5 encodes a strongly acidic protein while RTL6 encodes an extremely basic protein, and the former is well conserved and the latter extremely well conserved among the eutherians, indicating their unique and critically important roles as acquired genes. Here we report that RTL5 and RTL6 are microglial genes playing roles in the front line of brain innate immune responses against distinct pathogens. Venus and mCherry knock-in mice exhibited expression of RTL5-mCherry and RTL6-Venus fusion proteins in microglia and as extracellular granules in the central nervus system (CNS), and displayed a rapid response to pathogens such as lipopolysaccharide (LPS), double-stranded (ds) RNA analog and non-methylated CpG DNA. These proteins trapped pathogens in microglia in a variety of RTL-pathogen complexes depending on the pathogens. These results demonstrate that RTL5 and RTL6 exert functional effects against different hazardous substances cooperatively and/or independently to protect the developing and/or mature brain. This provides the first evidence that retrovirus-derived genes play a role in the innate immune system of the eutherian brain.
Structural insights into the ion selectivity of the MgtE channel for Mg2+ over Ca2+
Authors: Teng Xinyu , Sheng Danqi , Wang Jin , Yu Ye , Hattori Motoyuki
Published: December 2021

MgtE is a Mg2+-selective ion channel whose orthologs are widely distributed from prokaryotes to eukaryotes, including humans, and play an important role in the maintenance of cellular Mg2+ homeostasis. Previous functional analyses showed that MgtE transports divalent cations with high selectivity for Mg2+ over Ca2+. Whereas the high-resolution structure determination of the MgtE transmembrane (TM) domain in complex with Mg2+ ions revealed a Mg2+ recognition mechanism of MgtE, the previous Ca2+-bound structure of the MgtE TM domain was determined only at moderate resolution (3.2 Å resolution), which was insufficient to visualize the water molecules coordinated to Ca2+ ions. Thus, the structural basis of the ion selectivity of MgtE for Mg2+ over Ca2+ has remained unclear. Here, we showed that the metal-binding site of the MgtE TM domain binds to Mg2+ ∼500-fold more strongly than Ca2+. We then determined the crystal structure of the MgtE TM domain in complex with Ca2+ ions at a higher resolution (2.5 Å resolution), allowing us to reveal hexahydrated Ca2+, which is similarly observed in the previously determined Mg2+-bound structure but with extended metal-oxygen bond lengths. Our structural, biochemical, and computational analyses provide mechanistic insights into the ion selectivity of MgtE for Mg2+ over Ca2+.
DENA: training an authentic neural network model using Nanopore sequencing data of Arabidopsis transcripts for detection and quantification ofN6-methyladenosine on RNA
Authors: Qin Hang , Ou Liang , Gao Jian , Chen Longxian , Wang Jiawei , Hao Pei , Li Xuan
Published: December 2021

Models developed using Nanopore direct RNA sequencing data fromin vitrosynthetic RNA with all adenosine replaced byN6-methyladenosine (m6A), are likely distorted due to superimposed signals from saturated m6A residues. Here, we develop a neural network,DENA, for m6A quantification using the sequencing data ofin vivotranscripts from Arabidopsis. DENA identifies 90% of miCLIP-detected m6A sites in Arabidopsis, and obtains modification rates in human consistent to those found bySCARLET, demonstrating its robustness across species. We sequence the transcriptome of two additional m6A-deficient Arabidopsis,mtbandfip37-4, using Nanopore and evaluate their single-nucleotide m6A profiles usingDENA.
Macrophages break interneuromast cell quiescence by intervening the inhibition of Schwann cells in zebrafish lateral line
Authors: Lin Meng-Ju , Lee Chia-Ming , Hsu Wei-Lin , Chen Bi-Chang , Lee Shyh-Jye
Published: December 2021

In the zebrafish lateral line system, interneuromast cells (INCs) between neuromasts are normally kept quiescent by underlying Schwann cells (SWCs). Upon severe injuries that cause the complete loss of an entire neuromast, INCs can occasionally differentiate into neuromasts but how they escape from the inhibition by SWCs is still unclear. Using a genetic/chemical method to specifically ablate a neuromast, we found a small portion of larvae can regenerate a new neuromast, but the regeneration was hindered by inhibiting macrophages. By in toto imaging, we further discovered heterogeneities in macrophage behavior and distribution along lateral line. We witnessed the crawling of macrophages in between injured lateral line and SWCs during regeneration and also in between the second primordium and the first mature lateral line during development. It implies that macrophages may physically separate and alleviate the inhibition from pLLn and SWCs to break the quiescence of INCs during regeneration and development in the zebrafish lateral line.
Sequestration of histidine kinases by non-cognate response regulators establishes a threshold level of stimulation for bacterial two-component signaling
Authors: Sankhe Gaurav D. , Raja Rubesh , Dixit Narendra M. , Saini Deepak Kumar
Published: December 2021

Two-component signaling systems (TCSs) in bacteria are often positively auto-regulated, where the histidine kinase (HK) and response regulator (RR) proteins comprising a TCS are expressed downstream of the signal they transduce. This auto-regulation improves the sensitivity of the TCS to stimuli and amplifies adaptive responses. The downside, however, is that the TCS may mount disproportionately large responses to weak or fleeting signals. How bacteria prevent such disproportionate responses is not known. Here, we show that sequestration of phosphorylated HKs by non-cognate RRs serves as a design to prevent such disproportionate responses. Using TCSs of M. tuberculosis as model systems, we found that with every one of the five HKs we studied, there was at least one non-cognate RR with higher affinity than that of the cognate RR for the HK. Phosphorylated HKs would thus preferentially bind the non-cognate RRs, suppressing signal transduction through the cognate pathways, which we demonstrated in vitro. Using mathematical modeling of TCS signaling in vivo, we predicted that this sequestration would introduce a threshold level of stimulation for a significant response, preventing responses to signals below this threshold. Finally, we showed in vivo using tunable expression systems in M. bovis that upregulation of a higher affinity non-cognate RR substantially suppressed the output from the cognate TCS pathway, presenting strong evidence of sequestration by non-cognate RRs as a design to regulate TCS signaling. Blocking this sequestration may be a novel intervention strategy, as it would compromise bacterial fitness by letting it respond unnecessarily to signals.
Microfluidic single-cell scale-down bioreactors: A proof-of-concept for the growth of Corynebacterium glutamicum at oscillating pH values
Authors: Täuber Sarah , Blöbaum Luisa , Steier Valentin , Oldiges Marco , Grünberger Alexander
Published: December 2021

In large-scale bioreactors, gradients in cultivation parameters such as oxygen, substrate and pH result in fluctuating environments. pH fluctuations were identified as a critical parameter for bioprocess performance. Traditionally, scale-down systems at the laboratory scale are used to analyze the effects of fluctuating pH values on strain and thus process performance. Here, we demonstrate the application of dynamic microfluidic single-cell cultivation (dMSCC) as a novel scale-down system for the characterization of Corynebacterium glutamicum growth using oscillating pH conditions as a model parameter. A detailed comparison between two-compartment reactor (two-CR) scale-down experiments and dMSCC was performed for one specific pH oscillation between reference pH 7 (∼ 8 min) and disturbed pH 6 (∼2 min). Similar reductions in growth rates were observed in both systems (dMSCC 21% and two-CR 27%). Afterward, systematic experiments at different symmetric and asymmetric pH oscillations between pH ranges of 4–6 and 8–11 and different intervals from 1 minute to 20 minutes, were performed to demonstrate the unique application range and throughput of the dMSCC system. Finally, the strength of the dMSCC application was demonstrated by mimicking fluctuating environmental conditions within large-scale bioprocesses, which is difficult to conduct using two-CRs.
Substrate Specificity for Human Histidine Methyltransferase SETD3
Authors: Hintzen Jordi C. J. , Ma Huida , Deng Hao , Witecka Apolonia , Andersen Steffen B. , Drozak Jakub , Guo Hong , Qian Ping , Li Haitao , Mecinović Jasmin
Published: December 2021

Histidine methyltransferase SETD3 plays an important role in human biology and diseases. Previously, we showed that SETD3 catalyzes N3-methylation of histidine 73 in β-actin (Kwiatkowski et al., 2018). Here we report integrated synthetic, biocatalytic, biostructural and computational analyses on human SETD3-catalyzed methylation of β-actin peptides possessing histidine and its structurally and chemically diverse mimics. Our enzyme assays supported by biostructural analyses demonstrate that SETD3 has a broader substrate scope beyond histidine, including N-nucleophiles on the aromatic and aliphatic side chains. Quantum mechanical/molecular mechanical (QM/MM) molecular dynamics and free-energy simulations provide insight into binding geometries and the free energy barrier for the enzymatic methyl transfer to histidine mimics, further supporting experimental data that histidine is the superior SETD3 substrate over its analogs. This work demonstrates that human SETD3 has a potential to catalyze efficient methylation of several histidine mimics, overall providing mechanistic, biocatalytic and functional insight into β-actin histidine methylation by SETD3.
Ecological interactions: Patterns of host utilization by tropical butterflies
Authors: Naik Deepak , Bhat S. Srikrishna Ganaraja , Ghate Sudeep D. , Mustak M. S. , Prasad Rao R. Shyama
Published: December 2021

Structural complexity of ecological networks facilitate the functional robustness of natural ecosystems. Threatened by the human actions such as habitat destruction and climate change, species may be more or less prone to ecological perturbations depending on the nature of their interactions. We examined the host network of tropical butterflies from the Indian region to see their level of interconnectedness. We manually curated larval host utilization data for 1053 butterflies of India. About 98.8% of species that occur pan-India and 90.6% of species exclusive to the Western Ghats had known hosts whereas it was only 25.9% for species exclusive to north-east India. There were 2589 unique butterfly-host interactions comprising 519 butterfly species and their 1091 known hosts. However, nearly 30% of the species had only single hosts. The Fabaceae and Poaceae were the key host families that accounted for 32.8% of the interactions. There were clear host preferences and monocots hosted disproportionately more butterfly species and interactions. Vanessa cardui had at least 39 known hosts while Ochlandra travancorica supported 19 butterfly species. There were 2693 species-pairs and 4226 interactions among 469 butterflies due to shared hosts. Many butterfly species that have relatively few/unique hosts might be vulnerable in the context of habitat destruction and climate change. This work has great relevance to the ecology and conservation of butterflies in India.
Cortical glutamatergic projection neuron types contribute to distinct functional subnetworks
Authors: Mohan Hemanth , An Xu , Xu X. Hermione , Kondo Hideki , Zhao Shengli , Matho Katherine S. , Musall Simon , Mitra Partha , Huang Z. Josh
Published: December 2021

The cellular basis of cerebral cortex functional architecture remains not well understood. A major challenge is to monitor and decipher neural network dynamics across broad cortical areas yet with projection neuron (PN)-type resolution in real time during behavior. Combining genetic targeting and wide-field imaging, we monitored activity dynamics of subcortical-projecting (PTFezf2) and intratelencephalic-projecting (ITPlxnD1) types across dorsal cortex of mice during different brain states and behaviors. ITPlxnD1 and PTFezf2 neurons showed distinct activation patterns during wakeful resting, spontaneous movements, and upon sensory stimulation. Distinct ITPlxnD1 and PTFezf2 subnetworks were dynamically tuned to different sensorimotor components of a naturalistic feeding behavior, and optogenetic inhibition of ITsPlxnD1 and PTsFezf2 in subnetwork nodes disrupted distinct components of this behavior. Lastly, ITPlxnD1 and PTFezf2 projection patterns are consistent with their subnetwork activation patterns. Our results show that, in addition to the concept of columnar organization, dynamic areal and PN type-specific subnetworks are a key feature of cortical functional architecture linking microcircuit components with global brain networks.
BDNF induces its own release to mediate presynaptic plasticity
Authors: Berthoux Coralie , Nasrallah Kaoutsar , Milner Teresa A. , Castillo Pablo E.
Published: December 2021

The brain-derived neurotrophic factor (BDNF) and its effector Tropomyosin receptor kinase B (TrkB) mediate diverse forms of activity-dependent synaptic plasticity implicated in learning, neural circuit refinement, and brain diseases, including epilepsy and mood disorders. Here, we report that activity-dependent release of presynaptic BDNF elicits the release of postsynaptic BDNF in a TrkB- and calcium-dependent manner. This BDNF-induced BDNF release was required for the induction of presynaptic long-term potentiation (LTP) of excitatory transmission in the mouse dentate gyrus. Tonic and phasic activity of presynaptic type-1 cannabinoid receptors suppressed BDNF release and dampened LTP, while exposure to enriched environment elicited BDNF-mediated LTP. In addition to mediating presynaptic plasticity, BDNF-induced BDNF release could be an important mechanism in synaptic stabilization during the maturation and refinement of neuronal connections.

One-Sentence Summary

The brain-derived neurotrophic factor induces its own release to mediate long-lasting increase in neurotransmitter release.
Endosomal structure and APP biology are not altered in preclinical cellular models of Down syndrome
Authors: Cannavo Claudia , Cleverley Karen , Maduro Cheryl , Mumford Paige , Moulding Dale , Fisher Elizabeth M. C. , Wiseman Frances K.
Published: December 2021

Individuals who have Down syndrome (trisomy 21) are at greatly increased risk of developing Alzheimer’s disease – dementia. Alzheimer’s disease is characterised by the accumulation in the brain of amyloid-β plaques that are a product of amyloid precursor protein, encoded by the APP gene on chromosome 21. In Down syndrome the first site of amyloid-β accumulation is within endosomes and changes to endosome biology occur early in disease. Here we determine if primary mouse embryonic fibroblasts isolated from two mouse models of Down syndrome can be used to study endosome and APP cell biology. We report that in these cellular models of Down syndrome endosome number, size and APP processing are not altered, likely because APP is not dosage sensitive in these models, despite three copies of App.
FeIII in a high-spin state in bis(5-bromosalicylaldehyde 4-ethylthiosemicarbazonato-κ3
O,N
1,S)ferrate(III) nitrate monohydrate, the first example of such a cationic FeIII complex unit
Authors: Powell Robyn E. , Lees Martin R. , Tizzard Graham J. , Koningsbruggen Petra J. van
Published: December 2021

The synthesis and crystal structure (100 K) of the title compound, [Fe(C10H11BrN3OS)2]NO3·H2O, is reported. The asymmetric unit consists of an octahedral [FeIII(HL)2]+ cation, where HL
− is H-5-Br-thsa-Et or 5-bromosalicylaldehyde 4-ethylthiosemicarbazonate(1−) {systematic name: 4-bromo-2-[(4-ethylthiosemicarbazidoidene)methyl]phenolate}, a nitrate anion and a noncoordinated water molecule. Each HL
− ligand binds via the thione S, the imine N and the phenolate O atom, resulting in an FeIIIS2N2O2 chromophore. The ligands are orientated in two perpendicular planes, with the O and S atoms in cis and the N atoms in trans positions. This [Fe(HL)2](anion)·H2O compound contains the first known cationic FeIII entity containing two salicylaldehyde thiosemicarbazone derivatives. The FeIII ion is in the high-spin state at 100 K. In addition, a comparative IR spectroscopic study of the free ligand and the ferric complex is presented, demonstrating that such an analysis provides a quick identification of the degree of deprotonation and the coordination mode of the ligand in this class of metal compounds. The variable-temperature magnetic susceptibility measurements (5–320 K) are consistent with the presence of a high-spin FeIII ion with a zero-field splitting D = 0.439 (1) cm−1.
Food supply chain resilience model for critical infrastructure collapses due to natural disasters
Authors: Orengo Serra Karen L. , Sanchez-Jauregui Maria
Published: December 2021

Purpose

Critical infrastructure (CI) plays an essential role in reading, reacting and responding while dealing with natural disasters. This study address food supply chain resilience by proposing an FSC resilience model that explains the food product and transport flow via production, processing, distribution and retailing in circumstances of (CI) collapses post a natural disaster.

Design/methodology/approach

A combination of qualitative methods was conducted to obtain a comprehensive overview of the food and beverage sector in Puerto Rico. The full dataset comprised of seven focus groups for a total of 52 participants and 12 in-depth interviews.

Findings

FSC resilience is seen in this study through the managerial actions taken by members of the Chain: innovating, transforming, adapting, and flexibilising business models and operations.

Originality/value

This study is the first to address FSC resilience from the perspective of net food importer economy in the context of natural disasters and prolonged Critical infrastructure (CI) breakdown, and the first one in proposing an FSC resilience model that explains the food product and transport flow via production, processing, distribution and retailing in circumstances of CI collapses post a natural disaster.
Managers' understanding of artificial intelligence in relation to marketing financial services: insights from a cross-country study
Authors: Mogaji Emmanuel , Nguyen Nguyen Phong
Published: December 2021

Purpose

Given that managers play a crucial role in developing and deploying AI for marketing financial services, this study was aimed at better understanding their awareness regarding AI and the challenges they are facing in providing the attendant technologies, as well as highlighting key stakeholders and their collaborative efforts in providing financial services.

Design/methodology/approach

Exploratory, inductive research design. The data was gathered through semi-structured interviews with 47 bank managers in both developed and developing countries, including the United Kingdom, Canada, Nigeria and Vietnam.

Findings

Managers are aware of the prospects of AI and are making efforts to address AI as a business need but find that there often exist certain challenges in accelerating AI adoption. The study also presents a conceptual framework of AI in relation to financial service marketing, which captures and highlights the interactions among the customers, banks and external stakeholders, as well as the regulators.

Research limitations/implications

Banks must understand their business objectives, the available resources and the needs of their customers. Managers should keep the ethical implications of their working relationships in mind when selecting a team or collaborating with partners. In addition, managers should be trained and assisted in comprehending AI in relation to financial services, while the regulators must be involved in the development of AI for financial service marketing. Finally, it is critical to communicate the prospects for AI to consumers.

Originality/value

This study provides empirical insight into the opportunities, prospects and challenges pertaining to the use of AI in the area of financial service marketing. It also specifically calls into question certain preconceptions regarding AI and its role in financial services, the chatbots adopted for financial service delivery and the role of marketing managers in developing AI.
Social entrepreneurship organisations and collaboration: taking stock and looking forward
Authors: Kosmynin Mikhail
Published: December 2021

Purpose

The aim of this systematic literature review (SLR) is to map out the current state of the research on collaboration in the context of social entrepreneurship organisations (SEOs), synthesise this line of research and advance a research agenda.

Design/methodology/approach

A SLR of 40 scientific articles found in the Scopus and Web of Science databases built the foundation for an analysis of the state-of-the-art of the research addressing the interplay of SEOs and collaboration. This area of research has been very recent since the selected articles have been published since 2005 and more than half of which have appeared since 2017.

Findings

The findings suggest that collaboration is increasingly perceived as a crucial entrepreneurial activity and process for SEOs. The results indicate that collaboration is a vibrant and rapidly growing line of research which spans different fields of study, contexts, varied theoretical perspectives and multiple units of analysis. Furthermore, a total of five key research themes are identified pertaining to collaboration in the context of SEOs, such as motivations and strategies of collaboration, its antecedents, the interplay of institutional logics and tensions arising in collaboration, the impact of collaboration on the mission of SEOs and collaborative processes and practices.

Originality/value

To lend structure to this fragmented field of inquiry, this study systematically reviews and synthesises research on collaboration in the context of SEOs. In doing so, the study reveals that this line of research is under-researched, offering a significant scope for further scrutiny.
Impacts of a health crisis on music festivals: a qualitative approach
Authors: Orea-Giner Alicia , González-Reverté Francesc , Fuentes-Moraleda Laura
Published: December 2021

Purpose

This research explores the consequences of a health crisis provoked by a pandemic scenario on music festival impacts considered by the stakeholders involved. The purpose of this paper is to identify the perceptions from the stakeholders' point of view (host community, public and private sector) and to identify the impacts generated before and after a health crisis regarding the celebration of a festival.

Design/methodology/approach

The study offers a holistic insight into impact research by music festivals. The methodology implemented is based on qualitative techniques. By conducting 20 in-depth interviews with essential stakeholders, it is possible to determine their perceptions of the impact of the event and the effects of a health crisis.

Findings

The results allow detecting a gap between internal and external stakeholders due to poor communication and planning of the event. The results show that a health crisis provokes negative impacts on the economic benefits of events' organisation. However, the cultural city's identity suffers an important damage that it is difficult to overcome. The community and visitors are the stakeholders that suffer a detrimental impact on their experience when attending the festival, considering the security measures. Moreover, results allow us to identify practical implications for event management and planning in a health crisis scenario.

Originality/value

The most important contribution of this research is the theoretical model proposed to analyse stakeholders' perception of the event celebration in a context of a health crisis. The model also considers different moments of the social exchange. The theoretical approaches considered theory of social exchange (SET) and Visitor, Industry, Community and Environment (VICE) models allow analysing the stakeholder's perception of a case study of a music festival (Viña Rock Festival, Spain). The emerging and central role of the cooperation between stakeholders constitutes another notable contribution to the literature.