bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence of COVID-19 infection and its variation with demographic and clinical profile: lessons learned at a COVID-19 RT-PCR laboratory in Nagpur, India
Authors: Gade Neeta , Nag Soumyabrata , Mishra Meena , Akkilagunta Sujiv , Shete Vishal , Bidkar Vijay , Shendre Pooja , Patil Divya
Published: March 2022

Introduction. The coronavirus disease 2019 (COVID-19) pandemic emerged as a global health crisis in 2020. The first case in India was reported on 30 January 2020 and the disease spread throughout the country within months. Old persons, immunocompromised patients and persons with co-morbidities, especially of the respiratory system, have a more severe and often fatal outcome to the disease. In this study we have analysed the socio-demographic trend of the COVID-19 outbreak in Nagpur and adjoining districts.

Methods. The study was conducted from April to December 2020. Nasopharyngeal and oropharyngeal swabs collected from suspected cases of COVID-19 were tested using reverse-transcription polymerase chain reaction (RT-PCR) at a diagnostic molecular laboratory at a tertiary care hospital in central India. Patient-related data on demographic profile and indication for testing were obtained from laboratory requisition forms. The results of the inconclusive repeat samples were also noted. The data were analysed using SPSS v24.0.

Results. A total of 46 898 samples were received from April to December 2020, of which 41 410 were included in the study; 90.6 % of samples belonged to adults and 9.4 % belonged to children. The overall positivity rate in the samples was 19.3 %, although it varied over the period. The yield was significantly high in the elderly age group (25.5 %) and symptomatic patients (22.6 %). On repeat testing of patients whose first test was inconclusive, 17.1% were positive. There was a steady increase of both the number of tests and the rate of positivity in the initial period of the study, followed by a sharp decline.

Conclusion. We can conclude that rigorous contact tracing and COVID-appropriate behaviour (wearing a mask, social distancing and hand hygiene) are required to break the chain of transmission. Elderly people are more susceptible to infection and should follow stringent precautions. It is also important to perform repeat testing of those individuals whose tests are inconclusive with fresh samples so that no positive cases are missed. Understanding of demographics is crucial for better management of this crisis and proper allocation of resources.
Hanstruepera crassostreae He et al. 2018 is a later heterotypic synonym of Pseudobizionia ponticola Park et al. 2018 and transfer of Pseudobizionia ponticola to the genus Hanstruepera as Hanstruepera ponticola comb. nov
Authors: Huang Zhaobin , Du Yaping , Lai Qiliang
Published: March 2022

The 16S rRNA gene sequences of

Pseudobizionia ponticola

MM-14T and

Hanstruepera crassostreae

L53T shared 100 % sequence similarity. This study aimed to clarify the taxonomic position of the two species. Whole-genome comparisons showed that

P. ponticola

MM-14T and

H. crassostreae

L53T shared average nucleotide identity of 97.52 %, digital DNA–DNA hybridization of 75.30 % and average amino acid identity of 96.98 %. These values exceeded the threshold of bacterial species delineation. Furthermore, average amino acid identities of

P. ponticola

MM-14T and

H. crassostreae

L53T in comparison with

Hanstruepera neustonica

CC-PY-50T were 82.04 and 82.11 %, respectively. Phylogenetic analysis based on 16S rRNA gene and 120 bacterial conserved single-copy genes also supported that

P. ponticola

MM-14T and

H. crassostreae

L53T belonged to the genus

Hanstruepera

. Phenotypic and chemical taxonomic properties compared between

P. ponticola

MM-14T and

H. crassostreae

L53T were nearly identical. Colonies of the two species on marine agar plates were orange-pigmented, circular and smooth. Flexirubin-type pigments were present in both

H. crassostreae

L53T and

P. ponticola

MM-14T. The major fatty acids composition of the two species consisted of iso-C15 : 1 G, iso-C15 : 0, and iso-C17 : 0 3-OH, similar to

H. neustonica

CC-PY-50T. Based on priority,

H. crassostreae

He et al. 2018 is a later heterotypic synonym of

P. ponticola

Park et al. 2018, and

P. ponticola

should be transferred to the genus

Hanstruepera

as Hanstruepera ponticola comb. nov.
Visual Perception of 3D Space and Shape in Time - Part IV - 3D Shape Recognition by 3D Rotation
Authors: Le Caominh , Pedersen Samantha , Chen Nathaniel , Chan Jonathan , Ta Brian , Wilson Patrick , McCarthy Trevor , Barseghyan Emma , Chauhan Anushka , Saif Hind , Tu Jonathan , Wijaya Darren , Zhang Annika , Li Erica , Marangi Camille , Nekarae Setayesh , Wang Felicia , Yanovsky Alice , Afifa Umaima , Carmona Javier , Espino Diego , Schummer Leonard , Gudijanto Phillip , Kaur Gurleen , Lam Andrew , Mar Matthew , Mills Elizabeth , Nevins Alexandra , Ortiz Elijah , Wheeler Kyle , Blaisdell Aaron , Arisaka Katsushi
Published: March 2022

Human vision has a remarkable ability to recognize complex 3D objects such as faces that appear at any size and 3D orientations at any 3D location. If we initially memorize a face only with a normalized size upfront at the object center, the direct comparison between the one-sized memory and an incoming new image would demand tremendous mental frame translations in 7D. How can we perform such a demanding task so promptly as we experience it in our daily lives?

This paper specifically addresses the recognition of human faces with arbitrary 3D orientation in the [Roll, Yaw, Pitch] axes. According to our new model ofNHT(Neural Holography Tomography), space is represented by time utilizing the phase of the alpha brainwave. This principle should be applicable to any mental rotation in 3D; thus, it predicts that extra time is required to perceive a rotated face to revolve it back to upright by the constant-speed alpha wave.

To assess this hypothesis, we designed a reaction time (RT) experiment, where participants were first asked to memorize sets of upright unfamiliar faces. Following the memorization phase, similar stimuli with a wide range of rotating faces in 3D were presented, and RTs were recorded. As expected, the memorized upfront face was the fastest RT. The excess of the RT was observed proportional to the rotating angle in all [Roll, Yaw, Pitch] axes. Roll had the flattest slope, whereas upper Pitch was the steepest. We suspect that Roll is the swiftest mental operation because it can be conducted by the linear frame translation on the log-polar retinotopy of the visual cortex.
Chemo-architecture of area prostriata in adult and developing mice: comparison with presubiculum and parasubiculum
Authors: Chen Sheng-Qiang , Chen Chang-Hui , Xiang Xiao-Jun , Zhang Shun-Yu , Ding Song-Lin
Published: March 2022

Retrosplenial area 29e, which was a cortical region described mostly in earlier rodent literature, is often included in the dorsal presubiculum (PrSd) or postsubiculum (PoS) in modern literature and commonly used brain atlases. Recent anatomical and molecular studies have revealed that retrosplenial area 29e belongs to the superficial layers of area prostriata, which in primates is found to be important in fast analysis of quickly moving objects in far peripheral visual field. As in primates, the prostriata in rodents adjoins area 29 (granular retrosplenial area), area 30 (agranular retrosplenial area), medial visual cortex, PrSd-PoS, parasubiculum (PaS) and postrhinal cortex (PoR). The present study aims to reveal the chemo-architecture of the prostriata versus PrSd-PoS or PaS by means of a systematic survey of gene expression patterns in adult and developing mouse brains. First, we find many genes that display differential expression across the prostriata, PrSd-PoS and PaS and that show obvious laminar expression patterns. Second, we reveal subsets of genes that selectively express in the dorsal or ventral parts of the prostriata, suggesting the existence of at least two subdivisions. Third, we detect some genes that shows differential expression in the prostriata of postnatal mouse brains from adjoining regions, thus enabling identification of the developing area prostriata. Fourth, gene expression difference of the prostriata from the medial visual cortex and PoR is also observed. Finally, molecular and connectional features of the prostriata in rodents and non-human primates are discussed and compared.
Determining the optimal SARS-CoV-2 mRNA vaccine dosing interval for maximum immunogenicity
Authors: Asamoah-Boaheng Michael , Goldfarb David M. , Prusinkiewicz Martin A. , Golding Liam , Karim Mohammad Ehsanul , Barakauskas Vilte , Wall Nechelle , Jassem Agatha N. , Marquez Ana Citlali , MacDonald Chris , O’Brien Sheila F. , Lavoie Pascal , Grunau Brian
Published: March 2022

Objective

Emerging evidence indicates that longer SARS-CoV-2 vaccine dosing intervals results in an enhanced immune response. However, the optimal vaccine dosing interval for achieving maximum immunogenicity is unclear.

Methods

This study included samples from adult paramedics in Canada who received two doses of either BNT162b2 or mRNA-1273 vaccines and provided blood samples 6 months (170 to 190 days) after the first vaccine dose. The main exposure variable was vaccine dosing interval (days), categorized as “short” (first quartile), “moderate” (second quartile), “long” (third quartile), and “longest” interval (fourth quartile). The primary outcome was total spike antibody concentrations, measured using the Elecsys SARS-CoV-2 total antibody assay. Secondary outcomes included: spike and RBD IgG antibody concentrations, and inhibition of angiotensin-converting enzyme 2 (ACE-2) binding to wild-type spike protein and several different Delta variant spike proteins. We fit a multiple log-linear regression model to investigate the association between vaccine dosing intervals and the antibody concentrations.

Results

A total of 564 adult paramedics (mean age 40 years, SD=10) were included. Compared to “short interval” (≤30 days), higher dosing interval quartiles (moderate: 31-38 days; long: 39-73 days and longest: ≥74 days) were all associated with increased Elescys spike total antibody concentration. Compared to the short interval, “long” and “longest” interval quartiles were associated with higher spike and RBD IgG antibody concentrations. Similarly, increasing dosing intervals increased inhibition of ACE-2 binding to viral spike protein, regardless of the vaccine type.

Conclusion

Increased mRNA vaccine dosing intervals longer than 30 days result in higher levels of circulating antibodies and viral neutralization when assessed at 6 months.
Mathematical Analysis of a Zika Model with reservoirs and Human Movement
Authors: Al-Maqrashi Kifah , Al-Musalhi Fatma , Elmojtaba Ibrahim M. , Al-Salti Nasser
Published: March 2022

A mathematical model for Zika virus is proposed describing the spread of the disease in three interacting populations, namely, human, vector (mosquitoes) and non-human primate (monkeys) inhabiting forests area. Human movement between rural and forest areas has been also considered. It is assumed that Zika virus spreads within non-human primate population, which in turn acts as a reservoir of infection, and then transmitted to the human population through infected mosquitoes. The proposed model incorporates vertical transmission and direct transmission in all populations. The proposed model has been first normalized. The normalized model has been then fully analyzed both qualitatively and quantitatively to investigate the role of the interaction between forest mosquitoes and primates on the ZIKV transmission dynamics. The mathematical analysis includes positivity and boundedness of solutions, derivation of the basic reproduction numberR0using the next generation matrix method, sensitivity analysis, existence and stability analysis of all equilibria and bifurcation analysis. Finally, numerical simulations have been carried out to illustrate the obtained theoretical results and to demonstrate the effect of some model parameters in the disease transmission dynamics. The results show that the interaction between forest mosquitoes and primates has a significant impact on the ZIKV transmission dynamics among human population through the fraction of susceptible moving to forest areas. Furthermore, the results highlight that the transmission probabilities are as important as the ratios of population size between vector population and human or primate populations in the disease transmission dynamics.
A structural atlas of the developing zebrafish telencephalon based on spatially-restricted transgene expression
Authors: Turner Katherine J. , Hawkins Thomas A. , Henriques Pedro M. , Valdivia Leonardo E. , Bianco Isaac H. , Wilson Stephen W. , Folgueira Mónica
Published: March 2022

1.

Zebrafish telencephalon acquires an everted morphology by a two-step process that occurs from 1 to 5 days post-fertilization (dpf). Little is known about how this process affects the positioning of discrete telencephalic cell populations, hindering our understanding of how eversion impacts telencephalic structural organisation. In this study, we characterise the neurochemistry, cycle state and morphology of an EGFP positive (+) cell population in the telencephalon of Et(gata2:EGFP)bi105 transgenic fish during eversion and up to 20dpf. We map the transgene insertion to the early-growth-response-gene-3 (egr3) locus and show that EGFP expression recapitulates endogenous egr3 expression throughout much of the pallial telencephalon. Using the gata2:EGFPbi105 transgene, in combination with other well-characterised transgenes and structural markers, we track the development of various cell populations in the zebrafish telencephalon as it undergoes the morphological changes underlying eversion. These datasets were registered to reference brains to form an atlas of telencephalic development at key stages of the eversion process (1dpf, 2dpf and 5dpf) and compared to expression in adulthood. Finally, we registered gata2:EGFPbi105 expression to the Zebrafish Brain Browser 6dpf reference brain (ZBB, see Marquart et al., 2015, 2017; Tabor et al. 2019), to allow comparison of this expression pattern with anatomical data already in ZBB.
Defining cellular population dynamics at single cell resolution during prostate cancer progression
Authors: Germanos Alexandre A. , Arora Sonali , Zheng Ye , Goddard Erica T. , Coleman Ilsa M. , Ku Anson T. , Wilkinson Scott , Amezquita Robert A. , Zager Michael , Long Annalysa , Yang Yu Chi , Bielas Jason H. , Gottardo Raphael , Ghajar Cyrus M. , Nelson Peter S. , Sowalsky Adam G. , Setty Manu , Hsieh Andrew C.
Published: March 2022

Advanced prostate malignancies are a leading cause of cancer-related deaths in men, in large part due to our incomplete understanding of cellular drivers of disease progression. We investigated prostate cancer cell dynamics at single-cell resolution from disease onset to the development of androgen independence in vivo. We observe a dramatic expansion of a castration-resistant intermediate luminal cell type that correlates with treatment resistance and poor prognosis in human patients. Moreover, transformed epithelial cells and associated fibroblasts create a microenvironment conducive to pro-tumorigenic immune infiltration, which is in part androgen responsive. Androgen independent prostate cancer leads to significant diversification of intermediate luminal cell populations characterized by a range of androgen signaling activity inversely correlated with proliferation and mRNA translation. Accordingly, distinct epithelial populations are exquisitely sensitive to translation inhibition which leads to epithelial cell death, loss of pro-tumorigenic signaling, and decreased tumor heterogeneity. Our findings reveal a complex tumor environment largely dominated by castration-resistant luminal cells and immunosuppressive infiltrates.
Parametric effects of light acting via multiple photoreceptors contribute to circadian entrainment inDrosophila melanogaster
Authors: Abhilash Lakshman , Shafer Orie Thomas
Published: March 2022

Circadian rhythms in physiology and behavior have near 24-hour periodicities that must adjust to the exact 24-hour geophysical cycles on earth to ensure adaptive daily timing. Such adjustment is called entrainment. One major mode of entrainment is via the continuous modulation of circadian period by the prolonged presence of light. AlthoughDrosophila melanogasteris a prominent insect model of chronobiology, there is little evidence for such continuous effects of light in the species. In this study, we demonstrate that prolonged light exposure at specific times of the day shapes the daily timing of activity in flies. We also establish that continuous blue- and UV-blocked light lengthens the circadian period ofDrosophilaand provide evidence that this is produced by the combined action of multiple photoreceptors which, includes the cell autonomous photoreceptorcryptochrome. Finally, we introduce ramped light cycles as an entrainment paradigm that produces light entrainment that lacks the large light-driven startle responses typically displayed by flies and requires multiple days for entrainment to shifted cycles. These features are reminiscent of entrainment in mammalian models systems and make possible new experimental approaches to understanding the mechanisms underlying entrainment in the fly.
The Coronavirus Calendar (CoronaCal): a Simplified SARS-CoV-2 Test System for Sampling and Retrospective Analysis
Authors: Thaler David S. , Kazmi Manija A. , Åberg Karina C. , Mattheisen Jordan M. , Huber Thomas , Sakmar Thomas P.
Published: March 2022

Background

The testing of saliva samples for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA has become a useful and common method to diagnose coronavirus disease 2019 (Covid-19). However, there are limited examples of serial testing with correlated clinical metadata, especially in the outpatient setting.

Method

We developed a method to collect serial saliva samples on ordinary white printer paper, which can be subsequently analyzed for the presence of SARS-CoV-2 RNA using established polymerase chain reaction (PCR) procedures. The collection systems consisted of a biological diary (CoronaCal) where subjects dab their saliva onto ovals printed onto paper. The dried samples are covered with a sticker that includes a symptom checklist to create a biological diary. Each sheet of letter paper can accommodate up to 14 serial samples.

Results

In a pilot study, ten subjects used CoronaCals for durations of nine to 44 days. SARS-CoV-2 RNA was extracted and detected in CoronaCals from nine of nine people with either Covid-19 symptoms or exposure to someone with Covid-19, and in zero of one asymptomatic person. The CoronaCals were stored for up to 70 days at room temperature during collection and then frozen for up to four months before analysis, suggesting that SARS-CoV-2 RNA is stable once dried onto paper. Interestingly, the temporal pattern of symptoms was not well correlated with SARS-CoV-2 RNA in serial daily collections for up to 44 days. In addition, SARS-CoV-2 positivity was discontinuous over time in most cases but persisted for up to 24 days.

Conclusions

We conclude that sampling of saliva on simple paper CoronaCals may provide a useful method to study the natural history and epidemiology of Covid-19. The CoronaCal collection and testing method we developed is also easy to implement, inexpensive, non-invasive, and scalable. More broadly, the approach can be used to archive biological samples for retrospective analysis to deepen epidemiological understanding during viral disease outbreaks and to provide information about the natural history of emerging infections.
Endothelial FOXC1 and FOXC2 promote intestinal regeneration after ischemia-reperfusion injury
Authors: Tan Can , Norden Pieter R. , Liu Ting , Ujiie Naoto , Yan Xiaocai , Aoto Kazushi , Ortega Sagrario , De Plaen Isabelle G. , Kume Tsutomu
Published: March 2022

Intestinal ischemia induces mucosal damage while simultaneously activating intestinal stem cells (ISCs), which subsequently regenerate the damaged intestinal epithelium. However, whether paracrine factors secreted from vascular endothelial cells (ECs) - blood and lymphatic ECs (BECs and LECs, respectively) – regulate ISC-mediated regeneration have yet to be elucidated. Here, we identify FOXC1 and FOXC2 as essential regulators of paracrine signaling in regeneration of the small intestine after ischemia-reperfusion (I/R) injury. EC- and LEC-specific deletions of Foxc1, Foxc2, or both in mice augment I/R-induced intestinal damage by causing defects in vascular regrowth, expression of the chemokine CXCL12 and the Wnt activator R- spondin 3 in BECs and LECs, respectively, and activation of Wnt signaling in ISCs. Treatment with CXCL12 and R-spondin 3 rescues the I/R-induced intestinal damage in EC- and LEC-Foxc mutant mice, respectively. This study provides evidence that FOXC1 and FOXC2 are required for intestinal regeneration by stimulating paracrine CXCL12 and Wnt signaling.
Subgroups of Eating Behavior Traits Independent of Obesity Defined Using Functional Connectivity and Feature Representation Learning
Authors: Choi Hyoungshin , Byeon Kyoungseob , Lee Jong-eun , Hong Seok-Jun , Park Bo-yong , Park Hyunjin
Published: March 2022

Abstract

Eating behavior is highly heterogeneous across individuals, and thus, it cannot be fully explained using only the degree of obesity. We utilized unsupervised machine learning and functional connectivity measures to explore the heterogeneity of eating behaviors. This study was conducted on 424 healthy adults. We generated low-dimensional representations of functional connectivity defined using the resting-state functional magnetic resonance imaging, and calculated latent features using the feature representation capabilities of an autoencoder by nonlinearly compressing the functional connectivity information. The clustering approaches applied to latent features identified three distinct subgroups. The subgroups exhibited different disinhibition and hunger traits; however, their body mass indices were comparable. The model interpretation technique of integrated gradients revealed that these distinctions were associated with the functional reorganization in higher-order associations and limbic networks and reward-related subcortical structures. The cognitive decoding analysis revealed that these systems are associated with reward- and emotion-related systems. We replicated our findings using an independent dataset, thereby suggesting generalizability. Our findings provide insights into the macroscopic brain organization of eating behavior-related subgroups independent of obesity.
A selective bottleneck during host entry drives the evolution of new legume symbionts
Authors: Doin de Moura Ginaini Grazielli , Mouffok Saida , Gaudu Nil , Cazalé Anne-Claire , Milhes Marine , Bulach Tabatha , Valière Sophie , Roche David , Ferdy Jean-Baptiste , Masson-Boivin Catherine , Capela Delphine , Remigi Philippe
Published: March 2022

During the emergence of new host-microbe symbioses, multiple selective pressures-acting at the different steps of the microbial life cycle–shape the phenotypic traits that jointly determine microbial fitness. However, the relative contribution of these different selective pressures to the adaptive trajectories of microbial symbionts are still poorly known. Here we characterized the dynamics of phenotypic adaptation and its underlying genetic bases during the experimental evolution of a plant pathogenic bacterium into a legume symbiont. We observed that fast adaptation was predominantly driven by selection acting on competitiveness for host entry, which outweighed selection acting on within-host proliferation. Whole-population sequencing of evolved bacteria revealed that phenotypic adaptation was supported by the continuous accumulation of new mutations and the sequential sweeps of cohorts of mutations with similar temporal trajectories. The identification of adaptive mutations within the fixed mutational cohorts showed that all of them improved competitiveness for host entry, while only a subset of those also improved within host proliferation. Computer simulations predict that this effect emerges from the presence of a strong selective bottleneck at host entry. Together, these results show how selective bottlenecks can alter the relative influence of selective pressures acting during bacterial adaptation to multistep infection processes.
Universality of distribution of tumor mutation burden - a biomarker for the tumor evolution and disease risk
Authors: Li Xin , Sinha Sumit , Thirumalai D.
Published: March 2022

Cancers, resulting in uncontrolled cell proliferation, are driven by accumulation of somatic mutations. Genome-wide sequencing has produced a catalogue of millions of somatic mutations, which contain the evolutionary history of the cancers. However, the connection between the mutation accumulation and disease development and risks is poorly understood. Here, we analyzed more than 1,200,000 mutations from 5,000 cancer patients with whole-exome sequencing, and discovered two novel signatures for 16 cancer types in The Cancer Genome Atlas (TCGA) database. A clock-like mutational process, a strong correlation between Tumor Mutation Burden (TMB) and the Patient Age at Diagnosis (PAD), is observed for cancers with low TMB (mean value less than 3 mutations per million base pairs) but is absent in cancers with high TMB. We also validate this finding using whole-genome sequencing data from more than 2,000 patients for 24 cancer types. Surprisingly, we discovered that the distribution of TMB are universal. At low TMB it exhibits a Gaussian distribution and transitions to a power law at hight TMB. The differences in cancer risk between the sexes are also mainly driven by the disparity in mutation burden. The TMB variations, imprinted at the chromosome level, also reflect accumulation of mutation clusters within small chromosome segments in high TMB cancers. By analyzing the characteristics of mutations based on multi-region sequencing, we found that a combination of TMB and intratumor heterogeneity could be a potential biomarker for predicting the patient survival and response to treatment.
Concurrent mapping of brain ontogeny and phylogeny within a common connectivity space
Authors: Warrington S. , Thompson E. , Bastiani M. , Dubois J. , Baxter L. , Slater R. , Jbabdi S. , Mars R. B. , Sotiropoulos S. N.
Published: March 2022

Developmental and evolutionary effects on brain organisation are complex, yet linked, as evidenced by the striking correspondence in cortical expansion changes. However, it is still not possible to study concurrently the ontogeny and phylogeny of cortical areal connections, which is arguably more relevant to brain function than allometric changes. Here, we propose a novel framework that allows the integration of connectivity maps from humans (adults and neonates) and non-human primates (macaques) onto a common space. We use white matter bundles to anchor the definition of the common space and employ the uniqueness of the areal connection patterns to these bundles to probe areal specialisation. This enables us to quantitatively study divergences and similarities in cortical connectivity over both evolutionary and developmental scales. It further allows us to map brain maturation trajectories, including the effect of premature birth, and to translate cortical atlases between diverse brains.
MiR-182-5p regulates Nogo-A expression and promotes neurite outgrowth of hippocampal neurons in vitro
Authors: Soto Altea , Nieto-Díaz Manuel , Reigada David , Muñoz-Galdeano Teresa , Barreda-Manso M. Asunción , Maza Rodrigo M.
Published: March 2022

Nogo-A protein is a key myelin-associated inhibitor for axonal growth, regeneration, and plasticity in the central nervous system (CNS). Regulation of the Nogo-A/NgR1 pathway facilitates functional recovery and neural repair after spinal cord trauma and ischemic stroke. MicroRNAs are described as effective tools for the regulation of important processes in CNS such as neuronal differentiation, neuritogenesis, and plasticity. Our results showed that miR-182-5p mimic specifically downregulates the expression of the luciferase reporter gene fused to the mouse Nogo-A 3’UTR, and Nogo-A protein expression in Neuro-2a and C6 cells. Finally, we observed that when rat primary hippocampal neurons are co-cultured with C6 cells transfected with miR-182-5p mimic, there is a promotion of the outgrowth of neuronal neurites in length. From all these data we suggest that miR-182-5p may be a potential therapeutic tool for the promotion of axonal regeneration in different diseases of the CNS.

Graphical abstract

Highlights

Bioinformatics analyses show that miR-182-5p targets Nogo-A 3’UTR.

MiR-182-5p downregulates Nogo-A protein expression in murine cell lines.

MiR-182-5p promotes neurite outgrowth of rat primary hippocampal neurons in vitro.

MiR-182-5p is suggested as a potential therapeutic tool for the promotion of axonal regeneration in different pathologies/diseases of the central nervous system.
Z-RNA and the flipside of the SARS Nsp13 helicase
Authors: Herbert Alan , Poptsova Maria
Published: March 2022

We present evidence that the severe acute respiratory syndrome coronavirus (SARS) non-structural protein 13 (Nsp13) modulates the Z-RNA dependent regulated cell death pathways [1]. We show that Z-prone sequences (called flipons [2]) exist in coronavirus and provide a signature (Z-sig) that enables identification of the animal viruses from which the human pathogens arose. We also identify a potential RIP Homology Interaction Motif (RHIM) in the helicase Nsp13 that resembles those present in proteins that initiate Z-RNA-dependent cell death through interactions with the Z-RNA sensor protein ZBP1. These two observations allow us to suggest a model in which Nsp13 down regulates Z-RNA activated innate immunity by two distinct mechanisms. The first involves a novel ATP-independent Z-flipon helicase (flipase) activity in Nsp13 that differs from that of canonical A-RNA helicases. This flipase prevents formation of Z-RNAs that would otherwise activate cell death pathways. The second mechanism likely inhibits the interactions between ZBP1 and the Receptor Interacting Proteins Kinases RIPK1 and RIPK3 by targeting their RHIM domains. Together the described Nsp13 RHIM and flipase activities have the potential to alter the host response to coronaviruses and impact the design of drugs targeting the Nsp13 protein. The Z-sig and RHIM domains may provide a way of identifying previously uncharacterized viruses that are potentially pathogenic for humans.
Feedback Inhibition Underlies New Computational Functions of Cerebellar Interneurons
Authors: Halverson Hunter E. , Kim Jinsook , Khilkevich Andrei , Mauk Michael D. , Augustine George J.
Published: March 2022

The function of a feedback inhibitory circuit between cerebellar Purkinje cells and molecular layer interneurons (MLIs) was defined by combining optogenetics, neuronal activity recordings both in cerebellar slices and in vivo, and computational modeling. Purkinje cells inhibit a subset of MLIs in the inner third of the molecular layer. This inhibition is non-reciprocal, short-range (less than 200 μm) and is based on convergence of 1-2 Purkinje cells onto MLIs. During learning-related eyelid movements in vivo, the activity of a subset of MLIs progressively increases at the same time that Purkinje cell activity decreases, with Purkinje cells usually leading the MLIs. Computer simulations indicate that these relationships are best explained by the feedback circuit from Purkinje cells to MLIs and that this feedback circuit plays a central role in making cerebellar learning efficient.
Stress promotes RNA G-quadruplex folding in human cells
Authors: Kharel Prakash , Fay Marta , Manasova Ekaterina V. , Anderson Paul J. , Kurkin Aleksander V. , Guo Junjie U. , Ivanov Pavel
Published: March 2022

Guanine-rich nucleic acids can fold into G-quadruplex (G4) structures. Although endogenous RNAs contain sequences that can fold into RNA G4s (rG4s) in vitro, their folding and functions in vivo are not well understood. We show that the folding of putative rG4s in human cells into bona fide rG4 structures is dynamically regulated by stress. By using a high-throughput approach based on differential reactivity of dimethyl sulfate (DMS) towards Gs within folded vs unfolded rG4s, we identified hundreds of endogenous rG4s whose folding is promoted by cellular stress and validated them using a newly developed rG4-specific ligand. Stress-dependent rG4s are enriched in mRNA 3′-untranslated regions, suggesting their role in regulating mRNA stability under stress. Lastly, rG4 folding is reversible upon stress removal or adaptation. Our study show that rG4s function as regulatory elements in regulating mRNA stability and cellular stress response.

One-Sentence Summary

RNA G-quadruplexes assemble under stress in human cells
Synthesis and structure of two isomers of a molybdenum(II) 2-butyne complex stabilized by bioinspired S,N-bidentate ligands
Authors: Ehweiner Madeleine A. , Belaj Ferdinand , Mösch-Zanetti Nadia C.
Published: March 2022

The synthesis and structural determination of two isomers of the molybdenum(II) complex (η2-but-2-yne)carbonylbis[2-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)benzenethiolato-κ2
N,S]molybdenum(II), [Mo(C11H12NOS)2(C4H6)(CO)] or Mo(CO)(C2Me2)(S-Phoz)2, are presented. The N,N-cis–S,S-trans isomer 1 shows quite different bond lengths to the metal atom [Mo—N = 2.4715 (10) versus 2.3404 (11) Å; Mo—S = 2.4673 (3) versus 2.3665 (3) Å]. In the N,N-trans–S,S-cis isomer 2, which is isotypic with the corresponding W complex, the Mo—N bond lengths [2.236 (2) and 2.203 (2) Å], as well as the Mo—S bond lengths [2.5254 (8) and 2.5297 (8) Å], are almost the same.
Updated restraint dictionaries for carbohydrates in the pyranose form
Authors: Atanasova Mihaela , Nicholls Robert A. , Joosten Robbie P. , Agirre Jon
Published: March 2022

Restraint dictionaries are used during macromolecular structure refinement to encapsulate intramolecular connectivity and geometric information. These dictionaries allow previously determined `ideal' values of features such as bond lengths, angles and torsions to be used as restraint targets. During refinement, restraints influence the model to adopt a conformation that agrees with prior observation. This is especially important when refining crystal structures of glycosylated proteins, as their resolutions tend to be worse than those of nonglycosylated proteins. Pyranosides, the overwhelming majority component in all forms of protein glycosylation, often display conformational errors in crystal structures. Whilst many of these flaws usually relate to model building, refinement issues may also have their root in suboptimal restraint dictionaries. In order to avoid subsequent misinterpretation and to improve the quality of all pyranose monosaccharide entries in the CCP4 Monomer Library, new dictionaries with improved ring torsion restraints, coordinates reflecting the lowest-energy ring pucker and updated geometry have been produced and evaluated. These new dictionaries are now part of the CCP4 Monomer Library and will be released with CCP4 version 8.0.
Consumer acceptance of innovations in traditional foods: the case of extra-virgin olive oil
Authors: Carlucci Domenico , Roselli Luigi , Giannoccaro Giacomo , Cavallo Carla , Del Giudice Teresa , Vecchio Riccardo , Cicia Gianni , De Gennaro Bernardo Corrado
Published: March 2022

Purpose

This study aims to investigate consumer acceptance for a set of innovations that can be applied to the production process of extra-virgin olive oil. The final purpose is to verify whether, and to what extent, consumer acceptance of innovations varies depending on the type of technology used and the profile of consumers.

Design/methodology/approach

A cross-sectional consumer survey has been carried out in Italy. A structured questionnaire was administered to a national representative sample of individuals who are responsible for grocery shopping (N = 1,003). Consumer acceptance for a set of ten innovations has been measured. Statistical differences between the various measures have been analysed through pairwise comparisons using Wilcoxon's signed-rank test, and subsequent effect sizes have been estimated. A cluster analysis has been also performed to distinguish consumer segments with different response patterns.

Findings

The results showed that the type of technology affects significantly the level of consumer acceptance of the tested innovations. In addition, high heterogeneity has been detected among consumer responses, and this leads to identify three consumer segments with different response patterns.

Originality/value

The study is focused on extra-virgin olive oil, which is one of the most important traditional food product in Mediterranean countries. This is the first study where several innovations for extra-virgin olive oil were jointly tested and compared for acceptance through a survey on a nation-wide representative sample of consumers.
A smart web of firms, farms and internet of things (IOT): enabling collaboration-based business models in the agri-food industry
Authors: Mahdad Maral , Hasanov Mustafa , Isakhanyan Gohar , Dolfsma Wilfred
Published: March 2022

Purpose

All firms' business models are based on their interdependencies with other parties in their ecosystems. The Internet of Things (IoT) is beginning to fundamentally disrupt the agri-food industry, forcing the ecosystem to change. When an ecosystem is transforming, the interdependencies among its actors can create friction. Technology providers and core actors should consider these interdependencies as they update their strategies for value creation and capture. The purpose of the present research is to consider what it might take for agri-food firms to capitalize on these interdependencies by moving from traditional business models to business models based on collaboration and open innovation.

Design/methodology/approach

The present paper draws on data from four online focus groups that we created to discuss how to co-create the business models agri-food firms need in a constantly changing environment. The paper presents an application of phenomenon-driven research (PDR), an engaged methodology. The study method enables novel pathways to develop and implement innovative solutions. This study draws on the interaction of theory and practice and involves multiple stakeholders with varying roles in the agri-food ecosystem.

Findings

The authors found that any open innovation setup in agri-food needs to constantly reconfigure itself to balance the needs of farmers and the needs of the market. This interplay can only support the IoT-enabled ecosystem if continuous interaction and negotiation occur among various stakeholders of the food system. When the farmers' needs and the market's needs are aligned, the space for developing a collaborative and open business model is prepared.

Originality/value

The insights gained from this study inspire action and commitment to common goals when developing collaboration-based business models (CBMs). The paper offers insights for players in the agri-food industry who are considering CBMs in the course of digital transformation.
The effects of ethnic diversity and friendship ties on managers' emotional exhaustion: a network-based case study of Caribbean information technology firms
Authors: Galbraith Craig , Phillips-Hall Cheryl Ann , Merrill Gergory
Published: March 2022

Purpose

The purpose of this article is to empirically examine the relationship between managers' emotional exhaustion and the ethnic diversity, workload requirements, and friendship ties within their work-groups.

Design/methodology/approach

The research employs a full-network sample of all managers from an indigenously owned ethnically diverse IT firm located in the Caribbean island nation of Trinidad and Tobago. Using a social network design within a regression model, the relationship between managerial power and operational workload and the burnout dimension of emotional exhaustion is initially examined as a baseline model. Work-group ethnicity and friendship ties are then examined as moderators to this relationship. The authors then examine the role of work-group ethnicity and friendship ties as a buffer mechanism using an efficient frontier analysis where managers act as decision-making units.

Findings

The study indicates that ethnic diversity acts more as a “negative moderator” to emotional exhaustion, while friendship ties act as both a “positive moderator” and “buffer” to work-related emotional exhaustion.

Originality/value

This is one of the few empirical studies that has examined the issues of ethnic diversity and burnout using social network and efficient frontier methodologies. This is also one of the first empirical studies to investigate these issues using an in-depth, full-sample case study of actual, real-work network relationships.
Value creation process and outcomes in social inclusion focused services
Authors: Winston Emma , Ferdous Ahmed Shahriar , Rentschler Ruth , Azmat Fara , Robertson Nichola
Published: March 2022

Purpose

This study aims to elucidate the value creation process within a culturally diversified museum (CDM), which aims to achieve social inclusion, i.e. bridging the social divide between mainstream and minority communities, through the integration of CDM’s and visitors’ resources. Using service logic (SL) theory as the theoretical lens, we aim to unveil the CDM’s unique service provider and customer (visitor) resources, the corresponding resource integration process that explains value co-creation and co-destruction and the resultant value outcomes for social inclusion.

Design/methodology/approach

A case study of an Australian CDM is used, involving various qualitative data sources, including depth interviews, focus groups, visitor book content analysis, on-site observation and participation in the CDM’s events and forums.

Findings

The findings provide insights into the unique CDM and visitor resources that are integrated to achieve value outcomes that foster social inclusion. However, the results suggest that alongside value co-creation, co-destruction can unfold, causing a (mis)alignment with the aim of the CDM to bridge the social divide between mainstream and minority communities.

Practical implications

This study’s findings offer salient implications for CDMs and similar service providers that enables social inclusion and policymakers.

Originality/value

This study contributes to the service domain by highlighting the importance of the alignment between provider and customer resources to co-create value within a culturally diversified context. That is, CDMs can learn from the misalignment of their resources and those of their visitors to improve their resource offerings and achieve greater social inclusion outcomes in the future.
Healthcare services utilization in Iran: a systematic review and meta-analysis
Authors: Ahadinezhad Bahman , Khosravizadeh Omid , Rafiei Sima , Maleki Aisa
Published: March 2022

Purpose

It can be said that the most important function of the health system is to provide health-care services. This directly affects society’s health and justice. To the best of the authors’ knowledge, this study is the first study that has meta-analyzed the percentage of health services utilization among Iranians to answer this question “How much is the percentage of health-care services utilization in Iran?”

Design/methodology/approach

This study is a systematic review and meta-analysis conducted in 2020. The literature review was done by searching the databases of Google Scholar, Scopus, PubMed, Web of Science, Science Direct, SID, Magiran and Irandoc from January 2010 to August 2020. Pooled utilization percentage (UP) was estimated by STATA 15 through random-effects meta-analysis with 95% confidence interval. The I2 statistic was used to investigate the possibility of heterogeneity of articles (I2 ≥ 50% indicate heterogeneity). A forest plot was applied to report the results. A funnel plot exploited due to publication bias assessment.

Findings

Approximately 22% of the reviewed articles have been done at the national level of Iran. Most studies have examined the utilization of outpatient and inpatient services. Based on the random effects method, the pooled value of UP was obtained at 47.82%, (95% CI: 39.33–56.31). Also, the pooled percentage of utilization was statistically significant (Test of UP = 0, Z = 456.44, p = 0.000).

Practical implications

Policymakers can improve the level of utilization from health services by expanding universal coverage, expanding insurance coverage and removing direct and indirect barriers.

Originality/value

To the best of the authors’ knowledge, this is the first systematic review and meta-analysis on health services utilization in Iran that completely considers the utilization rate in all health services and states the practical solutions to cope with utilization deficiencies and barriers.
The landscape of post-institutional practice variation theories: from traveling ideas to institutional inertia
Authors: Firsova Svitlana , Bilorus Tetiana , Olikh Lesya , Salimon Olha
Published: March 2022

Purpose

Institutional theory assumes practice adoption and subsequent decoupling. However, there is a range of alternative organizational theories that challenge this view and offer instead their reinterpretation, extension and modification of institutional predictions with regard to the adoption and possible range of various responses and processes that follow the decision to adopt. This paper aims to review this spectrum of theories and suggest how they clarify, supplement, correct, restrict and/or abandon some institutional explanations and predictions.

Design/methodology/approach

Extensions and alternatives to institutional theory are mainly motivated by the need to have a theory of practice adoption and variation, and a plethora of alternative practice adoption theories currently exists in the literature. The authors review these theories and compare them against institutional theory and against each other.

Findings

The analysis revealed shortcomings and advantages of alternative theories compared to institutional theory and against each other. It is suggested which theory is most useful in each domain of application. The authors review and compare institutional theory, Scandinavian institutionalism, management fashion theory, virus theory and institutional inertia theory and analyze how and whether they are able to reproduce the success of institutional theory and successfully address and resolve its shortcomings and gaps. The authors conclude by discussing whether regular emergences of new theories that account for the idea-handling stage of diffusion signals institutional theory’s limit of validity in this domain.

Originality/value

The problem of idea emergence/diffusion/disappearance and adoption/variation/use are fundamentally different, but both of them motivated researchers to go beyond institutional theory. Despite being the dominant theory of organizations internally consistent and explaining a wide range of empirical observations, it is evident that institutional theory is not a complete theory. This paper contributes to this problem by exploring and comparing existing candidates for practice variation theory.