bluuebunny/crossref_metadata_2025 huggingface dataset:
Challenging diagnosis of cervical vagal nerve schwannoma
Authors: Pankratjevaite Lina , Dreyer Niloofar Sherazi , Dauksa Albertas , Sarauskas Valdas
Published: March 2022

Schwannoma arising from vagal nerve is a rare tumour. It is a slow-growing, benign mass, but rarely it might undergo malignant transformation. We report a case of a 55-year-old woman with asymptomatic Xth cranial nerve schwannoma in the left side of the neck. Initially, during the ultrasound examination, the tumour was misconceived to be a malignant lymph node. The patient underwent complete surgical excision of it. Histopathological examination revealed typical features of schwannoma. Clinical diagnose of cervical vagal nerve schwannoma is difficult. Magnetic resonance imaging is as an accurate diagnostic tool for these tumours. Surgical excision is the treatment of choice.
Facultative heterochromatin formation in rDNA is essential for cell survival during nutritional starvation
Authors: Hirai Hayato , Takemata Naomichi , Tamura Miki , Ohta Kunihiro
Published: March 2022

During the cellular adaptation to nutrient starvation, cells temporarily decelerate translation processes including ribosomal biogenesis. However, the mechanisms repressing robust gene expression from the ribosomal gene cluster (rDNA) are unclear. Here, we demonstrate that fission yeast cells facing glucose starvation assemble facultative heterochromatin in rDNA leading to its transcriptional repression. Glucose starvation induces quick dissociation of the ATF/CREB-family protein Atf1 from rDNA, where in turn the histone chaperone FACT is recruited to promote H3K9 methylation and heterochromatinization. We also identify the histone acetyltransferase Gcn5 as a repressor of rDNA heterochromatinization in glucose-rich conditions, and this protein dissociates from rDNA upon glucose starvation. Facultative heterochromatin formation in rDNA requires histone deacetylases Clr3 and both the RNAi-dependent and -independent gene silencing pathways. This is essential in adaptation to starvation since mutants lacking heterochromatin formation in rDNA lead to untimely cell death during glucose starvation.
Genetic control of branching patterns in grass inflorescences
Authors: Kellogg Elizabeth A
Published: March 2022

Inflorescence branching in the grasses controls the number of florets and hence the number of seeds. Recent data on the underlying genetics come primarily from rice and maize, although new data are accumulating in other systems as well. This review focuses on a window in developmental time from the production of primary branches by the inflorescence meristem through to the production of glumes, which indicate the transition to producing a spikelet. Several major developmental regulatory modules appear to be conserved among most or all grasses. Placement and development of primary branches are controlled by conserved auxin regulatory genes. Subtending bracts are repressed by a network including TASSELSHEATH4, and axillary branch meristems are regulated largely by signaling centers that are adjacent to but not within the meristems themselves. Gradients of SQUAMOSA-PROMOTER BINDING-like and APETALA2-like proteins and their microRNA regulators extend along the inflorescence axis and the branches, governing the transition from production of branches to production of spikelets. The relative speed of this transition determines the extent of secondary and higher order branching. This inflorescence regulatory network is modified within individual species, particularly as regards formation of secondary branches. Differences between species are caused both by modifications of gene expression and regulators and by presence or absence of critical genes. The unified networks described here may provide tools for investigating orphan crops and grasses other than the well-studied maize and rice.
Integrative analyses identify potential key genes and calcium-signaling pathway in familial AVNRT using whole-exome sequencing
Authors: Huang Jichang , Luo Rong , Zheng Chenqing , Cao Xin , Zhu Yuncai , He Tao , Liu Mingjiang , Yang Zhenglin , Wu Xiushan , Li Xiaoping
Published: March 2022

Background

Atrioventricular nodal reentrant tachycardia (AVNRT) is a common arrhythmia. Growing evidence suggests that family aggregation and genetic factors are involved in AVNRT. However, in families with a history of AVNRT, disease-causing genes have not been reported.

Objective

To investigate the genetic contribution of familial AVNRT using a WES approach.

Methods

Blood samples were collected from 20 patients from nine families with a history of AVNRT and 100 control participants, and we systematically analyzed mutation profiles using whole-exome sequencing. Gene-based burden analysis, integration of previous sporadic AVNRT data, pedigree-based co-segregation, protein-protein interaction network analysis, single-cell RNA sequencing, and confirmation of animal phenotype were performed.

Results

Among 95 reference genes, seven pathogenic genes have been identified both in sporadic and familial AVNRT, including CASQ2, AGXT, ANK2, SYNE2, ZFHX3, GJD3, and SCN4A. Among the 37 reference genes from sporadic AVNRT, five pathogenic genes were identified in patients with both familial and sporadic AVNRT: LAMC1, RYR2, COL4A3, NOS1, and ATP2C2. Considering the unique internal pathogenic gene within pedigrees, three genes, TRDN, CASQ2, and WNK1, were likely to be the pathogenic genes in familial AVNRT. Notably, the core calcium-signaling pathway may be closely associated with the occurrence of AVNRT, including CASQ2, RYR2, TRDN, NOS1, ANK2, and ATP2C2.

Conclusion

These results revealed the underlying mechanism for familial AVNRT.
Psychosis spectrum symptoms among individuals with schizophrenia-associated copy number variants and evidence of cerebellar correlates of symptom severity
Authors: Sefik Esra , Guest Ryan M. , Aberizk Katrina , Espana Roberto , Goines Katrina , Novacek Derek M. , Murphy Melissa M. , Goldman-Yassen Adam E. , Cubells Joseph F. , Ousley Opal , Li Longchuan , Shultz Sarah , Walker Elaine F. , Mulle Jennifer G.
Published: March 2022

The 3q29 deletion (3q29Del) is a copy number variant (CNV) with one of the highest effect sizes for psychosis- risk (>40-fold). Systematic research offers promising avenues for elucidating mechanism; however, compared to CNVs like 22q11.2Del, 3q29Del remains understudied. Emerging findings indicate that posterior fossa abnormalities are common among carriers, but their clinical relevance is unclear. Here, we report the first in- depth evaluation of psychotic symptoms in participants with 3q29Del (N=23), using the Structured Interview for Psychosis-Risk Syndromes, and compare this profile to 22q11.2Del (N=31) and healthy controls (N=279). By neuroimaging, we also explore correlations between psychotic symptoms and posterior fossa abnormalities in 3q29Del. Cumulatively, 48% of the 3q29Del sample exhibited a psychotic disorder or attenuated positive symptoms, with a subset meeting criteria for clinical high-risk. 3q29Del had more severe ratings than controls on all domains and only exhibited less severe ratings than 22q11.2Del in negative symptoms, with select sex differences. An inverse relationship was identified between positive symptoms and cerebellar cortex volume in 3q29Del, documenting the first clinically-relevant neuroanatomical connection in this syndrome. Our findings characterize the profile of psychotic symptoms in the largest 3q29Del sample reported to date, contrast with another high-impact CNV, and highlight cerebellar involvement in elevated psychosis-risk.

Highlights

The rare copy number variants (CNVs) 3q29Del and 22q11.2Del confer the largest known effect sizes for schizophrenia susceptibility.

While 22q11.2Del’s link with psychosis has been extensively studied, in-depth characterization of psychotic symptoms associated with 3q29Del is lacking.

This study fills this gap and provides the first phenotypic comparison of psychotic symptom profiles in carriers of these CNVs, and healthy controls.

Additionally, we uncover a novel genetic association between 3q29Del, psychotic symptoms, and cerebellar cortex development.
Oncomodulin (OCM) uniquely regulates calcium signaling in neonatal cochlear outer hair cells
Authors: Murtha Kaitlin E. , Yang Yang , Ceriani Federico , Jeng Jing-Yi , Climer Leslie K. , Jones Forrest , Charles Jack , Devana Sai K. , Hornak Aubrey J. , Marcotti Walter , Simmons Dwayne D.
Published: March 2022

In cochlear outer hair cells (OHCs), a network of Ca2+ channels, pumps and Ca2+-binding proteins (CaBPs) regulates the localization, spread, and magnitude of free Ca2+ ions. During early postnatal development, OHCs express three prominent mobile EF-hand CaBPs: oncomodulin (OCM), α-parvalbumin (APV) and sorcin. We have previously shown that deletion of Ocm (Ocm-/-) gives rise to progressive cochlear dysfunction in young adult mice. Here, we show that changes in Ca2+ signaling begin early in postnatal development of Ocm-/- mice. While mutant OHCs exhibit normal electrophysiological profiles compared to controls, their intracellular Ca2+ signaling is altered. The onset of OCM expression at postnatal day 3 (P3) causes a developmental change in KCl-induced Ca2+ transients in OHCs and leads to slower KCl-induced Ca2+ transients than those elicited in cells from Ocm-/- littermates. We compared OCM buffering kinetics with other CaBPs in animal models and cultured cells. In a double knockout of Ocm and Apv (Ocm-/-;Apv-/-), mutant OHCs show even faster Ca2+ kinetics, suggesting that APV may also contribute to early postnatal Ca2+ signaling. In transfected HEK293T cells, OCM slows Ca2+ kinetics more so than either APV or sorcin. We conclude that OCM controls the intracellular Ca2+ environment by lowering the amount of freely available [Ca2+]i in OHCs and in transfected HEK293T cells. We propose that OCM plays an important role in shaping the development of early OHC Ca2+ signals through its inimitable Ca2+ buffering capacity.
Pervasive Under-Dominance in Gene Expression Underlying Emergent Growth Trajectories inArabidopsis thalianaHybrids
Authors: Yuan Wei , Beitel Fiona , Srikant Thanvi , Bezrukov Ilja , Schäfer Sabine , Kraft Robin , Weigel Detlef
Published: March 2022

Complex traits, such as growth and fitness, are typically controlled by a very large number of variants, which can interact in both additive and non-additive fashion. In an attempt to gauge the relative importance of both types of genetic interactions, we have turned to hybrids, which provide a facile means for creating many novel allele combinations. We focused on the interaction between alleles of the same locus and performed a transcriptomic study involving 141 random crosses between different accessions of the plant model speciesArabidopsis thaliana. Additivity is rare, consistently observed for only about 300 genes enriched for roles in stress response and cell death. Regulatory rare-allele burden affects the expression level of these genes but does not correlate with F1rosette size. Non-additive gene expression in F1hybrids is much more common, with the vast majority of genes (over 90%) being expressed below parental average. Unlike in the additive genes, regulatory rare-allele burden in the non-additive gene set is strongly correlated with F1rosette size, even though it only mildly covary with the expression level of these genes. Our study underscores under-dominance as the predominant gene action associated with emergence of rosette growth trajectories in theA. thalianahybrid model. Our work lays the foundation for understanding molecular mechanisms and evolutionary forces that lead to dominance complementation of rare regulatory alleles.
Zinc pyrithione is a potent inhibitor of PLPro and cathepsin L enzymes with ex vivo inhibition of SARS-CoV-2 entry and replication
Authors: Kladnik Jerneja , Dolinar Ana , Kljun Jakob , Perea David , Grau-Expósito Judith , Genescà Meritxell , Novinec Marko , Buzon Maria J. , Turel Iztok
Published: March 2022

As SARS-CoV-2 triggered a global health crisis, there is an urgent need to provide patients with safe, effective, accessible, and preferably oral therapeutics for COVID-19 that complement mRNA vaccines. Zinc compounds are widely known for their antiviral properties. Therefore, we have prepared a library of zinc complexes with pyrithione (1-hydroxy-2(1H)-pyridinethione) and its analogues, all of which showed promising in vitro inhibition of cathepsin L, an enzyme involved in SARS-CoV-2 entry, and PLPro, an enzyme involved in SARS-CoV-2 replication both in (sub)micromolar range. Zinc pyrithione 1a is a well-established, commercially available antimicrobial agent and was therefore selected for further evaluation of its SARS-CoV-2 entry and replication inhibition in an ex vivo system derived from primary human lung tissue. Our results suggest that zinc pyrithione complex 1a provides a multitarget approach to combat SARS-CoV-2 and should be considered for repurposing as a potential therapeutic against the insidious COVID-19 disease.

Featured image

In our study, we show that zinc pyrithione holds immense potential for the development of a possible out-patient treatment for SARS-CoV-2 due to its inhibition of viral entry and replication.
ACCUMULATION OF MICROPLASTIC AND MICRORUBBER PARTICLES IN STORMWATER POND FISH AND INVERTEBRATES
Authors: LaPlaca Stephanie B. , van den Hurk Peter
Published: March 2022

Stormwater ponds serve as best management practices to trap or remove both physical and chemical pollutants before further discharge of stormwater into receiving natural waterbodies. Stormwater ponds can therefore accumulate high levels of pollutants, including microplastics (MP) and microrubber (MR) from road runoff. It was hypothesized that biota in stormwater ponds that receive large amounts of road runoff, or are in proximity to roadways and major developments, would contain significant amounts of MP per individual, with high abundances of tire particles (TP). Fish and invertebrates were collected from five stormwater ponds and their adjacent tidal creeks in Mt. Pleasant, SC, USA. Whole organisms were digested using KOH and digested contents were filtered and analyzed by visual microscopy to identify and count MPs.

The majority (>80%) of MP recovered from biota across all sites were suspected TP. The average number of MP per individual ranged from 0.3 to 71 MP and the average number of suspected tire particles per individual ranged from 0 to 57.7 tire particles.

There were significant differences in MP per individual observed between sites and between species. A combination of factors such as availability of MPs based on surrounding land use, pond hydrodynamics, organism size, and species feeding habitat likely influenced the total MP observed among the different sites and species analyzed. These data provide preliminary examination into the fate and transport of MP and MR in stormwater ponds and an evaluation of MP and MR abundance in organisms from stormwater ponds in the coastal zone.
Maternal immune activation and adolescent alcohol exposure increases alcohol drinking and disrupts cortical-striatal-hippocampal oscillations in adult offspring
Authors: Henricks Angela M , Sullivan Emily DK , Dwiel Lucas L , Li Judy Y , Wallin Diana J , Khokhar Jibran Y. , Doucette Wilder T
Published: March 2022

Maternal immune activation (MIA) is strongly associated with an increased risk of developing mental illness in adulthood, which often co-occurs with alcohol misuse. The current study aimed to begin to determine whether MIA, combined with adolescent alcohol exposure (AE), could be used as a model with which we could study the neurobiological mechanisms behind such co-occurring disorders. Pregnant Sprague-Dawley rats were treated with PolyI:C or saline on gestational day 15. Half of the offspring were given continuous access to alcohol during adolescence, leading to four experimental groups: controls, MIA, AE, and Dual (MIA + AE). We then evaluated whether MIA and/or AE alters: 1) alcohol consumption; and 2) cortical-striatal-hippocampal oscillations in adult offspring. Dual rats, particularly females, drank significantly more alcohol in adulthood compared to all other groups. Using machine learning to build predictive models from oscillations, we were able to differentiate Dual rats from control rats and AE rats in both sexes, and Dual rats from MIA rats in females. The current data suggest that MIA+AE (Dual “hits”) is a valuable model that we can use to study the neurobiological underpinnings of co-occurring disorders. Our future work aims to extend these findings to other addictive substances to enhance the translational relevance of this model.
The role of TGFβ signaling in Gli1+ tendon and enthesis cells
Authors: Song Lee , Golman Mikhail , Abraham Adam C. , Zelzer Elazar , Thomopoulos Stavros
Published: March 2022

The development of musculoskeletal tissues such as tendon, enthesis, and bone relies on proliferation and differentiation of mesenchymal progenitor cells. Gli1+ cells have been described as putative stem cells in several tissues and are presumed to play critical roles in tissue formation and maintenance. For example, the enthesis, a fibrocartilage tissue that connects tendon to bone, is mineralized postnatally by a pool of Gli1+ progenitor cells. These cells are regulated by hedgehog signaling, but it is unclear if TGFβ signaling, necessary for tenogenesis, also plays a role in their behavior. To examine the role of TGFβ signaling in Gli1+ cell function, the receptor for TGFβ, TbR2, was deleted in Gli1-lineage cells in mice at P5. Decreased TGFβ signaling in these cells led to defects in enthesis formation by P56, including deficient bone morphometry underlying the enthesis and decreased mechanical properties.In vitroexperiments using Gli1+ cells isolated from mouse tail tendons demonstrated that TGFβ controls cell proliferation and differentiation through canonical and non-canonical pathways and that TGFβ directly controls the tendon transcription factor scleraxis by binding to its distant enhancer. These results have implications in the development of treatments for tendon and enthesis pathologies.
The Ferrous Iron Transporter FeoB1 is Essential for Clostridioides difficile Toxin Production and Pathogenesis in Mice
Authors: Deshpande Aditi , Olaitan Abiola O. , Mckelvey Ann M. , Rutherford Jacob T. , Hurdle Julian G.
Published: March 2022

Ferrous iron is the dominant form of iron in the oxygen-limited large intestine, the site for Clostridioides difficile infection (CDI). We investigated the extent to which C. difficile requires the ferrous iron transporter 1 (FeoB1), a main permease for iron acquisition, using in vitro and in vivo approaches. Construction of feoB1 deletion mutant in C. difficile R20291 (i.e., R20291ΔfeoB1) decreased intracellular iron content by ~25%. This was accompanied by reduced synthesis of TcdA and TcdB toxins and downregulation of tcdA and tcdB genes, which was reflected by a ~1000-fold reduction in cytopathy against Vero cells. Complementation with WT feoB1 restored toxin production. R20291ΔfeoB1 was avirulent in mice with underlying colitis. In this model, mice are prone to develop severe CDI, but mice infected with the mutant lacked diarrheal symptoms, had lesser inflammatory responses, bacterial bioburdens and cecal toxin titers. Transcriptional and biochemical analyses revealed ΔfeoB1 altered metabolic pathways that negatively impact toxin production, including downregulation of the oxidative branch of the Kreb cycle and an associated cellular accumulation of pyruvate. Hence FeoB1 influences multiple bioenergetic and redox pathways, which in turn inhibits toxin biosynthesis. Targeting FeoB1 could be a potential therapeutic strategy to impede the colonization and pathogenesis of C. difficile, even in the setting of colitis where CDI is more severe and intestinal bleeding may occur.

AUTHOR SUMMARY

Clostridioides difficile is a major cause of antibiotic associated diarrhea that result in significant morbidity and mortality in hospitals. The ability of C. difficile to cause disease and damage the gut is directly related to the production of toxin A and toxin B. Without these toxins, C. difficile is not virulent. There is need to identify drug targets and therapeutic strategies that prevent C. difficile from producing toxins A and B. For C. difficile to colonize the large bowel, it must acquire ferrous iron, which is thought to be the main form of iron within the oxygen-limited large bowel environment. We show that genetic deletion of the ferrous iron transporter FeoB1 stops C. difficile from producing significant amounts of toxins under in vitro conditions. Importantly, the mutant R20291ΔfeoB1 was avirulent when tested in a mouse model that favors the development of severe infections. Avirulence of R20291ΔfeoB1 was related to the strain having significant metabolic changes that negatively impact toxin production. For example, cells could not properly metabolize pyruvate, which became accumulated in cells; pyruvate is known to reduce the production of toxins A and B. Our study provides new insights into how FeoB1 affects C. difficile colonization and disease development, indicating FeoB1 could be a drug target to stop toxin production in this bacterium.
Information Decay and Enzymatic Information Recovery for DNA Data Storage
Authors: Meiser Linda C. , Gimpel Andreas L. , Deshpande Tejas , Libort Gabriela , Chen Weida D. , Heckel Reinhard , Nguyen Bichlien H. , Strauss Karin , Stark Wendelin J. , Grass Robert N.
Published: March 2022

Synthetic DNA has been proposed as a storage medium for digital information due to its high theoretical storage density and anticipated long storage horizons. However, under all ambient storage conditions, DNA undergoes a slow chemical decay process resulting in nicked (broken) DNA strands, and the information stored in these strands is no longer readable. In this work we design an enzymatic repair procedure, which is applicable to the DNA pool prior to readout and can partially reverse the damage. Through a chemical understanding of the decay process, an overhang at the 3’ end of the damaged site is identified as obstructive to repair via the base excision-repair (BER) mechanism. The obstruction can be removed via the enzyme apurinic/apyrimidinic endonuclease I (APE1), thereby enabling repair of hydrolytically damaged DNA via Bst polymerase and Taq ligase. Simulations of damage and repair reveal the benefit of the enzymatic repair step for DNA data storage, especially when data is stored in DNA at high storage densities (= low physical redundancy) and for long time durations.
ReLo is a simple and quick colocalization assay to identify and characterize direct protein-protein interactions
Authors: Salgania Harpreet Kaur , Metz Jutta , Jeske Mandy
Published: March 2022

The characterization of protein-protein interactions (PPIs) is fundamental for understanding biochemical processes. Many methods have been established to identify and study direct PPIs; however, the screening and investigation of PPIs involving large or poorly soluble proteins remain challenging. As a result, we developed ReLo, a simple, rapid, and versatile cell culture-based method for detecting and investigating interactions in a cellular context. Importantly, our data strongly suggest that with ReLo specifically direct binary PPIs are detected. By applying additional bridging experiments ReLo can also be used to determine the binding topology of subunits within multiprotein complexes. Moreover, ReLo has the potential to identify protein domains that mediate complex formation, screen for interfering point mutations, study interactions that depend on conformation or protein arginine methylation, and it is sensitive to drugs that mediate or interfere with an interaction. Taken together, ReLo is a simple and quick alternative for the study of PPIs particularly when established methods fail.
A family of unusual immunoglobulin superfamily genes in an invertebrate histocompatibility complex
Authors: Huene Aidan L. , Sanders Steven M. , Ma Zhiwei , Nguyen Anh-Dao , Koren Sergey , Michaca Manuel H. , Mullikin James C. , Phillippy Adam M. , Schnitzler Christine E. , Baxevanis Andreas D. , Nicotra Matthew L.
Published: March 2022

Most colonial marine invertebrates are capable of allorecognition, the ability to distinguish between themselves and conspecifics. One long-standing question is whether invertebrate allorecognition genes are homologous to vertebrate histocompatibility genes. In the cnidarian Hydractinia symbiolongicarpus, allorecognition is controlled by at least two genes, Allorecognition 1 (Alr1) and Allorecognition 2 (Alr2), which encode highly polymorphic cell surface proteins that serve as markers of self. Here, we show that Alr1 and Alr2 are part of a family of 41 Alr genes, all of which reside a single genomic interval called the Allorecognition Complex (ARC). Using sensitive homology searches and highly accurate structural predictions, we demonstrate that the Alr proteins are members of the immunoglobulin superfamily (IgSF) with V-set and I-set Ig domains unlike any previously identified in animals. Specifically, their primary amino acid sequences lack many of the motifs considered diagnostic for V-set and I-set domains, yet they adopt secondary and tertiary structures nearly identical to canonical Ig domains. Thus, the V-set domain, which played a central role in the evolution of vertebrate adaptive immunity, was present in the last common ancestor of cnidarians and bilaterians. Unexpectedly, several Alr proteins also have immunoreceptor tyrosine-based activation motifs (ITAMs) and immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in their cytoplasmic tails, suggesting they could participate in pathways homologous to those that regulate immunity in humans and flies. This work expands our definition of the IgSF with the addition of a family of unusual members, several of which play a role in invertebrate histocompatibility.

Significance Statement

The immunoglobulin superfamily (IgSF) is one of the largest and most functionally versatile domain families in animal genomes. Although their amino acid sequences can vary considerably, IgSF domains have been traditionally defined by conserved residues at several key positions in their fold. Here, we sequenced an invertebrate histocompatibility complex and discovered a family of IgSF genes with amino acid sequences that lack most of these residues yet are predicted to adopt folds virtually identical to canonical V-set and I-set IgSF domains. This work broadens the definition of the IgSF and shows that the V-set domain was present earlier in animal evolution than previously appreciated.
FAM172A controls the nuclear import and alternative splicing function of AGO2
Authors: Sallis Sephora , Bérubé-Simard Félix-Antoine , Grondin Benoit , Leduc Elizabeth , Azouz Fatiha , Bélanger Catherine , Pilon Nicolas
Published: March 2022

The poorly characterized protein FAM172A is mutated in some individuals affected by a disorder of neural crest development called CHARGE syndrome. We also know that FAM172A can interact with the main CHARGE syndrome-associated protein CHD7 and the small RNA-binding protein AGO2 at the chromatin-spliceosome interface. Focusing on this intriguing FAM172A-AGO2 interaction, we now report that FAM172A is one of the long sought-after regulator of AGO2 nuclear import. This FAM172A function relies on its nuclear localization signal, being enhanced by CK2-mediated phosphorylation and abrogated by a CHARGE syndrome-associated missense mutation. Accordingly, Fam172a and Ago2 genetically interact in mice, and neural crest-specific depletion of Ago2 is sufficient to phenocopy CHARGE syndrome without impacting post-transcriptional gene silencing. Rapamycin-mediated rescue suggests that observed morphological anomalies are instead due to alternative splicing defects. This work thus demonstrates that non-canonical nuclear functions of AGO2 and associated regulatory mechanisms may be clinically relevant.
Morph-dependent nematode infection and its association with host movement in the land snail Cepaea nemoralis (Mollusca, Gastropoda)
Authors: Dahirel Maxime , Proux Marine , Gérard Claudia , Ansart Armelle
Published: March 2022

Host behaviour can be influenced by parasitic risk and infection through a variety of direct and indirect mechanisms. We can expect individuals expressing different phenotypes to also differ in the ways their behaviour is altered by parasites. We used the land snail Cepaea nemoralis, a species with various shell colour morphs differing in behaviour and physiology, as a model to study the link between parasite response and individual behaviour variation. We analysed metazoan parasite abundance and its relation to behaviour (movement and food intake) in snails from three shell morphs (from light unbanded to darker five-banded) and from two neighbouring populations from contrasted environments. Snails were parasitized by mites, trematodes and nematodes, from rarest to most frequent. We confirm that terrestrial gastropods can defend against infection by trapping parasitic nematodes in their shell. We show that nematode encapsulated in shells can uncover past infections even when a snail population is currently nematode-free, possibly due to parasite seasonality. We present new observations suggesting that not only nematodes but also mites might be encapsulated in shells. Infection levels varied between morphs, with darker snails harbouring fewer nematodes. Behaviour (movement and food intake) was linked to nematode, but not trematode infection. Individuals with higher nematode load ate less, irrespective of morph and population. The most-infected morph (unbanded snails) showed reduced activity in the nematode-infected population compared to the one that was nematode-free at sampling time. As a result, parasites may cancel previously described behavioural differences between morphs. We discuss the possible mechanisms explaining morph-dependent responses to parasites, and how parasite risk may be an unseen force shaping C. nemoralis morph variation in space and time. We conclude on the possible ecological consequences of the link, mediated by shell colour, between thermal and immune responses.
Extrafollicular responses are sufficient to drive initiation of autoimmunity and early disease hallmarks of lupus
Authors: Voss Lasse F. , Howarth Amanda J. , Wittenborn Thomas R. , Hummelgaard Sandra , Juul-Madsen Kristian , Kastberg Kristian S. , Pedersen Mathias K. , Jensen Lisbeth , Papanastasiou Anastasios D. , Vorup-Jensen Thomas , Weyer Kathrin , Degn Søren E.
Published: March 2022

Many autoimmune diseases are characterized by germinal center (GC) derived affinity-matured, class-switched autoantibodies. Strategies to block GC formation and progression are currently being explored clinically, however, extrafollicular responses may also contribute to early events in autoimmunity. To investigate the relative contribution of these two pathways in autoimmune disease development, we leveraged a transgenic strategy to genetically block the GC pathway. Surprisingly, this accelerated extrafollicular responses and failed to curb autoimmune progression in two lupus models.In vitro, loss of the GC transcription factor Bcl-6 prevented cellular expansion and accelerated plasma cell differentiation, suggesting thein vivophenotype was caused by rewiring of B cell intrinsic transcriptional programming. In a competitive scenarioin vivo, B cells harboring the genetic GC block contributed disproportionately to the plasma cell output. Taken together, this emphasizes the extrafollicular pathway as a key contributor to autoimmune progression, and suggests that strategies aimed at blocking GCs should simultaneously target this pathway to avoid rerouting the pathogenic response.

Highlights

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A genetic GC block fails to prevent autoimmune progression in two lupus models

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An intrinsic GC block drives B cell differentiation into terminally differentiated plasma cellsin vitro

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B cells harboring a GC block competitively contribute to the plasma cell compartment in an autoreactive settingin vivo

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Lupus mice with a GC block display immune complex deposition in kidney glomeruli that is indistinguishable from their wild-type counterparts

Affinity-matured autoantibodies generated in germinal centers are a hallmark of autoimmune diseases. Voss et al. block germinal centers in two autoimmune models, but surprisingly find that disease progresses unimpeded. They identify the extrafollicular pathway as a ‘backdoor to autoimmunity’.
The importance of m6A topology in chicken embryo mRNA; a precise mapping of m6A at the conserved chicken β-actin zipcode
Authors: Baron Francis , Zhang Mi , Archer Nathan , Bellows Eleanor , Knight Helen M. , Welham Simon , Rutland Catrin S , Mongan Nigel P. , Hayes Christopher J. , Fray Rupert G. , Bodi Zsuzsa
Published: March 2022

N6-Methyladenosine (m6A) in mRNA regulates almost every stage in the mRNA life cycle, and the development of methodologies for the high throughput detection of methylated sites in mRNA using m6A-specific methylated RNA immunoprecipitation with next-generation sequencing (MeRIPSeq) or m6A individual-nucleotide-resolution cross-linking and immunoprecipitation (miCLIP) have revolutionized the m6A research field. Both of these methods are based on immunoprecipitation of fragmented mRNA. However, it is well documented that antibodies often have nonspecific activities, thus verification of identified m6A sites using an antibody-independent method would be highly desirable. We mapped and quantified the m6A site in the chicken β-actin zipcode based on the data from chicken embryo MeRIPSeq results and our RNA-Epimodification Detection and Base-Recognition (RedBaron) antibody independent assay. We also demonstrated that methylation of this site in the β-actin zipcode enhances ZBP1 binding in vitro, whilst methylation of a nearby adenosine abolishes binding. This suggests that m6A may play a role in regulating localised translation of β-actin mRNA, and the ability of m6A to enhance or inhibit a reader protein’s RNA binding highlights the importance of m6A detection at nucleotide resolution.
Applying an interactive learning approach provided by an academic coach in a graduate-level accounting course
Authors: Wen Lei , Wang Yingqi
Published: March 2022

Purpose

The paper makes a significant contribution to the accounting education literature by examining the impact of using online meetings with an academic coach on student-perceived learning outcomes, course and instructor evaluations in an online graduate-level accounting course.

Design/methodology/approach

A quasi-experimental design is adopted by the author to compare the students' evaluations in fall 2018 and in spring 2019 in an online graduate-level accounting course taught by the same instructor and assisted by the same academic coach.

Findings

The study finds that the use of online meetings with an academic coach helps students have a much positive view about the course and a better perception about the instructor's teaching effectiveness for the course. The offering of online meetings by an academic coach also improves students' evaluation about the academic coach in an online graduate-level accounting course.

Originality/value

The paper provides a new perspective to investigate students' perception with the use of online meetings with an academic coach.
Building a bridge between civic agriculture and civic engagement: farmers’ markets as communication infrastructure
Authors: Witzling Laura , Shaw Bret R.
Published: March 2022

Purpose

This work aimed to show how farmers’ markets can act as communication infrastructure, and by doing so, facilitate civic engagement. We used communication infrastructure theory (CIT) as a guide.

Design/methodology/approach

We integrated findings from two surveys that took place in the US state of Wisconsin. In a survey of Wisconsin farmers’ market leaders, we considered what features farmers’ markets have that may help them act as communication infrastructure. Using data from a survey of Wisconsin residents, we ran a regression model to demonstrate the relationship between farmers’ market attendance and micro-level storytelling about local food.

Findings

We found that farmers’ markets can act as meso-level storytellers and provide a communication action context supportive of civic engagement. Through the farmers’ market leader survey, we found that over half of the markets noted existing partnerships with media outlets. Furthermore, farmers’ markets may connect residents to important organizations in the community. Many farmers’ markets had features to make them more physically and financially accessible, such as accepting food assistance benefits. With the Wisconsin resident survey, we found that farmers’ market attendance predicted storytelling about local food better than overall local food purchasing, further suggesting that markets can facilitate social interactions.

Originality/value

We document an important benefit that farmers’ markets can offer communities: they have the potential to act as communication infrastructure. As stronger communication infrastructure can facilitate civic engagement, this work provides a mechanism by which to connect civic agriculture activities and increased levels of civic engagement.
Research on the identification of medical service quality factors: based on a data-driven method
Authors: Gao Huiying , Lu Shan , Kou Xiaojin
Published: March 2022

Purpose

The purpose of this study is to identify medical service quality factors that patients care about and establish a medical service quality evaluation index system by analyzing online reviews of medical and healthcare service platforms in combination with a questionnaire survey.

Design/methodology/approach

This study adopts a combination of review mining and questionnaire surveys. The latent Dirichlet allocation (LDA) model was used to mine hospital reviews on the medical and healthcare service platform to obtain the medical service quality factors that patients pay attention to, and then the questionnaire was administered to obtain the relative importance of these factors to patients' perception of service quality. Finally, the index system was established.

Findings

The medical service quality factors patients care about include medical skills and ethics, registration service, operation effect, consulting communication, drug therapy, diagnosis process and medical equipment.

Research limitations/implications

The identification of medical service quality factors provides a reference for medical institutions to improve their medical service quality.

Originality/value

This study uses online review mining to obtain medical service quality factors from the perspective of patients, which is different from previous methods of obtaining factors from relevant literature or expert judgments; then, based on the mining results, a medical service quality evaluation index system is established by using questionnaire data.
The digital transformation of Swiss small and medium-sized enterprises: insights from digital tool adoption
Authors: Kraft Corin , Lindeque Johan P. , Peter Marc K.
Published: March 2022

Purpose

The study explores the alignment of Swiss small and medium-sized enterprise (SME) managers' understanding of digital transformation, with evidence of digital tool adoption in managerial and operative work. This reveals opportunities for more fully realizing the potential of digital transformation for SMEs.

Design/methodology/approach

This multiple-case study, with four theoretically sampled cases, analyzes data from the qualitative answers of 1,593 respondents to a survey of Swiss SMEs about digital transformation. The study draws on a convenience sample of Swiss SME managers.

Findings

The analysis shows little understanding of digital transformation as related to managerial work. However, there are two clear digital tool adoption patterns for managerial work: (1) workflow and workforce management and (2) work-flow and team management. Understandings of digital transformation and operative work focus on the (1) organization of operational work or (2) a combination of organization and changing the way people work. The digital tool adoption in operational work additionally focuses on the digital skills of operational employees.

Research limitations/implications

The study is only able to identify patters of understanding of digital transformation and digital tool adoption in managerial and operative work. More research is needed to understand why these patterns are observed.

Practical implications

SME managers need to think far more carefully about aligning their vision for digital transformation and the digital tools they adopt in both managerial and operational work, but especially in managerial work.

Originality/value

This is the first empirical study of the digital transformation of Swiss SMEs and their digital tool adoption. Significant potential for alignment is revealed, suggesting potential performance gains are possible.
The survival of bike-sharing startups in China: an empirical analysis of the influencing factors
Authors: Zhou Yan , Park Sangmoon , Wang Qifeng , Zhang Justin Zuopeng , Behl Abhishek
Published: March 2022

Purpose

Bike-sharing is popular worldwide, and it has led to a new development direction in green transportation. However, the collapse of many bike-sharing startups and residual social problems has brought about contradictions and challenges to the development of the industry. The purpose of this paper is to determine how internal factors affect the survival of bike-sharing startups.

Design/methodology/approach

The authors used binary logit regression as the measurement model to conduct an empirical analysis based on 137 bike-sharing startups in China. The study focuses on using traditional theoretical evidence and considers the uniqueness of the industry to jointly explore the survival factors that influence the emerging business model of bike-sharing.

Findings

The results show that entrepreneurial team size and differentiation strategy positively influence survival. Founder-CEOs have a negative impact on survival. Founders' entrepreneurial experience and venture capital have no significant influence on survival.

Originality/value

The results verify the role of traditional survival factors in the new business model of sharing economy and fill the research gap on the survival strategy of startups. This study offers a unique perspective for researchers to better understand the sharing economy industry and provides practical guidance for entrepreneurs and investors to enter the market.
Measuring Internet banking service quality: an empirical evidence
Authors: Mir Rouf Ahmad , Rameez Raja , Tahir Nida
Published: March 2022

Purpose

This study aims to empirically develop a reliable and valid instrument measuring the online service quality in the context of the banking sector in India.

Design/methodology/approach

The methodological framework of this research comprises developing an instrument that is based on previous literature, qualitative and quantitative procedure. The study used the survey method and collected data via a well-structured questionnaire from a sample of active Internet banking users. The proposed instrument is identified by the data-reduction technique that is exploratory factor analysis (EFA), and validated through the confirmatory factor analysis (CFA).

Findings

The results confirmed that the digital banking service quality scale (DBSQual) contains 24 items in seven dimensions: (1) web architecture, (2) user friendliness, (3) efficiency of website, (4) reliability, (5) responsiveness, (6) security and (7) personalization. The relationship between digital banking service quality and e-customer satisfaction has also been found to be significant in this study.

Research limitations/implications

The results of this study do not find general application for different banks operating in the same sector in India. More testing of DBSQual is required across various different contexts for validity augmentation. In addition, findings would be more reliable if the non-Indian context could be taken into consideration. Thus, such limitations open a window for future research.

Practical implications

This study is quite fruitful for the banking organizations in measuring their online services, and enables them to implement their marketing and operational strategies more effectively and efficiently.

Originality/value

The contribution of this study is the development and validation of a new instrument that is DBSQual that contains seven determinants of customers' e-service quality perception, emphasis on measuring online service quality in the Indian banking sector. These determinants will offer banks a promising starting idea for establishing an effective quality management for their online businesses. They will be able to increase the opportunities by tapping themselves at a competitive edge.
Negotiating mental illness across the lay‐professional divide: Role play in peer work consultations
Authors: Kessing Malene Lue , Mik‐Meyer Nanna
Published: March 2022

Patient involvement is a prominent policy aim in modern health care. Today, mental health services employ peer workers (PWs) who have personal experiences with mental illness. Based on 22 interviews with PWs and 26 audio recordings of real‐life consultations, we show how PWs talk about their personal experiences as professional qualifications. Furthermore, we demonstrate how in real‐life encounters, PWs and patients convert personal experiences into a professional approach through an interactionist role play that balance PWs role as former patients and current professionals. Our analysis shows that PWs combine the personal pronoun ‘I’ (stressing that it is personal) with the indefinite pronoun ‘one’ (referring to generalised patient experiences) when they recount illness experiences. This convey that PWs engage with mental illness as both a personal and professional topic. In addition, the analysis shows that PWs (and patients) use professional clues to manifest PWs’ positions as professionals. Overall, the article demonstrates that instead of focussing on authentic patient relationships, as previous research has done, it is beneficial to investigate peer work from a symbolic interactionist approach revealing how PWs and patients skilfully manoeuvre the contradictions embedded in the PWs’ dual role as former patients and current professionals.
International airports as agents of resilience
Authors: Horton Robert , Kiker Gregory A. , Trump Benjamin D. , Linkov Igor
Published: March 2022

The Dallas‐Fort Worth International Airport is used as an example of how traditional approaches of hardening isolated components of critical infrastructure against specific threats leaves critical assets exposed to significant, expensive, and unacceptable levels of cascading failure. Optimizing the entire airport supply chain requires the development of an interdisciplinary approach that incorporates the complexities of the airports' supply chain including numerous dependent, interdependent and independent relationships. Far greater return‐on‐investment will be yielded through resilience‐focused approaches that address the entire life cycle of disruptions including planning, absorption, recovery and adaptation.