bluuebunny/crossref_metadata_2025 huggingface dataset:
Beetles provide directed dispersal of viable spores of a keystone wood decay fungus
Authors: Lunde Lisa Fagerli , Boddy Lynne , Sverdrup-Thygeson Anne , Jacobsen Rannveig M. , Kauserud Håvard , Birkemoe Tone
Published: March 2022

Wood decay fungi are considered to be dispersed by wind, but dispersal by animals may also be important, and more so in managed forests where dead wood is scarce. We investigated whether beetles could disperse spores of the keystone species Fomitopsis pinicola. Beetles were collected on sporocarps and newly felled spruce logs, a favourable habitat for spore deposition. Viable spores (and successful germination) of F. pinicola were detected by dikaryotization of monokaryotic bait mycelium from beetle samples. Viable spores were on the exoskeleton and in the faeces of all beetles collected from sporulating sporocarps. On fresh spruce logs, nine beetle species transported viable spores, of which several bore into the bark. Our results demonstrate that beetles can provide directed dispersal of wood decay fungi. Potentially, it could contribute to a higher persistence of some species in fragmented forests where spore deposition by wind on dead wood is less likely.
MHC-I binding affinity derived metrics fail to predict tumor specific neoantigen immunogenicity
Authors: Nibeyro Guadalupe , Girotti Romina , Prato Laura , Moron Gabriel , Luján Hugo D. , Fernandez Elmer A.
Published: March 2022

Tumor-specific antigens emerging through somatic genomic rearrangements, known as neoantigens, play a critical role in current anticancer immunotherapy. They may or may not elicit an immune response when presented on the tumor cell surface bound to the MHC-I molecule, whose strength has been assumed as an indicator of immunogenicity. Several in silico peptide-MHC-I binding affinity predictors are used to prioritize putative immunogenic neoantigens to be experimentally and clinically explored either as biomarkers or targets for anticancer vaccines. This claims for a fair evaluation of such predictors, making essential the development of appropriate databases with experimentally validated, immunogenic/non-immunogenic neoantigens. Thus far, such a database is lacking. We herein present ITSNdb, a new and curated immunogenic neoantigen database and use it to benchmark current neoantigen immunogenicity predictors. Benchmark results failed to support the application of the predicted peptide- MHC-I binding affinity or its derived metrics as a tool to estimate neoantigen immunogenicity and the tumor neoantigen burden as an immunotherapy response biomarker. Moreover, binding affinity based immunogenicity definition leads to identifying wild-type peptide counterparts as predictors of immunotherapy response. We demonstrate that MHC-I binding affinity is insufficient to define neoantigen immunogenicity, despite being necessary for neoantigen tumor cell presentation suggesting that a paradigm shift for the emergence of new rules to identify immunogenic neoantigens is required.
Eco-evolutionary dynamics of clonal multicellular life cycles
Authors: Ress Vanessa , Traulsen Arne , Pichugin Yuriy
Published: March 2022

The evolution of multicellular life cycles is a central process in the course of the emergence of multicellularity. The simplest multicellular life cycle is comprised from the growth of the propagule into a colony and its fragmentation to give rise to new propagules. The majority of theoretical models assume selection among life cycles to be driven by internal properties of multicellular groups resulting in growth competition. At the same time, the influence of interactions between groups on the evolution of life cycles is rarely even considered. Here, we present a model of colonial life cycles evolution taking into account group interactions. Our work shows that the outcome of evolution could be coexistence between multiple life cycles or that the outcome may depend on the initial state of the population – scenarios impossible without group interactions. At the same time, we found that some results of these simpler models remain relevant: Evolutionary stable strategies in our model are restricted to binary fragmentation – the same class of life cycles which contains all evolutionarily optimal life cycles in the model without interactions. Our results demonstrate that while models neglecting interactions can capture short-term dynamics, they fall short in predicting the population-scale picture of the evolution.
Brain Capillary Pericytes are Metabolic Sentinels that Control Blood Flow through KATP Channel Activity
Authors: Hariharan Ashwini , Robertson Colin D. , Garcia Daniela C.G. , Longden Thomas A.
Published: March 2022

Capillary pericytes and their processes cover ∼90% of the total length of the brains capillary bed. Despite their abundance, little is known of pericyte function, and their contributions to the control of brain hemodynamics remain unclear. Here, we report that deep capillary pericytes possess a mechanistic ‘energy switch’ that, when activated by a decrease in glucose, elicits robust KATP channel activation to increase blood flow and protect energy substrate availability. We demonstrate that pharmacological activation of KATP channels profoundly hyperpolarizes capillary pericytes and leads to dilation of upstream penetrating arterioles and arteriole-proximate capillaries covered with contractile pericytes, leading to an increase in local capillary blood flow. Stimulation of a single capillary pericyte with a KATP channel agonist is sufficient to evoke this response, which is mediated via KIR channel-dependent retrograde propagation of hyperpolarizing electrical signals. Genetic inactivation of pericyte KATP channels via expression of a dominant-negative version of KIR6.1 eliminates these effects. Critically, we show that lowering extracellular glucose below 1 mM evokes dramatic KATP channel-mediated pericyte hyperpolarization. Inhibiting glucose uptake by blocking GLUT1 transporters in vivo also activates this energy switch to increase pericyte KATP channel activity, dilate arterioles and increase blood flow. Together, our findings recast capillary pericytes as metabolic sentinels that respond to local energy deficits by robustly increasing blood flow to protect metabolic substrate delivery to neurons and prevent energetic shortfalls.
Age-dependent lipid droplet-rich microglia worsen stroke outcome in old mice
Authors: Arbaizar-Rovirosa Maria , Gallizioli Mattia , Pedragosa Jordi , Lozano Juan J. , Casal Carme , Pol Albert , Planas Anna M.
Published: March 2022

Microglial cells of the aged brain manifest signs of dysfunction that could contribute to the worse neurological outcome of stroke in the elderly. Treatment with colony-stimulating factor-1 receptor antagonists enable transient microglia depletion that can be followed by microglia repopulation after interruption of the treatment, causing no known harm to mice. Using this strategy, we aimed to restore microglia function and ameliorate stroke outcome in aged mice. Cerebral ischemia/reperfusion induces strong innate immune responses in microglia highlighted by prominent type I interferon signaling, together with cellular metabolic perturbances and lipid droplet biogenesis in young mice. In aged mice, a subset of microglia accumulates lipid droplets under steady state and displays exacerbated innate immune responses after stroke. Microglia renewal in old mice reduces the lipid droplet content, prevents the ischemia-induced exaggerated type I interferon response, and improves the neurological outcome of stroke. This study shows that age-dependent lipid droplet-enriched microglia contribute to impair stroke outcome in old mice.
Systematic evaluation of chromatin immunoprecipitation sequencing to study histone occupancy in dormancy transitions of grapevine buds
Authors: Hermawaty Dina , Cahn Jonathan , Chabikwa Tinashe G. , Lister Ryan , Considine Michael J.
Published: March 2022

1.

The regulation of DNA accessibility by histone modification has emerged as a paradigm of developmental and environmental programming. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is a versatile tool widely used to investigate in vivo protein-DNA interaction. The technique has been successfully demonstrated in several plant species and tissues; however, it has remained challenging in woody tissues. Here we developed a ChIP method specifically for mature dormant grapevine buds (Vitis vinifera cv. Cabernet Sauvignon). Each step of the protocol was systematically optimised, including crosslinking, chromatin extraction, sonication, and antibody validation. Analysis of histone H3-enriched DNA was performed to evaluate the success of the protocol and identify occupancy of histone H3 along grapevine bud chromatin. To our best knowledge, this is the first ChIP experiment protocol optimised for grapevine bud system.
Pre-Existing Comorbidities Diminish the Likelihood of Seropositivity After SARS-CoV-2 Vaccination
Authors: Amraotkar Alok R. , Bushau-Sprinkle Adrienne M. , Keith Rachel J. , Hamorsky Krystal T. , Palmer Kenneth E. , Gao Hong , Rai Shesh N. , Bhatnagar Aruni
Published: March 2022

Background

The impact of chronic health conditions (CHC) on serostatus post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is unknown.

Methods

We assessed serostatus post-SARS-CoV-2 vaccination among fully vaccinated adult residents of Jefferson County, Kentucky, USA from April 2021 through August 2021. Serostatus was determined by qualitative analysis of SARS-CoV-2 specific Spike IgG antibodies via enzyme-linked immunoassay (ELISA) in peripheral blood samples.

Results

Of the 5,178 fully vaccinated participants, 51 were seronegative and 5,127 were seropositive. Chronic kidney disease (CKD) and autoimmune disease showed highest association with negative serostatus in fully vaccinated individuals. The absence of any CHC was strongly associated with positive serostatus. The risk of negative serostatus increased as the total number of pre-existing CHCs increased. Similarly, use of 2 or more CHC related medications was associated with seronegative status.

Conclusions

Presence of any CHC, especially CKD or autoimmune disease, increased the likelihood of seronegative status among individuals who were fully vaccinated to SAR-CoV-2. This risk increased with a concurrent increase in number of comorbidities, especially with multiple medications. Absence of any CHC was protective and increased the likelihood of a positive serological response. These results will help develop appropriate guidelines for booster doses and targeted vaccination programs.
COVID-19 Vaccine Hesitancy among Marginalized Populations in the U.S. and Canada: Protocol for a Scoping Review
Authors: Newman Peter A. , Reid Luke , Tepjan Suchon , Fantus Sophia , Allan Kate , Nyoni Thabani , Guta Adrian , Williams Charmaine C.
Published: March 2022

Introduction

Despite the development of safe and highly efficacious COVID-19 vaccines, extensive barriers to vaccine deployment and uptake threaten the effectiveness of vaccines in controlling the pandemic. Notably, marginalization produces structural and social inequalities that render certain populations disproportionately vulnerable to COVID-19 incidence, morbidity, and mortality, and less likely to be vaccinated. The purpose of this scoping review is to provide a comprehensive overview of definitions/conceptualizations, elements, and determinants of COVID-19 vaccine hesitancy among marginalized populations in the U.S. and Canada.

Materials and Methods

The proposed scoping review follows the framework outlined by Arksey and O’Malley, and further developed by the Joanna Briggs Institute. It will comply with reporting guidelines from the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The overall research question is: What are the definitions/conceptualizations and factors associated with vaccine hesitancy in the context of COVID-19 vaccines among adults from marginalized populations in the U.S. and Canada. Search strategies will be developed using controlled vocabulary and selected keywords, and customized for relevant databases, in collaboration with a research librarian. The results will be analyzed and synthesized quantitatively (i.e., frequencies) and qualitatively (i.e., thematic analysis) in relation to the research questions, guided by a revised WHO Vaccine Hesitancy Matrix.

Discussion

This scoping review will contribute to honing and advancing the conceptualization of COVID-19 vaccine hesitancy and broader elements and determinants of underutilization of COVID-19 vaccination among marginalized populations, identify evidence gaps, and support recommendations for research and practice moving forward.
Mutation-Attention (MuAt): deep representation learning of somatic mutations for tumour typing and subtyping
Authors: Sanjaya Prima , Waszak Sebastian M. , Stegle Oliver , Korbel Jan O. , Pitkänen Esa
Published: March 2022

Cancer genome sequencing enables accurate classification of tumours and tumour sub-types. However, prediction performance is still limited using exome-only sequencing and for tumor types with low somatic mutation burden such as many pediatric tumours. Moreover, the ability to leverage deep representation learning in discovery of tumour entities remains unknown. We introduce here Mutation-Attention (MuAt), a deep neural network to learn representations of simple and complex somatic alterations for prediction of tumour types and subtypes. MuAt achieved prediction accuracy of 89% for whole genomes (24 tumour types) and 64% for whole exomes (20 types), and a top-5 accuracy of 97% and 90%, respectively. Tumour representations learnt by MuAt included tumour entities such as acral melanoma, SHH-activated medulloblastoma, SPOP-associated prostate cancer, microsatellite instability, and MUTYH-associated pancreatic endocrine tumours although these tumour subtypes and subgroups were not used as training labels. Integrated representations of somatic alterations hold significant potential to drive discovery of novel tumour entities and clinical application.
Epistatic Modifiers Influence the Expression of Continual Flowering in Strawberry
Authors: Cockerton Helen Maria , Nellist Charlotte Florence , Hytönen Timo , Litthauer Suzanne , Hopson Katie , Whitehouse Adam , Sobczyk Maria , Harrison Richard Jonathan
Published: March 2022

Previous work within the community led to the identification of a single dominant allele that controls the everbearing trait. However, frequent observations have indicated that crosses do not segregate in a Mendelian fashion, as would be expected for a trait controlled by a single dominant gene. Therefore, it was hypothesised that one or more unidentified epistatic alleles interact with the major gene.

A GWAS was conducted on 587 June-bearers and 207 everbearers to assess the genetic components associated with flowering habit. The segregation ratios of parental strawberry lines with known phenotypes were used to validate the identified alleles.

Three loci including the known, major FaPFRU locus and two epistatic modifiers were identified. These modifiers function as enhancers of the everbearing trait in individuals containing a single copy of the FaPFRU everbearing allele and appear to be functionally redundant. Principally, heterozygous individuals required the presence of two modifying alleles in order to allow expression of the everbearing trait.

Inclusion of the epistatic alleles improved the prediction of everbearing segregation ratios, beyond that of a single allele model, however, a large proportion of the variation remained unexplained. Future work should identify the additional repressor and enhancer modifiers not identified here. Discovering the genetic components controlling the everbearing trait can enable genetic informed strawberry improvement.

Society Impact Statement

Until the 1970s, the majority of commercial strawberry varieties produced a single bloom of flowers. However, continuously flowering, everbearing strawberries are now routinely cultivated and use is increasing. Indeed, introgression of the everbearing flowering trait can lead to economic benefits for growers through the production of a continual crop from the same plant. Utilising genetic guided improvement has the power to streamline everbearing generation. As such, utilising the genetic markers reported here, can help to identify everbearing individuals at an early time point in the breeding process. Furthermore, these markers can help to improve the predictions of progeny segregation ratios.
Segregational instability of multicopy plasmids: a population genetics approach
Authors: Pina V Miró , Hernández JCR , Siri-Jégousse A , Peña-Miller R , Palau S , González Casanova A
Published: March 2022

Plasmids are extra-chromosomal genetic elements that encode a wide variety of phenotypes and can be maintained in bacterial populations through vertical and horizontal transmission, thus increasing bacterial adaptation to hostile environmental conditions like those imposed by antimicrobial sub-stances. To circumvent the segregational instability resulting from randomly distributing plasmids between daughter cells upon division, non-transmissible plasmids tend to be carried in multiple copies per cell, with the added benefit of exhibiting increased gene dosage and resistance levels. But carrying multiple copies also results in a high metabolic burden to the bacterial host, therefore reducing the overall fitness of the population. This trade-off poses an existential question for plasmids: What is the optimal plasmid copy number? In this manuscript, we address this question by postulating and analyzing a population genetics model to evaluate the interaction between selective pressure, the number of plasmid copies carried by each cell, and the metabolic burden associated with plasmid bearing in the absence of selection for plasmid-encoded traits. Parameter values of the model were estimated experimentally usingEscherichia coliK12 carrying a multicopy plasmid encoding for a fluorescent protein andblaTEM-1, a gene conferring resistance toβ-lactam antibiotics. By numerically determining the optimal plasmid copy number for constant and fluctuating selection regimes, we show that plasmid copy number is a highly optimized evolutionary trait that depends on the rate of environmental fluctuation and balances the benefit between increased stability in the absence of selection with the burden associated with carrying multiple copies of the plasmid.
Genome-wide binding of Multiple ankyrin repeats single KH domain reveals its role in maintenance of gene activation by trithorax group proteins in Drosophila
Authors: Shaukat Ammad , Khan Muhammad Haider Farooq , Akhtar Jawad , Bakhtiari Mahnoor Hussain , Haseeb Muhammad Abdul , Mazhar Khalida , Umer Zain , Tariq Muhammad
Published: March 2022

The Trithorax group (trxG) proteins counteract repressive effect of Polycomb group (PcG) complexes and maintain transcriptional memory of active states of key developmental genes. Although, chromatin structure and modifications appear to play a fundamental role in this process, it is not clear how trxG prevents PcG-silencing and heritably maintain an active gene expression state. Here, we report a hitherto unknown role of Drosophila Multiple ankyrin repeats single KH domain (Mask), which emerged as one of the candidate trxG genes in our reverse genetic screen. The genome-wide binding profile of Mask correlates with known trxG binding sites across Drosophila genome. In particular, association of Mask at chromatin overlaps with CBP and H3K27ac, which are known hallmarks of actively transcribed genes by trxG. Importantly, Mask predominantly associates with actively transcribed genes in Drosophila. Depletion of Mask not only results in downregulation of trxG targets but also correlates with drastic reduction in H3K27ac levels and an increased H3K27me3 levels. The fact that MASK positively regulates H3K27ac levels in flies was also found to be conserved in human cells. Finally, strong suppression of Pc mutant phenotype by mutation in mask provides physiological relevance that Mask contributes to the anti-silencing effect of trxG, maintaining expression of key developmental genes. Since Mask is a downstream effector of multiple cell signaling pathways, we propose that Mask may connect cell signaling with chromatin mediated epigenetic cell memory governed by trxG.
Uterine injury during diestrus leads to embryo spacing defects and perturbations in the COX pathway in subsequent pregnancies
Authors: Zhang Elisa T. , Wells Kristen L. , Steinmetz Lars , Baker Julie C.
Published: March 2022

Uterine injury from procedures such as Cesarean sections (C-sections) often have severe consequences on subsequent pregnancy outcomes, leading to disorders such as placenta previa, placenta accreta, and infertility. With rates of C-section at approximately 30% of deliveries in the US and that are projected to continue to climb, a deeper understanding of the mechanisms by which these pregnancy disorders arise and opportunities for intervention are needed. However, there are no animal models to date that comprehensively assess the consequences of uterine injury. Here we describe a rodent model of uterine injury on subsequent in utero outcomes. We observed three distinct phenotypes: increased rates of resorption and death, embryo spacing defects, and placenta accreta-like features of reduced decidua and expansion of invasive trophoblasts. We show that the appearance of embryo spacing defects depends entirely on the phase of estrous cycle at the time of injury. Using RNA-seq, we identified perturbations in the expression of components of the COX/prostaglandin pathway after recovery from injury, a pathway that has previously been demonstrated to play an important role in embryo spacing. Therefore, we demonstrate that uterine damage in this mouse model causes morphological and molecular changes, most notably perturbed expression of COX/prostaglandin pathway-related genes, that ultimately lead to placental and embryonic developmental defects.
Tales of Two α-Carboxysomes: the Structure and Assembly of Cargo Rubisco
Authors: Ni Tao , Sun Yaqi , Seaton-Burn William , Al-Hazeem Monsour M. J. , Zhu Yanan , Yu Xiulian , Liu Lu-Ning , Zhang Peijun
Published: March 2022

Carboxysomes are a family of bacterial microcompartments in cyanobacteria and chemoautotrophs. It encapsulates carbonic anhydrase and Ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalysing carbon fixation inside a proteinaceous shell. How Rubisco packs into the carboxysomes is unknown. Using cryo-electron tomography and subtomogram averaging, we present 3D organization of Rubisco inside two types of native α-carboxysomes from a marine α-cyanobacterium Cyanobium sp. PCC 7001 and a chemoautotrophic bacterium Halothiobacillus neapolitanus. We determined the structures of Rubiscos within native Halothiobacillus and Cyanobium carboxysomes at 3.3 Å and 3.8 Å resolution respectively and further identified an associated CsoS2 segment. Interestingly, CsoS2 is only associated with a sub-population of Rubiscos that are close to the shell in Halothiobacillus, but with all Rubiscos throughout Cyanobium carboxysome. Moreover, Rubiscos in Cyanobium carboxysomes are organized in three concentric layers whereas Rubiscos in Halothiobacillus carboxysomes are arranged in spiral arrays. Calcium treatment induced a drastic re-organization of Rubiscos, converting these two distinct assemblies into ordered lattice arrays in both α-carboxysomes. Our findings provide critical knowledge of the assembly principles of α-carboxysomes, which may aid in rational design and repurpose of carboxysome structures for new functions.
Validating methods to eradicate Select Agent and phylotype I Ralstonia solanacearum strains reveals that growth in planta increases bacterial stress tolerance
Authors: Hayes Madeline M. , Dewberry Ronnie J. , Babujee Lavanya , Moritz Rebecca , Allen Caitilyn
Published: March 2022

Ralstonia solanacearum is a destructive pathogen that causes bacterial wilt disease of diverse crops. Wilt disease prevention and management is difficult because R. solanacearum persists in soil, water, and plant material. Growers need practical methods to kill R. solanacearum in irrigation water, a common source of disease outbreaks. Additionally, the Race 3 biovar 2 (R3bv2) subgroup is a quarantine pest in many countries and a highly regulated U.S. Select Agent. Plant protection officials and researchers need validated protocols to eradicate R. solanacearum for regulatory compliance. To meet these needs, we measured survival of four R3bv2 and three phylotype I R. solanacearum strains following treatment with hydrogen peroxide, stabilized hydrogen peroxide (HuwaSan), active chlorine, heat, ultraviolet radiation, and desiccation. No surviving R. solanacearum cells were detected after cultured bacteria were exposed for ten minutes to 400 ppm hydrogen peroxide, 50 ppm HuwaSan, 50 ppm active chlorine, or temperatures above 50°C. R. solanacearum cells on agar plates were eradicated by 30s UV irradiation and killed by desiccation on most biotic and all abiotic surfaces tested. R. solanacearum did not survive the cell lysis steps of four nucleic acid extraction protocols. However, bacteria in planta were more difficult to kill. Stems of infected tomato plants contained a subpopulation of bacteria with increased tolerance of heat and UV light, but not oxidative stress. This result has significant management implications. We demonstrate the utility of these protocols for compliance with Select Agent research regulations and for management of a bacterial wilt outbreak in the field.

Importance

Ralstonia solanacearum, a globally distributed wilt pathogen of many high-value crops, is spread via diseased plant material and contaminated soil, tools, and irrigation water. The Race 3 biovar 2 Select Agent subgroup of R. solanacearum is subject to stringent and constantly evolving regulations intended to prevent pathogen introduction or release. We validated eradication and inactivation methods that can be used by: 1) growers seeking to disinfest water and manage bacterial wilt disease outbreaks; 2) researchers who must remain in compliance with regulations; and 3) regulators who are expected to define containment practices. Relevant to all these stakeholders, we show that while cultured R. solanacearum cells are sensitive to relatively low levels of oxidative chemicals, dessication, and heat, more aggressive treatment such as autoclaving or incineration is required to eradicate R. solanacearum cells growing inside plant material.
Evolution of transposable element-derived enhancer activity
Authors: Du Alan Y. , Zhuo Xiaoyu , Sundaram Vasavi , Jensen Nicholas O. , Chaudhari Hemangi G. , Saccone Nancy L. , Cohen Barak A. , Wang Ting
Published: March 2022

Many transposable elements (TEs) contain transcription factor binding sites and are implicated as potential regulatory elements. However, TEs are rarely functionally tested for regulatory activity, which in turn limits our understanding of how TE regulatory activity has evolved. We systematically tested the human LTR18A subfamily for regulatory activity using massively parallel reporter assay (MPRA) and found AP-1 and C/EBP-related binding motifs as drivers of enhancer activity. Functional analysis of evolutionarily reconstructed ancestral sequences revealed that LTR18A elements have generally lost regulatory activity over time through sequence changes, with the largest effects occurring due to mutations in the AP-1 and C/EBP motifs. We observed that the two motifs are conserved at higher rates than expected based on neutral evolution. Finally, we identified LTR18A elements as potential enhancers in the human genome, primarily in epithelial cells. Together, our results provide a model for the origin, evolution, and co-option of TE-derived regulatory elements.
The effect of waning on antibody levels and memory B cell recall following SARS-CoV-2 infection or vaccination
Authors: Forgacs David , Moraes Vanessa S. , Hanley Hannah B. , Gattiker Jasper L. , Jefferson Alexandria M. , Ross Ted M.
Published: March 2022

As of March 2022, there have been over 450 million reported SARS-CoV-2 cases worldwide, and more than 4 billion people have received their primary series of a COVID-19 vaccine. In order to longitudinally track SARS-CoV-2 antibody levels in people after vaccination or infection, a large-scale COVID-19 sero-surveillance progam entitled SPARTA (SeroPrevalence and Respiratory Tract Assessment) was established early in the pandemic. Anti-RBD antibody levels were tracked in more than 1,000 people. There was no significant decrease in antibody levels during the first 14 months after infection in unvaccinated participants, however, significant waning of antibody levels was observed following vaccination, regardless of previous infection status. Moreover, participants who were pre-immune to SARS-CoV-2 prior to vaccination seroconverted to significantly higher antibody levels, and antibodies were maintained at significantly higher levels than in previously infected, unvaccinated participants. This pattern was entirely due to differences in the magnitude of the initial seroconversion event, and the rate of antibody waning was not significantly different based on the pre-immune status. Participants who received a third (booster) dose of an mRNA vaccine not only increased their anti-RBD antibody levels ∼14-fold, but they also had ∼3 times more anti-RBD antibodies compared to the peak of their antibody levels after receiving their primary vaccine series. In order to ascertain whether the presence of serum antibodies is important for long-term seroprotection, PBMCs from 13 participants who lost all detectable circulating antibodies after vaccination or infection were differentiated into memory cells in vitro. There was a significant recall of memory B cells in the absence of serum antibodies in 70% of the vaccinated participants, but not in any of the infected participants. Therefore, there is a strong connection between anti-RBD antibody levels and the effectiveness of memory B cell recall.
A coevolution experiment reveals parallel mutations in the AcrA-AcrB-TolC efflux pump that contributes to bacterial antibiotic resistance
Authors: Chodkowski John L. , Shade Ashley
Published: March 2022

One interference mechanism of bacterial competition is the production of antibiotics. Bacteria exposed to antibiotics can resist antibiotic inhibition through intrinsic and/or acquired mechanisms. Here, we performed a coevolution experiment to understand long-term consequences of antibiotic production and antibiotic resistance for two environmental bacterial strains. We grew five independent lines of the antibiotic-producing environmental strain, Burkholderia thailandensis E264, and the antibiotic-inhibited environmental strain, Flavobacterium johnsoniae UW101, together and separately on agar plates for 7.5 months (1.5 month incubations), transferring each line five times to new agar plates. We first observed that the F. johnsoniae ancestor could tolerate the B. thailandensis-produced antibiotic through efflux mechanisms. We then sequenced the genomes of clonal isolates from the coevolved and monoculture F. johnsoniae lines, and uncovered mutational ramifications to the long-term antibiotic exposure. The coevolved genomes from F. johnsoniae revealed four potential mutational signatures of antibiotic resistance that were not observed in the evolved monoculture lines. Two mutations were found in tolC: one corresponding to a 33 bp deletion and the other corresponding to a nonsynonymous mutation. A third mutation was observed as a 1 bp insertion coding for a RagB/SusD nutrient uptake protein. The last mutation was a G83R nonsynonymous mutation in acetyl-coA carboxylayse carboxyltransferase subunit alpha (AccA). Placing the tolC 33 bp deletion back into the F. johnsoniae ancestor conferred some antibiotic resistance, but not to the degree of resistance observed in coevolved lines. Furthermore, the accA mutation matched a previously described mutation conferring resistance to B. thailandensis-produced thailandamide. Analysis of B. thailandensis transposon mutants for thailandamide production revealed that thailandamide was bioactive against F. johnsoniae, but also suggested that additional B. thailandensis-produced antibiotics were involved in the inhibition of F. johnsoniae. This study reveals how long-term interspecies chemical interactions can result in a novel mutation in efflux that contribute to antibiotic resistance.
The DNA methylation landscape of the human oxytocin receptor gene (OXTR): Recommendations for future research
Authors: Müller Svenja , Sicorello Maurizio , Moser Dirk , Frach Leonard , Limberg Alicia , Gumpp Anja M. , Ramo-Fernandez Laura , Köhler-Dauner Franziska , Fegert Joerg M. , Waller Christiane , Kumsta Robert , Kolassa Iris-Tatjana
Published: March 2022

The oxytocin receptor gene (OXTR) is of interest when investigating the effects of early adversity on DNA methylation. However, there is heterogeneity regarding the selection of the most promising CpG sites to target for analyses. The goal of this study was to determine functionally relevant clusters of CpG sites within the OXTR CpG island in 113 mother-infant dyads, with 58 of the mothers having experienced childhood maltreatment (CM). OXTR DNA methylation and gene expression was analyzed in peripheral/umbilical blood mononuclear cells. Different complexity reduction approaches were used to reduce the 188 CpG sites into clusters of co-methylated sites. Furthermore, associations between OXTR DNA methylation (cluster- and site-specific level) and OXTR gene expression and CM were investigated. Results showed that, first, CpG sections differed strongly regarding their statistical utility for research of individual differences in DNA methylation. Second, cluster analyses and Partial Least Squares (PLS) suggested two clusters consisting of intron1/exon2 and the protein-coding region of exon 3, respectively, as most strongly associated with outcome measures. Third, cross-validated PLS regression explained 7% of variance in CM, with low cross-validated variance explained for the prediction of gene expression. Fourth, very high mother-child correspondence was observed in correlation patterns within the identified clusters, but only modest correspondence outside these clusters. This study characterized the DNA methylation landscape of the OXTR CpG island by highlighting clusters of CpG sites that show desirable statistical properties and predictive value. We provide a Companion Web Application to guide future studies in their choice of CpG sites.
Carbon dots boost dsRNA delivery in plants and increase local and systemic siRNA production
Authors: Delgado-Martín Josemaría , Delgado-Olidén Alejo , Velasco Leonardo
Published: March 2022

Carbon dots (CDs) have been proposed for nucleic acid delivery in many biological applications. In this work we have obtained carbon dots by a hydrothermal synthesis method for developing nanocomposites with dsRNA. These CDs were produced using glucose or saccharose as the nucleation source and passivated with branched polyethyleneimines for conferring positive charges. Hydrodynamic analyses and transmission electron microscopy TEM showed that they sized on average 4 and 5 nm, depending on the sugar. The CDs were fluorescent and showed a peak at 468 nm when excited with UV light. Physicochemical characteristics of their surfaces were revealed by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FT-IR). The ζ potential determined that both types of CDs had positive charges as well as good electrophoretic mobility and conductivity. Coating of the CDs to dsRNA was efficient but did not protect from nucleases. DsRNA naked or coated with the CDs were delivered to leaves of cucumber plants by spraying at 2.5 bar. Quantitation of the dsRNA that entered the leaves showed that when coated with the CDs, 50-fold more dsRNA was detected than when naked dsRNA was applied. Moreover, specific siRNAs derived from the sprayed dsRNAs were 130 times more abundant when the dsRNA was coated with the CDs. Systemic dsRNAs were determined in distal leaves showing a dramatic increase in concentration when delivered as a nanocomposite. Similarly, systemic siRNAs were significantly more abundant in distal leaves when spraying with the CD-dsRNA nanocomposite. Furthermore, FITC-labeled dsRNA was shown to accumulate in the apoplast and increase its entry in the plant when coated with CDs. These results indicate that CDs obtained by hydrothermal synthesis are suitable for dsRNA foliar delivery in RNAi plant applications and provide insight into CD-dsRNA translocations.
The pyruvate dehydrogenase complex regulates matrix protein phosphorylation and mitophagic selectivity
Authors: Kolitsida Panagiota , Nolic Vladimir , Zhou Jianwen , Stumpe Michael , Niemi Natalie M. , Dengjel Jörn , Abeliovich Hagai
Published: March 2022

The mitophagic degradation of mitochondrial matrix proteins inS. cerevisiaewas previously shown to be selective, reflecting a pre-engulfment sorting step within the mitochondrial network. This selectivity is regulated through phosphorylation of mitochondrial matrix proteins by the matrix kinases Pkp1 and Pkp2, which in turn appear to be regulated by the phosphatase Aup1/Ptc6. However, these same proteins also regulate the phosphorylation status and catalytic activity of the yeast pyruvate dehydrogenase complex, which is critical for mitochondrial metabolism. To understand the relationship between these two functions, we evaluated the role of the pyruvate dehydrogenase complex in mitophagic selectivity. Surprisingly, we identified a novel function of the complex in regulating mitophagic selectivity, which is independent of its enzymatic activity. Our data support a model in which the pyruvate dehydrogenase complex directly regulates the activity of its associated kinases and phosphatases. This regulatory interaction then determines the phosphorylation state of mitochondrial matrix proteins and their mitophagic fates.
Long-term T cell perturbations and waning antibody levels in individuals needing hospitalization for COVID-19
Authors: Govender Melissa , Hopkins Francis R. , Göransson Robin , Svanberg Cecilia , Shankar Esaki M. , Hjorth Maria , Augustinsson Åsa Nilsdotter , Sjöwall Johanna , Nyström Sofia , Larsson Marie
Published: March 2022

COVID-19 is being extensively studied, and much remains unknown regarding the long-term consequences of the disease on immune cells. The different arms of the immune system are interlinked, with humoral responses and the production of high-affinity antibodies being largely dependent on T cell immunity. Here, we longitudinally explored the effect COVID-19 has on T cell populations and the virus-specific T cells, as well as neutralizing antibody responses, for 6-7 months following hospitalization. The CD8+ TEMRA and exhausted CD57+CD8+ T cells were markedly affected with elevated levels that lasted long into convalescence. Further, markers associated with T-cell activation were upregulated at the inclusion, and in the case of CD69+CD4+ T cells this lasted all through the study duration. The levels of T cells expressing negative immune checkpoint molecules were increased in COVID-19 patients and sustained for a prolonged duration following recovery. Within 2-3 weeks after symptom onset, all COVID-19 patients developed anti-nucleocapsid IgG and spike-neutralizing IgG as well as SARS-CoV-2-specific T cell responses. In addition, we found alterations in follicular T helper (TFH) cell populations, such as enhanced TFH-TH2 following recovery from COVID-19. Our study revealed significant and long-term alterations in T cell populations and key events associated with COVID-19 pathogenesis.
Invasion genetics of the longhorn crazy ant: the global expansion of a double-clonal reproduction system
Authors: Tseng Shu-Ping , Darras Hugo , Hsu Po-Wei , Yoshimura Tsuyoshi , Lee Chow-Yang , Wetterer James K. , Keller Laurent , Yang Chin-Cheng Scotty
Published: March 2022

Reproduction mode represents a key determinant for success of biological invasion as it influences the genetic variation and evolutionary potential of introduced populations. The world’s most widespread invasive ant, Paratrechina longicornis, was found to display an unusual double-clonal reproduction system, whereby both males and queens were produced clonally, while workers are produced sexually. Despite its worldwide distribution, the origin of this ant species and the prevalence of the double-clonal reproductive system across the ant’s geographic range remain unknown. To retrace the evolutionary history of this global invasive species and its reproductive system, we examined genetic variation and characterized the mode of reproduction of P. longicornis sampled worldwide using both microsatellite genotyping and mitochondrial DNA sequencing approaches. Analyses of global genetic variations indicate that the Indian subcontinent is a genetic diversity hotspot of this species, suggesting that this geographic area is at least part of its native range. Our analyses revealed that inferred native and introduced populations both exhibit double-clonal reproduction. Remarkably, queens and males worldwide belong to two separate, non-recombining clonal lineages. Workers are highly heterozygous and first-generation inter- lineage hybrids, a pattern strongly supportive of a strict worldwide prevalence of double clonality. By maintaining heterozygosity in the worker force, this unusual genetic system allows P. longicornis to avoid inbreeding during colonization bottlenecks and may have acted as an adaptive trait linked to the species’ invasion success.
Barriers to external knowledge search for innovation: empirical evidence from the Korean manufacturing industry
Authors: Mun Hee Jin
Published: March 2022

Purpose

This study focuses on resolving empirical inconsistencies in the relationship between external search breadth and innovation performance. Based on research on the knowledge-based view and innovation barriers, three internal barriers that weaken the effectiveness of external search breadth are discerned: information, rigidity and financial barriers.

Design/methodology/approach

For empirical analysis, the Korean Innovation Survey 2016 of manufacturing firms was utilized. This study defines innovation performance as the number of patent applications and new product introduction that are analyzed through zero-inflated negative binomial and logistic regressions, respectively.

Findings

The empirical analysis showed three findings. First, external search breadth has a positive relationship with the number of patent applications but not with new product introduction. Second, financial barrier weakens the positive association of external search breadth with the number of patent applications. Third, the interactions of external search breadth with the three internal barriers are negatively related to new product introduction.

Originality/value

This study makes two theoretical contributions. First, by examining barriers to external knowledge search, this research helps identify potential bottlenecks in this search. Second, the study reveals that the effectiveness of external search breadth may have a boundary in firm innovation by showing that this search affects patent application and new product introduction differently.
Shared transformational leadership and emergent team processes: determinants of team viability and team satisfaction
Authors: Prabhu Nandan , Modem Roopa
Published: March 2022

Purpose

The purpose of this study is to examine the effects of shared transformational leadership and its components on team viability and team satisfaction through the mediating processes of workplace spirituality and team trust, the emergent states of team processes.

Design/methodology/approach

This study is based on software project teams working in India’s information technology sector. The study adopts a cross-sectional research design to investigate the relationships between the study’s constructs.

Findings

This study shows varying effects of the components of shared transformational leadership on team viability and team satisfaction. The study has shown empirical evidence for the mediating role of workplace spirituality in the relationship between shared transformational leadership components and team effectiveness components. This study reveals the intervening roles of workplace spirituality and team trust in the relationship between shared transformational leadership as a unidimensional construct and team viability and effectiveness.

Research limitations/implications

Team rewards and team autonomy can cultivate a sense of community and trust among team members. Team trust facilitates autonomy, and workplace spirituality helps develop connectedness among team members.

Originality/value

This study has contributed to the research discourse on team effectiveness by demonstrating that workplace spirituality and team trust act as mediators in the relationship between shared transformational leadership and team effectiveness. This study has shown the relative strength of the effects of the components of shared transformational leadership on workplace spirituality, team viability and team satisfaction.
Using single impact metrics to assess research in business and economics: why institutions should use multi-criteria systems for assessing research
Authors: Olavarrieta Sergio
Published: March 2022

Purpose

Despite the general recommendation of using a combination of multiple criteria for research assessment and faculty promotion decisions, the raise of quantitative indicators is generating an emerging trend in Business Schools to use single journal impact factors (IFs) as key (unique) drivers for those relevant school decisions. This paper aims to investigate the effects of using single Web of Science (WoS)-based journal impact metrics when assessing research from two related disciplines: Business and Economics, and its potential impact for the strategic sustainability of a Business School.

Design/methodology/approach

This study collected impact indicators data for Business and Economics journals from the Clarivate Web of Science database. We concentrated on the IF indicators, the Eigenfactor and the article influence score (AIS). This study examined the correlations between these indicators and then ranked disciplines and journals using these different impact metrics.

Findings

Consistent with previous findings, this study finds positive correlations among these metrics. Then this study ranks the disciplines and journals using each impact metric, finding relevant and substantial differences, depending on the metric used. It is found that using AIS instead of the IF raises the relative ranking of Economics, while Business remains basically with the same rank.

Research limitations/implications

This study contributes to the research assessment literature by adding substantial evidence that given the sensitivity of journal rankings to particular indicators, the selection of a single impact metric for assessing research and hiring/promotion and tenure decisions is risky and too simplistic. This research shows that biases may be larger when assessment involves researchers from related disciplines – like Business and Economics – but with different research foundations and traditions.

Practical implications

Consistent with the literature, given the sensibility of journal rankings to particular indicators, the selection of a single impact metric for assessing research, assigning research funds and hiring/promotion and tenure decisions is risky and simplistic. However, this research shows that risks and biases may be larger when assessment involves researchers from related disciplines – like Business and Economics – but with different research foundations and trajectories. The use of multiple criteria is advised for such purposes.

Originality/value

This is an applied work using real data from WoS that addresses a practical case of comparing the use of different journal IFs to rank-related disciplines like Business and Economics, with important implications for faculty tenure and promotion committees and for research funds granting institutions and decision-makers.