bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between COVID-19 Risk-Mitigation Behaviors and Specific Mental Disorders in Youth
Authors: Conway Kevin P. , Bhardwaj Kriti , Michel Emmanuella , Paksarian Diana , Nikolaidis Aki , Kang Minji , Merikangas Kathleen R. , Milham Michael P.
Published: March 2022

Importance

Although studies of adults show that pre-existing mental disorders increase risk for COVID–19 infection and severity, there is limited information about this association among youth. Mental disorders in general as well as specific types of disorders may influence their ability to comply with risk-mitigation strategies to reduce COVID-19 infection and transmission.

Objective

To examine associations between specific mental disorders and COVID-19 risk-mitigation practices among 314 female and 514 male youth.

Design

Youth compliance (rated as “Never,” “Sometimes,” “Often,” or “Very often/Always”) with risk mitigation was reported by parents on the CoRonavIruS Health Impact Survey (CRISIS) in January 2021. Responses were summarized using factor analysis of risk mitigation, and their associations with lifetime mental disorders (assessed via structured diagnostic interviews) were identified with linear regression analyses (adjusted for covariates). All analyses used R Project for Statistical Computing for Mac (v.4.0.5).

Setting

The Healthy Brain Network (HBN) in New York City Participants. 314 female and 514 male youth (ages 5-21)

Main Outcome(s) and Measure(s)

COVID-19 risk mitigation behaviors among youth

Results

A two-factor model was the best-fitting solution. Factor 1 (avoidance behaviors) included avoiding groups, indoor settings, and other peoples’ homes; avoidance was more likely among youth with any anxiety disorder (p=.01). Factor 2 (hygiene behaviors) included using hand sanitizer, washing hands, and maintaining social distance; practicing hygiene was less likely among youth with ADHD (combined type) (p=.02). Mask wearing, which did not load on either factor, was not associated with any mental health disorder.

Conclusion and Relevance

Findings suggest that education and monitoring of risk-mitigation strategies in certain subgroups of youth may reduce risk of exposure to COVID-19 and other contagious diseases. Additionally, they highlight the need for greater attention to vaccine prioritization for individuals with ADHD.

Key Points

Question

Are mental disorders among youth associated with COVID-19 risk-mitigation behaviors?

Findings

Based on the parent CoRonavIruS Health Impact Survey (CRISIS) of 314 females and 514 males aged 5-21, youth with anxiety disorders were more likely to avoid high-risk exposure settings, and those with ADHD (combined type) were less likely to follow hygiene practices. In contrast, mask wearing was not associated with youth mental disorders.

Meaning

Specific types of disorders in youth may interfere with their ability to employ risk-mitigation strategies that may lead to greater susceptibility to COVID-19.
Adiposity and the risk of dementia: mediating effects from inflammation and lipid levels
Authors: Karlsson Ida K , Zhan Yiqiang , Wang Yunzhang , Li Xia , Jylhava Juulia , Hagg Sara , Dahl Aslan Anna K , Gatz Margaret , Pedersen Nancy L , Reynolds Chandra A
Published: March 2022

Objective: While midlife adiposity is a risk factor for dementia, adiposity in late-life appears to be associated with lower risk. What drives the associations is poorly understood, especially the inverse association in late-life.
Methods: Using results from genome-wide association studies, we identified inflammation and lipid metabolism as biological pathways involved in both adiposity and dementia. To test if these factors mediate the effect of midlife and/or late-life adiposity on dementia, we then used cohort data from the Swedish Twin Registry, with measures of adiposity and potential mediators taken in midlife (age 40-64, n=5999) or late-life (age 65-90, n=7257). Associations between body-mass index (BMI), waist-hip ratio (WHR), C-reactive protein (CRP), lipid levels, and dementia were tested in survival and mediation analyses.
Results: One standard deviation (SD) higher WHR in midlife was associated with 25% (95% CI 2-52%) higher dementia risk, with slight attenuation when adjusting for BMI. No evidence of mediation through CRP or lipid levels was present. After age 65, one SD higher BMI, but not WHR, was associated with 8% (95% CI 1-14%) lower dementia risk. The association was partly mediated by higher CRP and suppressed by lower high-density lipoprotein.
Interpretation: The negative effects of midlife adiposity on dementia risk were driven directly by factors associated with body fat distribution, and not mediated by inflammation or lipid levels. There was an inverse association between late-life adiposity and dementia risk, especially where the body's inflammatory response and lipid homeostasis is intact.
Nanopore quality score resolution can be reduced with little effect on downstream analysis
Authors: Rivara-Espasandín Martín , Balestrazzi Lucía , Dufort y Álvarez Guillermo , Ochoa Idoia , Seroussi Gadiel , Smircich Pablo , Sotelo-Silveira José , Martín Álvaro
Published: March 2022

We investigate the effect of quality score information loss on downstream analysis from nanopore sequencing FASTQ files. We polished denovo assemblies for a mock microbial community and a human genome, and we called variants on a human genome. We repeated these experiments using various pipelines, under various coverage level scenarios, and various quality score quantizers. In all cases we found that the quantization of quality scores cause little difference on (or even improves) the results obtained with the original (non-quantized) data. This suggests that the precision that is currently used for nanopore quality scores is unnecessarily high, and motivates the use of lossy compression algorithms for this kind of data. Moreover, we show that even a non-specialized compressor, like gzip, yields large storage space savings after quantization of quality scores.
Reduced childhood social attention in an autism model marmoset predicts impaired social skills and inflexible behavior in adulthood
Authors: Nakagami Akiko , Yasue Miyuki , Nakagaki Keiko , Nakamura Madoka , Kawai Nobuyuki , Ichinohe Noritaka
Published: March 2022

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication impairments and restricted and repetitive behavior. Although currently no established cure exists for ASD, early intervention to the deficits of attention to other individuals is expected to reduce the progression of ASD symptoms in later life. In order to confirm this hypothesis and improve early therapeutic interventions, it is desirable to develop an animal model of ASD in which social attention is impaired in childhood and ASD-like social behavior is observed in adulthood. However, rodent models of ASD have difficulty in recapitulating the deficit of gaze-based social attention. In this study, we examined the direction of gaze towards other conspecifics during childhood and puberty in a three-chamber test setting using an ASD model of marmoset produced by maternal exposure to valproic acid (VPA). We also conducted a reversal learning test in an adult VPA-exposed marmoset as an indicator of perseveration, a core symptom of ASD that has not previously been investigated in this model. The results showed that time spent gazing at other conspecifics was reduced in VPA-exposed marmosets in childhood, and adults displayed rigidity of response. In a longitudinal study using the same animals, deficits in social attention in childhood correlated well with ASD-like social disturbance (inequity aversion and third-party reciprocity) and inflexible behavior in adulthood. Since VPA-exposed marmosets exhibit these diverse ASD-like behaviors that are coherent from childhood to adulthood, VPA-exposed marmosets will provide a valuable opportunity to elucidate mechanisms for early intervention and contribute to the development of early therapies.
Periventricular nodular heterotopia is functionally coupled with the neocortex during resting and task states
Authors: Gao Yayue , Chen Guanpeng , Teng Pengfei , Zhang Xin , Fang Fang , Englot Dario J. , Luan Guoming , Wang Xiongfei , Wang Qian
Published: March 2022

Periventricular nodular heterotopia (PVNH) is a well-defined developmental disorder characterized by failed neuronal migration, which forms ectopic neuronal nodules along the ventricular walls. Previous studies mainly focus on clinical symptoms caused by the PVNH tissue, such as seizures. However, little is known about whether and how neurons in the PVNH tissue functionally communicate with neurons in the neocortex. To probe this, we applied magnetoencephalography (MEG) and stereo-electroencephalography (sEEG) recordings to patients with PVNH during resting and task states. By estimating frequency-resolved phase coupling strength of the source-reconstructed neural activities, we found that the PVNH tissue was spontaneously coupled with the neocortex in the α to β frequency range, which was consistent with the synchronization pattern within the neocortical network. Furthermore, the coupling strength between PVNH and sensory areas effectively modulated the local neural activity in sensory areas. In both MEG and sEEG visual experiments, the PVNH tissue exhibited visual evoked responses, with a similar pattern and latency as the ipsilateral visual cortex. These findings demonstrate that PVNH is functionally integrated into cognition-related cortical circuits, suggesting a co-development perspective of ectopic neurons after their migration failure.
Thoracic crop formation is spatiotemporally coordinated with flight muscle histolysis during claustral colony foundation of a Lasius japonicus queen
Authors: Kurihara Yuta , Ogawa Kota , Chiba Yudai , Hayashi Yoshinobu , Miyazaki Satoshi
Published: March 2022

In a majority of ants, a newly mated queen independently founds a colony and claustrally raises her first brood without foraging outside the nest. During claustral independent colony foundation (ICF) in several ants, the esophagus of the founding queen expands and develops into a thoracic crop, which is then filled with a liquid substrate for larval feeding. It has been suggested that these substrates are converted from her body reserves (e.g., histolyzed flight muscles) or redistributed from a gastral crop. Here, we examined thoracic crop development in Lasius japonicus during claustral ICF. The foundresses claustrally fed their larvae from week 2 to 5 after ICF onset, and the first worker emerged at week 6. The development proceeded as follows: in week 0, foundress dorsal esophagus wall was pleated and thickened. Then, from week 2 to 5, the esophagus expanded dorsally toward where flight muscles had been present, following flight muscle histolysis. Gastral crop expansion followed esophagus expansion. Thus, thoracic crop formation may be spatiotemporally coordinated with flight muscle histolysis in Lasius japonicus queens, and similar developmental regulations might be common in other claustral ICF ants.
Deep Learning for MYC binding site recognition
Authors: Fioresi R. , Demurtas P. , Perini G.
Published: March 2022

Motivation

The definition of the genome distribution of the Myc transcription factor is extremely important since it may help predict its transcriptional activity particularly in the context of cancer. Myc is among the most powerful oncogenes involved in the occurrence and development of more than 80% of different types of pediatric and adult cancers. Myc regulates thousands of genes which can be in part different, depending on the type of tissues and tumours. Myc distribution along the genome has been determined experimentally through chromatin immunoprecipitation This approach, although powerful, is very time consuming and cannot be routinely applied to tumours of individual patients. Thus, it becomes of paramount importance to develop in-silico tools that can effectively and rapidly predict its distribution on a given cell genome. New advanced computational tools (DeeperBind) can then be successfully employed to determine the function of Myc in a specific tumour, and may help to devise new directions and approaches to experiments first and personalized and more effective therapeutic treatments for a single patient later on.

Results

The use of DeeperBind with DeepRAM on Colab platform can effectively predict the binding sites for the MYC factor with an accuracy above 0.96 AUC, when trained with multiple cell lines. The analysis of the filters in DeeperBind trained models shows, besides the consensus sequence CACGTG classically associated to the MYC factor, also the other consensus sequences G/C box or TGGGA, respectively bound by the SP1 and MIZ-1 transcription factors, which are known to mediate the MYC repressive response. Overall, our findings suggest a stronger sinergy between the machine learning tools as DeeperBind and biological experiments, which may reduce the time consuming experiments by providing a direction to guide them.
Host control and species interactions jointly determine microbiome community structure
Authors: Abbasi Eeman , Akçay Erol
Published: March 2022

1

The host microbiome can be considered an ecological community of microbes present inside a complex and dynamic host environment. The host is under selective pressure to ensure that its microbiome remains beneficial. The host can impose a range of ecological filters including the immune response that can influence the assembly and composition of the microbial community. How the host immune response interacts with the within-microbiome community dynamics to affect the assembly of the microbiome has been largely unexplored. We present here a mathematical framework to elucidate the role of host immune response and its interaction with the balance of ecological interactions types within the microbiome community. We find that highly mutualistic microbial communities characteristic of high community density are most susceptible to changes in immune control and become invasion prone as host immune control strength is increased. Whereas highly competitive communities remain relatively stable in resisting invasion to changing host immune control. Our model reveals that the host immune control can interact in unexpected ways with a microbial community depending on the prevalent ecological interactions types for that community. We stress the need to incorporate the role of host-control mechanisms to better understand microbiome community assembly and stability.
Control of contextual memory through interneuronal α5-GABAAreceptors
Authors: Zhu Mengwen , Abdulzahir Alifayaz , Perkins Mark G , Chu Chan C , Krause Bryan M , Casey Cameron , Lennertz Richard , Ruhl David , Hentschke Harald , Nagarajan Rajasekar , Chapman Edwin R , Rudolph Uwe , Fanselow Michael S , Pearce Robert A
Published: March 2022

γ-aminobutyric acid type A receptors that incorporate α5 subunits (α5-GABAARs) are highly enriched in the hippocampus and are strongly implicated in control of learning and memory. Receptors located on pyramidal neuron dendrites have long been considered responsible, but here we report that their selective knockout from either interneurons (α5-i-KO) or pyramidal neurons (α5-pyr-KO) interferes with the ability of the general anesthetic etomidate to suppress contextual conditioning. Using Ca2+imaging of CA1 pyramidal neuron activity in freely exploring mice to assess hippocampal function directly, we found that etomidate blocked the development of place cells and spatial engrams in wild type (WT) and α5-pyr-KO mice, but not in α5-i-KO mice. In addition, α5-i-KO mice developed weaker spatial engrams than WT mice under control conditions. These findings show that interneuronal α5-GABAARs serve a physiological role in promoting spatial learning, and that they mediate the suppression of hippocampus-dependent memory by etomidate.
Stimulation-Evoked Effective Connectivity (SEEC): An in-vivo approach for defining mesoscale corticocortical connectivity
Authors: Bundy David T. , Barbay Scott , Hudson Heather M. , Frost Shawn B. , Nudo Randolph J. , Guggenmos David J.
Published: March 2022

Background

Cortical electrical stimulation has been a versatile technique for examining the structure and function of cortical regions as well as for implementing novel therapies. While electrical stimulation has been used to examine the local spread of neural activity, it may also enable longitudinal examination of mesoscale interregional connectivity. Recent studies have used focal intracortical microstimulation (ICMS) with optical imaging to show cross-region spread of neural activity, but techniques are limited to utilizing hemodynamic responses within anesthetized preparations.

Objective

Here, we sought to use ICMS in conjunction with recordings of multi-unit action potentials to assess the mesoscale effective connectivity within sensorimotor cortex.

Methods

Neural recordings were made from multielectrode arrays placed into sensory, motor, and premotor regions during surgical experiments in three squirrel monkeys. During each recording, single-pulse ICMS was repeatably delivered to a single region. Mesoscale effective connectivity was calculated from ICMS-evoked changes in multi-unit firing.

Results

Multi-unit action potentials were able to be detected on the order of 1 ms after each ICMS pulse. Across sensorimotor regions, short-latency (< 2.5 ms) ICMS-evoked neural activity strongly correlated with known anatomic connections. Additionally, ICMS-evoked responses remained stable across the experimental period, despite small changes in electrode locations and anesthetic state.

Conclusions

These results show that monitoring ICMS-evoked neural activity, in a technique we refer to as Stimulation-Evoked Effective Connectivity (SEEC), is a viable way to longitudinally assess effective connectivity enabling studies comparing the time course of connectivity changes with the time course of changes in behavioral function.

Highlights

Short-latency neural responses to ICMS were evaluated in multiple cortical regions.

Neural responses strongly correlated with known anatomical connections.

Stimulation-evoked neural responses were maintained across repeated tests.

ICMS-evoked activity can show longitudinal changes in effective connectivity.
Development of a dual fluorescent reporter system in Clostridioides difficile reveals a division of labor between virulence and transmission gene expression
Authors: Donnelly M. Lauren , Shrestha Shailab , Ribis John , Kuhn Pola , Krasilnikov Maria , Feliciano Carolina Alves , Shen Aimee
Published: March 2022

The bacterial pathogen Clostridioides difficile causes gastroenteritis through its production of toxins and transmits disease through its production of resistant spores. Toxin and spore production are energy-expensive processes that are regulated by multiple transcription factors in response to many nutritional inputs. While toxin and sporulation genes are both heterogeneously expressed in only a subset of C. difficile cells, the relationship between these two sub-populations remains unclear. To address whether C. difficile coordinates the generation of these sub-populations, we developed a dual transcriptional reporter system that allows toxin and sporulation gene expression to be simultaneously visualized at the single-cell level using chromosomally-encoded mScarlet and mNeonGreen fluorescent transcriptional reporters. We then adapted an automated image analysis pipeline to quantify toxin and sporulation gene expression in thousands of individual cells in different media conditions and genetic backgrounds. These analyses revealed that toxin and sporulation gene expression rarely overlap during growth on agar plates, but broth culture increases this overlap in a manner dependent on the multifunctional RstA transcriptional regulator. Our results suggest that certain growth conditions promote a “division of labor” between transmission and virulence gene expression, highlighting how these subpopulations are influenced by environmental inputs. Given that recent work has revealed population-wide heterogeneity for numerous cellular processes in C. difficile, we anticipate that our dual reporter system will be broadly useful for determining the overlap in these subpopulations.

IMPORTANCE

Clostridioides difficile is an important nosocomial pathogen that causes severe diarrhea by producing toxins and is transmitted by producing spores. While both processes are crucial for C. difficile disease, only a subset of cells express toxins and/or undergo sporulation. Whether C. difficile coordinates the relationship between these energy-expensive processes remains unknown. We developed a dual fluorescent reporter system coupled with an automated image analysis pipeline to rapidly characterize expression two genes of interest across thousands of bacterial cells. Using this reporter system, we discovered that toxin and sporulation gene expression appear to undergo a “division of labor” in certain growth conditions, particularly during growth on agar plates. Since C. difficile specializes into subpopulations for numerous vital cellular processes, this novel dual reporter system will enable future studies aimed at understanding how C. difficile coordinates various subpopulations throughout its infectious disease cycle.
High salt intake activates the hypothalamic-pituitary-adrenal axis, amplifies the stress response, and alters tissue glucocorticoid exposure in mice
Authors: Costello Hannah M , Krilis Georgios , Grenier Celine , Severs David , Ivy Jessica R. , Nixon Mark , Holmes Megan C , Livingstone Dawn E.W. , Hoorn Ewout J , Dhaun Neeraj , Bailey Matthew A
Published: March 2022

High salt intake is common and contributes to poor cardiovascular health. Sustained cortisol excess also induces an adverse cardiovascular profile. Urinary cortisol excretion positively correlates with urinary sodium excretion. We hypothesised that this was due to hypothalamic-pituitary-adrenal axis activation by high salt intake.

In male C57BL6/J mice, 2 weeks of high salt intake increased Crh and Pomc mRNA abundance in the hypothalamus and anterior pituitary, respectively and caused a sustained rise in plasma corticosterone. Plasma copeptin and anterior pituitary V1b receptor mRNA expression was elevated, which may contribute to basal HPA axis activation. Additionally, high salt intake amplified glucocorticoid response to restraint stress, indicative of enhanced HPA axis sensitivity. In the periphery, high salt intake reduced the binding capacity of corticosteroid-binding globulin, enhancing glucocorticoid bioavailability. Within several tissues, the expression of glucocorticoid-regenerating enzyme, 11β-hydroxysteroid dehydrogenase type 1, was increased and the glucocorticoid receptor downregulated. Overall, high salt intake increased glucocorticoid exposure in the hippocampus, anterior pituitary and liver.

Chronic high salt intake amplifies basal and stress-induced glucocorticoid levels and resets glucocorticoid biology centrally, peripherally and within cells. This shows direct connectivity between salt homeostasis and HPA axis function. The cumulative effect is likely maladaptive and may contribute to the long-term health consequences of a high salt diet.
CRISPR-Cas guided mutagenesis of chromosome and virulence plasmid inShigella flexneriby cytosine base editing
Authors: Sharma Atin , Aden Ruqiya Omer , Puhar Andrea , Cisneros David A.
Published: March 2022

Shigellais a Gram-negative bacterium that invades the human gut epithelium. The resulting infection, shigellosis, is the deadliest bacterial diarrheal disease. Much of the information about the genes dictating the pathophysiology ofShigella, both on the chromosome and the virulence plasmid, was obtained by classical reverse genetics. However, technical limitations of the prevalent mutagenesis techniques restrict the generation of mutants in a single reaction to a small number, preventing large scale targeted mutagenesis ofShigellaand the subsequent assessment of phenotype. We adopted a CRISPR-Cas dependent approach, where a nickase Cas9 and cytidine deaminase fusion is guided by sgRNA to introduce targeted C→T transitions, resulting in internal STOP codons and premature termination of translation. In proof-of-principle experiments using anmCherryfluorescent reporter, we were able to generate loss-of-function mutants in bothE. coliandShigellawith up to 100% efficacy. Using a modified fluctuation assay, we determined that under optimized conditions, the frequency of untargeted mutations introduced by the Cas9-deaminase fusion is in the same range as spontaneous mutations, making our method a safe choice for bacterial mutagenesis. Further, we programmed the method to mutate well-characterized chromosomal and plasmid-borneShigellagenes and found the mutant phenotype to be similar to that of the reported gene deletion mutants, with no apparent polar effects at the phenotype level. This method can be used in a 96-well plate format to increase the throughput and generate an array of targeted loss-of-function mutants in a few days.

Importance

Loss-of-function mutagenesis is critical in understanding the physiological role of genes. Therefore, high-throughput techniques to generate such mutants are important for facilitating the assessment of gene function at a pace that matches system biology approaches. However, to our knowledge, no such method was available for generating an array of single gene mutants in an important enteropathogen -Shigella. This pathogen causes high morbidity and mortality in children and antibiotic resistant strains are quickly emerging. Therefore, determination of the function of unknownShigellagenes is of utmost importance to develop effective strategies to control infections. Our present work will bridge this gap by providing a rapid method for generating loss-of-function mutants. The highly effective and specific method has the potential to be programmed to generated multiple mutants in a single, massively parallel, reaction. By the virtue of plasmid compatibility, this method can be extended to other members of Enterobacteriaceae.
Adolescent parvalbumin expression in the left orbitofrontal cortex shapes sociability in female mice
Authors: Jeon Yi-Seon , Jeong Daun , Kweon Hanseul , Kim Jae-Hyun , Kim Choong Yeon , Oh Youngbin , Lee Young-Ho , Kim Chan Hyuk , Kim Sang-Gyu , Jeong Jae-Woong , Kim Eunjoon , Lee Seung-Hee
Published: March 2022

The adolescent social experience is essential for the maturation of the prefrontal cortex in mammalian species. However, it still needs to be determined which cortical circuits mature with such experience and how it shapes adult social behaviors in a sex-specific manner. Here, we examined social approaching behaviors in male and female mice after post-weaning social isolation (PWSI), which deprives social experience during adolescence. We found that the PWSI, particularly isolation during late adolescence, caused an abnormal increase in social approaches (hypersociability) only in female mice. We further found that the PWSI female mice showed reduced parvalbumin (PV) expression in the left orbitofrontal cortex (OFCL). When we measured neural activity in the female OFCL, a substantial number of neurons showed higher activity when mice sniffed other mice (social sniffing) than when they sniffed an object (object sniffing). Interestingly, the PWSI significantly reduced both the number of activated neurons and the activity level during social sniffing in female mice. Similarly, the CRISPR/Cas9-mediated knock-down of PV in the OFCLduring late adolescence enhanced sociability and reduced the social sniffing-induced activity in adult female mice via decreased excitability of PV+neurons and reduced synaptic inhibition in the OFCL. Moreover, optogenetic activation of excitatory neurons or optogenetic inhibition of PV+neurons in the OFCLenhanced sociability in female mice. Our data demonstrate that the adolescent social experience is critical for the maturation of PV+inhibitory circuits in the OFCL; this maturation shapes female social behavior via enhancing social representation in the OFCL.

Significance Statement

Adolescent social isolation often changes adult social behaviors in mammals. Yet, we do not fully understand the sex-specific effects of social isolation and the brain areas and circuits that mediate such changes. Here, we found that adolescent social isolation causes three abnormal phenotypes in female but not male mice: hypersociability, decreased PV+neurons in the OFCL, and decreased socially evoked activity in the OFCL. Moreover, PV deletion in the OFCLin vivocaused the same phenotypes in female mice by increasing excitation compared with inhibition within the OFCL. Our data suggest that adolescent social experience is required for PV maturation in the OFCL, which is critical for evoking OFCLactivity that shapes social behaviors in female mice.
Loss of the adhesion protein Kindlin-1 stimulates tumor clearance via modulation of Tregs
Authors: Webb Emily R , Dodd Georgia , Bullock Esme , Muir Morwenna , Frame Margaret C , Serrels Alan , Brunton Valerie G
Published: March 2022

The adhesion protein Kindlin-1 is over-expressed in breast cancer where it has been shown to be associated with metastasis-free survival, however, the mechanisms involved are poorly understood. Here, we report that Kindlin-1 promotes anti-tumor immune evasion in a mouse model of breast cancer. Deletion of Kindlin-1 in Met-1 mammary tumor cells leads to tumor regression following injection into immunocompetent hosts. This was associated with a reduction in tumor infiltrating Tregs and impairment of their immune-suppressive activities in Kindlin-1 depleted tumors. Similar changes in T cell populations were seen following depletion of Kindlin-1 in the polyomavirus middle T antigen (PyV MT)-driven mouse model of mammary tumorigenesis. Analysis of cytokines secreted from the Met-1 cells identified a significant increase in IL-6 secretion when Kindlin-1 was depleted. Conditioned media from Kindlin-1 depleted cells lead to a decrease in the ability of Tregs to suppress the proliferation of CD8+ T cells, which was dependent on IL-6 and depletion of CD25+ Tregs resulted in a reduction of Met-1 tumor growth in mice. Overall, these data identify a novel function for Kindlin-1 in the regulation of anti-tumor immunity through cytokine regulation of Treg number and function.
Confinement of unliganded EGFR by tetraspanin nanodomains gates EGFR ligand binding and signaling
Authors: Sugiyama Michael G. , Brown Aidan I. , Vega-Lugo Jesus , Scott Andrew M. , Jaqaman Khuloud , Fairn Gregory D. , Antonescu Costin N.
Published: March 2022

The epidermal growth factor receptor (EGFR) is a central regulator of cell physiology. EGFR is activated by ligand binding, triggering receptor dimerization, activation of kinase activity, and intracellular signaling. EGFR is transiently confined within various plasma membrane nanodomains, yet how this may contribute to regulation of EGFR ligand binding is poorly understood. To resolve how EGFR nanoscale compartmentalization gates ligand binding, we developed single-particle tracking methods to track the mobility of ligand-bound and total EGFR, in combination with modeling of EGFR ligand binding. In comparison to unliganded EGFR, ligand-bound EGFR was more confined and distinctly regulated by clathrin and tetraspanin nanodomains. Ligand binding to unliganded EGFR occurred preferentially in tetraspanin nanodomains, and disruption of tetraspanin nanodomains impaired EGFR ligand binding and altered the conformation of the receptor’s ectodomain. We thus reveal a novel mechanism by which EGFR confinement within tetraspanin nanodomains regulates receptor signaling at the level of ligand binding.
Theoretical Quantification of the Polyvalent Binding of Nanoparticles Coated with Peptide-MHC to TCR-Nanoclusters
Authors: Pineros-Rodriguez Manuela , Richez Louis , Khadra Anmar
Published: March 2022

Nanoparticles (NPs) coated with pMHCs can reprogram a specific type of CD4+ T cells into diseasesuppressing T regulatory type 1 cells by binding to their TCRs expressed as TCR-nanoclusters (TCRnc). NP size and number of pMHCs coated on them (called valence) can be adjusted to increase their efficacy. Here we explore how this polyvalent interaction is manifested and examine if it can facilitate T cell activation. This is done by developing a multiscale biophysical model that takes into account the complexity of this interaction. Using the model, we quantify pMHC insertion probabilities, dwell time of NP binding, TCRnc carrying capacity, the distribution of covered and bound TCRs by NPs, and cooperativity in the binding of pMHCs within the contact area. Model fitting and parameter sweeping further reveal that moderate jumps between IFNγ dose-response curves at low valences can occur, suggesting that the geometry of NP binding can prime T cells for activation.
A method to estimate the effective point spread function of static single molecule localization microscopy images
Authors: Shaw Thomas R. , Fazekas Frank J. , Kim Sumin , Flanagan-Natoli Jennifer C. , Sumrall Emily R. , Veatch S. L.
Published: March 2022

Single molecule localization microscopy (SMLM) permits the visualization of cellular structures an order of magnitude smaller than the diffraction limit of visible light, and an accurate, objective evaluation of the resolution of an SMLM dataset is an essential aspect of the image processing and analysis pipeline. Here we present a simple method that uses the pair autocorrelation function evaluated both in space and time to measure the time-interval dependent effective point spread function of SMLM images of static samples. Using this approach, we demonstrate that experimentally obtained images typically have effective point spread functions that are broader than expected from the localization precision alone, due to additional uncertainty arising from factors such as drift and drift correction algorithms. The method is demonstrated on simulated localizations, DNA origami rulers, and cellular structures labelled by dye-conjugated antibodies, DNA-PAINT, or fluorescent fusion proteins.

STATEMENT OF SIGNIFICANCE

Single molecule localization microscopy (SMLM) is a class of imaging methods that resolve fluorescently labeled structures beyond the optical resolution limit of visible light. SMLM detects stochastically blinking labels over time, and localizes each blink with precision of order 10 nm. The effective resolution depends on factors such as signal-to-noise ratio, localization algorithm, and several post-processing steps such as stage drift correction. We present a method to evaluate this effective resolution by taking advantage of temporal correlations of fluorophore blinking to separate the distribution of pairs of localizations from the same molecule from those from different molecules. The method is robust on useful timescales for a range of SMLM probes.
Predicting and promoting the consumption of plant-based meat
Authors: Carfora Valentina , Morandi Maria , Catellani Patrizia
Published: March 2022

Purpose

The present research aimed to understand how to predict and promote plant-based meat (PBM) consumption.

Design/methodology/approach

In Study 1 (N = 550), the authors investigated the psychosocial antecedents of the intentions to add PBM and to replace animal meat with PBM. In Study 2 (N = 390), the authors tested the effectiveness of different environmental messages promoting PBM consumption. The authors compared the effects of an addition message condition (i.e. a message promoting the addition of PBM to one's diet), a replacement message condition (i.e. a message promoting the replacement of animal meat with PBM) and a control condition (i.e. no message). In both studies, the authors considered the moderation of past PBM consumption (PMB eaters vs PBM noneaters).

Findings

Study 1 showed that a positive attitude towards eating PBM and a high awareness of the environmental consequences of meat production were key antecedents of participants' intention to eat PBM. The role of the other psychosocial antecedents varied according to past PBM consumption. Study 2 showed that both addition and replacement messages increased non-PBM eaters' positive attitude towards eating PBM and in turn willingness to pay for PBM. Instead, only replacement messages increased PBM eaters' willingness to pay for PBM.

Originality/value

The present research developed a model integrating the key psychosocial predictors of people's intentions to eat PBM. Furthermore, it is the first research that compared the persuasiveness of different environment messages to promote PBM consumption.
Confident or captured? Commercial producers in South Africa
Authors: Cloete Kandas , Mann Stefan , Delport Marion
Published: March 2022

Purpose

Among the many things that land reform in South Africa suffers from is the lack of scientific attention paid to the willingness of commercial producers to exit or contract. This research aims to contribute to literature on this phenomenon.

Design/methodology/approach

The interplay between the business confidence and the opportunity costs of a farming enterprise represented in a survey sample of 450 commercial farm owners is investigated, paying special attention to owners who want to, but cannot exit.

Findings

The regression analysis suggests that both forces have a strong influence on structural change, as they depict the rather complex interplay between the two main factors that may keep farms in business, one of which is a positive business climate and the other the capital invested. A subsequent cluster analysis indicates that there is a major cluster of producers who are pessimistic about the prospects of their farming business, but who are unable or unwilling to leave their farms.

Research limitations/implications

A limitation of our study is the fairly small sample size (91 exiters in the sample), so caution is advised in generalising the results. Another limitation is the overrepresentation of the Western Cape.

Practical implications

It is likely that the productivity of South African agriculture could improve if some of these producers caught in the “system” could leave farming to create new opportunities for entrepreneurial entrants.

Originality/value

The importance of a captured state has been neglected both in theoretical frameworks and in practical concepts of commercial agriculture in South Africa.
In search of a fertile entrepreneurial landscape: how to keep it on the level
Authors: Claar Victor V.
Published: March 2022

Purpose

Recent analysis suggests entrepreneurship is in decline. If so, some argue that the appropriate policy response is to devote even further government intervention to nurture both fledgling ventures as well as entirely new undertakings, lamenting the fact that much current economic policy caters to already-successful firms – thereby creating a decision-making environment that stacks the deck against would-be entrepreneurs. While it is indeed true that entrepreneurial ventures lead to value creation over time, this paper argues that the answer to any slowdown in entrepreneurship is not to add even more policy Band-Aids to an already broken system of carve-outs, exemptions, subsidies and tax breaks. Instead the solution to bad policy is to unwind bad policy that favors Goliaths over Davids, thereby creating a level playing field for all. Any attempt to use government initiatives to spur entrepreneurship will, over the longer term, only serve to distort the economic outcomes society would have observed as the product of a system of rule-of-law, clearly defined and enforced property rights and freely functioning markets that permit entrepreneurs, investors, consumers and savers to make the most sensible choices available to them.

Design/methodology/approach

This essay cites fundamental pieces of existing entrepreneurial research to make its argument.

Findings

Rather than adding even more policy initiatives to address any slowdown in entrepreneurship, policymakers should aspire to create the most fertile environment possible to foster entrepreneurial activity. Adding more policies on top of existing ones presumes to know which policies are better than others. Even when perceived as neutral, policy incentives cannot improve upon the outcomes of the unseen price system.

Originality/value

This paper reminds readers that entrepreneurship is vital to economic flourishing, while reminding readers that even policy actions presumed to be beneficial likely bear unintended consequences because they bring their own disruptions to the decision-making environment.
Frontline leadership for implementing clinical guidelines in Norwegian mental health services: a qualitative study
Authors: Nordin Håkan , Rørtveit Kristine , Mathisen Gro Ellen , Joa Inge , Johannessen Jan Olav , Ruud Torleif , Hartveit Miriam
Published: March 2022

Purpose

The purpose of this study was to explore and interpret how frontline leaders define, experience and rationalise their approaches to the successful implementation of clinical guidelines in mental health care.

Design/methodology/approach

Employing an interpretative phenomenological design, the authors conducted and analysed individual interviews of frontline leaders at 14 psychiatric clinics involved in a national study of implementing evidence-based clinical guidelines in mental health.

Findings

The authors found a broad spectrum of attitudes and attributes, as well as a wide repertoire of strategies for frontline implementation leadership. Three main approaches were revealed, comprising “Curious and welcoming”, “Integrity and setting standards” and “Caring and collegial”.

Research limitations/implications

The study present what experienced frontline leaders emphasise to enable implementation of guidelines, not empirical pieces of evidences for what they in fact do or if these actions lead to implementation. The generalisability to other settings is unknown. Another sample profile, context or organisational level may have impacted the result. The concreteness of the frontline leaders’ considerations, approaches and actions gives important knowledge about frontline leaders leadership across traditional leadership theories.

Originality/value

Existing leadership theories describe different leadership styles, while this study reveals the need for a wide range of approaches to balance the many needs and demands. The complexity of leadership approaches this study found is in line with implementation theories; thus, the present study incorporates implementation science into the leadership literature.
Can the components of green intellectual capital influence employee green behavior? An empirical analysis on Indian energy sector using the partial least squares method
Authors: Ghosh Arpita , Haque Shamima
Published: March 2022

Purpose

The study aims to explore the relationship between the dimensions of green intellectual capital (GIC) and employee green behavior (EGB).

Design/methodology/approach

A survey has been conducted among a random representative population of employees working for the energy-sector organizations in India to collect data for this study. Exploratory factor analysis (EFA) for GIC supports the inclusion of the new dimension in its construct. Confirmatory factor analysis (CFA) validates the measurement model. Hypothesized relationships have been examined by applying structural equation modeling using partial least squares method.

Findings

Results corroborate that all the four dimensions of GIC have varying degrees of significant positive impact on EGB. The study contributes to the existing literature by extending the understanding of the concept of GIC and its connection with EGB using natural-resource based theory and social cognitive theory (SCT).

Originality/value

The study has empirically examined the relationship between GIC and EGB in the context of a developing country like India. Moreover, unlike the existing literature that have classified GIC into green human capital (GHC), green structural capital (GSC) and green relational capital (GRC), the study identifies green spiritual capital (GSpC) as another important dimension of GIC which is an intangible asset and highly relevant in influencing altruistic activities like green behavior. The study presents significant implications for managers and policy-makers for ensuring EGB by investing in GIC resources.
The impact of supplier innovation on buyer innovation and the moderating effects of geographic distance, financial interdependence and technical similarity
Authors: Elking Isaac , Cantor David E. , Hofer Christian
Published: March 2022

Purpose

This study aims to examine the extent to which a buying firm can leverage the firm's supplier's innovations to boost the firm's own innovation performance and key moderators to this relationship. Grounded in social embeddedness theory, the authors explore the role of dyadic embeddedness between a buyer and supplier as a facilitator of buyer innovation.

Design/methodology/approach

Negative binomial regression was used to empirically analyze a large sample of dyadic observations from the USA manufacturing industry. Measures were developed from data acquired from Compustat, LexisNexis and Bloomberg.

Findings

The findings indicate that supplier innovation has a positive impact on a buyer firm's innovation output, particularly when the firms are technically similar and when there is a higher degree of financial interdependence in the buyer–supplier dyad.

Originality/value

This study provides important insights into how supplier firms can facilitate buyer innovation as and how relational factors suggested by social embeddedness theory act to strengthen this effect. Through a theoretical-based empirical examination of supply chain dyads, the findings highlight the importance of financial interdependence and technical similarity when buyers seek to benefit from supplier innovation capabilities.
The influence of organizational learning on library service innovation
Authors: Zhou Zifan , Duan Yufeng , Qiu Junping , Yang Li
Published: March 2022

Purpose

This article intends to explore how organizational learning affects innovation in public library services, and the role of public librarians in innovation in library services.

Design/methodology/approach

This study collected 375 valid questionnaires from 19 public libraries in Shanghai and Zhejiang based on organizational learning, organizational innovation and employee psychological empowerment theory. Additionally, SPSS and HLM are used to analyze the relationship among the three processes of organizational learning: knowledge acquisition, knowledge sharing and knowledge application, and public library service innovation.

Findings

Results show that organizational learning has a significant positive effect on the service innovation of public libraries. Knowledge acquisition and knowledge application in the process of organizational learning have a significant positive influence on the service innovation of public libraries, but the impact of knowledge sharing on service innovation is weak. Employee psychological empowerment has a negative regulating influence on knowledge sharing–public library service innovation, but no significant influence on knowledge application–public library service innovation and knowledge acquisition–public library service innovation.

Originality/value

This research explores the effectiveness of the theory of organizational learning in the field of public libraries and also confirms the role of librarians in the work of public libraries. Together, they promote the innovation of public libraries.