bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-regulation of the brain’s right frontal Beta rhythm using a brain-computer interface
Authors: Enz Nadja , Schmidt Jemima , Nolan Kate , Mitchell Matthew , Gomez Sandra Alvarez , Alkayyali Miryam , Cambay Pierce , Gippert Magdalena , Whelan Robert , Ruddy Kathy L.
Published: October 2021

Neural oscillations, or brain rhythms, fluctuate in a manner reflecting ongoing behavior. Whether these fluctuations are instrumental or epiphenomenal to the behavior remains elusive. Attempts to experimentally manipulate neural oscillations exogenously using non-invasive brain stimulation have shown some promise, but difficulty with tailoring stimulation parameters to individuals has hindered progress in this field. We demonstrate here using electroencephalography (EEG) neurofeedback in a brain-computer interface that human participants (n=44) learned over multiple sessions across a 6-day period to self-regulate their Beta rhythm (13-20 Hz) over the right inferior frontal cortex (rIFC). The modulation was evident only during neurofeedback task performance but did not lead to offline alteration of Beta rhythm characteristics at rest, nor to changes in subsequent cognitive behavior. Likewise, a control group (n=38) who underwent training of the Alpha rhythm (8-12 Hz) did not exhibit behavioral changes. Although the right frontal Beta rhythm has been repeatedly implicated as a key component of the brain’s inhibitory control system, the present data suggest that its manipulation offline prior to cognitive task performance does not result in behavioral change. Thus, this form of neurofeedback training of the tonic Beta rhythm would not serve as a useful therapeutic target for disorders with dysfunctional inhibitory control as their basis.
Shiitake mycelium fermentation improves digestibility, nutritional value, flavor and functionality of plant proteins
Authors: Clark Anthony , Soni Bhupendra K , Sharkey Brendan , Acree Terry , Lavin Edward , Bailey Hannah M. , Stein Hans H. , Han Ashley , Elie Marc , Nadal Marina
Published: October 2021

Plant proteins can serve as inexpensive and environmentally friendly meat-replacements. However, poor taste characteristics and relatively low nutritional value prevent their full acceptance as meat substitutes. Fermentation of food has been historically used to improve the quality of foods. In this work we describe the improvement in digestibility, nutritional value, physical properties, and organoleptic characteristics, of a pea and rice protein concentrate blend through fermentation with shiitake mushroom mycelium. Ileal digestibility pig studies show increases in the DIAAS for the shiitake fermented pea and rice protein blend turning the blend into an “excellent source” of protein for humans. The fermentation also increases the solubility of the protein blend and reduces the content of the antinutrient compounds phytates and protease inhibitor. Mass spectrometry and sensory analyses of fermented protein blend indicates that fermentation leads to a reduction in off-note compounds substantially improving its organoleptic performance.
Punch in the gut: Parasite tolerance of phytochemicals reflects host diet
Authors: Palmer-Young Evan C , Schwarz Ryan S , Chen Yan Ping , Evans Jay D
Published: October 2021

Gut parasites of plant-eating insects are exposed to antimicrobial phytochemicals that can reduce infection. Trypanosomatid gut parasites infect insects of diverse nutritional ecologies as well as mammals and plants, raising the question of how host diet-associated phytochemicals shape parasite evolution and host specificity. To test the hypothesis that phytochemical tolerance of trypanosomatids reflects the chemical ecology of their hosts, we compared related parasites from honey bees and mosquitoes- hosts that differ in phytochemical consumption- and contrasted our results with previous studies on phylogenetically related, human-parasitic Leishmania.

We identified one bacterial and ten plant-derived substances with known antileishmanial activity that also inhibited honey bee parasites associated with colony collapse. Bee parasites exhibited greater tolerance of chrysin- a flavonoid found in nectar, pollen, and plant resin-derived propolis. In contrast, mosquito parasites were more tolerant of cinnamic acid- a product of lignin decomposition present in woody debris-rich larval habitats. Parasites from both hosts tolerated many compounds that inhibit Leishmania, hinting at possible trade-offs between phytochemical tolerance and mammalian infection. Our results implicate the phytochemistry of host diets as a potential driver of insect-trypanosomatid associations, and identify compounds that could be incorporated into colony diets or floral landscapes to ameliorate infection in bees.
Cytoplasmic dynein-1 cargo diversity is mediated by the combinatorial assembly of FTS-Hook-FHIP complexes
Authors: Christensen Jenna R. , Kendrick Agnieszka A. , Truong Joey B. , Aguilar-Maldonado Adriana , Adani Vinit , Dzieciatkowska Monika , Reck-Peterson Samara L.
Published: October 2021

In eukaryotic cells, intracellular components are organized by the microtubule motors cytoplasmic dynein-1 (dynein) and kinesins, which are linked to cargos via adaptor proteins. While ∼40 kinesins transport cargo toward the plus end of microtubules, a single dynein moves cargo in the opposite direction. How dynein transports a wide variety of cargos remains an open question. The FTS-Hook-FHIP (“FHF”) cargo adaptor complex links dynein to cargo in mammals and fungi. As human cells have three Hooks and four FHIP proteins, we hypothesized that the combinatorial assembly of different Hook and FHIP proteins could underlie dynein cargo diversity. Using proteomic approaches, we determine the protein ‘interactome’ of each FHIP protein. Live-cell imaging and biochemical approaches show that different FHF complexes associate with distinct motile cargos. These complexes also move with dynein and its cofactor dynactin in single-molecule in vitro reconstitution assays. Complexes composed of FTS, FHIP1B, and Hook1/Hook3 co-localize with Rab5-tagged early endosomes via a direct interaction between FHIP1B and GTP-bound Rab5. In contrast, complexes composed of FTS, FHIP2A and Hook2 colocalize with Rab1A-tagged ER-to-Golgi cargos and FHIP2A is involved in the motility of Rab1A tubules. Our findings suggest that combinatorial assembly of different FTS-Hook-FHIP complexes is one mechanism dynein uses to achieve cargo specificity.
The Role of the Temporal Pole in Temporal Lobe Epilepsy: A Diffusion Kurtosis Imaging Study
Authors: Kasa Loxlan W , Peters Terry , Mirsattari Seyed M. , Jurkiewicz Michael T. , Khan Ali R. , Haast Roy A.M
Published: October 2021

Objective

This study aims to evaluate the use of diffusion kurtosis imaging (DKI) to detect microstructural abnormalities within the temporal pole (TP) in temporal lobe epilepsy (TLE) patients.

Methods

DKI quantitative maps were obtained from fourteen lesional (MRI+) and ten non-lesional (MRI-) TLE patients, along with twenty-one healthy controls. This included mean (MK); radial (RK) and axial kurtosis (AK); mean diffusivity (MD) and axonal water fraction (AWF). Automated fiber quantification (AFQ) was used to quantify DKI measurements along the inferior longitudinal (ILF) and uncinate fasciculus (Unc). ILF and Unc tract profiles were compared between groups and tested for correlation with seizure duration. To characterize temporopolar cortex (TC) microstructure, DKI maps were sampled at varying depths from superficial white matter (WM) towards the pial surface. Each patient group was separated according to side ipsilateral to the epileptogenic temporal lobe and their AFQ results were used as input for statistical analyses.

Results

Significant differences were observed between MRI+ and controls (p < 0.005), towards the most anterior of ILF and Unc proximal to the TP of the left (not right) ipsilateral temporal lobe for MK, RK, AWK and MD. Noticeable differences were also observed mostly towards the TP for MK, RK and AWK in the MRI-group. DKI measurements correlated with seizure duration, mostly towards the anterior segments of the WM bundles. Stronger differences in MK, RK and AWF within the TC were observed in the MRI+ and noticeable differences (except for MD) in MRI-groups compared to controls.

Significance

The study demonstrates that DKI has potential to detect subtle microstructural alterations within the anterior segments of the ILF and Unc and the connected TC in TLE patients including MRI-subjects. This could aid our understanding of the extrahippocampal areas involved in seizure generation in TLE and might inform surgical planning, leading to better seizure outcomes.
High Expression of Glycolytic Genes in Clinical Glioblastoma Patients Correlates with Lower Survival
Authors: Stanke Kimberly M , Wilson Carrick , Kidambi Srivatsan
Published: October 2021

Glioblastoma (GBM), the most aggressive brain tumor, is associated with a median survival at diagnosis of 16-20 months and limited treatment options. The key hallmark of GBM is altered tumor metabolism and marked increase in the rate of glycolysis. Aerobic glycolysis along with elevated glucose consumption and lactate production supports rapid cell proliferation and GBM growth. In this study, we examined the gene expression profile of metabolic targets in GBM samples from patients with low grade glioma (LGG) and GBM. We found that gene expression of glycolytic enzymes is up-regulated in GBM samples and significantly associated with an elevated risk for developing GBM. Our findings of clinical outcomes showed that GBM patients with high expression of HK2 and PKM2 in the glycolysis related genes and low expression of genes involved in mitochondrial metabolism-SDHB and COX5A related to tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS), respectively, was associated with poor patient overall survival. Surprisingly, expression levels of genes involved in mitochondrial oxidative metabolism are markedly increased in GBM compared to LGG but was lower compared to normal brain. The fact that in GBM the expression levels of TCA cycle and OXPHOS-related genes are higher than those in LGG patients suggests the metabolic shift in GBM cells when progressing from LGG to GBM. These results are an important step forward in our understanding of the role of metabolic reprogramming in glioma as drivers of the tumor and could be potential prognostic targets in GBM therapies.
WUSCHEL-Related Homeobox Genes Cooperate with Cytokinin Signalling to Promote Bulbil Formation in Lilium lancifolium
Authors: He Guoren , Cao Yuwei , Wang Jing , Song Meng , Bi Mengmeng , Tang Yuchao , Xu Leifeng , Yang Panpan , Ming Jun
Published: October 2021

The bulbil is an important vegetative reproductive organ in triploid Lilium lancifolium. Based on our previously obtained transcriptome data, we screened two WUSCHCEL-related homeobox (WOX) genes closely related to bulbil formation, LlWOX9 and LlWOX11. However, the biological functions and regulatory mechanisms of LlWOX9 and LlWOX11 are unclear. In this study, we cloned the full-length coding sequences of LlWOX9 and LlWOX11. Transgenic Arabidopsis showed increased branch numbers, and the overexpression of LlWOX9 and LlWOX11 in stem segments promoted bulbil formation, while the silencing of LlWOX9 and LlWOX11 inhibited bulbil formation, indicating that LlWOX9 and LlWOX11 are positive regulators of bulbil formation. Cytokinins acting through type-B response regulators (type-B RRs) could bind to the promoters of LlWOX9 and LlWOX11 and promote their transcription. LlWOX11 could enhance cytokinin pathway signalling by inhibiting the transcription of type-A LlRR9. Our study enriches the understanding of the regulation of plant development by the WOX gene family and lays a foundation for further research on the molecular mechanism of bulbil formation in lily.
Suppression of B-Cell Activation by Human Cord Blood-Derived Stem Cells (CB-SC) through the Galectin-9-Dependent Cell Contact Mechanism
Authors: Hu Wei , Song Xiang , Yu Haibo , Fan Sophia , Shi Andrew , Sun Jingyu , Wang Hongjun , Zhao Laura , Zhao Yong
Published: October 2021

Background

We developed the Stem Cell Educator therapy among multiple clinical trials based on the immune modulations of multipotent cord blood-derived stem cells (CB-SC) on different compartments of immune cells such as T cells and monocytes/macrophages in diabetes and other autoimmune diseases. However, the effects of CB-SC on the B cells remained unclear. To better understand the molecular mechanisms underlying the immune education of CB-SC, we explored the modulations of CB-SC on human B cells.

Methods

CB-SC were isolated from human cord blood units and confirmed by flow cytometry with different markers for their purity. B cells were purified by using anti-CD19 immunomagnetic beads from human peripheral blood mononuclear cells (PBMC). Next, the activated B cells were treated in the presence or absence of coculture with CB-SC for 7 days before undergoing flow cytometry analysis of phenotypic change with different markers. RT-PCR was utilized to evaluate the levels of galectin expressions with or without treatment of activated B cells in order to find the key galectin contributing to the B-cell modulation.

Results

Flow cytometry demonstrated that the proliferation of activated B cells was markedly suppressed in the presence of CB-SC, leading to the down-regulation of immunoglobulin productions from the activated B cells. Phenotypic analysis revealed that treatment with CB-SC increased the percentage of IgD+CD27-naïve B cells, but decreased the percentage of IgD-CD27+switched B cells. Transwell assay showed that the immune suppression of CB-SC on B cells was dependent on the manner of cell-cell contact via Gal-9 molecule, as confirmed by the blocking experiment with the anti-Gal-9 monoclonal antibody. Mechanistic studies demonstrated that both calcium levels of cytoplasm and mitochondria were down-regulated after the treatment with CB-SC, causing the decline of mitochondrial membrane potential in the activated B cells. Western blot exhibited that the levels of phosphorylated Akt and Erk1/2 signaling proteins in the activated B cells were also markedly reduced in the presence of CB-SC.

Conclusions

CB-SC displayed multiple immune modulations on B cells through the Gal-9-mediated cell-cell contact mechanism and calcium flux/Akt/Erk1/2 signaling pathways. The data advances current understanding about the molecular mechanisms underlying the Stem Cell Educator therapy to treat autoimmune diseases in clinics.
Pseudofinder: detection of pseudogenes in prokaryotic genomes
Authors: Syberg-Olsen Mitchell J. , Garber Arkadiy I. , Keeling Patrick J. , McCutcheon John P. , Husnik Filip
Published: October 2021

Prokaryotic genomes are generally gene dense and encode relatively few pseudogenes, or nonfunctional/inactivated remnants of genes. However, in certain contexts, such as recent ecological shifts or extreme population bottlenecks (such as those experienced by symbionts and pathogens), pseudogenes can quickly accumulate and form a substantial fraction of the genome. Identification of pseudogenes is, thus, a critical step for understanding the evolutionary forces acting upon, and the functional potential encoded within, prokaryotic genomes. Here, we present Pseudofinder, an open-source software dedicated to pseudogene identification and analysis. With Pseudofinder’s multi-pronged, reference-based approach, we demonstrate its capacity to detect a wide variety of pseudogenes, including those that are highly degraded and typically missed by gene-calling pipelines, as well newly formed pseudogenes, which can have only one or a few inactivating mutations. Additionally, Pseudofinder can detect intact genes undergoing relaxed selection, which may indicate incipient pseudogene formation. Implementation of Pseudofinder in annotation pipelines will not only clarify the functional potential of sequenced microbes, but will also generate novel insights and hypotheses regarding the evolutionary dynamics of bacterial and archaeal genomes.
Comprehensive antibody profiling of mRNA vaccination in children
Authors: Bartsch Yannic C , St Denis Kerri J , Kaplonek Paulina , Kang Jaewon , Lam Evan C. , Burns Madeleine D , Farkas Eva J , Davis Jameson P , Boribong Brittany P , Edlow Andrea G , Fasano Alessio , Shreffler Wayne , Zavadska Dace , Johnson Marina , Goldblatt David , Balazs Alejandro B , Yonker Lael M , Alter Galit
Published: October 2021

While children have been largely spared from COVID-19 disease, the emergence of viral variants of concern (VOC) with increased transmissibility, combined with fluctuating mask mandates and school re-openings have led to increased infections and disease among children. Thus, there is an urgent need to roll out COVID-19 vaccines to children of all ages. However, whether children respond equivalently to adults to mRNA vaccines and whether dosing will elicit optimal immunity remains unclear. Given the recent announcement of incomplete immunity induced by the pediatric dose of the BNT162b2 vaccine in young children, here we aimed to deeply profile and compare the vaccine-induced humoral immune response in 6-11 year old children receiving the pediatric (50μg) or adult (100μg) dose of the mRNA-1273 vaccine compared to adults and naturally infected children or children that experienced multi inflammatory syndrome in children (MIS-C) for the first time. Children elicited an IgG dominant vaccine induced immune response, surpassing adults at a matched 100μg dose, but more variable immunity at a 50μg dose. Irrespective of titer, children generated antibodies with enhanced Fc-receptor binding capacity. Moreover, like adults, children generated cross-VOC humoral immunity, marked by a decline of omicron receptor binding domain-binding, but robustly preserved omicron Spike-receptor binding, with robustly preserved Fc-receptor binding capabilities, in a dose dependent manner. These data indicate that while both 50μg and 100μg of mRNA vaccination in children elicits robust cross-VOC antibody responses, 100ug of mRNA in children results in highly preserved omicron-specific functional humoral immunity.

One-Sentence Summary

mRNA vaccination elicits robust humoral immune responses to SARS-CoV-2 in children 6-11 years of age.
Longitudinal changes in home confinement and mental health implications: A 17-month follow-up study in England during the COVID-19 pandemic
Authors: Bu Feifei , Steptoe Andrew , Fancourt Daisy
Published: October 2021

Background

The COVID-19 pandemic has brought about significant behavioural changes, one of which is increased time spent at home. Although official lockdowns were typically short-term and allowed people to leave their homes for exercise and essential activities, some individuals did not leave their home for prolonged periods due to a range of factors including clinical vulnerability. This study aimed to explore longitudinal patterns of such ‘home confinement’ across different stages of the COVID-19 pandemic in the UK, and its associated predictors and mental health outcomes.

Methods

Data were from the UCL COVID -19 Social Study. The analytical sample consisted of 25,390 adults in England who were followed up for 17 months from March 2020 to July 2021. Data were analysed using growth mixture models.

Results

Our analyses identified three classes of growth trajectories, including one class showing a high level of persistent home confinement (24.8%), one changing class with clear alignment with national containment policy/advice (32.0%), and one class with a persistently low level of confinement (43.1%). A range of factors were found to be associated the class membership of home confinement trajectories, such as age, gender, income, employment status, social relationships and health. The class with a high level of confinement had the highest number of depressive and anxiety symptoms at the end of the follow-up independent of potential confounders.

Conclusions

There was substantial heterogeneity in longitudinal patterns of home confinement during the COVID-19 pandemic. However, a striking proportion of our sample maintained a high level of home confinement over the course of 17 months, even during periods when containment measures were eased or removed and when infection rates were low. They also had the worst mental health outcomes. This group warrants special attention in addressing the mental health impact of the COVID-19 pandemic.
Boston Cognitive Assessment (BOCA) — a comprehensive self-administered smartphone- and computer-based at-home test for longitudinal tracking of cognitive performance
Authors: Vyshedskiy Andrey , Netson Rebecca , Fridberg Elisabeth , Jagadeesan Priyanka , Arnold Matthew , Barnett Sophie , Gondalia Anjali , Maslova Victoria , deTorres Lauren , Ostrovsky Simone , Durakovic Danijel , Savchenko Andrei , McNett Sienna , Kogan Mikhail , Piryatinsky Irene , Gold Dov
Published: October 2021

Longitudinal cognitive testing is essential for developing novel preventive interventions for dementia and Alzheimer’s disease; however, the few available tools have significant practice effect and depend on an external evaluator. We developed a self-administered 10-minute at-home test intended for longitudinal cognitive monitoring, Boston Cognitive Assessment or BOCA. The goal of this project was to validate BOCA. BOCA uses randomly selected non-repeating tasks to minimize practice effects. BOCA evaluates eight cognitive domains: 1) Memory/Immediate Recall, 2) Language Comprehension/Prefrontal Synthesis, 3) Visuospatial Reasoning / Mental rotation, 4) Executive function / Clock Test, 5) Attention, 6) Mental math, 7) Orientation, and 8) Memory/Delayed Recall. BOCA was administered to patients with cognitive impairment (n = 50) and age- and education-matched controls (n = 50). Test scores were significantly different between patients and controls (p < 0.001) suggesting good discriminative ability. The Cronbach’s alpha was 0.87 implying good internal consistency. BOCA demonstrated strong correlation with Montreal Cognitive Assessment (MOCA) (R= 0.90, p <0.001). The study revealed strong (R=0.94, p <0.001) test-retest reliability of the total BOCA score one week after participants’ initial administration. The practice effect tested by daily BOCA administration over 10 days was insignificant (β=0.03, p=0.74). BOCA has the potential to reduce the cost and improve the quality of longitudinal cognitive tracking essential for testing novel interventions designed to reduce or reverse cognitive aging. BOCA is available online gratis at www.bocatest.org.
CRISPR-Cas9-mediated knockout of CYP79D1 and CYP79D2 in cassava attenuates toxic cyanogen production
Authors: Gomez Michael A. , Berkoff Kodiak C. , Gill Baljeet K. , Iavarone Anthony T. , Lieberman Samantha E. , Ma Jessica M. , Schultink Alex , Wyman Stacia K. , Chauhan Raj Deepika , Taylor Nigel J. , Staskawicz Brian J. , Cho Myeong-Je , Rokhsar Daniel S. , Lyons Jessica B.
Published: October 2021

Cassava (Manihot esculenta Crantz) is a starchy root crop that supports over a billion people in tropical and subtropical regions of the world. This staple, however, produces toxic cyanogenic compounds and requires processing for safe consumption. Excessive consumption of insufficiently processed cassava, in combination with protein-poor diets, can have neurodegenerative impacts. Reducing the cyanogen content by conventional breeding is problematic due to the heterozygous nature of the crop; recombination will generally disrupt a clonally propagated cultivar’s suite of desirable traits. To reduce cyanide levels in cassava, we used CRISPR-mediated mutagenesis to disrupt the cytochrome P450 genes CYP79D1 and CYP79D2 whose protein products catalyze the first step in cyanogenic glucoside biosynthesis. Knockout of both genes eliminated cyanide in leaves and storage roots of cassava accession 60444 and the West African, farmer-preferred cultivar TME 419. Although knockout of CYP79D2 alone resulted in significant reduction of cyanide, mutagenesis of CYP79D1 did not, indicating these paralogs have diverged in their function. Our work demonstrates cassava genome editing for food safety, reduced processing requirements, and environmental benefits that could be readily extended to other farmer-preferred cultivars.
Activation of the essential kinase PDK1 by phosphoinositide-driven trans-autophosphorylation
Authors: Levina Aleksandra , Fleming Kaelin D. , Burke John E. , Leonard Thomas A.
Published: October 2021

3-phosphoinositide-dependent kinase 1 (PDK1) is an essential serine/threonine protein kinase, which plays a crucial role in cell growth and proliferation. It is often referred to as a ‘master’ kinase due to its ability to activate at least 23 downstream protein kinases implicated in various signaling pathways. In this study, we have elucidated the mechanism of phosphoinositide-driven PDK1 auto-activation. We show that PDK1 trans- autophosphorylation is mediated by a PIP3-mediated face-to-face dimer. We report regulatory motifs in the kinase-PH interdomain linker that allosterically activate PDK1 autophosphorylation via a linker-swapped dimer mechanism. Finally, we show that PDK1 is autoinhibited by its PH domain and that positive cooperativity of PIP3binding drives switch- like activation of PDK1. Our work implies that the PDK1-mediated activation of effector kinases, including Akt, PKC, Sgk, S6K and RSK, many of whom are not directly regulated by phosphoinositides, is also likely to be dependent on PIP3or PI(3, 4)P2.
Impairment of the cellulose degradation machinery enhances fungal virulence but limits reproductive fitness
Authors: Gámez-Arjona Francisco M. , Vitale Stefania , Voxeur Aline , Dora Susanne , Müller Sascha , Sancho-Andrés Gloria , Montesinos Juan Carlos , Di Pietro Antonio , Sánchez-Rodríguez Clara
Published: October 2021

Fungal endophytes grow in the apoplastic space, in constant contact with the plant cell wall (CW) that hinders microbe progression, while representing a source of nutrients. Although numerous fungal CW modifying proteins have been identified, their role during host colonization remains underexplored. Here we show that the root-infecting plant pathogenFusarium oxysporum(Fo) does not require its complete arsenal of cellulases to infect the host plant. Quite the opposite, Fo mutants impaired in cellulose degradation become hypervirulent by enhancing the secretion of virulence factors. On the other hand, the reduction on cellulase activity had a severe negative effect on saprophytic growth and microconidia production during the final stages of the Fo infection cycle. These findings enhance our understanding on the function of plant CW degradation on the outcome of host-microbe interactions and reveal an unexpected role of cellulose degradation in a pathogen’s evolutionary success.

Teaser

Unexpectedly, fungi compromised in their capacity to degrade plant cellulose are hypervirulent but impaired in sporulation.
Analysis of DYRK1B, PPARG, and CEBPB Expression Patterns in Adipose-Derived Stem Cells from Patients carrying DYRK1B R102C and Healthy Individuals During Adipogenesis
Authors: Armanmehr Azam , Khamirani Hossein Jafari , Zoghi Sina , Dianatpour Mehdi
Published: October 2021

Background

Metabolic syndrome (MetS) is a group of signs and symptoms that are associated with higher risk of Type 2 Diabetes Mellitus (T2DM) and Cardiovascular Diseases (CVDs). The major risk factor for developing MetS is abdominal obesity that is caused by increase in adipocyte size or number. Adipocyte number multiplication is caused by differentiation of mesenchymal stem cells into adipose tissue. Numerous studies have evaluated the expression of key transcription factors including PPARG and CEBPB during adipocyte differentiation in murine cells such as 3T3-L1 cell line. In order to comprehend the expression changes during the process of fat accumulation in adipose tissue derived stem cells (ASCs), we compared the expression of DYRK1B, PPARG, and CEBPB in undifferentiated and differentiated ASCs into mature adipocytes between the patient (harboring DYRK1b R102C) and control (healthy individuals) groups.

Methods

Gene expression was evaluated on eighth days pre-induction and day 1, 5 and 15 post-induction. The pluripotent capacity of ASCs and the potential for differentiation into adipocyte were confirmed by flow cytometry analysis of surface markers (CD34, CD44, CD105 and CD90), and Oil red O staining, respectively. Expression of DYRK1B, PPARG, and CEBPB were assessed by RT-PCR in patients’ and normal individuals’ samples.

Results

The expression of DYRK1B kinase and transcription factors (CEBPB and PPARG) are significantly higher in adipose derived stem cells harboring DYRK1b R102C compared to non-carriers on day 5 and 15 during adipocyte differentiation. These proteins may be suitable targets for therapeutic strategies in obesity and obesity related disorders like metabolic syndrome. Furthermore, AZ191 exhibited a potent and selectively inhibitory activity toward DYRK1B and CEBPB.

Conclusion

CEBPB, PPARA and DYRK1B contribute to adipogenesis and the development of metabolic syndrome; thus, they can be harnessed in developing therapeutic agents against metabolic syndrome.
Single-cell RNA transcriptome analysis reveals CXCL16/CXCR6 as maintenance factors for CNS tissue resident T cells that drive synapse elimination during viral recovery
Authors: Rosen Sarah F. , Soung Allison L. , Yang Wei , Ai Shenjian , Kanmogne Marlene , Davé Veronica A. , Prabhakar Sairam , Swain Amanda , Artyomov Maxim , Magee Jeffrey A. , Klein Robyn S.
Published: October 2021

Background

Emerging RNA viruses that target the central nervous system (CNS) lead to cognitive sequelae in survivors. Studies in humans and mice infected with West Nile virus (WNV), a re-emerging RNA virus associated with learning and memory deficits, revealed microglial-mediated synapse elimination within the hippocampus. Moreover, CNS resident memory T (TRM) cells activate microglia, limiting synapse recovery and inducing spatial learning defects in WNV-recovered mice. The signals involved in T cell-microglia interactions are unknown.

Methods

Here, we examined the murine WNV-recovered forebrain using single-cell RNA sequencing to identify putative ligand-receptor pairs involved in intercellular communication between T cells and microglia. Clustering and differential gene analyses were followed by protein validation, genetic and antibody-based approaches utilizing an established murine model of WNV recovery in which microglia and complement promote ongoing hippocampal synaptic loss.

Results

Profiling of host transcriptome at 25 days post-infection revealed a shift in forebrain homeostatic microglia to activated subpopulations with transcriptional signatures that have previously been observed in studies of neurodegenerative diseases. Importantly, CXCL16/CXCR6, a chemokine signaling pathway involved in TRM cell biology, was identified as critically regulating CXCR6 expressing CD8+ TRM cell numbers within the WNV-recovered forebrain. We demonstrate that CXCL16 is highly expressed by all myeloid cells, and its unique receptor, CXCR6, is highly expressed on all CD8+ T cells. Using genetic and pharmacological approaches, we demonstrate that CXCL16/CXCR6 is required not only for the maintenance of WNV-specific, CD8 TRM cells in the post-infectious CNS, but also contributes to their expression of TRM cell markers. Moreover, CXCR6+CD8+ T cells are required for glial activation and ongoing synapse elimination.

Conclusions

We provide a comprehensive assessment of the role of CXCL16/CXCR6 as an interaction link between microglia and CD8+ T cells that maintains forebrain TRM cells, microglial and astrocyte activation, and ongoing synapse elimination in virally recovered animals. We also show that therapeutic targeting of CXCL16 during recovery may reduce CNS CD8+ TRM cells.
Predicting student performance in a blended learning environment using learning management system interaction data
Authors: Fahd Kiran , Miah Shah Jahan , Ahmed Khandakar
Published: October 2021

Purpose

Student attritions in tertiary educational institutes may play a significant role to achieve core values leading towards strategic mission and financial well-being. Analysis of data generated from student interaction with learning management systems (LMSs) in blended learning (BL) environments may assist with the identification of students at risk of failing, but to what extent this may be possible is unknown. However, existing studies are limited to address the issues at a significant scale.

Design/methodology/approach

This study develops a new approach harnessing applications of machine learning (ML) models on a dataset, that is publicly available, relevant to student attrition to identify potential students at risk. The dataset consists of the data generated by the interaction of students with LMS for their BL environment.

Findings

Identifying students at risk through an innovative approach will promote timely intervention in the learning process, such as for improving student academic progress. To evaluate the performance of the proposed approach, the accuracy is compared with other representational ML methods.

Originality/value

The best ML algorithm random forest with 85% is selected to support educators in implementing various pedagogical practices to improve students’ learning.
What motivates Vietnamese enterprises to upgrade in global value chains? Closing the intention-behavior gap
Authors: Hoang Dung Phuong , Doan Ngoc Thang , Nguyen Thi Cam Thuy
Published: October 2021

Purpose

Upgrading in global value chains (GVCs) has become a crucial strategy for enhancing competitive advantage and attaining higher profitability, especially among firms in developing countries. Drawn from the sociological approach, this study treats GVC upgrading as an entrepreneurial act and examines factors affecting firms' intention to move up in their chains based on the theory of planned behavior. The authors also further test the moderating effects of firms' knowledge about rule of origin and governmental supports on the intention-behavior gap.

Design/methodology/approach

In-depth interviews with eight Vietnamese business managers were implemented to support the development of hypotheses and measurement scales. Afterwards, the authors conducted a survey on decision-makers of 402 Vietnamese firms which currently have export-import activities to collect quantitative data for testing the hypothesized relationships.

Findings

The empirical results indicate that both attitudes, behavioral control and social norms have significant positive impacts on the intention to upgrade in GVCs. In turn, such intention could further activate actual behaviors to move up in their chains. However, those who have better knowledge about rule of origin and receive governmental supports either in terms of finance, credit or technology have a higher probability of demonstrating actual behavior to upgrade in GVCs once their intentions are formed than those who do not.

Practical implications

This research provides valuable implications for policymakers in accelerating firms' actions to upgrade within their chains, hence, actively enhancing not only organizational performance but also significantly contributes to the national economic development.

Originality/value

While most of the previous studies examine the preconditions for firms to participate and upgrade in their GVCs, there is limited attention on determinants of firms' own intention and actual behavior to upgrade in their chains once they have participated in the GVC. Specifically, this research not only contributes to the existing knowledge regarding factors affecting firms' intention to upgrade in their chains but also closes the gap between the intention and the actual GVC upgrading behavior.
The hybrid career concept: creating hybrid career pathways
Authors: Gander Michelle
Published: October 2021

Purpose

Hybrid career has been discussed in the literature for some time but is still an emergent concept. The study investigated the careers of university professional staff working in universities in Australia and the UK to better understand the careers of this underresearched cohort of staff. The findings were used to extend the theory of the hybrid career.

Design/methodology/approach

A total of 139 career stories were collected via an open-ended question in an online survey. Inductive thematic analysis was used to create themes and theorise career pathways relevant to the participants' careers.

Findings

It was found that participants had a hybrid career orientation (HCO) based on their essential values and their reciprocal relationship with their employer. Four career pathways emerged from the data: intra-organisational advancement, inter-organisational advancement, work–life balance and dead end.

Research limitations/implications

There is a need for future research to investigate the HCO, both to add depth to the understanding of careers for university professional staff in universities and to examine the hybrid concept in other settings.

Practical implications

It is suggested that by grouping staff into career pathways, human resource practitioners could provide more targeted interventions to ensure that staff are motivated and productive for the benefit of the organisation.

Originality/value

The research has extended the concept of the hybrid career and discovered four career pathways relevant to university professional staff.
The dilemma of winners: market power, industry competition and subsidy efficiency
Authors: Song Jialin , Su Yiyi , Su Taoyong , Wang Luyu
Published: October 2021

Purpose

The purpose of this paper is, from a resource accumulation and resource allocation perspective, to examine the variant effects of government subsidies among firms with varying levels of market power and to test how industry competition moderates the relationship between market power and allocative efficiency of government subsidies.

Design/methodology/approach

This study explores the relationship between government subsidies and firm performance from a resource-based view. The authors study the moderating role of market power and three-way interaction between subsidy, market power and industry competition on firm performance. The authors test their hypotheses using a sample of Chinese A-share manufacturing firms from 2006–2019. The authors apply firm-level panel data regressions and conduct a series of robustness tests. The marginal effect of market power and industry competition is explored via three-way moderator effect models.

Findings

This study finds that government subsidies are negatively related to firm performance. Market power, on average, strengthens the negative effect of government subsidies on performance, but such a reinforcement effect is neutralized when industry competition is intense. Government subsidies are least efficiently used when firms have market power and industry competition is low. In addition, the authors use different forms of firm performance and a various of robustness tests to verify their assumptions.

Originality/value

This paper contributes to the literature as follows. First, the authors look into subsidy–performance problem from the perspective of the resource-based view and contribute to explaining and mitigating the divergence of current findings on the subsidy–performance relationship. Second, the authors introduce market power and industry competition as moderators to study how resource allocative efficiency affects the subsidy–performance relationship. Third, the authors propose that managerial incentives have played an important role in the allocation of government subsidies, which enriches management practices.
Definitions of work-life balance in childfree dual-career couples: an inductive typology
Authors: Boiarintseva Galina , Ezzedeen Souha R. , Wilkin Christa
Published: October 2021

Purpose

Work-life balance experiences of dual-career professional couples with children have received considerable attention, but there remains a paucity of research on the definitions of work-life balance among dual-career professional couples without children. This qualitative investigation sheds light on childfree couples' lives outside of work and their concomitant understanding of work-life balance.

Design/methodology/approach

The study draws on interviews with 21 dual-career professional couples in Canada and the US, exploring their non-work lives and how they conceive of work-life balance.

Findings

Thematic analyses demonstrate that this group, while free of child rearing responsibilities, still deals with myriad non-work obligations. These couples also defy uniform characterization. The inductive investigation uncovered four couple categories based on the individual members' career and care orientations. These included careerist, conventional, non-conventional and egalitarian couples. Definitions of work-life balance varied across couple type according to the value they placed on flexibility, autonomy and control, and their particular level of satisfaction with their work and non-work domains.

Originality/value

This study contributes to research at the intersection of work-life balance and various demographic groups by exploring the work-life balance of professional dual-career couples without children. Using an interpretive ontology, the study advances a typology of childfree dual-career professional couples. The findings challenge the rhetoric that these couples are primarily work-oriented but otherwise carefree. Thus, this study demonstrates ways that childfree couples are different as well as similar to those with children.
The Greek life-long learning centers in the post-debt crisis era: evaluation of the effectiveness of mentoring in adult trainers training
Authors: Dukakis Nick , Chasioti Angeliki , Valkanos Efthymios , Staboulis Miltiadis , Fragkoulis Iosif
Published: October 2021

Purpose

The purpose of this paper is to explore the views of Greek Life-Long Learning Centers (LLLCs) trainers, who worked as educational managers and took on informal mentoring roles in the context of counseling guidance and their trainees (who are adults’ trainers), on the effectiveness of mentoring in the post-Greek Debt Crisis era.

Design/methodology/approach

The authors performed a quantitative analysis using the SPSS software package’s simple random sampling. The bibliographic review, the identification and specialization of the research objectives, as well as the study of the participants’ unique characteristics, were used in the construction of a research tool.

Findings

The majority of participants confirmed the importance of mentoring as a human resource strategy. Regarding its effectiveness in the field of the Greek LLLCs, there were several discrepancies in the perceptions of trainers and trainees, as well as specific malfunctions in its implementation.

Research limitations/implications

The research omitted certain qualitative features and was conducted in a relatively limited geographical context.

Originality/value

Given the lack of similar studies in the field of the Greek LLLCs, this study illustrates the reality of the mentoring function in the training field of adult trainers, after the onset of the Greek economic crisis, while also highlighting realistic ways to improve the effectiveness of these organizations and conduct future, larger-scale research.
Exploring and measure the performance of the Indian petroleum supply chain
Authors: Kumar Sourabh , Barua Mukesh Kumar
Published: October 2021

Purpose

This research identifies the supply chain performance indices and designs an evaluation framework to assess and compare the Indian petroleum supply chain performance. We presented a case study of three Indian petroleum companies. For this purpose, we identified fifteen performance criteria extracted from previous literature and expert inputs and classified them into four groups.

Design/methodology/approach

A fuzzy technique for order preference by similarity to the ideal solution (TOPSIS) method is employed for evaluating the performance of the Indian petroleum supply chain.

Findings

The design and evaluation framework suggests that the top three performance measurement criteria, the purity of the products, compliance with environmental laws, and new technology adoption. The result findings also indicate that company C contributes to a maximum satisfaction level of 77%. Simultaneously, companies A and B hold satisfaction levels of 72% and 67%.

Practical implications

The managers should ensure that environmental standards, new technology adoption, and quality are significant concerns in the petroleum supply chain. The managers should follow national and international policies to preserve the environment and ensure safety in operational activities.

Originality/value

This paper makes two contributions in the domain of performance measurement of the petroleum supply chain. First, it identifies the prominent supply chain performance indices. Second, it proposes a model to assess and compare the performance of Indian petroleum companies.
A control chart based on Pearson residuals for a negative binomial regression: application to infant mortality data
Authors: García-Bustos Sandra , Cárdenas-Escobar Nadia , Debón Ana , Pincay César
Published: October 2021

Purpose

The study aims to design a control chart based on an exponentially weighted moving average (EWMA) chart of Pearson's residuals of a model of negative binomial regression in order to detect possible anomalies in mortality data.

Design/methodology/approach

In order to evaluate the performance of the proposed chart, the authors have considered official historical records of death of children of Ecuador. A negative binomial regression model was fitted to the data, and a chart of the Pearson residuals was designed. The parameters of the chart were obtained by simulation, as well as the performances of the charts related to changes in the mean of death.

Findings

When the chart was plotted, outliers were detected in the deaths of children in the years 1990–1995, 2001–2006, 2013–2015, which could show that there are underreporting or an excessive growth in mortality. In the analysis of performances, the value of λ = 0.05 presented the fastest detection of changes in the mean death.

Originality/value

The proposed charts present better performances in relation to EWMA charts for deviance residuals, with a remarkable advantage of the Pearson residuals, which are much easier to interpret and calculate. Finally, the authors would like to point out that although this paper only applies control charts to Ecuadorian infant mortality, the methodology can be used to calculate mortality in any geographical area or to detect outbreaks of infectious diseases.
Statistical and intelligent reliability analysis of multi-layer ceramic capacitor for ground mobile applications using Taguchi’s approach
Authors: Bhargava Cherry , Sharma Pardeep Kumar
Published: October 2021

Purpose

Although Multi-Layer Ceramic Capacitors (MLCC) are known for its better frequency performance and voltage handling capacity, but under various environmental conditions, its reliability becomes a challenging issue. In modern era of integration, the failure of one component can degrade or shutdown the whole electronic device. The lifetime estimation of MLCC can enhance the reuse capability and furthermore, reduces the e-waste, which is a global issue.

Design/methodology/approach

The residual lifetime of MLCC is estimated using empirical method i.e. Military handbook MILHDBK2017F, statistical method i.e. regression analysis using Minitab18.1 as well as intelligent technique i.e. artificial neural networks (ANN) using MATLAB2017b. ANN Feed-Forward Back-Propagation learning with sigmoid transfer function [3–10–1–1] is considered using 73% of available data for training and 27% for testing and validation. The design of experiments is framed using Taguchi’s approach L16 orthogonal array.

Findings

After exploring the lifetime of MLCC, using empirical, statistical and intelligent techniques, an error analysis is conducted, which shows that regression analysis has 97.05% accuracy and ANN has 94.07% accuracy.

Originality/value

An intelligent method is presented for condition monitoring and health prognostics of MLCC, which warns the user about its residual lifetime so that faulty component can be replaced in time.