bluuebunny/crossref_metadata_2025 huggingface dataset:
Vicarious touch: overlapping neural patterns between seeing and feeling touch
Authors: Smit S. , Moerel D. , Zopf R. , Rich A.N.
Published: June 2022

Simulation theories propose that vicarious touch arises when seeing someone else being touched triggers corresponding representations of being touched. Prior electroencephalography (EEG) findings show that seeing touch modulates both early and late somatosensory responses (measured with or without direct tactile stimulation). Functional Magnetic Resonance Imaging (fMRI) studies have shown that seeing touch increases somatosensory cortical activation. These findings have been taken to suggest that when we see someone being touched, we simulate that touch in our sensory systems. The somatosensory overlap when seeing and feeling touch differs between individuals, potentially underpinning variation in vicarious touch experiences. Increases in amplitude (EEG) or cerebral blood flow response (fMRI), however, are limited in that they cannot test for the information contained in the neural signal: seeing touch may not activate the sameinformationas feeling touch. Here, we use time-resolved multivariate pattern analysis on whole-brain EEG data from people with and without vicarious touch experiences to test whether seen touch evokes overlapping neural representations with the first-hand experience of touch. Participants felt touch to the fingers (tactiletrials) or watched carefully matched videos of touch to another person’s fingers (visualtrials). In both groups, EEG was sufficiently sensitive to allow decoding of touch location (little finger vs. thumb) ontactiletrials. However, only in individuals who reported feeling touch when watching videos of touch could a classifier trained ontactiletrials distinguish touch location onvisualtrials. This demonstrates that, for people who experience vicarious touch, there is overlap in the information about touch location held in the neural patterns when seeing and feeling touch. The timecourse of this overlap implies that seeing touch evokes similar representations tolater stagesof tactile processing. Therefore, while simulation may underlie vicarious tactile sensations, our findings suggest this involves an abstracted representation of directly felt touch.
Real-time molecular classification of leukemias
Authors: Sagniez Mélanie , Simpson Shawn M. , Caron Maxime , Rozendaal Marieke , Paré Bastien , Sontag Thomas , Langlois Sylvie , Rouette Alexandre , Lavallée Vincent-Philippe , Cellot Sonia , Sinnett Daniel , Tran Thai Hoa , Smith Martin A.
Published: June 2022

Gene expression profiling provides a detailed molecular snapshot of cellular phenotypes that can be used to compare different biological conditions. Nanopore sequencing technology can generate high-resolution transcriptomic data in real-time and at low cost, which heralds new opportunities for molecular medicine. In this study, we demonstrate the clinical utility of real-time transcriptomic profiling by processing RNA sequencing data from childhood acute lymphoblastic leukemia (ALL) patients on-the-fly with a trained neural network classifier. This strategy successfully distinguished 11/12 representative ALL molecular subtypes and one non-leukemia control in as little as 5 minutes of sequencing on a MinION sequencer or in less than 1 hour on disposable, low cost Flongle flow cells. Our findings suggest that real-time transcriptomics constitutes a drastically efficient solution for the molecular diagnosis of ALL and other diseases, where conventional clinical workflows require days if not weeks to achieve similar results.
Acute inhibition of the STA3 signaling pathway during epileptogenesis prevent GABAergic cells’ loss and imprinting of epileptic state: an in-vitro proof
Authors: Martín-Suárez S. , Cortes JM , Bonifazi P.
Published: June 2022

Epilepsy, the condition of recurrent unprovoked seizures resulting from a wide variety of causes, is one of the world’s most prominent brain syndrome. Seizures which are an expression of neuronal network dysfunction occur in a positive feedback loop of concomitant factors where seizures generate more seizures, including also neuro-inflammatory responses. Among other pathways involved in inflammatory responses, the JAK/STAT signaling pathway has been proposed to prevent epilepsy. In this work we tested on a model of temporal lobe epilepsy in-vitro, the hypothesis that acute inhibition of STAT3-phosphorylation - during epileptogenesis, can prevent structural damages in the hippocampal circuits, and the imprinting both of neural epileptic activity and inflammatory glial states. We performed calcium imaging of spontaneous circuits’ dynamics in organotypic hippocampal slices previously exposed to hyper-excitable conditions through the blockage of GABAergic synaptic transmission. Epileptogenic conditions lead to imprinted epileptic dynamics in the circuits in terms of higher frequency of neuronal firing and circuits’ synchronizations, higher correlated activity in neuronal pairs and decreased complexity in synchronization patterns. Acute inhibition of the STAT3-phosphorylation during epileptogenesis, prevented the imprinting of epileptic activity patterns, general cell loss, GABAergic cells’ loss and the persistence of inflammatory reactive glial states. This work provides further evidence that inhibiting the STAT3 signaling pathway under epileptogenesis can prevent patho-topological reorganization of neuro-glial circuits.
Effects of woody riparian vegetation on macroinvertebrates are context-specific and large in urban and especially agricultural landscapes
Authors: Palt Martin , Hering Daniel , Kail Jochem
Published: June 2022

Woody riparian vegetation (WRV) benefits benthic macroinvertebrates. However, in recent large scale studies, the effects of WRV on macroinvertebrates were small compared to catchment landuse, raising the question about the relevance of WRV in restoration. Limited effects of WRV might be due to context specificity: While some functions are provided by WRV irrespective of catchment landuse, others depend on the landscape setting.

Recursive partitioning modelling was used to identify context dependent effects of WRV on streams macroinvertebrates’ ecological status in small lowland (n = 361) and mountain streams (n = 748). WRV cover was quantified from orthophotos along the near (500 m) and far (5,000 m) upstream river network and used to predict the site’s ecological status. Agricultural, urban and woodland cover at the local and catchment scales along with hydromorphology were considered as partitioning variables.

In rural agricultural landscapes, the effect of WRV on the ecological status was large, indicating that establishing WRV can improve the ecological status by as much as two classes.

In streams impacted by catchment urbanization, effects of WRV were largest, but WRV cover and ecological status were both low, indicating practical limitations of WRV restoration in urban catchments.

Synthesis and applications:Independent effects of WRV on macroinvertebrates’ ecological status can be discerned from catchment landuse. While WRV can also improve the ecological status in urban settings, it is especially relevant for river management in rural agricultural catchments, where developing WRV potentially are effective measures to reach good ecological status
Primate neocortex performs balanced sensory amplification
Authors: Pattadkal Jagruti J. , Zemelman Boris V. , Fiete Ila , Priebe Nicholas J.
Published: June 2022

Sensory cortex amplifies relevant features of external stimuli. This sensitivity and selectivity arise through the transformation of inputs by cortical circuitry. We characterize the circuit mechanisms and dynamics of cortical amplification by making large-scale simultaneous measurements of single cells in awake primates and by testing computational models. By comparing network activity in both driven and spontaneous states with models, we identify the circuit as operating in a regime of balanced amplification. Incoming inputs are strongly but transiently amplified by recurrent excitation. Inhibition acts to counterbalance this excitation by rapidly quenching responses, thereby permitting tracking of time-varying stimuli.

One-Sentence Summary

Sensory cortex uses balanced excitatory and inhibitory circuitry to boost weak signals while maintaining fast sensory dynamics in a changing environment.
MB-SupCon: Microbiome-based predictive models via Supervised Contrastive Learning
Authors: Yang Sen , Wang Shidan , Wang Yiqing , Rong Ruichen , Kim Jiwoong , Li Bo , Koh Andrew Y. , Xiao Guanghua , Li Qiwei , Liu Dajiang , Zhan Xiaowei
Published: June 2022

Human microbiome consists of trillions of microorganisms. Microbiota can modulate the host physiology through molecule and metabolite interactions. Integrating microbiome and metabolomics data have the potential to predict different diseases more accurately. Yet, most datasets only measure microbiome data but without paired metabolome data. Here, we propose a novel integrative modeling framework, Microbiome-based Supervised Contrastive Learning Framework (MB-SupCon). MB-SupCon integrates microbiome and metabolome data to generate microbiome embeddings, which can be used to improve the prediction accuracy in datasets that only measure microbiome data. As a proof of concept, we applied MB-SupCon on 720 samples with paired 16S microbiome data and metabolomics data from patients with type 2 diabetes. MB-SupCon outperformed existing prediction methods and achieves high average prediction accuracies for insulin resistance status (84.62%), sex (78.98%), and race (80.04%). Moreover, the microbiome embeddings form separable clusters for different covariate groups in the lower-dimensional space, which enhances data visualization. We also applied MB-SupCon on a large inflammatory bowel disease study and observed similar advantages. Thus, MB-SupCon could be broadly applicable to improve microbiome prediction models in multi-omics disease studies.
E6AP is important for HPV E6’s role in regulating epithelial homeostasis and its loss impairs keratinocyte commitment to differentiation
Authors: Yin Wen , Egawa Nagayasu , Zheng Ke , Griffin Heather , Aiyenuro Ademola , Bornstein Jacob , Doorbar John
Published: June 2022

Human papillomaviruses (HPV) typically cause chronic infections by modulating homeostasis of infected basal cell to ensure persistence. Using FUCCI and cell-cell competition assays, we established the role of two common viral targets of low-risk and high-risk E6 proteins, E6AP and NHERF1, on four key components of epithelial homeostasis. These includes cell density, proliferation, commitment to differentiation and basal layer delamination. Our RNA sequencing results validated E6’s effects on homeostasis and revealed similar transcriptional gene regulation of E6-expressing cells and E6AP-/- cells. For example, yes-associated protein (YAP) target genes were up-regulated by either E6 expression or E6AP depletion. This is also supported by YAP expression pattern in both monolayer cell culture and HPV-infected clinical tissues. As the conserved binding partner of Alpha group HPV E6 proteins, the precise role of E6AP in modulating keratinocyte phenotype and associated signalling pathways have not been defined. We demonstrate that deletion of E6AP in keratinocytes delayed the onset of differentiation and the abundance of E6AP is reduced in HPV-infected tissue. This suggests that Alpha E6 regulates epithelium homeostasis by inhibiting E6AP’s activity, leading to alteration of multiple downstream pathways including YAP activation. Potential treatments can thus be developed to resolve the reservoir of HPV infection.
Sampling from commercial vessel routes can capture marine biodiversity distributions effectively
Authors: Boyse Elizabeth , Beger Maria , Valsecchi Elena , Goodman Simon
Published: June 2022

Collecting fine-scale occurrence data for marine species across large spatial scales is logistically challenging, but is important to determine species distributions and for conservation planning. Inaccurate descriptions of species ranges could result in designating protected areas with inappropriate locations or boundaries. Optimising sampling strategies therefore is a priority for scaling up survey approaches using tools such as environmental DNA (eDNA) to capture species distributions. eDNA can detect diverse taxa simultaneously, but to date has rarely been applied across large spatial scales relevant for conservation planning. In a marine context, commercial vessels, such as ferries, could provide sampling platforms allowing access to under-sampled areas and repeatable sampling over time to track community changes. However, sample collection from commercial vessels could be biased and may not represent biological and environmental variability. Here, we evaluate whether sampling along Mediterranean ferry routes can yield unbiased biodiversity survey outcomes, based on perfect knowledge from a stacked species distribution model (SSDM) of marine megafauna. Simulations were carried out representing different sampling strategies (random vs systematic), frames (ferry routes vs unconstrained) and number of sampling points. SSDMs were remade from different sampling simulations and compared to the ‘perfect knowledge’ SSDM to quantify the bias associated with different sampling strategies. Ferry routes detected more species and were able to recover known patterns in species richness at smaller sample sizes better than unconstrained sampling points. However, to minimise potential bias, ferry routes should be chosen to cover the variability in species composition and its environmental predictors in the SSDMs. The workflow presented here can be used to design effective eDNA sampling strategies using commercial vessel routes globally. This approach has potential to provide a cost-effective method to access remote oceanic areas on a regular basis, and can recover meaningful data on spatiotemporal biodiversity patterns.
Automatically annotated motion tracking identifies a distinct social behavioral profile following chronic social defeat stress
Authors: Bordes Joeri , Miranda Lucas , Reinhardt Maya , Brix Lea Maria , van Doeselaar Lotte , Engelhardt Clara , Pütz Benno , Agakov Felix , Müller-Myhsok Bertram , Schmidt Mathias V.
Published: June 2022

Severe stress exposure is a global problem with long-lasting negative behavioral and physiological consequences, increasing the risk of stress-related disorders such as major depressive disorder (MDD). An essential characteristic of MDD is the impairment of social functioning and lack of social motivation. Chronic social defeat stress is an established animal model for MDD research, which induces a cascade of physiological and social behavioral changes. The current developments of markerless pose estimation tools allow for more complex and socially relevant behavioral tests, but the application of these tools to social behavior remains to be explored. Here, we introduce the open-source tool “DeepOF” to investigate the individual and social behavioral profile in mice by providing supervised and unsupervised pipelines using DeepLabCut annotated pose estimation data. The supervised pipeline relies on pre-trained classifiers to detect defined traits for both single and dyadic animal behavior. Subsequently, the unsupervised pipeline explores the behavioral repertoire of the animals without label priming, which has the potential of pointing towards previously unrecognized motion motifs that are systematically different across conditions. We here provide evidence that the DeepOF supervised and unsupervised pipelines detect a distinct stress-induced social behavioral pattern, which was particularly observed at the beginning of a novel social encounter. The stress-induced social behavior shows a state of arousal that fades with time due to habituation. In addition, while the classical social avoidance task does identify the stress-induced social behavioral differences, both DeepOF behavioral pipelines provide a clearer and more detailed profile. DeepOF aims to facilitate reproducibility and unification of behavioral classification of social behavior by providing an open-source tool, which can significantly advance the study of rodent individual and social behavior, thereby enabling novel biological insights as well as drug development for psychiatric disorders.
Using canavanine resistance to measure mutation rates in Schizosaccharomyces pombe
Authors: Pai Chen-Chun , Heitzer Ellen , Bertrand Sibyl , Toumazou Sophia , Humphrey Timothy C. , Kearsey Stephen E.
Published: June 2022

We constructed a panel of S. pombe strains expressing DNA polymerase ε variants associated with cancer, specifically POLES297F, POLEV411L, POLEL424V, POLES4459F and used these to compare mutation rates determined by canavanine resistance with other selective methods. Canavanine-resistance mutation rates are broadly similar to those seen with reversion of the ade-485 mutation to adenine prototrophy, but lower than 5-fluoroorotic acid (FOA)-resistance rates (inactivation of ura4+ or ura5+ genes). Inactivation of several genes has been associated with canavanine-resistance in S. pombe but surprisingly whole genome sequencing showed that 8/8 spontaneous canavanine-resistance mutants have an R175C mutation in the any1/arn1 gene. This gene encodes a β-arrestin-like protein involved in mediating Pub1 ubiquitylation of target proteins, and the phenotypic resistance to canavanine by this single mutation is similar to that shown by the original “can1-1” strain, which also has the any1R175C mutation. Some of the spontaneous mutants have additional mutations in arginine transporters, suggesting that this may marginally increase resistance to canavanine. The any1R175C strain showed internalisation of the Cat1 arginine transporter, explaining the canavanine-resistance phenotype. In addition, any1R175C cells were elongated compared to wild type. The mitotic activator Cdc25 has been identified as a Pub1 ubiquitylation target, and since Wee1 inhibition of Cdc2 is counteracted by Cdc25, it is likely that Cdc25 ubiquitylation and downregulation by Any1R175C-Pub1 delays mitotic entry
Phenotypic screening of the ReFrame Drug Repurposing Library to discover new drugs for treating sickle cell disease
Authors: Metaferia Belhu , Cellmer Troy , Dunkelberger Emily B. , Li Quan , Henry Eric R. , Hofrichter James , Staton Dwayne , Hsieh Matthew M. , Conrey Anna K. , Tisdale John F. , Chatterjee Arnab K. , Thein Swee Lay , Eaton William A.
Published: June 2022

Stem-cell transplantation and genetic therapies offer potential cures for patients with sickle cell disease (SCD) but these options require advanced medical facilities and are expensive. Consequently, these treatments will not be available to the vast majority of patients suffering from this disease for many years. What is urgently needed now is an inexpensive oral drug in addition to hydroxyurea, the only successful drug approved by the FDA that inhibits sickle-hemoglobin polymerization. Here we report results of the first phase of our phenotypic screen of the 12,657 compounds of the Scripps ReFrame drug repurposing library using a recently developed high-throughput assay to measure sickling times following deoxygenation to 0% oxygen of red cells from sickle trait individuals. The ReFrame library is a very important collection because the compounds are either FDA-approved drugs or have been tested in clinical trials. From dose-response measurements, 106 of the 12,657 compounds exhibit statistically significant anti-sickling at concentrations ranging from 31 nM to 10 μM. Compounds that inhibit sickling of trait cells are also effective with SCD cells. As many as 21 of the 106 anti-sickling compounds emerge as potential drugs. This estimate is based on a comparison of inhibitory concentrations with free concentrations of oral drugs in human serum. Moreover, the expected therapeutic effect for each level of inhibition can be predicted from measurements of sickling times for cells from individuals with sickle-syndromes of varying severity. Our results should motivate others to develop one or more of these 106 compounds into drugs for treating SCD.

Significance Statement

The vast majority of patients suffering from sickle cell disease live in under-resourced countries. Consequently, advanced medical facilities required for curative therapies, such as stem cell transplantation and gene therapy, will be unavailable to them for a long time. Hydroxyurea, approved by the FDA in 1998, is the only effective drug that inhibits polymerization of the mutant hemoglobin S that stiffens and distorts (“sickles”) red cells, the root cause of the pathology. What is urgently needed now for these patients are additional, inexpensive oral anti-sickling drugs. Our high throughput phenotypic screen of the ReFrame drug repurposing library reported here discovered 106 compounds that are anti-sickling. On a statistical concentration basis, as many as 21 are predicted to be potential drugs.
Novel populations of CD4+T cells associated with vaccine efficacy
Authors: Woodring Therese , Dewey Colin N. , Dos Santos Dias Lucas , He Xin , Dobson Hannah E. , Wüthrich Marcel , Klein Bruce
Published: June 2022

Memory T cells underpin vaccine-induced immunity but are not yet fully understood. To distinguish features of memory cells that confer protective immunity, we used single cell transcriptome analysis to compare antigen-specific CD4+T cells recalled to lungs of mice that received a protective or nonprotective subunit vaccine followed by challenge with a fungal pathogen. We unexpectedly found populations specific to protection that expressed a strong type I interferon response signature, whose distinctive transcriptional signature appeared unconventionally dependent on IFN-γ receptor. We also detected a unique population enriched in protection that highly expressed the gene for the natural killer cell marker NKG7. Lastly, we detected differences in TCR gene use and in Th1- and Th17-skewed responses after protective and nonprotective vaccine, respectively, reflecting heterogeneousIfng- andIl17a-expressing populations. Our findings highlight key features of transcriptionally diverse and distinctive antigen-specific T cells associated with protective vaccine-induced immunity.
High content image analysis in routine diagnostic histopathology predicts outcomes in HPV-associated oropharyngeal squamous cell carcinomas
Authors: Hue Jonas , Valinciute Zaneta , Thavaraj Selvam , Veschini Lorenzo
Published: June 2022

Objective

Routine haematoxylin and eosin (H&E) photomicrographs from human papillomavirus-associated oropharyngeal squamous cell carcinomas (HPV+OpSCC) contain a wealth of prognostic information. In this study, we set out to develop a high content image analysis workflow to quantify features of H&E images from HPV+OpSCC patients to identify prognostic features which can be used for prediction of patient outcomes.

Methods

We have developed a dedicated image analysis workflow using open-source software, for single-cell segmentation and classification. This workflow was applied to a set of 567 images from diagnostic H&E slides in a retrospective cohort of HPV+OpSCC patients with favourable (n = 29) and unfavourable (n = 29) outcomes. Using our method, we have identified 31 quantitative prognostic features which were quantified in each sample and used to train a neural network model to predict patient outcomes. The model was validated by k-fold cross-validation using 10 folds and a test set.

Results

Univariate and multivariate statistical analyses revealed significant differences between the two patient outcome groups in 31 and 16 variables respectively (P<0.05). The neural network model had an overall accuracy of 78.8% and 77.7% in recognising favourable and unfavourable prognosis patients when applied to the test set and k-fold cross-validation respectively.

Conclusion

Our open-source H&E analysis workflow and model can predict HPV+OpSCC outcomes with promising accuracy. Our work supports the use of machine learning in digital pathology to exploit clinically relevant features in routine diagnostic pathology without additional biomarkers.
Comparative transcriptomic analysis of whole blood mycobacterial growth assays and tuberculosis patients’ blood RNA profiles
Authors: Bachanová Petra , Cheyne Ashleigh , Broderick Claire , Newton Sandra M. , Levin Michael , Kaforou Myrsini
Published: June 2022

In vitro whole blood infection models are used for elucidating the immune response to Mycobacterium tuberculosis (Mtb). They exhibit commonalities but also differences, to the in vivo blood transcriptional response during natural human Mtb disease. Here, we present a description of concordant and discordant components of the immune response in blood, quantified through transcriptional profiling in an in vitro whole blood infection model compared to whole blood from patients with tuberculosis disease. We identified concordantly and discordantly expressed gene modules and performed in silico cell deconvolution. A high degree of concordance of gene expression between both adult and paediatric in vivo-in vitro tuberculosis infection was identified. Concordance in paediatric in vivo vs in vitro comparison is largely characterised by immune suppression, while in adults the comparison is marked by concordant immune activation, particularly that of inflammation, chemokine, and interferon signalling. Discordance between in vitro and in vivo increases over time and is driven by T-cell regulation and monocyte-related gene expression, likely due to apoptotic depletion of monocytes and increasing relative fraction of longer-lived cell types, such as T and B cells. Our approach facilitates a more informed use of the whole blood in vitro model, while also accounting for its limitations.
A potential marker for problematic mother-infant bonding revealed by magnetoencephalography study of first-time mothers listening to infant cries
Authors: Hoegholt N.F , Bonetti L. , Stevner A.B.A. , Andersen C.E. , Hughes M , Fernandes H.M. , Vuust P. , Kringelbach M.L
Published: June 2022

Studies using magnetoencephalography (MEG) have identified the orbitofrontal cortex (OFC) to be an important early hub for a ‘parental instinct’ in the brain. This complements the finding from functional magnetic resonance imaging (fMRI) studies linking reward, emotion regulation, empathy and mentalisation networks to the ‘parental brain’. Here, we used MEG in 43 first-time mothers listening to infant and adult cry vocalisations to investigate the link with mother-infant postpartum bonding scores and their level of sleep deprivation (assessed using both actigraphy and sleep logs). We found significant differences 800-1000ms after onset of infant compared to adult cries in source-reconstructed brain activity in areas previously linked to the parental brain. Importantly, mothers with weaker bonding scores showed decreased brain responses to infant cries in the auditory cortex, middle and superior temporal gyrus, OFC, hippocampal areas, supramarginal gyrus and inferior frontal gyrus at around 100-200ms after stimulus onset. In contrast, we did not find correlations with sleep deprivation scores. The significant changes in brain processing of an infant’s distress signals could be a novel marker of weaker infant bonding in new mothers and should be investigated in vulnerable populations.
Cell-Type-Specific Epigenetic Priming of Gene Expression in Nucleus Accumbens by Cocaine
Authors: Mews Philipp , Van der Zee Yentl , Kronman Hope , Gurung Ashik , Ramakrishnan Aarthi , Browne Caleb , Futamura Rita , Estill Molly , Ryan Meagan , Reyes Abner A , Garcia Benjamin A , Sidoli Simone , Shen Li , Nestler Eric J
Published: June 2022

A hallmark of addiction is the ability of drugs of abuse to trigger relapse after periods of prolonged abstinence. Here, we describe a novel epigenetic mechanism whereby chronic cocaine exposure causes lasting chromatin and downstream transcriptional modifications in the nucleus accumbens (NAc), a critical brain region controlling motivation. We link prolonged withdrawal from cocaine to the depletion of the histone variant H2A.Z, coupled to increased genome accessibility and latent priming of gene transcription, in D1 dopamine receptor-expressing medium spiny neurons (D1 MSNs) that relates to aberrant gene expression upon drug relapse. The histone chaperone ANP32E removes H2A.Z from chromatin, and we demonstrate that D1 MSN-selective Anp32e knockdown prevents cocaine-induced H2A.Z depletion and blocks cocaine’s rewarding actions. By contrast, very different effects of cocaine exposure, withdrawal, and relapse were found for D2-MSNs. These findings establish histone variant exchange as an important mechanism and clinical target engaged by drugs of abuse to corrupt brain function and behavior.
Hepatocyte Rap1a Contributes To Obesity- and Statin-Associated Hyperglycemia
Authors: Wang Yating , Spolitu Stefano , Zadroga John A. , Sarecha Amesh K. , Ozcan Lale
Published: June 2022

Excessive hepatic glucose production contributes to the development of hyperglycemia and is a key feature of type 2 diabetes. Here, we report that activation of hepatic Rap1a suppresses gluconeogenic gene expression and glucose production, whereas Rap1a silencing stimulates them. Rap1a activation is suppressed in obese mouse liver and restoring its activity lowers blood glucose and improves glucose intolerance. As Rap1a’s membrane localization and activation depends on its geranylgeranylation, which is inhibited by statins, we found lower active-Rap1a levels in statin-treated hepatocytes and the human liver. Similar to Rap1a inhibition, statins stimulated hepatic gluconeogenesis and increased fasting blood glucose in obese mice. Geranylgeraniol treatment, which acts as the precursor for geranylgeranyl isoprenoids, restored Rap1a activity and improved statin-mediated glucose intolerance. Mechanistically, we show that Rap1a activation induces actin polymerization, which suppresses gluconeogenesis by Akt-mediated FoxO1 inhibition. Thus, Rap1a regulates hepatic glucose homeostasis, and blocking its activity, via lowering geranylgeranyl isoprenoids, contributes to statin-induced glucose intolerance.
Immuno-electron microscopy localizes Caenorhabditis elegans vitellogenins along the classic exocytosis route
Authors: Zhai Chao , Zhang Nan , Li Xi-Xia , Tan Xue-Ke , Sun Fei , Dong Meng-Qiu
Published: June 2022

Vitellogenins (VITs) are the most abundant proteins in adult hermaphrodite C. elegans. VITs are synthesized in the intestine, secreted to the pseudocoelom, matured into yolk proteins (YPs), and finally deposited in oocytes to support embryonic and larval development. How VITs are secreted out of the intestine remains unclear. In this study, we use immuno-electron microscopy (immuno-EM) to characterize the wild-type subcellular structures containing VITs or YPs. In the intestinal cells of young adult worms, we identify VITs along an exocytic pathway consisting of the rough ER, the Golgi, and the lipid bilayer bounded vesicles, which we call intestinal vitellogenin vesicles (VVs). This suggests that the classic exocytotic pathway mediates secretion of VITs from the intestine to the pseudocoelom. We also show that pseudocoelomic yolk patches (PYPs) are membrane-less and amorphous. The different VITs/YPs are packed as a mixture into the above structures. The size of VVs can vary with the VIT levels and the age of the worm. On adult day 2 (AD 2), intestinal VVs (∼200 nm in diameter) are smaller than gonadal yolk organelles (YOs, ∼500 nm in diameter). VVs, PYPs, and YOs share a uniform, medium electron density by conventional EM. The morphological profiles documented in this study can serve as a reference for future studies of VITs/YPs. Surveying the findings from this study and elsewhere, we review in the discussion the post-translational modifications and protein-protein interactions of C. elegans VITs/YPs.
Hspa13 Regulates Endoplasmic Reticulum and Cytosolic Proteostasis Through Modulation of Protein Translocation
Authors: Espinoza Mateo F. , Nguyen Khanh K. , Sycks Melody M. , Lyu Ziqi , Montoya Maureen R. , Genereux Joseph C.
Published: June 2022

Most eukaryotic secretory proteins are co-translationally translocated through Sec61 into the endoplasmic reticulum (ER). Because these proteins have evolved to fold in the ER, their mistargeting is associated with toxicity. Genetic experiments have implicated the ER Hsp70 Hspa13/STCH as involved in processing of nascent secretory proteins. Herein, we evaluate the role of Hspa13 in protein import and the maintenance of cellular proteostasis. We find that Hspa13 interacts primarily with the Sec61 translocon and its associated factors. Hspa13 overexpression inhibits translocation of the secreted protein transthyretin (TTR), leading to accumulation and aggregation of immature TTR in the cytosol. ATPase inactive mutants of Hspa13 further inhibit translocation and maturation of secretory proteins. While Hspa13 overexpression inhibits cell growth and ER quality control, HSPA13 knockout destabilizes proteostasis and increases sensitivity to ER disruption. Thus, we propose that Hspa13 regulates import through the translocon to maintain both ER and cytosolic protein homeostasis.

The raw mass spectrometry data associated with this manuscript has been deposited in the PRIDE archive and can be accessed at PXD033498.
Secreted Aeromonas GlcNAc binding protein GbpA stimulates epithelial cell proliferation in the zebrafish intestine
Authors: Banse Allison V. , VanBeuge Stephanie , Smith T. Jarrod , Logan Savannah L. , Guillemin Karen
Published: June 2022

In response to microbiota colonization, the intestinal epithelia of many animals exhibit increased rates of cell proliferation. We used gnotobiotic larval zebrafish to identify a secreted factor from the mutualist Aeromonas veronii that is sufficient to promote intestinal epithelial cell proliferation. This secreted A. veronii protein is a homologue of the Vibrio cholerae GlcNAc binding protein GbpA, which was identified as a chitin-binding colonization factor in mice. GbpA was subsequently shown to be a lytic polysaccharide monooxygenase (LPMO) that can degrade recalcitrant chitin. Our phenotypic characterization of gbpA deficient A. veronii found no alterations in the mutant cells’ biogeography in the zebrafish intestine and only a modest competitive disadvantage in chitin-binding and colonization fitness when competed against the wild type strain. These results argue against the model of GbpA being a secreted adhesin that binds simultaneously to bacterial cells and GlcNAc, and instead suggests that GbpA is part of a bacterial GlcNAc utilization program. We show that the host proliferative response to GbpA occurs in the absence of bacteria upon exposure of germ-free zebrafish to preparations of native GbpA secreted from either A. veronii or V. cholerae or recombinant A. veronii GbpA.

Furthermore, domain 1 of A. veronii GbpA, containing the predicted LPMO activity, is sufficient to stimulate intestinal epithelial proliferation. We conjecture that intestinal epithelia upregulate their rates of renewal in response to secreted bacterial GbpA proteins as an adaptive strategy for coexisting with bacteria that can degrade glycan constituents of the protective intestinal lining.
Assessing sustainability knowledge for undergraduate students in different academic programs and settings
Authors: Briens Elysa C.M. , Chiu Yiwen , Braun David , Verma Priya , Fiegel Gregg , Pompeii Brian , Singh Kylee
Published: June 2022

Purpose

As sustainability teaching and learning rises in importance, an increasing number of higher education institutions (HEIs) are assessing the effectiveness of their approach to sustainability education. However, most assessments fall short in determining the impacts of curriculum plans on learning outcomes. Therefore, this study aims to assess the impact of curricula on undergraduate sustainability knowledge and assess opportunities for improving sustainability education in HEIs.

Design/methodology/approach

A campus-wide survey deployed at California Polytechnic State University, San Luis Obispo, (Cal Poly) solicited data identifying students’ sustainability knowledge score (SKS). The survey collected responses from undergraduate student groups enrolled in different curriculum plans under different academic settings.

Findings

This study reveals that Cal Poly honors students enrolled in a structured sustainability curriculum have significantly higher SKS than general students (i.e. nonhonors students) enrolled in random sustainability courses. Further, taking at least three sustainability-related courses significantly distinguishes SKS for general students. The results also show that SKS does not significantly differ across colleges, suggesting that additional sustainability education can benefit all students.

Originality/value

Findings of this study provide statistical evidence to justify institutional efforts to integrate sustainability into existing courses, with the minimum requirement of three sustainability-related courses to make an impact on SKS for the general student population. Such efforts could represent the first steps toward developing sustainability education at a HEI and improving sustainability learning outcomes.
Middle-class people imagining democratic attitudes: the Pakistani experience
Authors: Shah Naimatullah , Soomro Bahadur Ali
Published: June 2022

Purpose

Measuring and understanding the dynamics of democracy as well as democratic attitudes of people have become a big challenge for every democratic state. The study proposes the investigation of middle-class peoples’ attitudes towards democracy in Pakistan.

Design/methodology/approach

The study employs a deductive approach based on cross-sectional data from Pakistan’s middle-class people. The researchers use a survey questionnaire through a convenience sampling technique. Finally, the study utilizes 1854 samples to conclude the findings.

Findings

The evidence confirms that trust in public institutions and political engagement positively and significantly impact peoples’ democratic attitudes. In addition, the investigation witnessed the preference for democracy also supports understanding middle-class peoples’ democratic attitudes.

Practical implications

The study would provide an endorsement for politicians of Pakistan to perceive the inclination of middle-class people towards democracy. The study would guide the researchers and policymakers and intellectualize the middle-class peoples’ opinions and attitudes. Moreover the study would support reflecting the public confidence in decision making and ability to deliver. Finally the study findings would contribute to the literature of political science and democracy to understand democratic attitudes mainly focusing on middle-class populations.

Originality/value

This study empirically confirms the Pakistani middle-class peoples’ attitudes towards democracy.
Navigating uncharted paths to the American professoriate: experiences of immigrant black female faculty
Authors: Tetteh Lilian Naa Obiorkor , Zaier Amani , Maina Faith
Published: June 2022

Purpose

This study aims to examine the challenges of immigrant black female faculty (IBFFs) from Africa who have joined the American professoriate and also explore the cognitive processing behind student and staff perception and expectations of immigrant professors of color. This category of scholars faces the intersectional “triple bind” of being females, immigrants and people of color; as a result, they may encounter peculiar challenges in their professional practice. Hence, throwing light on their experiences will help advance robust supportive systems that are essential to promoting all-inclusive staff productivity and the internationalization drive of post-secondary institutions.

Design/methodology/approach

Through the narrative analysis approach, the authors capitalized on the life histories, perspectives and experiences of eight IBFFs from Africa serving in US universities to offer new insights into this group’s roles, difficulties and triumphs. In-depth interviews that lasted for about 1–2 h per participant were transcribed and key themes were analyzed.

Findings

The authors found that IBBFs face a couple of challenges in their quest to transition and serve in the American professoriate. Some of the identified challenges include labor market discrimination, discounting of academic work and credentials, unfair evaluation, cultural taxation and lack of supportive work environment.

Originality/value

While previous studies focused on challenges that black female faculty (BFF) face in joining academia, little is known about the academic voyage of IBBFs pursuing careers in higher education. The objective of this study is to address this gap and, by extension, broaden the discourse on equity, diversity and inclusion within the academic landscape.
Lee Kuan Yew’s role in minimising corruption in Singapore
Authors: Quah Jon S.T.
Published: June 2022

Purpose

This paper analyses the role of Lee Kuan Yew, Singapore’s first prime minister from June 1959 to November 1990, in minimising corruption by implementing a zero-tolerance policy toward corruption in Singapore.

Design/methodology/approach

This paper is based on the analysis of Lee’s beliefs and the policies he introduced to curb corruption in Singapore.

Findings

Lee’s disdain for corruption and his beliefs in meritocracy and the importance of good leadership shaped his commitment to a zero-tolerance policy against corruption, which was enforced impartially and sustained in Singapore for the past 62 years.

Originality/value

This analysis of how Lee transformed Singapore into one of the least corrupt countries in the world would be of interest to policy-makers, practitioners and scholars concerned with minimising corruption in their own countries.
Managing employees’ performance in Indian public sector undertakings during COVID-19 pandemic-induced blended working
Authors: Sameer Sanjeet Kumar
Published: June 2022

Purpose

Acknowledging the significance of perceived organizational support (POS) for employees’ performance, this study aims to examine the underlying mechanism of task performance in a COVID-19 pandemic-induced blended working (TPBW) environment and the role of perceived usefulness of digitalization (PUDBW) in the process.

Design/methodology/approach

Survey data collected from 204 managers of Indian public sector undertakings pursuing blended working for the first time were analyzed using structural equation modelling. A qualitative study on 31 such managers was also performed.

Findings

Although employees perceived an improvement in POS, PUDBW and TPBW (during the COVID pandemic) in comparison to the pre-COVID time when traditional work design was operational, yet the improvement in task performance was not directly influenced by POS. POS had a positive effect on PUDBW, which in turn positively affected TPBW. PUD acted as a mediator. A negative moderation effect of POS on the relationship between PUDBW and TPBW was found.

Practical implications

Findings of the study may help organizations and policymakers to focus on key enablers, such as organizational support and relevant digital initiatives, for ensuring better task performance by their employees during a blended working environment, even in difficult times as the COVID-19 pandemic.

Originality/value

This study, for the first time, examined the proposed relationships in a new work setting of blended working and explained the underlying mediation and moderation mechanisms in their relationships.
In the Forefront and on the Margins: Jews, Secularism and Women's Liberation in Ontario and British Columbia, 1960s–1980s
Authors: Marks Lynne , Little Margaret
Published: June 2022

This article examines Jewish feminists in the British Columbia and Ontario women's movements, particularly among radical and socialist feminists. Feminists within these movements saw organised religion as patriarchal, hostile to the interests of women and thus to be rejected. Using archival and oral history sources, we argue that looking more closely at Jewish feminists within second‐wave feminism can help us to more clearly understand the nature of secularism in the women's movement, its implicit contradictions and unspoken Christian bias. Jewish feminists noted, for example, that Christian holidays such as Christmas or Easter could be seen as secular celebrations, while any celebration of Jewish heritage, even if it emerged from a very secular Jewish socialist culture, was suspect within secular feminist circles, and indeed could be denounced as an acceptance of patriarchy. We analyse the distinctive experiences of Jewish feminists as a minority community within an ostensibly secular women's movement. We argue that Jewish activist women, because of their liminal position within the movement, as both secular feminists and ethnic/religious other, could challenge and reveal the Christian roots of feminist secularism.
Facilitating Tacit Collusion Through Voluntary Disclosure: Evidence from Common Ownership
Authors: PAWLICZEK ANDREA , SKINNER A. NICOLE , ZECHMAN SARAH L. C.
Published: June 2022

We examine whether voluntary disclosure is associated with incentives for firms to collude. Public disclosure can facilitate collusion by aiding with coordination and monitoring for defections. Using common ownership (investors holding stock in competing firms) to identify reduced incentives to compete, we find a positive association between public disclosure and these incentives. We also find that common ownership is positively associated with measures of disclosure that are likely to facilitate tacit collusion and that this association is stronger in industries where collusion is easier. Our study expands the literature on disclosure and competition among firms by showing that public disclosure is positively associated with incentives for tacit collusion. This finding is consistent with managers facilitating anticompetitive outcomes using voluntary disclosure.
Increasing temperatures affect multiyear life cycle of the outbreak bush‐cricket Barbitistes vicetinus (Orthoptera, Tettigoniidae)
Authors: Ortis Giacomo , Marini Lorenzo , Cavaletto Giacomo , Mazzon Luca
Published: June 2022

Although outbreaks of rare species are unusual, several insect species have become emerging pests probably due to the ongoing environmental changes. Barbitistes vicetinus was first described in 1993 as an endemic bush‐cricket of north‐east Italy and was considered rare until 2008, when it became an established pest, causing severe damages to forests and crops. The possible role of temperature in changing its life cycle has still to be fully understood. Here, we explored the effect of summer temperature on egg diapause and the effect of winter temperature on egg survival. Field observations showed that the proportion of embryos that can complete development at the end of summer ranged from zero to nearly 90% depending on summer temperatures. A substantial shift in the rate of development from 20% to nearly 80% occurred in a thermal range of about 1 °C. On the contrary, overwinter egg survival was high and constant (90%) across a wide range of winter temperatures that go well beyond both the cold and warm thermal limits of the current species range. Overall, the results suggest a potential key role of summer temperature warming on the outbreak propensity of this species that is able to switch from a multiyear to an annual life cycle with just a 1–2 °C warming.