bluuebunny/crossref_metadata_2025 huggingface dataset:
TGF-β2 regulates neuronal Ankyrin-G and promotes its interaction with KCC2
Authors: Rigkou Anastasia , Pethe Abhishek , Roussa Eleni
Published: December 2023

The neuronal K+/Cl-cotransporter 2 (KCC2) is the major Cl-extruder in CNS neurons and responsible for fast hyperpolarizing postsynaptic inhibition in mature neurons. Impaired KCC2 function has been associated with several brain pathologies. KCC2 forms immunocomplexes with several proteins that may regulate KCC2 membrane trafficking, stability and function, thus, tuning important cellular processes, including chloride homeostasis and dendritic spine development. In the brain, the scaffold protein Ankyrin-G, encoded by theAnk3gene, is expressed in several isoforms with distinct spatial and temporal expression patterns, is regulated by TGF-β signalling and is proposed as a KCC2 interaction partner. Moreover,Ank3gene has been implicated in several neuropsychiatric disorders.

Here, we investigated a putative impact of transforming growth factor beta 2 (TGF-β2) on KCC2/Ankyrin-G interaction using quantitative RT-PCR, immunoblotting, immunoprecipitation and immunofluorescence in mouse immature and differentiated hippocampal neurons and in forebrain and brainstem tissue fromTgf-β2deficient mice. The results show TGF-β2-dependent downregulation ofAnk3transcripts, as well as KCC2/Ankyrin-G interaction in mouse brainstem tissue at embryonic day (E) 17.5.In vitro, loss ofTgf-β2resulted in significantly reduced axonal and somatic Ankyrin-G in immature neurons and significantly reduced somatic Ankyrin-G abundance in differentiated mouse hippocampal neurons. Membrane abundance of Ankyrin-G was downregulated inTgf-β2mutants as well, a phenotype rescued by application of exogenous TGF-β2. Moreover, the results suggest the presence of a Golgi-associated Ankyrin-G isoform in neurons and significantly impaired membrane KCC2 abundance following knock down ofAnk3. Thus, the present study provides new insights into Ankyrin-G regulation by TGF-β2 in neurons and first evidence of a TGF-β2-regulated interaction of KCC2 with Ankyrin-G. Moreover, these results strengthen the notion for TGF-β2 as pivotal regulator of KCC2 abundance and function.
Sexual Dimorphism, Altered Hippocampal Glutamatergic Neurotransmission and Cognitive Impairment in APP Knock-In Mice
Authors: Findley Caleigh A. , McFadden Samuel .A. , Hill Tiarra , Peck Mackenzie R. , Quinn Kathleen , Hascup Kevin N. , Hascup Erin R.
Published: December 2023

Background

It is well established that glutamatergic neurotransmission plays an essential role in learning and memory. Previous studies indicate that glutamate dynamics shift with Alzheimer’s disease (AD) progression, contributing to negative cognitive outcomes.

Objective

In this study, we characterized hippocampal glutamatergic signaling with age and disease progression in a knock-in mouse model of AD (APPNL-F/NL-F).

Methods

At 2-4 and 18+ months old, male and female APPNL/NL, APPNL-F/NL-F, and C57BL/6 mice underwent cognitive assessment using Morris water maze (MWM) and Novel Object Recognition (NOR). Then, basal and 70 mM KCl stimulus-evoked glutamate release was measured in the dentate gyrus (DG), CA3, and CA1 regions of the hippocampus using a glutamate-selective microelectrode in anesthetized mice.

Results

Glutamate recordings support elevated stimulus-evoked glutamate release in the DG and CA3 of young APPNL-F/NL-Fmale mice that declined with age compared to age-matched control mice. Young female APPNL-F/NL-Fmice exhibited increased glutamate clearance in the CA1 that slowed with age compared to age-matched control mice. Male and female APPNL-F/NL-Fmice exhibited decreased CA1 basal glutamate levels, while males also showed depletion in the CA3. Cognitive assessment demonstrated impaired spatial cognition in aged male and female APPNL-F/NL-Fmice, but only aged females displayed recognition memory deficits compared to age-matched control mice.

Conclusions

These findings confirm a sex-dependent hyper-to-hypoactivation glutamatergic paradigm in APPNL-F/NL-Fmice. Further, data illustrate a sexually dimorphic biological aging process resulting in a more severe cognitive phenotype for female APPNL-F/NL-Fmice than their male counterparts. Research outcomes mirror that of human AD pathology and provide further evidence of divergent AD pathogenesis between sexes.
Intracellular defensive symbiont is culturable and capable of transovarial, vertical transmission
Authors: Maeda Gerald P. , Kelly Mary Katherine , Sundar Aadhunik , Moran Nancy A.
Published: December 2023

Insects frequently form heritable associations with beneficial bacteria that are vertically transmitted from parent to offspring. Long term vertical transmission has repeatedly resulted in genome reduction and gene loss rendering many such bacteria incapable of independent culture. Among aphids, heritable endosymbionts often provide a wide range of context-specific benefits to their hosts. Although these associations have large impacts on host phenotypes, experimental approaches are often limited by an inability to independently cultivate these microbes. Here, we report the axenic culture ofCandidatusFukatsuia symbiotica strain WIR, a heritable bacterial endosymbiont of the pea aphid,Acyrthosiphon pisum. Whole genome sequencing revealed similar genomic features and high sequence similarity to previously described strains, suggesting the cultivation techniques used here may be applicable toCa. F. symbiotica strains from distantly related aphids. Microinjection of the isolated strain into uninfected aphids revealed that it can reinfect developing embryos, and is maintained in subsequent generations via transovarial maternal transmission. Artificially infected aphids exhibit similar phenotypic and life history traits compared to native infections, including protective effects against an entomopathogenicFusariumspecies. Overall, our results show thatCa. F. symbiotica may be a useful tool for experimentally probing the molecular mechanisms underlying heritable symbioses and antifungal defense in the pea aphid system.

IMPORTANCE

Diverse eukaryotic organisms form stable, symbiotic relationships with bacteria that provide benefits to their hosts. While these associations are often biologically important, they can be difficult to probe experimentally, because intimately host-associated bacteria are difficult to access within host tissues, and most cannot be cultured. This is especially true of the intracellular, maternally inherited bacteria associated with many insects, including aphids. Here, we demonstrate that a pea aphid-associated strain of the heritable endosymbiont,CandidatusFukatsuia symbiotica, can be grown outside of its host using standard microbiology techniques, and can readily re-establish infection that is maintained across host generations. These artificial infections recapitulate the effects of native infections making this host-symbiont pair a useful experimental system. Using this system, we demonstrate thatCa. F. symbiotica infection reduces host fitness under benign conditions, but protects against a previously unreported fungal pathogen.
The trichothecene mycotoxin deoxynivalenol facilitates cell-to-cell invasion during wheat-tissue colonisation byFusarium graminearum
Authors: Armer Victoria , Urban Martin , Ashfield Tom , Deeks Michael J. , Hammond-Kosack Kim E.
Published: December 2023

Fusarium Head Blight (FHB) disease on small grain cereals is primarily caused by the ascomycete fungal pathogenFusarium graminearum.Infection of floral spike tissues is characterised by the biosynthesis and secretion of potent trichothecene mycotoxins, of which deoxynivalenol (DON) is widely reported due to its negative impacts on grain quality and consumer safety. TheTRI5gene encodes an essential enzyme in the DON biosynthesis pathway and the single gene deletion mutant,ΔTri5, is widely reported to restrict disease progression to the inoculated spikelet. In this study, we present novel bioimaging evidence revealing that DON facilitates the traversal of the cell wall through plasmodesmata, a process essential for successful colonisation of host tissue. Chemical complementation ofΔTri5did not restore macro- or microscopic phenotypes, indicating that DON secretion is tightly regulated both spatially and temporally. A comparative qualitative and quantitative morphological cellular analysis revealed infections had no impact on plant cell wall thickness. Immuno- labelling of callose at plasmodesmata during infection indicates that DON can increase deposits when applied exogenously, but is reduced whenF. graminearumhyphae are present. This study highlights the complexity of the inter-connected roles of mycotoxin production, cell wall architecture and plasmodesmata in this highly specialised interaction.
Enhancing Recognition and Interpretation of Functional Phenotypic Sequences through Fine-Tuning Pre-Trained Genomic Models
Authors: Du Duo , Zhong Fan , Liu Lei
Published: December 2023

Decoding high-quality human genomic sequences requires comprehensive analysis of DNA sequence functionality. Through computational and experimental approaches, researchers study the genotype-phenotype relationship and generate important datasets that help unravel complicated genetic blueprints. This study explores the use of deep learning, particularly pre-trained models like DNA_bert_6 and human_gpt2-v1, in interpreting and representing human genome sequences. We meticulously construct multiple datasets linking genotypes and phenotypes to fine-tune pre-trained models for precise DNA sequence classification. Furthermore, we specifically focused on the human endogenous retrovirus (HERV) dataset with commendable classification performance (both binary and multi-classification accuracy and F1 values above 0.935 and 0.888, respectively). We evaluate the influence of sequence length on classification results and analyze the impact of feature extraction in the model’s hidden layers using the HERV dataset. To further understand the phenotype-specific patterns learned by the model, we perform enrichment, pathogenicity and conservation analyzes of specific motifs in the HERV sequence with high average local representation weight (LRAW) scores. Overall, the generated datasets further provide numerous additional genotype-phenotype datasets for evaluating the performance of genomic models. The findings highlight the potential of large models in learning DNA sequence representations, particularly when utilizing the HERV dataset, and provide valuable insights for future research. This work represents an innovative strategy that combines pre-trained model representations with classical omics methods for analyzing the functionality of genome sequences, fostering cross-fertilization between genomics and advanced AI. The source code and data are available athttps://github.com/GeorgeBGM/Genome_Fine-Tuning.
Consensus scHPF Identifies Cell Type-Specific Drug Responses in Glioma by Integrating Large-Scale scRNA-seq
Authors: Levitin Hanna Mendes , Zhao Wenting , Bruce Jeffrey N. , Canoll Peter , Sims Peter A.
Published: December 2023

Single-cell transcriptomic analyses now frequently involve elaborate study designs including samples from multiple individuals, experimental conditions, perturbations, and batches from complex tissues. Dimensionality reduction is required to facilitate integration, interpretation, and statistical analysis. However, these datasets often include subtly different cellular subpopulations or state transitions, which are poorly described by clustering. We previously reported a Bayesian matrix factorization algorithm called single-cell hierarchical Poisson factorization (scHPF) that identifies gene co-expression patterns directly from single-cell RNA-seq (scRNA-seq) count matrices while accounting for transcript drop-out and noise. Here, we describe consensus scHPF, which analyzes scHPF models from multiple random initializations to identify the most robust gene signatures and automatically determine the number of factors for a given dataset. Consensus scHPF facilitates integration of complex datasets with highly multi-modal posterior distributions, resulting in factors that can be uniformly analyzed across individuals and conditions. To demonstrate the utility of consensus scHPF, we performed a meta-analysis of a large-scale scRNA-seq dataset from drug-treated, human glioma slice cultures generated from surgical specimens across three major cell types, 19 patients, 10 drug treatment conditions, and 52 samples. In addition to recapitulating previously reported cell type-specific drug responses from smaller studies, consensus scHPF identified disparate effects of the topoisomerase poisons etoposide and topotecan that are highly consistent with the distinct roles and expression patterns of their respective protein targets.
Genomic location dictates lytic promoter activity during herpes simplex virus latency
Authors: Singh Navneet , Zachariah Sherin , Phillips Aaron T. , Tscharke David
Published: December 2023

Herpes simplex virus 1 (HSV-1) is a significant pathogen that establishes life-long latent infections with intermittent episodes of resumed disease. In mouse models of HSV infection, persistent low-level lytic gene expression has been detected during latency in the absence of spontaneous reactivation events leading to new virus production. This viral activity during latency has been reported using a sensitive Cre-marking model for several lytic gene promoters placed in one location in the HSV-1 genome. Here we extend these findings in the same model by examining first, the activity of an ectopic lytic gene promoter in other places in the genome and second, whether native promoter activity might be detectable. We found that both for ectopic and native lytic gene promoters,Creexpression during latency was detected in our model, but only when the promoter was located near the ends of the unique long genome segment. This location is significant because it is in close proximity to the region from which latency associated transcripts (LAT) are derived. These results show for the first time that native HSV-1 lytic gene promoters can produce protein products during latency, but that this activity is only detectable when they are located close to the LAT locus.

Author summary

HSV is a significant human pathogen and the best studied model of mammalian virus latency. Traditionally the active (lytic) and inactive (latent) phases of infection were considered to be distinct, but the notion of latency being entirely quiescent is evolving due to the detection of some lytic gene expression during latency. Here we add to this literature by finding that activity can be found for native lytic gene promotors as well as for constructs placed ectopically in the HSV genome. However, this activity was only detectable when these promoters were located close by a region known to be transcriptionally active during latency. These data have implications for our understanding of HSV gene regulation during latency and the extent to which transcriptionally active regions are insulated from adjacent parts of the viral genome.
Molecular determinants of SEC61A1 mutant R236C in two patient-derived cellular platforms
Authors: Weiand Matthias , Sandfort Vanessa , Nadzemova Oksana , Schierwagen Robert , Trebicka Jonel , Kabar Iyad , Schmidt Hartmut , Zibert Andree
Published: December 2023

Background & objectives

SEC61A1 encodes a central protein of the mammalian translocon machinery residing in the ER. Mutations ofSEC61A1are implicated to result in various severe diseases. Recently, mutation R236C was identified in patients having autosomal dominant polycystic liver disease (ADPLD), which originates from defects of cholangiocytes in the liver. The molecular phenotype of R236C was assessed.

Methods

Two cellular platforms were established from the same cell source of an ADPLD patient by different methodology. Cells were immortalized by retroviral transduction of an oncogene (UCi) or reprogrammed to induced pluripotent stem cells (iPSC) that were differentiated to cholangiocyte progenitor-like cells (CPLC). UCi and CPLC were subjected to several analyses of molecular pathways that were previously associated with development of polycystic disease.

Results

UCi displayed markers of epithelial cells, while CPLCs expressed typical markers of both cholangiocytes and hepatocytes. Cells encoding R236C showed a stable, continuous proliferation in both platforms, however growth rates were reduced as compared to wildtype control. Autophagy, cAMP synthesis, and secretion of important marker proteins were reduced in R236C-expressing cells. In addition, R236C induced increased calcium leakiness from the ER to the cytoplasm. Upon oxidative stress, R236C led to a high induction of apoptosis and necrosis.

Conclusion

Although the grade of aberrant cellular functions differed between the two platforms, overall the molecular phenotype of R236C was shared suggesting that the mutation, regardless of the cell type, has a dominant impact on disease-associated pathways that cause ADPLD. Our approach may be valuable to decipher the molecular pathways of other rare genetic diseases using patient-specific cell models.
Spike synchrony as a measure of Gestalt structure
Authors: Zemliak Viktoria , Mayer Julius , Nieters Pascal , Pipa Gordon
Published: December 2023

The function of spike synchrony has long been debated in the neuroscience community. Some researchers view synchrony as a byproduct of brain activity, while others argue that it serves as a mechanism for binding perceptual features. We, however, argue for an alternative view on the computational role of synchrony: it can serve as a mechanism for estimating the prior probability of incoming stimuli. In V1, this probability can be estimated by comparing the input stimulus with previously acquired visual experience. Such experience is encoded in horizontal intracortical connections, as they are subject to change, learn, and adapt to incoming visual stimuli throughout the course of life. Thus, the V1 connectivity structure can encode the acquired visual experience in the form of its aggregate statistics. Since the aggregate statistics of natural images tend to follow the Gestalt principles, we can assume that V1 is more often exposed to Gestalt-like stimuli, and this is manifested in its connectivity structure. At the same time, the connectivity structure has an impact on the synchrony of neuronal firings in V1. In our work, we used a spiking model with V1-like connectivity to demonstrate that spike synchrony reflects the Gestalt structure of the stimulus. We conducted simulation experiments with three Gestalt laws: proximity, similarity, and continuity, and found significant differences in firing synchrony for stimuli with varying degrees of Gestalt-likeness. This allows us to conclude that spike synchrony indeed reflects the Gestalt structure of the stimulus, which can be interpreted as a mechanism for prior probability estimation.

Author Summary

Neurons in the brain fire synchronously in different contexts, in response to different stimuli. However, the function of synchrony is very debatable in the neuroscience community. We suggest that synchrony plays an important role in brain computations: it can estimate how well a network is familiar with the incoming stimulus. We tested our hypothesis on the simulation of neuronal activity in a model of primary visual cortex - a brain region which is processing simple visual features, such as lines of different angle orientation. The connections between neurons in this brain area store the acquired visual experience in the form of its statistics, such as edge cooccurrences. We built the connectivity in our model in accordance with principles of connectivity in primary visual cortex, assuming that it reflects natural images statistics. We tested our model on artificial stimuli, which represented more and less experienced visual features. Our results showed that spike synchrony is a global phenomenon which emerges across the large parts of the network, and it reflects the familiarity of the network with the stimulus. Thus, it can serve as a form of recognition memory and has a potential for usage in various applications which require estimation of input familiarity.
Neuronal avalanches in temporal lobe epilepsy as a diagnostic tool: a noninvasive investigation of intrinsic resting state dynamics
Authors: Corsi Marie-Constance , Lopez Emahnuel Troisi , Sorrentino Pierpaolo , Danieli Alberto , Cuozzo Simone , Bonanni Palo , Duma Gian Marco
Published: December 2023

Background and Objectives

The epilepsy diagnosis still represents a complex process, with misdiagnosis reaching 40%. Here, we aimed at building an automatable workflow, to help the clinicians in the diagnostic process, differentiating between controls and a population of patients with temporal lobe epilepsy (TLE). While primarily interested in correctly classifying the participants, we used data features providing hints on the underlying pathophysiological processes. Specifically, we hypothesized that neuronal avalanches (NA) may represent a feature that encapsulates the rich brain dynamics better than the classically used functional connectivity measures (Imaginary Coherence; ImCoh).

Methods

We recorded 10 minutes of resting state activity with high-density scalp electroencephalography (hdEEG; 128 channels). We analyzed large-scale activation bursts (NA) from source activation, to capture altered dynamics. Then, we used machine-learning algorithms to classify epilepsy patients vs. controls, and we described the goodness of the classification as well as the effect of the durations of the data segments on the performance.

Results

Using a support vector machine (SVM), we reached a classification accuracy of 0.87 ± 0.10 (SD) and an area under the curve (AUC) of 0.94 ± 0.06. The use of avalanches-derived features, generated a mean increase of 16% in the accuracy of diagnosis prediction, compared to ImCoh. Investigating the main features informing the model, we observed that the dynamics of the entorhinal cortex, superior and inferior temporal gyri, cingulate cortex and prefrontal dorsolateral cortex were informing the model with NA. Finally, we studied the time-dependent accuracy in the classification. While the classification performance grows with the duration of the data length, there are specific lengths, at 30s and 180s at which the classification performance becomes steady, with intermediate lengths showing greater variability. Classification accuracy reached a plateau at 5 minutes of recording.

Discussion

We showed that NA represents a better EEG feature for an automated epilepsy identification, being related with neuronal dynamics of pathology-relevant brain areas. Furthermore, the presence of specific durations and the performance plateau might be interpreted as the manifestation of the specific intrinsic neuronal timescales altered in epilepsy. The study represents a potentially automatable and noninvasive workflow aiding the clinicians in the diagnosis.
Development of a human heart-on-a-chip model using induced pluripotent stem cells, fibroblasts and endothelial cells
Authors: Liu Yun , Kamran Rumaisa , Han Xiaoxia , Wang Mengxue , Li Qiang , Lai Daoyue , Naruse Keiji , Takahashi Ken
Published: December 2023

In recent years, research on organ-on-a-chip technology has been flourishing, particularly for drug screening and disease model development. Fibroblasts and vascular endothelial cells engage in crosstalk through paracrine signaling and direct cell-cell contact, which is essential for the normal development and function of the heart. Therefore, to faithfully recapitulate cardiac function, it is imperative to incorporate fibroblasts and vascular endothelial cells into a heart-on-a-chip model. Here, we report the development of a human heart-on-a-chip composed of induced pluripotent stem cell (iPSC)-derived cardiomyocytes, fibroblasts, and vascular endothelial cells. Vascular endothelial cells cultured on microfluidic channels responded to the flow of culture medium mimicking blood flow by orienting themselves parallel to the flow direction, akin toin vivovascular alignment in response to blood flow. Furthermore, the flow of culture medium promoted stronger junction formation between vascular endothelial cells, as evidenced by CD31 staining and lower apparent permeability. The triculture condition of iPSC-derived cardiomyocytes, fibroblasts, and vascular endothelial cells resulted in higher expression of the ventricular cardiomyocyte marker IRX4 and increased contractility compared to the biculture condition with iPSC-derived cardiomyocytes and fibroblasts alone. Such triculture-derived cardiac tissues exhibited cardiac responses similar toin vivohearts, including an increase in heart rate upon noradrenaline administration. In summary, we have achieved the development of a heart-on-a-chip composed of cardiomyocytes, fibroblasts, and vascular endothelial cells that mimicsin vivocardiac behavior.
A fur plucking model to study herpes simplex virus reactivation and recurrent disease
Authors: Philip Drake T. , Goins Nigel M. , Lazear Helen M.
Published: December 2023

Herpes simplex viruses (HSV-1 and HSV-2) most commonly cause ulcerative epithelial lesions (cold sores, genital herpes). Importantly, HSV establishes life-long persistent (latent) infection in sensory neurons. Reactivation from latency produces recurrent epithelial lesions, which constitute the greatest burden of HSV disease in people. The mechanisms that regulate latency and reactivation remain poorly understood, in part due to limitations in the animal models available for studying HSV reactivation. We have developed a simple and tractable model to induce HSV-1 and HSV-2 reactivation from latently infected sensory ganglia. We infected C57BL/6 mice with 1 × 106FFU of HSV-1 (strain NS) or 500 FFU of HSV-2 (strain 333) on flank skin depilated by manual plucking. 35 days post-infection (dpi) we re-plucked the fur from the infected flank and observed recurrent lesions in the same dermatome as the primary infection. We detected HSV DNA in dermatome skin through 4 days post-re-plucking. We found that shaving the ipsilateral flank or plucking the contralateral flank did not induce recurrent skin lesions, suggesting that fur plucking is a specific stimulus that induces HSV reactivation. Further, we were able to induce multiple rounds of plucking induced recurrent disease, providing a model to investigate the lifelong nature of HSV infection. This new model provides a tractable system for studying pathogenic mechanisms of and therapeutic interventions against HSV reactivation and recurrent disease.
CRISPR screens in 3D tumourspheres identified miR-4787-3p as a transcriptional start site miRNA essential for breast tumour-initiating cell growth
Authors: Stiff Tom , Bayraktar Salih , Dama Paola , Stebbing Justin , Castellano Leandro
Published: December 2023

Breast cancer (BC) is a heterogeneous malignancy with distinct molecular subtypes and clinical characteristics. Tumour-initiating cells (TICs) are a small subset of cancer cells that are responsible for tumour initiation and progression.

Our study employed pooled CRISPR screens, integrating 2D and 3D culture models, to identify miRNAs critical in BC tumorsphere formation. These screens combined with RNA-seq experiments allowed us to identify the miRNA signature and their targets that are essential for tumoursphere growth. Amongst them, miR-4787-3p exhibited significant up-regulation in BC, particularly in basal-like BCs, suggesting its association with aggressive disease phenotypes. Surprisingly, despite its location within the 5’UTR of a protein coding gene, which define DROSHA-independent transcription start site (TSS)-miRNAs, our findings revealed its dependence on both DROSHA and DICER1 for maturation. Inhibition of miR-4787-3p hindered tumorsphere formation, highlighting its potential as a therapeutic target in BC. Moreover, our study proposes elevated miR-4787-3p expression as a potential prognostic biomarker for adverse outcomes in BC patients. We found that protein-coding genes positively selected in the CRISPR screens were enriched of miR-4787-3p putative targets. Amongst these identified key targets, we selected ARHGAP17, FOXO3A, and PDCD4 because are known tumour suppressors in cancer and experimentally validated the interaction of miR-4787-3p with their 3’UTRs. Our work illuminates the molecular mechanisms underpinning miR-4787-3p’s oncogenic role in BC. These findings advocate for further clinical investigations targeting miR-4787-3p and underscore its prognostic significance, offering promising avenues for tailored therapeutic interventions and prognostic assessments in BC.
Identification of the modulatory Ca2+binding sites of acid-sensing ion channel 1a
Authors: Molton Ophélie , Bignucolo Olivier , Kellenberger Stephan
Published: December 2023

Acid-sensing ion channels (ASICs) are neuronal H+-gated, Na+-permeable channels involved in learning, fear sensing, pain sensation and neurodegeneration. An increase in the extracellular Ca2+concentration shifts the pH dependence of ASIC1a to more acidic values. Here, we predicted candidate residues for Ca2+binding on ASIC1a, based on available structural information and molecular dynamics simulations; the function of channels carrying mutations of these residues was then measured. We identify several residues in cavities previously associated with pH-dependent gating, whose mutation decreased the Ca2+-induced shift in ASIC1a pH dependence, likely due to a disruption of Ca2+binding. We show also that Mg2+shares some of the binding sites with Ca2+, and that some of the Ca2+binding sites are functionally conserved in the splice variant ASIC1b. Our identification of divalent cation binding sites in ASIC1a shows how Ca2+affects ASIC1a gating, elucidating a regulatory mechanism present in many ion channels.
Cooperativity in RNA chemical probing experiments modulates RNA 2D structure
Authors: Arnold Ethan B , Cohn Daniel D , Bose Emma M , Wolfe Gregory , Jones Alisha N
Published: December 2023

Small molecule chemical probes that covalently bond atoms of flexible nucleotides are widely employed in RNA structure determination. Atomistic molecular dynamic (MD) simulations recently revealed that the binding of RNA by chemical probes is influenced by cooperative effects, leading to measured reactivities that depend on the concentration of the chemical probe. In this work, we used selective 2’ hydroxyl acylation analyzed by primer extension (SHAPE) and dimethyl sulfate (DMS) chemical probing experiments to explore whether RNA structures are modulated by chemical probe binding events. We find that as the concentration of a chemical probe increases, modified nucleotides locally modulate the RNA structure, resulting in the increase or decrease of chemical probe reactivity in surrounding nucleotides. This cooperative effect is dependent on both chemical probe concentration and size. We find that these cooperative effects can be used to link structurally related nucleotides, and that the cooperative effects result in strikingly different 2D structure predictions as probe concentrations are varied.
Effects of atmospheric CO2concentration on transpiration and leaf elongation responses to drought in wheat, perennial ryegrass and tall fescue
Authors: Acker Victoria , Durand Jean-Louis , Perrot Cédric , Roy Eric , Frak Elzbieta , Barillot Romain
Published: December 2023

We studied the effects of atmospheric CO2concentration ([CO2]) on the leaf growth response to drought in perennial ryegrass, tall fescue and wheat.

Plants were grown in growth chambers at either 200 or 800 ppm of CO2. At leaf 6-7 unfolding, half of the plants were subjected to severe drought. Leaf elongation rate (LER) was measured daily, while plant transpiration was continuously recorded gravimetrically. Water-soluble carbohydrate concentration, water and osmotic potentials in the leaf growing zone were measured at drought onset, at mid-drought and at the time of leaf growth cessation.

[CO2] caused stomata closure and therefore reduction of instantaneous transpiration rate and water loss. As a result, CO2mitigated the impacts of drought on LER and delayed growth cessation for all three species. For ryegrass, LER and soil relative water content (SRWC) relation was improved with CO2, presumably due to a better stomatal regulation. CO2did not affect nighttime water potential nor osmotic potential of the growing zone. Related to leaf growth, we observed the main effect of CO2on tillering but no effect on the plant development. In total, water consumption was similar (wheat, tall fescue) or greater (ryegrass) with CO2.
Microbiota of the sulfur cycle in an extremely contaminated Technosol undergoing pedogenesis: A culture-dependent and metagenomic approach
Authors: Demin K. , Minkina T. , Sushkova S. , Delegan Y. , Kocharovskaya Y. , Gorovtsov A.
Published: December 2023

Understanding the microbial communities involved in the global sulfur cycle is crucial for comprehending key biogeochemical processes on Earth. However, most studies tend to focus on marine ecosystems, while investigations into the terrestrial sulfur cycle are scarce. In this study, we employed culture-dependent techniques and metagenomics to characterize sulfur-cycling microbiota in extremely contaminated soils. We analyzed shotgun and amplicon sequencing data to assess taxonomical diversity, metagenome-assembled genomes (MAGs) for functional diversity, and also calculated the most probable numbers (MPN) of sulfur-oxidizing and sulfate-reducing bacteria based on culture-dependent data. Our taxonomic profiling, using both shotgun and amplicon data, revealed a high diversity of sulfur cycle bacteria, which was found to be dependent on pH levels. Additionally, our findings confirmed recent modelling of specific taxa biogeographical distribution, such as the sulfur-reducing Mesotoga. Using a functional metagenomics approach, we identified non-canonical taxa involved in dissimilatory sulfur metabolism (e.g., sulfate-reducing acidobacteria and members of the Binatota phylum), and canonical taxa engaged in various oxidative, reductive, and organosulfur transformations (e.g., sulfur-oxidizing alpha-, beta-, and gammaproteobacteria). Furthermore, we discovered that multiple taxa in the studied Technosol encoded different enzymes capable of sulfite transformation and the removal of sulfite from various organosulfonate molecules, thus contributing to the cryptic cycling of sulfur compounds. Estimated MPNs of sulfur-oxidizing bacteria aligned with our shotgun and amplicon data, while those of sulfate-reducing bacteria contradicted functional metagenomic findings. Based on our overall analysis, we support the idea that sulfate-reducers belong to the rare biosphere in soil. We suggest that they behave differently in soils compared to aquatic habitats due to the high taxonomic diversity along with low absolute abundance. Our findings unveil a diverse and unique community of sulfur-metabolizing bacteria that has evolved in soil under severe technogenic pollution, high bulk sulfur content, and fluctuating redox states.
Social cognitive regions of human association cortex are selectively connected to the amygdala
Authors: Edmonds Donnisa , Salvo Joseph J. , Anderson Nathan , Lakshman Maya , Yang Qiaohan , Kay Kendrick , Zelano Christina , Braga Rodrigo M.
Published: December 2023

Reasoning about someone’s thoughts and intentions – i.e., forming a theory of mind – is an important aspect of social cognition that relies on association areas of the brain that have expanded disproportionately in the human lineage. We recently showed that these association zones comprise parallel distributed networks that, despite occupying adjacent and interdigitated regions, serve dissociable functions. One network is selectively recruited by theory of mind processes. What circuit properties differentiate these parallel networks? Here, we show that social cognitive association areas are intrinsically and selectively connected to regions of the anterior medial temporal lobe that are implicated in emotional learning and social behaviors, including the amygdala at or near the basolateral complex and medial nucleus. The results suggest that social cognitive functions emerge through coordinated activity between amygdala circuits and a distributed association network, and indicate the medial nucleus may play an important role in social cognition in humans.
RAPIDASH: A tag-free enrichment of ribosome-associated proteins reveals compositional dynamics in embryonic tissues and stimulated macrophages
Authors: Susanto Teodorus Theo , Hung Victoria , Levine Andrew G , Kerr Craig H , Yoo Yongjin , Chen Yuxiang , Oses-Prieto Juan A , Fromm Lisa , Fujii Kotaro , Wernig Marius , Burlingame Alma , Ruggero Davide , Barna Maria
Published: December 2023

Ribosomes are emerging as direct regulators of gene expression, with ribosome-associated proteins (RAPs) allowing ribosomes to modulate translational control. However, a lack of technologies to enrich RAPs across many sample types has prevented systematic analysis of RAP number, dynamics, and functions. Here, we have developed a label-free methodology called RAPIDASH to enrich ribosomes and RAPs from any sample. We applied RAPIDASH to mouse embryonic tissues and identified hundreds of potential RAPs, including DHX30 and LLPH, two forebrain RAPs important for neurodevelopment. We identified a critical role of LLPH in neural development that is linked to the translation of genes with long coding sequences. Finally, we characterized ribosome composition remodeling during immune activation and observed extensive changes post-stimulation. RAPIDASH has therefore enabled the discovery of RAPs ranging from those with neuroregulatory functions to those activated by immune stimuli, thereby providing critical insights into how ribosomes are remodeled.
New understanding on the critical factors determining stability of passive film on Fe-Cr alloy based on aberration-corrected TEM study
Authors: Zhang B. , Wei X.X. , Ma X.L.
Published: December 2023

Purpose

In recent years, using aberration-corrected transmission electron microscopy, the authors have achieved precisely detecting the structural evolution of passive film as well as its interface zone at atomic scale. The purpose of this paper aims to make a brief review to show the authors’ new understanding and perspective on the issue of critical factors determining stability of passive film of Fe-Cr alloy.

Design/methodology/approach

The introduction of single crystal enabled the authors to obtain a distinct metal/passive film interface and better characterize the structure of the interface region. The authors use aberration-corrected TEM to conduct cross-sectional observation and directly capture the details across the entire film at a high spatial and energy resolution.

Findings

Apart from the passive film itself, the interface zone, including metal/film (Me/F) interface and the adjacent metal side, is also the site which is attacked. Accordingly, the nature of the interface zone, such as microstructure, composition and atomic configuration, is one of the critical factors determining the stability of passive film.

Originality/value

Deciphering the critical factors determining the stability of passive film is of great significance and has been a fundamental issue in corrosion science. Great attention has been paid to the nature of the passive film itself. In contrast, the possible role of the interface between the passive film and the metal is rarely taken into account. Based on the advanced analytical tool with high spatial resolution, the authors have specified the significant role of interface structures on the macro-scale stability of passive film.
Pandemic-related changes in alcohol use among LGB+ people with and without mental health and neurodevelopmental conditions: a multinational cross-sectional study
Authors: Connolly Dean J. , Gilchrist Gail , Ferris Jason , Puljević Cheneal , Maier Larissa , Barratt Monica J. , Winstock Adam , Davies Emma L.
Published: December 2023

Purpose

Using data from 36,981 respondents to the Global Drug Survey (GDS) COVID-19 Special Edition, this study aims to compare changes, following the first “lockdown,” in alcohol consumption between lesbian, gay, bisexual and other sexual minority (LGB+) and heterosexual respondents with and without lifetime mental health and neurodevelopmental (MHND) conditions.

Design/methodology/approach

Characteristics and drinking behavior of respondents to GDS who disclosed their sexual orientation and past 30-day alcohol use were described and compared. LGB+ participants with and without MHND conditions were compared, and logistic regression models identified correlates of increased drinking among LGB+ people. The impact of changed drinking on the lives of LGB+ participants with and without MHND conditions was assessed.

Findings

LGB+ participants who reported that they were “not coping well at all” with the pandemic had twofold greater odds of reporting increased binge drinking. LGB+ participants with MHND conditions were significantly more likely than those without to report increased drinking frequency (18.7% vs 12.4%), quantity (13.8% vs 8.8%) and that changed drinking had impacted their lives.

Originality/value

This study, which has a uniquely large and international sample, explores aspects of alcohol use not considered in other COVID-19 alcohol use research with LGB+ people; and to the best of the authors’ knowledge, this is the first study to explore alcohol use among LGB+ people with MHND conditions.
Navigating management changes in the post-COVID era: suggestions for adapting to the new dynamic work landscape
Authors: Insch Gary S. , Green Karen Yvonne , Franz Diana
Published: December 2023

Purpose

The study investigates the current changes and future challenges in management practice as a result of the Covid-19 pandemic. According to creative destruction theory, industry disruptions (e.g., advancements in technology) combined with economic shocks (e.g., effects of the pandemic) often force impacted industries to undergo significant changes in order to survive. Therefore, it is important to investigate the changes on current and future management practice in the post-Covid world.

Design/methodology/approach

This exploratory study uses semi-structured interviews with 20 experienced public accounting leaders (PAL) whose titles include partner, director, CFO, senior manager, and manager.

Findings

This study provides PAL perspectives on the challenges of managing in an increasingly hybrid environment, the shift of the organizational structure of firms, the changes in responsibilities/skill sets needed at all levels of the firm, and the expectation that these challenges will continue to evolve.

Originality/value

This study contributes to the literature by showcasing how management practice (through the lens of accounting leaders) has significantly changed. The accounting profession was deemed an essential industry and continued in operation throughout the COVID pandemic. This study identifies six issues that will continue to influence management practice and provides topics for future research.
Reconceptualising diversity management from a paradox lens
Authors: Brøgger Stina Rydell , Andersen Maria Dahl
Published: December 2023

Purpose

Since the 1980's, diversity management (DM) has been regarded as a relevant scholarly and practical endeavour laden with different and often contrasting rationales and conceptualisations. In this regard, the current literature on DM largely differentiates between two overarching approaches – the instrumental and the critical approach with varying conceptualisations and underlying understandings of DM. The purpose of this paper is to discuss how a paradox lens can be utilised to bridge existing understandings of diversity management.

Design/methodology/approach

The authors aim to discuss the current state of DM literature and reconceptualise DM from a paradox lens.

Findings

The authors argue that the use of a paradox lens on DM allows for challenges to be brought forward instead of ignored or hidden away by illuminating and actively acknowledging both the liberating but also the challenging and oftentimes constraining experiences for the actors involved. Thus, a Paradox lens offers space for embracing and utilising paradoxes when working with diversity.

Originality/value

Diversity management is no new concept in the field of human resource management and several scholars argue that the longstanding divide between the instrumental and critical approach remains problematic and limiting for the practice of DM. Hence, the value of reconceptualising DM from a paradox lens lies in bridging the two approaches in order to give way to viewing DM as a nuanced, dynamic and multifaceted practice that can accommodate complexity and contradictions in new and potentially beneficial manners.
Innovation and happiness management enhancing transcendence at work in the banking sector in Spain
Authors: Sánchez-Hernández M. Isabel , Robina-Ramirez Rafael , Stankevičiūtė Živilė
Published: December 2023

Purpose

The purpose of the paper is to delve into innovation and happiness management linked to the definition of transcendence at work. The paper analyses in the context of innovation and happiness management the relation of the three dimensions taken from Khari and Sinha (2020: Sense of we-ness, self-connectedness and work as a service. The paper also proposed indicators to applied transcendence and moral competencies to the banking sector guiding behaviour toward successful experiences at work as an antecedent of both, transcendence and employees´ performance.

Design/methodology/approach

The article starts with a VOSviewer-based bibliometric analysis to examine the recent development of happiness management as an emergent topic of research. A co-word analysis served to identify that the main research theme related to the topic is transcendence at work. The theoretical framework serves for developing a conceptual model that is analysed by taking structural equations modelling (SEM) as the method and partial least squares (PLS) as the technique. To test the hypotheses, the authors employed a sample of 354 employees from the main banks in Spain in 2021 (Santander, Banco Bilbao Vizcaya Argentaria (BBVA), CaixaBank, Bankia and Sabadell).

Findings

The results confirm that Innovation and happiness management is related to moral competencies, which refer to the set of knowledge, skills and abilities that facilitate ethical behaviour in the banking sector. Innovation and happiness management include individual attributes for good performance in each job; this research is in line with the prominent call in the literature to consider moral competencies in human resources management.

Originality/value

Originality lies on the answer of the question: what is the role of employee transcendence in the turbulent banking sector today? This paper seeks to approach and measure the relation of innovation, happiness and transcendence at work, Transcendence at work often arises when individuals connect their work to a higher purpose or mission, that connection is based on the idea that any effort to improve any of these three attributes provides successful solutions for the complex banking sector's performance.