bluuebunny/crossref_metadata_2025 huggingface dataset:
MANGEM: a web app for Multimodal Analysis of Neuronal Gene expression, Electrophysiology and Morphology
Authors: Olson Robert Hermod , Kalafut Noah Cohen , Wang Daifeng
Published: April 2023

Single-cell techniques have enabled the acquisition of multi-modal data, particularly for neurons, to characterize cellular functions. Patch-seq, for example, combines patch-clamp recording, cell imaging, and single-cell RNA-seq to obtain electrophysiology, morphology, and gene expression data from a single neuron. While these multi-modal data offer potential insights into neuronal functions, they can be heterogeneous and noisy. To address this, machine-learning methods have been used to align cells from different modalities onto a low-dimensional latent space, revealing multi-modal cell clusters. However, the use of those methods can be challenging for biologists and neuroscientists without computational expertise and also requires suitable computing infrastructure for computationally expensive methods. To address these issues, we developed a cloud-based web application, MANGEM (Multimodal Analysis of Neuronal Gene expression, Electrophysiology, and Morphology) athttps://ctc.waisman.wisc.edu/mangem. MANGEM provides a step-by-step accessible and user-friendly interface to machine-learning alignment methods of neuronal multi-modal data while enabling real-time visualization of characteristics of raw and aligned cells. It can be run asynchronously for large-scale data alignment, provides users with various downstream analyses of aligned cells and visualizes the analytic results such as identifying multi-modal cell clusters of cells and detecting correlated genes with electrophysiological and morphological features. We demonstrated the usage of MANGEM by aligning Patch-seq multimodal data of neuronal cells in the mouse visual cortex.

Author Summary

The human brain is made up of billions of tiny cells called neurons, each with their own important job. Scientists are now able to study individual neurons in more detail than ever before using new advanced techniques. They can look at different data of individual neurons like how genes are being used (gene expression), how the neuron responds to electrical signals (electrophysiology), and what it looks like (morphology). By combining all of this information, they can start to group similar neurons together and figure out what they do. However, due to the data complexity, this process can be very complicated and hard for researchers without sufficient computational skills. To address this, we developed a web app, MANGEM (Multimodal Analysis of Neuronal Gene Expression, Electrophysiology, and Morphology). It lets scientists upload their data and select emerging machine-learning approaches to find groups of similar neurons. It also makes interactive visualizations to help them explore the characteristics of neuron groups and understand what they do.
Engineering a material-genetic interface as safety switch for embedded therapeutic cells
Authors: Jerez-Longres Carolina , Gómez-Matos Marieta , Becker Jan , Hörner Maximilian , Wieland Franz-Georg , Timmer Jens , Weber Wilfried
Published: April 2023

Encapsulated cell-based therapies involve the use of genetically-modified cells embedded in a material in order to produce a therapeutic agent in a specific location in the patient’s body. This approach has shown great potential in animal model systems for treating diseases such as type I diabetes or cancer, with selected approaches having been tested in clinical trials. Despite the promise shown by encapsulated cell therapy, though, there are safety concerns yet to be addressed, such as the escape of the engineered cells from the encapsulation material and the resulting production of therapeutic agents at uncontrolled sites of the body. For that reason, there is great interest in the implementation of safety switches that protect from those side effects. Here, we develop a material-genetic interface as safety switch for engineered mammalian cells embedded into hydrogels. Our switch allows the therapeutic cells to sense whether they are embedded in the hydrogel by means of a synthetic receptor and signaling cascade that link transgene expression to the presence of an intact embedding material. The system design is highly modular, allowing its flexible adaptation to other cell types and embedding materials. This autonomously acting switch constitutes an advantage over previously described safety switches, which rely on user-triggered signals to modulate activity or survival of the implanted cells. We envision that the concept developed here will advance the safety of cell therapies and facilitate their translation to clinical evaluation.

Graphical abstract
Bi-functional particles for real-time acidification and proteolysis multiplex assay in macrophages
Authors: Méndez-Alejandre Alba , Armando Raymond Benjamin Bernard , Trost Matthias , Marín-Rubio José Luis
Published: April 2023

Phagosome acidification and proteolysis are essential processes in the immune response to contain and eliminate pathogens. In recent years, there has been an increased desire for a rapid and accurate method of assessing these processes in real-time. Here, we outline the development of a multiplexed assay that allows simultaneous monitoring of phagosome acidification and proteolysis in the same sample using silica beads conjugated to pHrodo and DQ BSA. We describe in detail how to prepare the bi-functional particles and show proof of concept using differentially activated macrophages. This multiplexed spectrophotometric assay allows rapid and accurate assessment of phagosome acidification and proteolysis in real-time and could provide valuable information for understanding the immune response to pathogen invasion.
Increased Cerebral Serum Amyloid A2 and Parameters of Oxidation in Arylsulfatase B (N-Acetylgalactosamine-4-Sulfatase)-Null Mice
Authors: Bhattacharyya Sumit , Tobacman Joanne K.
Published: April 2023

Introduction

Chondroitin sulfate and chondroitin sulfate proteoglycans have been associated with Alzheimer’s Disease (AD), and the impact of modified chondroitin sulfates is being investigated in several animal and cell-based models of AD. Published reports have shown the role of accumulation of chondroitin 4-sulfate and decline in Arylsulfatase B (ARSB; B-acetylgalactosamine-4-sulfatase) in other pathology, including nerve injury, traumatic brain injury, and spinal cord injury. However, the impact of ARSB deficiency on AD pathobiology has not been reported, although changes in ARSB were associated with AD in two prior reports. The enzyme ARSB removes 4-sulfate groups from the non-reducing end of chondroitin 4-sulfate and dermatan sulfate and is required for their degradation. When ARSB activity declines, these sulfated glycosaminoglycans accumulate, as in the inherited disorder Mucopolysaccharidosis VI.

Methods

Reports about chondroitin sulfate, chondroitin sulfate proteoglycans and chondroitin sulfatases in Alzheimer’s Disease were reviewed. Measurements of SAA2, iNOS, lipid peroxidation, chondroitin sulfate proteoglycan 4, and other parameters were performed in cortex and hippocampus from ARSB-null mice and controls by QRT-PCR, ELISA, and other standard assays.

Results

SAA2 mRNA expression and protein, CSPG4 mRNA, chondroitin 4-sulfate and i-NOS were increased significantly in ARSB-null mice. Measures of lipid peroxidation and redox state were significantly modified.

Discussion

Findings indicate that decline in ARSB leads to changes in expression of parameters associated with AD in the hippocampus and cortex of the ARSB-deficient mouse.

Conclusions

Further investigation of the impact of decline in ARSB on the development of AD may provide a new approach to prevent and treat AD.
Action does not enhance but attenuates predicted touch
Authors: Job Xavier , Kilteni Konstantina
Published: April 2023

Dominant motor control theories propose that the brain predicts and attenuates the somatosensory consequences of actions, referred to as somatosensory attenuation. Support comes from psychophysical and neuroimaging studies showing that touch applied on a passive hand elicits attenuated perceptual and neural responses if it is actively generated by one’s other hand, compared to identical touch from an external origin. However, recent experimental findings have challenged this view by providing psychophysical evidence that the perceived intensity of touch on the passive hand is enhanced if the active hand does not receive touch simultaneously with the passive hand (somatosensory enhancement) and by further attributing attenuation to the double tactile stimulation of the hands upon contact. Here, we directly contrasted the hypotheses of the attenuation and enhancement models regarding how action influences somatosensory perception by manipulating whether the active hand contacts the passive hand. We further assessed somatosensory perception in the absence of any predictive cues in a condition that turned out to be essential for interpreting the experimental findings. In three preregistered experiments, we demonstrate that action does not enhance the predicted touch (Experiment 1), that the previously reported “enhancement” effects are driven by the reference condition used (Experiment 2), and that self-generated touch is robustly attenuated regardless of whether the two hands make contact (Experiment 3). Our results provide conclusive evidence that action does not enhance but attenuates predicted touch and prompt a reappraisal of recent experimental findings upon which theoretical frameworks proposing a perceptual enhancement by action prediction are based.

Highlights

Dominant motor control theories propose that action attenuates or cancels predicted touch.

Recent theories propose that action enhances predicted touch.

We show that action does not enhance but attenuates predicted touch.
A monoclonal antibody raised against human EZH2 cross-reacts with the RNA-binding protein SAFB
Authors: Cherney Rachel E. , Mills Christine A. , Herring Laura E. , Braceros Aki K. , Calabrese J. Mauro
Published: April 2023

The Polycomb Repressive Complex 2 (PRC2) is a conserved enzyme that tri-methylates Lysine 27 on Histone 3 (H3K27me3) to promote gene silencing. PRC2 is remarkably responsive to the expression of certain long noncoding RNAs (lncRNAs). In the most notable example, PRC2 is recruited to the X-chromosome shortly after expression of the lncRNAXistbegins during X-chromosome inactivation. However, the mechanisms by which lncRNAs recruit PRC2 to chromatin are not yet clear. We report that a broadly used rabbit monoclonal antibody raised against human EZH2, a catalytic subunit of PRC2, cross-reacts with an RNA-binding protein called Scaffold Attachment Factor B (SAFB) in mouse embryonic stem cells (ESCs) under buffer conditions that are commonly used for chromatin immunoprecipitation (ChIP). Knockout of EZH2 in ESCs demonstrated that the antibody is specific for EZH2 by western blot (no cross-reactivity). Likewise, comparison to previously published datasets confirmed that the antibody recovers PRC2-bound sites by ChIP-Seq. However, RNA-IP from formaldehyde-crosslinked ESCs using ChIP wash conditions recovers distinct peaks of RNA association that co-localize with peaks of SAFB and whose enrichment disappears upon knockout of SAFB but not EZH2. IP and mass spectrometry-based proteomics in wild-type and EZH2 knockout ESCs confirm that the EZH2 antibody recovers SAFB in an EZH2-independent manner. Our data highlight the importance of orthogonal assays when studying interactions between chromatin-modifying enzymes and RNA.
Taste papilla cell differentiation requires tongue mesenchyme via ALK3-BMP signaling to regulate the production of secretory proteins
Authors: Ishan Mohamed , Wang Zhonghou , Zhao Peng , Yao Yao , Stice Steven , Wells Lance , Mishina Yuji , Liu Hong-Xiang
Published: April 2023

Taste papillae are specialized organs each of which is comprised of an epithelial wall hosting taste buds and a core of mesenchymal tissue. In the present study, we report that during the early stages of embryonic development, bone morphogenetic protein (BMP) signaling mediated by type 1 receptor ALK3 in the tongue mesenchyme is required for the epithelial Wnt/β-catenin activity and taste papilla cell differentiation. Mesenchyme-specific knockout (cKO) ofAlk3usingWnt1-CreandSox10-Creresulted in an absence of taste papillae at E12.0. Biochemical and cell differentiation analyses demonstrated that mesenchymal ALK3-BMP signaling governs the production of previously unappreciated secretory proteins, i.e., suppresses those that inhibiting and facilitates those promoting taste cell differentiation. Bulk RNA-Sequencing analysis revealed many more differentially expressed genes (DEGs) in the tongue epithelium than in the mesenchyme inAlk3 cKOvs control. Moreover, we detected a down-regulated epithelial Wnt/β-catenin signaling, and taste papilla development in theAlk3 cKOwas rescued by GSK3β inhibitor LiCl, but not Wnt3a. Our findings demonstrate for the first time the requirement of tongue mesenchyme in taste papilla cell differentiation.

Summary statement

This is the first set of data to implicate the requirement of tongue mesenchyme in taste papilla cell differentiation.
Deep mutational scanning highlights a new role for cytosolic regions in Hrd1 function
Authors: Peterson Brian G. , Hwang Jiwon , Russ Jennifer E. , Schroeder Jeremy , Freddolino Peter L. , Baldridge Ryan D.
Published: April 2023

Misfolded endoplasmic reticulum proteins are degraded through a process called endoplasmic reticulum associated degradation (ERAD). Soluble, lumenal ERAD targets are recognized, retrotranslocated across the ER membrane, ubiquitinated, extracted from the membrane, and degraded by the proteasome using an ERAD pathway containing a ubiquitin ligase called Hrd1. To determine how Hrd1 mediates these processes, we developed a deep mutational scanning approach to identify residues involved in Hrd1 function, including those exclusively required for lumenal degradation. We identified several regions required for different Hrd1 functions. Most surprisingly, we found two cytosolic regions of Hrd1 required for lumenal ERAD substrate degradation. Using in vivo and in vitro approaches, we defined roles for disordered regions between structural elements that were required for Hrd1’s ability to autoubiquitinate and interact with substrate. Our results demonstrate that disordered cytosolic regions promote substrate retrotranslocation by controlling Hrd1 activation and establishing directionality of retrotranslocation for lumenal substrate across the endoplasmic reticulum membrane.
Structure of Trypanosoma peroxisomal import complex unveils conformational dynamics
Authors: Sonani Ravi R. , Blat Artur , Jemiola-Rzeminska Malgorzata , Lipinski Oskar , Patel Stuti N. , Sood Tabassum , Dubin Grzegorz
Published: April 2023

Peroxisomes are membrane enclosed organelles hosting diverse metabolic processes in eukaryotic cells. Having no protein synthetic abilities, peroxisomes import all required enzymes from the cytosol through a peroxin (pex) import system. Peroxisome targeting sequence 1 (PTS1)-tagged cargo is recognized by soluble receptor, Pex5. The cargo-Pex5 complex docks at the peroxisomal membrane translocon, composed of Pex14 and Pex13, facilitating translocation into the peroxisomal lumen. Despite its significance, the structural basis of this process is poorly understood. Here, we present a cryo-electron microscopy (cryo-EM) structure of cargo-Pex5-Pex14 ternary complex fromTrypanosoma cruzi,the causative agent of human Chagas disease. The atomic model of the Pex5 (residues 327-653) bound to malate dehydrogenase (MDH, cargo) tetramer and Pex14NTD(residues 21-85) reveals dynamic motions and secondary interfaces. Specifically, we observe a swinging motion of Pex5 at the MDH-Pex5 interface. Additionally, the noncanonical contact surfaces are observed at the MDH-Pex5 and Pex5-Pex14 interfaces. Mutational analysis of the former interface indicates that it does not significantly enhance the affinity, underscoring the dynamic nature of cargo-Pex5 interactions. The latter interface constitutes an extended binding site of Pex14NTDover Pex5. We discuss the implications of these findings for understanding peroxisomal transport mechanisms.

HIGHLIGHTS

The structure of the peroxisomal import ternary complex (MDH-Pex5TPR-Pex14NTD) is determined using cryo-EM.

Pex5 interface with the cargo (MDH) is characterized by significant conformational dynamics.

The extended binding site of Pex14NTDon Pex5 is revealed.
Astrocyte-Secreted Neurocan Controls Inhibitory Synapse Formation and Function
Authors: Irala Dolores , Wang Shiyi , Sakers Kristina , Nagendren Leykashree , Ulloa-Severino Francesco Paolo , Bindu Dhanesh Sivadasan , Eroglu Cagla
Published: April 2023

Astrocytes strongly promote the formation and maturation of synapses by secreted proteins. To date, several astrocyte-secreted synaptogenic proteins controlling different stages of excitatory synapse development have been identified. However, the identities of astrocytic signals that induce inhibitory synapse formation remain elusive. Here, through a combination ofin vitroandin vivoexperiments, we identified Neurocan as an astrocyte-secreted inhibitory synaptogenic protein. Neurocan is a chondroitin sulfate proteoglycan that is best known as a protein localized to the perineuronal nets. However, Neurocan is cleaved into two after secretion from astrocytes. We found that the resulting N- and C-terminal fragments have distinct localizations in the extracellular matrix. While the N-terminal fragment remains associated with perineuronal nets, the Neurocan C-terminal fragment localizes to synapses and specifically controls cortical inhibitory synapse formation and function. Neurocan knockout mice lacking the whole protein or only its C-terminal synaptogenic region have reduced inhibitory synapse numbers and function. Through super-resolution microscopy andin vivoproximity labeling by secreted TurboID, we discovered that the synaptogenic domain of Neurocan localizes to somatostatin-positive inhibitory synapses and strongly regulates their formation. Together, our results unveil a mechanism through which astrocytes control circuit-specific inhibitory synapse development in the mammalian brain.
Stratified microbial communities in Australia’s only anchialine cave are taxonomically novel and drive chemotrophic energy production via coupled nitrogen-sulphur cycling
Authors: Ghaly Timothy M. , Focardi Amaranta , Elbourne Liam D. H. , Sutcliffe Brodie , Humphreys William , Paulsen Ian T. , Tetu Sasha G.
Published: April 2023

Background

Anchialine environments, in which oceanic water mixes with freshwater in coastal aquifers, are characterised by stratified water columns with complex physicochemical profiles. These environments, also known as subterranean estuaries, support an abundance of endemic macro and microorganisms. There is now growing interest in characterising the metabolisms of anchialine microbial communities, which is essential for understanding how complex ecosystems are supported in extreme environments, and assessing their vulnerability to environmental change. However, the diversity of metabolic strategies that are utilised in anchialine ecosystems remains poorly understood.

Results

Here, we employ shotgun metagenomics to elucidate the key microorganisms and their dominant metabolisms along a physicochemical profile in Bundera Sinkhole, the only known continental subterranean estuary in the Southern Hemisphere. Genome-resolved metagenomics suggests that the communities are largely represented by novel taxonomic lineages, with 75% of metagenome-assembled genomes assigned to entirely new or uncharacterised families. These diverse and novel taxa displayed depth-dependent metabolisms, reflecting distinct phases along dissolved oxygen and salinity gradients. In particular, the communities appear to drive nutrient feedback loops involving nitrification, nitrate ammonification, and sulphate cycling. Genomic analysis of the most highly abundant members in this system suggests that an important source of chemotrophic energy is generated via the metabolic coupling of nitrogen and sulphur cycling.

Conclusion

These findings substantially contribute to our understanding of the novel and specialised microbial communities in anchialine ecosystems, and highlight key chemosynthetic pathways that appear to be important in these energy-limited environments. Such knowledge is essential for the conservation of anchialine ecosystems, and sheds light on adaptive processes in extreme environments.
Dissociable contributions of basolateral amygdala and ventrolateral orbitofrontal cortex to flexible learning under uncertainty
Authors: Aguirre C.G. , Woo J.H. , Romero-Sosa J.L. , Rivera Z.M. , Tejada A.N. , Munier J. J. , Perez J. , Goldfarb M. , Das K. , Gomez M. , Ye T. , Pannu J. , Evans K. , O’Neill P.R. , Spigelman I. , Soltani A. , Izquierdo A.
Published: April 2023

Reversal learning measures the ability to form flexible associations between choice outcomes with stimuli and actions that precede them. This type of learning is thought to rely on several cortical and subcortical areas, including highly interconnected orbitofrontal cortex (OFC) and basolateral amygdala (BLA), and is often impaired in various neuropsychiatric and substance use disorders. However, unique contributions of these regions to stimulus- and action-based reversal learning have not been systematically compared using a chemogenetic approach and particularly before and after the first reversal that introduces new uncertainty. Here, we examined the roles of ventrolateral OFC (vlOFC) and BLA during reversal learning. Male and female rats were prepared with inhibitory DREADDs targeting projection neurons in these regions and tested on a series of deterministic and probabilistic reversals during which they learned about stimulus identity or side (left or right) associated with different reward probabilities. Using a counterbalanced within-subject design, we inhibited these regions prior to reversal sessions. We assessed initial and pre-post reversal changes in performance to measure learning and adjustments to reversals, respectively. We found that inhibition of vlOFC, but not BLA, eliminated adjustments to stimulus-based reversals. Inhibition of BLA, but not vlOFC, selectively impaired action-based probabilistic reversal learning, leaving deterministic reversal learning intact. vlOFC exhibited a sex-dependent role in early adjustment to action-based reversals, but not in overall learning. These results reveal dissociable roles for BLA and vlOFC in flexible learning and highlight a more crucial role for BLA in learning meaningful changes in the reward environment.

Significance Statement

Inflexible learning is a feature of several neuropsychiatric disorders. We investigated how the ventrolateral orbitofrontal cortex (vlOFC) and basolateral amygdala (BLA) are involved in learning of stimuli or actions under reinforcement uncertainty. Following chemogenetic inhibition of these regions in both male and females, we measured learning and adjustments to deterministic and probabilistic reversals. For action learning, BLA, but not vlOFC, is needed for probabilistic reversal learning. However, BLA is not necessary for initial probabilistic learning or retention, indicating a critical role for learning of unexpected changes. For stimulus learning, vlOFC, but not BLA, is required for adjustments to reversals, particularly in females. These findings provide insight into the complementary cortico-amygdalar substrates of learning under different forms of uncertainty.
Stratification of Pediatric COVID-19 cases by inflammatory biomarker profiling and machine learning
Authors: Subramanian Devika , Vittala Aadith , Chen Xinpu , Julien Christopher , Acosta Sebastian , Rusin Craig , Allen Carl , Rider Nicholas , Starosolski Zbigniew , Annapragada Ananth , Devaraj Sridevi
Published: April 2023

An objective method to identify imminent or current Multi-Inflammatory Syndrome in Children (MIS-C) infected with SARS-CoV-2 is highly desirable. The aims was to define an algorithmically interpreted novel cytokine/chemokine assay panel providing such an objective classification. This study was conducted on 4 groups of patients seen at multiple sites of Texas Children’s Hospital, Houston, TX who consented to provide blood samples to our COVID-19 Biorepository. Standard laboratory markers of inflammation and a novel cytokine/chemokine array were measured in blood samples of all patients. Group 1 consisted of 72 COVID-19, 66 MIS-C and 63 uninfected control patients seen between May 2020 and January 2021 and predominantly infected with pre-alpha variants. Group 2 consisted of 29 COVID-19 and 43 MIS-C patients seen between January-May 2021 infected predominantly with the alpha variant. Group 3 consisted of 30 COVID-19 and 32 MIS-C patients seen between August-October 2021 infected with alpha and/or delta variants. Group 4 consisted of 20 COVID-19 and 46 MIS-C patients seen between October 2021-January 2022 infected with delta and/or omicron variants. Group 1 was used to train a L1-regularized logistic regression model which was validated using 5-fold cross validation, and then separately validated against the remaining naïve groups. The area under receiver operating curve (AUROC) and F1-score were used to quantify the performance of the algorithmically interpreted cytokine/chemokine assay panel. Standard laboratory markers predict MIS-C with a 5-fold cross-validated AUROC of 0.86 ± 0.05 and an F1 score of 0.78 ± 0.07, while the cytokine/chemokine panel predicted MIS-C with a 5-fold cross-validated AUROC of 0.95 ± 0.02 and an F1 score of 0.91 ± 0.04, with only sixteen of the forty-five cytokines/chemokines sufficient to achieve this performance. Tested on Group 2 the cytokine/chemokine panel yielded AUROC =0.98, F1=0.93, on Group 3 it yielded AUROC=0.89, F1 = 0.89, and on Group 4 AUROC= 0.99, F1= 0.97). Adding standard laboratory markers to the cytokine/chemokine panel did not improve performance. A top-10 subset of these 16 cytokines achieves equivalent performance on the validation data sets. Our findings demonstrate that a sixteen-cytokine/chemokine panel as well as the top ten subset provides a sensitive, specific method to identify MIS-C in patients infected with SARS-CoV-2 of all the major variants identified to date.
Estimating and visualising multivariable Mendelian randomization analyses within a radial framework
Authors: Spiller Wes , Bowden Jack , Sanderson Eleanor
Published: April 2023

Background

Multivariable Mendelian randomization (MVMR) is a statistical approach using genetic variants as instrumental variables to estimate direct causal effects of multiple exposures on an outcome simultaneously. In univariable MR findings are typically illustrated through plots created using summary data from genome-wide association studies (GWAS), yet analogous plots for MVMR have so far been unavailable due to the multidimensional nature of the analysis.

Methods

We propose a radial formulation of MVMR, and an adapted Galbraith radial plot, which allows for the direct effect of each exposure within an MVMR analysis to be visualised. Radial MVMR plots facilitate the detection of outlier variants, indicating violations of one or more assumptions of MVMR. In addition, the RMVMR R package is presented as accompanying software for implementing the methods described.

Results

We demonstrate the effectiveness of the radial MVMR approach through simulations and applied analyses, estimating the effect of lipid fractions on coronary heart disease (CHD). We find evidence of a protective effect of high-density lipoprotein (HDL) and a positive effect of low-density lipoprotein (LDL) on CHD, however, the protective effect of HDL appeared to be smaller in magnitude when removing outlying variants. In combination with simulated examples, we highlight how important features of MVMR analyses can be explored using a range of tools incorporated within the RMVMR R package.

Conclusions

Radial MVMR effectively visualises causal effect estimates, and provides valuable diagnostic information with respect to the underlying assumptions of MVMR.
Harnessing Nature’s nanoSecrets: biocompatibility, biodistribution and bioactivity of extracellular vesicles derived from microalgae
Authors: Adamo Giorgia , Santonicola Pamela , Picciotto Sabrina , Gargano Paola , Nicosia Aldo , Longo Valeria , Aloi Noemi , Romancino Daniele P. , Paterna Angela , Rao Estella , Raccosta Samuele , Noto Rosina , Salamone Monica , Deidda Irene , Costa Salvatore , Di Sano Caterina , Zampi Giuseppina , Morsbach Svenja , Landfester Katharina , Colombo Paolo , Wei Mingxing , Bergese Paolo , Touzet Nicolas , Manno Mauro , Di Schiavi Elia , Bongiovanni Antonella
Published: April 2023

Nanoalgosomes are extracellular vesicles (EVs) released by microalgal cells that can mediate intercellular and cross-kingdom communication. In the present study, starting from the optimized nanoalgosome manufacturing from cultures of marine microalgae, we evaluated their innate biological properties in preclinical models. Our investigation of nanoalgosome biocompatibility included toxicological analyses, starting from studies on the invertebrate model organismCaenorhabditis elegans,proceeding to hematological and immunological evaluations in mice and immune-compatibilityex vivo. Nanoalgosome biodistribution was evaluated in mice with accurate space-time resolution, and inC. elegansat cellular and subcellular levels. Further examination highlighted the antioxidant and anti-inflammatory bioactivities of nanoalgosomes. This holistic approach to nanoalgosome functional characterization showcases that nanoalgosomes are innate effectors and potential drug delivery system for novel cosmetic formulations and EV-based therapies.
Caleosin 1 contributes to seed lipid droplet degradation by interaction with autophagy-related protein ATG8
Authors: Miklaszewska Magdalena , Zienkiewicz Krzysztof , Klugier-Borowska Ewa , Rygielski Marcin , Feussner Ivo , Zienkiewicz Agnieszka
Published: April 2023

Triacylglycerols (TAGs) accumulate in lipid droplets (LDs) of seed tissues to provide energy and carbon for seedling establishment. In the major route of LD degradation (lipolysis), TAGs are mobilized by lipases. However, LDs may be also degradedvialipophagy, a type of selective autophagy, which mediates LDs delivery to vacuoles or lysosomes. The exact mechanism of this process in plants still remains unresolved. Here, we provide evidence that duringArabidopsis thalianaseed germination, LDs are degraded by microlipophagy and that this process requires caleosin 1 (CLO1), a LD surface protein. We show co-localization of autophagy-related protein 8b (ATG8b) and LDs during seed germination and localization of lipidated ATG8 (ATG8-PE) to the LD fraction. We further demonstrate that CLO1, CLO2 and CLO3 interact with ATG8 proteinsviatheir ATG8-interacting motifs (AIMs). Deletion of AIM localized directly before the proline knot disrupts CLO1 interaction with ATG8b, suggesting the essential role of this region in the interaction between the two proteins. Collectively, we provide new insights into the molecular mechanisms governing the interaction of LDs with the autophagy machinery in plant cells, contributing to understanding of the role of structural LD proteins in lipid mobilization.
A simple model for Behavioral Time Scale Synaptic Plasticity provides content addressable memory with binary synapses and one-shot learning
Authors: Wu Yujie , Maass Wolfgang
Published: April 2023

Recent experimental studies in the awake brain have identified a rule for synaptic plasticity that is instrumental for the instantaneous creation of memory traces in area CA1 of the mammalian brain: Behavioral Time scale Synaptic Plasticity. This one-shot learning rule differs in five essential aspects from previously considered plasticity mechanisms. We introduce a transparent model for the core function of this learning rule and establish a theory that enables a principled understanding of the system of memory traces that it creates. Theoretical predictions and numerical simulations show that our model is able to create a functionally powerful content-addressable memory without the need for high-resolution synaptic weights. Furthermore, it reproduces the repulsion effect of human memory, whereby traces for similar memory items are pulled apart to enable differential downstream processing. Altogether, our results create a link between synaptic plasticity in area CA1 of the hippocampus and its network function. They also provide a promising approach for implementing content-addressable memory with on-chip learning capability in highly energy-efficient crossbar arrays of memristors.
Shunt faults detection and classification in electrical power transmission line systems based on artificial neural networks
Authors: Assadi Khaoula , Slimane Jihane Ben , Chalandi Hanene , Salhi Salah
Published: April 2023

Purpose

This study aims to focus on an adaptive method for fault detection and classification of fault types that trigger in three-phase transmission lines using artificial neural networks (ANNs). The proposed scheme can detect and classify several types of faults, including line-to-ground, line-to-line, double-line-to-ground, triple-line and triple-line-to-ground faults.

Design/methodology/approach

The fundamental components of three-phase current and voltage were used as inputs in the ANNs. An analysis of the impact of variations in the fault resistance, fault type and fault inception time was conducted to evaluate the ANNs performance. The survey compares the performance of the multi-layer perceptron neural network (MLPNN) and Elman recurrent neural network trained with the backpropagation learning technique to improve each of the three phases of the fault detection and classification process. A detailed analysis validates the choice of the ANNs architecture based on the variation in the number of hidden neurons in each step.

Findings

The mean square error, root mean square error, mean absolute error and linear regression are measured to improve the efficiency of the ANN models for both fault detection and classification. The results indicate that the MLPNN can detect and classify faults with a satisfactory performance.

Originality/value

The smart adaptive scheme is fast and accurate for fault detection and classification in a single circuit transmission line when faced with different conditions and can be useful for transmission line protection schemes.
A meta-analysis of a comprehensive m-health technology acceptance
Authors: Calegari Luiz Philipi , R.D. Barkokebas , Fettermann Diego Castro
Published: April 2023

Purpose

The evolution of e-health technologies presents promising alternatives for health-care excellence. Despite the benefits arising from mobile e-health (m-health) and wearables technologies, the literature stands many contradictories signs regarding how users accept and engage in using these technologies. This study aims to synthesize the estimations about m-health user acceptance technologies.

Design/methodology/approach

A meta-analytic structural equation modeling was carried out using the 778 relationships estimated by 100 previous research. The estimations follow the relations and constructs proposed in the UTAUT2 technological acceptance model.

Findings

The results indicate the performance expectancy, effort expectancy, social influence and habit constructs are most important for predicting the behavioral intention of use of m-health technologies. The Latin American users of e-health technologies are still underestimated in the literature.

Originality/value

The study presents a guide to understanding the acceptance process of m-health technologies and delivers a general orientation for developing new m-health devices considering their acceptance by users.
The performance effects of supply chain agility with sensing and responding as formative capabilities
Authors: Park Soomin , Braunscheidel Michael J. , Suresh Nallan C.
Published: April 2023

Purpose

The study presents a conceptual model of a firm's supply chain agility (FSCA) as a formative construct formed by sensing and responding capabilities. Both construct validity and predictive validity of the model are tested by investigating nuanced effects of FSCA on business performance. The study aims to empirically validate the sensing-responding theoretical framework of Overbyet al.(2006) and extend the emergent stream on sensing-responding frameworks for supply chain agility.

Design/methodology/approach

Survey research is employed. Data are analysed using partial least squares technique and mediation tests by Hayes PROCESS macro.

Findings

FSCA is established as a revised construct formed by the distinct capabilities of sensing and responding. The efficacy of utilizing FSCA as a formative 2nd order construct was established. In addition, FSCA is shown to affect business performance through mediations of cost efficiency and customer effectiveness, establishing its predictive validity.

Originality/value

This study contributes significantly to the literature on supply chain agility in terms of both theory and practice for cultivating supply chain agility. Drawing on resource-based view and resource-advantage theories, as reformulation of supply chain agility as a formative construct of sensing and responding capabilities, this research opens up new lines of inquiry on agility.
Application and realization of key technologies in China railway e-ticketing system
Authors: Shan Xinghua , Zhang Zhiqiang , Ning Fei , Li Shida , Dai Linlin
Published: April 2023

Purpose

With the yearly increase of mileage and passenger volume in China's high-speed railway, the problems of traditional paper railway tickets have become increasingly prominent, including complexity of business handling process, low efficiency of ticket inspection and high cost of usage and management. This paper aims to make extensive references to successful experiences of electronic ticket applications both domestically and internationally. The research on key technologies and system implementation of railway electronic ticket with Chinese characteristics has been carried out.

Design/methodology/approach

Research in key technologies is conducted including synchronization technique in distributed heterogeneous database system, the grid-oriented passenger service record (PSR) data storage model, efficient access to massive PSR data under high concurrency condition, the linkage between face recognition service platforms and various terminals in large scenarios, and two-factor authentication of the e-ticket identification code based on the key and the user identity information. Focusing on the key technologies and architecture the of existing ticketing system, multiple service resources are expanded and developed such as electronic ticket clusters, PSR clusters, face recognition clusters and electronic ticket identification code clusters.

Findings

The proportion of paper ticket printed has dropped to 20%, saving more than 2 billion tickets annually since the launch of the application of E-ticketing nationwide. The average time for passengers to pass through the automatic ticket gates has decreased from 3 seconds to 1.3 seconds, significantly improving the efficiency of passenger transport organization. Meanwhile, problems of paper ticket counterfeiting, reselling and loss have been generally eliminated.

Originality/value

E-ticketing has laid a technical foundation for the further development of railway passenger transport services in the direction of digitalization and intelligence.
Generating complete synthetic datasets for high‐resolution amplitude‐versus‐offset attributes deep learning inversion
Authors: Sun Shuai , Nie Junguang , Wang Benfeng , Zhao Luanxiao , He Zhiliang , Zhang Hong , Chen Dong , Geng Jianhua
Published: April 2023

Deep learning has been used in seismic exploration to solve seismic inversion problems, however it requires sufficient and diverse training samples and labels to obtain satisfactory results. Insufficient training labels are a common problem since labels usually come from well‐logging data, which are limited and sparsely distributed. This can result in a trained network with poor generalizability. A novel complete synthetic dataset‐driven method utilizing convolutional neural network is presented for seismic amplitude‐versus‐offset attributes P and G inversion. Gaussian simulation sampling with physical constraints is used to generate a complete elastic parameter dataset by traversing the entire elastic parameter model space. By randomly combining elastic parameters from the full elastic parameters model space, sufficient synthetic pre‐stack amplitude‐versus‐offset gathers and attribute datasets are generated for training the convolutional neural network. Compared with the limited real data‐driven convolutional neural network, the complete synthetic dataset‐driven convolutional neural network has better generalizability. Broadband training labels improve the accuracy and resolution of the complete synthetic dataset‐driven convolutional neural network's inversion results beyond that of the conventional least‐square data‐fitting method. The complete synthetic dataset‐driven convolutional neural network is robust for processing noise‐contaminated seismic data, but if the frequency band of the labels for training the network is too wide and the signal‐to‐noise ratio of pre‐stack amplitude‐versus‐offset gathers is too low, the quality of the inversion results will reduce. The Marmousi II model and field data examples show that the novel complete synthetic dataset‐driven convolutional neural network can extract higher‐resolution amplitude‐versus‐offset attributes P and G.
Prognostic research methodology: Tools to help predict the future
Authors: Combs C. Andrew
Published: April 2023

Linked article: This is a mini commentary on Hughes et al. To view this article visit https://doi.org/10.1111/1471-0528.17443.
What can supraspecies richness tell us?
Authors: Volvenko Igor V. , Gebruk Andrey V. , Katugin Oleg N. , Vinogradov Georgy M. , Orlov Alexei M.
Published: April 2023

Biogeographers, ecologists, palaeontologists, and conservation managers often deal with checklists in which not all individuals have been identified to a species level, or the accuracy of species identification is questionable. Is it possible and credible to investigate species richness based on such checklists? Studies on macrofauna in the Far Eastern seas, eastern Arctic seas, and adjacent waters of the Pacific and Arctic Oceans suggest that in different habitats and for diverse taxa, species, and higher taxa richness strongly correlate with each other and increase with an expansion in the study area and sample size according to the species–area law. Such an increase is higher in the bottom zone than in the pelagic. Species and higher taxa richness also show a decrease from lower to higher latitudes, which is in line with the Humboldt–Wallace’s law. According to Willis’ law and self‐similarity in the organisation of taxonomic levels, species richness can be assessed based on the genus, family, and order richness. In other words, supraspecies richness itself can tell us the same as species richness and therefore certain global patterns revealed at the species level may also be revealed at the supraspecies level. Such a concordance in general trends among richness parameters at different taxonomic levels in practice implies that species richness can be studied based on lists that lack species identifications or lists with doubtful species identification. We suggest bolder use of supraspecies richness in science and practice, discussing the disadvantages and advantages of this approach.
Co‐encapsulation of rutinoside and β‐carotene in liposomes modified by rhamnolipid: Antioxidant activity, antibacterial activity, storage stability, and in vitro gastrointestinal digestion
Authors: Ji Ying , Wang Zhigao , Ju Xingrong , Deng Feng , Yang Feiyu , He Rong
Published: April 2023

The surfactant rhamnolipid (RL) was used to modify the liposomes. β‐carotene (βC) and rutinoside (Rts) were utilized to generate co‐encapsulated liposomes through an ethanol injection method that used both hydrophilic and hydrophobic cavities to fabricate a novel cholesterol‐free composite delivery system. The RL complex‐liposomes loaded with βC and Rts (RL–βC–Rts) showed higher loading efficiency and good physicochemical properties (size = 167.48 nm, zeta‐potential = −5.71 mV, and polydispersity index = 0.23). Compared with other samples, the RL–βC–Rts showed better antioxidant activities and antibacterial ability. Moreover, dependable stability was uncovered in RL–βC–Rts with still 85.2% of βC storage from nanoliposome after 30 days at 4°C. Furthermore, in simulated gastrointestinal digestion, βC exhibited good release kinetic properties. The present study demonstrated that liposomes constructed from RLs offer a promising avenue for the design of multicomponent nutrient delivery systems using both hydrophilic.
Influence of microhabitat structure on large‐ and medium‐sized mammals in South African forests
Authors: Sosibo Mbalenhle T. , Ehlers Smith David A. , Ehlers Smith Yvette C. , Gumede S. Thobeka , Ngcobo Samukelisiwe P. , Downs Colleen T.
Published: April 2023

Microhabitats play a significant role in the persistence of mammalian species and communities. In South Africa, the forest biome is the smallest. It includes the naturally fragmented Southern Mistbelt Forest group, where little is known about contemporary mammalian assemblage dynamics concerning these forest's microhabitats. We determined the microhabitat characteristics that best explained mammalian species' presence and absence in these forests in the northern Eastern Cape and southern KwaZulu‐Natal provinces. We deployed a minimum of 60 camera traps at any time for 24 h/day to monitor mammalian species' presence/absence. We recorded a habitat foliage profile within a 20 m radius around each camera trap. The species most often photographed were Tragelaphus scriptus and Cercopithecus albogularis labiatus, with the least photographed species being Leptailurus serval and Felis silvestris cafra. All mammalian species detected in our study had a negative association with bare ground. Cercopithecus albogularis labiatus, an arboreal species that requires a dense connecting canopy for movement, showed a positive association with crown closure. Our study highlighted that microhabitat variables: leaf litter, crown closure and grass cover played an important role in the presence and persistence of large and medium‐sized mammalian species that inhabit the Southern Mistbelt Forests, which benefits forest conservation management plans.