bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptomic balance and optimal growth are determined by cell size
Authors: Vidal Pedro J. , Pérez Alexis P. , Aldea Martí
Published: November 2022

Cell size and growth are intimately related across the evolutionary scale, and the molecular pathways underlying cell size homeostasis have received much attention over the last decades. However, whether cell size is important to attain maximal growth or fitness is still an open question, and the reasons why a critical size is needed for triggering key transitions of the cell cycle are unknown. We show that growth is a non-monotonic function of volume in yeast cells, with maximal values around the critical size. Comparing small to normal, large and outsized cells, the transcriptome undergoes an extensive inversion that correlates with RNA polymerase II occupancy. Accordingly, highly expressed genes impose strong negative effects on growth when their DNA/mass ratio is altered. A similar transcriptomic inversion is displayed by mouse liver cells of different sizes, suggesting that the uncovered mechanistic implications of cell size on growth and fitness are universal. We propose that cell size is set to attain a properly balanced transcriptome and, hence, maximize growth during cell proliferation.
Silencing hippocampal CA2 reduces behavioral flexibility in spatial learning
Authors: Lehr Andrew B. , Hitti Frederick L. , Deibel Scott H. , Stöber Tristan M.
Published: November 2022

The hippocampus is a key structure involved in learning and remembering spatial information. However the extent to which hippocampal region CA2 is involved in these processes remains unclear. Here we show that chronically silencing dorsal CA2 impairs reversal learning in the Morris water maze. After platform relocation, CA2-silenced mice spent more time in the vicinity of the old platform location and less time in the new target quadrant. Accordingly, behavioral strategy analysis revealed increased perseverance in navigating to the old location during the first day and an increased use of non-spatial strategies during the second day of reversal learning. Confirming previous indirect indications, these results demonstrate that CA2 is recruited when mice must flexibly adapt their behavior as task contingencies change. We discuss how these findings can be explained by recent theories of CA2 function and outline testable predictions to understand the underlying neural mechanisms. Demonstrating a direct involvement of CA2 in spatial learning, this work lends further support to the notion that CA2 plays a fundamental role in hippocampal information processing.
Segregation of pathways leading to pexophagy
Authors: Barone Francesco G. , Urbé Sylvie , Clague Michael J.
Published: November 2022

Peroxisomes are organelles with key roles in metabolism including long-chain fatty acid production. Their metabolic functions overlap and interconnect with mitochondria, with which they share an overlapping but distinct proteome. Both organelles are degraded by selective autophagy processes termed pexophagy and mitophagy. Whilst mitophagy has received intense attention, the pathways linked to pexophagy and associated tools are less well developed. We have identified the neddylation inhibitor, MLN4924, as a potent activator of pexophagy and show that this is mediated by the HIF1α-dependent upregulation of BNIP3L/NIX, a known adaptor for mitophagy. We show that this pathway is distinct from pexophagy induced by the USP30 deubiquitylase inhibitor, CMPD-39, for which we identify the adaptor NBR1 as a central player. Our work suggests a level of complexity to the regulation of peroxisome turnover that includes the capacity to co-ordinate with mitophagy, via NIX, which acts as a rheostat for both processes.
Microfluidic device combining hydrodynamic and dielectrophoretic trapping for the controlled contact between single micro-sized objects and application to adhesion assays
Authors: Lipp Clémentine , Koebel Laure , Loyon Romain , Bolopion Aude , Spehner Laurie , Gauthier Michaël , Borg Christophe , Bertsch Arnaud , Renaud Philippe
Published: November 2022

The understanding of cell-cell and cell-matrix interactions via receptor and ligand binding relies on our ability to study the very first events of their contact. Of particular interest is the interaction between a T cell receptor and its cognate peptide-major histocompatibility complex. Indeed analyzing their binding kinetics and cellular avidity in large-scale low-cost and fast cell sorting would largely facilitate the access to cell-based cancer immunotherapies. We thus propose a microfluidic tool able to independently control two types of micro-sized objects, put them in contact for a defined time and probe their adhesion state. The device consists in hydrodynamic traps holding the first type of cells from below against the fluid flow, and a dielectrophoretic system to force the second type of object to remain in contact to the first one. First the device is validated by performing an adhesion frequency assay between fibroblasts and fibronectin coated bead. Then, a study is conducted on the modification of the cellular environment to match the dielectrophoretic technology requirements without modifying the cells viability and interaction functionalities. Finally, we demonstrate the capability of the developed device to put cancer cells and a population of T cells in contact and show the discrimination between specific and non specific interactions based on pairs lifetime.
Acyl plastoquinol is a major substance that co-migrates with triacylglycerol in cyanobacteria
Authors: Mori-Moriyama Natsumi , Yoshitomi Toru , Sato Naoki
Published: November 2022

Various studies have suggested the presence of triacylglycerol in cyanobacteria, but no convincing evidence exists. We purified a substance co-migrating with triacylglycerol and determined its structure using mass spectrometry, gas chromatography, and1H- and13C-NMR. The major components were palmitoyl and stearoyl plastoquinols (acyl plastoquinol). Acyl plastoquinol has never been described before. The level of acyl plastoquinol was 0.4% of the total lipids. We still do not have clear evidence for the presence of triacylglycerol. If present, the maximum triacylglycerol level, must be at most 10% of acyl plastoquinol or less. TheSynechocystisSlr2103 protein was suggested to synthesize triacylglycerol, but the product could be acyl plastoquinol. The possible roles of this novel compound in photosynthesis should be a new focus of research.
RBPamp: Quantitative Modeling of Protein-RNA Interactionsin vitroPredictsin vivoBinding
Authors: Jens Marvin , McGurk Michael , Bundschuh Ralf , Burge Christopher B.
Published: November 2022

RNA-binding proteins (RBPs) control the processing and function of cellular transcripts to effect post-transcriptional gene regulation. Sequence-specific binding of RBPs to millions of synthetic RNAs has been probed in vitro by RNA Bind-n-Seq (RBNS). Here we describe RBPamp, a bio-physically-based model of protein-RNA interactions and associated algorithm that inferred affinity spectra of 79 diverse human RBPs from RBNS data. RBPamp supports multiple motifs per RBP, models RBP concentration and binding site saturation, and accounts for the effects of RNA secondary structure. RBPamp affinities along transcripts are predictive of in vivo binding, as measured by eCLIP density. For many RBPs, average local eCLIP density increases monotonically with predicted affinity, and the shape of this relationship can suggest free protein concentrations and potential cooperativity. Together, these analyses demonstrate a powerful integrative approach for the quantitative dissection of RBP function.
Trait diversity metrics can perform well with highly incomplete datasets
Authors: Stewart Kerry , Carmona Carlos P. , Clements Chris , Venditti Chris , Tobias Joseph A. , González-Suárez Manuela
Published: November 2022

Characterizing changes in trait diversity at large spatial scales provides insight into the impact of human activity on ecosystem structure and function. However, the approach is often based on trait datasets that are incomplete and unrepresentative, with uncertain impacts on trait diversity estimates.

To address this knowledge gap, we simulated random and biased removal of data from a near complete avian trait dataset (9579 species) and assessed whether trait diversity metrics were robust to data incompleteness with and without using imputation to fill data gaps. Specifically, we compared two commonly used metrics each calculated with two methods: trait richness (calculated with convex hulls and trait probabilities densities) and trait divergence (calculated with distance-based Rao and trait probability densities).

Without imputation, estimates of global avian trait diversity (richness and divergence) were robust when 30-70% of species had missing data for four out of 11 continuous traits, depending on severity of bias and the method used. However, when missing traits were imputed based on present morphological trait data and phylogeny, trait diversity metrics consistently remained representative of the true value, even when 70% of species were missing data for four out of 11 traits and data were not missing at random (biased with respect to body mass). Trait probability densities and distance-based Rao were particularly robust to missingness and bias when combined with imputation, with convex hull-based trait richness being less reliable.

Expanding global morphometric datasets to represent more taxa and traits, and to quantify intraspecific variation, remains a priority. In the meantime, our results show that widely used methods can successfully quantify large-scale trait diversity even when data are missing for two-thirds of species, so long as missing traits are estimated using imputation.
The enzyme Rnf completes the pathway for forming propionate during fermentation inPrevotella
Authors: Zhang Bo , Lingga Christopher , De Groot Hannah , Hackmann Timothy J.
Published: November 2022

Propionate is a microbial metabolite that is formed in the gastrointestinal tract, and it affects host physiology as a source of energy and signaling molecule. Despite the importance of propionate, the biochemical pathways responsible for its formation are not clear in all microbes. For the succinate pathway used during fermentation, a key enzyme appears to be missing—one that can oxidize ferredoxin and reduce NAD. Here we show that Rnf [ferredoxin--NAD(+) oxidoreductase (Na(+)-transporting)] is this key enzyme in two abundant bacteria of the rumen (Prevotella brevisandPrevotella ruminicola). We found these bacteria form propionate, succinate, and acetate with the classic succinate pathway. At first, this pathway appears unbalanced, forming reduced ferredoxin and oxidized NAD in excess. If this continued unabated, fermentation would halt within 1.5 s. We found these bacteria solve this problem by oxidizing ferredoxin and reducing NAD with Rnf. This is demonstrated using growth experiments, genomics, proteomics, and enzyme assays. Genomic and phenotypic data suggest many bacteria use Rnf similarly. We cataloged fermentation products of >1,400 species of prokaryotes, and nearly 10% formed propionate, succinate, and acetate. Over 40% of species carrying out this fermentation also had genes for Rnf. This work shows Rnf is important to propionate formation in many bacteria from the environment, and it provides fundamental knowledge for manipulating fermentative propionate production.
dipwmsearch: a python package for searching di-PWM motifs
Authors: Mille Marie , Ripoll Julie , Cazaux Bastien , Rivals Eric
Published: November 2022

Motivation

Seeking probabilistic motifs in a sequence is a common task to annotate putative transcription factor binding sites (TFBS). Useful motif representations include Position Weight Matrices (PWMs), dinucleotidic PWMs (di-PWMs), and Hidden Markov Models (HMMs). Dinucleotidic PWMs combine the simplicity of PWMs – a matrix form and a cumulative scoring function –, but also incoporate dependency between adjacent positions in the motif (unlike PWMs which disregard any dependency). For instance, to represent binding sites, the HOCOMOCO database provides di-PWM motifs derived from experimental data. Currently, two programs, SPRy-SARUS and MOODS, can search for di-PWMs in sequences.

Results

We propose a Python package,dipwmsearch, which provides an original and efficient algorithm for this task (it first enumerates matching words for the di-PWM, and then search them at once in the sequence even if it contains IUPAC codes). The user benefits from an easy installation viaPypiorconda, a documented Python interface, and reusable example scripts that smooth the use of di-PWMs.

Availability and Implementation

dipwmsearchis available athttps://pypi.org/project/dipwmsearch/andhttps://gite.lirmm.fr/rivals/dipwmsearch/under Cecill license.
Interpersonal alignment of neural evidence accumulation to social exchange of confidence
Authors: Esmaily Jamal , Zabbah Sajjad , Bahrami Bahador , Ebrahimpour Reza
Published: November 2022

Private, subjective beliefs about uncertainty have been found to have idiosyncratic computational and neural substrates yet, humans share such beliefs seamlessly and cooperate successfully. Bringing together decision making under uncertainty and interpersonal alignment in communication, in a discovery plus pre-registered replication design, we examined the neuro-computational basis of the relationship between privately-held and socially-shared uncertainty. Examining confidence-speed-accuracy trade-off in uncertainty-ridden perceptual decisions under social vs isolated context, we found that shared (i.e., reported confidence) and subjective (inferred from pupillometry) uncertainty dynamically followed social information. An attractor neural network model incorporating social information as top-down additive input captured the observed behaviour and spontaneously demonstrated the emergence of social alignment in virtual dyadic simulations. Electroencephalography showed that social exchange of confidence modulated the neural signature of perceptual evidence accumulation in the central parietal cortex and produced a sustained top-down flow of information from prefrontal to parietal cortex. Our findings offer a neural population model for interpersonal alignment of shared beliefs.
Temporal changes in the individual size distribution decouple long-term trends in abundance, biomass, and energy use of North American breeding bird communities
Authors: Diaz Renata M. , Ernest S. K. Morgan
Published: November 2022

Aim

A core objective of contemporary biodiversity science is to understand long-term trends in the structure and function of ecological communities. Different currencies of ecological function – specifically, total abundance, total standing biomass, and total metabolic flux – are naturally linked, but may become decoupled if the underlying size structure of a system changes. Here, we seek to establish how changes in community size composition modulate long-term relationships between different currencies of ecological function for North American birds.

Location

North America, north of Mexico.

Time period

1988-2018.

Major taxa studied

Breeding birds.

Methods

We used species’ traits and allometric scaling to estimate individual size measurements and basal metabolic rate for birds observed in the North American Breeding Bird Survey. We compared the long-term trajectories for community-wide standing biomass and energy use to the long-term trends driven by changes in individual abundance alone. Finally, we used dissimilarity metrics to evaluate the link between changes in species and size composition and changes in the relationship between abundance- and size-driven dynamics.

Results

For a substantial minority of communities, shifts in community size composition have decoupled the long-term dynamics of biomass, energy use, and individual abundance. While trends in abundance were dominated by decreases, trends in biomass were evenly divided between decreases and increases, and trends in energy use featured more increases than expected given changes in abundance alone. Communities with decoupled dynamics showed greater increases in community-wide mean body size than other communities, but did not differ from other communities in overall turnover in species or size composition.

Main conclusions

Size- and abundance-based currencies of ecological function are linked, but not necessarily equivalent. For North American breeding birds, shifts in species composition favoring larger-bodied species may have partially offset declines in standing biomass driven by losses of individuals over the past 30 years.
RAD-TGTs: Measurement of cellular tensions via flow cytometry and DNA sequencing enabled by force-dependent rupture and delivery of DNA tension probes
Authors: Pawlak Matthew R. , Smiley Adam T. , Kelly Marcus D. , Shamsan Ghaidan A. , Anderson Sarah M. , Smeester Branden A. , Largaespada David A. , Odde David J. , Gordon Wendy R.
Published: November 2022

Mechanical force is a key driver of cellular processes and is dysregulated in many diseases. Measuring cellular tensions to elucidate mechanotransduction pathways typically involves high-resolution but low throughput imaging of surfaces and arduous experimental preparation of materials. We present here Rupture and Deliver DNA-duplex based molecular tension sensors-RAD-TGTs. RAD-TGTs consist of immobilized DNA duplexes conjugated to a ligand and indicator (fluorophore, barcode etc) which rupture in a force-dependent manner when cells are bound. Readout of rupture is performed in cells of interest using high throughput methods such as flow cytometry and leveraging covalent DNA-protein linking HUH-tags simplifies the preparation of the tension sensor to allow use of “off-the-shelf” oligos. We demonstrate that rupture and delivery is decreased by inhibitors of cytoskeletal dynamics and knockout of mechanosensing proteins. We also show that rupture and delivery correlates with ligand affinity. Excitingly, we demonstrate that rupture and delivery of barcoded DNA-duplexes can be quantified using DNA sequencing, propelling cellular force measurements into the -omics era.
Extracting Mitochondrial Cristae Characteristics from 3D Focused Ion Beam Scanning Electron Microscopy Data
Authors: Wang Chenhao , Østergaard Leif , Hasselholt Stine , Sporring Jon
Published: November 2022

1

Mitochondria are the main suppliers of energy for cells and their bioenergetic function is regulated bymitochondrial dynamics: the constant changes in mitochondria size, shape, and cristae morphology to secure cell homeostasis. Although mitochondrial dysfunction is implicated in a wide range of diseases, our understanding of mitochondrial function remains limited by the complexity of inferring these spatial features from 2D electron microscopical (EM) images of intact tissue. Here, we present a semi-automatic method for segmentation and 3D reconstruction of mitochondria, cristae, and intracristal spaces based on 2D EM images of the murine hippocampus. We show that our method provides a more accurate characterization of mitochondrial ultrastructure in 3D than common 2D approaches and propose an operational index of mitochondria’s internal organization. We speculate that this tool may help increase our understanding of mitochondrial dynamics in health and disease.
Pipeline for transferring annotations between proteins beyond globular domains
Authors: Martínez-Pérez Elizabeth , Pajkos Mátyás , Tosatto Silvio C.E. , Gibson Toby J. , Dosztanyi Zsuzsanna , Marino-Buslje Cristina
Published: November 2022

Background

DisProt is the primary repository of Intrinsically Disordered Proteins. This database is manually curated and the annotations there have strong experimental support. Currently DisProt contains a relatively small number of proteins highlighting the importance of transferring verified disorder and other annotations, in such a way as to increase the number of proteins that could benefit from this valuable information. While the principles and practicalities of homology transfer are well-established for globular proteins, these are largely lacking for disordered proteins.

Methods

We used DisProt to evaluate the transferability of the annotation terms to orthologous proteins. For each protein, we looked for their orthologs, with the assumption that they will have a similar function. Then, for each protein and their orthologs we made multiple sequence alignments (MSAs). Global and regional quality of the MSAs was evaluated with the NorMD score.

Results

We have designed a pipeline to obtain good quality MSAs and to transfer annotations from any protein to their orthologs. Applying the pipeline to DisProt proteins, from the 1931 entries with 5,623 annotations we can reach 97,555 orthologs and transfer a total of 301,190 terms by homology. We also provide a web server for consulting the results of DisProt proteins and execute the pipeline for any other protein. The server Homology Transfer IDP (HoTIDP) is accessible athttp://hotidp.leloir.org.ar.
Thermal acclimation in a non-migratory songbird occurs via changes to thermogenic capacity, but not conductance
Authors: Schweizer Rena M. , Romero Abimael , Tobalske Bret W. , Semenov Georgy , Carling Matt D. , Rice Amber M. , Taylor Scott A. , Cheviron Zachary A.
Published: November 2022

Thermoregulatory performance can be modified through changes in various subordinate traits, including thermal conductance, basal and summit metabolic rates, and body composition. We investigated physiological differences between black-capped chickadees (Poecile atricapillus) acclimated for six weeks to cold (−5°C) or control (25°C) environments (n = 7 per treatment) by measuring traits that affect thermal balance. We made repeated measurements of basal and summit metabolic rates via flow-through respirometry and body composition using quantitative magnetic resonance of live birds. At the end of the acclimation, we measured thermal conductance of the combined feathers and skins. Cold-acclimated birds had a higher summit metabolic rate, reflecting a greater capacity for endogenous heat generation, and an increased lean mass. However, birds did not alter their thermal conductance. These results suggest that, while birds can use multiple mechanisms to acclimate to their thermal environment, they use a subset of potential changes over varying timescales.
Technical Note: STRATIS: A Cloud-enabled Software Toolbox for Radiotherapy and Imaging Analysis
Authors: Apte Aditya P. , LoCastro Eve , Iyer Aditi , Jiang Jue , Oh Jung Hun , Veeraraghavan Harini , Shukla-Dave Amita , Deasy Joseph O.
Published: November 2022

Purpose

Recent advances in computational resources, including software libraries and hardware, have enabled the use of high-dimensional, multi-modal datasets to build Artificial Intelligence (AI) models and workflows for radiation therapy and image analysis. The purpose of Software Toolbox for RAdioTherapy and Imaging analysiS (STRATIS) is to provide cloud-enabled, easy-to-share software workflows to train and deploy AI models for transparency and multi-institutional collaboration.

Method

STRATIS leverages open source medical image informatics software for application-specific analysis. Jupyter notebooks for AI modeling workflows are provided with Python language as the base kernel. In addition to Python, workflows use software written in other languages, such as MATLAB, GNU-Octave, R, and C++, with the help of bridge libraries. The workflows can be run on a cloud platform, local workstation, or an institutional HPC cluster. Computational environments are provided in the form of publicly available docker images -and build scripts for local Anaconda environments. Utilities provided with STRATIS simplify bookkeeping of associations between imaging objects and allow chaining data processing operations defined via a setting file for AI models.

Results

Workflows available on STRATIS can be broadly categorized into image segmentation, deformable image registration, and outcomes modeling for radiotherapy toxicity and tumor control using radiomics and dosimetry features. The STRATIS-forge GitHub organizationhttps://www.github.com/stratis-forgehosts build-scripts for Docker and Anaconda as well as Jupyter notebooks for analysis workflows. The software for building environments and workflow notebooks has open source-GNU-GPL copyright, and AI models retain the copyright chosen by their original developers.

Conclusion

STRATIS enables researchers to deploy and share AI modeling workflows for radiotherapy and image analysis. STRATIS is publicly available on Terra.bio’s FireCloud platform with a pre-deployed computational environment and on GitHub organization for users pursuing local deployment.
Non-invasive disruption of the blood-brain barrier in the marmoset monkey
Authors: Szuzupak Diego , Choi Sang-Ho , Alikaya Aydin , Mou Yongshan , Silva Afonso C. , Schaeffer David J.
Published: November 2022

The common marmoset monkey (Callithrix jacchus) is a species of rising prominence in the neurosciences due to their small size, ease of handling, fast breeding, and their shared functional and structural brain characteristics with Old World primates. With increasing attention on modeling human brain diseases in marmosets, understanding how to deliver therapeutic or neurotropic agents to the marmoset brain non-invasively is of great preclinical importance. In other species, including humans, transcranial focused ultrasound (tFUS) aided by intravenously injected microbubbles has proven to be a transient, reliable, and safe method for disrupting the blood-brain barrier (BBB), allowing for the focal passage of therapeutic agents that do not otherwise readily traverse the tight endothelial junctions of the BBB. The critical gap that we address here is to document parameters to disrupt the BBB reliably and safely in marmosets using tFUS. By integrating our marmoset brain atlases and the use of a marmoset-specific stereotactic targeting system, we conducted a series of systematic transcranial sonication experiments in nine marmosets. We demonstrate the effects of center frequency, acoustic pressure, burst period and duration, establish a minimum microbubble dose, estimate microbubble clearance time, and estimate the duration that the BBB remained open to passage. Successful BBB disruption was reportedin vivowith MRI-based contrast agents, as well as Evans blue staining assessedex vivo. Histology (Hematoxylin and Eosin staining) and immunohistochemistry indicated that the BBB can be safely and reliably opened with the parameters derived from these experiments.
The genome of the blind bee louse fly reveals deep convergences with its social host and illuminates Drosophila origins
Authors: Bastide Héloïse , Legout Hélène , Dogbo Noé , Ogereau David , Prediger Carolina , Carcaud Julie , Filée Jonathan , Garnery Lionel , Gilbert Clément , Marion-Poll Frédéric , Requier Fabrice , Sandoz Jean-Christophe , Yassin Amir
Published: November 2022

The nests of social insects often harbor a rich fauna of intruders known as inquilines.1Social inquilines are usually closely-related to their host due to potential genetic predispositions,2,3but how phylogenetically distant non-social inquilines adapt to their hosts remains unclear. Here, we analyzed the genome of the wingless and blind bee louse flyBraula coeca, an inquiline kleptoparasite of the Western honey beeApis mellifera.4,5Using large phylogenomic data, we confirmed recent accounts that the bee louse fly is an aberrant drosophilid,6,7and showed that it had likely evolved from a sap-breeder ancestor associated with honeydew and scale insects wax. Unlike many parasites, such as the human louse, the bee louse fly genome did not show significant erosion or strict reliance on an endosymbiont, likely due to a relatively recent age of inquilinism. However, a striking parallel evolution in a set of gene families was observed between the honey bee and the bee louse fly. Convergences included genes potentially involved in metabolism and immunity and the loss of nearly all bitter-tasting gustatory receptors in agreement with life in a protective nest and a major diet of honey, pollen, and beeswax. Vision-related and odorant receptor genes also exhibited rapid losses. Only genes whose orthologs in the closely relatedDrosophila melanogasterrespond to honey bee pheromones components or floral aroma were retained, whereas the losses included orthologous receptors responsive to the anti-ovarian honey bee queen pheromones. These results indicate that deep genomic convergences can underlie major morphological and neuroethological transitions during the evolution of inquilinism between non-social parasites and their social hosts.
Microglial process dynamics enhance neuronal activity by shielding GABAergic synaptic inputs
Authors: Haruwaka Koichiro , Ying Yanlu , Liang Yue , Umpierre Anthony D. , Yi Min-Hee , Kremen Vaclav , Chen Tingjun , Xie Tao , Dong Hailong , Worrell Gregory A. , Wu Long-Jun
Published: November 2022

Microglia are resident immune cells of the central nervous system (CNS) and play key roles in brain homeostasis. During anesthesia, microglia increase their dynamic process surveillance and interact more closely with neurons. However, the functional significance of microglial process dynamics and neuronal interaction has remained unclear. Usingin vivotwo-photon imaging in awake mice, we discover that microglia enhance neuronal activity after the cessation of general anesthesia. Hyperactive neuron somata are directly contacted by microglial processes, which specifically co-localize with GABAergic boutons. Electron microscopy-based synaptic reconstruction after two-photon imaging reveals that microglial processes enter into the synaptic cleft to shield GABAergic inputs. Microglial ablation or loss of microglial β2-adrenergic receptors prevent post-anesthesia neuronal hyperactivity. Together, our study demonstrates a previously unappreciated function of microglial process dynamics, which allow microglia to transiently boost neuronal activity by physically shielding inhibitory inputs.
Signature morpho-electric properties of diverse GABAergic interneurons in the human neocortex
Authors: Lee Brian , Dalley Rachel , Miller Jeremy A , Chartrand Thomas , Close Jennie , Mann Rusty , Mukora Alice , Ng Lindsay , Alfiler Lauren , Baker Katherine , Bertagnolli Darren , Brouner Krissy , Casper Tamara , Csajbok Eva , Dee Nick , Donadio Nicholas , Driessens Stan L.W. , Egdorf Tom , Enstrom Rachel , Galakhova Anna A , Gary Amanda , Gelfand Emily , Goldy Jeff , Hadley Kristen , Heistek Tim S. , Hill Dijon , Johansen Nelson , Jorstad Nik , Kim Lisa , Kocsis Agnes Katalin , Kruse Lauren , Kunst Michael , Leon Gabriela , Long Brian , Mallory Matthew , Maxwell Michelle , McGraw Medea , McMillen Delissa , Melief Erica J , Molnar Gabor , Mortrud Marty T , Newman Dakota , Nyhus Julie , Opitz-Araya Ximena , Pham Trangthanh , Pom Alice , Potekhina Lydia , Rajanbabu Ram , Ruiz Augustin , Sunkin Susan M , Szots Ildiko , Taskin Naz , Thyagarajan Bargavi , Tieu Michael , Trinh Jessica , Vargas Sara , Vumbaco David , Waleboer Femke , Weed Natalie , Williams Grace , Wilson Julia , Yao Shenqin , Zhou Thomas , Barzo Pal , Bakken Trygve , Cobbs Charles , Ellenbogen Richard G. , Esposito Luke , Ferreira Manuel , Gouwens Nathan W , Grannan Benjamin , Gwinn Ryder P. , Hauptman Jason S. , Hodge Rebecca , Jarsky Tim , Keene C.Dirk , Ko Andrew L. , Levi Boaz , Ojemann Jeffrey G. , Patel Anoop , Ruzevick Jacob , Silbergeld Daniel L. , Smith Kim , Waters Jack , Zeng Hongkui , Berg Jim , Goriounova Natalia A. , Kalmbach Brian , de Kock Christiaan P.J. , Mansvelder Huib D , Sorensen Staci A , Tamas Gabor , Lein Ed S. , Ting Jonathan T
Published: November 2022

Human cortical interneurons have been challenging to study due to high diversity and lack of mature brain tissue platforms and genetic targeting tools. We employed rapid GABAergic neuron viral labeling plus unbiased Patch-seq sampling in brain slices to define the signature morpho-electric properties of GABAergic neurons in the human neocortex. Viral targeting greatly facilitated sampling of the SST subclass, including primate specialized double bouquet cells which mapped to two SST transcriptomic types. Multimodal analysis uncovered an SST neuron type with properties inconsistent with original subclass assignment; we instead propose reclassification into PVALB subclass. Our findings provide novel insights about functional properties of human cortical GABAergic neuron subclasses and types and highlight the essential role of multimodal annotation for refinement of emerging transcriptomic cell type taxonomies.

One Sentence Summary

Viral genetic labeling of GABAergic neurons in humanex vivobrain slices paired with Patch-seq recording yields an in-depth functional annotation of human cortical interneuron subclasses and types and highlights the essential role of multimodal functional annotation for refinement of emerging transcriptomic cell type taxonomies.
Limitations of Solar-Induced Chlorophyll Fluorescence (SIF) for Estimating Photosynthesis Under Stress
Authors: Mayo Amir M. , Moshelion Menachem , Liran Oded
Published: November 2022

High-throughput measurements of photosynthesis of plants grown under various conditions may provide important insights into the plasticity of the photosynthetic performance of plants. Remote sensing of photosynthetic activity is the next generation of fast scanning techniques, enabling high-throughput photosynthesis measurements under controlled conditions. We hypothesized that by measuring SIF simultaneously with whole-plant water relations in a standardized controlled drought experiment, we would be able to quantify photosynthetic activity and to detect water stress at an early stage. A functional-phenotyping platform was used to apply the controlled drought treatment and to monitor the growth and water balance of tomato introgression lines (ILs). A new SIF-derived index, electron transport rate (RS-ETRi), was found to be negatively correlated with whole-plant stomatal conductance (Gsc) under non-stressed conditions. No significant relationships were found between SIF and plant biomass or Gsc. SIF687responded to drought earlier than any of the other measured vegetation indices. SIF based indices could not differentiate between introgressed lines of tomato; whereas differences between Introgression Lines were clearly identified by the water-relations measurements. We concluded that SIF did not provide any advantage over commonly used methods for detecting physiological differences between the Introgression Lines. Overall, although SIF plays a significant role in photosynthesis, the relationship between SIF and photosynthesis is complex and we believe it would be an oversimplification to use SIF to quantify photosynthetic activity on close canopy spatial resolution level.
Impact of variants of concern on SARS-CoV-2 viral dynamics in non-human primates
Authors: Marc Aurélien , Marlin Romain , Donati Flora , Prague Mélanie , Kerioui Marion , Hérate Cécile , Alexandre Marie , Dereuddre-bosquet Nathalie , Bertrand Julie , Contreras Vanessa , Behillil Sylvie , Maisonnasse Pauline , Van Der Werf Sylvie , Grand Roger Le , Guedj Jérémie
Published: November 2022

The impact of variants of concern (VoC) on SARS-CoV-2 viral dynamics remains poorly understood and essentially relies on observational studies subject to various sorts of biases. In contrast, experimental models of infection constitute a powerful model to perform controlled comparisons of the viral dynamics observed with VoC and better quantify how VoC escape from the immune response.

Here we used molecular and infectious viral load of 78 cynomolgus macaques to characterize in detail the effects of VoC on viral dynamics. We first developed a mathematical model that recapitulate the observed dynamics, and we found that the best model describing the data assumed a rapid antigen-dependent stimulation of the immune response leading to a rapid reduction of viral infectivity. When compared with the historical variant, all VoC except beta were associated with an escape from this immune response, and this effect was particularly sensitive for delta and omicron variant (p<10−6for both). Interestingly, delta variant was associated with a 1.8-fold increased viral production rate (p=0.046), while conversely omicron variant was associated with a 14-fold reduction in viral production rate (p<10−6). During a natural infection, our models predict that delta variant is associated with a higher peak viral RNA than omicron variant (7.6 log10copies/mL 95% CI 6.8 – 8 for delta; 5.6 log10copies/mL 95% CI 4.8 – 6.3 for omicron) while having similar peak infectious titers (3.7 log10PFU/mL 95% CI 2.4 – 4.6 for delta; 2.8 log10PFU/mL 95% CI 1.9 – 3.8 for omicron). These results provide a detailed picture of the effects of VoC on total and infectious viral load and may help understand some differences observed in the patterns of viral transmission of these viruses.
SARS-CoV-2 ORF8 limits expression levels of Spike antigen
Authors: Kim Ik-Jung , Lee Yong-ho , Khalid Mir M. , Zhang Yini , Ott Melanie , Verdin Eric
Published: November 2022

Survival from COVID-19 depends on the ability of the host to effectively neutralize virions and infected cells, a process largely driven by antibody-mediated immunity. However, with the newly emerging variants that evade Spike-targeting antibodies, re-infections and breakthrough infections are increasingly common. A full characterization of SARS-CoV-2 mechanisms counteracting antibody-mediated immunity is needed. Here, we report that ORF8 is a SARS-CoV-2 factor that controls cellular Spike antigen levels. ORF8 limits the availability of mature Spike by inhibiting host protein synthesis and retaining Spike at the endoplasmic reticulum, reducing cell-surface Spike levels and recognition by anti-SARS-CoV-2 antibodies. With limited Spike availability, ORF8 restricts Spike incorporation during viral assembly, reducing Spike levels in virions. Cell entry of these virions leaves fewer Spike molecules at the cell surface, limiting antibody recognition of infected cells. Our studies propose an ORF8-dependent SARS-CoV-2 strategy that allows immune evasion of infected cells for extended viral production.
Persulfidation of DJ-1 : Mechanism and Consequences
Authors: Galardon Erwan , Mathas Nicolas , Padovani Dominique , Le Corre Laurent , Poncet Gabrielle , Dairou Julien
Published: November 2022

DJ-1 (also called PARK7) is a ubiquitously expressed protein involved in the etiology of Parkinson disease and cancers. At least one of its three cysteine residue is functionally essential, and its oxidation state determines the specific function of the enzyme. DJ-1 was recently reported to be persulfidated in mammalian cell lines, but the implications of this post-translational modification have not yet been analyzed. Here, we report that recombinant DJ-1 is reversibly persulfidated at cysteine 106 by reaction with various sulfane donors and subsequently inhibited. Strikingly, this reaction is orders of magnitude faster than C106 oxidation by H2O2, and persulfidated DJ-1 behaves differently than sulfinylated DJ-1. Both these PTM most likely play a dedicated role in DJ-1 signaling or protective pathways.
Halogen, chalcogen, and hydrogen bonding in organoiodine cocrystals of heterocyclic thiones: imidazolidine-2-thione, 2-mercaptobenzimidazole, 2-mercapto-5-methylbenzimidazole, 2-mercaptobenzoxazole, and 2-mercaptobenzothiazole
Authors: Watts Spencer , Peloquin Andrew J. , Bandara Madhushi , McMillen Colin D. , Pennington William T.
Published: November 2022

Through the combination of heterocyclic thiones with variation in the identity of the heterocyclic elements, namely, imidazolidine-2-thione, 2-mercaptobenzimidazole, 2-mercapto-5-methylbenzimidazole, 2-mercaptobenzoxazole, and 2-mercaptobenzothiazole with the common halogen-bond donors 1,2-, 1,3-, and 1,4-diiodotetrafluorobenzene, 1,3,5-trifluorotriiodobenzene, and tetraiodoethylene, a series of 18 new crystalline structures were characterized. In most cases, N—H...S hydrogen bonding was observed, with these interactions in imidazole-containing structures typically resulting in two-dimensional motifs (i.e. ribbons). Lacking the second N—H group, the thiazole and oxazole hydrogen bonding resulted in only dimeric pairs. C—I...S and C—I...I halogen bonding, as well as C=S...I chalcogen bonding, served to consolidate the packing by linking the hydrogen-bonding ribbons or dimeric pairs.
Bending properties in the 4-halobenzonitrile crystals and C–halogen...N[triple-bond]C halogen bonds
Authors: Veluthaparambath Ragima V. P. , Krishna G Vibha , Pancharatna Pattath D. , Saha Binoy K.
Published: November 2022

The single crystal of 4-iodobenzonitrile (C7H4IN) is brittle, whereas those of 4-bromobenzonitrile (C7H4BrN) and one of the two forms of 4-chlorobenzonitrile (C7H4ClN) are compliant in nature. The chloro crystal exhibits elastic bending, but in spite of having stronger halogen bonds, the bromo crystal exhibits plastic bending. Crystal structures have been analyzed to understand the different bending properties of these three crystals. In all three cases, the molecules form C—X...N[triple-bond]C (X = halogen) halogen-bonded chains in their respective crystal structures. Statistical analyses and DFT calculations on the C—X...N[triple-bond]C halogen bonds reveal that the optimum geometry of all three halogen bonds is linear and the C—I...N[triple-bond]C bond is strongest among the three. However, when the geometry deviates from linearity, the energy loss is very high in the case of the C—I...N[triple-bond]C bond compared to the other two systems. This explains why 4-iodobenzonitrile is brittle, whereas the other two are flexible. The interactions in 4-bromobenzonitrile are more isotropic than those in 4-chlorobenzonitrile. The iodo and chloro compounds crystallize in centrosymmetric space groups, whereas the crystal of the bromo compound lacks inversion symmetry. In spite of this difference in their space groups, the chloro and bromo crystals have very similar crystal packing. In the case of the bromo crystal, the halogen-bonded chains are parallel to the bending axis (long axis) of the crystal. However, these chains are significantly tilted in the case of the chloro crystal. The isotropic/anisotropic interactions, presence/absence of an inversion centre and the different alignment of the halogen-bonded chains with respect to the bending axis could explain the different bending properties of the chloro and bromo crystals.
Advance in grey system theory and applications in science and engineering
Authors: Liu Sifeng , Tao Yong , Xie Naiming , Tao Liangyan , Hu Mingli
Published: November 2022

Purpose

The purpose of this paper is to summarize the advances in grey system theory research and various application achievements in science and engineering. At the same time, it commemorates the 40th anniversary of the birth of grey system theory and the 10th anniversary of Grey Systems–Theory and Application.

Design/methodology/approach

Firstly, the innovations of theoretical research in grey system theory were summarized and some of the widely recognized new results are briefly described. By searching and combing the research results of grey system theory in China national knowledge infrastructure (CNKI) database and Web of Science by Institute for Scientific Information (ISI), this paper shows the rapid development trend of grey system theory in the past 40 years, and the successful applications of grey system theory in the fields of social sciences, natural sciences and engineering technologies.

Findings

More than 227 thousands literature were found by input 10 phrases such as grey system, grey number and sequence operator etc. in CNKI database. After entering the new century, the number of grey system papers included in CNKI database is increasing rapidly. Since 2008, more than 10 thousands papers have been included per year and more than 15 thousands papers have been included per year since 2014. Grey system method and model are widely used in physics, chemistry, biology and other fields of natural science, as well as transportation, electric power, machinery and other fields of engineering technology, and a large number of valuable results have been achieved.

Practical implications

It can be seen that the grey system theory plays an important role in promoting China’s scientific and technological progress, innovation and development and high-level talent training from tens of thousands of literatures marked with important national science and technology projects and a large number of grey system literatures published by China’s double first-class universities and double first-class discipline construction universities.

Originality/value

Both innovations of theoretical research and practical application play important role in the growth of new theory. The innovations of theoretical research provide methods and tools for practical application, which is conducive to improve application efficiency and broaden application fields. A large number of practical applications needs have become the source of theoretical innovation and the solid background for the birth of theoretical innovation achievements.
Examining the functionality of digital platform capability in driving B2B firm performance: evidence from emerging market
Authors: Liu Longjun , Long Jing , Fan Qing , Wan Wenhai , Liu Ruhong
Published: November 2022

Purpose

This study aims to explore the influence mechanism of digital platform capability on firm performance in the business-to-business (B2B) context. This study draws on the core competence theory and the resource-based view and includes resource identification, resource allocation and intrapreneurship into the research framework.

Design/methodology/approach

Data were collected from 167 B2B firms with survey questionnaires in central, eastern and southeastern coastal areas of China. The firms were mainly involved in e-commerce, manufacturing, service industry and internet technology. Participants were mainly middle and senior managers with a comprehensive grasp of their firms’ information.

Findings

This study found that digital platform capability has a positive impact on a B2B firm’s performance. Resource identification, resource allocation and intrapreneurship play a chain mediating role between digital platform capability and firm performance. That is, digital platform capability could promote employee intrapreneurship through resource identification and resource allocation, thereby improving firm performance.

Practical implications

Aiming to gain performance, firms should pay attention to the construction of digital platforms, increase venture capital investment and provide more resources to support intrapreneurship.

Originality/value

Based on empirical evidence, to the best of authors’ knowledge, this is the first attempt to link digital platform capability and firm performance in the B2B context of emerging markets, providing a new perspective to clarify its relationship mechanism.