bluuebunny/crossref_metadata_2025 huggingface dataset:
Single cell analysis of human CD8+T cells reveals CD45RClow/-TNFR2+CD29lowCD8+Tregs with superior activity
Authors: Sérazin Céline , Flippe Léa , Streitz Mathias , Wendering Désirée-Jacqueline , Schlickeiser Stephan , Heinrich Frederik , Durek Pawel , Guerra Gabriela , Lehmann Katrin , Mashreghi Mir-Farzin , Wajant Harald , Volk Hans Dieter , Anegon Ignacio , David Laurent , Bézie Séverine , Guillonneau Carole
Published: December 2023

Although described in the 70’s, CD8+regulatory T cells (Tregs) remain incompletely understood and to date, although several markers are used to define them, they remain poorly defined. The identification of reliable and consistent markers, as it was done for CD4+Tregs, remains an urgent task and a challenge to advance our understanding. Herein, we analyzed total CD8+T cells using single cell CITEseq and VDJ T cell receptor sequencing utilizing markers used previously to identify Tregs, in particular CD45RC described by our team and others to divide pro-inflammatory (CD45RChigh) and pro-regulatory (CD45RClow/-) CD8+T cells in rat, mice and human. 7000 freshly isolated, non-stimulated CD8+T lymphocytes of four healthy volunteers were analyzed. Combining at a single cell level transcriptome and protein expression data led for the first time to the characterization and definition of three subsets of regulatory CD8+T cells. Furtherin vitrofunctional analysis based on three markers highlighted the superior suppressive activity of the CD8+CD45RClow/-TNFR2+CD29lowTregs subset.

To our knowledge, this is the largest characterization of human CD8+Tregs to date. This data resource will help improve our understanding of CD8+T cells heterogeneity and will help to translate CD8+Tregs to the clinic.
Genomic Revisitation and Reclassification of the GenusProvidencia
Authors: Dong Xu , Jia Huiqiong , Yu Yuyun , Xiang Yanghui , Zhang Ying
Published: December 2023

Members ofProvidencia, although typically opportunistic, can cause severe infections in immunocompromised hosts. Recent advances in genome sequencing provide an opportunity for more precise study of this genus. In this study, we first identified and characterized a novel species namedProvidencia zhijiangensissp. nov. It has ≤88.23% average nucleotide identity (ANI) and ≤31.8% in silico DNA-DNA hybridization (dDDH) values with all knownProvidenciaspecies, which fall significantly below the species-defining thresholds. Interestingly, we found thatProvidencia stuartiiandProvidencia thailandensisactually fall under the same species, evidenced by an ANI of 98.59% and a dDDH value of 90.4%. By fusing ANI with phylogeny, we have reclassified 545 genomes within this genus into 20 species, including seven unnamed taxa (provisionally titled Taxon1-7), which can be further subdivided into 23 lineages. Pangenomic analysis identified 1,550 genus-core genes inProvidencia, with coenzymes being the predominant category at 10.56%, suggesting significant intermediate metabolism activity. Resistance analysis revealed that most lineages of the genus (82.61%, 19/23) carry a high number of antibiotic resistance genes (ARGs) and display diverse resistance profiles. Notably, the majority of ARGs are located on plasmids, underscoring the significant role of plasmids in the resistance evolution within this genus. Three species or lineages (P. stuartii, Taxon 3, andProvidencia hangzhouensisL12) that possess the highest number of carbapenem resistance genes suggest their potential influence on clinical treatment. These findings underscore the need for continued surveillance and study of this genus, particularly due to their role in harboring antibiotic resistance genes.
Phosphorylation Promotes Liquid-Liquid Phase Separation of GRP8 and Its Assembly into Stress Granules Upon Salinity Stress in Arabidopsis
Authors: Kasztelan Adrian , Maszkowska Justyna , Anielska-Mazur Anna , Cieślak Dominika , Polkowska-Kowalczyk Lidia , Poznański Jarosław , Dadlez Michał , Nöh Christiane , Steffen Alexander , Kasztelan Karolina , Bucholc Maria , Szymańska Katarzyna Patrycja , Gutierrez-Beltran Emilio , Staiger Dorothee , Sztatelman Olga , Dobrowolska Grażyna
Published: December 2023

Drought and salinity are major environmental stresses affecting plant development and growth. SNF1–related protein kinases type 2 (SnRK2s) are key regulators of the plant responses to water deficit and salt stress. Here, we show thatArabidopsis thalianaGlycine-Rich RNA-Binding Protein 8 (GRP8) is a target of abscisic acid (ABA)-non-activated SnRK2s and negatively regulates root growth and seed germination under salt stress. In response to salinity, GRP8 assembles into stress granules (SGs). We show that in addition to the GRP8 C-terminal glycine-rich intrinsically disordered region (IRD), the N-terminal RNA recognition motif (RRM) plays a key role in this process. Phosphorylation of S27 in the RRM by SnRK2s significantly affects the structural dynamics of GRP8, facilitates its dimerization and subsequent liquid-liquid phase separation. Thus, we show that in addition to the known role of IDRs in recruitment into SGs, the RRM plays a decisive role.
MAGqual: A standalone pipeline to assess the quality of metagenome-assembled genomes
Authors: Cansdale Annabel , Chong James P.J.
Published: December 2023

Metagenomics, the whole genome sequencing of microbial communities, has provided insight into complex ecosystems. It has facilitated the discovery of novel microorganisms, explained community interactions, and found applications in various fields. Advances in high-throughput and third-generation sequencing technologies have further fuelled its popularity. Nevertheless, managing the vast data produced and addressing variable dataset quality remain ongoing challenges. Another challenge arises from the number of assembly and binning strategies used across studies. Comparing datasets and analysis tools is complex as it requires a measure of metagenome quality. The inherent limitations of metagenomic sequencing, which often involves sequencing complex communities means community members are challenging to interrogate with traditional culturing methods leading to many lacking reference sequences.

The MIMAG standards (Bowerset al., 2017) aim to provide a method to assess metagenome quality for comparison but have not been widely adopted. To bridge this gap, the MAGqual pipeline outlined here offers an accessible way to evaluate metagenome quality and generate metadata on a large scale. MAGqual is built in Snakemake to ensure readability and scalability and its open-source nature promotes accessibility, community development, and ease of updates. Here, we introduce the pipeline MAGqual (metagenome-assembled genome qualifier) and demonstrate its effectiveness at determining metagenomic dataset quality when compared to the MIMAG standards. MAGqual is built in Snakemake, R, and Python and is available under the MIT License on GitHub athttps://github.com/ac1513/MAGqual.
Melanoma innervation is associated with cancer progression in a zebrafish xenograft model
Authors: Lorenzini Francesca , Marines Johanna , Friec Julien Le , Do Khoa Nam , Nieto Maria Angela , Sanchez-Laorden Berta , Mione Maria Caterina , Fontenille Laura , Kissa Karima
Published: December 2023

The peripheral nervous system has a key role in regulating tumour biology in different types of cancer. Here, by modelling aggressive melanoma in larval zebrafish xenografts, we highlight the dynamics of tumour innervation in the tumour microenvironment (TME). Axonogenesis and dendritogenesis are detected in the motoneurons surrounding the melanoma niche and neurogenesis is observed in the nearby population of the enteric nervous system. We also demonstrate the crucial role of catecholamines in promoting melanoma progression, supportingin vivocancer cell dissemination and invasion. Thiszebrafishmodel will allow to uncover neural markers associated with melanoma progression to help in the design of innovative anti-neurogenic therapies targeting specifically the neuronal signals that regulate melanoma progression.

Graphical abstract

Highlights

Transplantation of human melanoma cells in 3 dpf zebrafish swim bladder allows the development of aggressive melanoma, which cells invade the surrounding organs and migrate over distant locations.

The presence of melanoma cells in the larval zebrafish induces morphological changes in the motoneurons inside the tumour niche, including increased axon length and dendritic arborization.

The invasion of melanoma cells in the larval intestine promotes neurogenesis of enteric neurons.

Transplanted melanoma cells display direct contact with enteric neurons in the intestinal region and migrate along axons to escape from the primary cancer mass, as a mechanism similar to vessel co-option during metastatic dissemination.

Catecholamines promote melanoma cell migration and invasion in the zebrafish, modelling melanoma progression.
chronODE: A framework to integrate time-series multi-omics data based on ordinary differential equations combined with machine learning
Authors: Borsari Beatrice , Frank Mor , Wattenberg Eve S. , Xu Ke , Liu Susanna X. , Yu Xuezhu , Gerstein Mark
Published: December 2023

Most functional genomic studies are conducted in steady-state conditions, therefore providing a description of molecular processes at a particular moment of cell differentiation or organismal development. Longitudinal studies can offer a deeper understanding of the kinetics underlying epigenetic events and their contribution to defining cell-type-specific transcriptional programs. Here we developchronODE, a mathematical framework based on ordinary differential equations that uniformly models the kinetics of temporal changes in gene expression and chromatin features.chronODEemploys biologically interpretable parameters that capture tissue-specific kinetics of genes and regulatory elements. We further integrate this framework with a neural-network architecture that can link and predict changes across different data modalities by solving multivariate time-series regressions. Next, we apply this framework to investigate region-specific kinetics of epigenome rewiring in the developing mouse brain, and we demonstrate that changes in chromatin accessibility within regulatory elements can accurately predict changes in the expression of putative target genes over the same time period. Finally, by integrating single-cell ATAC-seq data generated during the same time course, we show that regulatory elements characterized by fast activation kinetics in bulk measurements are active in early-appearing cell types, such as radial glial and other neural progenitors, whereas elements characterized by slow activation kinetics are specific to more differentiated cell types that emerge at later stages of brain development.
Characterization of bovine vaginal microbiota and its relationship with host fertility, health, and production
Authors: Brulin L , Ducrocq S , Even G , Sanchez MP , Martel S , Merlin S , Audebert C , Croiseau P , Estellé J
Published: December 2023

Background

Because of its potential influence on the host’s phenotype, increasing attention is paid to organ-specific microbiota in several animal species, including cattle. However, ecosystems other than those related to the digestive tract remain largely understudied. In particular, little is known about the vaginal microbiota of ruminants despite the importance of the reproductive functions of cows in a livestock context, where fertility disorders represent one of the primary reasons for culling.

Results

In the present study, we aimed at better characterizing the vaginal microbiota of dairy cows through 16S rRNA sequencing, using a large cohort of Holstein cows from Northern France. Our results allowed to define a core microbiota of the dairy cows’ vagina, and highlighted that 90% of the sequences belonged to the Firmicutes, the Proteobacteria, and the Bacteroidetes phyla. The core microbiota was composed of four phyla, 16 families, 14 genera and only one amplicon sequence variant (ASV), supporting the idea of the high diversity of vaginal microbiota within the studied population. This variability was partly explained by various environmental factors such as the herd, the sampling season, the lactation rank and the lactation stage. In addition, we investigated potential associations between the diversity and the composition of the vaginal microbiota and several health-, performance-, and fertility-related phenotypes. Our analyses highlighted significant associations between the α and β- diversities and several traits including the first insemination outcome, the productive longevity, and the culling. Besides, relevant phenotypes were correlated with the abundance of several genera, some of which, such asLeptotrichia,Streptobacillus,Methylobacterium-Methylorubrum, orNegativibacillus, were linked to multiple traits.

Conclusion

Considering the large number of samples, which were collected in commercial farms, and the diversity of the phenotypes considered, this study represents a first step towards a better understanding of the close relationship between the vaginal and the dairy cow’s phenotypes.
Biosynthesis of Strained Amino Acids Through a PLP-Dependent Enzyme via Cryptic Halogenation
Authors: Sosa Max B. , Leeman Jacob T. , Washington Lorenzo J. , Scheller Henrik V. , Chang Michelle C. Y.
Published: December 2023

Amino acids (AAs) are modular and modifiable building blocks which nature uses to synthesize both macromolecules, such as proteins, and small molecule natural products, such as alkaloids and non-ribosomal peptides (NRPs). While the 20 main proteinogenic AAs display relatively limited side-chain diversity, a wide range of non-canonical amino acids (ncAAs) exist that are not used by the ribosome for protein synthesis but contain a broad array of structural features and functional groups not found in proteinogenic AAs. In this communication, we report the discovery of the biosynthetic pathway for a new ncAA, pazamine, which contains a cyclopropane ring formed in two steps. In the first step, a chlorine is added onto the C4position of lysine by a radical halogenase PazA. The cyclopropane ring is then formed in the next step by a pyridoxal-5’-phosphate-dependent enzyme, PazB, via an SN2-like attack onto C4to eliminate chloride. Genetic studies of this pathway in the native host,Pseudomonas azotoformans, show that pazamine and its succinylated derivative, pazamide, potentially inhibit ethylene biosynthesis in growing plants based on alterations in the root phenotype ofArabidopsis thalianaseedlings. We further show that PazB can be utilized to make an alternative cyclobutane-containing AA. These discoveries may lead to advances in biocatalytic production of specialty chemicals and agricultural biotechnology.
Pigs are highly susceptible to but do not transmit mink-derived highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b
Authors: Kwon Taeyong , Trujillo Jessie D. , Carossino Mariano , Lyoo Eu Lim , McDowell Chester D. , Cool Konner , Matias-Ferreyra Franco S. , Jeevan Trushar , Morozov Igor , Gaudreault Natasha N. , Balasuriya Udeni B.R. , Webby Richard J. , Osterrieder Nikolaus , Richt Juergen A.
Published: December 2023

Rapid evolution of highly pathogenic avian influenza viruses (HPAIVs) is driven by antigenic drift but also by reassortment, which might result in robust replication in and transmission to mammals. Recently, spillover of clade 2.3.4.4b HPAIV to mammals including humans, and their transmission between mammal species has been reported. This study aimed to evaluate the pathogenicity and transmissibility of a mink-derived clade 2.3.4.4b H5N1 HPAIV isolate from Spain in pigs. Experimental infection caused moderate to severe interstitial pneumonia with necrotizing bronchiolitis with high titers of virus present in the lower respiratory tract of principal-infected pigs and 100% seroconversion. Principal-infected pigs shed limited amount of virus through the nasal and oral cavities, and importantly, there was no transmission to contact sentinel pigs. Notably, critical mammalian-like mutations such as PB2-E627K and HA-Q222L emerged at low frequencies in clinical samples and tissues derived from principal-infected pigs. It is concluded that pigs are highly susceptible to infection with the mink-derived clade 2.3.4.4b H5N1 HPAIV and provide a favorable environment for HPAI viruses to acquire mammalian-like adaptations. This work is critical for further risk assessment on the ability of the newly emerging H5N1 clade 2.3.4.4b HPAIVs to cross the species barriers into mammals.
ATOM-1: A Foundation Model for RNA Structure and Function Built on Chemical Mapping Data
Authors: Boyd Nicholas , Anderson Brandon M. , Townshend Brent , Chow Ryan , Stephens Connor J. , Rangan Ramya , Kaplan Matias , Corley Meredith , Tambe Akshay , Ido Yuzu , Yukich Jake , Tcheau Tabitha , Abdeldayem Ayah , Ferns Gabriel , Patel Harsh , Barman Shaon , Schleck April , Sanborn Adrian L. , Eismann Stephan , Townshend Raphael J. L.
Published: December 2023

RNA-based medicines and RNA-targeting drugs are emerging as promising new approaches for treating disease. Optimizing these therapeutics by naive experimental screening is a time-consuming and expensive process, while rational design requires an accurate understanding of the structure and function of RNA. To address this design challenge, we present ATOM-1, the first RNA foundation model trained on chemical mapping data, enabled by data collection strategies purposely developed for machine learning training. Using small probe neural networks on top of ATOM-1 embeddings, we demonstrate that this model has developed rich internal representations of RNA. Trained on limited amounts of additional data, these small networks achieve state-of-the-art accuracy on key RNA prediction tasks, suggesting that this approach can enable the design of therapies across the RNA landscape.
Long-range action of an HDAC inhibitor treats chronic pain in a spared nerve injury rat model
Authors: Centeno Maria Virginia , Alam Md. Suhail , Haldar Kasturi , Apkarian Apkar Vania
Published: December 2023

Histone deacetylase inhibitors (HDACi) that modulate epigenetic regulation and are approved for treating rare cancers have, in disease models, also been shown to mitigate neurological conditions, including chronic pain. They are of interest as non-opioid treatments, but achieving long-term efficacy with limited dosing has remained elusive. Here we utilize a triple combination formulation (TCF) comprised of a pan-HDACi vorinostat (Vo at its FDA-approved daily dose of 50mg/Kg), the caging agent 2-hydroxypropyl-β-cyclodextrin (HPBCD) and polyethylene glycol (PEG) known to boost plasma and brain exposure and efficacy of Vo in mice and rats, of various ages, spared nerve injury (SNI) model of chronic neuropathic pain. Administration of the TCF (but not HPBCD and PEG) decreased mechanical allodynia for 4 weeks without antagonizing weight, anxiety, or mobility. This was achieved at less than 1% of the total dose of Vo approved for 4 weeks of tumor treatment and associated with decreased levels of major inflammatory markers and microglia in ipsilateral (but not contralateral) spinal cord regions. A single TCF injection was sufficient for 3-4 weeks of efficacy: this was mirrored in repeat injections, specific for the injured paw and not seen on sham treatment. Pharmacodynamics in an SNI mouse model suggested pain relief was sustained for days to weeks after Vo elimination. Doubling Vo in a single TCF injection proved effectiveness was limited to male rats, where the response amplitude tripled and remained effective for > 2 months, an efficacy that outperforms all currently available chronic pain pharmacotherapies. Together, these data suggest that through pharmacological modulation of Vo, the TCF enables single-dose effectiveness with extended action, reduces long-term HDACi dosage, and presents excellent potential to develop as a non-opioid treatment option for chronic pain.
Amyloid-motif-dependent tau self-assembly is modulated by isoform sequence context
Authors: Bali Sofia , Singh Ruhar , Wydorski Pawel M. , Van Nuland Nico E. , Wosztyl Aleksandra , Perez Valerie A. , Chen Dailu , Chen Jie , Rizo Josep , Joachimiak Lukasz A.
Published: December 2023

The microtubule-associated protein tau is implicated in neurodegenerative diseases characterized by amyloid formation. Mutations associated with frontotemporal dementia increase tau aggregation propensity and disrupt its endogenous microtubule-binding activity. However, the structural relationship between aggregation propensity and biological activity remains unclear. We employed a multi-disciplinary approach, including computational modeling, NMR, cross-linking mass spectrometry, and cell models to engineer tau sequences that modulate its structural ensemble. Our findings show that substitutions near the conserved ‘PGGG’ β-turn motif informed by tau isoform context reduce tau aggregation in vitro and cells and can even counteract aggregation induced by turn destabilizing disease-associated proline-to-serine mutations. Engineered tau sequences maintain microtubule binding and explain why 3R isoforms exhibit reduced pathogenesis compared to 4R. We propose a simple mechanism to reduce the formation of pathogenic species while preserving biological function, thus offering insights for therapeutic strategies aimed at reducing tau protein misfolding in neurodegenerative diseases.

Abstract Figure
Multivalent DNA-encoded lectins on phage enable detecting compositional glycocalyx differences
Authors: Lima Guilherme Meira , Chenarboo Zeinab Jame , Sojitra Mirat , Sarkar Susmita , Carpenter Eric J. , Yang Claire Yi-Ling , Schmidt Edward , Lai Justine , Atrazhev Alexey , Yazdan Danial , Peng Chuanhao , Volker Elizabeth Anne , Ho Ray , Monteiro Gisele , Lai Raymond , Mahal Lara K. , Macauley Matthew S. , Derda Ratmir
Published: December 2023

Selective detection of disease-associated changes in the cellular glycocalyx is a foundation of modern targeted therapies. Detecting minor changes in the density and identity of glycans on the cell surface is a technological challenge exacerbated by lack of 1:1 correspondence between cellular DNA/RNA and glycan structures on cell surface. We demonstrate that multivalent displays of up to 300 lectins on DNA-barcoded M13 phage on a liquid lectin array (LiLA), detects subtle differences in composition and density of glycans on cellsex vivoand in immune cells or organs in animals. For example, constructs displaying 73 copies of diCBM40 lectin per 700×5 nm virion (φ-CBM73) exhibit non-linear ON/OFF-like recognition of sialoglycans on the surface of normal and cancer cells. In contrast, a high-valency φ-CBM290 display, or soluble diCBM40, exhibit canonical progressive scaling in binding with increased epitope density; these constructs cannot amplify the subtle differences detected by φ-CBM73. Similarly, multivalent displays of diCBM40 and Siglec-7 detect differences in the glycocalyx between stem-like and non-stem populations in cancer cells that are not detected with soluble lectins. Multivalent display of lectins on M13 scaffold with protected DNA inside the phage offer non-destructive detection of minor differences in glycocalyx in cellsin vitroandin vivonot feasible to currently available technologies.
Interplay between m6A modification and overall transcripts quantity: Impacts on mRNA composition in plant stress granules
Authors: Kubiak Dawid Jakub , Szczesniak Michal Wojciech , Ostrowska Karolina , Bielewicz Dawid , Bhat Susheel Sagar , Niedojadlo Katarzyna , Szweykowska-Kulinska Zofia , Jarmolowski Artur , Fray Rupert George , Niedojadlo Janusz
Published: December 2023

Stress granules (SGs) are cytoplasmic structures that emerge in response to unfavorable environmental conditions. They contain a rich pool of RNA, including non-translated mRNA. The mechanisms governing transcripts accumulation in SGs is only partially understood. Despite the recognized role of m6A in plant transcriptome regulation, its impact on SGs’ composition and assembly remains elusive. We examined the formation of SGs, the presence of m6A, and the transcription-level-dependent localization of selected mRNAs within these granules during hypoxia in the roots ofLupinus angustifoliusandArabidopsis thaliana. In lupine, SGs exhibit a distinctive bi-zonal structure, comprising of a ring and a central area with differences in ultrastructure and composition. Following the transcriptome analysis, mRNAs were selected for examination of their localization in SGs and m6A levels. Transcripts from genes responsive to hypoxia (ADH1 and HUP7) exhibited significant lower levels of m6A compared to housekeeping genes but only ADH1 was not present in SGs. HUP7 mRNA with low quantity of m6A, is present both in the SGs and cytoplasm probably due to extremely high expression level. It was also shown that the amount of m6A in SGs was higher than in the cytoplasm only in the first hours of hypoxia and then decreased. In mutants of A. thaliana with reduced level of m6A, formation and quantity of SGs were studied. In this line, ECT2 was not observed and poly(A) RNA levels were slightly reduced in SGs. Additionally the number of SGs was lower than that of the wild type. In summary, our findings demonstrate the limited impact of m6A modification on SGs assembly. However the interplay between m6A modification and the overall transcript quantity in the cytoplasm plays a regulatory role in mRNA partitioning into SGs.
Cyanobacterial sigma factor controls biofilm-promoting genes through intra- and intercellular pathways
Authors: Suban Shiran , Yemini Sapir , Shor Anna , Ben-Asher Hiba Waldman , Yaron Orly , Lampert Sarit , Sendersky Eleonora , Golden Susan S , Schwarz Rakefet
Published: December 2023

Cyanobacteria frequently constitute integral components of microbial communities known as phototrophic biofilms. These assemblages are not only widespread in various environmental contexts but also hold significant industrial relevance. Nevertheless, the governing elements responsible for cyanobacterial biofilm development have remained elusive. This study, which employs the model cyanobacteriumSynechococcus elongatusPCC 7942, demonstrates that the RNA polymerase sigma factor SigF1, but not its paralog SigF2, is required for a biofilm-suppression mechanism that operates in this organism. Comprehensive transcriptome analyses identified distinct regulons under the control of each of these sigma factors. Additional data indicate that SigF1 regulates biofilm through its involvement in transcriptional induction of genes that include those for the primary pilus subunit:sigF1inactivation both prevents pilus assembly and abrogates secretion of a biofilm inhibitor. Consequently, expression is significantly upregulated for theebfG-operon that encodes matrix components and the genes that encode their corresponding secretion system. Thus, this study uncovers a basic regulatory component of cyanobacterial communal behavior. Elevated expression of biofilm-promoting genes in asigF1mutant supports an additional layer of regulation by SigF1 that operates via an intracellular mechanism.
Closure of the γ-tubulin ring complex by CDK5RAP2 activates microtubule nucleation
Authors: Xu Yixin , Muñoz-Hernández Hugo , Krutyhołowa Rościsław , Marxer Florina , Cetin Ferdane , Wieczorek Michal
Published: December 2023

Microtubule nucleation in cells is templated by the γ-tubulin ring complex (γ-TuRC), a 2.3 MDa multiprotein assembly concentrated at microtubule organizing centers (MTOCs). Current γ-TuRC structures exhibit an open conformation that deviates from the geometry of α/β-tubulin in the microtubule, potentially explaining their low in vitro microtubule-nucleating activity. Several proteins have been proposed to activate the γ-TuRC, but the mechanisms underlying activation are not known. Here, we isolated the porcine γ-TuRC using CDK5RAP2’s centrosomin motif 1 (CM1) and determined its structure with cryo-electron microscopy. 3D heterogeneity analysis revealed an unexpected conformation of the γ-TuRC, in which five protein modules containing MZT2, GCP2, and CDK5RAP2 decorate the outer face of the holocomplex. These decorations drive a long-range constriction of the γ-tubulin ring, bringing the GCP2/GCP3-rich core of the complex in close agreement with the architecture of a microtubule. A purified CDK5RAP2 fragment stimulated the microtubule nucleating-activity of the porcine γ-TuRC as well as a reconstituted, CM1-free human complex in single molecule assays. Our results show that CDK5RAP2 activates the γ-TuRC by promoting γ-tubulin ring closure, providing a structural mechanism for the regulation of microtubule nucleation by CM1 motif proteins in mammals and revealing conformational transitions in γ-tubulin that prime it for templating microtubule nucleation at MTOCs.
Predicting neutralization susceptibility to combination HIV-1 monoclonal broadly neutralizing antibody regimens
Authors: Williamson Brian D. , Wu Liana , Huang Yunda , Hudson Aaron , Gilbert Peter B.
Published: December 2023

Combination monoclonal broadly neutralizing antibodies (bnAbs) are currently being developed for preventing HIV-1 infection. Recent work has focused on predicting in vitro neutralization potency of both individual bnAbs and combination regimens against HIV-1 pseudoviruses using Env sequence features. To predict in vitro combination regimen neutralization potency against a given HIV-1 pseudovirus, previous approaches have applied mathematical models to combine individual-bnAb neutralization and have predicted this combined neutralization value; we call this the combine-then-predict (CP) approach. However, prediction performance for some individual bnAbs has exceeded that for the combination, leading to another possibility: combining the individual-bnAb predicted values and using these to predict combination regimen neutralization; we call this the predict-then-combine (PC) approach. We explore both approaches in both simulated data and data from the Los Alamos National Laboratory’s Compile, Neutralize, and Tally NAb Panels repository. The CP approach is superior to the PC approach when the neutralization outcome of interest is binary (e.g., neutralization susceptibility, defined as inhibitory concentration<1 µg/mL. For continuous outcomes, the CP approach performs at least as well as the PC approach, and is superior to the PC approach when the individual-bnAb prediction algorithms have poor performance. This knowledge may be used when building prediction models for novel antibody combinations in the absence of in vitro neutralization data for the antibody combination; this, in turn, will aid in the evaluation and down-selection of these antibody combinations into prevention efficacy trials.
Ultrasound-Assisted Hydrolysis of Food Waste using Glucoamylase: Statistical Optimization and Mechanistic Analysis with Molecular Simulations
Authors: Anand Avinash , Kumar Karan , Khaire Kaustubh Chandrakant , Roy Kuldeep , Moholkar Vijayanand Suryakant
Published: December 2023

Food waste represents a promising and cost-effective resource for synthesizing value-added products through a fermentative pathway. Preceding fermentation, the hydrolysis of food waste into monomeric sugars is a crucial step. This study presents a comprehensive investigation of food waste hydrolysis, encompassing experimental and computational approaches, using glucoamylase (GLCM) enzyme. Initial optimization of hydrolysis parameters was conducted through the Box–Behnken design of experiments, resulting in a total reducing sugar yield (TRS) of 263.4 mg/g biomass under optimized conditions within 42 hours. Sonication of hydrolysis mixture at 35 kHz at 20% duty cycle, yielded a 4× reduction in hydrolysis time with 22% enhancement in TRS yield (320 mg/g biomass). Analysis of GLCM’s secondary structure revealed sonication-induced changes through FTIR spectra deconvolution in both control and test experiments. Sonication led to a reduction in α-helix content and an increase in random coil content. Molecular dynamics simulations, including molecular docking, unveiled the majority of amino acid residues associated with the GLCM binding pocket in the α-helix and random coil regions. Consequently, sonication widened the binding pockets, facilitating easier transport of substrate and product. This effect translated into improved reaction kinetics in food waste hydrolysis.

Research Highlights

Statistical optimization of food waste hydrolysis: TRS yield = 263.4 mg/g in 42 h

4x reduction of hydrolysis time, 22% rise in TRS yield with 35 kHz sonication

Sonication reduced α-helix content & increased random coil content of glucoamylase

Molecular docking simulation to deduce mechanism of ultrasound-assisted hydrolysis

MD simulations reveal widening of binding pockets and enhancing catalytic efficiency
Structure determination using high-order spatial correlations in single-particle X-ray scattering
Authors: Zhao Wenyang , Miyashita Osamu , Nakano Miki , Tama Florence
Published: December 2023

Single-particle imaging using X-ray free-electron lasers (XFELs) is a promising technique for observing nanoscale biological samples under near-physiological conditions. However, as the sample's orientation in each diffraction pattern is unknown, advanced algorithms are required to reconstruct the 3D diffraction intensity volume and subsequently the sample's density model. While most approaches perform 3D reconstruction via determining the orientation of each diffraction pattern, a correlation-based approach utilizes the averaged spatial correlations of diffraction intensities over all patterns, making it well suited for processing experimental data with a poor signal-to-noise ratio of individual patterns. Here, a method is proposed to determine the 3D structure of a sample by analyzing the double, triple and quadruple spatial correlations in diffraction patterns. This ab initio method can reconstruct the basic shape of an irregular unsymmetric 3D sample without requiring any prior knowledge of the sample. The impact of background and noise on correlations is investigated and corrected to ensure the success of reconstruction under simulated experimental conditions. Additionally, the feasibility of using the correlation-based approach to process incomplete partial diffraction patterns is demonstrated. The proposed method is a variable addition to existing algorithms for 3D reconstruction and will further promote the development and adoption of XFEL single-particle imaging techniques.
Dynamic X-ray speckle-tracking imaging with high-accuracy phase retrieval based on deep learning
Authors: Yu Fucheng , Du Kang , Ju Xiaolu , Wang Feixiang , Li Ke , Chen Can , Du Guohao , Deng Biao , Xie Honglan , Xiao Tiqiao
Published: December 2023

Speckle-tracking X-ray imaging is an attractive candidate for dynamic X-ray imaging owing to its flexible setup and simultaneous yields of phase, transmission and scattering images. However, traditional speckle-tracking imaging methods suffer from phase distortion at locations with abrupt changes in density, which is always the case for real samples, limiting the applications of the speckle-tracking X-ray imaging method. In this paper, we report a deep-learning based method which can achieve dynamic X-ray speckle-tracking imaging with high-accuracy phase retrieval. The calibration results of a phantom show that the profile of the retrieved phase is highly consistent with the theoretical one. Experiments of polyurethane foaming demonstrated that the proposed method revealed the evolution of the complicated microstructure of the bubbles accurately. The proposed method is a promising solution for dynamic X-ray imaging with high-accuracy phase retrieval, and has extensive applications in metrology and quantitative analysis of dynamics in material science, physics, chemistry and biomedicine.
LMX and a perceived supportive environment for corporate entrepreneurship: the mediating role of psychological empowerment
Authors: Yasmin Mariam , Zeytonli Asiye , Houghton Jeffery D. , Hardway Lewis
Published: December 2023

Purpose

This paper aims to explore the potential explanatory mechanisms linking leader–member exchange (LMX) and a perceived supportive environment for corporate entrepreneurship. Specifically, this paper develops and tests a hypothesized moderated mediation model of the relationship between LMX and a perceived supportive environment for corporate entrepreneurship through psychological empowerment as conditional upon the level of control orientation.

Design/methodology/approach

Data were collected from a sample of 682 full-time working adults in the USA and were examined in a moderated mediation model in PROCESS.

Findings

The findings suggest that higher LMX augments perceptions of a supportive environment for corporate entrepreneurship with a mediating role for psychological empowerment and a moderating role for control orientation on that conditional relationship.

Research limitations/implications

This research suggests that high quality LMX relationships may enrich the human capital of firms, helping them to innovate and outperform competitors in the context of modern competitive dynamics. The study findings are limited by several factors including a cross-sectional design and a student-recruited sampling approach.

Originality/value

The study offers unique contributions to the leadership and entrepreneurship literature by being among the first to empirically investigate the relationship between LMX and a perceived supportive environment for corporate entrepreneurship as mediated by psychological empowerment and moderated by control orientation, yielding important insights regarding effective leadership practices for facilitating innovative behaviors and corporate entrepreneurship.
Linking interacting/engaging environmental CSR communication strategy and employees' pro-environmental behaviors (PEBs): mediating roles of communal relationship and employee empowerment
Authors: Dong Enzhu , Sun Ruoyu , Lee Yeunjae
Published: December 2023

Purpose

With the growing concern for environmental and sustainability issues, especially in the aftermath of the coronavirus disease 2019 (COVID-19) pandemic, organizations feel compelled to pursue green sustainability in their operations. In this regard, the active involvement of employees in pro-environmental behaviors (PEBs) is crucial for achieving organizational environmental sustainability goals (Saeed et al., 2019). To shed light on this important issue, this study aims to investigate the impact of interacting/engaging environmental corporate social responsibility (CSR) communication strategy on employees' PEBs through the mediating effects of communal relationship and employee empowerment.

Design/methodology/approach

A total of 443 full-time USA employees working across various industries participated in an online survey.

Findings

The interacting/engaging environmental CSR communication strategy fosters employees' perceived communal relationship with their organizations and empowers them to support their organization's environmental initiatives, which, in turn, positively influences employees' PEBs at work.

Originality/value

This study advances CSR and internal communication literature through the lens of relationship management and self-determination theories. The findings theoretically suggest the effectiveness of the interacting/engaging environmental CSR communication strategy in nurturing favorable employee–organization relationships (EORs), employee empowerment and PEBs at work. The practical implications of CSR communication are also elaborated.
“We don’t even know where it’s kept”: exploring perspectives on naloxone administration by provincial correctional workers in Manitoba, Canada
Authors: Ricciardelli Rose Rosemary , Johnston Matthew S. , Maier Katharina
Published: December 2023

Purpose

Prisonersare at disproportionate risk of suffering substance-related harms. The administration of naloxone is essential to reversing opioid overdose and minimizing substance-related harms in prison and the community. The purpose of this study is to examine how naloxone administration is practiced and perceived in prison settings.

Design/methodology/approach

The authors conducted surveys with correctional workers in Manitoba, Canada (n = 257) to examine how they understand and feel about the need for and practice of administering naloxone in their everyday work with criminalized populations.

Findings

Respondents reported feeling a great need to administer naloxone, but most did not feel adequately trained to administer naloxone, creating the perception that criminalized populations remain at enhanced risk.

Originality/value

Findings provide emerging evidence of the need for training and accompanying policies and procedures for correctional workers on how to access and administer naloxone.
Income diversification and bank performance: an evidence from emerging economy of Pakistan
Authors: Ashraf Yasir , Nazir Mian Sajid
Published: December 2023

Purpose

The income structure of banks has undergone a notable change in recent decades; therefore, non-interest-based activities have gained much attention. This paper aims to examine the impact of income diversification on bank performance in Pakistan.

Design/methodology/approach

A balanced panel data set of 20 Pakistani commercial banks is used from 2007 to 2020. The random effect model is employed to test the relationship between income diversification and financial performance.

Findings

The empirical results indicate a significant positive impact of income diversification of banks on risk-adjusted returns on assets and equity. Moreover, while banks' risk-adjusted profit performance improves with the increase in bank size, equity ratio and loan ratio, it deteriorates with high credit risk and technology. However, geographical diversification does not explain financial performance in all the risk-adjusted return on equity models. Among the macroeconomic factors, the interest rate influences bank risk-adjusted returns positively, whereas gross domestic product and inflation rate have a negative effect on banks' financial performance.

Originality/value

To the best of the author's knowledge, this study is the first to empirically investigate the relationships between income diversification and the risk-adjusted profits of Pakistani-listed commercial banks. This study has implications for regulators and policymakers of commercial banks.
Remittances and economic growth: a blessing for middle-income countries, ineffective for low-income countries
Authors: Azizi SeyedSoroosh , Aftabi Abed , Azizkhani Mohsen , Yektansani Kiana
Published: December 2023

Purpose

This study investigates the impact of international remittances on the economic growth of remittance-receiving countries, using data from 113 developing countries between 1990 and 2015.

Design/methodology/approach

The authors used a novel approach to address the potential endogeneity of remittances. The authors estimated bilateral remittances and use them to create weighted indicators of remittance-sending countries, which the authors then use as instruments for remittance inflows to remittance-receiving countries.

Findings

The results indicate that while remittances have a positive impact on economic growth in developing countries with high human capital, they do not contribute to growth in developing countries with low human capital. The authors also examined the channels through which remittances affect growth. The findings suggested that remittances do not impact labor supply in developing countries with high human capital, but they reduce labor supply in countries with low human capital. Additionally, remittances increase investment in physical capital in developing countries with high human capital, but they do not have an effect on investment in developing countries with low human capital.

Originality/value

The authors investigated the impact of remittances on economic growth using a novel approach to address the endogeneity of remittances. Additionally, the authors examined the different indirect channels through which remittances can impact economic growth, such as their effect on labor supply and investment.
SDG commentary: collaboration services for sustainable development goal (SDG) partnerships
Authors: Fisk Raymond P. , Kabadayi Sertan , Sidaoui Karim , Tsiotsou Rodoula H.
Published: December 2023

Purpose

The purpose of this commentary is to complete the synthesis of the United Nations 17 Sustainable Development Goals (SDGs) into Seven Commentaries on Service Research Themes developed by ServCollab and the Journal of Services Marketing. As an approach to achieving SDG #17, ServCollab’s collaborative logic and design perspective for collaboration services for sustainable development partnerships are presented.

Design/methodology/approach

Collaboration is ServCollab’s Service Research Theme #7, which reframes the UN SDG meta goal #17 of Partnerships. In prior ServCollab research, four possible human interactions were identified: conflict, competition, cooperation and collaboration. Only the shared purpose of collaboration enables elevating the human experience.

Findings

The authors found no published service research that studied SDG #17, which means there are huge opportunities for service research on the role of collaboration in service systems. The alignment between the UN SDGs and ServCollab’s goals is explored. A research agenda for service research and SDG goals was proposed for collaborative communications, collaborative technologies and collaborative projects.

Practical implications

Practical ideas are offered for serving humanity through collaboration. Collaborations are the only practical solutions to humanity’s myriad sustainable development problems.

Social implications

When the United Nations developed its first 16 SDGs, they knew that accomplishing these goals required complex collaborations. That is why SDG #17 is Partnerships. ServCollab’s serving humanity logic applies collaboration to all social settings (large or small) where working together can sustain and regenerate the service ecosystem of Planet Earth.

Originality/value

This commentary describes a unique approach to building collaborative capacity for conducting service research projects for sustaining and regenerating the service ecosystem of Planet Earth.
The role of environmental work in supporting child desistance
Authors: Oswald Rebecca
Published: December 2023

Purpose

This paper aims to explore how environmental employment can promote desistance among criminalised children. Research demonstrates that being immersed in and interacting with the natural environment has a positive impact upon well-being and behaviour, including reduced aggressive and violent behaviours. However, how exposure to the natural environment might promote desistance amongst children with persistent criminal involvement is unclear.

Design/methodology/approach

This paper examines, through semi-structured interviews and participant observations, the experiences of n = 23 criminalised children aged 16–18 employed in outdoor work at a UK social enterprise.

Findings

The findings demonstrate how working in the natural environment can provide a safe space for children, where they can build positive relationships, learn valuable skills and reconnect with the world outside of the high-pressure, conflict-driven spaces in which they typically occupy.

Originality/value

This research highlights the relevance of the setting in which child rehabilitation takes place and the potential role of natural environments in providing places and opportunities which support pro-social identity development and desistance for children.