bluuebunny/crossref_metadata_2025 huggingface dataset:
Nociceptive neurons interact directly with gastric cancer cells via a CGRP/Ramp1 axis to promote tumor progression
Authors: Zhi Xiaofei , Wu Feijing , Qian Jin , Ochiai Yosuke , Lian Guodong , Malagola Ermanno , Chen Duan , Ryeom Sandra W , Wang Timothy C
Published: March 2024

Cancer cells have been shown to exploit neurons to modulate their survival and growth, including through establishment of neural circuits within the central nervous system (CNS)1–3. Here, we report a distinct pattern of cancer-nerve interactions between the peripheral nervous system (PNS) and gastric cancer (GC). In multiple GC mouse models, nociceptive nerves demonstrated the greatest degree of nerve expansion in an NGF-dependent manner. Neural tracing identified CGRP+ peptidergic neurons as the primary gastric sensory neurons. Three-dimensional co-culture models showed that sensory neurons directly connect with gastric cancer spheroids through synapse-like structures. Chemogenetic activation of sensory neurons induced the release of calcium into the cytoplasm of cancer cells, promoting tumor growth and metastasis. Pharmacological ablation of sensory neurons or treatment with CGRP inhibitors suppressed tumor growth and extended survival. Depolarization of gastric tumor membranes throughin vivooptogenetic activation led to enhanced calcium flux in nodose ganglia and CGRP release, defining a cancer cell-peptidergic neuronal circuit. Together, these findings establish the functional connectivity between cancer and sensory neurons, identifying this pathway as a potential therapeutic target.
An anti-depressant drug vortioxetine suppresses malignant glioblastoma cell growth
Authors: Devare Mayur Nimbadas , Kaeberlein Matt
Published: March 2024

Glioblastoma (GBM) stands as the predominant primary malignant brain tumor in adults, characterized by an exceedingly grim prognosis. Urgent efforts are essential to pioneer effective therapeutics capable of addressing both the intrinsic and acquired resistance exhibited by GBM towards existing treatments. This study employs a drug repurposing strategy to explore the anti-cancer potential of vortioxetine in malignant U251 and T98G glioblastoma cells. Findings from WST-8 cell counting assay and clonogenic assays indicated that vortioxetine effectively suppressed the short-term viability and long-term survival of glioblastoma cells. We also showed that vortioxetine inhibited migration of glioblastoma cells as compared to the control. Our findings encourage further exploration and validation of the use of vortioxetine in the treatment of glioblastoma.
The Unfolded Protein Response Sensor PERK Mediates Mechanical Stress-induced Maturation of Focal Adhesion Complexes in Glioblastoma Cells
Authors: Khoonkari Mohammad , Liang Dong , Kamperman Marleen , van Rijn Patrick , Kruyt Frank A.E.
Published: March 2024

Stiffening of the brain extracellular matrix (ECM) in glioblastoma leads to mechanical stress, which is known to contribute to tumor formation and progression. Previously, we found that protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), a component of the unfolded protein response (UPR), plays a role in the adaptation of glioblastoma stem cells (GSCs) to matrix stiffness through PERK/FLNA dependent F-Actin remodeling. Here, we found that increases in matrix stiffness induces differentiation of GSCs that was not seen in PERK deficient GSCs. Furthermore, we investigated whether PERK is involved in detecting changes in matrix stiffness through focal adhesion complex (FAC) formation and maturation, which are instrumental for transmitting ECM dependent signaling. In PERK deficient GSCs, Vinculin and Tensin expression was decreased, while Talin and Integrin-β1 expression was kept at the same level compared to PERK proficient cells. In addition, in the absence of PERK, Tubulin expression is sharply increased coupled with low Vimentin expression, which was observed as an opposite trend in the presence of PERK. In conclusion, our study reveals a novel role for PERK in regulating the formation of FACs during matrix stiffening, possibly associated with its regulatory capacity in F-Actin remodeling.
GRASPS: a simple-to-operate translatome technology reveals omics-hidden disease-associated pathways in TDP-43-related amyotrophic lateral sclerosis
Authors: Lin Ya-Hui , Dodd Jennifer E. , Cutillo Luisa , Castelli Lydia M. , Mihaylov Simeon R. , Norris Karl , Higginbottom Adrian , Walsh Matthew J. , Cooper-Knock Johnathan , Highley J. Robin , Granata Ilaria , Evans Caroline A. , Guarracino Mario R. , Campbell Susan G. , Dickman Mark J. , Shaw Pamela J. , Milo Marta , Hautbergue Guillaume M.
Published: March 2024

Transcriptomes and translatomes measure genome-wide levels of total and ribosome-associated RNAs. A few hundred translatomes were reported over >250,000 transcriptomes highlighting the challenges of identifying translating RNAs. Here, we used a human isogenic inducible model of TDP-43-linked amyotrophic lateral sclerosis, which exhibits altered expression of thousands of transcripts, as a paradigm for the direct comparison of whole-cell, cytoplasmic and translating RNAs, showing broad uncoupling and poor correlation between disease-altered transcripts. Moreover, based on precipitation of endogenous ribosomes, we developed GRASPS (Genome-wide RNA Analysis of Stalled Protein Synthesis), a simple-to-operate translatome technology. Remarkably, GRASPS identified three times more differentially-expressed transcripts with higher fold changes and statistical significance, providing unprecedented opportunities for data modeling at stringent filtering and discovery of previously omics-missed disease-relevant pathways, which functionally map on dense gene regulatory networks of protein-protein interactions. Based on its simplicity and robustness, GRASPS is widely applicable across disciplines in the biotechnologies and biomedical sciences.
Species-specific variation in mitochondrial genome tandem repeat polymorphisms in hares (Lepus spp., Lagomorpha, Leporidae) provides insight into their evolution
Authors: Tapanainen Riikka , Aasumets Koit , Fekete Zsofia , Goffart Steffi , Dufour Eric , Pohjoismaki Jaakko L. O.
Published: March 2024

The non-coding regions of the mitochondrial DNAs (mtDNAs) of hares, rabbits, and pika (Lagomorpha) contain short (~20 bp) and long (130-160 bp) tandem repeats, absent in related mammalian orders. In the presented study, we provide functional annotation for mountain hare (Lepus timidus) and brown hare (L. europaeus) mtDNA non-coding regions, together with a species- and population-level analysis of tandem repeat variation. Mountain hare short tandem repeats (SRs) as well as other analyzed hare species consist of two conserved 10 bp motifs, with only brown hares exhibiting a single, more variable motif. Long tandem repeats (LRs) also differ in sequence and copy number between species. Mountain hares have four to seven LRs, median value five, while brown hares exhibit five to nine LRs, median value six. Interestingly, introgressed mountain hare mtDNA in brown hares obtained an intermediate LR length distribution, with median copy number being the same as with conspecific brown hare mtDNA. In contrast, transfer of brown hare mtDNA into cultured mtDNA-less mountain hare cells maintained the original LR number, whereas the reciprocal transfer caused copy number instability, suggesting that cellular environment rather than the nuclear genomic background plays a role in the LR maintenance. Due to their dynamic nature and separation from other known conserved sequence elements on the non-coding region of hare mitochondrial genomes, the tandem repeat elements are unlikely to have regulatory roles but are likely to represent selfish genetic elements.
N-acetylation of α-synuclein enhances synaptic vesicle clustering mediated by α-synuclein and lysophosphatidylcholine
Authors: Wang Chuchu , Zhao Chunyu , Hu Xiao , Qiang Jiali , Liu Zhenying , Gu Jinge , Zhang Shengnan , Li Dan , Zhang Yaoyang , Burré Jacqueline , Diao Jiajie , Liu Cong
Published: March 2024

Post-translational modifications (PTMs) of α-synuclein (α-syn) such as acetylation and phosphorylation play important yet distinct roles in regulating α-syn conformation, membrane binding, and amyloid aggregation. However, how PTMs regulate α-syn function in presynaptic terminals remains unclear. Previously, we reported that α-syn clusters synaptic vesicles (SV)1, and neutral phospholipid lysophosphatidylcholine (LPC) can mediate this clustering2. Here, based on our previous findings, we further demonstrate that N-terminal acetylation, which occurs under physiological conditions and is irreversible in mammalian cells, significantly enhances the functional activity of α-syn in clustering SVs. Mechanistic studies reveal that this enhancement is caused by the N-acetylation-promoted insertion of α-syn’s N-terminus and increased intermolecular interactions on the LPC-containing membrane. Our work demonstrates that N-acetylation fine-tunes α-syn–LPC interaction for mediating α-syn’s function in SV clustering.
Computationally accelerated identification of P-glycoprotein inhibitors
Authors: McCormick Lauren A. , McCormick James W. , Park Chanyang , Follit Courtney A. , Wise John G. , Vogel Pia D.
Published: March 2024

Overexpression of the polyspecific efflux transporter, P-glycoprotein (P-gp, MDR1,ABCB1), is a major mechanism by which cancer cells acquire multidrug resistance (MDR), the resistance to diverse chemotherapeutic drugs. Inhibiting drug transport by P-gp can resensitize cancer cells to chemotherapy, but there are no P-gp inhibitors available to patients. Clinically unsuccessful P-gp inhibitors tend to bind at the pump’s transmembrane drug binding domains and are often P-gp transport substrates, resulting in lowered intracellular concentration of the drug and altered pharmacokinetics. In prior work, we used computationally accelerated drug discovery to identify novel P-gp inhibitors that target the pump’s cytoplasmic nucleotide binding domains. Our first-draft study provided conclusive evidence that the nucleotide binding domains of P-gp are viable targets for drug discovery. Here we develop an enhanced, computationally accelerated drug discovery pipeline that expands upon our prior work by iteratively screening compounds against multiple conformations of P-gp with molecular docking. Targeted molecular dynamics simulations with our homology model of human P-gp were used to generate docking receptors in conformations mimicking a putative drug transport cycle. We offset the increased computational complexity using custom Tanimoto chemical datasets, which maximize the chemical diversity of ligands screened by docking. Using our expanded, virtual-assisted pipeline, we identified nine novel P-gp inhibitors that reverse MDR in two types of P-gp overexpressing human cancer cell lines, reflecting a 13.4% hit rate. Of these inhibitors, all were non-toxic to non-cancerous human cells, and six were not likely to be transport substrates of P-gp. Our novel P-gp inhibitors are chemically diverse and are good candidates for lead optimization. Our results demonstrate that the nucleotide binding domains of P-gp are an underappreciated target in the effort to reverse P-gp-mediated multidrug resistance in cancer.
A Human Brain Map of Mitochondrial Respiratory Capacity and Diversity
Authors: Mosharov Eugene V. , Rosenberg Ayelet M , Monzel Anna S , Osto Corey A. , Stiles Linsey , Rosoklija Gorazd B. , Dwork Andrew J. , Bindra Snehal , Zhang Ya , Fujita Masashi , Mariani Madeline B , Bakalian Mihran , Sulzer David , De Jager Philip L. , Menon Vilas , Shirihai Orian S , Mann J. John , Underwood Mark , Boldrini Maura , Thiebaut de Schotten Michel , Picard Martin
Published: March 2024

Mitochondrial oxidative phosphorylation (OxPhos) powers brain activity1,2, and mitochondrial defects are linked to neurodegenerative and neuropsychiatric disorders3,4, underscoring the need to define the brain’s molecular energetic landscape5–10. To bridge the cognitive neuroscience and cell biology scale gap, we developed a physical voxelization approach to partition a frozen human coronal hemisphere section into 703 voxels comparable to neuroimaging resolution (3×3×3 mm). In each cortical and subcortical brain voxel, we profiled mitochondrial phenotypes including OxPhos enzyme activities, mitochondrial DNA and volume density, and mitochondria-specific respiratory capacity. We show that the human brain contains a diversity of mitochondrial phenotypes driven by both topology and cell types. Compared to white matter, grey matter contains >50% more mitochondria. We show that the more abundant grey matter mitochondria also are biochemically optimized for energy transformation, particularly among recently evolved cortical brain regions. Scaling these data to the whole brain, we created a backward linear regression model integrating several neuroimaging modalities11, thereby generating a brain-wide map of mitochondrial distribution and specialization that predicts mitochondrial characteristics in an independent brain region of the same donor brain. This new approach and the resulting MitoBrainMap of mitochondrial phenotypes provide a foundation for exploring the molecular energetic landscape that enables normal brain functions, relating it to neuroimaging data, and defining the subcellular basis for regionalized brain processes relevant to neuropsychiatric and neurodegenerative disorders.
Locus-specific stratification and prioritization unveil high risk genes underlying hyperuricemia
Authors: Zhang Jing , Guo Yue , Gong Luyu , Xia Limei , Liu Qiaoqiao , Wang Kangchun , Wang Qi , Liu Zhaojun , Qin Zhaohui , Shi Shaolin , Yang Jingping
Published: March 2024

The development of alternative medications for urate-lowering therapies is imperative for patients that are intolerant to current treatments. Despite GWAS have identified hundreds of loci associated with serum urate levels, the mechanistic understanding and discovery of drug targets remain difficult. This difficulty arises from the multiple-independent-associations challenge in the genomic studies of complex diseases as hyperuricemia. Here, we introduced a locus-specific stratification (LSS) and gene regulatory prioritization score (GRPS) approach to address the multiple-independent-associations challenge. By integrating with kidney single-cell chromatin accessibility and gene expression, LSS identified functional SNPs, regulatory elements, and genes for 118 loci. The interpretability was increased by 1.4 to 5.2 fold. GRPS prioritized genes and nominated under-explored drug target with high confidence, which was validated using CRISPR activation and phenotypic assays. Our findings not only identified top causal genes but also proposed the regulatory mechanisms for pathogenic genes, expanding our knowledge of the genetic contribution in complex diseases as hyperuricemia.

One-sentence summary

A novel approach to comprehensively explore genetic contribution and nominate reliable causal genes for complex diseases as hyperuricemia.
DeepPrep: An accelerated, scalable, and robust pipeline for neuroimaging preprocessing empowered by deep learning
Authors: Ren Jianxun , An Ning , Lin Cong , Zhang Youjia , Sun Zhenyu , Zhang Wei , Li Shiyi , Guo Ning , Cui Weigang , Hu Qingyu , Wang Weiwei , Wu Xuehai , Wang Yinyan , Jiang Tao , Satterthwaite Theodore D , Wang Danhong , Liu Hesheng
Published: March 2024

Neuroimaging has entered the era of big data. However, the advancement of preprocessing pipelines falls behind the rapid expansion of data volume, causing significant computational challenges. Here, we present DeepPrep, a pipeline empowered by deep learning and workflow manager. Evaluated on over 55,000 scans, DeepPrep demonstrates a 11-fold acceleration, exceptional scalability, and robustness compared to the current state-of-the-art pipeline, providing a promising solution to meet the scalability requirements of neuroimaging.
Impacts of yeast Tma20/MCTS1, Tma22/DENR and Tma64/eIF2D on translation reinitiation and ribosome recycling
Authors: Jendruchová Kristína , Gaikwad Swati , Poncová Kristýna , Gunišová Stanislava , Valášek Leoš Shivaya , Hinnebusch Alan G.
Published: March 2024

Recycling of 40S ribosomal subunits following translation termination, entailing release of deacylated tRNA and dissociation of the empty 40S subunit from mRNA, involves yeast Tma20/Tma22 heterodimer and Tma64, counterparts of mammalian MCTS1/DENR and eIF2D. MCTS1/DENR enhance reinitiation at short upstream open reading frames (uORFs) harboring penultimate codons that confer dependence on these factors in bulk 40S recycling. Tma factors, by contrast, inhibited reinitiation at particular uORFs in extracts; however, their roles at regulatory uORFs in vivo were unknown. We examined effects of eliminating Tma proteins on reinitiation at regulatory uORFs mediating translational control ofGCN4optimized for either promoting (uORF1) or preventing (uORF4) reinitiation. We found that the Tma proteins generally impede reinitiation at native uORF4 and uORF4 variants equipped with various penultimate codons regardless of their Tma-dependence in bulk recycling. The Tma factors have no effect on reinitiation at native uORF1, and equipping uORF1 with Tma-dependent penultimate codons generally did not confer Tma-dependent reinitiation; nor did converting the uORFs to AUG-stop elements. Thus, effects of the Tma proteins vary depending on the reinitiation potential of the uORF and the penultimate codon, but unlike in mammals, are not principally dictated by the Tma-dependence of the codon in bulk 40S recycling.
A history of repeated antibiotic usage leads to microbiota-dependent mucus defects
Authors: Krigul Kertu Liis , Feeney Rachel H. , Wongkuna Supapit , Aasmets Oliver , Holmberg Sandra M. , Andreson Reidar , Puértolas-Balint Fabiola , Pantiukh Kateryna , Sootak Linda , Org Tõnis , Tenson Tanel , Org Elin , Schroeder Bjoern O.
Published: March 2024

Recent evidence indicates that repeated antibiotic usage lowers microbial diversity and lastingly changes the gut microbiota community. However, the physiological effects of repeated – but not recent – antibiotic usage on microbiota-mediated mucosal barrier function are largely unknown. By selecting human individuals from the deeply-phenotyped Estonian Microbiome Cohort (EstMB) we here utilised human-to-mouse faecal microbiota transplantation to explore long-term impacts of repeated antibiotic use on intestinal mucus function. While a healthy mucus layer protects the intestinal epithelium against infection and inflammation, usingex-vivomucus function analyses of viable colonic tissue explants, we show that microbiota from humans with a history of repeated antibiotic use causes reduced mucus growth rate and increased mucus penetrability compared to healthy controls in the transplanted mice. Moreover, shotgun metagenomic sequencing identified a significantly altered microbiota composition in the antibiotic-shaped microbial community, with known mucus-utilising bacteria, includingAkkermansia muciniphilaandBacteroides fragilis, dominating in the gut. The altered microbiota composition was further characterised by a distinct metabolite profile, which may be caused by differential mucus degradation capacity. Consequently, our findings suggest that long-term antibiotic use in humans results in an altered microbial community that has reduced capacity to maintain proper mucus function in the gut.
DNA binding site II is required for RAD51 recombinogenic activity inArabidopsis thaliana
Authors: Petiot Valentine , White Charles , Ines Olivier Da
Published: March 2024

Homologous recombination is a major pathway for the repair of DNA double strand breaks, essential both to maintain genomic integrity and to generate genetic diversity. Mechanistically, homologous recombination involves the use of a homologous DNA molecule as a template to repair the break. In eukaryotes, the search for and invasion of the homologous DNA molecule is carried out by two recombinases, RAD51 in somatic cells and RAD51 and DMC1 in meiotic cells. During recombination, the recombinases bind overhanging single-stranded DNA ends to form a nucleoprotein filament, which is the active species in promoting DNA invasion and strand exchange. RAD51 and DMC1 carry two major DNA binding sites - essential for nucleofilament formation and DNA strand exchange, respectively. Here, we show that the function of RAD51 DNA binding Site II is conserved in the plant, Arabidopsis. Mutation of three key amino acids in Site II does not affect RAD51 nucleofilament formation but inhibits its recombinogenic activity, analogous to results from studies of the yeast and human proteins. We further confirm that recombinogenic function of RAD51 DNA binding site II is not required for meiotic DSB repair when DMC1 is present. The Arabidopsis RAD51-II3A separation of function mutant shows a dominant negative phenotype, pointing to distinct biochemical properties of eukaryotic RAD51 proteins.

Summary blurb

The activity promoted by RAD51 DNA binding site II is not required for nucleofilament formation, but is essential for subsequent invasion and strand exchange activity of RAD51 inArabidopsis thaliana.
Mapping the mutational landscape of a full viral proteome reveals distinct profiles of mutation tolerability
Authors: Álvarez-Rodríguez Beatriz , Velandia-Álvarez Sebastian , Toft Christina , Geller Ron
Published: March 2024

RNA viruses have notoriously high mutation rates due to error-prone replication by their RNA polymerase. However, natural selection concentrates variability in a few key viral proteins. To test whether this stems from different mutation tolerance profiles among viral proteins, we measured the effect of >40,000 non-synonymous mutations across the full proteome of coxsackievirus B3 as well as >97% of all codon deletions in the non-structural proteins. We find significant variation in mutational tolerance within and between individual viral proteins, which correlated with both general and protein-specific structural and functional attributes. Further, mutational fitness effects remained largely constant across cell lines, highlighting conserved selection pressures. In addition to providing a rich dataset for understanding virus biology and evolution, our results illustrate that incorporation of mutational tolerance data into druggable pocket discovery can aid in selecting targets with high barriers to drug resistance.
Pinhole camera for electron beam size diagnostic at storage ring with an ultralow emittance
Authors: Trebushinin Andrei , Geloni Gianluca , Serkez Svitozar , Khubbutdinov Ruslan , Saldin Evgeny
Published: March 2024

In this work, we propose to use a pinhole camera at high photon energies, specifically 200–300 keV, to measure ultra-small electron beam size by means of bending magnet radiation. We show that there is a sufficient photon flux at the detector position. Our theoretical analysis includes an examination of the applicability of the van Cittert-Zernike theorem for the bending magnet radiation generated by an ultralow emittance electron beam and a detailed analysis of the imaging properties of rectangular pinhole cameras. This led us to practical, universal formulas. We identify the optimal aperture size and resolution of the camera in the given geometry. The theoretical findings are further substantiated by wavefront propagation numerical simulations of partially coherent radiation. This study serves both as a practical guide for optical engineering and an educational resource for explaining the imaging properties of pinhole cameras.

Published by the American Physical Society
2024
Synthetic dimension-induced pseudo Jahn-Teller effect in one-dimensional confined fermions
Authors: Becker A. , Koutentakis G. M. , Schmelcher P.
Published: March 2024

We demonstrate the failure of the adiabatic Born-Oppenheimer approximation to describe the ground state of a quantum impurity within an ultracold Fermi gas despite substantial mass differences between the bath and impurity species. Increasing repulsion leads to the appearance of nonadiabatic couplings between the fast bath and slow impurity degrees of freedom, which reduce the parity symmetry of the latter according to the pseudo Jahn-Teller effect. The presence of this mechanism is associated to a conical intersection involving the impurity position and the inverse of the interaction strength, which acts as a synthetic dimension. We elucidate the presence of these effects via a detailed ground-state analysis involving the comparison of fully correlated simulations with effective models. Our study suggests ultracold atomic ensembles as potent emulators of complex molecular phenomena.

Published by the American Physical Society
2024
Dynamically emergent quantum thermodynamics: Non-Markovian Otto cycle
Authors: Picatoste Irene Ada , Colla Alessandra , Breuer Heinz-Peter
Published: March 2024

Employing a recently developed approach to dynamically emergent quantum thermodynamics, we revisit the thermodynamic behavior of the quantum Otto cycle with a focus on memory effects and strong system-bath couplings. Our investigation is based on an exact treatment of non-Markovianity by means of an exact quantum master equation, modeling the dynamics through the Fano-Anderson model featuring a peaked environmental spectral density. By comparing the results to the standard Markovian case, we find that non-Markovian baths can induce work transfer to the system, and identify specific parameter regions which lead to enhanced work output and efficiency of the cycle. In particular, we demonstrate that these improvements arise when the cycle operates in a frequency interval which contains the peak of the spectral density. This can be understood from an analysis of the renormalized frequencies emerging through the system-bath couplings.

Published by the American Physical Society
2024
Machine eye for defects: Machine learning-based solution to identify and characterize topological defects in textured images of nematic materials
Authors: Ren Haijie , Wang Weiqiang , Tang Wentao , Zhang Rui
Published: March 2024

Topological defects play a key role in the structures and dynamics of liquid crystals and other ordered systems. There is a recent interest in studying defects in different biological systems with distinct textures. However, a robust method to directly recognize defects and extract their structural features from various traditional and nontraditional nematic systems remains challenging to date. Here we present a machine learning solution, termed machine eye for defects (MED), for automated defect analysis in images with diverse nematic textures. MED seamlessly integrates state-of-the-art object detection networks, segment anything model, and vision transformer algorithms with tailored computer vision techniques. We show that MED can accurately identify the positions, winding numbers, and orientations of ±1/2 defects across distinct cellular contours, sparse vector fields of nematic directors, actin filaments, microtubules, and simulation images of Gay-Berne particles. MED performs faster than conventional defect detection methods and can achieve over 90% accuracy on recognizing ±1/2 defects and their orientations from vector fields and experimental tissue images. We further demonstrate that MED can identify defect types that are not included in the training data, such as giant-core defects and defects with higher winding numbers. Remarkably, MED provides correct structural information about ±1 defects, i.e., the phase angle for +1 defects and the orientation angle for −1 defects. As such, MED stands poised to transform studies of diverse ordered systems by providing automated, rapid, accurate, and insightful defect analysis.

Published by the American Physical Society
2024
Evolutionary Conservation of Mechanical Strain Distributions in Functional Transitions of Protein Structures
Authors: Sartori Pablo , Leibler Stanislas
Published: March 2024

One of the tenets of molecular biology is that dynamic transitions between three-dimensional structures determine the function of proteins. Therefore, it seems only natural that evolutionary analysis of proteins, presently based mainly on their primary sequence, needs to shift its focus toward their function as assessed by corresponding structural transitions. This can be facilitated by recent progress in cryogenic electron microscopy that provides atomic structures of multiple conformational states for proteins and protein assemblies isolated from evolutionarily related species. In this work, we study evolutionary conservation of multiprotein assembly function by using mechanical strain as a quantitative footprint of structural transitions. We adopt the formalism of finite strain theory, developed in condensed matter physics, and apply it, as a case study, to a classical multiprotein assembly, the ATP synthase. Protein strain analysis provides a precise characterization of rotation domains that agrees with the present biophysical knowledge. In addition, we obtain a strain distribution on the protein structure associated with functional transitions. By analyzing in detail the strain patterns of the chains responsible for ATP synthesis across distinct species, we show that they are evolutionarily conserved for the same functional transition. Such conservation is not revealed by displacement or rotation patterns. Furthermore, within each functional transition, we can identify conserved strain patterns for ATP synthases isolated from different organisms. The observed strain conservation across evolutionary distant species indicates that strain should be essential in future structure-based evolutionary studies of protein function.

Published by the American Physical Society
2024
A bibliometric review of IFRS adoption and compliance research in Africa
Authors: Effah Nana Adwoa Anokye
Published: March 2024

Purpose

This article aims to identify and review existing studies on the adoption and compliance of International Financial Reporting Standards (IFRS) in Africa.

Design/methodology/approach

The methodology involves a sole focus on studies conducted with an African sample, using a bibliometric method and data from the Web of Science (WoS) database. Visualizations from VOSViewer and Biblioshiny software are employed to identify the dominant authors, journals and countries contributing to research in the region.

Findings

The findings reveal existing collaborations among authors in the field. However, the study emphasizes the need for additional research to enhance the intellectual structure of the research domain, as the majority of related documents are concentrated within twenty articles with at least one citation.

Practical implications

The practical implications underscore the importance of collaboration in practice, emphasizing the need for cooperation among corporations, experts and regulatory agencies involved in IFRS adoption and compliance in Africa. By fostering collaborative efforts and knowledge-sharing among corporations, experts and regulatory agencies, practitioners can enhance their understanding, streamline implementation processes and improve compliance methods.

Originality/value

This review is one of the few to explicitly conduct a bibliometric review of IFRS adoption and compliance studies in Africa, providing a foundation for future research to determine the current direction of IFRS studies in this region.
External pressure, internal managerial interpretation and green entrepreneurial orientation
Authors: Zhang Xiu-e , Yang Liu , Teng Xinyu , Li Yijing
Published: March 2024

Purpose

Based on the attention-based view (ABV), this study examines the mechanism of external pressure and internal managerial interpretation affecting the promotion of green entrepreneurial orientation (GEO) of agricultural enterprises.

Design/methodology/approach

Based on data collected from 208 agricultural enterprises in China, the conceptual model was tested by using hierarchical regression.

Findings

The results show that managerial interpretation can affect the promotion of GEO. Command and control regulation, market-based regulation and green market pressure are important external pressures that affect the promotion of GEO. In addition, managerial interpretation mediates the relationship between command and control regulation and GEO, market-based regulation and GEO, as well as green market pressure and GEO.

Practical implications

This study proposes a key path for promoting the adoption and implementation of GEO by agricultural enterprises. The research results provide experience for emerging and developing countries to promote the GEO of agricultural enterprises, which is helpful to alleviate the environmental problems caused by the development of agricultural enterprises.

Originality/value

For the first time, this study introduced the ABV into the research of GEO. The research results enrich the theoretical perspective of GEO and expand the research field of the ABV. In addition, this study fills the research gap that existing research has not paid enough attention to the internal driving factors of GEO and opens the black box between the external pressure and GEO.
Comparative genomics reveals the adaptation of ammonia‐oxidising Thaumarchaeota to arid soils
Authors: Li Chaonan , Liao Haijun , Xu Lin , Wang Changting , Yao Minjie , Wang Junming , Li Xiangzhen
Published: March 2024

Thaumarchaeota are predominant in oligotrophic habitats such as deserts and arid soils, but their adaptations to these arid conditions are not well understood. In this study, we assembled 23 Thaumarchaeota genomes from arid and semi‐arid soils collected from the Inner Mongolia Steppe and the Qinghai‐Tibet Plateau. Using a comparative genomics approach, integrated with 614 Thaumarchaeota genomes from public databases, we identified the traits and evolutionary forces that contribute to their adaptations to aridity. Our results showed that the newly assembled genomes represent an early diverging group within the lineage of ammonia‐oxidising Thaumarchaeota. While the genomic functions previously identified in arid soil lineages were conserved across terrestrial, shallow‐ocean and deep‐ocean lineages, several traits likely contribute to Thaumarchaeota's adaptation to aridity. These include chlorite dismutase, arsenate reductase, V‐type ATPase and genes dealing with oxidative stresses. The acquisition and loss of traits at the last common ancestor of arid soil lineages may have facilitated the specialisation of Thaumarchaeota in arid soils. Additionally, the acquisition of unique adaptive traits, such as a urea transporter, Ca2+:H+ antiporter, mannosyl‐3‐phosphoglycerate synthase and phosphatase, DNA end‐binding protein Ku and phage shock protein A, further distinguishes arid soil Thaumarchaeota. This study provides evidence for the adaptations of Thaumarchaeota to arid soil, enhancing our understanding of the nitrogen and carbon cycling driven by Thaumarchaeota in drylands.
Active coexistence of the novel gammaproteobacterial methanotroph ‘Ca.Methylocalor cossyra’ CH1 and verrucomicrobial methanotrophs in acidic, hot geothermal soil
Authors: Liu Changqing , Schmitz Rob A. , Pol Arjan , Hogendoorn Carmen , Verhagen Daniël , Peeters Stijn H. , van Alen Theo A. , Cremers Geert , Mesman Rob A. , Op den Camp Huub J. M.
Published: March 2024

Terrestrial geothermal ecosystems are hostile habitats, characterized by large emissions of environmentally relevant gases such as CO2, CH4, H2S and H2. These conditions provide a niche for chemolithoautotrophic microorganisms. Methanotrophs of the phylum Verrucomicrobia, which inhabit these ecosystems, can utilize these gases and grow at pH levels below 1 and temperatures up to 65°C. In contrast, methanotrophs of the phylum Proteobacteria are primarily found in various moderate environments. Previously, novel verrucomicrobial methanotrophs were detected and isolated from the geothermal soil of the Favara Grande on the island of Pantelleria, Italy. The detection of pmoA genes, specific for verrucomicrobial and proteobacterial methanotrophs in this environment, and the partially overlapping pH and temperature growth ranges of these isolates suggest that these distinct phylogenetic groups could coexist in the environment. In this report, we present the isolation and characterization of a thermophilic and acid‐tolerant gammaproteobacterial methanotroph (family Methylococcaceae) from the Favara Grande. This isolate grows at pH values ranging from 3.5 to 7.0 and temperatures from 35°C to 55°C, and diazotrophic growth was demonstrated. Its genome contains genes encoding particulate and soluble methane monooxygenases, XoxF‐ and MxaFI‐type methanol dehydrogenases, and all enzymes of the Calvin cycle. For this novel genus and species, we propose the name ‘Candidatus Methylocalor cossyra’ CH1.
Does calcium prevent pre‐eclampsia?
Authors: Thornton Steve
Published: March 2024

Linked article: This is a mini commentary on Wright et al., pp. 1524–1529 in this issue. To view this article visit https://doi.org/10.1111/1471-0528.17769.
A winged relative of ice‐crawlers in amber bridges the cryptic extant Xenonomia and a rich fossil record
Authors: Cui Yingying , Bardin Jérémie , Wipfler Benjamin , Demers‐Potvin Alexandre , Bai Ming , Tong Yi‐Jie , Chen Grace Nuoxi , Chen Huarong , Zhao Zhen‐Ya , Ren Dong , Béthoux Olivier
Published: March 2024

Until the advent of phylogenomics, the atypical morphology of extant representatives of the insect orders Grylloblattodea (ice‐crawlers) and Mantophasmatodea (gladiators) had confounding effects on efforts to resolve their placement within Polyneoptera. This recent research has unequivocally shown that these species‐poor groups are closely related and form the clade Xenonomia. Nonetheless, divergence dates of these groups remain poorly constrained, and their evolutionary history debated, as the few well‐identified fossils, characterized by a suite of morphological features similar to that of extant forms, are comparatively young. Notably, the extant forms of both groups are wingless, whereas most of the pre‐Cretaceous insect fossil record is composed of winged insects, which represents a major shortcoming of the taxonomy. Here, we present new specimens embedded in mid‐Cretaceous amber from Myanmar and belonging to the recently described species Aristovia daniili. The abundant material and pristine preservation allowed a detailed documentation of the morphology of the species, including critical head features. Combined with a morphological data set encompassing all Polyneoptera, these new data unequivocally demonstrate that A. daniili is a winged stem Grylloblattodea. This discovery demonstrates that winglessness was acquired independently in Grylloblattodea and Mantophasmatodea. Concurrently, wing apomorphic traits shared by the new fossil and earlier fossils demonstrate that a large subset of the former “Protorthoptera” assemblage, representing a third of all known insect species in some Permian localities, are genuine representatives of Xenonomia. Data from the fossil record depict a distinctive evolutionary trajectory, with the group being both highly diverse and abundant during the Permian but experiencing a severe decline from the Triassic onwards.
Intrauterine exposure to maternal opioid maintenance treatment and associated risk factors may impair child growth
Authors: Kanervo Minna , Luoto Liina , Tupola Sarimari , Nikkola Eeva , Kahila Hanna , Rantakari Krista
Published: March 2024

Aim

How maternal opioid maintenance treatment (OMT) affects children is under‐researched. This population‐based registry study investigated child growth and somatic health following intrauterine exposure to this treatment.

Methods

Children born between 1 March 2011 and 30 May 2021 to mothers who used buprenorphine, buprenorphine‐naloxone, or methadone throughout their pregnancies were followed for 2 years at the Helsinki University Hospital, Finland. Appropriate statistical tests were used to compare the treatment groups.

Results

Of the 67 neonates, 52% were male, 96% were born full‐term and 63% were treated for neonatal opioid withdrawal syndrome. Otherwise, the children were predominantly healthy, although relatively small: 22% were small for gestational age, the methadone group children being the smallest. Foetal exposure to maternal methadone treatment, illicit drugs, hepatitis C and smoking were associated with small for gestational age; the former two were also associated with later slower growth, especially head growth and weight gain (p < 0.001). However, 29% were overweight at 2 years.

Conclusion

Using child growth as the outcome, we found that buprenorphine‐naloxone and buprenorphine‐monotherapy had equal effects as forms of maternal OMT. Exposure to multiple risk factors may harm foetal and subsequent growth. We recommend long‐term follow‐up of children exposed to maternal OMT.
Child Welfare Workers' Perceptions of Intimate Partner Violence and Mandatory Reporting in Norway
Authors: Dahl Silje Louise , Leer‐Salvesen Kjartan , Øvrelid Malene , Vatnar Solveig Karin Bø
Published: March 2024

Intimate partner violence (IPV) is a major criminal, social and public health problem. As one effort to prevent IPV and intimate partner homicide, several countries have adopted legislation requiring professionals to disclose IPV to the authorities (commonly referred to as mandatory reporting). The child welfare service (CWS) is centrally positioned for detecting, reporting and preventing IPV, but there is limited empirical knowledge concerning how the service handles IPV cases or of social workers' awareness of mandatory reporting of IPV. Using qualitative interviews, we explore how CWS workers in Norway describe their discretionary space and mandatory obligations towards adults subjected to IPV. Our findings indicate an inexpedient interplay between understandings of professional mandate and individual responsibility and local routines and organisation and insufficient knowledge about IPV and mandatory reporting. We suggest that a reframing of CWS workers' understanding of their discretionary space is needed to ensure that their individual responsibility towards adults subjected to IPV is understood as part of their mandate. This reframing presupposes structural efforts, such as formal training. We propose further investigations concerning how local organisation and routines either facilitate or interfere with systematic and thorough handling of IPV in families with which the municipal CWS meets.
Prenatal diagnosis, pregnancy determination and follow up of sex chromosome aneuploidy screened by non‐invasive prenatal testing from 122 453 unselected singleton pregnancies: A retrospective analysis of 7‐year experience
Authors: Luo Xiaojin , Liu Weiqiang , Hu Liang , Cong Xiaoyi , Liu Xiaoyi , Niu Hongyan , Zhou Fei , Li Gaochi , Wen Lijuan , Guo Yanyun
Published: March 2024

The phenotype of SCA patients are diversities, make prenatal counseling and parental decision‐making following the prenatal diagnosis of SCA more complicated and challenging. NIPT has higher sensitivity and specificity in screening trisomy 21 syndrome, but the effectiveness of NIPT in detecting SCA is still controversial. This study is a large‐scale retrospective cohort of positive SCA screened from unselected singleton pregnancies by non‐invasive prenatal testing (NIPT) from a single prenatal center of a tertiary hospital. Clinical information, indications, diagnostic results, ultrasound findings, pregnancy determinations, and follow‐up were reviewed and analyzed. 596 cases of SCA positive were screened out of 122 453, giving a positive detection rate of 0.49%. 510 cases (85.6%) conducted with amniocentesis to detect fetal chromosome, of which 236 were confirmed as true positive of SCA with PPV of 46.3% (236/510). Of the 236 cases confirmed as true positive SCA, 114 cases (48.3%)chose to terminate the pregnancy (93.0%, 65.3%, 15.4% and 10.9% for 45,X, 47,XXY, 47,XXX and 47,XYY, respectively), 122 cases (51.7%) elected to continue the pregnancy. In conclusions, NIPT as a first‐tier routine method for screening autosomal aneuploidies, also could play an important role in screening SCA. Low‐risk pregnant women are the main indication for the detection of SCA as NIPT test provides to non‐selective population. For 47,XXX and 47,XYY with mild phenotype, couples would like to continue the pregnancy. But for 45,X and 47,XXY, parents apt to terminate pregnancy no matter ultrasound abnormalities were found or not.
Delays in the diagnosis and surgical treatment of drug‐resistant epilepsy: A cohort study
Authors: Campbell Justin M. , Yost Samantha , Gautam Diwas , Herich Alysha , Botros David , Slaughter Mason , Chodakiewitz Michael , Arain Amir , Peters Angela , Richards Sindhu , Newman Blake , Johnson Brian , Rahimpour Shervin , Shofty Ben
Published: March 2024

Objective

Delay in referral for epilepsy surgery of patients with drug‐resistant epilepsy (DRE) is associated with decreased quality of life, worse surgical outcomes, and increased risk of sudden unexplained death in epilepsy (SUDEP). Understanding the potential causes of delays in referral and treatment is crucial for optimizing the referral and treatment process. We evaluated the treatment intervals, demographics, and clinical characteristics of patients referred for surgical evaluation at our level 4 epilepsy center in the U.S. Intermountain West.

Methods

We retrospectively reviewed the records of patients who underwent surgery for DRE between 2012 and 2022. Data collected included patient demographics, DRE diagnosis date, clinical characteristics, insurance status, distance from epilepsy center, date of surgical evaluation, surgical procedure, and intervals between different stages of evaluation.

Results

Within our cohort of 185 patients with epilepsy (99 female, 53.5%), the mean ± standard deviation (SD) age at surgery was 38.4 ± 11.9 years. In this cohort, 95.7% of patients had received definitive epilepsy surgery (most frequently neuromodulation procedures) and 4.3% had participated in phase 2 intracranial monitoring but had not yet received definitive surgery. The median (1st–3rd quartile) intervals observed were 10.1 (3.8–21.5) years from epilepsy diagnosis to DRE diagnosis, 16.7 (6.5–28.4) years from epilepsy diagnosis to surgery, and 1.4 (0.6–4.0) years from DRE diagnosis to surgery. We observed significantly shorter median times from epilepsy diagnosis to DRE diagnosis (p < .01) and epilepsy diagnosis to surgery (p < .05) in patients who traveled further for treatment. Patients with public health insurance had a significantly longer time from DRE diagnosis to surgery (p < .001).

Significance

Both shorter distance traveled to our epilepsy center and public health insurance were predictive of delays in diagnosis and treatment intervals. Timely referral of patients with DRE to specialized epilepsy centers for surgery evaluation is crucial, and identifying key factors that may delay referral is paramount to optimizing surgical outcomes.