bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Plasticity of GABAergic Pallidothalamic Terminals in MPTP-treated Parkinsonian Monkeys: A 3D Electron Microscopic Analysis
Authors: Masilamoni GJ , Kelly H , Swain AJ , Pare JF , Villalba RM , Smith Y
Published: April 2023

The globus pallidus pars interna (GPi) is a major source of GABAergic inhibition upon the motor thalamus. GPi neurons are endowed with properties that allow them to fire at a high rate and maintain a tonic inhibitory influence upon thalamocortical neurons. In parkinsonism, the firing rate of GPi neurons is further increased and their firing pattern switches from a tonic to a bursty mode, two pathophysiological changes associated with increased GABAergic pallidothalamic activity. At the thalamic level, GPi terminals display ultrastructural features (large diameter, multiple synapses, large number of mitochondria) that allow them to maintain tonic synaptic inhibition at high firing rate upon thalamocortical neurons in the parvocellular ventral anterior nucleus (VApc) and the centromedian nucleus (CM), the two main GPi-recipient motor thalamic nuclei in nonhuman primates. To determine if changes of GPi neurons activity are associated with neuroplastic reorganization of GPi terminals and their synapses, we used a Single Block Facing/Scanning Electron Microscopy (SBF/SEM), high resolution 3D electron microscopic approach to compare the morphometry of GPi terminals between 2 control and 2 MPTP-treated parkinsonian monkeys. Our findings demonstrate that pallidothalamic terminals in VApc and CM undergo major ultrastructural changes in parkinsonian monkeys: (1) increased terminal volume in both nuclei, (2) increased surface area of synapses in both nuclei, (3) increased number of synapses/GPi terminals in the CM, but not VApc, (4) increased total volume of mitochondria/terminals in both nuclei but not in the number of mitochondria. In contrast, the ultrastructure of putative GABAergic terminals from the reticular thalamic nucleus was not affected in both the VApc and CM of parkinsonian monkeys. Our findings also show striking morphological differences in terminal volume, number/area of synapses and volume/number of mitochondria between GPi terminals in VApc and CM of control monkeys. In conclusion, results of this study demonstrate that GABAergic pallidothalamic terminals are endowed with a high level of structural plasticity that may contribute to the development and maintenance of the abnormal increase in pallidal GABAergic outflow to the thalamus in the parkinsonian state. Furthermore, the evidence for ultrastructural differences between GPi terminals in VApc and CM suggests that Morphologically distinct pallidothalamic terminals underlie specific physiological properties of pallidal inputs to VApc and CM in normal and diseased states.
Rev-Rev Response Element Activity Selection Bias at the HIV Transmission Bottleneck
Authors: Jackson Patrick E. H. , Holsey Jordan , Turse Lauren , Hammarskjold Marie-Louise , Rekosh David
Published: April 2023

HIV is not efficiently transmitted between hosts, and selection of viral variants occurs during the process of sexual transmission. The factors that confer selective advantage at the transmission bottleneck remain incompletely understood. We explored whether differences in the Rev-Rev Response Element (RRE) regulatory axis of HIV affect transmission fitness, since functional variation in the Rev-RRE axis in different viral isolates has been shown to affect replication kinetics and relative expression of many HIV proteins. Single genome HIV sequences were identified from nine linked subject pairs near the time of female-to-male transmission. Using a rapid flow-cytometric assay, we found that the functional Rev-RRE activity varied significantly between isolates. Moreover, it was generally lower in recipients’ viruses compared to the corresponding donor viruses. In six of nine transmission events, recipient virus Rev-RRE activity clustered at the extreme low end of the range of donor virus activity. Rev-RRE pair activity was an unpredictable product of component Rev and RRE activity variation. These data indicate selection pressure on the Rev-RRE axis during female-to-male sexual transmission. Variation in the activity of the Rev-RRE axis may permit viral adaptation to different fitness landscapes and could play an important role in HIV pathogenesis.
Predation and competition drive trait diversity across space and time
Authors: Neale Zoey , Rudolf Volker H. W.
Published: April 2023

Competition should play a key role in shaping community assembly and thereby local and regional biodiversity patterns. However, identifying its relative importance and effects in natural communities is challenging because theory suggests that competition can lead to different and even opposing patterns depending on the underlying mechanisms. Here, we’ve taken a different approach: rather than attempting to indirectly infer competition from diversity patterns, we compared trait diversity patterns in odonate (dragonfly and damselfly) communities across different spatial and temporal scales along a natural competition-predation gradient. At the local scale (within a community), we found that trait diversity increased with the size of top predators (from invertebrates to fish). This relationship is consistent with differences in taxonomic diversity, suggesting that competition reduces local trait diversity through competitive exclusion. Spatial (across communities) and temporal (within communities over time) trait variation peaked in communities with intermediated predators indicating that both high levels of competition or predation select for trait-convergence of communities. This indicates that competition acts as a deterministic force that reduces trait diversity at the local, regional, and temporal scales, which contrasts with patterns at the taxonomic level. Overall, results from this natural experiment reveal how competition and predation interact to shape biodiversity patterns in natural communities across spatial and temporal scales and provide new insights into the underlying mechanisms.

Open Research statement

Data and/or code are provided as private-for-peer review via the following link: [Link to external storage location] and will be made publicly available with publication
Ancient Fish Lineages Illuminate Toll-Like Receptor Diversification in Early Vertebrate Evolution
Authors: Carlson Kara B. , Nguyen Cameron , Wcisel Dustin J. , Yoder Jeffrey A. , Dornburg Alex
Published: April 2023

Since its initial discovery over 50 years ago, understanding the evolution of the vertebrate adaptive immune response has been a major area of research focus for comparative geneticists. However, how the evolutionary novelty of an adaptive immune response impacted the diversity of receptors associated with the innate immune response has received considerably less attention until recently. Here we investigate the diversification of vertebrate Toll-like receptors (TLRs), one of the most ancient and well conserved innate immune receptor families found across the Tree of Life, integrating genomic data that represent all major vertebrate lineages with new transcriptomic data from Polypteriformes, the earliest diverging ray-finned fish lineage. Our analyses reveal TLR sequences that reflect the 6 major TLR subfamilies, TLR1, TLR3, TLR4, TLR5, TLR7, and TLR11, and also currently unnamed, yet phylogenetically distinct TLR clades. We additionally recover evidence for a pulse of gene gain coincident with the rise of the adaptive immune response in jawed vertebrates, followed by a period of rapid gene loss during the Cretaceous. These gene losses are primarily concentrated in marine teleost fish and synchronous with the mid Cretaceous anoxic event, a period of rapid extinction for marine species. Finally, we reveal a mismatch between phylogenetic placement and gene nomenclature for up to 50% of TLRs found in clades such as ray-finned fishes, cyclostomes, amphibians, and elasmobranchs. Collectively these results provide an unparalleled perspective of TLR diversity, and offer a ready framework for testing gene annotations in non-model species.
A single amino acid substitution in MdLAZY1A dominantly impairs shoot gravitropism inMalus
Authors: Dougherty Laura , Borejsza-Wysocka Ewa , Miaule Alexandre , Wang Ping , Zheng Desen , Jansen Michael , Brown Susan , Piñeros Miguel , Dardick Christopher , Xu Kenong
Published: April 2023

Plant architecture is one of the most important factors that determines crop yield potential and productivity. In apple (Malus), genetic improvement of tree architecture has been challenging due to a long juvenile phase and their growth as complex trees composed of a distinct scion and a rootstock. To better understand the genetic control of apple tree architecture, the dominant weeping growth phenotype was investigated. We report the identification ofMdLAZY1A(MD13G1122400) as the genetic determinant underpinning theWeeping(W)locus that largely controls weeping growth inMalus.MdLAZY1Ais one of the four paralogs in apple that are most closely related toAtLAZY1involved in gravitropism inArabidopsis. The weeping allele (MdLAZY1A-W) contains a single nucleotide mutation c.584T>C that leads to a leucine to proline (L195P) substitution within a predicted transmembrane domain that co-localizes with Region III, one of the five conserved regions in LAZY1-like proteins. Subcellular localization revealed that MdLAZY1A localizes to the plasma membrane and nucleus in plant cells. Over-expressing the weeping allele in apple cultivar Royal Gala (RG) with standard growth habit impaired its gravitropic response and altered the growth to weeping-like. Suppressing the standard allele (MdLAZY1A-S) by RNA interference (RNAi) in RG similarly changed the branch growth direction to downward. Overall, the L195P mutation in MdLAZY1A is genetically causal for weeping growth, underscoring not only the crucial roles of residue L195 and Region III in MdLAZY1A-mediated gravitropic response, but also a potential DNA base editing target for tree architecture improvement inMalusand other crops.
Oncogenic Ras, Yki and Notch signals converge to confer clone competitiveness through Upd2
Authors: Wang Ying , He Jingjing , Deng Mingxi , Yan Yan
Published: April 2023

It has long been proposed that cell competition functions to remove precancerous clones. A classical model is the removal of polarity-deficient clones such as thescribble(scrib) mutant clones inDrosophilaimaginal discs. The activation of Ras, Yki or Notch signaling robustly reverses thescribmutant clonal fate from elimination to tumorous growth. Using single-cell transcriptomics techniques to profile wing imaginal discs harboring thescribmutant clones in combination with different signals, we found that a critical converging point downstream of Ras, Yki and Notch signals is the upregulation of Upd2, which is necessary to promote tumorous growth. Unexpectedly, while Upd2 is not required for cell survivalper se, Upd2-deficient clones are efficiently wiped out from epithelia, indicating that Upd2 is a previously unrecognized cell competition factor.
Mrs4 loss of function in fungi during adaptation to the cystic fibrosis lung
Authors: Murante Daniel , Demers Elora G. , Kurbessoian Tania , Ruzic Marina , Ashare Alix , Stajich Jason E. , Hogan Deborah A.
Published: April 2023

The genetic disease cystic fibrosis (CF) frequently leads to chronic lung infections by bacteria and fungi. We identified three individuals with CF with persistent lung infections dominated byClavispora(Candida)lusitaniae. Whole genome sequencing analysis of multiple isolates from each infection found evidence for selection for mutants in the geneMRS4in all three distinct lung-associated populations. In each population, we found one or two unfixed, non-synonymous mutations inMRS4relative to the reference allele found in multiple environmental and clinical isolates including the type strain. Genetic and phenotypic analyses found that all evolved alleles led to loss of function of Mrs4, a mitochondrial iron transporter. RNA Seq analyses found that Mrs4 variants with decreased activity led to increased expression of genes involved in iron acquisition mechanisms in both low iron and replete iron conditions. Furthermore, surface iron reductase activity and intracellular iron was much higher in strains with Mrs4 loss of function variants. Parallel studies found that a subpopulation of a CF-associatedExophiala dermatiditisinfection also had a non-synonymous loss of function mutation inMRS4.Together, these data suggest thatMRS4mutations may be beneficial during chronic CF lung infections in diverse fungi perhaps for the purposes of adaptation to an iron restricted environment with chronic infections.
Triggering receptor expressed on myeloid cells 2 (TREM2) regulates phagocytosis in glioblastoma
Authors: Peshoff Mekenzie M. , Gupta Pravesh , Trivedi Rakesh , Oberai Shivangi , Chakrapani Prashanth , Dang Minghao , Milam Nancy , Maynard Mark E. , Vaillant Brian D. , Huse Jason T. , Wang Linghua , Clise-Dwyer Karen , Bhat Krishna P.
Published: April 2023

Glioblastomas (GBMs) are tumors of the central nervous system that remain recalcitrant to both standard of care chemo-radiation and immunotherapies. Emerging approaches to treat GBMs include depletion or re-education of innate immune cells including microglia (MG) and macrophages (MACs). Here we show myeloid cell restricted expression of triggering receptor expressed on myeloid cells 2 (TREM2) across low- and high-grade human gliomas. TREM2 expression did not correlate with immunosuppressive pathways, but rather showed strong positive association with phagocytosis markers such as lysozyme (LYZ) and CD163 in gliomas. In line with these observations in patient tumors,Trem2-/-mice did not exhibit improved survival compared to wildtype (WT) mice when implanted with mouse glioma cell lines, unlike observations previously seen in peripheral tumor models. Gene expression profiling revealed pathways related to inflammation, adaptive immunity, and autophagy that were significantly downregulated in tumors fromTrem2-/-mice compared to WT tumors. Using ZsGreen-expressing CT-2A orthotopic implants, we found higher tumor antigen engulfment in Trem2+MACs, MG, and dendritic cells. Our data uncover TREM2 as an important immunomodulator in gliomas and inducing TREM2 mediated phagocytosis can be a potential immunotherapeutic strategy for brain tumors.

Key points

TREM2 is not associated with immunosuppressive molecules in GBM

TREM2 is associated with phagocytosis in both human and mouse gliomas

Deletion of Trem2 in mice does not improve survival in glioma models

Importance of the study

Triggering receptor expressed on myeloid cells 2 (TREM2) has been implicated as a major immunoregulator in both neurodegenerative diseases and systemic cancers, yet its functional role in gliomas remains unclear. This study reveals that unlike in other cancers, TREM2 is not associated with immunosuppression in the glioma microenvironment. In fact, TREM2 expression is associated with phagocytosis in both human and mouse gliomas, similar to its role in Alzheimer’s disease. These findings indicate that TREM2 blockade will not be a viable treatment strategy for gliomas. Instead, TREM2 induction may boost the potential of myeloid cells in the tumor microenvironment to engulf cancer cells.
The third symbiotic partner of the volcano lichenCladonia vulcaniSavicz drove adaptation to an extreme environment
Authors: Kono Mieko , Terai Yohey
Published: April 2023

Chemosynthetic symbioses between sulfur-oxidizing bacteria and aquatic eukaryotes have been discovered globally in sulfide-rich environments, notably deep-sea hydrothermal vents, cold seeps, and sulfidic cave systems. However, to the best of our knowledge, such chemosymbiotic lifestyles have not been reported from terrestrial eukaryotes. Here we report that the volcano lichenCladonia vulcaniSavicz ubiquitously associates with a single bacterial species that could potentially use hydrogen sulfide as a source of energy. We identified sequences of the bacterium in all 27 samples collected from five geothermal areas across Japan with cellular abundance comparable to the fungal partner. The assembled bacterial genome contained genes involved in sulfur oxidation. The stable association with a potential sulfur-oxidizer is likely to represent an obligate tripartite symbiotic system consisting of fungal, algal, and bacterial partners that has enabled adaptation to the extreme environment.
Development of a marker within the candidateUn8true loose smut resistance gene for use in barley breeding
Authors: Šķipars Vilnis , Sokolova Elīna , Seile Sanita , Ruņģis Dainis , Legzdiņa Linda
Published: April 2023

Breeding for resistance to true loose smut infection caused by the pathogen (Ustilago nuda(Jens.) Rostr.) is an economical and environmentally safe way to limit the effect of this pathogen on barley. However, screening for resistance using natural infection can lead to inconsistent results and artificial inoculation is labour intensive, and can fail, leading to erroneous phenotyping. Marker assisted selection of genes conferring disease resistance can increase the efficiency of breeding programs. A candidate gene forUn8resistance was used to develop a genetic marker which was tested on a recombinant inbred line (RIL) population derived from the resistant ‘CDC Freedom’ and the susceptible ‘Samson’ varieties. The RIL population (98 lines) was phenotyped for resistance to true loose smut by artificial inoculation and genotyped with the newly developed marker. The genotyping results obtained with the marker developed in this study were mostly consistent with true loose smut resistance determined by artificial inoculation. The markers was also tested in additional barley cultivars and breeding material. Repeated analysis of inconsistent results is required to confirm or revise these results, as well as further investigation of the candidate gene to confirm its role in barley true loose smut resistance is being planned.
CebraEM: A practical workflow to segment cellular organelles in volume SEM datasets using a transferable CNN-based membrane prediction
Authors: Hennies Julian , Lleti José Miguel Serra , Pape Constantin , Bekbayev Sultan , Gross Viktoriia , Kreshuk Anna , Schwab Yannick
Published: April 2023

Segmentation of large-volume datasets obtained by volume SEM techniques is a challenging task that generally requires a considerable amount of human effort. Despite recent advances in deep learning leading to the successful segmentation of cellular organelles in a variety of datasets, it is still challenging and time-consuming to produce the necessary data for training a convolutional neural network as well as to set up targeted post-processing pipelines to obtain a good quality full-volume semantic instance segmentation. We present CebraEM, a software package that uses a novel workflow for the segmentation of organelles in volume EM datasets, which helps to minimize the annotation time for the generation of training data. It relies on a generic CNN-based membrane prediction, followed by a well-established machine-learning pipeline that includes over-segmentation before random forest classification and graph multi-cut grouping. The workflow was tested for the segmentation of organelles on different datasets originating from various sample preparations and imaging modalities in volume SEM, in each case resulting in state-of-the-art semantic instance segmentations without additional post-processing. Importantly, by considerably simplifying the segmentation problem, CebraEM empowers single users with the ability to efficiently segment hundreds of gigabytes of data.
Loss of myeloid cannabinoid CB1 receptor confers atheroprotection by reducing macrophage proliferation and immunometabolic reprogramming
Authors: Wang Yong , Li Guo , Chen Bingni , Shakir George , Volz Mario , Vorst Emiel P.C. van der , Maas Sanne L. , Muley Carolin , Bartelt Alexander , Li Zhaolong , Sachs Nadja , Maegdefessel Lars , Jahantigh Maliheh Nazari , Hristov Michael , Lacy Michael , Lutz Beat , Weber Christian , Herzig Stephan , Prats Raquel Guillamat , Steffens Sabine
Published: April 2023

Although the cannabinoid CB1 receptor has been implicated in atherosclerosis, its cell-specific effects in this disease are not well understood. Here, we report that male mice with myeloid-specificCnr1deficiency on atherogenic background developed smaller lesions and necrotic cores than controls, while only minor genotype differences were observed in females. MaleCnr1deficient mice showed reduced arterial monocyte recruitment and macrophage proliferation with less inflammatory phenotype. The sex-specific differences were reproducible in bone marrow derived macrophages and blunted by estradiol. Kinase activity profiling revealed a CB1-dependent regulation of p53 and cyclin-dependent kinases. Transcriptomic profiling further unveiled chromatin modifications, mRNA processing and mitochondrial respiration among the key processes affected by CB1 signaling, which was supported by metabolic flux assays. Chronic administration of the peripherally-restricted CB1 antagonist JD5037 inhibited plaque progression and macrophage proliferation, but only in male mice. Finally,CNR1expression was detectable in human carotid endarterectomy plaques and inversely correlated with proliferation, oxidative metabolism and inflammatory markers, hinting to a possible implication of CB1-dependent regulation in human pathophysiology. In conclusion, impaired CB1 signaling in macrophages is atheroprotective by limiting their arterial recruitment, proliferation and inflammatory reprogramming. The importance of macrophage CB1 signaling seems to be more pronounced in male mice.

Abstract Figure

Graphical summary(created withBioRender.com)
Cellular energy regulates mRNA translation and degradation in a codon-specific manner
Authors: da Silva Pedro Tomaz , Zhang Yujie , Theodorakis Evangelos , Martens Laura D. , Yépez Vicente A. , Pelechano Vicent , Gagneur Julien
Published: April 2023

Background:

Codon optimality is a major determinant of mRNA translation and degradation rates. However, whether and through which mechanisms its effects are regulated remains poorly understood.

Results

Here we show that codon optimality associates with up to 2-fold change in mRNA stability variations between human tissues, and that its effect is attenuated in tissues with high energy metabolism and amplifies with age. Biochemical modeling and perturbation data through oxygen deprivation and ATP synthesis inhibition reveal that cellular energy variations non-uniformly affect the decoding kinetics of different codons.

Conclusions

This new mechanism of codon effect regulation, independent of tRNA regulation, provides a fundamental mechanistic link between cellular energy metabolism and eukaryotic gene expression.
GGoutlieR: an R package to identify and visualize unusual geo-genetic patterns of biological samples
Authors: Chang Che-Wei , Schmid Karl
Published: April 2023

Landscape genomics is an emerging field of research that integrates genomic and environmental information to explore the drivers of evolution. Reliable data on the geographical origin of biological samples is a prerequisite for accurate landscape genomics studies. Traditionally, researchers discover potentially questionable samples using visualization-based tools. However, such approaches cannot handle large sample sizes due to overlapping data points on a graph and can hinder reproducible research. To address this shortcoming, we developedGeo-Geneticoutlier(GGoutlieR), an R package of a heuristic framework for detecting and visualizing samples with unusual geo-genetic patterns. Outliers are identified by calculating empirical p-values for each sample, allowing users to identify them in data sets with thousands of samples. The package also provides a plotting function to display the geo-genetic patterns of outliers on a geographical map. GGoutlieR could significantly reduce the amount of data cleaning that researchers need to do before carrying out landscape genomics analyses.
Length of fermentation time affects microbiome composition and biological activity ofPanchgavya
Authors: Gajera Gemini , Funde Snehal , Palep Hanmanthrao , Kothari Vijay
Published: April 2023

Objective

This study aimed at investigating whether the duration of fermentingPanchgavya(PG) preparation in copper vessel affects its biological activity and microbiome composition.

Methods

Prophylactic potential of PG against bacterial infection was assessed through anin vivoassay employing the nematode wormCaenorhabditis elegansas a model host. Bacterial diversity of the PG samples was revealed through metagenomic analysis.

Results

Duration of fermentation was found to affect biological activity as well as microbiome composition of the PG samples. PG-samples fermented ≥60 min lost their prophylactic potential, and develop anthelmintic activity. Bacterial phyla whose relative abundance was significantly different between the prophylactic and anthelmintic PG samples were Planctomycetota, Proteabacteria, Bacteroidota, Verrucomicrobiota, Patescibacteria, Acidobacteriota, Chloroflexi, Firmicutes and Campilobacterota.

Conclusion

This study validates the prophylactic potential ofPanchgavyaagainst bacterial pathogens, and shows that duration of the fermentation time while preparing PG can have profound effect on its biological activities. Biological activities of PG samples seem to have a correlation with their inherent microbial community. Metagenomic profiling can be an effective tool for standardization of PG formulations.
M-Ionic: Prediction of metal ion binding sites from sequence using residue embeddings
Authors: Shenoy Aditi , Kalakoti Yogesh , Sundar Durai , Elofsson Arne
Published: April 2023

Motivation

Understanding metal-protein interaction can provide structural and functional insights into cellular processes. As the number of protein sequences increases, developing fast yet precise computational approaches to predict and annotate metal binding sites becomes imperative. Quick and resource-efficient pre-trained protein language model (PLM) embeddings have successfully predicted binding sites from protein sequences despite not using structural or evolutionary features (multiple sequence alignments). Using residue-level embeddings from the PLMs, we have developed a sequence-based method (M-Ionic) to identify metal-binding proteins and predict residues involved in metal-binding.

Results

On independent validation of recent proteins, M-Ionic reports an area under the curve (AUROC) of 0.83 (recall=84.6%) in distinguishing metal-binding from non-binding proteins compared to AUROC of 0.74 (recall =61.8%) of the next best method. In addition to comparable performance to the state-of-the-art method for identifying metal-binding residues (Ca2+, Mg2+, Mn2+, Zn2+), M-Ionic provides binding probabilities for six additional ions (i.e., Cu2+, Po43-, So42-, Fe2+, Fe3+, Co2+). We show that the PLM embedding of a single residue contains sufficient information about its neighbours to predict its binding properties.

Availability and Implementation

M-Ionic can be used on your protein of interest using a Google Colab Notebook (https://bit.ly/40FrRbK). GitHub repository (https://github.com/TeamSundar/m-ionic) contains all code and data.

Contact

arne@bioinfo.se

Supplementary information

Supplementary data are available atBioinformaticsonline.
Amine recognizing domain in diverse receptors from bacteria and archaea evolved from the universal amino acid sensor
Authors: Cerna-Vargas Jean Paul , Gumerov Vadim M. , Krell Tino , Zhulin Igor B.
Published: April 2023

Bacteria contain many different receptor families that sense different signals permitting an optimal adaptation to the environment. A major limitation in microbiology is the lack of information on the signal molecules that activate receptors. Due to a significant sequence divergence, the signal recognized by sensor domains is only poorly reflected in overall sequence identity. Biogenic amines are of central physiological relevance for microorganisms and serve for example as substrates for aerobic and anaerobic growth, neurotransmitters or osmoprotectants. Based on protein structural information and sequence analysis, we report here the identification of a sequence motif that is specific for amine-sensing dCache sensor domains (dCache_1AM). These domains were identified in more than 13,000 proteins from 8,000 bacterial and archaeal species. dCache_1AM containing receptors were identified in all major receptor families including sensor kinases, chemoreceptors, receptors involved in second messenger homeostasis and Ser/Thr phosphatases. The screening of compound libraries and microcalorimetric titrations of selected dCache_1AM domains confirmed their capacity to specifically bind amines. Mutants in the amine binding motif or domains that contain a single mismatch in the binding motif, had either no or a largely reduced affinity for amines, illustrating the specificity of this motif. We demonstrate that the dCache_1AM domain has evolved from the universal amino acid sensing domain, providing novel insight into receptor evolution. Our approach enables precise “wet”-lab experiments to define the function of regulatory systems and thus holds a strong promise to address an important bottleneck in microbiology: the identification of signals that stimulate numerous receptors.
CT Multi-Task Learning with a Large Image-Text (LIT) Model
Authors: Niu Chuang , Wang Ge
Published: April 2023

Large language models (LLM) not only empower multiple language tasks but also serve as a general interface across different spaces. Up to now, it has not been demonstrated yet how to effectively translate the successes of LLMs in the computer vision field to the medical imaging field which involves high-dimensional and multi-modal medical images. In this paper, we report a feasibility study of building a multi-task CT large image-text (LIT) model for lung cancer diagnosis by combining an LLM and a large image model (LIM). Specifically, the LLM and LIM are used as encoders to perceive multi-modal information under task-specific text prompts, which synergizes multi-source information and task-specific and patient-specific priors for optimized diagnostic performance. The key components of our LIT model and associated techniques are evaluated with an emphasis on 3D lung CT analysis. Our initial results show that the LIT model performs multiple medical tasks well, including lung segmentation, lung nodule detection, and lung cancer classification. Active efforts are in progress to develop large image-language models for superior medical imaging in diverse applications and optimal patient outcomes.
Expression of DNA repair genes is modulated during differentiation of olfactory sensory neurons
Authors: Rowies Fernanda T. , Batalha Caio M.P.F. , Nakahara Thiago S. , Malnic Bettina , de Souza-Pinto Nadja C.
Published: April 2023

Olfactory dysfunction is considered a biomarker of several pathological conditions, including age-associated neurodegenerations, glioblastoma and COVID-19. Olfactory sensory neurons (OSNs) are specialized neurons that detect odorants and send olfactory information to the brain through the olfactory bulb. To perform their function, they are in direct contact with the environment, where they are exposed to several environmental toxins such as atmospheric levels of O2and volatile molecules. Nonetheless, very little is known about DNA damage levels and expression of DNA repair pathways in these cells. Here we measured nuclear and mitochondrial DNA damage in olfactory epithelium (OE) and compared with levels detected in olfactory bulb (OB) and temporal cortex (TC), as a non-olfactory related central nervous system region. Surprisingly, DNA damage was lower in OE and OB when compared with TC, both for nuclear and mitochondrial genomes. Accordingly, expression of representative genes for all excision repair pathways was detected in OSNs. Moreover, expression of most evaluated DNA repair genes was lower in mature versus OSN progenitors, suggesting that DNA repair is downregulated during differentiation. Analysis of single cell expression data confirmed that expression of the most differentially expressed DNA repair genes decreased from progenitor to mature OSNs. Finally,in situhybridization data showed that APE1 mRNA levels are lower in the mature OSNs layer of the olfactory epithelium, closest to the nasal cavity lumen. Altogether, we show here that DNA repair pathways are relevant in protecting OSNs against DNA damage accumulation and that differentiation through the OE is accompanied by changes in the expression levels of DNA repair genes.
The shirker’s dilemma and the prospect of cooperation in large groups
Authors: Peña Jorge , Heifetz Aviad , Nöldeke Georg
Published: April 2023

Cooperation usually becomes harder to sustain as groups become larger because incentives to shirk increase with the number of potential contributors to collective action. But is this always the case? Here we study a binary-action cooperative dilemma where a public good is provided as long as not more than a given number of players shirk from a costly cooperative task. We find that at the stable polymorphic equilibrium, which exists when the cost of cooperation is low enough, the probability of cooperating increases with group size and reaches a limit of one when the group size tends to infinity. Nevertheless, increasing the group size may increase or decrease the probability that the public good is provided at such an equilibrium, depending on the cost value. We also prove that the expected payoff to individuals at the stable equilibrium (i.e., their fitness) decreases with group size. For low enough costs of cooperation, both the probability of provision of the public good and the expected payoff converge to positive values in the limit of large group sizes. However, we also find that the basin of attraction of the stable polymorphic equilibrium is a decreasing function of group size and shrinks to zero in the limit of very large groups. Overall, we demonstrate non-trivial comparative statics with respect to group size in an otherwise simple collective action problem.
Primary cilia promote the differentiation of human neurons through the WNT signaling pathway
Authors: Coschiera Andrea , Yoshihara Masahito , Lauter Gilbert , Ezer Sini , Kere Juha , Swoboda Peter
Published: April 2023

Primary cilia emanate from most human cell types, including neurons. Cilia are important for communicating with the cell’s immediate environment: signal reception and transduction to/from the ciliated cell. Deregulation of ciliary signaling can lead to ciliopathies and certain neurodevelopmental disorders. In the developing brain cilia play well-documented roles for the expansion of the neural progenitor cell pool, while information about the roles of cilia during post-mitotic neuron differentiation and maturation is scarce. We employed ciliated Lund Human Mesencephalic (LUHMES) cells in time course experiments to assess the impact of ciliary signaling on neuron differentiation. By comparing ciliated and non-ciliated neuronal precursor cells and neurons in wild type and a mutant with altered cilia (RFX2 -/-), we discovered an early-differentiation “ciliary time window” during which transient cilia promote axon outgrowth, branching and arborization. Cilia promote neuron differentiation by tipping WNT signaling toward the non-canonical pathway, in turn activating WNT pathway output genes implicated in cyto-architectural changes. We provide a mechanistic entry point into when and how ciliary signaling coordinates, promotes and translates into anatomical changes. We hypothesize that ciliary alterations causing neuron differentiation defects may result in “mild” impairments of brain development, possibly underpinning certain aspects of neurodevelopmental disorders.
Noncatalytic regulation of 18SrRNA methyltransferase DIMT1 in acute myeloid leukemia
Authors: Gonskikh Yulia , Stoute Julian , Shen Hui , Budinich Krista , Pingul Bianca , Schultz Kollin , Elashal Heidi , Marmorstein Ronen , Shi Junwei , Liu Kathy Fange
Published: April 2023

Several rRNA-modifying enzymes install rRNA modifications while participating in ribosome assembly. Here, we show that 18SrRNA methyltransferase DIMT1 is essential for acute myeloid leukemia (AML) proliferation through a noncatalytic function. We reveal that targeting a positively charged cleft of DIMT1, remote from the catalytic site, weakens the binding of DIMT1 to rRNA and mislocalizes DIMT1 to the nucleoplasm, in contrast to the primarily nucleolar localization of wild-type DIMT1. Mechanistically, rRNA binding is required for DIMT1 to undergo liquid–liquid phase separation, which explains the distinct nucleoplasm localization of the rRNA binding-deficient DIMT1. Re-expression of wild-type or a catalytically inactive mutant E85A, but not the rRNA binding-deficient DIMT1, supports AML cell proliferation. This study provides a new strategy to target DIMT1-regulated AML proliferation via targeting this essential noncatalytic region.
Syntheses and crystal structures of three salts of 1-(4-nitrophenyl)piperazine
Authors: Prasad Holehundi J. Shankara , Devaraju  , Yathirajan Hemmige S. , Akkurt Mehmet , Foro Sabine , Balerao Rishik , Butcher Ray J.
Published: April 2023

The crystal structures and Hirshfeld surface analyses of three salts of 1-(4-nitrophenyl)piperazine with 2-chlorobenzoic acid, 2-bromobenzoic acid and 2-iodobenzoic acid are reported. The chlorobenzoate salt, C10H14N3O2
+·C7H4ClO2
−, contains whole-ion-disordered cations and anions, which were modeled with two equivalent conformations with occupancies of 0.745 (10)/0.255 (10) and 0.563 (13)/0.437 (13), respectively. The bromobenzoate and iodobenzoate derivatives are isomorphous and crystallize as hemihydrates, viz. C10H14N3O2
+·C7H4BrO2
−·0.5H2O and C10H14N3O2
+·C7H4IO2
−·0.5H2O, respectively [the water molecule is disordered over two locations with occupancies of 0.276 (3)/0.223 (3) for the iodobenzoate derivative]. In the extended structures, all three salts feature an R
4
4(12) loop of two anions and two cations linked by N—H...O hydrogen bonds.
{N-[(4-Methoxy-2-oxidophenyl)(phenyl)methylidene]glycinato}diphenylsilicon(IV)
Authors: Böhme Uwe , Fels Sabine
Published: April 2023

The title compound, C28H23NO4Si, crystallizes in the monoclinic space group P21/c. The silicon complex consists of a tridentate dinegative Schiff base ligand bound to a diphenylsilyl unit. The coordination geometry of the pentacoordinate silicon atom is a distorted trigonal bipyramid.
Development of indicators of happiness in learning of Thai open university students
Authors: Laosum Thanyasinee
Published: April 2023

Purpose

This paper aims to develop indicators of happiness in learning of the Thai open university (TOU)'s undergraduate students.

Design/methodology/approach

Sampling for the study was comprised of two groups. Group I comprised eight lecturers who are experts in their disciplines and six students who were purposively sampled. The focus group was used to validate the appropriateness of the indicators. In Group II, 332 students were engaged in a multistage sampling process. The responses were analyzed using descriptive statistics, coefficient correlation, exploratory factor analysis (EFA) and confirmatory factor analysis (CFA).

Findings

The indicators of happiness in learning of undergraduate students of TOU were classified in six categories. These included satisfaction with learning environment (five indicators), learning anxiety (five indicators), satisfaction with learning (five indicators), enthusiasm to learn (six indicators), self-satisfaction (six indicators) and readiness to learn (seven indicators). The six categories explained happiness in learning of undergraduate students of TOU at the 65% and fit empirical data.

Practical implications

The TOU can use the indicators for the assessment of happiness in learning of its students as well as guidelines for the improvement of its student learning environments.

Originality/value

There have been very few studies on indicators of happiness in learning of TOU students. Most were done at the basic education level. This study disclosed the six factors affecting happiness in learning of TOU students; therefore, it should inspire and draw attention of many in the field of higher education distance learning.
Developing levodopa-modified sol-gel coating with enhanced anticorrosion performance on Mg alloy AZ31
Authors: Li Jiao , Li Tianshu , Yuwono Jodie A. , Meng Guozhe , Feng Zhiyuan
Published: April 2023

Purpose

This study aims to develop a sol-gel-based coating to provide a long-lasting corrosion protection on AZ31 Mg alloy. Silane-based sol-gel coatings have been successfully applied to Mg alloys for corrosion protection. However, the micro or nano defects formed during condensation and solidification will cause the coating failure during a long-lasting immersion in a saline solution. More durable corrosion-protective sol-gel coatings are needed.

Design/methodology/approach

A sol-gel-based coating was modified on AZ31 Mg alloy by levodopa (DOPA). The long-lasting corrosion protection mechanism was studied by multiple electrochemical testing methods and surface characterization techniques.

Findings

Long-term testing by electrochemical impedance spectroscopy in aqueous 0.1 M NaCl indicated that the modified DOPA@sol-gel coating exhibited significant corrosion protection performance (>14 days). In comparison, the DOPA-free sol-gel coating failed only after three days of testing. The improved corrosion protection is attributed to the self-polymerized DOPA filling to the micro or nano defects in the glassy cross-linked networks of the sol-gel coating, which greatly improves the compactness of the coating.

Originality/value

The method of this study is simple and easy to process, the raw materials are green and the protective effect is excellent, which is of significance for the study of magnesium alloy corrosion protection.
Constructing cultural space and telling cultural stories: a case study of regional cultural heritage preservation in Shichahai, Beijing
Authors: Liu Xiaojuan , Pan Yinrong , Han Yutong
Published: April 2023

Purpose

There is a wealth of value hidden in regional cultural heritage, but its preservation status is not optimistic. This study introduces a method that focuses on the inherent cultural value of regional cultural heritage to preserve it by value construction and release.

Design/methodology/approach

Based on the great value of regional cultural heritage due to spatial adjacency and temporal continuity, this paper focuses on its inherent cultural value to explore the preservation path and chooses Shichahai cultural heritage digital resources for a case study. This paper draws lessons from the narrative method of ancient Chinese historiography, constructs a cultural space and tells cultural stories. A linked data organization model for digital resources is created to construct a conceptual cultural space. Then, the space is materialized by linked dataset creation. The authors tell cultural stories discovered from the space, which are presented by various user interfaces using visualization technologies.

Findings

A cultural space promotes the development of a fine-grained description of regional cultural heritage and aids in relationship discovery to enhance the value construction ability. Additionally, storytelling via interactive user interfaces is helpful in the utilization and dissemination of knowledge extracted from a cultural space and enhances the value release of regional cultural heritage. In this way, a path with the inherent cultural value of regional cultural heritage as the core is established, and preservation is achieved.

Originality/value

This study focuses on the inherent cultural value of regional cultural heritage and proposes a new path to preserve these resources. This approach will enrich research on the preservation of regional cultural heritage and contribute to the construction and release of its cultural value.
Influence of substantive corporate social responsibility attribution on salespeople’s value-based selling: a resource perspective
Authors: Yan Aimin , Jiang Biyun , Zang Zhimei
Published: April 2023

Purpose

Drawing upon the conservation of resources theory, this study aims to investigate whether, how and when salespeople’s substantive attribution of the organization’s corporate social responsibility (CSR) affects value-based selling (VBS). The authors argue that salespeople’s substantive CSR attribution increase value-based selling through two mechanisms (i.e. by lowering emotional exhaustion and increasing empathy), and treatment by customers can increase or decrease the strength of these relationships.

Design/methodology/approach

B2B salespeople working in various industries in China were recruited through snowball sampling to participate in the study. There were 462 volunteers (57.58% women; aged 30–55; tenure ranging from six months to 15 years) who provided valid self-report questionnaires.

Findings

Hierarchical multiple regression supported the association between salespeople’s substantive CSR attribution and VBS. The results showed that salespeople’s emotional state (i.e. emotional exhaustion and empathy) mediated the association between substantive CSR attribution and VBS. As expected, salespeople’s experiences of customer incivility weakened the mediating effect of emotional exhaustion; contrary to expectations, customer-initiated interpersonal justice weakened the mediation effect of empathy.

Originality/value

This study makes a unique contribution to the existing marketing literature by first investigating the role of salespeople’s attribution of CSR motives in facilitating their VBS, which answers the call to identify factors that predict VBS. In addition, to the best of the authors’ knowledge, the authors are the first to test salespeople’s emotions as a mechanism of the link between their CSR attributions and selling behaviors.
Economic agglomeration in the age of Industry 4.0: developing a digital industrial cluster as a new policy tool for the digital world
Authors: Fernandez-Escobedo Rudy , Eguía-Peña Begoña , Aldaz-Odriozola Leire
Published: April 2023

Purpose

This conceptual paper aims to develop the vision of a novel policy tool called the digital industrial cluster (DIC) thought for a future context shaped by digital economies and Industry 4.0. The DIC departs from the industrial cluster’s precepts and take them into the digital agglomeration phenomenon.

Design/methodology/approach

This research uses a discursive and theoretical approach. To create a clear picture related to the research topic, this paper reviews the literature on how industrial clusters deal with digital transformation. The review takes a particular interest in industrial clusters, information and communication technologies, Industry 4.0 and policy tools for digital agglomeration.

Findings

The research develops the vision of the DIC as a new policy tool, building its foundations on both industrial clusters and digital economies; furthermore, the DIC was compared with other policy tools based on digital agglomeration to understand the similarities, differences and advantages of the former. Finally, this paper discussed where the DIC could find its way toward implementation and what externalities could be expected from doing so.

Practical implications

This research could be useful for policymakers and cluster organizations looking to deploy policy tools that take advantage of industrial clusters and digital transformation. Besides, the theoretical foundations presented could lead researchers to empirical identification of early incarnations of the DIC.

Originality/value

This paper develops theoretical principles for a new policy tool that connects industrial clusters, digital agglomeration and Industry 4.0 for the first time.