bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-cell Transcriptomic Analysis of Salivary Gland Endothelial Cells
Authors: Altrieth Amber L. , Suarez Emily , Nelson Deirdre A. , Gabunia Sergo , Larsen Melinda
Published: June 2023

Vascular endothelial cells have important functions in fibrosis via direct and indirect methods and in regeneration through secretion of tissue-specific, paracrine-acting angiocrine factors. In the salivary gland, endothelial cells are required for proper development, but their roles within adult glands are largely unknown. The goal of this work was to identify ligand-receptor interactions between endothelial cells and other cell types that are important during homeostasis, fibrosis, and regeneration. To model salivary gland fibrosis and regeneration, we utilized a reversible ductal ligation. To induce injury, a clip was applied to the primary ducts for 14 days, and to induce a regenerative response, the clip was subsequently removed for 5 days. To identify endothelial cell-produced factors, we used single-cell RNA-sequencing of stromal-enriched cells from adult submandibular and sublingual salivary glands. Transcriptional profiles of homeostatic salivary gland endothelial cells were compared to endothelial cells of other organs. Salivary gland endothelial cells were found to express unique genes and displayed the highest overlap in gene expression with other fenestrated endothelial cells from the colon, small intestine, and kidney. Comparison of the 14-day ligated, mock ligated, and 5-day deligated stromal-enriched transcripts and lineage tracing were used to identify evidence for a partial endoMT phenotype, which was observed in a small number of endothelial cell subsets with ligation. CellChat was used to predict changes in ligand-receptor interactions in response to ligation and deligation. CellChat predicted that after ligation, endothelial cells are sources of protein tyrosine phosphatase receptor type m, tumor necrosis factor ligand superfamily member 13, and myelin protein zero signaling and targets for tumor necrosis factor signaling. Following deligation, CellChat predicted that endothelial cells are sources of chemokine (C-X-C motif) and EPH signaling to promote regenerative responses. These studies will inform future endothelial cell-based regenerative therapies.
Thermosensitivity of translation underlies the mammalian nocturnal-diurnal switch
Authors: Beale Andrew D. , Rzechorzek Nina M. , Mihut Andrei , Zeng Aiwei , Smyllie Nicola J. , Pilorz Violetta , Richardson Rose , Bertlesen Mads F , James Nathan R. , Fazal Shaline V. , Voysey Zanna , Pelletier Jerry , Crosby Priya , Peak-Chew Sew Y , Lancaster Madeline A. , Hut Roelof A. , O’Neill John S.
Published: June 2023

Early mammals were nocturnal until the Cretaceous-Paleogene extinction facilitated their rapid expansion into daytime niches. Diurnality subsequently evolved multiple times, independently, but the mechanisms facilitating this switch are unknown. We found that physiological daily temperature shifts oppositely affect circadian clock rhythms in nocturnal versus diurnal mammals. This occurs through a cell-intrinsic signal inverter, mediated by global differences in protein phosphorylation, and effected at the level of bulk protein synthesis rates, with diurnal translation rate being less thermosensitive than nocturnal. Perturbations that reduce translational initiation or mTOR activity are sufficient to trigger the nocturnal-to-diurnal switch at the cellular, tissue, and organismal scale. Our results suggest a convergent selection pressure to attain diurnality by reducing the effect of temperature-dependent changes in protein synthesis on circadian clocks.

One sentence summary

Recalibrating the thermosensitivity of protein synthesis drives daytime-selective activity in mammals.
Structural and functional analysis of vaccinia viral fusion complex component protein A28 through NMR and molecular dynamic simulations
Authors: Kao Chi-Fei , Tsai Min-Hsin , Carillo Kathleen Joyce , Tzou Der-Lii , Chang Wen
Published: June 2023

Host cell entry of vaccinia virus (a poxvirus) proceeds through multiple steps that involve many viral proteins to mediate cell infection. Upon binding to cells, vaccinia virus membrane fuses with host membranes via a viral entry fusion protein complex comprising 11 proteins: A16, A21, A28, F9, G3, G9, H2, J5, L1, L5 and O3. Despite vaccinia virus having two infectious forms, mature and enveloped, that have different membrane layers, both forms require an identical viral entry fusion complex for membrane fusion. Components of the poxvirus entry fusion complex that have been structurally assessed to date share no known homology with all other type I, II and III viral fusion proteins, and the large number of fusion protein components renders it a unique system to investigate poxvirus-mediated membrane fusion. Here, we determined the NMR structure of a truncated version of vaccinia A28 protein. We also expressed a soluble H2 protein and showed that A28 interacts with H2 protein at a 1:1 ratioin vitro. Furthermore, we performed extensivein vitroalanine mutagenesis to identify A28 protein residues that are critical for H2 binding, entry fusion complex formation, and virus-mediated membrane fusion. Finally, we used molecular dynamic simulations to model full-length A28-H2 subcomplex in membranes. In summary, we characterized vaccinia virus A28 protein and determines residues important in its interaction with H2 protein and membrane components. We also provide a structural model of the A28-H2 protein interaction to illustrate how it forms a 1:1 subcomplex on a modeled membrane.
poloaffects cell fate upon ionizing radiation inDrosophilahematopoietic progenitors by negatively regulatinglok
Authors: Nguyen Tram Thi Ngoc , Chen Guang-Chao , Shim Jiwon , Song Young-Han
Published: June 2023

In response to ionizing radiation (IR), stem cells undergo cell cycle arrest, senescence, premature differentiation, or cell death. The decision between survival and death is critical during tumorigenesis and effective killing of cancer cells. We used the larvalDrosophilalymph gland, a hematopoietic organ, as a model to understand the mechanism for cell fate decisions during stem cell development. The hematopoietic progenitors survived or died via apoptosis when larvae were irradiated in early or late third instar larval (L3) stages, respectively. In late L3 progenitors, the basal level ofpolo(DrosophilaPLK1) was low, enabling IR-induced activation oflok(DrosophilaCHK2), which was necessary and sufficient for inducing autophagy and reactive oxygen species (ROS) production resulting in cell death. The high level ofpoloin early L3 progenitors negatively regulatedlokresulting in significantly low or undetectable levels of ROS or autophagy, respectively. The surviving early L3 progenitors underwent cell cycle arrest followed by premature differentiation affected bytefu(DrosophilaATM) andlokmutation. These results provide clues for designing effective therapeutic strategies for cancer.

Summary statement

We elucidated the mechanism underlying cell fate decisions during stem cell development in larvalDrosophila, which will help develop effective cancer treatment modalities.
Boosting class II HLA epitope presentation to T cells with endoplasmic reticulum transmembrane domain fusion proteins
Authors: Pinamonti Veronica , Fuentes Ana Mellado , Schmid Theresa , Cetin Miray , Lerner Taga , Hernandez Miguel Hernandez , Lindner John M.
Published: June 2023

Antigen processing and presentation are crucial for T-cell receptor engagement and potent adaptive immune responses. While establishing an antigen presentation system to identify TCR-epitope pairs from large libraries of genetically templated, ectopically expressed antigens, we observed a longitudinal suppression of antigen processing in B cells, which we call antigen processing attenuation (APA). Beyond its potential role in regulating B cell-enforced peripheral tolerance, APA represents a bottleneck to sustained antigen presentation in screening and vaccination approaches. To overcome APA we screened several pathways which might enhance processing. Notably, we identified several sequences derived from transmembrane domains (TM) of endoplasmic reticulum-resident proteins which promote sustained minigene-encoded antigen presentation. In particular, the first TM domain ofSYT6, a protein associated with synaptic vesicles, greatly enhances processing and ameliorates APA. These findings suggest a new entry point into antigen processing pathways, enabling the discovery of novel immune epitopes and improving T-cell based immunization strategies.
Endosymbiont diversity across native and invasive brown widow spider populations
Authors: Mowery Monica A. , Rosenwald Laura C. , Chapman Eric , Lubin Yael , Segoli Michal , Khoza Thembile , Lyle Robin , White Jennifer A.
Published: June 2023

The invasive brown widow spider,Latrodectus geometricus(Araneae: Theridiidae), has spread in multiple locations around the world and, along with it, brought associated organisms such as endosymbionts. We investigated endosymbiont diversity and prevalence across putative native and invasive populations of this spider, predicting lower endosymbiont diversity across the invasive range compared to the native range. First, we characterized the microbial community in the putative native (South Africa) and invasive (Israel and the United States) ranges via high throughput 16S sequencing of 103 adult females. All specimens were dominated by reads from only 1-3 amplicon sequence variants (ASV), and most individuals were infected with an apparently uniform strain ofRhabdochlamydia. We also foundRhabdochlamydiain spider eggs, indicating that it is a maternally-inherited endosymbiont. Relatively few other ASV were detected, but included two variantRhabdochlamydiastrains and severalWolbachia,Spiroplasmaand Enterobacteriaceae strains. We then diagnostically screened 118 adult female spiders from native and invasive populations specifically forRhabdochlamydiaandWolbachia.We foundRhabdochlamydiain 86% of individuals and represented in all populations, which suggests that it is a consistent and potentially important associate ofL. geometricus. Wolbachiawas found at lower overall prevalence (14%) and was represented in all countries, but not all populations. In addition, we found evidence for geographic variation in endosymbiont prevalence: spiders from Israel were more likely to carryRhabdochlamydiathan those from the US and South Africa, andWolbachiawas geographically clustered in both Israel and South Africa. Characterizing endosymbiont prevalence and diversity is a first step in understanding their function inside the host and may shed light on the process of spread and population variability in cosmopolitan invasive species.
Widespread gene regulator Psu inhibits transcription termination factor ρ by forced hyper-oligomerization
Authors: Gjorgjevikj Daniela , Kumar Naveen , Wang Bing , Hilal Tarek , Said Nelly , Loll Bernhard , Artsimovitch Irina , Sen Ranjan , Wahl Markus C.
Published: June 2023

Many bacteriophages modulate the host transcription machinery for efficient expression of their own genomes. Phage P4 polarity suppression protein, Psu, is a building block of the viral capsid and inhibits the hexameric transcription termination factor, ρ, by presently unknown mechanisms. We elucidated cryogenic electron microscopy structures of ρ-Psu complexes, showing that Psu dimers laterally clamp two inactive, open ρ rings and promote their expansion to higher-oligomeric states. Systematic ATPase, nucleotide binding and nucleic acid binding studies revealed that Psu hinders ρ ring closure and traps nucleotides in their binding pockets on ρ. Structure-guided mutagenesis in combination with growth, pull-down and termination assays further delineated the functional ρ-Psu interfaces. Bioinformatic analyses suggested that, in addition to guarding its own genome against ρ, Psu enables expression of diverse phage-defense systems commonly found in P4-like mobile genetic elements across bacteria. Thus, Psu is a widespread gene regulator that inhibits ρviaforced hyper-oligomerization.
Structural Basis for Regulated Assembly of the Mitochondrial Fission GTPase Drp1
Authors: Rochon Kristy , Bauer Brianna L. , Roethler Nathaniel A. , Buckley Yuli , Su Chih-Chia , Huang Wei , Ramachandran Rajesh , Stoll Maria S. K. , Yu Edward W. , Taylor Derek J. , Mears Jason A.
Published: June 2023

Mitochondrial fission is crucial for distributing cellular energy throughout cells and for isolating damaged regions of the organelle that are targeted for degradation. This multistep process is initiated by the enhanced recruitment and oligomerization of dynamin-related protein 1 (Drp1) at the surface of mitochondria. As such, Drp1 is essential for inducing mitochondrial division in mammalian cells, and homologous proteins are found in all eukaryotes.De novomissense mutations in the Drp1 gene, DNM1L, are associated with severe neurodevelopmental diseases in patients, and no effective treatments are available. As a member of the dynamin superfamily of proteins (DSPs), controlled Drp1 self-assembly into large helical polymers stimulates its GTPase activity to promote membrane constriction. Still, little is known about the regulatory mechanisms that determine when and where Drp1 self-assembles, and proper mitochondrial dynamics requires correct spatial and temporal assembly of the fission machinery. Here we present a cryo-EM structure of a full-length, native Drp1 dimer in an auto-inhibited state. This dimer reveals two key conformational rearrangements that must be unlocked through intermolecular interactions to achieve the assembly competent state previously observed in crystal and filament structures. Specifically, the G domain is closed against the stalk domain and occludes intermolecular interactions necessary for self-assembly beyond a dimer. Similarly, adjacent stalks in the dimer form a more continuous interface that further occludes conserved intermolecular contact sites. This structural insight provides a novel mechanism for regulated self-assembly of the mitochondrial fission machinery.
RyR2 Binding of an Antiarrhythmic Cyclic Depsipeptide Mapped Using Confocal Fluorescence Lifetime Detection of FRET
Authors: Seflova Jaroslava , Schwarz Jacob A. , Smith Abigail N. , Svensson Bengt , Blackwell Daniel J. , Phillips Taylor A. , Nikolaienko Roman , Bovo Elisa , Rebbeck Robyn T. , Zima Aleksey V. , Thomas David D. , Petegem Filip Van , Knollmann Björn C. , Johnston Jeffrey N. , Robia Seth L. , Cornea Răzvan L.
Published: June 2023

Hyperactivity of cardiac sarcoplasmic reticulum (SR) ryanodine receptor (RyR2) Ca2+-release channels contributes to heart failure and arrhythmias. Reducing RyR2 activity, particularly during cardiac relaxation (diastole), is a desirable therapeutic goal. We previously reported that the unnatural enantiomer (ent) of an insect-RyR activator, verticilide, inhibits porcine and mouse RyR2 at diastolic (nanomolar) Ca2+and has in vivo efficacy against atrial and ventricular arrhythmia. To determine theent-verticilide structural mode of action on RyR2 and guide its further development via medicinal chemistry structure-activity relationship studies, here we used fluorescence lifetime (FLT)-measurements of Förster resonance energy transfer (FRET) in HEK293 cells expressing human RyR2. For these studies, we used an RyR-specific FRET molecular-toolkit and computational methods for trilateration (i.e., using distances to locate a point of interest). Multi-exponential analysis of FLT-FRET measurements between four donor-labeled FKBP12.6 variants and acceptor-labeledent-verticilide, yielded distance relationships placing the acceptor probe at two candidate loci within the RyR2 cryo-EM map. One locus is within the Ry12 domain (at the corner periphery of the RyR2 tetrameric complex). The other locus is sandwiched at the interface between helical domain 1 and the SPRY3 domain. These findings document RyR2-target engagement byent-verticilide, reveal new insight into the mechanism of action of this new class of RyR2-targeting drug candidate, and can serve as input in future computational determinations of theent-verticilide binding site on RyR2 that will inform structure-activity studies for lead optimization.
ER-Mitochondria Contact Sites expand during mitosis
Authors: Yu Fang , Courjaret Raphael , Elmi Asha , Hammad Ayat , Fisher Melanie , Terasaki Mark , Machaca Khaled
Published: June 2023

Membrane contact sites between various organelles define specialized spatially defined signaling hubs, they are of great interest to better understand inter-organelle communication and its implications on cellular physiology. ER-mitochondria contact sites (ERMCS) are one of the best studied and mediate Ca2+signaling that regulates mitochondrial bioenergetics. However, little is known about ERMCS during mitosis. Here we show that ERMCS expand during mitosis using transmission electron microscopy, serial EM coupled to 3D reconstruction, and ERMCS markers. ERMCS expansion in mitosis is functionally significant as it is associated with enhanced Ca2+coupling between the ER and mitochondria resulting in heightened activation of mitochondrial dehydrogenases. Our data suggest that ERMCS remodeling in mitosis is important to meet the increased energy needs during cell division.
Cell-based assay to determine Type 3 Secretion System translocon assembly inPseudomonas aeruginosausing split luciferase
Authors: Guo Hanling , Geddes Emily , Opperman Timothy J. , Heuck Alejandro P.
Published: June 2023

Multidrug resistantPseudomonas aeruginosaposes a serious threat to hospitalized patients. This organism expresses an arsenal of virulence factors that enables it to readily establish infections and to disseminate in the host. The Type III secretion System (T3SS) and its associated effectors play a crucial role in the pathogenesis ofP. aeruginosa,making them attractive targets for the development of novel therapeutic agents. The T3SS translocon, comprised of PopD and PopB, is an essential component of the T3SS secretion apparatus. In the properly assembled translocon, the N-terminus of PopD protrudes into the cytoplasm of the target mammalian cell, which can be exploited as a molecular indicator of functional translocon assembly. In this manuscript, we describe a novel whole-cell-based assay that employs the split NanoLuc luciferase detection system to provide a readout for translocon assembly.

The assay demonstrates a favorable signal/noise ratio (17.9) and robustness (z’=0.73), making it highly suitable for high-throughput screening of small molecule inhibitors targeting T3SS translocon assembly.
Multifaceted roles of rice ABA/stress-induced intrinsically disordered proteins in augmenting drought resistance
Authors: Lin Meng-Chun , Tseng I-Chieh , Wang Ching-Lan , Hsiao Wen-Rong , Shih Yun-Jhih , Lin Wen-Dar , Yu Su-May , Ho Tuan-Hua David
Published: June 2023

Water deficit stress causes devastating loss of crop yield worldwide. Improving crop drought resistance has become an urgent issue. Here we report that a group of abscisic acid (ABA)/drought stress-induced monocot-specific, intrinsically disordered, and highly proline-rich proteins, REPETITIVE PROLINE-RICH PROTEINS (RePRPs), play pivotal roles in drought resistance in rice seedlings. Rice ectopically expressingRePRPs outlived wild-type rice under extreme drought conditions primarily due to two underlying mechanisms. First,RePRPreduces water loss by decreasing stomata conductance in shoot. In addition,RePRPoverexpression enhances the levels of extracellular water barriers such as lignin and suberin, primarily in the root vascular bundle. Several groups of genes involved in lignin biosynthesis, especially the wall-bound peroxidase responsible for the final assembly of the lignin network, were induced byRePRP. Second, overexpression ofRePRPleads to lowered root osmotic potential. Root cell osmotic pressure was more negative in rice plants overexpressingRePRP2than wild-type plants, and the concentration of a key osmolyte, proline, was enhanced. Furthermore, the protein levels of two aquaporins that are important for drought stress tolerance were elevated. Hence, ABA/stress-inducedRePRPexpression leads to several beneficial traits of drought resistance, including lower water loss rate upon dehydration and higher root water use efficiency under drought conditions. This group of unique stress proteins may be an important target for technology development in enhancing drought stress resistance in cereals.
Contrasting genes conferring short and long-term biofilm adaptation inListeria
Authors: Monteith William , Pascoe Ben , Mourkas Evangelos , Clark Jack , Hakim Maliha , Hitchings Matthew D. , McCarthy Noel , Yahara Koji , Asakura Hiroshi , Sheppard Samuel K.
Published: June 2023

Listeria monocytogenesis an opportunistic food-borne bacterium that is capable of infecting humans with high rates of hospitalisation and mortality. Natural populations are genotypically and phenotypically variable, with some lineages being responsible for most human infections. The success ofL. monocytogenesis linked to its capacity to persist on food and in the environment. Biofilms are an important feature that allow these bacteria to persist and infect humans, therefore, understanding the genetic basis of biofilm formation is key to understanding transmission. We sought to investigate the biofilm forming ability ofL. monocytogenesby identifying genetic variation that underlies biofilm formation in natural populations using genome-wide association studies. Changes in gene expression of specific strains during biofilm formation were then investigated using RNAseq. Genetic variation associated with enhanced biofilm formation was identified in 273 genes by GWAS and differential expression in 220 genes by RNAseq. Statistical analyses show that number of overlapping genes flagged by either type of experiment is less than expected by random sampling. This is consistent with an evolutionary scenario where rapid adaptation is driven by variation in gene expression of pioneer genes, and this is followed by slower adaptation driven by nucleotide changes within the core genome.

Impact statement

Listeria monocytogenesis a problematic food-borne bacterium that can cause severe illness and even death in humans. Some strains are known to be more common in disease and biofilms are crucial for survival in the environment and transmission to humans. To unravel the genetic basis of biofilm formation, we undertook a study employing genome-wide association studies (GWAS) and gene transcription profiling. We identified 273 genes associated with robust biofilm formation through GWAS and discovered differential expression in 220 genes through RNAseq. Statistical analysis revealed fewer overlapping genes than expected by chance, supporting an evolutionary scenario where initial adaptation relies on gene expression variation, followed by slower adaptation through genetic changes within the core genome.

Data summary

Short read genome data are available from the NCBI (National Center for Biotechnology Information) SRA (Sequence Read Archive), associated with BioProject PRJNA971143 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA971143). Assembled genomes and supplementary material are available from FigShare: doi: 10.6084/m9.figshare.23148029. RNA sequence data and differential gene expression profiles have been deposited in the NCBI Gene Expression Omnibus.
Demographic and genetic impacts of powdery mildew in a young oak cohort
Authors: Barrès Benoit , Dutech Cyril , Saint-Jean Gilles , Bodénès Catherine , Burban Christian , Fiévet Virgil , Lepoittevin Camille , Garnier-Géré Pauline , Desprez-Loustau Marie-Laure
Published: June 2023

The demographic and genetic impacts of powdery mildew on the early stages of an oak population were studied in anad hocfield design with two disease exposures. This enabled a detailed phenotypic monitoring of 1,733 emerging individuals from 15 progenies over nine years, and the genotyping of 68% of them. The pathogen induced high levels of seedling mortality several years after sowing, associated with reduced growth and capacity to overwinter. The probability of juvenile survival could be predicted from mean disease severity in early years and acorn weight. Fast-growing families showed the highest survival rate under both natural and protected disease exposure. Correlatively, no equalizing effect of increased powdery mildew pressure on the relative contribution of mother trees to the next generation could be detected. Contrary to a possible trade-off hypothesis between growth and defense, family height potential was not negatively related to disease resistance across the studied oak mother trees. Overall, our results suggest that inQuercus roburnatural populations, infection levels (related to resistancesensu stricto) may be less determinant than growth-related tolerance to infection for the fate of seedlings. However, an equalizing effect of powdery mildew on relative oak genotype performances cannot be excluded at later stages since such an effect was already visible on height. Average genomic diversity was not significantly affected by mortality associated with powdery mildew. However, our study brings support to a deleterious effect of very low individual heterozygosity on the probability of survival across the different families. Finally, our study points to a few candidate genes for several fitness-related traits.
Visual periodicity reveals distinct attentional signatures for face and non-face categories
Authors: Quek Genevieve L. , de Heering Adélaïde
Published: June 2023

Observers can selectively deploy attention to regions of space, moments in time, specific visual features, individual objects, and even specific high-level categories – for example, when keeping an eye out for dogs while jogging. Here we exploited visual periodicity to examine how category-based attention differentially modulates selective neural processing of face and non-face categories. We combined electroencephalography (EEG) with a novel frequency-tagging paradigm capable of capturing selective neural responses for multiple visual categories contained within the same rapid image stream (faces/birds in Exp 1; houses/birds in Exp 2). We found that the pattern of attentional enhancement and suppression for face-selective processing is unique compared to other object categories: Where attending to non-face objects strongly enhances their selective neural signals during a later stage of processing (300-500ms), attentional enhancement of face-selective processing is both earlier and comparatively more modest. Moreover, only the selective neural response for faces appears to be actively suppressed by attending towards an alternate visual category. These results underscore the special status that faces hold within the human visual system, and highlight the utility of visual periodicity as a powerful tool for indexing selective neural processing of multiple visual categories contained within the same image sequence.
Mammalian PIWI-piRNA-target complexes reveal features for broad and efficient target-silencing
Authors: Li Zhiqing , Li Zhenzhen , Li Lili , Zeng Lin , Xue Junchao , Niu Huilin , Zhong Jing , Yu Qilu , Li Dengfeng , Tu Shikui , Zhang ZZ Zhao , Song Chun-Qing , Wu Jianping , Shen En-Zhi
Published: June 2023

The PIWI-interacting RNA (piRNA) pathway is an adaptive defense system wherein piRNAs guide PIWI-family Argonaute proteins to recognize and silence ever-evolving selfish genetic elements and ensure genome integrity. Driven by this intensive host-pathogen arms race, piRNA pathway and its targeted transposons have co-evolved rapidly in a species-specific manner, but how the piRNA pathway specifically adapts to target silencing in mammals remains elusive. Here, we show that mouse MILI and human HILI piRISCs bind and cleave targets more efficiently than their invertebrate counterpart from spongeEphydatia fluviatilis. The inherent functional differences comport with structural features identified by cryo-EM studies of piRISCs. In the absence of target, MILI and HILI piRISCs adopt a wider nucleic-acid-binding channel and display an extended prearranged piRNA seed as compared toEfPiwi piRISC, consistent with their ability to capture targets more efficiently thanEfPiwi piRISC. In the presence of target, the seed gate—which enforces seed-target fidelity in microRNA RISC—adopts a relaxed state in mammalian piRISC, revealing how MILI and HILI tolerate seed-target mismatches to broaden the target spectrum. A vertebrate-specific lysine distorts the piRNA seed, shifting the trajectory of the piRNA-target duplex out of the central cleft and toward the PAZ lobe. Functional analyses reveal that this lysine promotes target binding and cleavage. Our study therefore provides a molecular basis for the piRNA targeting mechanism in mouse and human, and suggests that mammalian piRNA machinery can achieve broad target silencing using a limited supply of piRNA species.
Gestational diabetes augments group BStreptococcus perinatal infection through disruptions in maternal immunity and the vaginal microbiota
Authors: Mercado-Evans Vicki , Mejia Marlyd E. , Zulk Jacob J. , Ottinger Samantha , Hameed Zainab , Serchejian Camille , Marunde Madelynn G. , Robertson Clare M. , Ballard Mallory B. , Korotkova Natalia , Flores Anthony R. , Pennington Kathleen A. , Patras Kathryn A.
Published: June 2023

Group BStreptococcus(GBS) is a pervasive perinatal pathogen, yet factors driving GBS disseminationin uteroare poorly defined. Gestational diabetes mellitus (GDM), a complication marked by dysregulated immunity and maternal microbial dysbiosis, increases risk for GBS perinatal disease. We interrogated host-pathogen dynamics in a novel murine GDM model of GBS colonization and perinatal transmission. GDM mice had greater GBSin uterodissemination and subsequently worse neonatal outcomes. Dual-RNA sequencing revealed differential GBS adaptation to the GDM reproductive tract, including a putative glycosyltransferase (yfhO), and altered host responses. GDM disruption of immunity included reduced uterine natural killer cell activation, impaired recruitment to placentae, and altered vaginal cytokines. Lastly, we observed distinct vaginal microbial taxa associated with GDM status and GBS invasive disease status. Our translational model of GBS perinatal transmission in GDM hosts recapitulates several clinical aspects and enables discovery of host and bacterial drivers of GBS perinatal disease.
Cross-linking mass spectrometric analysis of the endogenous TREX complex fromS. cerevisiae
Authors: Kern Carina , Radon Christin , Wende Wolfgang , Leitner Alexander , Sträßer Katja
Published: June 2023

The conserved TREX complex has multiple functions in gene expression such as transcription elongation, 3’ end processing, mRNP assembly and nuclear mRNA export as well as the maintenance of genomic stability. InS. cerevisiae, TREX is composed of the pentameric THO complex, the DEAD-box RNA helicase Sub2, the nuclear mRNA export adaptor Yra1 and the SR-like proteins Gbp2 and Hrb1. Here, we present the structural analysis of the endogenous TREX complex ofS. cerevisiaepurified from its native environment. To this end, we used cross-linking mass spectrometry to gain structural information on regions of the complex that are not accessible to classical structural biology techniques. We also used negative-stain electron microscopy to investigate the organization of the cross-linked complex used for XL-MS by comparing our endogenous TREX complex with recently published structural models of recombinant THO-Sub2 complexes. According to our analysis, the endogenous yeast TREX complex preferentially assembles into a dimer. The overall structures of the recombinant yeast THO-Sub2 complexes strongly resemble the structural conformation of the monomers and the dimer interface of the endogenous TREX complex.
Metabolic and neurobehavioral disturbances induced by purine recycling deficiency inDrosophila
Authors: Petitgas Céline , Seugnet Laurent , Dulac Amina , Matassi Giorgio , Mteyrek Ali , Fima Rebecca , Strehaiano Marion , Dagorret Joana , Chérif-Zahar Baya , Marie Sandrine , Ceballos-Picot Irène , Birman Serge
Published: June 2023

Adenine phosphoribosyltransferase (APRT) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT) are two structurally related enzymes involved in purine recycling in humans. Inherited mutations that suppress HGPRT activity are associated with Lesch-Nyhan disease (LND), a rare X-linked metabolic and neurological disorder in children, characterized by hyperuricemia, dystonia and compulsive self-injury. To date, no treatment is available for these neurological defects and no animal model recapitulates all symptoms of LND patients. Here we studied LND-related mechanisms in the fruit fly. By combining enzymatic assays and phylogenetic analysis, we confirm that no HGPRT activity is expressed inDrosophila melanogaster, making the APRT homologue (Aprt) the only purine-recycling enzyme in this organism. Whereas APRT deficiency does not trigger neurological defects in humans, we observed thatDrosophila Aprtmutants show both metabolic and neurobehavioral disturbances, including increased uric acid levels, locomotor impairments, sleep alterations, seizure-like behavior, reduced lifespan, and reduction of adenosine signaling and content. Locomotor defects could be rescued by Aprt re-expression in neurons and reproduced by knocking downAprtselectively in the protocerebral anterior medial (PAM) dopaminergic neurons, the mushroom bodies or glia subsets. Ingestion of allopurinol rescued uric acid levels inAprt-deficient mutants but not neurological defects, as is the case in LND patients, while feeding adenosine orN6-methyladenosine (m6A) during development fully rescued the epileptic behavior. Intriguingly, pan-neuronal expression of an LND-associated mutant form of human HGPRT (I42T), but not the wild-type enzyme, resulted in early locomotor defects and seizure in flies, similar toAprtdeficiency. Overall, our results suggest thatDrosophilacould be used in different ways to better understand LND and seek a cure for this dramatic disease.
Multimodal 3D transport system implementation barriers in populated municipalities
Authors: Dziugiel Bartosz , Mazur Anna Maria , Liberacki Adam , Ginter Piotr , Utracka Agata , Wyka Sylwester , Di Vito Vittorio , Menichino Aniello
Published: June 2023

Purpose

Process of building and then implementation of integrated multimodal, passenger-centred and predominantly sustainable transport system will require a specific effort to be input in preparation, especially if it covers new entrants like passenger Urban Air Mobility. This paper aims to address the first step which is the identification of barriers to be overcome to turn the concept into reality.

Design/methodology/approach

Comparison of the current state-of-the-art in transportation, Information and Communication Technologies as well as other city planning domains to the forecasted ecosystem, described in the form of scenarios where base for definition of necessary actions, challenges as well as potential barriers and obstacles were identified and thoroughly specified.

Findings

Barriers grouped in five categories: policy, digitalisation, transportation technologies, integration technologies and passengers’ needs allow for formulation of the relevant roadmaps defining optimal development path towards fully integrated multimodal, passenger-centred and sustainable transport system.

Research limitations/implications

Conclusions can be a starting point in studies towards development of roadmap for implementation of truly integrated municipal transport system both sharing the resources as well as high-level objectives.

Practical implications

Conclusions can be exploited in various areas starting from preparation of strategies in cities aspirating to be smart, through definition of technology development priorities by relevant agencies ending with industry actors looking for better trimming their business.

Originality/value

The identified barriers as derived from detailed investigation enable deep insight into the total transport system vision in which Urban Air Mobility integrated within urban mobility ecosystem is considered as game-changing factor having large potential to contribute to both making cities smart and sustainable.
From harasser tourists to above the law managers: female tour guides strategies for coping with sexual harassment
Authors: Mousa Mohamed , Abdelgaffar Hala , Salem Islam Elbayoumi , Chaouali Walid , Elbaz Ahmed Mohamed
Published: June 2023

Purpose

This study examines how far female tour guides in Egypt experience sexual harassment and how they cope with it.

Design/methodology/approach

A qualitative research method is employed, and semi-structured interviews were conducted with 32 full-time female tour guides working for several travel agencies in Egypt. Thematic analysis was used to extract the main ideas from the transcripts.

Findings

The findings show that female tour guides in Egypt would encounter annoying gender harassment mostly from tourists they serve, and they might suffer from irresponsible behavior – gender harassment, unwanted sexual harassment, and sexual coercion – from their local managers. When facing sexual harassment, female tour guides usually tend to adopt one of the following three coping strategies: (a) indifference to sexual harassment they encounter, (b) heroism by taking legal action when exposed to sexual harassment or (c) fatalism by taking inconsequential action such as complaining the harasser to his direct manager or filling in an official complaint inside their workplace. The selection of the coping strategy is usually based on the female victim's personality and the organizational and social context she adapts to.

Originality/value

This paper contributes by filling a gap in tourism, human resources management and gender studies in which empirical studies on the sexual harassment that female tour guides encounter, particularly in non-Western contexts, have been limited so far.
Urban traffic flow management on large scale using an improved ACO for a road transportation system
Authors: Boubedra Somia , Tolba Cherif , Manzoni Pietro , Beddiar Djamila , Zennir Youcef
Published: June 2023

Purpose

With the demographic increase, especially in big cities, heavy traffic, traffic congestion, road accidents and augmented pollution levels hamper transportation networks. Finding the optimal routes in urban scenarios is very challenging since it should consider reducing traffic jams, optimizing travel time, decreasing fuel consumption and reducing pollution levels accordingly. In this regard, the authors propose an enhanced approach based on the Ant Colony algorithm that allows vehicle drivers to search for optimal routes in urban areas from different perspectives, such as shortness and rapidness.

Design/methodology/approach

An improved ant colony algorithm (ACO) is used to calculate the optimal routes in an urban road network by adopting an elitism strategy, a random search approach and a flexible pheromone deposit-evaporate mechanism. In addition, the authors make a trade-off between route length, travel time and congestion level.

Findings

Experimental tests show that the routes found using the proposed algorithm improved the quality of the results by 30% in comparison with the ACO algorithm. In addition, the authors maintain a level of accuracy between 0.9 and 0.95. Therefore, the overall cost of the found solutions decreased from 67 to 40. In addition, the experimental results demonstrate that the authors’ improved algorithm outperforms not only the original ACO algorithm but also popular meta-heuristic algorithms such as the genetic algorithm (GA) and particle swarm optimization (PSO) in terms of reducing travel costs and improving overall fitness value.

Originality/value

The proposed improvements to the ACO to search for optimal paths for urban roads include incorporating multiple factors, such as travel length, time and congestion level, into the route selection process. Furthermore, random search, elitism strategy and flexible pheromone updating rules are proposed to consider the dynamic changes in road network conditions and make the proposed approach more relevant and effective. These enhancements contribute to the originality of the authors’ work, and they have the potential to advance the field of traffic routing.
Middle of the road: the effects of political ideology on social status perceptions of and by political moderates in organisations
Authors: Zhang Teng , Soderberg Andrew T.
Published: June 2023

Purpose

Drawing on research in the social psychology and political science literatures, this research aims to examine how political moderates perceive, and are perceived by, their co-workers with differing political ideologies in an organisational context, with a focus on the perceptions of social status.

Design/methodology/approach

To test the hypotheses regarding the social status perceptions of and by political moderates in the workplace, the authors conducted an online experiment in which working adults read a hypothetical workplace scenario and then assessed the social status of a co-worker based on the political ideology of that co-worker.

Findings

The results largely supported the two hypothesised asymmetries of social perceptions of and by political moderates in an organisational context. Specifically, political moderates were perceived to have higher social status by their moderate and conservative co-workers than by their liberal co-workers. In addition, political moderates perceived moderate co-workers to have higher social status than conservative ones.

Originality/value

This research investigates the influence of political ideology on social status perceptions in organisations by focusing on the previously underexamined political moderates. The findings illustrate the importance of political moderates, who tend to espouse a moderate level of resistance to social change, in the process of developing a functional hierarchy and balancing change and stability in organisations.
Influences of parental occupation on children's occupational choices
Authors: Abdul Rahaman Wassiuw , Mohammed Ibrahim , Turkson Festus Ebo , Baffour Priscilla Twumasi
Published: June 2023

Purpose

This study examines the relationships between parents' and children's occupations to determine the existence of intergenerational transmission of occupations.

Design/methodology/approach

To achieve the purpose of the study, four predominant occupational types based on the International Standard Classification of Occupations (ISCO): agriculture and forestry; services and sales; managerial/administrative; and professional/technical are examined using data from the latest (7th) round of the Ghana Living Standards Survey (GLSS). Two complementary methods involving the correlational analysis and regression-based techniques are used.

Findings

The findings indicate the presence of parental influences on children's occupational choices (same-sex and cross-sex) in the Ghanaian labour market, with maternals and same-sector effects having a more substantial influence on children's occupational choices, especially in agriculture and forestry, and services and sales sectors.

Research limitations/implications

The lack of panel data in observing children's occupational choices over time makes it challenging to assume direct causation.

Originality/value

The study is the first to highlight the relative strengths of paternal influence (father's effect) and maternal impact (mother's effect) on sons' and daughters' occupational choices in Africa. The findings have several implications for intergenerational (im)mobility of occupations including how policymakers can make career guidance more effective.

Peer review

The peer-review history for this article is available at: https://publons.com/publon/10.1108/IJSE-10-2022-0705
A comprehensive literature review of the impact of child tax credit/child allowance in the United States and South Korea
Authors: Choi Hyeri , Lee Jiwan
Published: June 2023

Purpose

The America Rescue Plan (ARP) transformed the Child Tax Credit (CTC) into a more generous, inclusive monthly payment from July through December 2021. However, the expansion has been terminated and the annual CTC has been reinstated. The United States is one of the few OECD countries that do not have a child allowance system and South Korea has recently adopted child allowance in 2018. This study aims to comprehensively review the existing literature and evidence on ARP-CTC in the United States and Universal Child Allowance (CA) in Korea.

Design/methodology/approach

The researchers completed a database search between July 1, 2022 and July 20, 2022. For the United States, the search keywords were child tax credit OR expanded child tax credit OR CTC OR child allowance. For Korea, the search keyword was child allowance. Searches were conducted using 79 databases. A total of 36 US studies and 7 Korean studies met all the inclusion criteria and proceeded to the extraction process. A narrative thematic synthesis approach was employed to identify themes in the findings. The results were organized based on the characteristics of the studies and the post-intervention outcomes.

Findings

Studies in the United States focused primarily on economic outcomes, including poverty and material hardship, reflecting the concern policymakers and researchers have about child poverty. On the other hand, Korean studies examined employment, economic well-being, psychological well-being and expenditures in a relatively balanced share. Overall, studies found that both ARP-Child Tax Credits and Universal Child Allowance reduced child poverty and improved material hardship. Also, studies in both countries suggested that both policies had positive impacts on parental psychological well-being.

Originality/value

To the authors knowledge, this paper is the first to comprehensively review the impact of the US ARP-CTC in comparison with the Korean child allowance. Two studies reviewed and updated the literature on US ARP-CTC as a round-up paper. Moreover, the authors conduct cross-national comparative analyses between the United States and Korea. The contexts of the child allowance system in the two nations have both similarities and differences, thereby offering a unique opportunity for a comparative study.