bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Analysis and Functional Assessment of aTGFBR2Variant in Micrognathia and Cleft Palate
Authors: Michaels JES-Rite , Husami Ammar , Vontell Andrew M. , Brugmann Samantha A. , Stottmann Rolf W.
Published: April 2024

Cleft lip and cleft palate are among the most common congenital anomalies and are the result of incomplete fusion of embryonic craniofacial processes or palatal shelves, respectively. We know that genetics play a large role in these anomalies but the list of known causal genes is far from complete. As part of a larger sequencing effort of patients with micrognathia and cleft palate we identified a candidate variant intransforming growth factor beta receptor 2(TGFBR2) which is rare, changing a highly conserved amino acid, and predicted to be pathogenic by a number of metrics. The family history and population genetics would suggest this specific variant would be incompletely penetrant, but this gene has been convincingly implicated in craniofacial development. In order to test the hypothesis this might be a causal variant, we used genome editing to create the orthologous variant in a new mouse model. Surprisingly,Tgfbr2V387Mmice did not exhibit craniofacial anomalies or have reduced survival suggesting this is, in fact, not a causal variant for cleft palate/ micrognathia. The discrepancy between in silico predictions and mouse phenotypes highlights the complexity of translating human genetic findings to mouse models. We expect these findings will aid in interpretation of future variants seen inTGFBR2from ongoing sequencing of patients with congenital craniofacial anomalies.
Plasma membrane and cytoplasmic compartmentalization: a dynamic structural framework required for pollen tube tip growth
Authors: Fritz Carolin , Reimann Theresa Maria , Adler Jeremy , Knab Johanna , Schulmeister Sylwia , Kriechbaum Choy , Müller Sabine , Parmryd Ingela , Kost Benedikt
Published: April 2024

Rapid, unidirectional pollen tube tip growth is essential for fertilization and is widely employed as a model of polar cell expansion, a process crucial for plant morphogenesis. Different proteins and lipids with key functions in the control of polar cell expansion are associated with distinct domains of the plasma membrane (PM) at the pollen tube tip. These domains need to be dynamically maintained during tip growth, which depends on massive secretory and endocytic membrane traffic. Very little is currently known about the regulatory and cellular mechanisms responsible for the compartmentalization of the pollen tube PM. To provide a reliable structural framework for the further characterization of these mechanisms, an integrated quantitative map was compiled of the relative positions in normally growing tobacco pollen tubes of PM domains 1) enriched in key signaling proteins or lipids, 2) displaying high membrane order, or 3) in contact with cytoplasmic structures playing important roles in apical membrane traffic. Previously identified secretory and endocytic PM domains were also included into this map. Internalization of regulatory proteins or lipids associated with PM regions overlapping with the endocytic domain was assessed based on brefeldin A (BFA) treatment. These analyses revealed remarkable aspects of the structural organization of tobacco pollen tube tips, which enhance our understanding of tip growth by providing important insights into 1) RAC/ROP signaling, 2) phosphatidylinositol 4,5-bisphosphate (PI4,5P2) metabolism and functions, 3) trafficking of signaling lipids, 4) functions of domains displaying high membrane order, and 5) Ca2+regulation of secretion.

Quantitative mapping of plasma membrane and cytoplasmic domains at the tip of elongating tobacco pollen provides important insights into regulatory and cellular mechanisms essential for tip growth.
Targeting phosphatase DUSP22 ameliorates skeletal muscle wasting via Akt independent JNK-FOXO3a repression
Authors: Lee Sang-Hoon , Kim Hyun-Jun , Kim Seon-Wook , Lee Hyunju , Jung Da-Woon , Williams Darren Reece
Published: April 2024

Skeletal muscle wasting results from numerous conditions, such as sarcopenia, glucocorticoid therapy or intensive care. It prevents independent living in the elderly, predisposes to secondary diseases, and ultimately reduces lifespan. There is no approved drug therapy and the major causative mechanisms are not fully understood. Dual specificity phosphatase 22 (DUSP22) is a pleiotropic signaling molecule that plays important roles in immunity and cancer. However, the role of DUSP22 in skeletal muscle wasting is unknown. In this study, DUSP22 was found to be upregulated in sarcopenia patients and models of skeletal muscle wasting. DUSP22 knockdown or pharmacological inhibition prevented multiple forms of muscle wasting. Mechanistically, targeting DUSP22 suppressed FOXO3a, a master regulator of skeletal muscle wasting, via downregulation of the stress-activated kinase JNK, which occurred independently of aberrant Akt activation. DUSP22 targeting was also effective in human skeletal muscle cells undergoing atrophy. In conclusion, phosphatase DUSP22 is a novel target for preventing skeletal muscle wasting. The DUSP22-JNK-FOXO3a axis could be exploited to treat sarcopenia or related aging disorders.
Metaproteomics and DNA metabarcoding as tools to assess dietary intake in humans
Authors: Petrone Brianna L. , Bartlett Alexandria , Jiang Sharon , Korenek Abigail , Vintila Simina , Tenekjian Christine , Yancy William S. , David Lawrence A. , Kleiner Manuel
Published: April 2024

Objective biomarkers of food intake are a sought-after goal in nutrition research. Most biomarker development to date has focused on metabolites detected in blood, urine, skin or hair, but detection of consumed foods in stool has also been shown to be possible via DNA sequencing. An additional food macromolecule in stool that harbors sequence information is protein. However, the use of protein as an intake biomarker has only been explored to a very limited extent. Here, we evaluate and compare measurement of residual food-derived DNA and protein in stool as potential biomarkers of intake. We performed a pilot study of DNA sequencing-based metabarcoding (FoodSeq) and mass spectrometry-based metaproteomics in five individuals’ stool sampled in short, longitudinal bursts accompanied by detailed diet records (n=27 total samples). Dietary data provided by stool DNA, stool protein, and written diet record independently identified a strong within-person dietary signature, identified similar food taxa, and had significantly similar global structure in two of the three pairwise comparisons between measurement techniques (DNA-to-protein and DNA-to-diet record). Metaproteomics identified proteins including myosin, ovalbumin, and beta-lactoglobulin that differentiated food tissue types like beef from dairy and chicken from egg, distinctions that were not possible by DNA alone. Overall, our results lay the groundwork for development of targeted metaproteomic assays for dietary assessment and demonstrate that diverse molecular components of food can be leveraged to study food intake using stool samples.
The neuroendocrine transition in prostate cancer is dynamic and dependent on ASCL1
Authors: Romero Rodrigo , Chu Tinyi , González-Robles Tania J. , Smith Perianne , Xie Yubin , Kaur Harmanpreet , Yoder Sara , Zhao Huiyong , Mao Chenyi , Kang Wenfei , Pulina Maria V. , Lawrence Kayla E. , Gopalan Anuradha , Zaidi Samir , Yoo Kwangmin , Choi Jungmin , Fan Ning , Gerstner Olivia , Karthaus Wouter R. , DeStanchina Elisa , Ruggles Kelly V. , Westcott Peter M.K. , Chaligné Ronan , Pe’er Dana , Sawyers Charles L.
Published: April 2024

Lineage plasticity is a recognized hallmark of cancer progression that can shape therapy outcomes. The underlying cellular and molecular mechanisms mediating lineage plasticity remain poorly understood. Here, we describe a versatilein vivoplatform to identify and interrogate the molecular determinants of neuroendocrine lineage transformation at different stages of prostate cancer progression. Adenocarcinomas reliably develop following orthotopic transplantation of primary mouse prostate organoids acutely engineered with human-relevant driver alterations (e.g.,Rb1-/-;Trp53-/-;cMyc+orPten-/-;Trp53-/-;cMyc+), but only those withRb1deletion progress to ASCL1+ neuroendocrine prostate cancer (NEPC), a highly aggressive, androgen receptor signaling inhibitor (ARSI)-resistant tumor. Importantly, we show this lineage transition requires a nativein vivomicroenvironment not replicated by conventional organoid culture. By integrating multiplexed immunofluorescence, spatial transcriptomics and PrismSpot to identify cell type-specific spatial gene modules, we reveal that ASCL1+ cells arise from KRT8+ luminal epithelial cells that progressively acquire transcriptional heterogeneity, producing large ASCL1+;KRT8-NEPC clusters.Ascl1loss in established NEPC results in transient tumor regression followed by recurrence; however,Ascl1deletion prior to transplantation completely abrogates lineage plasticity, yielding adenocarcinomas with elevated AR expression and marked sensitivity to castration. The dynamic feature of this model reveals the importance of timing of therapies focused on lineage plasticity and offers a platform for identification of additional lineage plasticity drivers.
A promiscuous mechanism to phase separate eukaryotic carbon fixation in the green lineage
Authors: Barrett James , Naduthodi Mihris I.S. , Mao Yuwei , Dégut Clément , Musiał Sabina , Salter Aidan , Leake Mark C. , Plevin Michael J. , McCormick Alistair J. , Blaza James N. , Mackinder Luke C.M.
Published: April 2024

CO2fixation is commonly limited by inefficiency of the CO2-fixing enzyme Rubisco. Eukaryotic algae concentrate and fix CO2in phase-separated condensates called pyrenoids, which complete up to one-third of global CO2fixation. Condensation of Rubisco in pyrenoids is dependent on interaction with disordered linker proteins that show little conservation between species. We developed a sequence-independent bioinformatic pipeline to identify linker proteins in green algae. We report the linker fromChlorellaand demonstrate that it binds a conserved site on the Rubisco large subunit. We show theChlorellalinker phase separatesChlamydomonasRubisco and that despite their separation by ∼800 million years of evolution, theChlorellalinker can support the formation of a functional pyrenoid inChlamydomonas. This cross-species reactivity extends to plants, with theChlorellalinker able to drive condensation of some native plant Rubiscosin vitroandin planta. Our results represent an exciting frontier for pyrenoid engineering in plants, which is modelled to increase crop yields.
Characterization of liver-pancreas crosstalk following β-cell loss reveals a role for the molybdenum cofactor in β-cell regeneration
Authors: Karampelias Christos , Băloiu Bianca , Rathkolb Birgit , Silva-Buttkus Patricia da , Bachar-Wikström Etty , Marschall Susan , Fuchs Helmut , Durner Valerie Gailus- , Chu Lianhe , de Angelis Martin Hrabě , Andersson Olov
Published: April 2024

Regeneration of insulin-producing β-cells is an alternative avenue to manage diabetes, and it is crucial to unravel this process in vivo during physiological responses to the lack of β-cells. Here, we aimed to characterize how hepatocytes can contribute to β-cell regeneration in a zebrafish model of β-cell ablation. Using lineage-tracing, we show that hepatocytes do not directly convert into β-cells even under extreme β-cell ablation conditions. A transcriptomics analysis of isolated hepatocytes following β-cell ablation displayed altered lipid- and glucose-related processes. Based on the transcriptomics, we performed a genetic screen that uncovers a potential role for the molybdenum cofactor (Moco) biosynthetic pathway in β-cell regeneration and glucose metabolism in zebrafish. Consistently,Mocs2haploinsufficiency in mice indicated dysregulated glucose metabolism and liver function. Together, our study sheds light on the liver-pancreas crosstalk and suggests that the molybdenum cofactor biosynthesis pathway should be further studied in relation to glucose metabolism and diabetes.
HeterozygousEif4nif1Stop Gain Mice Replicate the Primary Ovarian Insufficiency Phenotype in Women
Authors: Moriwaki Mika , Liu Lihua , James Emma R , Tolley Neal , O’Connora Ashley M , Emery Benjamin , Aston Kenneth Ivan , Campbell Robert A. , Welt Corrine K.
Published: April 2024

We created the c.1286C>G stop-gain mutation found in a family with primary ovarian insufficiency (POI) at age 30 years. TheEif4enif1C57/Bl6 transgenic mouse model contained a floxed exon 10-19 cassette with a conditional knock-in cassette containing the c.1286C>G stop-gain mutation in exon 10. The hybrid offspring of CMV-Cremice withEif4enif1WT/flxmice were designatedEif4enif1WT/Δfor simplicity. A subset of female heterozygotes (Eif4enif1WT/Δ)had no litters. In those with litters, the final litter was earlier (5.4±2.6 vs. 10.5±0.7 months; p=0.02). Heterozygous breeding pair (Eif4enif1WT/Δx Eif4enif1WT/Δ)litter size was 60% of WT litter size (3.9±2.0 vs. 6.5±3.0 pups/litter;p<0.001). The genotypes were 35%Eif4enif1WT/flxand 65%Eif4enif1WT/Δ, with no homozygotes. Homozygote embryos did not develop beyond the 4-8 cell stage. The number of follicles in ovaries fromEif4enif1WT/Δmice was lower starting at the primordial (499±290 vs. 1445±381) and primary follicle stage (1069±346 vs. 1450±193) on day 10 (p<0.05). The preantral follicle number was lower starting on day 21 (213±86 vs. 522±227; p<0.01). Examination of ribosome protected mRNAs (RPR) demonstrated altered mRNA expression. TheEif4enif1stop-gain mice replicate the POI phenotype in women. The unique mouse model provides a platform to study regulation of protein translation across oocyte and embryo development in mammals.
A Ratiometric Catalog of Protein Isoform Shifts in the Cardiac Fetal Gene Program
Authors: Han Yu , Wennersten Sara A. , Pandi Boomathi P. , Ng Dominic C. M. , Lau Edward , Lam Maggie P. Y.
Published: April 2024

The fetal genetic program orchestrates cardiac development and the re-expression of fetal genes is thought to underlie cardiac disease and adaptation. Here, a proteomics ratio test using mass spectrometry is applied to find protein isoforms with statistically significant usage differences in the fetal vs. postnatal mouse heart. Changes in isoform usage ratios are pervasive at the protein level, with 104 significant events observed, including 88 paralog-derived isoform switching events and 16 splicing-derived isoform switching events between fetal and postnatal hearts. The ratiometric proteomic comparisons rediscovered hallmark fetal gene signatures including a postnatal switch from fetal β (MYH7) toward α (MYH6) myosin heavy chains and from slow skeletal muscle (TNNI1) toward cardiac (TNNI3) troponin I. Altered usages in metabolic proteins are prominent, including a platelet to muscle phosphofructokinase (PFKP - PFKM), enolase 1 to 3 (ENO1 - ENO3), and alternative splicing of pyruvate kinase M2 toward M1 (PKM2 - PKM1) isoforms in glycolysis. The data also revealed a parallel change in mitochondrial proteins in cardiac development, suggesting the shift toward aerobic respiration involves also a remodeling of the mitochondrial protein isoform proportion. Finally, a number of glycolytic protein isoforms revert toward their fetal forms in adult hearts under pathological cardiac hypertrophy, suggesting their functional roles in adaptive or maladaptive response, but this reversal is partial. In summary, this work presents a catalog of ratiometric protein markers of the fetal genetic program of the mouse heart, including previously unreported splice isoform markers.
Spatiotemporal cerebral blood flow dynamics underlies emergence of the limbic-sensorimotor-association cortical gradient in human infancy
Authors: Ouyang Minhui , Detre John A. , Hyland Jessica L. , Sindabizera Kay L. , Kuschner Emily S , Edgar J. Christopher , Peng Yun , Huang Hao
Published: April 2024

Infant cerebral blood flow (CBF) delivers nutrients and oxygen to fulfill brain energy consumption requirements for the fastest period of postnatal brain development across lifespan. However, organizing principle of whole-brain CBF dynamics during infancy remains obscure. Leveraging a unique cohort of 100+ infants with high-resolution arterial spin labeled MRI, we found the emergence of the cortical hierarchy revealed by highest-resolution infant CBF maps available to date. Infant CBF across cortical regions increased in a biphasic pattern with initial rapid and sequentially slower rate, with break-point ages increasing along the limbic-sensorimotor-association cortical gradient. Increases in CBF in sensorimotor cortices were associated with enhanced language and motor skills, and frontoparietal association cortices for cognitive skills. The study discovered emergence of the hierarchical limbic-sensorimotor-association cortical gradient in infancy, and offers standardized reference of infant brain CBF and insight into the physiological basis of cortical specialization and real-world infant developmental functioning.
Modulation of biphasic pattern of cortical reorganization in spinal cord transected rats by external magnetic fields
Authors: Kaur Sajeev , Kochhar Kanwal Preet , Jain Suman
Published: April 2024

Magnetic field induces electric field in the brain and has the potential to modulate cortical plasticity giving rise to sustained excitability as well as behavioral modifications. The present study demonstrates the effect of extremely low frequency magnetic field (ELF-MF) on cortical reorganization after SCI in complete transection rat model. The spinal cord of male albino Wistar rats was completed transected at T-13 spinal level and ELF-MF (50 Hz, 17.96 µT) exposure given either for 5 or 12 or 32 days for temporal observations. A significant functional recovery was evident in locomotor, sensorimotor and motor behavioral tests after 32 days of magnetic field exposure. This was associated with an amelioration in cortical electrical activity, decrease in the lesion area and volume and modulation of plasticity associated proteins like Nogo-A and BDNF in a biphasic pattern. The results suggest improvement of functional, electrical and morphological parameters along with upregulation of plasticity associated proteins in an in-vivo SCI rat model following ELF-MF exposure for 32 days but not after 5, 12 days exposure
How fast are viruses spreading in the wild?
Authors: Dellicour Simon , Bastide Paul , Rocu Pauline , Fargette Denis , Hardy Olivier J. , Suchard Marc A. , Guindon Stéphane , Lemey Philippe
Published: April 2024

Genomic data collected from viral outbreaks can be exploited to reconstruct the dispersal history of viral lineages in a two-dimensional space using continuous phylogeographic inference. These spatially explicit reconstructions can subsequently be used to estimate dispersal metrics allowing to unveil the dispersal dynamics and evaluate the capacity to spread among hosts. Heterogeneous sampling intensity of genomic sequences can however impact the accuracy of dispersal insights gained through phylogeographic inference. In our study, we implement a simulation framework to evaluate the robustness of three dispersal metrics — a lineage dispersal velocity, a diffusion coefficient, and an isolation-by-distance signal metric — to the sampling effort. Our results reveal that both the diffusion coefficient and isolation-by-distance signal metrics appear to be robust to the number of samples considered for the phylogeographic reconstruction. We then use these two dispersal metrics to compare the dispersal pattern and capacity of various viruses spreading in animal populations. Our comparative analysis reveals a broad range of isolation-by-distance patterns and diffusion coefficients mostly reflecting the dispersal capacity of the main infected host species but also, in some cases, the likely signature of rapid and/or long-distance dispersal events driven by human-mediated movements through animal trade. Overall, our study provides key recommendations for the lineage dispersal metrics to consider in future studies and illustrates their application to compare the spread of viruses in various settings.
Deciphering the phospho-signature induced by hepatitis B virus in primary human hepatocytes
Authors: Pastor Florentin , Charles Emilie , Belmudes Lucid , Chabrolles Hélène , Cescato Marion , Rivoire Michel , Burger Thomas , Passot Guillaume , Durantel David , Lucifora Julie , Couté Yohann , Salvetti Anna
Published: April 2024

Phosphorylation is a major post-translation modification (PTM) of proteins which is finely tuned by the activity of several hundred kinases and phosphatases. It controls most if not all cellular pathways including anti-viral responses. Accordingly, viruses often induce important changes in the phosphorylation of host factors that can either promote or counteract viral replication. Among more than 500 kinases constituting the human kinome only few have been described as important for the Hepatitis B virus (HBV) infectious cycle, and most of them intervene during early or late infectious steps by phosphorylating the viral Core protein (HBc) protein. In addition, little is known on the consequences of HBV infection on the activity of cellular kinases.

The objective of this study was to investigate the global impact of HBV infection on the cellular phosphorylation landscape early after infection. For this, primary human hepatocytes (PHHs) were challenged or not with HBV, and a mass spectrometry (MS)-based quantitative phosphoproteomic analysis was conducted two- and seven-days post-infection. The results indicated that while, as expected, HBV infection only minimally modified the cell proteome, significant changes were observed in the phosphorylation state of several host proteins at both times points. Gene enrichment and ontology analyses of up- and down-phosphorylated proteins revealed common and distinct signatures induced by infection. In particular, HBV infection resulted in up-phosphorylation of proteins involved in DNA damage signaling and repair, RNA metabolism, in particular splicing, and cytoplasmic cell-signaling. Down-phosphorylated proteins were mostly involved in cell signaling and communication. Validation studies carried out on selected up-phosphorylated proteins, revealed that HBV infection induced a DNA damage response characterized by the appearance of 53BP1 foci, the inactivation of which by siRNA increased cccDNA levels. In addition, among up-phosphorylated RNA binding proteins (RBPs), SRRM2, a major scaffold of nuclear speckles behaved as an antiviral factor. In accordance with these findings, kinase prediction analysis indicated that HBV infection upregulates the activity of major kinases involved in DNA repair. These results strongly suggest that HBV infection triggers an intrinsic anti-viral response involving DNA repair factors and RBPs that contribute to reduce HBV replication in cell culture models.
p53-induced GDF-15 expression promotes a pro-regenerative response in human chondrocytes upon cartilage injury
Authors: Marques Sara Sofi , Liebaug Alexandra , Maurer Svenja , Rothenbacher Dietrich , Brenner Rolf E , Riegger Jana
Published: April 2024

Posttraumatic osteoarthritis (PTOA) is a special form of OA, developing after joint injuries. Except for some minor differences between the clinical characteristics of patients suffering from idiopathic OA (IOA) and PTOA, no biologic marker has yet been identified to distinguish IOA from PTOA. In this study, we investigated the expression of the stress-responsive cytokine growth differentiation factor 15 (GDF-15) in clinical samples from the Ulm OA study cohort (PTOA: n =12; IOA: n=54) and in a human ex vivo cartilage trauma model.

We found significantly higher GDF-15 levels in synovial fluid of end-stage PTOA patients as compared to IOA patients. Further, we confirmed that fibroblast-like synoviocytes secreted increased levels of GDF-15 after stimulation with medium ofex vivo-traumatized cartilage. GDF-15 and its receptor, GFRAL, were significantly elevated in highly degenerated OA cartilage. By means of a human cartilage trauma model, we discovered that chondrocytes produced GDF-15 upon tissue injury, while antioxidative treatment attenuated GDF-15 secretion. We confirmed that oxidative stress and subsequent activation of p53 resulted in GDF-15 expression. As a transcriptional target of p53, GDF-15 was associated with chondrosenescence. Although the cytokine might therefore represent a senescence-associated secretory phenotype (SASP) factor, stimulation with exogenous GDF-15 did not cause detrimental effects but induced a pro-regenerative response in chondrocytes, characterized by enhanced proliferation as well as chondro- and cell protection after cartilage trauma. Overall, this study first describes GDF-15 as a stress-responsive and potentially pro-regenerative cytokine in the context of human PTOA.
The host GTPase Dynamin 2 modulates apical junction structure to control cell-to-cell spread ofListeria monocytogenes
Authors: Tijoriwalla Serena , Liyanage Thiloma , Herath Thilina U.B. , Lee Nicole , Rehman Attika , Gianfelice Antonella , Ireton Keith
Published: April 2024

The food-borne pathogenListeria monocytogenesuses actin-based motility to generate plasma membrane protrusions that mediate the spread of bacteria between host cells. In polarized epithelial cells, efficient protrusion formation byListeriarequires the secreted bacterial protein InlC, which binds to a carboxyl-terminal Src Homology 3 (SH3) domain in the human scaffolding protein Tuba. This interaction antagonizes Tuba, thereby diminishing cortical tension at the apical junctional complex and enhancingL. monocytogenesprotrusion formation and spread. Tuba contains five SH3 domains apart from the domain that interacts with InlC. Here we show that the human GTPase Dynamin 2 associates with two SH3 domains in the amino terminus of Tuba and acts together with this scaffolding protein to control spread ofL. monocytogenes. Genetic or pharmacological inhibition of Dynamin 2 or knockdown of Tuba each restored normal protrusion formation and spread to a bacterial strain deleted for theinlCgene (ΔinlC). Dynamin 2 localized to apical junctions in uninfected human cells and to protrusions in cells infected withListeria. Localization of Dynamin 2 to junctions and protrusions depended on Tuba. Knockdown of Dynamin 2 or Tuba diminished junctional linearity, indicating a role for these proteins in controlling cortical tension. Collectively, our results show that Dynamin 2 cooperates with Tuba to promote intercellular tension that restricts spread of ΔinlC Listeria. By expressing InlC, wild-typeL. monocytogenesovercomes this restriction.
Assembly of the Bacterial Ribosome with Circularly Permuted rRNA
Authors: Dong Xiyu , Sheng Kai , Gebert Luca F.R. , Aiyer Sriram , MacRae Ian J. , Lyumkis Dmitry , Williamson James R.
Published: April 2024

Co-transcriptional assembly is an integral feature of the formation of RNA-protein complexes that mediate translation. For ribosome synthesis, prior studies have indicated that the strict order of transcription of rRNA domains may not be obligatory during bacterial ribosome biogenesis, since a series of circularly permuted rRNAs are viable. In this work, we report the insights into assembly of the bacterial ribosome large subunit (LSU) based on cryo-EM density maps of intermediates that accumulate duringin vitroribosome synthesis using a set of circularly permuted (CiPer) rRNAs. The observed ensemble of twenty-three resolved ribosome large subunit intermediates reveals conserved assembly routes with an underlying hierarchy among cooperative assembly blocks. There are intricate interdependencies for the formation of key structural rRNA helices revealed from the circular permutation of rRNA. While the order of domain synthesis is not obligatory, the order of domain association does appear to proceed with a particular order, likely due to the strong evolutionary pressure on efficient ribosome synthesis. This work reinforces the robustness of the known assembly hierarchy of the bacterial large ribosomal subunit, and offers a coherent view of how efficient assembly of CiPer rRNAs can be understood in that context.
Ribosome-binding protein 1, RRBP1, maintains peroxisomal biogenesis
Authors: Fatima Kaneez , Vihinen Helena , Akpinar Bala Ani , Somborac Tamara , Jokitalo Eija , Katajisto Pekka , Konovalova Svetlana
Published: April 2024

Peroxisomes are single membrane-bound organelles essential for human health, yet the mechanism of peroxisomal biogenesis remains poorly described. Here using a systematic double screening approach, we identified ribosome-binding protein 1, RRBP1, as a novel peroxisomal biogenesis factor in human cells. We showed that the number of peroxisomes and the levels of peroxisomal proteins are reduced by RRBP1 KO in HEK293T cells. In addition, the processing of peroxisomal matrix proteins, such as ACOX1 and thiolase was affected in RRBP1 KO HEK293T cells. Using electron microscopy, we showed that RRBP1, an ER membrane protein, is involved in the maintaining of the long-distance contact sites between ER and peroxisomal membranes, suggesting that the role of RRBP1 in peroxisomal biogenesis is mediated through inter-organellar contact sites. Altogether our results showed that RRBP1 promotes peroxisomal biogenesis in human cells highlighting the power of systematic approaches in discovering novel factors of organellar biogenesis.
Self-incompatibility phenotypes of SRK mutants can be predicted with high accuracy
Authors: Yamamoto Masaya , Ohtake Shotaro , Shinosawa Akihisa , Shirota Matsuyuki , Mitsui Yuki , Kitashiba Hiroyasu
Published: April 2024

Only very limited information is available on why some non-synonymous variants severely alter gene function while others have no effect. To identify the characteristic features of mutations that strongly influence gene function, this study focused onS-locus receptor kinase,SRK, which encodes a highly polymorphic receptor kinase expressed in stigma papillary cells that underlies a female determinant of self-incompatibility in Brassicaceae. A set of 299Arabidopsis thalianatransformants expressing mutatedSRKbfromA. lyratawas constructed and analyzed to determine the genotype and self-incompatibility phenotype of each transformant. Almost all the transformants showing the self-incompatibility defect contained mutations in AlSRKb that altered localization to the plasma membrane. The observed mutations occurred in amino acid residues that were highly conserved acrossShaplotypes and whose predicted locations were in the interior of the protein. These mutations were likely to underlie the self-incompatibility defect as they caused significant changes to amino acid properties. Such findings suggested that mutations causing the self-incompatibility defect were more likely to result from changes to AlSRKb biosynthesis than from loss of function. In addition, this study showed the RandomForest and Extreme Gradient Boosting methods could predict self-incompatibility phenotypes of SRK mutants with high accuracy.
Lung megakaryocytes are long-lived, arise from Flt3-negative bone marrow cells, and contribute to platelet recovery in thrombocytopenia
Authors: Livada Alison C. , McGrath Kathleen E. , Malloy Michael , Li Chen , Ture Sara K. , Kingsley Paul D. , Koniski Anne D. , Vit Leah A. , Nolan Katherine E. , Mickelsen Deanne , Monette Grace E. , Maurya Preeti , Palis James , Morrell Craig N.
Published: April 2024

We previously characterized lung megakaryocytes (Mks) as largely extravascular cells with an immune modulatory phenotype (Pariser et al., 2021). Because bone marrow (BM) Mks are relatively short lived, it is assumed that extravascular lung Mks are constantly ‘seeded’ from the BM, but there are no experimental data to validate this concept. To investigate lung Mk origin and how their origin may impact lung Mk functions, we developed novel models using CFSE dye delivered oropharyngeal (OP) and biotin labeling to specifically label lung Mks and identify lung Mk derived platelets. Labeled lung Mks were present for up to four months, while BM Mks had a less than 1 week lifespan. In a parabiosis model, lung Mks were only partially replaced by a circulating source over a 1-month time period. Unlike tissue resident lung macrophages, we determined using MDS1-Cre-ERT2TdTomato mice that lung Mks arise from a hematopoietic stem cell (HSC) source. However, studies with FlkSwitch mTmG mice showed that lung Mks originate from a Flt3-negative cell lineage, that does not go through a multipotent progenitor stage. CFSE labeling of lung cells enabled us to track lung Mk-derived platelets and we found that about 10% of circulating platelets at steady-state are lung resident Mk-derived, but in the context of sterile thrombocytopenia there was a doubling of lung Mk derived platelets (about 20%). Lung-derived platelets were similarly increased in a murine malaria infection model (Plasmodium yoelii) typified by chronic thrombocytopenia. Taken together, our studies indicate that lung Mks arise from a Flt3-negative, HSC-dependent pathway and contribute relatively more platelets during thrombocytopenia.
Fine-Structure Qubit Encoded in Metastable Strontium Trapped in an Optical Lattice
Authors: Pucher S. , Klüsener V. , Spriestersbach F. , Geiger J. , Schindewolf A. , Bloch I. , Blatt S.
Published: April 2024

We demonstrate coherent control of the fine-structure qubit in neutral strontium atoms. This qubit is encoded in the metastable P23 and P03 states, coupled by a Raman transition. Using a magnetic quadrupole transition, we demonstrate coherent state initialization of this THz qubit. We show Rabi oscillations with more than 60 coherent cycles and single-qubit rotations on the μs scale. With spin echo, we demonstrate coherence times of tens of ms. Our results pave the way for fast quantum information processors and highly tunable quantum simulators with two-electron atoms.

Published by the American Physical Society
2024
How to reduce construction risks in rural areas: an evolutionary game analysis
Authors: Chen Wei , Yang Zhuzhang , Yan Hang , Zhao Ying
Published: April 2024

Purpose

The construction industry is widely recognized as one of the most hazardous sectors in the world. Despite extensive research on safety management, a critical issue remains that insufficient attention is devoted to safety practices in rural areas. Notably, accidents frequently occur during the construction of rural self-built houses (RSH) in China. Safety management tends to be overlooked due to the perceived simplicity of the construction process. Furthermore, it is essential to acknowledge that China currently lacks comprehensive laws and regulations governing safety management in RSH construction. This paper aims to analyze the behavior of key stakeholders (including households, workmen, rural village committee and the government) and propose recommendations to mitigate safety risks associated with RSH construction.

Design/methodology/approach

This paper applies evolutionary game theory to analyze the symbiotic evolution among households, workmen and rural village committee, in situations with or without government participation. Additionally, numerical simulation is utilized to examine the outcomes of various strategies implemented by the government.

Findings

Without government participation, households, workmen, and rural village committee tend to prioritize maximizing apparent benefits, often overlooking the potential safety risks. Numerical simulations reveal that while government involvement can guide these parties towards safer decisions, achieving the desired outcomes necessitates the adoption of reasonable and effective strategies. Thus, the government needs to offer targeted subsidies to these stakeholders.

Originality/value

Considering that during the construction phase, stakeholders are the main administrators accountable for safety management. However, there exists insufficient research examining the impact of stakeholder behavior on RSH construction safety. This study aims to analyze the behavior of stakeholders about how to reduce the safety risks in building RSH. Thus, the authors intend to contribute to knowledge in this area by establishing evolutionary game model. Firstly, this study carried out a theoretical by using tripartite evolutionary game to reveal the reasons for the high safety risk during building RSH. Practically, this research points out the important role of households, workmen and rural village committee in improving safety management in rural areas. Besides, some suggestions are proposed to the government about how to reduce construction safety risks in rural areas.
The influence of dark triad on knowledge hiding behavior with workplace spirituality as a moderator in higher education institutions
Authors: Joshi Parikshit , Singh Anshu , Joshi Garima , Singh Preeti
Published: April 2024

Purpose

In the knowledge management (KM) literature, there are umpteen discussions on knowledge sharing; however, the scholarly community still faces a dearth of literature on knowledge hiding behavior (KHB) and its determinants. The current study aims to examine the direct effect of dark triad (DT) personality dimensions (machiavellianism, narcissism and psychopathy) on KHB dimensions (rationalized hiding, evasive hiding and playing dumb). Drawing on social control theory, this study also explores the moderating effect of workplace spirituality (WS) on the direct relationship between DT and KHB.

Design/methodology/approach

Using purposive sampling, 281 matched-pair datasets from faculty members working with higher education institutions (HEI) in India have been obtained. The direct relationship has been tested through regression analysis and moderation analysis has been performed using the PROCESS macro for SPSS.

Findings

The study has successfully mapped DT dimensions with KHB dimensions, and it is observed that machiavellians mostly use evasive hiding, narcissists believe in rationalized hiding and paying dumb is mostly used by psychopaths. Workplace spirituality (WS) weakens the direct relationship between DT and KHB.

Practical implications

HEIs are advised to foster a climate conducive to WS by getting faculty to realize that their job is something larger than themselves through developing a sense of community among faculty members.

Originality/value

This empirical study extends the KM literature and expands the scope of bridging the gaps on KHB. It is one of the few studies to examine the impact of DT on KHB with WS as a moderator in HEIs.
The role of Sharia governance in minimizing credit risk in Islamic banking: a systematic literature review
Authors: Minaryanti Annisa Adha , Fitrijanti Tettet , Sukmadilaga Citra , Mihajat Muhammad Iman Sastra
Published: April 2024

Purpose

The purpose of this paper is to engage in a systematic examination of previous scholarship on the relationship between Sharia governance (SG), which is represented by the Sharia Supervisory Board (SSB), and the Internal Sharia Review (ISR), to determine whether the ISR can minimize financing risk in Islamic banking.

Design/methodology/approach

The literature search consisted of two steps: a randomized and systematic literature review. The methodology adopted in this article is a systematic literature review.

Findings

To reduce the risk of financing in Islamic banking, SG must be implemented optimally by making rules regarding the role of the SSB in supervising customer financing. In addition, it is a necessary to establish an entity that assists the SSB in the implementation of SG, namely, the ISR section, but there is still very little research on the role of the SSB and ISR in minimizing financing risk.

Practical implications

Establishing an ISR to assist the SSB in carrying out its duties has direct practical implications for Islamic banking: minimizing financing risks and compliance with Islamic Sharia principles. In addition, new rules regarding the role of SSBs and the ISR in reducing credit risk include monitoring customers to ensure that they fulfill their financing commitments on time. This new form of regulation and review can be used as a reference by the Otoritas Jasa Keuangan or Finance Service Authority to create new policies or regulations regarding SG, especially in Indonesia.

Originality/value

Subsequent research may introduce other more relevant variables, such as empirically testing the competence, independence or integrity of SSB and the ISR team as it attempts to minimize the risk of financing in Islamic banks. In addition, further research is expected to examine whether the SSB or the ISR team has a positive or negative influence on the risk of financing Islamic banks with secondary data.
Does the entrepreneur intention vary among university students?
Authors: Maslakci Ahmet , Sürücü Lütfi , Şeşen Harun
Published: April 2024

Purpose

To encourage entrepreneurship, which accelerates economic growth by increasing employment opportunities and competitiveness, stakeholders must conduct studies and develop policies that consider both the current situation and future expectations. This study aims to examine the environmental and personal factors that influence students’ entrepreneurial intentions (EIs), using a model based on the theory of planned behaviour (TPB) and social cognitive theories (SCT).

Design/methodology/approach

This study proposed an institutional framework demonstrating contextual features to achieve this objective. This theoretical framework is evaluated using a sample of 375 university students in Türkiye.

Findings

The empirical findings can help policymakers develop effective policies to encourage entrepreneurship.

Research limitations/implications

The study focuses on EIs; it is possible that even if a participant indicated a high EI in the survey, they will ultimately pursue a completely different career path.

Practical implications

The study also contributes to entrepreneurship literature studies investigating the relationships between the TPB and SCT.

Social implications

By testing specific hypotheses for Türkiye, this study contributes to the demand for entrepreneurship research in countries that are major global players but have vastly different sociocultural contexts than Western countries.

Originality/value

The study draws a theoretical model that explains the factors affecting the EIs of university students and attempts to explain the EIs of university students with and without business education within this model.
The introspections of contemporary business research: a call for scientific creativity
Authors: Singh Kuldeep
Published: April 2024

Purpose

This study aims to squeeze some critical viewpoints from the shifting landscape of business research (she), that conceals her true personality. Today, she is relentlessly struggling to strike a good balance between science and creativity. Therefore, she resolves to pivot the scholarly attention towards “scientific creativity”.

Design/methodology/approach

Business research is personified in this viewpoint paper. By adopting the methodology of third-person omniscient, the author pens the introspections of contemporary business research, and how she would express herself in modern times if she were a living person.

Findings

Business research introspects that she is suffering from the phenomena of “existential crisis” and “popularity fallacy” in contemporary times. Though she believes that the science of business research is evolving significantly, worries about becoming scientifically monotonous grip her in the dark of the nights. She laments the grim reality of today; studies of a similar nature dominate the research literature while the philosopher in her is fading gradually. Therefore, she calls for more “scientific creativity”. She realises that solving societal problems must remain her foremost priority. However, she believes that her priorities towards society and world peace depend on whether she could revitalise the fading philosopher of personality.

Originality/value

The current viewpoint paper is an attempt to shed some light on the landscape of contemporary business research, which is undergoing unremitting changes. It also highlights the desirable changes in the context of business research.
Tanzania’s repeat tourists: unraveling choice of attractions patterns through demographic perspectives
Authors: Begashe Betty Amos , Mgonja John Thomas , Matotola Salum
Published: April 2024

Purpose

This study aims to explore the connection between demographic traits and the choice of attraction patterns among international repeat tourists.

Design/methodology/approach

The study employed a questionnaire survey to collect data from 1550 international repeat tourists who visited Tanzania between November 2022 and July 2023. Convenient sampling was employed as tourists were selected from the three international airports of Tanzania, namely Kilimanjaro International Airport, Julius Nyerere International Airport, and Abeid Aman Karume International Airport. A multinomial logistic regression model was used to examine the impact of socio-demographic characteristics on the selection of attraction patterns among international repeat tourists.

Findings

The study revealed that demographic factors, including age, marital status, income level, occupation, and education level, exhibit statistically significant correlations with preferences for distinct attraction patterns. This significance was established through a p-value of less than 0.05 for all the aforementioned variables.

Research limitations/implications

This study is primarily focused on international repeat tourists, thereby limiting insights into the preferences of domestic tourists. To better inform strategies aimed at attracting a larger domestic tourist base, future research may prioritize the investigation of choice of attractions patterns among domestic tourists in relation to their demographic characteristics.

Originality/value

This study contributes to the nuanced understanding of international tourist behavior by unraveling the extent to which demographic traits impact tourists’ choices of attraction patterns, thereby providing insights crucial for effective marketing strategies, improved visitor experiences, and sustainable tourism development strategies.
Evaluating layperson interpretation of actuarial sexual violence risk data: A multi‐method comparison of risk communication with attention to gender bias
Authors: Coaker Lauren C. , Batastini Ashley B. , Davis Riley M. , Lester Michael E.
Published: April 2024

Forensic clinicians are often called upon to help courts determine the likelihood that someone will continue to commit sexually violent acts in the future. The utility of these evaluations depends largely on how effectively the results are communicated to and understood by the trier of fact. Actuarial results, such as those commonly reported in sexual offense risk assessments, appear particularly challenging for laypersons to understand. Using a representative sample of 206 U.S. adults, this study examines three methods of communicating actuarial risk via simulated expert testimony on participants' ratings of a hypothetical evaluee's risk of sexual re‐offending. The results suggested that all participants, regardless of how results were communicated, over‐estimated the examinee's risk level relative to the expert's probabilistic findings, but tended to agree with the expert's categorical predictions. Participants who were only shown actuarial data consistently rated the evaluee as more dangerous and likely to commit future sexually violent acts. Additionally, it was found that gender significantly impacted participants' perceptions, such that women found the evaluee more dangerousness and desired greater social distance from him. This study has implications for best practices regarding expert communication of actuarial results in cases involving sexual violence.