bluuebunny/crossref_metadata_2025 huggingface dataset:
Feedback modulation of Orai1α and Orai1β protein content mediated by STIM proteins
Authors: Nieto-Felipe Joel , Macias-Díaz Alvaro , Jimenez-Velarde Vanesa , Lopez Jose J. , Salido Gines M. , Smani Tarik , Jardin Isaac , Rosado Juan A.
Published: March 2024

Store-operated Ca2+entry (SOCE) is a mechanism controlled by the filling state of the intracellular Ca2+stores, predominantly the endoplasmic reticulum (ER), where ER-resident proteins STIM1 and STIM2 orchestrate the activation of Orai channels in the plasma membrane, and Orai1 playing a predominant role. Two forms of Orai1, Orai1α and Orai1β, have been identified, which arises the question whether they are equally regulated by STIM proteins. We demonstrate that STIM1 preferentially activates Orai1α over STIM2, yet both STIM proteins similarly activate Orai1β. Under resting conditions, there is a pronounced association between STIM2 and Orai1α, implying their significance in maintaining basal Ca2+levels within the cytosol and ER. STIM1 and STIM2 are also shown to influence the protein levels of the Orai1 variants, independent of Ca2+influx, via lysosomal degradation. Interestingly, Orai1α and Orai1β appear to selectively regulate the protein level of STIM1, but not STIM2. These observations offer crucial insights into the regulatory dynamics between STIM proteins and Orai1 variants, enhancing our understanding of the intricate processes that fine-tune intracellular Ca2+signaling.
Technical and biological variations in the purification of extrachromosomal circular DNA (eccDNA) and the finding of more eccDNA in the plasma of lung adenocarcinoma patients compared with healthy donors
Authors: Zole Egija , Hansen Lasse Bøllehuus , Haskó János , Gerovska Daniela , Araúzo-Bravo Marcos J. , Noer Julie Boertmann , Luo Yonglun , Johansen Jakob Sidenius , Regenberg Birgitte
Published: March 2024

Human plasma DNA originates from all tissues and organs, holding the potential as a versatile marker for diseases such as cancer, as fragments of cancer-specific alleles can be found circulating in the blood. While linear DNA has been studied intensely as a liquid biomarker, the role of circular circulating DNA in cancer is more unknown due, in part, to a lack of comprehensive testing methods. Our developed method profiles extrachromosomal circular DNA (eccDNA) in plasma, integrating Solid-Phase Reversible Immobilization (SPRI) bead purification, the removal of linear DNA and mitochondrial DNA, and DNA sequencing. As an initial assessment, we examined the method, biological variations, and technical variations using plasma samples from four patients with lung adenocarcinoma and four healthy and physically fit individuals. Despite the small sample group, we observed a significant eccDNA increase in cancer patients in two independent laboratories and that eccDNA covered up to 0.4 % of the genome/mL plasma. We found a subset of eccDNA from recurrent genes present in cancer samples but not in every control. In conclusion, our data reflect the large variation found in eccDNA sequence content and show that the variability observed among replicates in eccDNA stems from a biological source and can cause inconclusive findings for biomarkers. This suggests the need to explore other biological markers, such as epigenetic features on eccDNA.
Uncovering the transcriptional molecular dynamics of shelf life extension and system acquired resistance induction toFusarium pallidoroseumin melon fruits by the use of pulsed-light
Authors: Arge Luis Willian Pacheco , Morais Guilherme Loss , Carvalho Joseane Biso , Zocolo Guilherme Julião , Oster Andréia Hansen , Vasconcelos Ana Tereza Ribeiro de , Diniz Leandro Eugenio Cardamone , Silva Ebenézer de Oliveira , Bordallo Patricia do Nascimento
Published: March 2024

Melon is a globally commercialized fruit, and Fusarium rot disease poses a significant threat to post-harvest losses. The conventional use of fungicides raises concerns about chemical residues, prompting exploration into alternative technologies such as Pulsed Light (PL). While PL has been effective in controlling infections in various fruits and vegetables, the precise physiological responses and molecular mechanisms in melon fruits remain incompletely understood. In this study, melon fruits infected with theFusarium pallidoroseumwere treated with different doses of PL (0, 6, 9, and 12 J cm−2), and the impact on both fungal control and fruit shelf life extension was investigated. The 9 J cm−2dose emerged as the most effective in controlling fungal growth without causing damage, inducing beneficial responses. This optimal PL dose upregulated genes in the lignan biosynthesis pathway and the infection upregulated genes involved with systemic acquired resistance, triggered by the pipecolic acid. In this way, the PL treatment and the infection trigger a double mechanism of resistance in melon fruits. A second and third experiment focused on evaluating the extension of melon fruit shelf life and the safe manipulation window post-PL treatment. The results revealed an average shelf life extension of six days and a safe manipulation period of 24 hours. The extension in shelf life was associated with a deviation in information flux from the ethylene biosynthesis to upregulation of the polyamine biosynthesis pathway, which produces nitric oxide, a product that can inhibit ethylene biosynthesis and its action. Furthermore, the observed 24-hour safety period against fungal infection post-PL treatment was characterized as a memory response resistance caused by the upregulation of lignan biosynthesis, which is a potential and efficient alternative to chemical products like fungicides. Overall, this study provides insights into the transcriptional molecular mechanisms through which PL promotes systemic acquired resistance and extends the shelf life of melon fruits.
Visualizing the Spatio-Temporal Dynamics of Clonal Evolution withLinG3Dsoftware
Authors: Hu Anjun , Ojwang’ Awino Maureiq E. , Olumoyin Kayode D. , Rejniak Katarzyna A.
Published: March 2024

Cancer clonal evolution, especially following anti-cancer treatments, depends on the locations of the mutated cells within the tumor tissue. Cells near the vessels, exposed to higher concentrations of drugs, will undergo a different evolutionary path than cells residing far from the vasculature in the areas of lower drug levels. However, classical representations of cell lineage trees do not account for this spatial component of emerging cancer clones. Here, we propose theLinG3D(Lineage Graphs in 3D) algorithms to trace clonal evolution in space and time. These are an open-source collection of routines (in MATLAB, Python, and R) that enables spatio-temporal visualization of clonal evolution in a two-dimensional tumor slice from computer simulations of the tumor evolution models. These routines draw traces of tumor clones in both time and space, with an option to include a projection of a selected microenvironmental factor, such as the drug or oxygen distribution within the tumor. The utility ofLinG3Dhas been demonstrated through examples of simulated tumors with different number of clones and, additionally, in experimental colony growth assay. This routine package extends the classical lineage trees, that show cellular clone relationships in time, by adding the space component to show the locations of cellular clones within the 2D tumor tissue patch from computer simulations of tumor evolution models.
Exploring the role of temperature and other environmental factors in West Nile virus incidence and prediction in California counties from 2017-2022
Authors: Parker Noah
Published: March 2024

West Nile virus (WNV) is the most common mosquito-borne disease in the United States, resulting in hundreds of reported cases yearly in California alone. The transmission cycle occurs mostly in birds and mosquitoes, making meteorological conditions, such as temperature, especially important to transmission characteristics. Given that future increases in temperature are all but inevitable due to worldwide climate change, determining associations between temperature and WNV incidence in humans, as well as making predictions on future cases, are incredibly important to public health agencies in California. Using surveillance data from the California Department of Public Health (CDPH), meteorological data from the National Oceanic and Atmospheric Administration (NOAA), and vector and host data from VectorSurv, we created GEE autoregressive and zero-inflated regression models to determine the role of temperature and other environmental factors in WNV incidence and predictions. An increase in temperature was found to be associated with an increase in incidence in 11 high-burden Californian counties between 2017-2022 (IRR = 1.06), holding location, time of year, and rainfall constant. A hypothetical increase of two degrees Fahrenheit — predicted for California by 2040 — would have resulted in upwards of 20 excess cases per year during our study period. Using 2017-2021 as a training set, meteorological and host/vector data were able to well-predict 2022 incidence, though the models did overestimate the peak number of cases. The zero-inflated model closely predicted the low number of cases in winter months but performed worse than the GEE model during high-transmission periods. These findings suggests that climate change will, and may be already, altering transmission dynamics and incidence of WNV in California, and provides tools to help predict incidence into the future.

Author Summary

West Nile Virus is a disease that is spread by mosquitoes. Though it commonly infects birds, transmission to humans is possible and can lead to severe health effects. Temperature is known to affect the transmission cycle of West Nile virus, but it is unclear how global warming might change who, or how many people, may get infected with the virus. In this study, the researchers looked at how climate change may affect West Nile virus in California, and how health officials may better be able to predict future cases. The study found that there could be an increase in West Nile virus cases in humans due to increases in temperature in the next 20 years, but that we already have many tools and sources of data to predict cases. These findings reinforce the possible consequences of climate change on human health, and aid in the understanding in the complex relationship between climate and infectious diseases.
Fine-scale oceanographic processes shape marine biodiversity patterns in the Galápagos Islands
Authors: Holman Luke E , Pazmiño Diana A. , Gopalakrishnan Shyam , Forryan Alexander , Hearn Alex R. , Naveira-Garabato Alberto C. , Rius Marc
Published: March 2024

Uncovering the drivers that shape biodiversity patterns is critical to understand ecological and evolutionary dynamics. Despite evidence that biodiversity composition is influenced by processes at different spatial scales, little is known about the role of fine-scale oceanographic processes on the structure of marine communities. This is particularly important in biodiversity hotspot regions, where small changes in environmental conditions may lead to substantial changes in species composition. We combined ocean modelling and 12S environmental DNA (eDNA) metabarcoding, targeting teleost and elasmobranch species, to explore if oceanographic processes influenced biogeographic patterns around the biodiverse Galápagos Islands. We first detected significant differences in eDNA-measured community structure across the archipelago’s diverse seascape. We found no significant relationship between Lagrangian particle tracking metrics and nektonic biodiversity, and thus developed a novel metric to measure the cumulative seawater flow resistance between pairs of geographic sites. This metric explained a significant proportion of variation in eDNA-measured beta dissimilarity between sites, comparable in influence to important abiotic drivers, such as temperature and geographic distance between sites. Cumulatively, our results indicate that marine communities are particularly sensitive to changes in local current systems, and suggest that fine-scale oceanographic processes may have an underappreciated role in structuring marine communities globally.
PRDM9 drives the location and rapid evolution of recombination hotspots in salmonids
Authors: Raynaud Marie , Sanna Paola , Joseph Julien , Clément Julie , Imai Yukiko , Lareyre Jean-Jacques , Laurent Audrey , Galtier Nicolas , Baudat Frédéric , Duret Laurent , Gagnaire Pierre-Alexandre , de Massy Bernard
Published: March 2024

In many eukaryotes, meiotic recombination occurs preferentially at discrete sites, called recombination hotspots. In various lineages, recombination hotspots are located in regions with promoter-like features and are evolutionarily stable. Conversely, in some mammals, hotspots are driven by PRDM9 that targets recombination away from promoters. Paradoxically, PRDM9 induces the self-destruction of its targets and this triggers an ultra-fast evolution of mammalian hotspots. PRDM9 is ancestral to all animals, suggesting a critical importance for the meiotic program, but has been lost in many lineages with surprisingly little effect on meiosis success. However, it is unclear whether the function of PRDM9 described in mammals is shared by other species. To investigate this, we analyzed the recombination landscape of several salmonids, the genome of which harbors one full-length PRDM9 and several truncated paralogs. We identified recombination initiation sites inOncorhynchus mykissby mapping meiotic DNA double-strand breaks (DSBs). We found that DNA DSBs clustered at hotspots positioned away from promoters, enriched for the H3K4me3 and H3K4me36 marks and the location of which depended on the genotype of full-lengthPrdm9. We observed a high level of polymorphism in the zinc finger domain of full-lengthPrdm9, but not of the truncated paralogs. Moreover, population-scaled recombination maps inO. mykiss,Oncorhynchus kisutchandSalmo salarrevealed a rapid turnover of recombination hotspots caused by PRDM9 target motif erosion. Our results imply that PRDM9 function is conserved across vertebrates and that the peculiar evolutionary runaway caused by PRDM9 has been active for several hundred million years.
Seasonal Patterns of Viromes in Urban Aquatic Environments of Manitoba
Authors: Francis Jhannelle D. , Uyaguari Miguel
Published: March 2024

Although wastewater and treatment plants harbor many pathogenic organisms’ traditional methods that monitor the microbial quality of wastewater have not changed since the early 1900s and often disregard the presence of other types of significant waterborne pathogens such as viruses. Using advanced technology, our study aims to characterize the taxonomy, functional profiling and seasonal patterns of viral DNA and RNA community structures using metagenomics and quantitative-PCR, for the purpose of establishing the virome distribution in aquatic environment’s receiving wastewater discharge. Environmental water samples were collected at 11 locations in Winnipeg, Manitoba along the Red and Assiniboine Rivers during the Spring, Summer and Fall 2021. Samples were filtered and underwent skimmed milk flocculation for viral concentration.

The taxonomic classification of DNA viruses identified from the RefSeq database (available from MG-RAST) and Kraken 2 Viral Genome database were predominately DNA bacteriophages (Myoviridae, Podoviridae and Siphoviridae) which accounted for approximately 90% of each aquatic sample location along the Red and Assiniboine Rivers. Phage related functionalities such as phage tail fiber proteins, phage replication, and phage packaging machinery accounted for 40% of each aquatic samples collected which possibly correspond to the DNA phages that were previously identified. RNA phages such asCystoviridaeandLeviviridaewere identified to a lesser extent accounting for approximately 3 % of each aquatic sample collected, while other viruses such asVirgaviridae, Retroviridae, PicobirnaviridaeandPartiviridaeaccounted for 7%–100% of aquatic samples. The functionalities of RNA viruses were primarily related to metabolic pathways such as potassium homeostasis, respiratory complexes and sialic acid metabolism, essential for RNA viruses to survive in their host.

IMPORTANCE

Municipal wastewater effluents discharged into the Red and Assiniboine Rivers of Winnipeg, Manitoba relies on traditional methods that monitor the microbial quality of wastewater focus solely on the detection of fecal bacteria, which are not necessarily good indicators of viruses or other pathogens. There is also a lack of current wastewater system effluent regulations at the federal and provincial level. Furthermore, previous literature has shown that when viral DNA and RNA sequences are blasted against current genomic databases, approximately 50 % of the viral reads are classified as unknown. The significance of our research in characterizing the virome distribution in aquatic environments addresses a knowledge gap in the current effluent guidelines and a need for regulatory practices. In the long run, fecal indicator bacteria combined with the detection of enteric viruses, may complement assessment of water quality in effluents discharged into rivers.
Adaptive admixture atACKR1(the Duffy locus) may have shapedPlasmodium vivaxprevalence in Oman
Authors: Haffener Paige E. , Al-Riyami Arwa Z. , Al-Zadjali Shoaib , Busby George B. J. , Mahdhuri Sulaiman Al , Al-Rawahi Mohammed , Hosni Saif Al , Marhoobi Ali Al , Sheriyani Ammar Al , Leffler Ellen M.
Published: March 2024

Malaria in humans is largely caused by two divergent species ofPlasmodiumparasites,P. vivaxandP. falciparum, both of which have driven the spread of protective alleles in human populations. Notably, an erythrocyte-specific Duffy null allele (FyES) confers resistance toP. vivaxmalaria and has been identified as a target of strong, recent positive selection in multiple African admixed populations. Here, we evaluate evidence for selection via adaptive admixture in Oman, where compared to neighboring countries,P. vivaxhas recently been less common. Genetic ancestry inference using whole genome sequence data from 100 Omanis suggests 9.8% (95% CI: 7.3-12.2%) of their genetic ancestry is shared with east Africa. At the Duffy locus, we find a high frequency of FyESand an increase to 76% African ancestry. Comparing with blood group serology for the same individuals, we identify an additional Duffy-null allele that is rare but present across multiple Arabian Peninsula (AP) populations. Finally, we estimate the selection coefficient at FyESas 0.031 (95% CI: 0.029-0.034) with likely introduction at least 59 generations ago, older than estimates in other African admixed populations. Although we also observe higher frequency of someP. falciparum-protective alleles in Oman than in other AP populations, African ancestry is not enriched indicating a lack of evidence for adaptive admixture driven byP. falciparumselective pressure. Together, our analyses suggest that Oman’s long history with east African populations resulted in early introduction and selection for Duffy null alleles and may have influenced the prevalence ofP. vivaxin the region.
Long distance avian migrants fail to bring 2.3.4.4b HPAI H5N1 into Australia for a second year in a row
Authors: Wille Michelle , Atkinson Robyn , Barr Ian G. , Burgoyne Charlotte , Bond Alexander L. , Boyle David , Christie Maureen , Dewar Meagan , Douglas Tegan , Fitzwater Teagan , Hassell Chris , Jessop Roz , Klaassen Hiske , Lavers Jennifer L. , Leung Katherine K.-S. , Ringma Jeremy , Sutherland Duncan R. , Klaassen Marcel
Published: March 2024

There is an ongoing and profound burden of lineage 2.3.4.4b high pathogenicity avian influenza (HPAI) H5N1 on wildlife and poultry, globally. Herein we report the continued absence of HPAI and antibodies against lineage 2.3.4.4b HPAI from October – December 2023, in migratory birds shortly after their arrival in Australia. Given the ever-changing phenotype of this virus, worldwide studies on the occurrence, or here absence of the virus, are of critical importance to understand the virus’ dispersal and incursion risk and development of response strategies.
Field size as a predictor of “excellence.” The selection of subject fields in Germany’s Excellence Initiative
Authors: Heinze Thomas , Habicht Isabel M. , Eberhardt Paul , Tunger Dirk
Published: March 2024

We investigate the selection of subject fields in Germany’s “excellence initiative,” a two-phase funding scheme administered by the German Research Foundation (DFG) from 2005 to 2017 to increase international competitiveness of scientific research at German universities. While most empirical studies have examined the “excellence initiative’s” effects at the university level (“elite universities”), we focus on subject fields within universities. Based on both descriptive and logistic regression analyses, we find that the “excellence initiative” reveals a stable social order of public universities based on organizational size, that field selection is biased toward those fields with many professors and considerable grant funding, and that funding success in the second phase largely follows decisions from the first phase. We discuss these results and suggest avenues for future research.
Dissecting depression symptoms: multi-omics clustering uncovers immune-related subgroups and cell-type specific dysregulation
Authors: Hagenberg Jonas ,   BeCOME study group,   OPTIMA study group, Brückl Tanja M. , Erhart Mira , Kopf-Beck Johannes , Ködel Maik , Rehawi Ghalia , Röh-Karamihalev Simone , Sauer Susann , Yusupov Natan , Rex-Haffner Monika , Spoormaker Victor I. , Sämann Philipp , Binder Elisabeth , Knauer-Arloth Janine
Published: March 2024

In a subset of patients with mental disorders, such as depression, low-grade inflammation and altered immune marker concentrations are observed. However, these immune alterations are often assessed by only one data type and small marker panels. Here, we used a transdiagnostic approach and combined data from two cohorts to define subgroups of depression symptoms across the diagnostic spectrum through a large-scale multi-omics clustering approach in 237 individuals. The method incorporated age, body mass index (BMI), 43 plasma immune markers and RNA-seq data from peripheral mononuclear blood cells (PBMCs). Our initial clustering revealed four clusters, including two immune-related depression symptom clusters characterized by elevated BMI, higher depression severity and elevated levels of immune markers such as interleukin-1 receptor antagonist (IL-1RA), C-reactive protein (CRP) and C-C motif chemokine 2 (CCL2 or MCP-1). In contrast, the RNA-seq data mostly differentiated a cluster with low depression severity, enriched in brain related gene sets. This cluster was also distinguished by electrocardiography data, while structural imaging data revealed differences in ventricle volumes across the clusters. Incorporating predicted cell type proportions into the clustering resulted in three clusters, with one showing elevated immune marker concentrations. The cell type proportion and genes related to cell types were most pronounced in an intermediate depression symptoms cluster, suggesting that RNA-seq and immune markers measure different aspects of immune dysregulation. Lastly, we found a dysregulation of theSERPINF1/VEGF-A pathway that was specific to dendritic cells by integrating immune marker and RNA-seq data. This shows the advantages of combining different data modalities and highlights possible markers for further stratification research of depression symptoms.
Sickle Cell Disease and Uterine Fibroids: Evaluation of the Prevalence of Fibroids across Sickle Cell Genotypes
Authors: Martin Jonathan G. , Medema Alexis M. , Rikard Blaire K. , van den Hoek Gabrielle , Chisholm Miriam
Published: March 2024

Introduction

Uterine fibroids are known to affect >80% of premenopausal American women of African descent, and sickle cell disease is known to disproportionately affect people of varying geographical ancestries, particularly those of sub-Saharan African descent. However, previous studies have suggested the two pathologies less frequently co-occur. This study aims to evaluate the prevalence of uterine fibroids in patients with sickle cell disease across a large metropolitan area in the United States.

Methods

African American women with sickle cell disease (including HbSS, HbSC, and sickle cell trait genotypes) underwent pelvic imaging (CT/MRI/ultrasound) between February 2011 and August 2018 at two large hospital systems within a single academic institution. Based on retrospective review, the prevalence of uterine fibroids among this cohort was analyzed and compared to published data of fibroid prevalence amongst African American patients without sickle cell disease.

Results

Prior data estimates that the prevalence of uterine fibroids in African American women is about 32 to 40% for those aged 32 to 35 years and up to >80% in premenopausal African American women overall. When compared to the expected prevalence in this cohort, with a median age of 31 years, women with HbSS or HbSC sickle cell disease had a significantly decreased prevalence of uterine fibroids (9.6 to 10.3%), while those with sickle cell trait reflected a prevalence (44.4%) like that of the general population.

Conclusion

There was a significantly lower prevalence of uterine fibroids in premenopausal American women of African heritage with sickle cell disease in the study cohort when compared to premenopausal American women of African heritage in the general population. This suggests a higher threshold to ascribe dysfunctional uterine bleeding in premenopausal African-American women with sickle cell disease to uterine fibroids, and a lower threshold to pursue an alternative diagnosis.
Celsr3 drives development and connectivity of the acoustic startle hindbrain circuit
Authors: Meserve Joy H. , Navarro Maria F. , Ortiz Elelbin A. , Granato Michael
Published: March 2024

In the developing brain, groups of neurons organize into functional circuits that direct diverse behaviors. One such behavior is the evolutionarily conserved acoustic startle response, which in zebrafish is mediated by a well-defined hindbrain circuit. While numerous molecular pathways that guide neurons to their synaptic partners have been identified, it is unclear if and to what extent distinct neuron populations in the startle circuit utilize shared molecular pathways to ensure coordinated development. Here, we show that the planar cell polarity (PCP)-associated atypical cadherins Celsr3 and Celsr2, as well as the Celsr binding partner Frizzled 3a/Fzd3a, are critical for axon guidance of two neuron types that form synapses with each other: the command-like neuron Mauthner cells that drive the acoustic startle escape response, and spiral fiber neurons which provide excitatory input to Mauthner cells. We find that Mauthner axon growth towards synaptic targets is vital for Mauthner survival. We also demonstrate that symmetric spiral fiber input to Mauthner cells is critical for escape direction, which is necessary to respond to directional threats. Moreover, we identify distinct roles for Celsr3 and Celsr2, as Celsr3 is required for startle circuit development while Celsr2 is dispensable, though Celsr2 can partially compensate for loss of Celsr3 in Mauthner cells. This contrasts with facial branchiomotor neuron migration in the hindbrain, which requires Celsr2 while we find that Celsr3 is dispensable. Combined, our data uncover critical and distinct roles for individual PCP components during assembly of the acoustic startle hindbrain circuit.

Highlights

The PCP cadherin Celsr3 regulates startle circuit development in zebrafish

Celsr3 and other PCP-associated proteins promote Mauthner axon growth and guidance

Celsr3 is required for spiral fiber and glia targeting to the Mauthner axon cap

Symmetric spiral fiber input to Mauthners is critical for escape direction
Subnanometer structure of medusavirus capsid during maturation using cryo-electron microscopy
Authors: Watanabe Ryoto , Song Chihong , Takemura Masaharu , Murata Kazuyoshi
Published: March 2024

Medusavirus is a giant virus classified into an independent family ofMamonoviridae. Medusavirus-infected amoebae release immature particles in addition to the virions. These particles were suggested to exhibit the maturation process of this virus, but the structure of these capsids during maturation remains unknown. Here, we applied a block-based reconstruction method in cryo-electron microscopy (cryo-EM) single particle analysis to these viral capsids, extending these resolutions to 7-10 Å. The map revealed a novel network consisted of minor capsid proteins (mCPs), supporting major capsid proteins (MCPs). A predicted molecular model of the MCP fitted into the cryo-EM map clarified the boundaries between the MCP and the underlining mCPs and between the MCP and the outer spikes, identifying the molecular interactions between the MCP and these components. Several structural changes of mCPs were observed beneath the 5-fold vertices of immature particles, depending on the presence or absence of the underlying internal membrane. Furthermore, the lower part of penton proteins on the 5-fold vertices were also lost in the mature virions. These dynamic structural changes of mCPs exhibit important functions in the maturation process of medusavirus.

Importance

Structural changes in giant virus capsids during maturation have not been known. Medusavirus is a unique giant virus, where amoebae infected with the virus release immature particles in addition to mature virions. In this study, immature and mature medusavirus particles were investigated using cryo-electron microscopy, and firstly reported the structural changes in the viral capsid during maturation. In DNA empty particles, the conformation of the minor capsid proteins dynamically changed depending on the presence or absence of the underlying internal membranes. In DNA full particles, the lower part of the penton proteins was lost. These are the first report of the structural changes in the viral capsid during giant virus maturation.
Endogenous oligomer formation underlies DVL2 condensates and promotes Wnt/β-catenin signaling
Authors: Ntourmas Senem , Sachs Martin , Paclíková Petra , Brückner Martina , Bryja Vítĕzslav , Behrens Jürgen , Bernkopf Dominic B.
Published: March 2024

Activation of the Wnt/β-catenin pathway crucially depends on polymerization of dishevelled 2 (DVL2) into biomolecular condensates. However, given the low affinity of known DVL2 self-interaction sites and its low cellular concentration it is unclear how polymers can form. Here, we detect oligomeric DVL2 complexes at endogenous protein levels, using a biochemical ultracentrifugation assay. We identify a low-complexity region (LCR4) in the C-terminus whose deletion and fusion decreased and increased the complexes, respectively. Notably, LCR4-induced complexes correlated with the formation of microscopically visible multimeric condensates. Adjacent to LCR4, we mapped a conserved domain (CD2) promoting condensates only. Molecularly, LCR4 and CD2 mediated DVL2 self-interaction via aggregating residues and phenylalanine stickers, respectively. Point mutations inactivating these interaction sites impaired Wnt pathway activation by DVL2. Our study discovers DVL2 complexes with functional importance for Wnt/β-catenin signaling. Moreover, we provide evidence that DVL2 condensates form in two steps by pre-oligomerization via high-affinity interaction sites, such as LCR4, and subsequent condensation via low-affinity interaction sites, such as CD2.
HPV18 E7 inhibits LATS1 kinase and activates YAP1 by degrading PTPN14
Authors: Blakely William J. , Hatterschide Joshua , White Elizabeth A.
Published: March 2024

High-risk human papillomavirus (HPV) oncoproteins inactivate cellular tumor suppressors to reprogram host cell signaling pathways. HPV E7 proteins bind and degrade the tumor suppressor PTPN14, thereby promoting the nuclear localization of the YAP1 oncoprotein and inhibiting keratinocyte differentiation. YAP1 is a transcriptional coactivator that drives epithelial cell stemness and self-renewal. YAP1 activity is inhibited by the highly conserved Hippo pathway, which is frequently inactivated in human cancers. MST1/2 and LATS1/2 kinases form the core of the Hippo kinase cascade. Active LATS1 kinase is phosphorylated on threonine 1079 and inhibits YAP1 by phosphorylating it on amino acids including serine 127. Here, we tested the effect of high-risk (carcinogenic) HPV18 E7 on Hippo pathway activity. We found that either PTPN14 knockout or PTPN14 degradation by HPV18 E7 decreased phosphorylation of LATS1 T1079 and YAP1 S127 in human keratinocytes and inhibited keratinocyte differentiation. Conversely, PTPN14-dependent differentiation required LATS kinases and certain PPxY motifs in PTPN14. Neither MST1/2 kinases nor the putative PTPN14 phosphatase active site were required for PTPN14 to promote differentiation. Taken together, these data support that PTPN14 inactivation or degradation of PTPN14 by HPV18 E7 reduce LATS1 activity, promoting active YAP1 and inhibiting keratinocyte differentiation.

SIGNIFICANCE

The Hippo kinase cascade inhibits YAP1, an oncoprotein and driver of cell stemness and self-renewal. There is mounting evidence that the Hippo pathway is targeted by tumor viruses including human papillomavirus. The high-risk HPV E7 oncoprotein promotes YAP1 nuclear localization and the carcinogenic activity of high-risk HPV E7 requires YAP1 activity. Blocking HPV E7-dependent YAP1 activation could inhibit HPV-mediated carcinogenesis, but the mechanism by which HPV E7 activates YAP1 has not been elucidated. Here we report that by degrading the tumor suppressor PTPN14, HPV18 E7 inhibits LATS1 kinase, reducing inhibitory phosphorylation on YAP1. These data support that an HPV oncoprotein can inhibit Hippo signaling to activate YAP1 and strengthen the link between PTPN14 and Hippo signaling in human epithelial cells.
Symmetry Breaking and Ascending in the Magnetic Kagome Metal FeGe
Authors: Wu Shangfei , Klemm Mason L. , Shah Jay , Ritz Ethan T. , Duan Chunruo , Teng Xiaokun , Gao Bin , Ye Feng , Matsuda Masaaki , Li Fankang , Xu Xianghan , Yi Ming , Birol Turan , Dai Pengcheng , Blumberg Girsh
Published: March 2024

Spontaneous symmetry breaking—the phenomenon in which an infinitesimal perturbation can cause the system to break the underlying symmetry—is a cornerstone concept in the understanding of interacting solid-state systems. In a typical series of temperature-driven phase transitions, higher-temperature phases are more symmetric due to the stabilizing effect of entropy that becomes dominant as the temperature is increased. However, the opposite is rare but possible when there are multiple degrees of freedom in the system. Here, we present such an example of a symmetry-ascending phenomenon upon cooling in a magnetic kagome metal FeGe by utilizing neutron Larmor diffraction and Raman spectroscopy. FeGe has a kagome lattice structure with simple A-type antiferromagnetic order below Néel temperature TN≈400  K and a charge density wave (CDW) transition at TCDW≈110  K, followed by a spin-canting transition at around 60 K. In the paramagnetic state at 460 K, we confirm that the crystal structure is indeed a hexagonal kagome lattice. On cooling to around TN, the crystal structure changes from hexagonal to monoclinic with in-plane lattice distortions on the order of 10−4 and the associated splitting of the double-degenerate phonon mode of the pristine kagome lattice. Upon further cooling to TCDW, the kagome lattice shows a small negative thermal expansion, and the crystal structure gradually becomes more symmetric upon further cooling. A tendency of increasing the crystalline symmetry upon cooling is unusual; it originates from an extremely weak structural instability that coexists and competes with the CDW and magnetic orders. These observations are against the expectations for a simple model with a single order parameter and hence can only be explained by a Landau free energy expansion that takes into account multiple lattice, charge, and spin degrees of freedom. Thus, the determination of the crystalline lattice symmetry as well as the unusual spin-lattice coupling is a first step towards understanding the rich electronic and magnetic properties of the system, and it sheds new light on intertwined orders where the lattice degree of freedom is no longer dominant.

Published by the American Physical Society
2024
Risk analysis of electrical power grids in India using best-worst method and grey causal modelling
Authors: Yash Dhobale , Rajesh R.
Published: March 2024

Purpose

The study aims to identify the possible risk factors for electricity grids operational disruptions and to determine the most critical and influential risk indicators.

Design/methodology/approach

A multi-criteria decision-making best-worst method (BWM) is employed to quantitatively identify the most critical risk factors. The grey causal modeling (GCM) technique is employed to identify the causal and consequence factors and to effectively quantify them. The data used in this study consisted of two types – quantitative periodical data of critical factors taken from their respective government departments (e.g. Indian Meteorological Department, The Central Water Commission etc.) and the expert responses collected from professionals working in the Indian electric power sector.

Findings

The results of analysis for a case application in the Indian context shows that temperature dominates as the critical risk factor for electrical power grids, followed by humidity and crop production.

Research limitations/implications

The study helps to understand the contribution of factors in electricity grids operational disruptions. Considering the cause consequences from the GCM causal analysis, rainfall, temperature and dam water levels are identified as the causal factors, while the crop production, stock prices, commodity prices are classified as the consequence factors. In practice, these causal factors can be controlled to reduce the overall effects.

Practical implications

From the results of the analysis, managers can use these outputs and compare the risk factors in electrical power grids for prioritization and subsequent considerations. It can assist the managers in efficient allocation of funds and manpower for building safeguards and creating risk management protocols based on the severity of the critical factor.

Originality/value

The research comprehensively analyses the risk factors of electrical power grids in India. Moreover, the study apprehends the cause-consequence pair of factors, which are having the maximum effect. Previous studies have been focused on identification of risk factors and preliminary analysis of their criticality using autoregression. This research paper takes it forward by using decision-making methods and causal analysis of the risk factors with blend of quantitative and expert response based data analysis to focus on the determination of the criticality of the risk factors for the Indian electric power grid.
Is more always better? The influences of guanxi beliefs, participative decision-making and perceived organizational politics on HK and US nurses’ job satisfaction
Authors: Chen Yu-Ping , Shaffer Margaret , Joplin Janice R.W. , Posthuma Richard
Published: March 2024

Purpose

Drawing on the challenge–hindrance stressor framework and the “too-much-of-a-good-thing” principle, this study examined the curvilinear effects of two emic social challenge stressors (guanxi beliefs and participative decision-making (PDM)) and the moderating effect of an etic social hindrance stressor (perceived organizational politics) on Hong Kong and United States nurses’ job satisfaction.

Design/methodology/approach

A quantitative survey method was implemented, with the data provided by 355 Hong Kong nurses and 116 United States nurses. Structural equation modeling was used to examine the degree of measurement equivalence across Hong Kong and US nurses. The proposed model and the research questions were tested using nonlinear structural equation modeling analyses.

Findings

The results show that while guanxi beliefs only showed an inverted U-shaped relation on Hong Kong nurses’ job satisfaction, PDM had an inverted U-shaped relation with both Hong Kong and United States nurses’ job satisfaction. The authors also found that Hong Kong nurses experienced the highest job satisfaction when their guanxi beliefs and perceived organization politics were both high.

Research limitations/implications

The results add to the comprehension of the nuances of the often-held assumption of linearity in organizational sciences and support the speculation of social stressors-outcomes linkages.

Practical implications

Managers need to recognize that while the nurturing and development of effective relationships with employees via social interaction are important, managers also need to be aware that too much guanxi and PDM may lead employees to feel overwhelmed with expectations of reciprocity and reconciliation to such an extent that they suffer adverse outcomes and become dissatisfied with their jobs.

Originality/value

First, the authors found that influences of guanxi beliefs and PDM are not purely linear and that previous research may have neglected the curvilinear nature of their influences on job satisfaction. Second, the authors echo researchers’ call to consider an organization’s political context to fully understand employees’ attitudes and reactions toward social interactions at work. Third, the authors examine boundary conditions of curvilinear relationships to understand the delicate dynamics.
Do military expenditures have an impact on the adoption of renewable energy in OECD nations? Evidence from a panel cointegration test approach
Authors: Kilinc-Ata Nurcan , Barut Abdulkadir , Citil Mücahit
Published: March 2024

Purpose

Today, many industries are implementing creative approaches in response to increasing environmental awareness. It is of great importance to answer the question of whether the military sector, one of the most important sectors, can support renewable energy (RE) adaptation. This study aims to examine how military spending affects the supply of RE in 27 Organization for Economic Cooperation and Development (OECD) nations as well as the regulatory function of factors such as innovation, international trade and oil prices between 1990 and 2021.

Design/methodology/approach

The study examines the effects of military spending, income, green innovation, international trade, oil prices and the human development index on the supply of RE using various econometric approaches, which are the cointegration test, moments quantile regression and robustness test.

Findings

The findings demonstrate that all factors, excluding military spending, quite likely affect the expansion of the renewable supply. Military spending negatively influences the RE supply; specifically, a 1% increase in military spending results in a 0.88 reduction in the renewable supply. In addition, whereas income elasticity, trade and human development index in OECD nations are higher in the last quantiles of the regression than in the first quantiles, the influence of military spending and innovation on renewable supply is about the same in all quantiles.

Practical implications

OECD nations must consider the practical implications, which are essential to assess and update the military spending of OECD countries from a green energy perspective to transition to clean energy. Based on the study’s overall findings, the OECD countries should incorporate the advantages of innovation, economic growth and international trade into their clean energy transition strategies to lessen the impact of military spending on renewables.

Originality/value

The study aims to fill a gap in the literature regarding the role of military expenditures in the RE development of an OECD country. In addition, the results of the methodological analysis can be used to guide policymakers on how military spending should be in the field of RE.
Economic and non-economic determinants of renewable energy consumption (REC): evidence from BRICS nations
Authors: Gogoi Mayuri , Hussain Farah
Published: March 2024

Purpose

This study aims to identify the various economic and non-economic determinants of renewable energy consumption (REC) in Brazil, Russia, India, China and South Africa (BRICS). Due to the adverse effect of carbon emission on the environment, every country is trying for a transition from fossil fuel towards renewable energy. Renewable energy plays a crucial role in reducing carbon emission and combating climate change. Understanding the determinants that influence REC helps to promote this transition.

Design/methodology/approach

The study is based on an unbalanced panel data over the period 2002–2019 for all five BRICS nations. The panel corrected standard error (PCSE) method has been adopted to examine the determinants of REC.

Findings

Industrialization, population growth and foreign direct investment (FDI) are found to be significant economic determinants of REC while patent on environmental technologies, political instability and industrial design are significant non-economic determinants of REC in the BRICS nations.

Research limitations/implications

The findings imply that to increase REC in BRICS nations, policymakers should incentivize industries for investments in renewable energy, attract FDI aligned with environmental regulations, raise population awareness through training, enforce industrial design standards, establish fair technology transfer frameworks to overcome patent barriers and create stable, long-term renewable energy policies with risk mitigation instruments to address political instability.

Originality/value

The study captures the effect of patents on environmental technologies and industrial design on the consumption of renewable energy. Thus, the novelty lies in investigating unexplored variables in the previous literature likely to affect REC.
Improving performance evaluation based on the balanced scorecard with data envelopment analysis and game theory approaches: a case study
Authors: Abedian Mansour , Shirouyehzad Hadi , Davoodi Sayyed Mohammad Reza
Published: March 2024

Purpose

This paper aims to propose an integrated use of balanced scorecard (BSC), data envelopment analysis (DEA) and game theory approach as an enhanced performance measurement technique to determine and rank the importance of manufacturing indicators of a steel company as a real case study.

Design/methodology/approach

An efficiency change ratio is defined to examine the characteristic function of each coalition which is super-additive. Then, the Shapley value index is used as the solution of the cooperative game to determine the importance of the BSC indicators of the company and rank order them.

Findings

The results reveal that “profitability rate” is the most important BSC indicator, whereas “customer satisfaction” is the least significant one. The ranking order of the importance of all BSC indicators makes it possible for the senior managers of the organization to realize the importance of each index separately and to improve the profitability and the number of customers by presenting programs according to the budget and time constraints.

Originality/value

The main contribution of this paper lies in the adoption of a game theory approach to performance measurement in the industrial sector that determines and ranks the importance of manufacturing indicators.