bluuebunny/crossref_metadata_2025 huggingface dataset:
Aberrant Local Synchrony in Distinct Mouse Models of Epileptic Encephalopathy
Authors: Ressler Andrew K. , Dugger Sarah A. , Colombo Sophie , Petri Sabrina , Krizay Daniel , Frankel Wayne N. , Goldstein David B. , Boland Michael J.
Published: October 2023

Identifying and quantifying synchronous activity of primary neuronal networks using multielectrode arrays (MEAs) can potentially provide a medium-throughput platform to screen potential therapeutics for genetic epileptic encephalopathies (EEs). However, successfully identifying screenable synchrony phenotypesin vitroposes significant experimental and analytical challenges. Primary neuronal cultures quickly become highly synchronous and certain measures of synchrony tend to peak and plateau, while other network activity features remain dynamic. High levels of synchrony may confound the ability to identify reproducible phenotypesin vitrofor a subset of EEs. Reducing, or delaying the onset of, high levels of synchronyin vitromay increase the dynamic range of global synchrony measures to identify disease-relevant phenotypesin vitro,but such measures have not been established. We hypothesized that an emphasis on local (nearby) connectivity could elucidate reproducible disease-relevant synchrony phenotypes in cortical cultures not identified by current approaches. We show clear evidence of enriched local synchrony in 48-well MEAs that varies in amplitude during development of neuronal networks. Then, we show new topological-based measures are capable of identifying novel phenotypes of aberrant synchrony in distinct mouse models of EEs. Such topological synchrony measures may provide screenable phenotypes for certain brain diseases and may be further enhanced by experimental innovation reducing global levels of synchrony in primary neuronal networks.

Significance

In vitrosynchrony phenotypes may provide disease-relevant features that can be used for screening potential therapeutic candidates for epileptic encephalopathies. Here, we incorporate inter-electrode distance to generate tools capable of identifying novel synchrony phenotypes in distinct neurodevelopmental disorders. We additionally report robust topological and globalin vitrosynchrony phenotypes, alongsidein vivosynchrony phenotypes inStxbp1+/-mice. While singular features of disease in anin vitromodel are unlikely to effectively test therapeutic candidates, compounds that reverse a larger subset of distinct features may translate to human patients, suggesting such a model may be ideally suited for therapeutic development using MEAs. Across multiple disease models, the topological tools developed here are complimentary to and expand upon those within meaRtools (Gelfman 2018), which is a suite of computational tools to identify network phenotypes using MEAs.
Deep-mining of vertebrate genomes reveals an unexpected diversity of endogenous viral elements
Authors: Barreat Jose Gabriel Nino , Katzourakis Aris
Published: October 2023

Endogenous viral elements (EVEs) are key to our understanding of the diversity, host range and evolutionary history of viruses. Given the increasing amounts of virus and host sequence data, a systematic search for EVEs is becoming computationally challenging. We used ElasticBLAST on the Google Cloud Platform to perform a comprehensive search for EVEs (kingdomsShotokuviraeandOrthornavirae) across vertebrates. We provide evidence for the first EVEs belonging to the familiesChuviridae,Paramyxoviridae,NairoviridaeandBenyviridaein vertebrate genomes. We also find an EVE from theHepacivirusgenus of flaviviruses with orthology across murine rodents. Phylogenetic analysis of hits closely related to reptarenavirus and filovirus ectodomains suggest three independent captures from a retroviral source. Our findings increase the family-level diversity of non-retroviral EVEs in vertebrates by 44%. In particular, our results shed light on key aspects of the natural history and evolution of viruses in the phylaNegarnaviricotaandKitrinoviricota.
Natural variation in oxytocin receptor signaling causes widespread changes in brain transcription: a link to the natural killer gene complex
Authors: Boender Arjen J. , Johnson Zachary V. , Gruenhagen George W. , Horie Kengo , Hegarty Brianna E. , Streelman Jeffrey T. , Walum Hasse , Young Larry J.
Published: October 2023

Oxytocin (OXT) is a highly conserved neuropeptide that modulates social cognition, and variation in its receptor gene (Oxtr) is associated with divergent social phenotypes. The cellular mechanisms connectingOxtrgenotype to social phenotype remain obscure. We exploit an association betweenOxtrpolymorphisms and striatal-specific OXTR density in prairie voles to investigate how OXTR signaling influences the brain transcriptome. We discover widespread, OXTR signaling- dependent transcriptomic changes. Interestingly, OXTR signaling robustly modulates gene expression of C-type lectin-like receptors (CTLRs) in the natural killer gene complex, a genomic region associated with immune function. CTLRs are positioned to control microglial synaptic pruning; a process important for shaping neural circuits. Similar relationships betweenOXTRRNA and CTLR gene expression were found in human striatum. These data suggest a potential molecular mechanism by which variation in OXTR signaling due to genetic background and/or life-long social experiences, including nurturing/neglect, may affect circuit connectivity and social behavior.
Impact of repeated cryopreservation on embryo health and implantation potential
Authors: Li Tong , Li Shan , Chow Darren J.X. , Rose Ryan D. , Tan Tiffany C.Y. , Dunning Kylie R.
Published: October 2023

In IVF clinics, preimplantation genetic testing (PGT) is a common practice that involves a biopsy and cryopreservation of embryos for genetic evaluation. When testing fails – or is required for already cryopreserved embryos – multiple freeze-thaw cycles occur. Though known to impact live birth rates, the exclusive influence of cryopreservation has not been elucidated. Here, we evaluate the effect of repeated cryopreservation on embryo health and implantation potential.

Blastocyst-stage murine embryos were subjected to one, two or three freeze-thaw cycles with fresh embryos serving as a control. Outcomes assessed included post-thaw survival rate, allocation of cells to the inner cell mass (ICM)vs. trophectoderm cell lineages, implantation potential and offspring health.

Post-thawing, embryos that were subjected to three freeze-thaw cycles had a significantly lower survival rates compared to embryos that had undergone one cycle (P<0.001). Additionally, the number of ICM cells was significantly reduced in embryos subjected to two or three freeze-thaw cycles compared to fresh or single-cycle embryos (P<0.001). No statistically significant differences were found for pregnancy rate, number of implantations, viable fetuses or resorption sites between treatment groups. We did however, find a non-significant yet interesting trend: three freeze-thaw cycles were associated with a 20% decrease in viable fetuses and a 20% increase in resorption sites compared to one freeze-thaw cycle group.

These findings demonstrate that repeated cryopreservation adversely affects embryo health and may decrease implantation potential. Consequently, caution is advised regarding the repeated application of cryopreservation in IVF clinics, underscoring the need for further research to optimise cryopreservation protocols.
Atypical Protein Kinase C Promotes its own Asymmetric Localisation by Phosphorylating Cdc42 in theC. eleganszygote
Authors: Packer John , Gubieda Alicia G. , Brooks Aaron , Deutz Lars N. , Squires Iolo , Ellison Shona , Schneider Claudia , Naganathan Sundar Ram , Wollman Adam J.M. , Dickinson Daniel J. , Rodriguez Josana
Published: October 2023

Atypical protein kinase C (aPKC) is a major regulator of cell polarity. Acting in conjunction with Par6, Par3 and the small GTPase Cdc42, aPKC becomes asymmetrically localised and drives the polarisation of cells. aPKC activity is crucial for its own asymmetric localisation, suggesting a hitherto unknown feedback mechanism contributing to polarisation. Here we show in theC. eleganszygote that the feedback relies on aPKC phosphorylation of Cdc42 at serine 71. The turnover of CDC-42 phosphorylation ensures optimal aPKC asymmetry and activity throughout polarisation by tuning Par6/aPKC association with Par3 and Cdc42. Moreover, turnover of Cdc42 phosphorylation regulates actomyosin cortex dynamics that are known to drive aPKC asymmetry. Given the widespread role of aPKC and Cdc42 in cell polarity, this form of self-regulation of aPKC may be vital for the robust control of polarisation in many cell types.

Key findings/graphical abstract

- Phosphorylation of CDC-42 by aPKC accelerates aPKC dissociation from CDC-42, limiting aPKC activity

- CDC-42/aPKC dissociation promotes aPKC association with PAR-3 and, thereby, aPKC asymmetry due to actomyosin flow

- Cycling of CDC-42 phosphorylation fuels the exchange of aPKC between anteriorly transported PAR-3 and aPKC-active CDC-42 complexes

- Turnover of CDC-42 phosphorylation alternates its association with effectors, aPKC and MRCK-1, ensuring proper actomyosin dynamics
ATR promotes mTORC1 activity viade novocholesterol synthesis
Authors: Tangudu Naveen Kumar , Grumet Alexandra N. , Fang Richard , Buj Raquel , Cole Aidan R. , Uboveja Apoorva , Amalric Amandine , Yang Baixue , Huang Zhentai , Happe Cassandra , Sun Mai , Gelhaus Stacy L. , MacDonald Matthew L. , Hempel Nadine , Snyder Nathaniel W. , Kedziora Katarzyna M. , Valvezan Alexander J. , Aird Katherine M.
Published: October 2023

DNA damage and cellular metabolism exhibit a complex interplay characterized by bidirectional feedback mechanisms. Key mediators of the DNA damage response and cellular metabolic regulation include Ataxia Telangiectasia and Rad3-related protein (ATR) and the mechanistic Target of Rapamycin Complex 1 (mTORC1), respectively. Previous studies have established ATR as a regulatory upstream factor of mTORC1 during replication stress; however, the precise mechanisms by which mTORC1 is activated in this context remain poorly defined. Additionally, the activity of this signaling axis in unperturbed cells has not been extensively investigated. Here, we demonstrate that ATR promotes mTORC1 activity across various cellular models under basal conditions. This effect is particularly enhanced in cells following the loss of p16, which we have previously associated with hyperactivation of mTORC1 signaling and here found have increased ATR activity. Mechanistically, we found that ATR promotesde novocholesterol synthesis and mTORC1 activation through the upregulation of lanosterol synthase (LSS), independently of both CHK1 and the TSC complex. Furthermore, the attenuation of mTORC1 activity resulting from ATR inhibition was rescued by supplementation with lanosterol or cholesterol in multiple cellular contexts. This restoration corresponded with enhanced localization of mTOR to the lysosome. Collectively, our findings demonstrate a novel connection linking ATR and mTORC1 signaling through the modulation of cholesterol metabolism.
Trait selection strategy in multi-trait GWAS: Boosting SNPs discoverability
Authors: Suzuki Yuka , Ménager Hervé , Brancotte Bryan , Vernet Raphaël , Nerin Cyril , Boetto Christophe , Auvergne Antoine , Linhard Christophe , Torchet Rachel , Lechat Pierre , Troubat Lucie , Cho Michael H. , Bouzigon Emmanuelle , Aschard Hugues , Julienne Hanna
Published: October 2023

Since the first Genome-Wide Association Studies (GWAS), thousands of variant-trait associations have been discovered. However, the sample size required to detect additional variants using standard univariate association screening is increasingly prohibitive. Multi-trait GWAS offers a relevant alternative: it can improve statistical power and lead to new insights about gene function and the joint genetic architecture of human phenotypes. Although many methodological hurdles of multi-trait testing have been discussed, the strategy to select trait, among overwhelming possibilities, has been overlooked. In this study, we conducted extensive multi-trait tests using JASS (Joint Analysis of Summary Statistics) and assessed which genetic features of the analysed sets were associated with anincreased detection of variants as compared to univariate screening. Our analyses identified multiple factors associated with the gain in the association detection in multi-trait tests. Together, these factors of the analysed sets are predictive of the gain of the multi-trait test (Pearson’s ρ equal to 0.43 between the observed and predicted gain,P< 1.6 × 10-60). Applying an alternative multi-trait approach (MTAG, multi-trait analysis of GWAS), we found that in most scenarios but particularly those with larger numbers of traits, JASS outperformed MTAG. Finally, we benchmark several strategies to select set of traits including the prevalent strategy of selecting clinically similar traits, which systematically underperformed selecting clinically heterogenous traits or selecting sets that issued from our data-driven models. This work provides a unique picture of the determinant of multi-trait GWAS statistical power and outline practical strategies for multi-trait testing.
Pervasive relaxed selection on spermatogenesis genes coincident with the evolution of polygyny in gorillas
Authors: Bowman Jacob D. , Silva Neide , Schüftan Erik , Almeida Joana M. , Brattig-Correia Rion , Oliveira Raquel A. , Tüttelmann Frank , Enard David , Navarro-Costa Paulo , Lynch Vincent J.
Published: October 2023

Gorillas have a polygynous social system in which the highest-ranking male has almost exclusive access to females and sires most of the offspring in the troop. Such behavior results in a dramatic reduction of sperm competition, which is ultimately associated with numerous traits that cause low efficacy of gorilla spermatogenesis. However, the molecular basis behind the remarkable erosion of the gorilla male reproductive system remains unknown. Here, we explored the genetic consequences of the polygynous social system in gorillas by testing for altered selection intensity across 13,310 orthologous protein-coding genes from 261 Eutherian mammals. We identified 578 genes with relaxed purifying selection in the gorilla lineage, compared with only 96 that were positively selected. Genes under relaxed purifying selection in gorillas have accumulated numerous deleterious amino acid substitutions, their expression is biased towards male germ cells, and are enriched in functions related to meiosis and sperm biology. We tested the function of gorilla relaxed genes previously not implicated in sperm biology using theDrosophilamodel system and identified 41 novel spermatogenesis genes required for normal fertility. Furthermore, by exploring exome/genome sequencing data of infertile men with severe spermatogenic impairment, we found that the human orthologs of the gorilla relaxed genes are enriched for loss-of-function variants in infertile men. These data provide compelling evidence that reduced sperm competition in gorillas is associated with relaxed purifying selection on genes related to male reproductive function. The accumulation of deleterious mutations in these genes likely provides the mechanistic basis behind the low efficacy of gorilla spermatogenesis and uncovers new candidate genes for human male infertility.
Engineered Reversible Inhibition of SpyCatcher Reactivity Enables Rapid Generation of Bispecific Antibodies
Authors: Hentrich Christian , Putyrski Mateusz , Hanuschka Hanh , Preis Waldemar , Kellmann Sarah-Jane , Wich Melissa , Cavada Manuel , Hanselka Sarah , Ylera Francisco
Published: October 2023

The precise regulation of protein function is essential in biological systems, and achieving such control is a fundamental objective in the fields of chemical biology and protein engineering. Here, we describe a straightforward method to engineer functional control into the isopeptide bond-forming SpyTag/SpyCatcher protein ligation system. First, we performed a cysteine scan of SpyCatcher, exchanging each amino acid in the structured region against cysteine. Except for the two known reactive and catalytic residues, none of these mutations abolished reactivity. In a second screening step, we modified the cysteines with disulfide bond-forming small molecules and screened for reactivity again. Here we found 8 positions that, when modified, strongly inhibited reactivity. This inhibition could be reversed by treatment with reducing agents. We call such a reversibly inhibitable SpyCatcher “SpyLock”.

We then used “BiLock”, a fusion of SpyLock and wildtype SpyCatcher, in combination with SpyTagged antibody fragments to generate bispecific antibodies. A first antibody was reacted with the regular SpyCatcher moiety, followed by unlocking of the SpyLock through reduction and its reaction with a second antibody. This method to generate bispecific antibodies requires only a single antibody format and is readily scalable, facilitating the screening of a large number of antibody combinations. We demonstrate the utility of this approach to screen anti-PD-1/anti-PD-L1 bispecific antibodies using a cellular reporter assay.
The molecular architecture of the kidney slit diaphragm
Authors: Birtasu Alexandra N. , Wieland Konstantin , Ermel Utz H. , Rahm Johanna V. , Scheffer Margot P. , Flottmann Benjamin , Heilemann Mike , Grahammer Florian , Frangakis Achilleas S.
Published: October 2023

Vertebrate life depends on renal function to filter excess fluid and remove low-molecular-weight waste products. An essential component of the kidney filtration barrier is the slit diaphragm (SD), a specialized cell-cell junction between podocytes. Although the constituents of the SD are largely known, its molecular organization remains elusive. Here, we use super-resolution correlative light and electron microscopy to quantify a linear rate of reduction in albumin concentration across the filtration barrier. Next, we use cryo-electron tomography of vitreous lamellae from high-pressure frozen native glomeruli to analyze the molecular architecture of the SD. The resulting densities resemble a fishnet pattern. Fitting of Nephrin and Neph1, the main constituents of the SD, results in a complex interaction pattern with multiple contact sites between the molecules. Using molecular dynamics flexible fitting, we construct a blueprint of the SD, where we describe all interactions. Our architectural understanding of the SD reconciles previous findings and provides a mechanistic framework for the development of novel therapies to treat kidney dysfunction.
Drosophilamodels of PIGA-CDG mirror patient phenotypes
Authors: Thorpe Holly J. , Owings Katie G. , Aziz Miriam C. , Haller Madelyn , Coelho Emily , Chow Clement Y.
Published: October 2023

Mutations in the phosphatidylinositol glycan biosynthesis class A (PIGA) gene cause a rare, X-linked recessive congenital disorder of glycosylation (CDG). PIGA-CDG is characterized by seizures, intellectual and developmental delay, and congenital malformations. ThePIGAgene encodes an enzyme involved in the first step of GPI anchor biosynthesis. There are over 100 GPI anchored proteins that attach to the cell surface and are involved in cell signaling, immunity, and adhesion. Little is known about the pathophysiology of PIGA-CDG. Here we describe the firstDrosophilamodel of PIGA-CDG and demonstrate that loss ofPIG-Afunction inDrosophilaaccurately models the human disease. As expected, complete loss ofPIG-Afunction is larval lethal. Heterozygous null animals appear healthy, but when challenged, have a seizure phenotype similar to what is observed in patients. To identify the cell-type specific contributions to disease, we generated neuron- and glia-specific knockdown ofPIG-A. Neuron-specific knockdown resulted in reduced lifespan and a number of neurological phenotypes, but no seizure phenotype. Glia-knockdown also reduced lifespan and, notably, resulted in a very strong seizure phenotype. RNAseq analyses demonstrated that there are fundamentally different molecular processes that are disrupted whenPIG-Afunction is eliminated in different cell types. In particular, loss ofPIG-Ain neurons resulted in upregulation of glycolysis, but loss ofPIG-Ain glia resulted in upregulation of protein translation machinery. Here we demonstrate thatDrosophilais a good model of PIGA-CDG and provide new data resources for future study of PIGA-CDG and other GPI anchor disorders.

Article Summary

PIGA-CDG is a rare genetic disorder. In order to study this rare disease, we generated and characterized several Drosophila models of PIGA-CDG. These models faithfully recapitulate different patient phenotypes, including movement disorder and seizures. Drosophila is a good model for PIGA-CDG and other GPI anchor disorders.
Overexpression of Alpha-1 Antitrypsin Increases the Proliferation of Mesenchymal Stem Cells by Upregulation of Cyclin D1 and is Independent of the Wnt Signaling Pathway
Authors: Wolf Bryan , Muralidharan Prasanth , Lee Michael , Hua Wei , Green Erica , Wang Hongjun , Strange Charlie
Published: October 2023

Alaph-1 antitrypsin overexpressing mesenchymal stromal/stem cells (AAT-MSCs) showed improved innate properties with a faster proliferation rate when studied for their protective effects in mouse models of diseases. Here, we investigated the potential mechanism(s) by which AAT gene insertion increases MSC proliferation. Human bone marrow-derived primary or immortalized MSCs (iMSCs) or AAT-MSCs (iAAT-MSCs) were used in the study. Cell proliferation was measured by cell counting and cell cycle analysis. Possible pathways involved in the pro-proliferation effect of AAT were investigated by measuring mRNA and protein expression of key cell cycle genes. Interval cell counting showed increased proliferation in AAT-MSCs or iAAT-MSCs compared to their corresponding MSC controls. Cell cycle analysis revealed more cells progressing into the S and G2/M phases in iAAT-MSCs, with a notable increase in the cell cycle protein, Cyclin D1. Moreover, treatment with Cyclin D1 inhibitors showed that the increase in proliferation is due to Cyclin D1 and that the AAT protein is upstream and a positive regulator of Cyclin D1. Furthermore, AAT’s effect on Cyclin D1 is independent of the Wnt signaling pathway as there were no differences in the expression of regulatory proteins, including GSK3β and β-Catenin in iMSC and iAAT-MSCs. In summary, our results indicate that AAT gene insertion in an immortalized MSC cell line increases cell proliferation and growth by increasing Cyclin D1 expression and consequently causing cells to progress through the cell cycle at a significantly faster rate.
“Safety and security are everything”: a qualitative study on the quality of life of Syrian refugees living in Za’atari camp
Authors: Momani Aaliyah M. , Alduraidi Hamza , Zaghmouri Abeer
Published: October 2023

Purpose

Many refugees around the world are forced to leave their counties seeking safety and security. Millions of Syrian refugees fled their country since the conflict started in Syria. Jordan is one of the host countries for refugees from different countries including Syria. Health-related quality of life of individuals influences both the individual and the community, and how these two interact with one another. This study aims to explore the four domains – physical health, psychological health, social relationships and environment domains – of health-related quality of life of adults residing in Za’atari camp in the North of Jordan.

Design/methodology/approach

A constructivist grounded theory approach was used. Data were collected using semi-structured, face-to-face, audio-recorded interviews. Data were analysed using different levels of coding, constant comparative analysis and writing reflective memos.

Findings

Pursuing safety and security emerged as a core theme in this study. Participants were pursuing safety and security since the conflict started in Syria. Lack of safety and security led them to flee Syria. For participants, safety and security were among the most important aspects of their lives. The meaning of safety and security for Syrian refugees is presented in this paper.

Originality/value

To the best of the authors’ knowledge, this is the first study exploring the health-related quality of life of Syrian refugees residing in Za’atari camp using a qualitative approach.
The effects of supply chain governance on supply chain resilience based on information processing theory
Authors: Lu Qiang , Jiang Yu , Wang Yu
Published: October 2023

Purpose

This study investigates the impact of supply chain governance (SCG, which includes relational governance and contractual governance) on supply chain resilience (SCR) using the information processing theory. Moreover, the study also examines the mediating role of information processing capability and the moderating role of digital technology (DT) deployment.

Design/methodology/approach

A total of 288 questionnaires were collected from the Chinese manufacturing industry, and hierarchical regression was used to empirically test the proposed model.

Findings

This study reveals that SCG positively impacts SCR. Moreover, information processing capability plays a mediating role between SCG and SCR. Furthermore, the breadth of DT deployment positively moderates the effect of relational governance on information processing capability, and the depth of DT deployment positively moderates the effects of both relational governance and contractual governance on information processing capability.

Originality/value

This study offers a novel perspective that helps to understand the importance of the supply chain-wide information acquired by SCG in respect of improving SCR. Furthermore, this article extends the application of information processing theory by providing empirical evidence of the mediating role of information processing capability and elucidating the moderating role of DT deployment.
Key drivers for the adoption of circular economy practices in the tourist accommodation sector
Authors: Santos Margarida Custódio , Veiga Célia , Dantas Samara Santiago , Águas Paulo , Santos José António C.
Published: October 2023

Purpose

This article assesses the degree of adoption of the circular economy model in the tourist accommodation sector. Additionally, the study aims to understand whether the type of accommodation, size and year of construction or remodelling have an impact on the adoption of circular economy practices.

Design/methodology/approach

The study is based on a survey administered to directors and owners of tourist accommodation facilities in Portugal. The questionnaire was developed based on an extensive literature review of circular economy practices in the accommodation sector.

Findings

Accommodation companies currently operate in a linear economy model and are still in the early stages of transitioning to a more circular economic model. Among the most commonly implemented practices are those that represent expenditure savings for accommodation companies. The findings also suggest a growing awareness and commitment to sustainability and circular economy practices in the tourist accommodation sector, particularly in more recently constructed or renovated accommodation.

Originality/value

To the best of the authors' knowledge, this study is the first to evaluate the accommodation characteristics that impact the adoption of sustainability and circular economy practices in the tourist accommodation sector. It contributes to the literature by providing primary quantitative data supporting the adoption of such practices.
Molecular evolution of wound healing‐related genes during cetacean secondary aquatic adaptation
Authors: KANG Jieqiong , GU Long , GUO Boxiong , RONG Wenqi , XU Shixia , YANG Guang , REN Wenhua
Published: October 2023

The marine environment presents challenges for wound healing in cetaceans, despite their remarkable recovery abilities with minimal infections or complications. However, the molecular mechanism underlying this efficient wound healing remains underexplored. To better understand the molecular mechanisms behind wound healing in cetaceans, we investigated the evolutionary patterns of 37 wound healing‐related genes in representative mammals. We found wound healing‐related genes experience adaptive evolution in cetaceans: (1) Three extrinsic coagulation pathway‐related genes—tissue factor (F3), coagulation factor VII (F7), and coagulation factor X (F10)—are subject to positive selection in cetaceans, which might promote efficient hemostasis after injury; positive selection in transforming growth factor‐beta 2 (TGF‐β2), transforming growth factor‐beta 3 (TGF‐β3), and platelet‐derived growth factor D (PDGFD), which play immunological roles in wound healing, may help cetaceans enhance inflammatory response and tissue debridement. (2) Coagulation factor XII (F12) is the initiation factor in the intrinsic coagulation pathway. It had a premature stop codon mutation and was subjected to selective stress relaxation in cetaceans, suggesting that the early termination of F12 may help cetaceans avoid the risk of vascular blockage during diving. (3) Fibrinogen alpha chain (FGA) and FIII, which were detected to contain the specific amino acid substitutions in marine mammals, indicating similar evolutionary mechanisms might exist among marine mammals to maintain strong wound‐healing ability. Thus, our research provides further impetus to study the evolution of the wound healing system in cetaceans and other marine mammals, extending knowledge of preventing coagulation disorder and atherosclerosis in humans.
Metabolic regulation reduces the oxidative damage of arid lizards in response to moderate heat events
Authors: HAN Xingzhi , SUN Baojun , ZHANG Qiong , TENG Liwei , ZHANG Fushun , LIU Zhensheng
Published: October 2023

Climate warming poses a significant threat to species worldwide, particularly those inhabiting arid and semi‐arid regions where extreme temperatures are increasingly prevalent. However, empirical studies investigating how moderate heat events affect the physiological processes of arid and semi‐arid animals are largely scarce. To address this knowledge gap, we used an arid and semi‐arid lizard species (Phrynocephalus przewalskii) as a study system. We manipulated thermal environments to simulate moderate heat events (43.5 ± 0.3°C during the heating period) for lizards and examined physiological and biochemical traits related to survival, metabolism, locomotion, oxidative stress, and telomere length. We found that the body condition and survival of the lizards were not significantly affected by moderate heat events, despite an increase in body temperature and a decrease in locomotion at high test temperatures were detected. Mechanistically, we found that the lizards exhibited down‐regulated metabolic rates and enhanced activities of antioxidative enzymes, resulting in reduced oxidative damage and stable telomere length under moderate heat events. Based on these findings, which indicated a beneficial regulation of fitness by physiological and biochemical processes, we inferred that moderate heat events did not have a detrimental effect on the toad‐headed agama, P. przewalskii. Overall, our research contributes to understanding the impacts of moderate heat events on arid and semi‐arid species and highlights the adaptive responses and resilience exhibited by the toad‐headed agama in the face of climate warming.
Structural, 40Ar/39Ar Geochronological and Rheological Feature Analysis of the Guoxuepu Shear Zone: Indications for the Jitang Metamorphic Complex in the Northern Lancangjiang Zone
Authors: FENG Yipeng , WANG Genhou , WANG Shulai , LI Dian , WANG Huan , LU Yang , LIU Han , ZHANG Peilie
Published: October 2023

The Jitang metamorphic complex is key to studying the tectonic evolution of the Northern Lancangjiang zone. Through structural‐lithological mapping, structural analysis and laboratory testing, the composition of the Jitang metamorphic complex was determined. The macro‐ and microstructural analyses of the ductile detachment shear zone (Guoxuepu ductile shear zone, 2–4 km wide) between the metamorphic complex and the overlying sedimentary cap show that the shear sense of the ductile shear zones is top‐to‐the‐southeast. The presence of various deformation features and quartz C‐axis electron backscatter diffraction (EBSD) fabric analysis suggests multiple deformation events occurring at different temperatures. The average stress is 25.68 MPa, with the strain rates (έ) ranging from 9.77×10–14 s–1 to 6.52×10–16 s‐1. The finite strain of the Guoxuepu ductile shear zone indicates an elongated strain pattern. The average kinematic vorticity of the Guoxuepu ductile shear zone is 0.88, implying that the shear zone is dominated by simple shear. The muscovite selected from the protomylonite samples in the Guoxuepu ductile shear zone yields a 40Ar‐39Ar age of 60.09 ± 0.38 Ma. It is suggested that, coeval with the initial Indo–Eurasian collision, the development of strike‐slip faults led to a weak and unstable crust, upwelling of lower crust magma, then induced the detachment of the Jitang metamorphic complex in the Eocene.
Genesis of the Nuri Cu‐W‐Mo Deposit, Tibet, China: Constraints from in situ Trace Elements and Sr Isotopic Analysis of Scheelite
Authors: WANG Yiyun , WU Zhishan , CHEN Wenqing , DU Qing'an , TANG Liwei , SHI Hongzhao , MA Guotao , ZHANG Zhi , LIANG Wei , WU Bo , MIAO Hengyi
Published: October 2023

The Nuri deposit is the only Cu‐W‐Mo polymetallic deposit with large‐scale WO3 resources in the eastern section of the Gangdese metallogenic belt, Tibet, China. However, the genetic type of this deposit has been controversial since its discovery. Based on a study of the geological characteristics of the deposit, this study presents mineralization stages, focusing on the oxide stage and the quartz‐sulfide stage where scheelite is mainly formed, referred to as Sch‐A and Sch‐B, respectively. Through LA‐ICP‐MS trace element and Sr isotope analyses, the origin, evolutionary process of the ore‐forming fluid and genesis of the ore deposit are investigated. Scanning Electron Microscope‐Cathodoluminescence (SEM‐CL) observations reveal that Sch‐A consists of three generations, with dark gray homogenous Sch‐A1 being replaced by relatively lighter and homogeneous Sch‐A2 and Sch‐A3, with Sch‐A2 displaying a gray CL image color with vague and uneven growth bands and Sch‐A3 has a light gray CL image color with hardly any growth band. In contrast, Sch‐B exhibits a ‘core‐rim’ structure, with the core part (Sch‐B1) being dark gray and displaying a uniform growth band, while the rim part (Sch‐B2) is light gray and homogeneous. The normalized distribution pattern of rare earth elements in scheelite and Sr isotope data suggest that the early ore‐forming fluid in the Nuri deposit originated from granodiorite porphyry and, later on, some country rock material was mixed in, due to strong water‐rock interaction. Combining the O‐H isotope data further indicates that the ore‐forming fluid in the Nuri deposit originated from magmatic‐hydrothermal sources, with contributions from metamorphic water caused by water‐rock interaction during the mineralization process, as well as later meteoric water. The intense water‐rock interaction likely played a crucial role in the precipitation of scheelite, leading to varying Eu anomalies in different generations of scheelite from the oxide stage to the quartz‐sulfide stage, while also causing a gradual decrease in oxygen fugacity (fO2) and a slow rise in pH value. Additionally, the high Mo and low Sr contents in the scheelite are consistent with typical characteristics of magmatic‐hydrothermal scheelite. Therefore, considering the geological features of the deposit, the geochemical characteristics of scheelite and the O‐H isotope data published previously, it can be concluded that the genesis of the Nuri deposit belongs to porphyry‐skarn deposit.
Reactive Transport Process of Earthquake‐induced Hydro‐chemical Changes in Guanding Thermal Spring, Western Sichuan, China
Authors: NA Jin , JIANG Xue , SHI Zheming , CHEN Yanmei
Published: October 2023

Earthquake‐related hydrochemical changes in thermal springs have been widely observed; however, quantitative modeling of the reactive transport process is absent. In the present study, we apply reactive transport simulation to capture the hydrochemical responses in a thermal spring following the Wenchuan Ms 8.0 and Lushan Ms 7.0 earthquakes. We first constrain deep reservoir geothermal fluid compositions and temperature by multicomponent geothermometry, and then a reactive geochemical transport model is constructed to reproduce the hydrochemical evolution process. The results show that the recharge from the shallow aquifer increases gradually until it reaches a peak because of the permeability enhancement caused by the Lushan earthquake, which may be the mechanism to explain the earthquake‐related hydrochemical responses. In contrast to the postseismic effect of the Wenchuan earthquake, the chemical evolution can be considered as hydrochemical anomalies related to the Lushan earthquake. This study proves that the efficient simulation of reactive transport processes is useful for investigating earthquake‐related signals in hydrochemical time series.
Petrogenesis and Tectonic Significance of Shenxianshui Alkaline Granite in Gejiu, Yunnan Province, China
Authors: YANG Rong , CHEN Yongqing
Published: October 2023

The Shenxianshui granites in the western Gejiu area were formed in the Late Cretaceous. Laser ablation inductively coupled plasma mass spectrometry indicates zircon U‐Pb ages ranging from 90.67 ± 0.7 to 85.97 ± 0.6 Ma. The intrusive rocks are peraluminous (A/CNK = 1.03 to 1.33) and calc‐alkaline, showing an affinity towards I‐type granite. Large ion lithophilic elements are enriched in K and Rb, while high field strength elements are depleted. Moreover, light rare earth elements are significantly enriched, showing a slight negative Eu anomaly (Eu/Eu* = 0.39 to 0.58). Shenxianshui granite has a relatively high initial Sr isotope ratio (87Sr/86Sr)i (0.7098–0.7105), negative εNd(t) values (−7.99 to −7.44) and negative εHf(t) values (−8.37 to −2.58). Combined with previous studies, these characteristics suggest that the Shenxianshui alkaline granites were formed in a post‐collision extensional environment. The alkaline granitic magma possibly originated from the partial melting of the lower crust during the Mesoproterozoic era and may have contained mantle source materials. Shenxianshui alkaline granite was formed from mixed magma with a high degree of crystal differentiation. The abundance of ore‐forming elements indicates that Shenxianshui granite has the potential to mineralize key metals and rare earth elements.
Geology and Geochemistry of K‐feldspar Veins in Lamprophyre at the Zhenyuan Gold Deposit, Yunnan, Southwest China: Implications for Gold Mineralization
Authors: ZHANG Huichao , CHAI Peng , ZHANG Hongrui , ZHOU Limin , HOU Zengqian
Published: October 2023

Lamprophyres typically appear in hydrothermal gold deposits. The relationship between lamprophyres and gold deposits is investigated widely. Some researchers suggest that the emplacement of lamprophyres triggers gold mineralization, whereas others hypothesize that the formation of lamprophyres increases the fertility of mantle sources and ore‐forming fluids. K‐feldspar veins, with ages between those of lamprophyres and gold deposits, appear in lamprophyres in Zhenyuan. Therefore, K‐feldspar veins are ideal for investigating the relationship between lamprophyres and gold deposits. Phlogopite in K‐feldspar veins has lower Mg#, Ni, and Cr contents and higher TiO2, Li, Ba, Sr, Sc, Zr, Nb, and Cs contents than phlogopite in lamprophyres. The in‐situ Sr isotopic values of apatites (0.7063–0.7066) in K‐feldspar veins are within the range for apatites (0.7064–0.7078) from lamprophyres. High large‐ion lithophile element concentrations and low Nb and Ta concentrations in phlogopite from lamprophyres, in addition to high (87Sr/86Sr)i values of apatite (0.7064–0.7078), indicate that the magma parental to these phlogopite and apatite crystals is derived from an enriched mantle. K‐feldspar veins are genetically correlated with lamprophyres, whereas sulfide mineral assemblage and trace element compositions of pyrite in K‐feldspar veins suggest that K‐feldspar veins in lamprophyres are not directly related to gold mineralization of the Zhenyuan deposit.
Sedimentary Environment and Mineralization of the Black Shale Polymetallic Layer in the Early Cambrian, SW China: Constraints from in situ LA‐ICP‐MS Analysis of Pyrite
Authors: YANG Zhen , FU Yong , LI Chao , CAI Xi , GUO Chuan
Published: October 2023

A polymetallic layer is usually developed at the bottom of the early Cambrian black shale in Guizhou Province. The mineral that makes up the polymetallic layer is related to the sedimentary facies. To analyze the differentiation mechanism between polymetallic deposits (Ni‐Mo and V), the Zhijin Gezhongwu profile located in the outer shelf and the Sansui Haishan V deposit located in the lower slope are selected to study the in situ sulfur isotopes and trace elements of pyrite. The results show that δ34S values of pyrite vary widely from −7.8 ‰ to 28 ‰ in the Gezhongwu profile, while the δ34S values are relatively uniform (from 27.8 ‰ to 38.4 ‰) in the Haishan profile. The isotopic S composition is consistent with the transition that occurs in the sedimentary phase from the shelf to the deep sea on the transgressive Yangtze platform; this indicates that the δ34SO42– values in seawater must be differently distributed in depositional environments. The sulfur in the Ni‐Mo layer is produced after the mixing of seawater and hydrothermal fluid, while the V layer mainly originates from seawater. Overall, the Ni‐Mo and V deposits have been differentiated primarily on the basis of the combined effect of continental weathering and hydrothermal fluid.
Hypertension in the emergency department: A missed opportunity to screen for primary aldosteronism?
Authors: Graven Rachel D. , Lee Ignatius , Ren Jing , Yang Jun , Egerton‐Warburton Diana
Published: October 2023

Objectives

Primary aldosteronism (PA) is a common but underdiagnosed secondary cause of hypertension. Emergency departments (EDs) often assess patients with severe hypertension or its sequelae, some of whom have underlying PA. We aimed to determine the proportion of patients presenting to the ED with hypertension who meet the Endocrine Society criteria for PA testing and the proportion who were screened.

Methods

We performed a structured retrospective chart review of adults who presented to three EDs in an Australian tertiary health network between August 2019 and February 2020, with a coded presenting complaint of hypertension. Clinical parameters to determine whether the patients met the criteria for PA testing were extracted from electronic medical records.

Results

Of the 418 patients who presented to the EDs with documented elevated blood pressure (BP), 181 patients (43.3%) fulfilled PA screening criteria and nine patients (2.2%) underwent PA testing. Individuals who fulfilled screening criteria were older; had higher prevalence of Type 2 diabetes, coronary artery disease, and congestive heart failure; took more antihypertensive medications; and had lower estimated glomerular filtration rate. Individuals who were tested for PA were younger and had higher BP on presentation. Screening for PA was more frequent in patients who were referred to medical teams.

Conclusions

As far as we are aware, our study is the first to evaluate PA testing in hypertensive patients who present to ED. More than 40% of adults presenting to the EDs with hypertension met the current criteria for testing for PA but only few were tested. These results emphasize that increased awareness of PA in the ED is needed to encourage opportunistic testing, referral, and treatment, especially in patients who present with hypertensive emergencies. Prospective studies are required to determine the feasibility and effectiveness of this.
Corporate sexual orientation equality and carbon emission
Authors: Hossain Ashrafee Tanvir , Hossain Amir , Cooper Tom , Islam Majidul
Published: October 2023

Does a firm's tolerance and nurturing of its employees with different sexual orientations influence its long‐term sustainability? Based on corporate sexual orientation equality (CSOE), we find that firms with higher CSOE ratings emit less greenhouse gases (GHGs) that thereby ensure long‐term sustainability. In addition, we report that the CSOE–GHG relationship is stronger for firms with less agency issues (e.g., less powerful CEOs and more monitoring). Finally, we find that carbon emitting firms (CEFs) that invest in more CSOE initiatives do not do it for external rewards (e.g., they suffer from lower valuations and face higher costs of raising capital).
Market power in California's water market
Authors: Tomori Françeska , Ansink Erik , Houba Harold , Hagerty Nick , Bos Charles
Published: October 2023

We estimate market power in California's surface water market. Market power may distort the potential welfare gains from water marketing. We use a Nash‐Cournot model and derive a closed‐form solution for the extent of market power in a water market setting. We then use this solution to estimate market power in a newly assembled dataset on California's water economy. We show that, under the assumptions of the Nash‐Cournot model, market power in this thin market is limited.
Exploring Parkinson's disease prevalence in regional, rural and remote Australia: A systematic scoping review
Authors: Fealy Shanna , Logan Patricia A. , Micalos Peter S. , Rossiter Rachel , Jones Donovan , Irwin Pauletta , Schwebel Deborah , Carroll Vincent , Wong Alfred , Fung Victor S. C. , Morales‐Briceno Hugo , Bramble Marguerite
Published: October 2023

Introduction

Idiopathic Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide. Due to ageing populations, prevalence estimates for PD are set to increase in western countries including Australia.

Objective

This study aims to investigate the prevalence of PD in regional, rural and remote areas of Australia, to inform the provision of equitable PD‐specific care.

Design

A scoping review, following the Joanna Briggs Institute methodology for scoping reviews and the Preferred Reporting Items for Systematic reviews and Meta‐Analyses extension for Scoping Reviews (PRISMA‐ScR), was conducted. An electronic search of four databases and the search engine google scholar was completed in May 2022 and updated in September 2023. Article screening and quality appraisal were undertaken independently by at least two reviewers.

Findings

Of 514 records screened, six articles (between 1966 and 2019) were identified and included for review. Wide variations in PD prevalence were evident, ranging from 0.58 to 8.5 per 1000 people. Two studies suggested prevalence may be higher in regional, rural and remote areas of Australia than in urban localities.

Discussion

The limited number of studies identified, and wide variation in prevalence rates makes it difficult to draw firm conclusions to inform heath care planning and resource allocation.

Conclusion

A paucity of reliable prevalence data indicates the need for well‐designed, country‐specific epidemiological studies to be conducted to estimate the actual impacts of the disease to inform public health planning, particularly in regional, rural and remote areas where access to PD‐specific care is already inequitable.