bluuebunny/crossref_metadata_2025 huggingface dataset:
Infection by the Lungworm Rhabdias pseudosphaerocephala Affects the Expression of Immune‐Related microRNAs by Its Co‐Evolved Host, the Cane Toad Rhinella marina
Authors: Chan Tsering C. L. , Yagound Boris , Brown Gregory P. , Eyck Harrison J. F. , Shine Richard , Rollins Lee A.
Published: November 2024

Parasites may suppress the immune function of infected hosts using microRNAs (miRNAs) to prevent protein production. Nonetheless, little is known about the diversity of miRNAs and their mode(s) of action. In this study, we investigated the effects of infection by a parasitic lungworm (Rhabdias pseudosphaerocephala) on miRNA and mRNA expression of its host, the invasive cane toad (Rhinella marina). To investigate the cane toad's innate and adaptive immune response to this parasite, we compared miRNA and mRNA expression in naïve toads that had never been infected by lungworms to toads that were infected with lungworms for the first time in their lives, and toads that were infected the second time in their lives (i.e., had two consecutive infections). In total, we identified 101 known miRNAs and 86 potential novel miRNAs. Compared to uninfected and single‐infection toads, multiple‐infection animals drastically downregulated three miRNAs. These miRNAs were associated with gene pathways related to the immune response, potentially reflecting the immunosuppression of cane toads by their parasites. Infected hosts did not respond with substantially differential mRNA transcription; only one gene was differentially expressed between control and single‐infection hosts. Our study suggests that miRNA may play an important role in mediating host–parasite interactions in a system in which an ongoing range expansion by the host has generated substantial divergence in host–parasite interactions.
Bacterial Organelles in Iron Physiology
Authors: Ferrara Kristina M. , Gupta Kuldeepkumar R. , Pi Hualiang
Published: November 2024

Bacteria were once thought to be simple organisms, lacking the membrane‐bound organelles found in eukaryotic cells. However, recent advancements in microscopy have changed this view, revealing a diverse array of organelles within bacterial cells. These organelles, surrounded by lipid bilayers, protein‐lipid monolayers, or proteinaceous shells, play crucial roles in facilitating biochemical reactions and protecting cells from harmful byproducts. Unlike eukaryotic organelles, which are universally present, bacterial organelles are species‐specific and induced only under certain conditions. This review focuses on the bacterial organelles that contain iron, an essential micronutrient for all life forms but potentially toxic when present in excess. To date, three types of iron‐related bacterial organelles have been identified: two membrane‐bound organelles, magnetosomes and ferrosomes, and one protein‐enclosed organelle, the encapsulated ferritin‐like proteins. This article provides an updated overview of the genetics, biogenesis, and physiological functions of these organelles. Furthermore, we discuss how bacteria utilize these specialized structures to adapt, grow, and survive under various environmental conditions.
Small, but mitey: investigating the molecular genetic basis for mite domatia development and intraspecific variation in Vitis riparia using transcriptomics
Authors: Ritter Eleanore Jeanne , Graham Carolyn D. K. , Niederhuth Chad , Weber Marjorie Gail
Published: November 2024

Here, we investigated the molecular genetic basis of mite domatia, structures on the underside of leaves that house mutualistic mites, and intraspecific variation in domatia size in Vitis riparia (riverbank grape).

Domatia and leaf traits were measured, and the transcriptomes of mite domatia from two genotypes of V. riparia with distinct domatia sizes were sequenced to investigate the molecular genetic pathways that regulate domatia development and intraspecific variation in domatia traits.

Key trichome regulators as well as auxin and jasmonic acid are involved in domatia development. Genes involved in cell wall biosynthesis, biotic interactions, and molecule transport/metabolism are upregulated in domatia, consistent with their role in domatia development and function.

This work is one of the first to date that provides insight into the molecular genetic bases of mite domatia. We identified key genetic pathways involved in domatia development and function, and uncovered unexpected pathways that provide an avenue for future investigation. We also found that intraspecific variation in domatia size in V. riparia seems to be driven by differences in overall leaf development between genotypes.
Phosphorylation‐dependent activation of the bHLH transcription factor ICE1/SCRM promotes polarization of the Arabidopsis zygote
Authors: Chen Houming , Xiong Feng , Wangler Alexa‐Maria , Bischoff Torren , Wang Kai , Miao Yingjing , Slane Daniel , Schwab Rebecca , Laux Thomas , Bayer Martin
Published: November 2024

In Arabidopsis thaliana, the asymmetric cell division (ACD) of the zygote gives rise to the embryo proper and an extraembryonic suspensor, respectively. This process is controlled by the ERECTA‐YODA‐MPK3/6 receptor kinase‐MAP kinase‐signaling pathway, which also orchestrates ACDs in the epidermis. In this context, the bHLH transcription factor ICE1/SCRM is negatively controlled by MPK3/6‐directed phosphorylation. However, it is unknown whether this regulatory module is similarly involved in the zygotic ACD.

We investigated the function of SCRM in zygote polarization by analyzing the effect of loss‐of‐function alleles and variants that cannot be phosphorylated by MPK3/6, protein accumulation, and target gene expression.

Our results show that SCRM has a critical function in zygote polarization and acts in parallel with the known MPK3/6 target WRKY2 in activating WOX8. Our work further demonstrates that SCRM activity in the early embryo is positively controlled by MPK3/6‐mediated phosphorylation.

Therefore, the effect of MAP kinase‐directed phosphorylation of the same target protein fundamentally differs between the embryo and the epidermis, shedding light on cell type‐specific, differential gene regulation by common signaling pathways.
Plant organic nitrogen nutrition: costs, benefits, and carbon use efficiency
Authors: Tünnermann Laura , Aguetoni Cambui Camila , Franklin Oskar , Merkel Patrizia , Näsholm Torgny , Gratz Regina
Published: November 2024

Differences in soil mobility and assimilation costs between organic and inorganic nitrogen (N) compounds would hypothetically induce plant phenotypic plasticity to optimize acquisition of, and performance on, the different N forms. Here we evaluated this hypothesis experimentally and theoretically.

We grew Arabidopsis in split‐root setups combined with stable isotope labelling to study uptake and distribution of carbon (C) and N from l‐glutamine (l‐gln) and NO3− and assessed the effect of the N source on biomass partitioning and carbon use efficiency (CUE).

Analyses of stable isotopes showed that 40–48% of C acquired from l‐gln resided in plants, contributing 7–8% to total C of both shoots and roots. Plants grown on l‐gln exhibited increased root mass fraction and root hair length and a significantly lower N uptake rate per unit root biomass but displayed significantly enhanced CUE.

Our data suggests that organic N nutrition is linked to a particular phenotype with extensive growth of roots and root hairs that optimizes for uptake of less mobile N forms. Increased CUE and lower N uptake per unit root growth may be key facets linked to the organic N phenotype.
On Being Open in Closed Places: Vulnerability and Violence in Inpatient Psychiatric Settings
Authors: Brooks Cat Papastavrou , Johnston Isobel , Gilson Erinn
Published: November 2024

High levels of violence and conflict occur in inpatient psychiatric settings, causing a range of psychological and physical harms to both patients and staff. Drawing on critiques of vulnerability from the philosophical literature, this paper contends that staff's understanding of their relationship with patients (including how they should respond to violence and conflict) rests on the dominant, reductive account of vulnerability. This account frames vulnerability as an increased susceptibility to harm and so regards ‘invulnerable’ staff's responsibility to be protecting and managing vulnerable patients. We offer an alternative view of vulnerability as an openness and capability to be changed, which illuminates how the common account of vulnerability is used to justify staff's coercive power over patients and to control staff behaviour. Our main argument is that staff's adoption of this negative approach to vulnerability is associated with a range of factors that are connected to the violence and conflict endemic to these settings. Staff's need to situate themselves as invulnerable and therefore incapable of harm, we argue, leads to significant issues through: damaging staff ability to emotionally regulate; coercing patients into an asymmetrical openness leading to aggression to restore status; damaging therapeutic relationships by enforcing separation between staff and patients; increasing staff's reliance on unhelpful and rigid techniques (such as de‐escalation); repressing staffs’ ability to learn and grow through encounters with patients. Finally, we offer recommendations for how vulnerability and openness could be cultivated as a relational and radical practice in spaces that are traditionally closed and hostile to it.
Active‐Matrix Metalloproteinase‐8, Myeloperoxidase in Relation With Periodontics, Preterm Birth
Authors: Alan Murat , Sorsa Timo , Meriç Kantar Pınar , Raisanen Ismo T. , Gürlek Önder , Kanmaz Burcu , Buduneli Nurcan
Published: November 2024

Objective

To investigate serum, placental levels of active‐matrix metalloproteinase‐8 (aMMP‐8), myeloperoxidase (MPO) in preterm‐birth with/without pre‐eclampsia and term counterparts in relation with clinical periodontal parameters.

Methods

Clinical periodontal measurements were recorded. Serum and placenta samples were collected during 173 full‐term (FT), pre‐term (PT) or pre‐term complicated by pre‐eclampsia (PTPE) deliveries. aMMP‐8 levels were measured by IFMA. MPO levels in the serum and placenta samples were determined by ELISA. Data were tested using non‐parametric tests.

Results

PTBE group exhibited higher full‐mouth probing depth and clinical attachment loss values than the other two groups (p < 0.05). Percentages of sites with plaque and bleeding on probing were lower in the PTBE group than in the other groups (p < 0.05). Serum aMMP‐8 and MPO concentrations were higher in PTPE group than in the other groups (p < 0.05). Placenta aMMP‐8 level was higher in the control group than in the PTPE group (p < 0.05). There was no significant difference between the groups in the placenta MPO levels (p > 0.05).

Conclusions

Within the limits of this cross‐sectional study, it may be suggested that serum aMMP‐8 and MPO concentrations together with placenta aMMP‐8 levels may be associated with and reflect adverse pregnancy outcomes. Clinical periodontal findings did not reveal significant associations with these proteolytic and oxidative biomarkers.
Protein Involved in Tip Elongation (PITE) regulates root hair growth in rice
Authors: Yun Chan Mi , Hong Woo‐Jong , Kim Hyo‐Jeong , Kim Ji‐Hyun , Son Ye‐Jin , Noh Gayoung , Park Chan‐Woo , Li HuanJun , Liang Wanqi , Hong Chang‐Oh , Lee Kwang Min , Jung Ki‐Hong , Kim Yu‐Jin
Published: November 2024

Polar tip growth in plants occurs only in root hairs and pollen tubes. In particular, root hair growth is considered very important in the growth of plants, as it is critical for water and nutrient absorption. Polar tip growth is regulated by various factors, including plant hormones such as abscisic acid (ABA) and gibberellin (GA) and cell wall modifications. We aimed to elucidate the effects and mechanisms on tip growth of a novel gene containing the domain of unknown function (DUF) 3511. We found that Protein Involved in Tip Elongation (PITE) is involved in root hair development in rice (Oryza sativa L.). PITE protein was observed in the plasma membrane and cytoplasm of root hairs. Pite mutants generated by the CRISPR/Cas9 system showed a shorter root hair phenotype compared to the wild type. Through RNA sequencing and quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) analysis, we found that the expression of genes that affect cell wall rigidity and GA metabolism‐related genes were differently regulated in pite mutants. PITE could interact with acyl transferase and haloacid dehalogenase‐like hydrolase (HAD9) in the nucleus and cytoplasm. Our study suggests that PITEs containing the DUF3511 domain regulate root hair growth in rice by mediating the expression of genes that can regulate cell wall rigidity or cause changes in GA metabolism through interactors such as HAD9.
Comparative nutrient concentration and resorption dynamics in petals and leaves
Authors: Tong Bao‐Jie , Zhao Qiu‐Ju , Li Hong‐Yan , Zhou Yi , Li Huan , Li Jia‐Wei
Published: November 2024

Chemical elements support various plant functions, and their reutilization is important for plant ecological adaptation. However, there is a lack of studies comparing the elemental concentration and their reutilization in floral petals and leaves of the same plant. To address this research gap, we conducted a comparative study across 38 plant species with diverse life forms in a common garden. Our investigation focused on the nutrient concentration of 10 elements in both petals and leaves and functional traits, including flower lifespan, dry mass per unit area, water concentration, and vein density. We have found that the elements of nitrogen (N), calcium (Ca), magnesium (Mg), iron (Fe), and manganese (Mn) were more abundant in leaves. In contrast, petals contained higher concentrations of phosphorus (P) and potassium (K). N, P, K, Ca, Mg, and sodium (Na) concentrations of petals were positively related to leaves. In herbaceous plants, their petals showed significant resorption of P and K, while N, P, and K were detected with significant resorption in leaves from all life forms. A positive correlation was found between the resorption of P in leaves and petals. From the perspective of the carbon economic spectrum, N and P showed a negative correlation with dry mass per unit area in leaves. Meanwhile, petal dry mass per area and floral longevity were significantly negatively correlated with P. Our findings elucidate the nutritional basis for the functional differentiation between petals and leaves.
Seasonally stable wetted width elucidates freshwater mussel species richness and endangered species presence: implications for T&E management programs and stream restoration design
Authors: Hawley Robert J. , Cooper Kurt , McGregor Monte , Acosta Shelby , Mulhall Bethany , Raetz Abi , Korth Nora L.
Published: November 2024

Centuries of beaver extirpation, deforestation, and other anthropogenic impacts have disconnected North American rivers from their floodplains and concentrated more hydraulic energy within their channels, degrading aquatic habitat and making the streambed more prone to erosion. Rivers naturally adjust via systematic downcutting, bank erosion, channel widening, bar building, and the gradual recovery of geomorphic equilibrium with well‐connected benches that dissipate hydraulic energy and restore a more natural streambed disturbance regime. The life histories of two endangered freshwater mussels, the fanshell (Cyprogenia stegaria) and snuffbox (Epioblasma triquetra), suggest they have evolved to and depend on the natural disturbance regime. Young juveniles excyst from their host fish in early summer, burrow into the top few millimeters of the streambed, and then need ca. 3 months of streambed stability prior to growing large enough to be less vulnerable to streambed mobilization. We propose a conceptual model that suggests a potential prerequisite to supporting fanshell and snuffbox populations is a geomorphically recovering (i.e. at least one stable bank and a wide enough channel corridor for at least partially vegetated bars/benches) or recovered (i.e. stable banks and vegetated benches) channel and floodplain corridor that sufficiently dissipates its hydraulic energy to maintain seasonal streambed stability during typical (non‐hurricane) summer/autumns. To explore this conceptual model, we conducted mussel and geomorphic surveys in a reach of the Rolling Fork River that spanned a range of channel conditions from chronically failing streambanks to a geomorphically recovered channel with wide, vegetated benches. Our analyses documented increasing mussel species richness, including the presence of the endangered fanshell or snuffbox, with increasing width of seasonally stable streambed habitat.
Oral complications associated with trigeminal trophic syndrome: A case report
Authors: Omolehinwa Temitope , Davila Andres , Mahajan Roopali , Sollecito Thomas P. , Stoopler Eric T. , Kulkarni Roopali
Published: November 2024

Introduction

Destruction of the trigeminal (Gasserian) ganglion or peripheral damage to the trigeminal nerve may lead to trigeminal trophic syndrome (TTS), a rare condition characterized by self‐inflicted trauma. To date, under 200 cases of TTS are documented in medical literature, with only sparse studies reporting on oral complications secondary to this condition.

Case report

The following report presents a well‐documented case of oral complications associated with TTS in an 83‐year‐old Caucasian female presenting with right‐sided lesions on her nasal ala, scalp, buccal mucosa, and tongue, secondary to self‐inflicted injury following their second microvascular decompression for surgical management of trigeminal neuralgia.

Discussion/conclusion

The paucity of literature on oral complications associated with TTS supports the need for understanding guiding management modalities of such lesions for clinical practice. To the authors’ knowledge, this is the first manuscript detailing present and potential intraoral complications associated with TTS alongside treatment modalities for the practicing clinician.
Are orofacial pain assessment tools for adults who cannot self‐report pain suitable for dental practice? A scoping review
Authors: Mac Giolla Phadraig Caoimhin , Lawler Alva , MacHesney Georgia , Fleischmann Isabel , McElroy Lisa , Dimitrijevic Ivana , Smith Jill , Canavan Dermot , Dougall Alison
Published: November 2024

Introduction

This study aims to identify and appraise orofacial pain assessment tools designed to score pain in adults who cannot self‐report and rate their suitability for dental practice.

Methods

A protocolled systematic scoping review, in accordance with Joanna Briggs Institute methods was completed. A development panel (n = 7) reviewed attributes of each tool for suitability for use in dental practice, using predefined criteria.

Results

Nine studies were included. Sample size ranged from n = 22 to n = 348; all participants were 65 years plus and had a cognitive impairment or dementia, excluding controls. Four tools were identified: Facial action coding system (FACS), mobilization‐observation‐behavior‐intensity in dementia pain scale (MOBID I & II) and, orofacial pain scale–non‐verbal individuals (OPS‐NVI). Tools scored between two and thirteen out of twenty according to modified quality assessment criteria. No tool was deemed suitable for use in dental surgery, with the OPS‐NVI scoring most favorably.

Conclusions

No tools were deemed ideal for use within a dental clinic. Elements of some, particularly the OPS‐NVI, may be adaptable for this purpose. Despite the difficulties dental practitioners face trying to assess pain in non‐speaking patients, there was no suitable tool identified. Pathways need to be designed to facilitate inclusive orofacial pain assessment for those who cannot self‐report pain.
Defense‐related callose synthase PMR4 promotes root hair callose deposition and adaptation to phosphate deficiency in Arabidopsis thaliana
Authors: Okada Kentaro , Yachi Koei , Nguyen Tan Anh Nhi , Kanno Satomi , Yasuda Shigetaka , Tadai Haruna , Tateda Chika , Lee Tae‐Hong , Nguyen Uyen , Inoue Kanako , Tsuchida Natsuki , Ishihara Taiga , Miyashima Shunsuke , Hiruma Kei , Miwa Kyoko , Maekawa Takaki , Notaguchi Michitaka , Saijo Yusuke
Published: November 2024

Plants acquire phosphorus (P) primarily as inorganic phosphate (Pi) from the soil. Under Pi deficiency, plants induce an array of physiological and morphological responses, termed phosphate starvation response (PSR), thereby increasing Pi acquisition and use efficiency. However, the mechanisms by which plants adapt to Pi deficiency remain to be elucidated. Here, we report that deposition of a β‐1,3‐glucan polymer called callose is induced in Arabidopsis thaliana root hairs under Pi deficiency, in a manner independent of PSR‐regulating PHR1/PHL1 transcription factors and LPR1/LPR2 ferroxidases. Genetic studies revealed PMR4 (GSL5) callose synthase being required for the callose deposition in Pi‐depleted root hairs. Loss of PMR4 also reduces Pi acquisition in shoots and plant growth under low Pi conditions. The defects are not recovered by simultaneous disruption of SID2, mediating defense‐associated salicylic acid (SA) biosynthesis, excluding SA defense activation from the cause of the observed pmr4 phenotypes. Grafting experiments and characterization of plants expressing PMR4 specifically in root hair cells suggest that a PMR4 pool in the cell type contributes to shoot growth under Pi deficiency. Our findings thus suggest an important role for PMR4 in plant adaptation to Pi deficiency.
Recent advances in bioactive wound dressings
Authors: Nur Md Golam , Rahman Mustafijur , Dip Tanvir Mahady , Hossain Md Hasibul , Hossain Nusrat Binta , Baratchi Sara , Padhye Rajiv , Houshyar Shadi
Published: November 2024

Traditional wound dressings, despite their widespread use, face limitations, such as poor infection control and insufficient healing promotion. To address these challenges, bioactive materials have emerged as a promising solution in wound care. This comprehensive review explores the latest developments in wound healing technologies, starting with an overview of the importance of effective wound management, emphasising the need for advanced bioactive wound dressings. The review further explores various bioactive materials, defining their characteristics. It covers a wide range of natural and synthetic biopolymers used to develop bioactive wound dressings. Next, the paper discusses the incorporation of bioactive agents into wound dressings, including antimicrobial and anti‐inflammatory agents, alongside regenerative components like growth factors, platelet‐rich plasma, platelet‐rich fibrin and stem cells. The review also covers fabrication techniques for bioactive wound dressings, highlighting techniques like electrospinning, which facilitated the production of nanofibre‐based dressings with controlled porosity, the sol–gel method for developing bioactive glass‐based dressings, and 3D bioprinting for customised, patient‐specific dressings. The review concludes by addressing the challenges and future perspectives in bioactive wound dressing development. It includes regulatory considerations, clinical efficacy, patient care protocol integration and wound healing progress monitoring. Furthermore, the review considers emerging trends such as smart materials, sensors and personalised medicine approaches, offering insights into the future direction of bioactive wound dressing research.
The Emergence of Cat‐Transmitted Sporotrichosis Driven by Sporothrix brasiliensis in Piauí, Brazil
Authors: Pinheiro Raizza Eveline Escórcio , Santana Clara Cecília Azevedo , Martins Liline Maria Soares , Veloso Dilbert Silva , Luz Jardenio Assis dos Santos , Lima Oriana Bezerra , Santos Namir Clementino , Gonsales Fernanda Fidelis , de Carvalho Jamile Ambrósio , Rodrigues Anderson Messias
Published: November 2024

Introduction

In Brazil, the emergence of feline sporotrichosis, a neglected subcutaneous mycosis primarily transmitted by cats and caused by the fungus Sporothrix brasiliensis, has been monitored via molecular tools. This approach underscores the geographic expansion of this disease and highlights the critical role of molecular surveillance in understanding its epidemiology and guiding public health interventions.

Methods

We investigated three domestic cats (Felis catus) with multiple skin lesions in Picos, Piauí, Brazil. The cats were examined, and samples were collected for laboratory diagnosis, including cytological evaluation, fungal culture, and molecular characterisation. The molecular analysis involved a one‐tube multiplex probe‐based qPCR assay for the diagnosis of Sporothrix species, mating‐type determination, and amplified fragment length polymorphism (AFLP, EcoRI‐GA/MseI‐AG) to assess genetic similarity and potential origin.

Results

All three cats were diagnosed with sporotrichosis caused by the hypervirulent S. brasiliensis. A probable case of zoonotic transmission has been reported in a 12‐year‐old girl who developed Parinaud oculoglandular syndrome after contact with one of the cats with sporotrichosis. The molecular analysis revealed that the cat isolates were MAT 1‐2 and formed a single cluster according to the AFLP analysis, suggesting direct transmission (cat‐cat) and a potential founder effect. The isolates were also closely related to strains from Pernambuco and Southeast Brazil, indicating a possible introduction from these regions.

Conclusions

Identifying S. brasiliensis in Piauí emphasises the need for increased awareness and control measures to prevent further spread. The predominance of the MAT1‐2 idiomorphs and the genetic similarity among outbreak isolates suggest clonal expansion, which could have significant implications for public health and veterinary practices. Considering its zoonotic potential and environmental adaptability, a One Health approach is crucial for managing and controlling the spread of cat‐transmitted sporotrichosis.
A Better Way to Visualize the Cervix: A Low-Cost Cervical Cancer Screening Device for LMIC Settings
Authors: Barsukova Anita Dey , Jebran Ahmad Mujtaba , Lynch Naomi , Galgali Amit , Moncada Andrea , Sakerka Lauren , Cotner Cody , Davey Sonya , Nimgaonkar Vivek , Ying Binbin , Mendez Keegan , Traverso Giovanni
Published: November 2024

Cervical cancer is a leading cause of cancer-related mortality worldwide, killing over 300,000 women annually. Lack of resources to perform screening and treatment of cervical cancer in low- and middle-income countries (LMICs) as well as the stigma associated with screening has led to high mortality rates in these regions. Specifically, the speculum—a duck bill-shaped device used to open the vaginal canal for visualization of the cervix by a clinician—does not always provide a clear line of sight to the cervix and can cause patient discomfort due to the concentrated stress it exerts on the vaginal canal. To overcome these barriers, we developed a low-cost screening device for use in LMIC settings that enables better visualization of the cervix at low cervical angles and exerts less pressure on the vaginal walls compared to a speculum in finite element (FE) models.
Numerical Analysis of Gas Generation and Migration in a Radioactive Waste Disposal Cell of a Deep Geological Repository
Authors: Sun Lan , Qiu Liyan
Published: November 2024

In a deep geological repository (DGR) for the long-term disposal of radioactive waste, gases (e.g., hydrogen (H2), carbon dioxide (CO2) and methane (CH4)) can be generated through a number of processes, such as corrosion of various metals and alloys and degradation of organic materials. If gas induced pressure exceeds the containment capacity of the engineered barrier systems (EBS) or the host rock, the gases could migrate through these barriers and potentially expose people and the environment to radiation. Therefore, a good understanding on the long-term performance of these barriers against gas migration is an important component in DGR design and safety assessment. In the present work, a numerical model has been developed to simulate the diffusion of CO2 (one of the gas species) in the near field of a DGR with the generation from related chemical reactions. The generation of CO2 was investigated to determine if it is a critical factor to impact the DGR safety under Canadian geological formations. A commercial computational fluid dynamics (CFD) code, ANSYS Fluent was used for the calculations. The model considered pH and temperature effects on CO2 migration under Canadian DGR geochemistry conditions.
Development of Large-Diameter Hybrid Film-Riding Seals for Supercritical Carbon Dioxide Turbines
Authors: Bidkar Rahul A. , Kumar Uttara , Trivedi Deepak , Zhang Xiaohua , Rambacher Collin , Rimpel Aaron , Kerr Thomas , Johnson Jeremy
Published: November 2024

Compared to traditional labyrinth seals, large-diameter (about 24 in or 609.6 mm) film-riding face seals are worth 0.55–0.65% points efficiency for utility-scale supercritical carbon dioxide (sCO2) turbines. Conventional dry gas seals (DGS) that rely on aerodynamic spiral grooves cannot be used at such large diameters due to manufacturability limitations and mechanical deformations. Hybrid film-riding face seals are excellent compromise candidates that can operate at large diameters with slightly increased albeit leakier films. This paper presents the development and test data for a hybrid face seal developed for the utility-scale sCO2 turbine application. A high-level overview of the seal design considerations is presented followed by test data on three seals—a small-size seal (5.7 in or 144.8 mm diameter), an intermediate-size seal (14 in or 355.6 mm diameter), and two full-size seals (24 in or 609.6 mm diameter) tested over a range of pressures and temperatures with both air and CO2 as the working fluid. This paper presents nondimensional seal film thickness and seal leakage (effective clearance) data as a function of the pressure ratios, speed, and temperature. The film thickness measurements presented in this paper agree well with the computational fluid dynamics (CFD)-based film thickness predictions. The measured seal effective clearance for the seals was around 0.001 in (0.0254 mm) effective clearance, which is better than published data on aerostatic face seals and less risky compared to conventional DGS. Rotating test data across all three length scales presented in this work show successful laboratory-scale seal operation for the newly design hybrid face seals.
Who Wants To Be a Physical Education Teacher? Identity Development
Authors: Simon Eitan , Weissblueth Eyal
Published: November 2024

Purpose: This article delves into analyzing professional identity development among Israeli physical education preservice teachers (PSTs), examining shifts in training programs mandated by the Ministry of Education. Method: One hundred and twenty-three physical education PSTs in three different years answered a validated teacher’s professional identity questionnaire. Two-way analysis of variance was used to detect significant differences between subgroups. Results: Analysis revealed variations among PSTs based on an academic year, with third-year students showing higher levels of commitment and identity. Discussion/Conclusion: The results trace how identity evolves dynamically over 3 years, emphasizing how interactions with stakeholders shape and underscore the importance of these early stages in fostering future professional competence and values, underlining the significance of gradual training. We suggest that teacher educators should acknowledge this dynamic process and consistently support PSTs throughout their training.
Cell response to extracellular matrix viscous energy dissipation outweighs high-rigidity sensing
Authors: Huerta-López Carla , Clemente-Manteca Alejandro , Velázquez-Carreras Diana , Espinosa Francisco M. , Sanchez Juan G. , Martínez-del-Pozo Álvaro , García-García María , Martín-Colomo Sara , Rodríguez-Blanco Andrea , Esteban-González Ricardo , Martín-Zamora Francisco M. , Gutierrez-Rus Luis I. , Garcia Ricardo , Roca-Cusachs Pere , Elosegui-Artola Alberto , del Pozo Miguel A. , Herrero-Galán Elías , Sáez Pablo , Plaza Gustavo R. , Alegre-Cebollada Jorge
Published: November 2024

The mechanics of the extracellular matrix (ECM) determine cell activity and fate through mechanoresponsive proteins including Yes-associated protein 1 (YAP). Rigidity and viscous relaxation have emerged as the main mechanical properties of the ECM steering cell behavior. However, how cells integrate coexisting ECM rigidity and viscosity cues remains poorly understood, particularly in the high-stiffness regime. Here, we have exploited engineered stiff viscoelastic protein hydrogels to show that, contrary to current models of cell-ECM interaction, substrate viscous energy dissipation attenuates mechanosensing even when cells are exposed to higher effective rigidity. This unexpected behavior is however readily captured by a pull-and-hold model of molecular clutch–based cell mechanosensing, which also recapitulates opposite cellular response at low rigidities. Consistent with predictions of the pull-and-hold model, we find that myosin inhibition can boost mechanosensing on cells cultured on dissipative matrices. Together, our work provides general mechanistic understanding on how cells respond to the viscoelastic properties of the ECM.
B cell adapter for PI 3-kinase (BCAP) coordinates antigen internalization and trafficking through the B cell receptor
Authors: Lagos Jonathan , Holder Ursula , Sagadiev Sara , Montiel-Armendariz Andrea , Li Lucy Z. , Pasare Chandrashekhar , Hou Baidong , Hamerman Jessica A. , Acharya Mridu
Published: November 2024

B cell adapter for PI 3-kinase (BCAP) is an adaptor molecule associated with signaling through multiple immune receptors, including the B cell receptor (BCR). However, B cell–intrinsic role of BCAP in antibody responses is unclear. We investigated the role of BCAP in B cell response to viral particles and found a previously unidentified mechanism by which BCAP regulates antigen-specific responses. B cell–specific deletion of BCAP in mice leads to decreases in antigen-specific responses through defects in BCR-antigen endocytosis. BCAP is necessary to orchestrate actin reorganization around the antigen for efficient endocytosis through BCR and intracellular processing of antigens. Therefore, loss of BCAP from B cells leads to defects in antigen endocytosis, hampering the propagation of antigen-derived signals and decreasing the ability of B cells to present antigens to T cells. Thus, our study clarifies how BCAP regulates B cell responses to complex antigens and elucidates that antigen positioning inside B cells determines different B cell activation outcomes.
Mechano-gradients drive morphogen-noise correction to ensure robust patterning
Authors: Aoki Kana , Higuchi Taiki , Akieda Yuki , Matsubara Kotone , Ohkawa Yasuyuki , Ishitani Tohru
Published: November 2024

Morphogen gradients instruct cells to pattern tissues. Although the mechanisms by which morphogens transduce chemical signals have been extensively studied, the roles and regulation of the physical communication between morphogen-receiver cells remain unclear. Here, we show that the Wnt/β-catenin–morphogen gradient, which patterns the embryonic anterior-posterior (AP) axis, generates intercellular tension gradients along the AP axis by controlling membrane cadherin levels in zebrafish embryos. This “mechano-gradient” is used for the cell competition–driven correction of noisy morphogen gradients. Naturally and artificially generated unfit cells, producing noisy Wnt/β-catenin gradients, induce local deformation of the mechano-gradients that activate mechanosensitive calcium channels in the neighboring fit cells, which then secrete annexin A1a to kill unfit cells. Thus, chemo-mechanical interconversion–mediated competitive communication between the morphogen-receiver cells ensures precise tissue patterning.
The HDAC6 inhibitor AVS100 (SS208) induces a pro-inflammatory tumor microenvironment and potentiates immunotherapy
Authors: Kovalovsky Damian , Noonepalle Satish , Suresh Manasa , Kumar Dileep , Berrigan Michael , Gajendran Nithya , Upadhyay Sumit , Horvath Anelia , Kim Allen , Quiceno-Torres David , Musunuri Karthik , Villagra Alejandro
Published: November 2024

Histone deacetylase 6 (HDAC6) inhibition is associated with an increased pro-inflammatory tumor microenvironment and antitumoral immune responses. Here, we show that the HDAC6 inhibitor AVS100 (SS208) had an antitumoral effect in SM1 melanoma and CT26 colon cancer models and increased the efficacy of anti–programmed cell death protein 1 treatment, leading to complete remission in melanoma and increased response in colon cancer. AVS100 treatment increased pro-inflammatory tumor-infiltrating macrophages and CD8 effector T cells with an inflammatory and T cell effector gene signature. Acquired T cell immunity and long-term protection were evidenced as increased immunodominant T cell clones after AVS100 treatment. Last, AVS100 showed no mutagenicity, toxicity, or adverse effects in preclinical good laboratory practice studies, part of the package that has led to US Food and Drug Administration clearance of an investigational new drug application for initiating clinical trials. This would be a first-in-human combination therapy of pembrolizumab with HDAC6 inhibition for locally advanced or metastatic solid tumors.
Archaeal type six secretion system mediates contact-dependent antagonism
Authors: Zachs Tobias , Malit Jessie James L. , Xu Jingwei , Schürch Alexandra , Sivabalasarma Shamphavi , Nußbaum Phillip , Albers Sonja-Verena , Pilhofer Martin
Published: November 2024

Microbial communities are shaped by cell-cell interactions. Although archaea are often found in associations with other microorganisms, the mechanisms structuring these communities are poorly understood. Here, we report on the structure and function of haloarchaeal contractile injection systems (CISs). Using a combination of functional assays and time-lapse imaging, we show that
Halogeometricum borinquense
exhibits antagonism toward
Haloferax volcanii
by inducing cell lysis and inhibiting proliferation. This antagonism is contact-dependent and requires a functional CIS, which is encoded by a gene cluster that is associated with toxin-immunity pairs. Cryo–focused ion beam milling and imaging by cryo–electron tomography revealed that these CISs are bound to the cytoplasmic membrane, resembling the bacterial type six secretion systems (T6SSs). We show that related T6SS gene clusters are conserved and expressed in other haloarchaeal strains, which exhibit antagonistic behavior. Our data provide a mechanistic framework for understanding how archaea may shape microbial communities and affect the food webs they inhabit.
Tumor-specific delivery of clickable inhibitor for PD-L1 degradation and mitigating resistance of radioimmunotherapy
Authors: Hou Bo , Ye Jiayi , Huang Lujia , Cheng Wenhao , Chen Fangmin , Zhou Huiling , Pan Jiaxing , Gao Jing , Lai Yi , Zhao Yujun , Huang Wei , Yu Haijun , Xu Zhiai
Published: November 2024

Achieving selective and durable inhibition of programmed death ligand 1 (PD-L1) in tumors for T cell activation remains a major challenge in immune checkpoint blockade therapy. We herein presented a set of clickable inhibitors for spatially confined PD-L1 degradation and radioimmunotherapy of cancer. Using metabolic glycan engineering click bioorthogonal chemistry, PD-L1 expressed on tumor cell membranes was labeled with highly active azide groups. This enables covalently binding of the clickable inhibitor with PD-L1 and subsequent PD-L1 degradation. A pH-activatable nanoparticle responding to extracellular acidic pH of tumor was subsequently used to deliver the clickable PD-L1 inhibitor into extracellular tumor microenvironment for depleting PD-L1 on the surface of tumor cell and macrophage membranes in vivo. We further demonstrated that a combination of the clickable PD-L1 inhibitor with radiotherapy (RT) eradicated the established tumor by inhibiting RT–up-regulated PD-L1 in the tumor tissue. Therefore, selective PD-L1 blockade in tumors via the clickable PD-L1 inhibitor offers a versatile approach to promote cancer immunotherapy.
A sample of the Moon’s far side retrieved by Chang’e-6 contains 2.83-billion-year-old basalt
Authors: Cui Zexian , Yang Qing , Zhang Yan-Qiang , Wang Chengyuan , Xian Haiyang , Chen Zhiming , Xiao Zhiyong , Qian Yuqi , Head James W. , Neal Clive R. , Xiao Long , Luo Fanglu , Chen Jingyou , He Pengli , Cao Yonghua , Zhou Qin , Huang Fangfang , Chen Linli , Wei Bo , Wang Jintuan , Yang Ya-Nan , Li Shan , Yang Yiping , Lin Xiaoju , Zhu Jianxi , Zhang Le , Xu Yi-Gang
Published: November 2024

Remote sensing observations have shown that the far side of the Moon (lunar farside) has different geology and rock composition to those of the nearside, including the abundances of potassium, rare earth elements, and phosphorus (collectively known as KREEP). The Chang’e-6 (CE-6) spacecraft collected samples from the South Pole–Aitken (SPA) basin on the farside and brought them to Earth. We used lead-lead and rubidium-strontium isotope systems to date low-titanium basalt in a CE-6 sample, finding a consistent age of 2830 (±5) million years. We interpret this as the date of volcanism in SPA and incorporate it into lunar crater chronology. Strontium, neodymium, and lead isotopes indicate that the volcanic magma was from a lunar mantle source depleted in incompatible elements and containing almost no KREEP component.
Mutant prevention concentrations,
in vitro
resistance evolution dynamics, and mechanisms of resistance to imipenem and imipenem/relebactam in carbapenem-susceptible
Klebsiella pneumoniae
isolates showing ceftazidime/avibactam resistance
Authors: Blanco-Martín Tania , González-Pinto Lucía , Aja-Macaya Pablo , Rodríguez-Pallares Salud , Sánchez-Peña Lucía , Gato Eva , Fernández-López María del Carmen , Outeda-García Michelle , Rodríguez-Coello Arianna , Pedraza-Merino Rosa , Alonso-García Isaac , Vázquez-Ucha Juan Carlos , Martínez-Martínez Luis , Arca-Suárez Jorge , Beceiro Alejandro , Bou Germán
Published: November 2024

Klebsiella pneumoniae
carbapenemase (KPC) variants selected during ceftazidime/avibactam treatment usually develop susceptibility to carbapenems and carbapenem/β-lactamase inhibitors, such as imipenem and imipenem/relebactam. We analyzed imipenem and imipenem/relebactam single-step mutant frequencies, resistance development trajectories and differentially selected resistance mechanisms using two representative
K. pneumoniae
isolates that had developed ceftazidime/avibactam resistance during therapy (ST512/KPC-31 and ST258/KPC-35). Mutant frequencies and mutant prevention concentrations were measured in Mueller–Hinton agar plates containing incremental concentrations of imipenem or imipenem/relebactam. Resistance dynamics were determined after incubation for 7 days in 10 mL MH tubes containing incremental concentrations of each antibiotic or combination, up to 64 times their baseline MIC. Two colonies per strain from each experiment were characterized by antimicrobial susceptibility testing and whole genome sequencing. The impact of KPC variants identified in resistant mutants on β-lactam resistance was investigated by cloning experiments. Imipenem/relebactam suppressed the emergence of resistant mutants at lower concentrations than imipenem, slowed down resistance development for both strains, and the resulting mutants yielded lower MICs of carbapenems and carbapenem/β-lactamase inhibitors than those selected with imipenem alone. Characterization of resistant mutants revealed that imipenem resistance was mainly caused by inactivation of OmpK36 and mutations in the KPC β-lactamase. Imipenem/relebactam-resistant mutants also maintained OmpK36 alterations, but mutations in KPC were much less frequent compared with those selected with imipenem alone. Genetic and biochemical characterization of the KPC derivatives identified in the resistant mutants confirmed their role in carbapenem resistance. Our data positions imipenem/relebactam as an attractive therapeutic option for combating ceftazidime/avibactam-resistant KPC-producing
K. pneumoniae
infections.
The extended recovery ring-stage survival assay is a scalable alternative for artemisinin susceptibility phenotyping of fresh
Plasmodium falciparum
isolates
Authors: Okitwi Martin , Shoue Douglas A. , Checkley Lisa A. , Orena Stephen , Ceja Frida G. , Taremwa Yoweri , Tumwebaze Patrick K. , Katairo Thomas , Byaruhanga Oswald , Sievert Mackenzie A.C. , Garg Shreeya , Kreutzfeld Oriana K. , Legac Jennifer , Bailey Jeffrey A. , Nsobya Sam L. , Conrad Melissa D. , Rosenthal Philip J. , Ferdig Michael T. , Cooper Roland A.
Published: November 2024

Artemisinin partial resistance (ART-R) has emerged in eastern Africa, necessitating regular surveillance of susceptibility of
Plasmodium falciparum
to artemisinins. The microscopy-based ring-stage survival assay (RSA) provides a laboratory correlate of ART-R but is limited by low throughput and subjectivity of microscopic counts of viable parasites. The extended recovery ring-stage survival assay (eRRSA) replaces microscopy with efficient quantitative PCR (qPCR) readouts but has been studied only with culture-adapted
P. falciparum
clones. We measured susceptibility to dihydroartemisinin (DHA) after a 6-h incubation with 700-nM DHA, followed by culture without drug, by comparing survival with that of untreated controls by microscopy (the RSA) or qPCR (the eRRSA) and also performed standard growth inhibition (half-maximal inhibitory concentration [IC
50
]) assays for 122
P. falciparum
isolates freshly collected in eastern and northern Uganda from March to July 2022. The median values for RSA survival, eRRSA fold change, and DHA IC
50
were 3.0%, 46.2, and 3.2 nM, respectively. RSA percent survival and eRRSA fold changes correlated strongly (Spearman correlation coefficient [
r

s

] = −0.7411,
P
< 0.0001), with modest associations between the presence of validated
P. falciparum
Kelch13 ART-R mutations (C469Y or A675V) and RSA (median survival 2.6% for wild type [WT] vs 4.1% for mutant,
P
= 0.01), or eRRSA (median fold change 63.4 for WT vs 30.9 for mutant,
P
= 0.003) results. Significant correlations were also observed between DHA IC
50
values and both RSA percent survival (

r
s

= 0.4235,
P
< 0.0001) and eRRSA fold changes (

r
s

= −0.4116,
P
< 0.0001). The eRRSA is a scalable alternative for phenotyping fresh
P. falciparum
isolates, providing similar results with improved throughput.