bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between middle childhood executive control aspects and adolescent substance use and externalizing and internalizing problems
Authors: Mason W. Alex , Fleming Charles B. , Patwardhan Irina , Guo Ying , James Tiffany D. , Nelson Jennifer Mize , Espy Kimberly Andrews , Nelson Timothy D.
Published: May 2024

This study examines the degree to which two middle childhood executive control aspects, working memory and combined inhibitory control/flexible shifting, predict adolescent substance use and externalizing and internalizing problems. Participants were 301 children (ages 3–6 years; 48.2% male) recruited from a Midwestern city in the United States and followed into adolescence (ages 14–18 years). Working memory had a statistically significant unadjusted association with externalizing problems (r = −.30, p = .003) in a confirmatory factor analysis. Neither factor significantly predicted any of the adolescent outcomes in a structural equation model that adjusted for each EC aspect, sociodemographic covariates, and middle childhood externalizing and internalizing problems. Stronger prediction of EC aspects might not emerge until they become more fully differentiated later in development.
Periodontal pathogen Aggregatibacter actinomycetemcomitansJP2 correlates with colonic leukocytes decrease and gut microbiome imbalance in mice
Authors: da Costa André L. A. , Soares Mariana A. , Lourenço Talita G. B. , Guimarães‐Pinto Kamila , Filardy Alessandra D. , de Oliveira Adriana Miranda , de Luca Beatriz Gouvêa , Magliano D’ Angelo Carlo , Araujo Olga M. O. , Moura Larissa , Lopes Ricardo Tadeu , Palhares de Miranda Ana Luisa , Tributino Jorge L. M. , Vieira Colombo Ana Paula
Published: May 2024

Aim

Evidence suggests that translocation of oral pathogens through the oral–gut axis may induce intestinal dysbiosis. This study aimed to evaluate the impact of a highly leukotoxic Aggregatibacter actinomycetemcomitans (Aa) strain on the gut microbiota, intestinal mucosal integrity and immune system in healthy mice.

Methods

Eight‐week‐old male C57BL6 mice were divided into control (n = 16) and JP2 groups (n = 19), which received intragastric gavage with PBS and with a suspension of Aa JP2 (HK921), respectively, twice a week for 4 weeks. Colonic lamina propria, fecal material, serum, gingival tissues, and mandibles were obtained for analyses of leukocyte populations, inflammatory mediators, mucosal integrity, alveolar bone loss, and gut microbiota. Differences between groups for these parameters were examined by non‐parametric tests.

Results

The gut microbial richness and the number of colonic macrophages, neutrophils, and monocytes were significantly lower in Aa JP2‐infected mice than in controls (p < .05). In contrast, infected animals showed higher abundance of Clostridiaceae, Lactobacillus taiwanensis, Helicobacter rodentium, higher levels of IL‐6 expression in colonic tissues, and higher splenic MPO activity than controls (p < .05). No differences in tight junction expression, serum endotoxin levels, and colonic inflammatory cytokines were observed between groups. Infected animals presented also slightly more alveolar bone loss and gingival IL‐6 levels than controls (p < .05).

Conclusion

Based on this model, intragastric administration of Aa JP2 is associated with changes in the gut ecosystem of healthy hosts, characterized by less live/recruited myeloid cells, enrichment of the gut microbiota with pathobionts and decrease in commensals. Negligible levels of colonic pro‐inflammatory cytokines, and no signs of mucosal barrier disruption were related to these changes.
Mandibular morphology in four species of insectivorous bats: the impact of sexual dimorphism and geographical differentiation
Authors: Crampton D. A. , Giacomini G. , Meloro C.
Published: May 2024

Chiroptera is the only mammalian order that has adapted to active flight, offering a unique platform to study ecomorphological adaptations. While bats exhibit a diverse diet, the focus of this study is on insectivorous bats, specifically four species: Myotis daubentonii, Nyctalus noctula, Plecotus austriacus and Rhinolophus ferrumequinum. It is important to note that despite sharing an insectivorous diet, these species occupy different ecological niches, perform distinct feeding strategies and explore varied habitats to capture prey. Using 2‐D geometric morphometrics, we analysed a sample of mandibles to identify differences in size and shape among these species. We also investigated ecogeographical variation within their overlapping distribution across continental Europe. Significant differences in both mandibular size and shape were found among the four species. Sexual dimorphism influenced only the mandibular shape of R. ferrumequinum. A latitudinal gradient in mandibular size was found solely in N. noctula, while longitude significantly explained shape variation in M. daubentonii. These findings suggest that even within the ecological guild of insectivorous bats, there exists a diverse range of morphological adaptations that allow these species to occupy distinct ecological niches.
Navigating the paradox: Exploring resident experiences of vulnerability
Authors: Nichol Heather , Turnnidge Jennifer , Dalgarno Nancy , Trier Jessica
Published: May 2024

Introduction

Learning and growth in postgraduate medical education (PGME) often require vulnerability, defined as a state of openness to uncertainty, risk, and emotional exposure. However, vulnerability can threaten a resident's credibility and professional identity. Despite this tension, studies examining vulnerability in PGME are limited. As such, this study aims to explore residents' experiences of vulnerability, including the factors that influence vulnerability in PGME.

Methods

Using a constructivist grounded theory approach, individual semi‐structured interviews were conducted with 15 residents from 10 different specialities. Interview transcripts were coded and analysed iteratively. Themes were identified and relationships among themes were examined to develop a theory describing vulnerability in PGME.

Results

Residents characterised vulnerability as a paradox represented by two overarching themes. ‘Experiencing the tensions of vulnerability’ explores the polarities between being a fallible, authentic learner and an infallible, competent professional. ‘Navigating the vulnerability paradox’ outlines the factors influencing the experience of vulnerability and its associated outcomes at the intrapersonal, interpersonal, and systems levels. Residents described needing to have the bandwidth to face the risks and emotional labour of vulnerability. Opportunities to build connections with social agents, including clinical teachers and peers, facilitated vulnerability. The sociocultural context shaped both the experience and outcomes of vulnerability as residents faced the symbolic mask of professionalism.

Conclusion

Residents experience vulnerability as a paradox shaped by intrapersonal, interpersonal, and systems level factors. These findings capture the nuance and complexity of vulnerability in PGME and offer insight into creating supportive learning environments that leverage the benefits of vulnerability while acknowledging its risks. There is a need to translate this understanding into systems‐based change to create supportive PGME environments, which value and celebrate vulnerability.
The recombination initiation functions DprA and RecFOR suppress microindel mutations in Acinetobacter baylyiADP1
Authors: Liljegren Mikkel M. , Gama João A. , Johnsen Pål J. , Harms Klaus
Published: May 2024

Short‐Patch Double Illegitimate Recombination (SPDIR) has been recently identified as a rare mutation mechanism. During SPDIR, ectopic DNA single‐strands anneal with genomic DNA at microhomologies and get integrated during DNA replication, presumably acting as primers for Okazaki fragments. The resulting microindel mutations are highly variable in size and sequence. In the soil bacterium Acinetobacter baylyi, SPDIR is tightly controlled by genome maintenance functions including RecA. It is thought that RecA scavenges DNA single‐strands and renders them unable to anneal. To further elucidate the role of RecA in this process, we investigate the roles of the upstream functions DprA, RecFOR, and RecBCD, all of which load DNA single‐strands with RecA. Here we show that all three functions suppress SPDIR mutations in the wildtype to levels below the detection limit. While SPDIR mutations are slightly elevated in the absence of DprA, they are strongly increased in the absence of both DprA and RecA. This SPDIR‐avoiding function of DprA is not related to its role in natural transformation. These results suggest a function for DprA in combination with RecA to avoid potentially harmful microindel mutations, and offer an explanation for the ubiquity of dprA in the genomes of naturally non‐transformable bacteria.
Exploring the connections between ER‐based lipid metabolism and plasma membrane nanodomain signaling
Authors: Pan Xue , Mastrella Sophia , Khamzaaliyeva Mohinur , Ashley Didier‐Deschamps
Published: May 2024

Recent advancements in our understanding of cell membrane dynamics have shed light on the importance of plasma membrane (PM) nanodomains in plant cell signaling. Nevertheless, many aspects of membrane nanodomains, including their regulatory mechanisms and biological functions, remain enigmatic. To address this knowledge gap, our review article proposes a novel perspective wherein signaling pathways target endoplasmic reticulum (ER)‐based lipid metabolism to exert control over the formation and function of membrane nanodomains. Subsequently, these nanodomains reciprocate by influencing the localization and activity of signaling molecules at the PM. We place a specific emphasis on ER‐based enzymatic reactions, given the ER's central role in membrane lipid biosynthesis and its capacity to directly impact PM lipid composition, particularly with regard to saturation levels – an essential determinant of nanodomain properties. The interplay among cell signaling, glycerolipid metabolism, and PM nanodomain may create feedforward/feedback loops that fine‐tune cellular responses to developmental and environmental cues.
A genome‐wide association study uncovers a ZmRap2.7‐ZCN9/ZCN10 module to regulate ABA signalling and seed vigour in maize
Authors: Guo Shasha , Ai Junmin , Zheng Nannan , Hu Hairui , Xu Zhuoyi , Chen Quanquan , Li Li , Liu Yunjun , Zhang Hongwei , Li Jieping , Pan Qingchun , Chen Fanjun , Yuan Lixing , Fu Junjie , Gu Riliang , Wang Jianhua , Du Xuemei
Published: May 2024

Seed vigour, including rapid, uniform germination and robust seedling establishment under various field conditions, is becoming an increasingly essential agronomic trait for achieving high yield in crops. However, little is known about this important seed quality trait. In this study, we performed a genome‐wide association study to identify a key transcription factor ZmRap2.7, which regulates seed vigour through transcriptionally repressing expressions of three ABA signalling genes ZmPYL3, ZmPP2C and ZmABI5 and two phosphatidylethanolamine‐binding genes ZCN9 and ZCN10. In addition, ZCN9 and ZCN10 proteins could interact with ZmPYL3, ZmPP2C and ZmABI5 proteins, and loss‐of‐function of ZmRap2.7 and overexpression of ZCN9 and ZCN10 reduced ABA sensitivity and seed vigour, suggesting a complex regulatory network for regulation of ABA signalling mediated seed vigour. Finally, we showed that four SNPs in ZmRap2.7 coding region influenced its transcriptionally binding activity to the downstream gene promoters. Together with previously identified functional variants within and surrounding ZmRap2.7, we concluded that the distinct allelic variations of ZmRap2.7 were obtained independently during maize domestication and improvement, and responded separately for the diversities of seed vigour, flowering time and brace root development. These results provide novel genes, a new regulatory network and an evolutional mechanism for understanding the molecular mechanism of seed vigour.
Salt tolerance in mungbean is associated with controlling Na and Cl transport across roots, regulating Na and Cl accumulation in chloroplasts and maintaining high K in root and leaf mesophyll cells
Authors: Iqbal Md Shahin , Clode Peta L. , Malik Al Imran , Erskine William , Kotula Lukasz
Published: May 2024

Salinity tolerance requires coordinated responses encompassing salt exclusion in roots and tissue/cellular compartmentation of salt in leaves. We investigated the possible control points for salt ions transport in roots and tissue tolerance to Na+ and Cl– in leaves of two contrasting mungbean genotypes, salt‐tolerant Jade AU and salt‐sensitive BARI Mung‐6, grown in nonsaline and saline (75 mM NaCl) soil. Cryo‐SEM X‐ray microanalysis was used to determine concentrations of Na, Cl, K, Ca, Mg, P, and S in various cell types in roots related to the development of apoplastic barriers, and in leaves related to photosynthetic performance. Jade AU exhibited superior salt exclusion by accumulating higher [Na] in the inner cortex, endodermis, and pericycle with reduced [Na] in xylem vessels and accumulating [Cl] in cortical cell vacuoles compared to BARI Mung‐6. Jade AU maintained higher [K] in root cells than BARI Mung‐6. In leaves, Jade AU maintained lower [Na] and [Cl] in chloroplasts and preferentially accumulated [K] in mesophyll cells than BARI Mung‐6, resulting in higher photosynthetic efficiency. Salinity tolerance in Jade AU was associated with shoot Na and Cl exclusion, effective regulation of Na and Cl accumulation in chloroplasts, and maintenance of high K in root and leaf mesophyll cells.
Indian Preference and the status of American Indians and Alaska Natives in the federal service: Employment, earnings, authority, and perceptions of fairness
Authors: Lewis Gregory B. , Williams Jack F.
Published: May 2024

Public administration scholars have largely ignored American Indians and Alaska Natives in their studies of racial disparities in the federal service, despite strong reasons to believe they face discrimination. Using three large federal data sets (the American Community Survey, federal personnel records, and the Federal Employee Viewpoint Survey), we compare the status of American Indians and Alaska Natives in the federal service to both Whites and other minorities. We find that, largely due to Indian Preference, American Indians and Alaska Natives are much more likely than Blacks, Whites, Latinos, and Asians to hold federal jobs, but they are highly concentrated in the Bureau of Indian Affairs and the Indian Health Service, agencies with which they have a sordid and fraught history. This concentration allows them to work in positions that may advance the interests of their communities and increases their probabilities of being supervisors, but it does not prevent them from being among the poorest‐paid and least‐satisfied employees in the federal service.
IFIH1 loss of function predisposes to inflammatory and SARS‐CoV‐2‐related infectious diseases
Authors: Najm Rania , Yavuz Lemis , Jain Ruchi , El Naofal Maha , Ramaswamy Sathishkumar , Abuhammour Walid , Loney Tom , Nowotny Norbert , Alsheikh‐Ali Alawi , Abou Tayoun Ahmad , Kandasamy Richard K.
Published: May 2024

The IFIH1 gene, encoding melanoma differentiation‐associated protein 5 (MDA5), is an indispensable innate immune regulator involved in the early detection of viral infections. Previous studies described MDA5 dysregulation in weakened immunological responses, and increased susceptibility to microbial infections and autoimmune disorders. Monoallelic gain‐of‐function of the IFIH1 gene has been associated with multisystem disorders, namely Aicardi–Goutieres and Singleton–Merten syndromes, while biallelic loss causes immunodeficiency. In this study, nine patients suffering from recurrent infections, inflammatory diseases, severe COVID‐19 or multisystem inflammatory syndrome in children (MIS‐C) were identified with putative loss‐of‐function IFIH1 variants by whole‐exome sequencing. All patients revealed signs of lymphopaenia and an increase in inflammatory markers, including CRP, amyloid A, ferritin and IL‐6. One patient with a pathogenic homozygous variant c.2807+1G>A was the most severe case showing immunodeficiency and glomerulonephritis. The c.1641+1G>C variant was identified in the heterozygous state in patients suffering from periodic fever, COVID‐19 or MIS‐C, while the c.2016delA variant was identified in two patients with inflammatory bowel disease or MIS‐C. There was a significant association between IFIH1 monoallelic loss of function and susceptibility to infections in males. Expression analysis showed that PBMCs of one patient with a c.2016delA variant had a significant decrease in ISG15, IFNA and IFNG transcript levels, compared to normal PBMCs, upon stimulation with Poly(I:C), suggesting that MDA5 receptor truncation disrupts the immune response. Our findings accentuate the implication of rare monogenic IFIH1 loss‐of‐function variants in altering the immune response, and severely predisposing patients to inflammatory and infectious diseases, including SARS‐CoV‐2‐related disorders.
Sex differences in 3‐ to 5‐year‐old children's motor competence: A pooled cross‐sectional analysis of 6241 children
Authors: Martins Clarice , Webster Elizabeth K. , Romo‐Perez Vicente , Duncan Michael , Lemos Luís Filipe , Staiano Amanda , Okely Anthony , Magistro Daniele , Carlevaro Fabio , Bardid Farid , Magno Francesca , Nobre Glauber , Estevan Isaac , Mota Jorge , Ning Ke , Robinson Leah E. , Lenoir Matthieu , Quan Minghui , Valentini Nadia , Dehkordi Parvaneh S. , Cross Penny , Jones Rachel , S. Henrique Rafael , Salami Sedigheh , Chen Sitong , Diao Yucui , Bandeira Paulo R. , Barnett Lisa M.
Published: May 2024

There is some, albeit inconsistent, evidence supporting sex differences in preschoolers' motor competence (MC), with these observations not uniform when analyzed by age, and cultural groups. Thus, this study examined sex differences across ages in 3‐ to 5‐year‐old children's MC. A cross‐country pooled sample of 6241 children aged 3–5 years (49.6% girls) was assessed for MC using the Test of Gross Motor Development—2nd/3rd edition, and children were categorized into groups of age in months. Multiple linear regression models and predictive margins were calculated to explore how sex and age in months affect scores of MC (i.e., locomotor and ball skills), with adjustments for country and BMI. The Chow's Test was used to test for the presence of a structural break in the data. Significant differences in favor of girls were seen at 57–59 and 66–68 months of age for locomotor skills; boys performed better in ball skills in all age periods, except for 42–44 and 45–47 months of age. The higher marginal effects were observed for the period between 45–47 and 48–50 months for locomotor skills (F = 30.21; and F = 25.90 for girls and boys, respectively), and ball skills (F = 19.01; and F = 42.11 for girls and boys, respectively). A significantly positive break point was seen at 45–47 months, highlighting the age interval where children's MC drastically improved. The identification of this breakpoint provides an evidence‐based metric for when we might expect MC to rapidly increase, and an indicator of early delay when change does not occur at that age.
Rice myo‐inositol‐3‐phosphate synthase 2 (RINO2) alleviates heat injury‐induced impairment in pollen germination and tube growth by modulating Ca2+ signaling and actin filament cytoskeleton
Authors: Zhou Lujian , Asad Muhammad‐Asad‐Ullah , Guan Xianyue , Pan Gang , Zhang Yan , Cheng Fangmin
Published: May 2024

Low phytic acid (lpa) crop is considered as an effective strategy to improve crop nutritional quality, but a substantial decrease in phytic acid (PA) usually has negative effect on agronomic performance and its response to environment adversities. Myo‐inositol‐3‐phosphate synthase (MIPS) is the rate‐limiting enzyme in PA biosynthesis pathway, and regarded as the prime target for engineering lpa crop. In this paper, the rice MIPS gene (RINO2) knockout mutants and its wild type were performed to investigate the genotype‐dependent alteration in the heat injury‐induced spikelet fertility and its underlying mechanism for rice plants being imposed to heat stress at anthesis. Results indicated that RINO2 knockout significantly enhanced the susceptibility of rice spikelet fertility to heat injury, due to the severely exacerbated obstacles in pollen germination and pollen tube growth in pistil for RINO2 knockout under high temperature (HT) at anthesis. The loss of RINO2 function caused a marked reduction in inositol and phosphatidylinositol derivative concentrations in the HT‐stressed pollen grains, which resulted in the strikingly lower content of phosphatidylinositol 4,5‐diphosphate (PI (4,5) P2) in germinating pollen grain and pollen tube. The insufficient supply of PI (4,5) P2 in the HT‐stressed pollen grains disrupted normal Ca2+ gradient in the apical region of pollen tubes and actin filament cytoskeleton in growing pollen tubes. The severely repressed biosynthesis of PI (4,5) P2 was among the regulatory switch steps leading to the impaired pollen germination and deformed pollen tube growth for the HT‐stressed pollens of RINO2 knockout mutants.
A Solanum lycopersicum polyamine oxidase contributes to the control of plant growth, xylem differentiation, and drought stress tolerance
Authors: D'Incà Riccardo , Mattioli Roberto , Tomasella Martina , Tavazza Raffaela , Macone Alberto , Incocciati Alessio , Martignago Damiano , Polticelli Fabio , Fraudentali Ilaria , Cona Alessandra , Angelini Riccardo , Tavazza Mario , Nardini Andrea , Tavladoraki Paraskevi
Published: May 2024

Polyamines are involved in several plant physiological processes. In Arabidopsis thaliana, five FAD‐dependent polyamine oxidases (AtPAO1 to AtPAO5) contribute to polyamine homeostasis. AtPAO5 catalyzes the back‐conversion of thermospermine (T‐Spm) to spermidine and plays a role in plant development, xylem differentiation, and abiotic stress tolerance. In the present study, to verify whether T‐Spm metabolism can be exploited as a new route to improve stress tolerance in crops and to investigate the underlying mechanisms, tomato (Solanum lycopersicum) AtPAO5 homologs were identified (SlPAO2, SlPAO3, and SlPAO4) and CRISPR/Cas9‐mediated loss‐of‐function slpao3 mutants were obtained. Morphological, molecular, and physiological analyses showed that slpao3 mutants display increased T‐Spm levels and exhibit changes in growth parameters, number and size of xylem elements, and expression levels of auxin‐ and gibberellin‐related genes compared to wild‐type plants. The slpao3 mutants are also characterized by improved tolerance to drought stress, which can be attributed to a diminished xylem hydraulic conductivity that limits water loss, as well as to a reduced vulnerability to embolism. Altogether, this study evidences conservation, though with some significant variations, of the T‐Spm‐mediated regulatory mechanisms controlling plant growth and differentiation across different plant species and highlights the T‐Spm role in improving stress tolerance while not constraining growth.
Implementation of sexual risk behavior donor screening in Canada
Authors: Goldman Mindy , Lewin Antoine , Renaud Christian , O'Brien Sheila F.
Published: May 2024

Background

The two Canadian blood suppliers, Canadian Blood Services and Héma‐Québec, removed the time‐based deferral for men who have sex with men and adopted criteria assessing sexual risk behaviors. We report the impact of these changes on the safety and adequacy of the Canadian blood supply.

Study Design and Methods

Since 2022, all donors are asked if (1) they have had a new partner and (2) more than one sexual partner in the last 3 months. Donors answering yes to either question are asked if they had anal sex in the last 3 months; if yes, they are deferred for 3 months. We followed HIV rates for the 18 months before and 14 (Héma‐Québec) or 18 months (Canadian Blood Services) post‐implementation and interviewed HIV‐positive whole blood donors. We assessed the number and characteristics of whole blood donors answering yes to the two first questions with or without deferral.

Results

There were four HIV‐positive donations out of 1,492,355 donations pre‐implementation and four out of 1,447,772 post‐implementation (0.27/100,000 vs. 0.28/100,000, p = 1.00). Post‐implementation, one HIV‐positive donor was non‐compliant with multiple criteria, no risk factors were identified in the others. 3.2% of donors answered yes to questions (1) and/or (2); 0.17% were deferred for a new partner and/or more than one partner and anal sex. Deferral rates were highest in first time, younger donors, and similar in males and females.

Conclusion

Implementation of sexual risk behavior donor screening resulted in unchanged HIV rates to date and a manageable deferral rate.
Utilizing Vigna mungo wash water for simultaneous power generation and desalination using two distinct anodes in a microbial desalination cell
Authors: Prakash Sandhya , Naina Mohamed Samsudeen , Ponnusamy Kalaichelvi
Published: May 2024

This study aims to improve the performance of microbial desalination cell (MDC) using Vigna mungo (Black gram) wash water, reported for the first time as an anolyte utilizing a graphite plate and carbon brush as the anode. Power generation was facilitated by the exoelectrogen, Shewanella putrefaciens MTCC 8104. Polarization studies revealed that the graphite plate MDC attained a high power density of 2720 ± 50 μW/m2 compared to carbon brush for two electrode pairs. The COD removal and desalination efficiency were better for carbon brush MDC, achieving 58.17 ± 2% and 38.14 ± 2% removal, respectively. Power production can be enhanced by increasing the cathode's ability to accept the electrons, reducing the ageing of biofilm and promoting complete oxidation of the substrates. Upon improving its performance, MDC can act as a sustainable technology, collaborating with industries seeking solutions for wastewater treatment, energy generation and agricultural sectors on a large scale.
It’s a Material World
Authors: Smil Vaclav
Published: May 2024

One of the greatest challenges of this century is the reduction or elimination of worldwide greenhouse gas emissions, primarily by moving the global energy system from carbon-based fuels to low- or zero-carbon systems. The energy systems that produce carbon emissions are inherently physical and must be replaced by other physical systems, which means the material constraints of building this new infrastructure cannot be ignored.
Development and Preliminary Evaluation of a Bimodal Foot Prosthesis for Walking and Running
Authors: Ziemnicki David M. , McDonald Kirsty A. , Molitor Stephanie L. , Egolf Jeremiah B. , Cruz Justin P. , Lee Kathryn E. , Zelik Karl E.
Published: May 2024

People often alternate between bouts of walking and running, for instance, when adults participate in recreational activities. Transitioning between activities can be challenging for prosthesis users because existing prosthetic feet are not well-suited for both tasks. Meanwhile, switching between prostheses for different tasks is often impractical. Collectively, these challenges can present barriers to physical activity participation for people with limb loss, which can negatively impact social or physical health. This work describes the development and evaluation of a passive bimodal prosthetic foot prototype with different configurations and stiffnesses for walking and running. Users rated the bimodal prosthesis higher for standing and walking compared to a running prosthesis (+2.3 for both tasks on a seven-point Likert scale). Users rated the bimodal prosthesis higher for running compared to a walking prosthesis (+1.7 and +0.5 for 2.0 and 2.5 m/s running, respectively). Changing from walking to running mode increased the device's stiffness by 23–84%, depending on the user's preference. Users could switch between bimodal prosthesis walking and running modes quickly (21.3 ± 12.0 s). Overall, the preliminary results were encouraging in terms of user satisfaction, stiffness change between modes, and mode-switching speed. These findings motivate future exploration of this bimodal prosthesis concept.
Numerical Study on the Effect of Channel Configuration on Mixture Formation of an Axial Flow Wave Rotor Combustor
Authors: Feng Zhan , Li Jianzhong , Gong Erlei , Yao Qian , Chen Xinyu , Chen Yue
Published: May 2024

Wave rotor combustor technology is a new technical means to improve the thermal efficiency of aero-engine by using unsteady flow and constant volume combustion. In this article, the influence of wave rotor combustor channel structure on the mixture formation in the channel was studied by numerical simulation. The results showed that the internal flow field structure and change of any structure channel are similar. Flow separation will occur in all channels, and wake regions will be formed in the channels. The turbulence kinetic energy in the wake region was increased, and the velocity and pressure were decreased, resulting in the vortex in the channel. When the channel width was reduced to half of the original design, the relative standard deviation (RSD) of the mixture was reduced by at least 54.92% compared to the original design, and the global fuel mass fraction in the channel was increased by at least 27.32%. In addition, the fluctuation of discharge pressure was also reduced. The reduction of the channel height does not lead to a significant improvement in the aforementioned results. This study can provide guidance for the structural design of wave rotor combustor channel.
Optical Considerations for Designing Laser-Based Volumetric Particle Tracking Velocimetry
Authors: Abitan Haim , Zhang Yisheng , Ribergård Simon L. , Velte Clara M.
Published: May 2024

The trend to conduct volumetric particle tracking velocimetry (PTV) experiments with ever-increasing volumes, at a given particle density, poses increasing challenges on the design of such experiments in terms of the power of the laser source and the image analysis. These challenges, on one hand, require a reliable model to estimate the current signal from a pixel on a complementary metal-oxide semiconductor (CMOS) detector due to a Mie scattering particle. On the other hand, they require also a model for estimating the limiting factors upon the image resolution, where a large amount of particles within a three-dimensional (3D) volume are mapped into a two-dimensional (2D) image. Herein, we present a model that provides an analytical expression to estimate the current signal from a pixel of a CMOS detector due to a Mie scattering particle within an arbitrary large volume in a volumetric PTV experiments. We begin with a model for planar experiments and extend it into volumetric measurements. Our model considers the effect of the depth of field, particle density, Mie scattering signal and total Mie scattering loss, laser pulse energy, and other relevant optical parameters. Later, we investigate the consequence of the Rayleigh criterion upon the spatial resolution when it is applied to Mie particles within a volume of interest (VOI). Finally, we demonstrate how we applied our model to estimate the current signal and the limit upon the spatial resolution in three experiments carried out in our lab.
Hypoxia coordinates the spatial landscape of myeloid cells within glioblastoma to affect survival
Authors: Haley Michael J. , Bere Leoma , Minshull James , Georgaka Sokratia , Garcia-Martin Natalia , Howell Gareth , Coope David J. , Roncaroli Federico , King Andrew , Wedge David C. , Allan Stuart M. , Pathmanaban Omar N. , Brough David , Couper Kevin N.
Published: May 2024

Myeloid cells are highly prevalent in glioblastoma (GBM), existing in a spectrum of phenotypic and activation states. We now have limited knowledge of the tumor microenvironment (TME) determinants that influence the localization and the functions of the diverse myeloid cell populations in GBM. Here, we have utilized orthogonal imaging mass cytometry with single-cell and spatial transcriptomic approaches to identify and map the various myeloid populations in the human GBM tumor microenvironment (TME). Our results show that different myeloid populations have distinct and reproducible compartmentalization patterns in the GBM TME that is driven by tissue hypoxia, regional chemokine signaling, and varied homotypic and heterotypic cellular interactions. We subsequently identified specific tumor subregions in GBM, based on composition of identified myeloid cell populations, that were linked to patient survival. Our results provide insight into the spatial organization of myeloid cell subpopulations in GBM, and how this is predictive of clinical outcome.
Priority effects alter microbiome composition and increase abundance of probiotic taxa in treefrog tadpoles
Authors: Jones Korin Rex , Belden Lisa K. , Hughey Myra C.
Published: May 2024

Host-associated microbial communities, like other ecological communities, may be impacted by the colonization order of taxa through priority effects. Developing embryos and their associated microbiomes are subject to stochasticity during colonization by bacteria. For amphibian embryos, often developing externally in bacteria-rich environments, this stochasticity may be particularly impactful. For example, the amphibian microbiome can mitigate lethal outcomes from disease for their hosts; however, this may depend on microbiome composition. Here, we examined the assembly of the bacterial community in spring peeper (
Pseudacris crucifer
) embryos and tadpoles. First, we reared embryos from identified mating pairs in either lab or field environments to examine the relative impact of environment and parentage on embryo and tadpole bacterial communities. Second, we experimentally inoculated embryos to determine if priority effects (i) could be used to increase the relative abundance of
Janthinobacterium lividum
, an amphibian-associated bacteria capable of preventing fungal infection, and (ii) would lead to observed differences in the relative abundances of two closely related bacteria from the genus
Pseudomonas
. Using 16S rRNA gene amplicon sequencing, we observed differences in community composition based on rearing location and parentage in embryos and tadpoles. In the inoculation experiment, we found that priority inoculation could increase the relative abundance of
J. lividum
, but did not find that either
Pseudomonas
isolate was able to prevent colonization by the other when given priority. These results highlight the importance of environmental source pools and parentage in determining microbiome composition, while also providing novel methods for the administration of a known amphibian probiotic.

IMPORTANCE

Harnessing the functions of host-associated bacteria is a promising mechanism for managing disease outcomes across different host species. In the case of amphibians, certain frog-associated bacteria can mitigate lethal outcomes of infection by the fungal pathogen
Batrachochytrium dendrobatidis
. Successful probiotic applications require knowledge of community assembly and an understanding of the ecological mechanisms that structure these symbiotic bacterial communities. In our study, we show the importance of environment and parentage in determining bacterial community composition and that community composition can be influenced by priority effects. Further, we provide support for the use of bacterial priority effects as a mechanism to increase the relative abundance of target probiotic taxa in a developing host. While our results show that priority effects are not universally effective across all host-associated bacteria, our ability to increase the relative abundance of specific probiotic taxa may enhance conservation strategies that rely on captive rearing of endangered vertebrates.
Classical swine fever virus non-structural protein 4A recruits dihydroorotate dehydrogenase to facilitate viral replication
Authors: Zhao Bing-qian , Chen Jing , Chen Jin-Xia , Cheng Yan , Zhou Jiang-fei , Bai Ji-shan , Mao Ding-yi , Zhou Bin
Published: May 2024

Mitochondria are energy producers in cells, which can affect viral replication by regulating the host innate immune signaling pathways, and the changes in their biological functions are inextricably linked the viral life cycle. In this study, we screened a library of 382 mitochondria-targeted compounds and identified the antiviral inhibitors of dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme in the
de novo
synthesis pathway of pyrimidine ribonucleotides, against classical swine fever virus (CSFV). Our data showed that the inhibitors interfered with viral RNA synthesis in a dose-dependent manner, with half-maximal effective concentrations (EC
50
) ranging from 0.975 to 26.635 nM. Remarkably, DHODH inhibitors obstructed CSFV replication by enhancing the innate immune response including the TBK1-IRF3-STAT1 and NF-κB signaling pathways. Furthermore, the data from a series of compound addition and supplementation trials indicated that DHODH inhibitors also inhibited CSFV replication by blocking the
de novo
pyrimidine synthesis. Remarkably, DHODH knockdown demonstrated that it was essential for CSFV replication. Mechanistically, confocal microscopy and immunoprecipitation assays showed that the non-structural protein 4A (NS4A) recruited and interacted with DHODH in the perinuclear. Notably, NS4A enhanced the DHODH activity and promoted the generation of UMP for efficient viral replication. Structurally, the amino acids 65–229 of DHODH and the amino acids 25–40 of NS4A were pivotal for this interaction. Taken together, our findings highlight the critical role of DHODH in the CSFV life cycle and offer a potential antiviral target for the development of novel therapeutics against CSF.

IMPORTANCE

Classical swine fever remains one of the most economically important viral diseases of domestic pigs and wild boar worldwide. dihydroorotate dehydrogenase (DHODH) inhibitors have been shown to suppress the replication of several viruses
in vitro
and
in vivo
, but the effects on
Pestivirus
remain unknown. In this study, three specific DHODH inhibitors, including DHODH-IN-16, BAY-2402234, and Brequinar were found to strongly suppress classical swine fever virus (CSFV) replication. These inhibitors target the host DHODH, depleting the pyrimidine nucleotide pool to exert their antiviral effects. Intriguingly, we observed that the non-structural protein 4A of CSFV induced DHODH to accumulate around the nucleus in conjunction with mitochondria. Moreover, NS4A exhibited a strong interaction with DHODH, enhancing its activity to promote efficient CSFV replication. In conclusion, our findings enhance the understanding of the pyrimidine synthesis in CSFV infection and expand the novel functions of CSFV NS4A in viral replication, providing a reference for further exploration of antiviral targets against CSFV.
Framework for exploring the sensory repertoire of the human gut microbiota
Authors: Ross Patricia A. , Xu Wenhao , Jalomo-Khayrova Ekaterina , Bange Gert , Gumerov Vadim M. , Bradley Patrick H. , Sourjik Victor , Zhulin Igor B.
Published: May 2024

Bacteria sense changes in their environment and transduce signals to adjust their cellular functions accordingly. For this purpose, bacteria employ various sensors feeding into multiple signal transduction pathways. Signal recognition by bacterial sensors is studied mainly in a few model organisms, but advances in genome sequencing and analysis offer new ways of exploring the sensory repertoire of many understudied organisms. The human gut is a natural target of this line of study: it is a nutrient-rich and dynamic environment and is home to thousands of bacterial species whose activities impact human health. Many gut commensals are also poorly studied compared to model organisms and are mainly known through their genome sequences. To begin exploring the signals human gut commensals sense and respond to, we have designed a framework that enables the identification of sensory domains, prediction of signals that they recognize, and experimental verification of these predictions. We validate this framework’s functionality by systematically identifying amino acid sensors in selected bacterial genomes and metagenomes, characterizing their amino acid binding properties, and demonstrating their signal transduction potential.

IMPORTANCE

Signal transduction is a central process governing how bacteria sense and respond to their environment. The human gut is a complex environment with many living organisms and fluctuating streams of nutrients. One gut inhabitant,
Escherichia coli
, is a model organism for studying signal transduction. However,
E. coli
is not representative of most gut microbes, and signaling pathways in the thousands of other organisms comprising the human gut microbiota remain poorly understood. This work provides a foundation for how to explore signals recognized by these organisms.
The function of CozE proteins is linked to lipoteichoic acid biosynthesis in
Staphylococcus aureus
Authors: Barbuti Maria Disen , Lambert Elisabeth , Myrbråten Ine Storaker , Ducret Adrien , Stamsås Gro Anita , Wilhelm Linus , Liu Xue , Salehian Zhian , Veening Jan-Willem , Straume Daniel , Grangeasse Christophe , Perez Camilo , Kjos Morten
Published: May 2024

Coordinated membrane and cell wall synthesis is vital for maintaining cell integrity and facilitating cell division in bacteria. However, the molecular mechanisms that underpin such coordination are poorly understood. Here we uncover the pivotal roles of the staphylococcal proteins CozEa and CozEb, members of a conserved family of membrane proteins previously implicated in bacterial cell division, in the biosynthesis of lipoteichoic acids (LTA) and maintenance of membrane homeostasis in
Staphylococcus aureus
. We establish that there is a synthetic lethal relationship between CozE and UgtP, the enzyme synthesizing the LTA glycolipid anchor Glc
2
DAG. By contrast, in cells lacking LtaA, the flippase of Glc
2
DAG, the essentiality of CozE proteins was alleviated, suggesting that the function of CozE proteins is linked to the synthesis and flipping of the glycolipid anchor. CozE proteins were indeed found to modulate the flipping activity of LtaA
in vitro
. Furthermore, CozEb was shown to control LTA polymer length and stability. Together, these findings establish CozE proteins as novel players in membrane homeostasis and LTA biosynthesis in
S. aureus
.

IMPORTANCE

Lipoteichoic acids are major constituents of the cell wall of Gram-positive bacteria. These anionic polymers are important virulence factors and modulators of antibiotic susceptibility in the important pathogen
Staphylococcus aureus
. They are also critical for maintaining cell integrity and facilitating proper cell division. In this work, we discover that a family of membrane proteins named CozE is involved in the biosynthesis of lipoteichoic acids (LTAs) in
S. aureus
. CozE proteins have previously been shown to affect bacterial cell division, but we here show that these proteins affect LTA length and stability, as well as the flipping of glycolipids between membrane leaflets. This new mechanism of LTA control may thus have implications for the virulence and antibiotic susceptibility of
S. aureus
.
Higher odds of meniscectomy compared with meniscus repair in a young patient population with increased neighbourhood disadvantage
Authors: Dadoo Sahil , Keeling Laura E , Engler Ian D , Chang Audrey Y , Runer Armin , Kaarre Janina , Irrgang James J , Hughes Jonathan D , Musahl Volker
Published: May 2024

Objectives

To investigate the impact of demographic and socioeconomic factors on the management of isolated meniscus tears in young patients and to identify trends in surgical management of meniscus tears based on surgeon volume.

Methods

Data from a large healthcare system on patients aged 14–44 years who underwent isolated meniscus surgery between 2016 and 2022 were analysed. Patient demographics, socioeconomic factors and surgeon volume were recorded. Patient age was categorised as 14–29 years and 30–44 years old. Area Deprivation Index (ADI), a measure of neighbourhood disadvantage with increased ADI corresponding to more disadvantage, was grouped as <25th, 25–75th and >75th percentile. Multivariate comparisons were made between procedure groups while univariate comparisons were made between surgeon groups.

Results

The study included 1552 patients treated by 84 orthopaedic surgeons. Older age and higher ADI were associated with higher odds of undergoing meniscectomy. Patients of older age and with non-private insurance were more likely to undergo treatment by a lower-volume knee surgeon. Apart from the year 2022, higher-volume knee surgeons performed significantly higher rates of meniscus repair compared with lower-volume knee surgeons. When controlling for surgeon volume, higher ADI remained a significant predictor of undergoing meniscectomy over meniscus repair.

Conclusion

Significant associations exist between patient factors and surgical choices for isolated meniscus tears in younger patients. Patients of older age and with increased neighbourhood disadvantage were more likely to undergo meniscectomy versus meniscus repair. While higher-volume knee surgeons favoured meniscus repair, a growing trend of meniscus repair rates was observed among lower-volume knee surgeons.

Level of evidence

Retrospective cohort study, level III.
Early versus Late Application of Subthalamic deep brain Stimulation to Parkinson’s disease patients with motor complications (ELASS): protocol of a multicentre, prospective and observational study
Authors: Jiang Lulu , Poon Wai Sang , Moro Elena , Xian Wenbiao , Yang Chao , Zhu Xian Lun , Gu Jing , Cai Xiaodong , Liu Jinlong , Mok Vincent , Liu Yanmei , Xu Shaohua , Guo Qiyu , Chen Wanru , Chen Ling
Published: May 2024

Introduction

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established surgical treatment for Parkinson’s disease (PD). However, there is currently no consensus on the best timing for this surgery. The aim of our study is to compare the therapeutic efficacy of bilateral STN DBS in patients with PD with early and late motor complications.

Methods and analysis

200 patients with PD will be enrolled in this multicentre, prospective, observational study, and will be followed up for 4 years. Patients with PD who meet the criteria for STN DBS surgery will be allocated to either the early stimulation group or the late stimulation group based on the duration of their motor complications. The primary outcome will be changes in quality of life from baseline to 4 years, measured using the 39-item Parkinson’s Disease Questionnaire Summary Index. The secondary outcomes include changes in motor function measured using Movement Disorder Society-revised Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III, self-reported experiences of daily living measured using MDS-UPDRS Part I B and Part II, good ’on' time recorded by the patients using a diary and safety profile of both groups.

Ethics and dissemination

The study received ethical approval from the Medical Ethical Committee of the First Affiliated Hospital, Sun Yat-sen University. The results of this study will be published in peer-reviewed journals and presented at international conferences.

Trial registration number

NCT01922388; Pre-results.