bluuebunny/crossref_metadata_2025 huggingface dataset:
Effective efgartigimod treatment for severe thymoma‐associated myasthenia gravis experiencing myasthenic crisis: A case report
Authors: Morita Yukari , Osaki Yasushi , Shogase Tomohiro , Yoshimoto Daiji , Terada Tomomi , Ohtsuru Sho , Yamasaki Kako , Hashimoto Yu , Matsushita Takuya
Published: March 2024

We report the long‐term treatment of a 38‐year‐old man with generalized thymoma‐associated myasthenia gravis who was treated with efgartigimod. He received chemotherapy and oral prednisolone before the thymectomy. However, after initial improvement in symptoms, he deteriorated and needed continuous noninvasive positive‐pressure ventilation, with the highest Myasthenia Gravis‐Activities of Daily Living score of 14. Immunosuppressive therapy and plasma exchange showed limited benefit, and the anti‐acetylcholine receptor antibody titer peaked to 130 nmol/L. Seven cycles of efgartigimod treatment were administered, which improved the symptoms, achieving a Myasthenia Gravis‐Actvities of Daily Living score of 0. The anti‐acetylcholine receptor antibody titer fluctuated until the end of the fifth cycle, thereafter, plateauing at 22 nmol/L. These findings allowed the prednisolone dose to be tapered and the interval between the treatment cycles to be increased.
Incorporating plant phenological responses into species distribution models reduces estimates of future species loss and turnover
Authors: Peng Shijia , Ramirez‐Parada Tadeo H. , Mazer Susan J. , Record Sydne , Park Isaac , Ellison Aaron M. , Davis Charles C.
Published: March 2024

Anthropogenetic climate change has caused range shifts among many species. Species distribution models (SDMs) are used to predict how species ranges may change in the future. However, most SDMs rarely consider how climate‐sensitive traits, such as phenology, which affect individuals' demography and fitness, may influence species' ranges.

Using > 120 000 herbarium specimens representing 360 plant species distributed across the eastern United States, we developed a novel ‘phenology‐informed’ SDM that integrates phenological responses to changing climates. We compared the ranges of each species forecast by the phenology‐informed SDM with those from conventional SDMs. We further validated the modeling approach using hindcasting.

When examining the range changes of all species, our phenology‐informed SDMs forecast less species loss and turnover under climate change than conventional SDMs. These results suggest that dynamic phenological responses of species may help them adjust their ecological niches and persist in their habitats as the climate changes.

Plant phenology can modulate species' responses to climate change, mitigating its negative effects on species persistence. Further application of our framework will contribute to a generalized understanding of how traits affect species distributions along environmental gradients and facilitate the use of trait‐based SDMs across spatial and taxonomic scales.
Variation in leaf carbon economics, energy balance, and heat tolerance traits highlights differing timescales of adaptation and acclimation
Authors: Bison Nicole N. , Michaletz Sean T.
Published: March 2024

Multivariate leaf trait correlations are hypothesized to originate from natural selection on carbon economics traits that control lifetime leaf carbon gain, and energy balance traits governing leaf temperatures, physiological rates, and heat injury. However, it is unclear whether macroevolution of leaf traits primarily reflects selection for lifetime carbon gain or energy balance, and whether photosynthetic heat tolerance is coordinated along these axes.

To evaluate these hypotheses, we measured carbon economics, energy balance, and photosynthetic heat tolerance traits for 177 species (157 families) in a common garden that minimizes co‐variation of taxa and climate.

We observed wide variation in carbon economics, energy balance, and heat tolerance traits. Carbon economics and energy balance (but not heat tolerance) traits were phylogenetically structured, suggesting macroevolution of leaf mass per area and leaf dry matter content reflects selection on carbon gain rather than energy balance. Carbon economics and energy balance traits varied along a common axis orthogonal to heat tolerance traits.

Our results highlight a fundamental mismatch in the timescales over which morphological and heat tolerance traits respond to environmental variation. Whereas carbon economics and energy balance traits are constrained by species' evolutionary histories, photosynthetic heat tolerance traits are not and can acclimate readily to leaf microclimates.
Who is building peace? A latent class analysis of youth peacebuilders in a conflict‐affected setting
Authors: Taylor Laura K. , Merrilees Christine E. , Goeke‐Morey Marcie C. , Shirlow Pete , Cummings E. Mark
Published: March 2024

Rebuilding society in the wake of conflict often falls on the generation born in peace. Yet, youth contributions to peacebuilding are often overlooked. This article challenges the narrative that sidelines the constructive contributions of young people in conflict‐affected settings. Instead, we identify different kinds of youth peacebuilders. Using a person‐centered approach, we conduct a latent class analysis of 590 adolescents (Mage = 16.8, SDage = 2.0, years old), evenly split by sex (51% female) and representing both communities, or conflict‐related identity groups, in Northern Ireland (38% Catholic, 62% Protestant). Across 10 indicators capturing different types and targets of prosocial action, the best fit to the data was a four‐class model: Peace in Name Only (36%), Peace at Home (33%), Peace Within Community (13%), and Future Peacebuilder (16%). Class membership varied based on youth's prior exposure to intergroup threat, or sectarian antisocial behavior. Prior exposure was related to a higher probability of being in the Peace at Home or Future Peacebuilder, compared to the Peace in Name Only class. The importance of recognizing the different kinds of youth peacebuilders in a conflict‐affected society is discussed, along with implications for global policy.
Cloning and functional mechanism of the dwarf gene gba affecting stem elongation and cellulose biosynthesis in jute (Corchorus olitorius)
Authors: Li Qin , Chen Siyuan , Chen Lu , Zhuang Lingling , Wei Huawei , Jiang Shaolian , Wang Chuanyu , Qi Jianmin , Fang Pingping , Xu Jiantang , Tao Aifen , Zhang Liwu
Published: March 2024

Plant height (PH) is an important factor affecting bast fiber yield in jute. Here, we report the mechanism of dwarfism in the ‘Guangbaai’ (gba) of jute. The mutant gba had shorter internode length and cell length compared to the standard cultivar ‘TaiZi 4’ (TZ4). Exogenous GA3 treatment indicated that gba is a GA‐insensitive dwarf mutant. Quantitative trait locus (QTL) analysis of three PH‐related traits via a high‐density genetic linkage map according to re‐seq showed that a total of 25 QTLs were identified, including 13 QTLs for PH, with phenotypic variation explained ranging from 2.42 to 74.16%. Notably, the functional mechanism of the candidate gene CoGID1a, the gibberellic acid receptor, of the major locus qPHIL5 was evaluated by transgenic analysis and virus‐induced gene silencing. A dwarf phenotype‐related single nucleotide mutation in CoGID1a was identified in gba, which was also unique to the dwarf phenotype of gba among 57 cultivars. Cogid1a was unable to interact with the growth‐repressor DELLA even in the presence of highly accumulated gibberellins in gba. Differentially expressed genes between transcriptomes of gba and TZ4 after GA3 treatment indicated up‐regulation of genes involved in gibberellin and cellulose synthesis in gba. Interestingly, it was found that up‐regulation of CoMYB46, a key transcription factor in the secondary cell wall, by the highly accumulated gibberellins in gba promoted the expression of cellulose synthase genes CoCesA4 and CoCesA7. These findings provide valuable insights into fiber development affected by endogenous gibberellin accumulation in plants.
An evaluation of the usability and durability of 3D printed versus standard suture materials
Authors: Nguyen Thang T. , Langenfeld Jason G. , Reinhart Benjamin C. , Lyden Elizabeth I. , Campos Abraham S. , Wadman Michael C. , Jamison Matthew R. , Morin Stephen A. , Barksdale Aaron N.
Published: March 2024

The capability to produce suture material using three‐dimensional (3D) printing technology may have applications in remote health facilities where rapid restocking of supplies is not an option. This is a feasibility study evaluating the usability of 3D‐printed sutures in the repair of a laceration wound when compared with standard suture material. The 3D‐printed suture material was manufactured using a fused deposition modelling 3D printer and nylon 3D printing filament. Study participants were tasked with performing laceration repairs on the pigs' feet, first with 3‐0 WeGo nylon suture material, followed by the 3D‐printed nylon suture material. Twenty‐six participants were enrolled in the study. Survey data demonstrated statistical significance with how well the 3D suture material performed with knot tying, 8.9 versus 7.5 (p = 0.0018). Statistical significance was observed in the 3D‐printed suture's ultimate tensile strength when compared to the 3‐0 Novafil suture (274.8 vs. 199.8 MPa, p = 0.0096). The 3D‐printed suture also demonstrated statistical significance in ultimate extension when compared to commercial 3‐0 WeGo nylon suture (49% vs. 37%, p = 0.0215). This study was successful in using 3D printing technology to manufacture suture material and provided insight into its usability when compared to standard suture material.
Examining the Psychometric Properties of the Adolescent Students' Basic Psychological Needs at School Scale for the Azerbaijani Sample
Authors: Mammadov Maarif , Babayev Anar , Mukhtarov Mirsadig
Published: March 2024

The purpose of this study is to adapt the "The Adolescent Students' Basic Psychological Needs at School Scale (ASBPNSS)," which was developed to assess satisfaction with basic psychological needs at school, into Azerbaijani and evaluate its psychometric properties. Among the students involved in the study, 255 (50.5%) were female, and 250 (49.5%) were male. The average age of the participants was 14.65 (SD = 1.15), with an age range of 12-17. Exploratory and confirmatory factor analyses were conducted to assess the construct validity of the scale. The results of the exploratory factor analysis for the items of ASBPNSS revealed three factors: autonomy, relatedness, and competence. Confirmatory factor analysis supported this structure. The three factors collectively explained the overall structure with a total variance of 58.061%. Criterion-related validity was also examined for validity purposes. Internal consistency was assessed for the reliability of the scale, yielding an internal consistency coefficient of .82. The results indicate that the scale is a psychometrically sound measurement tool for assessing the extent to which adolescent students' basic psychological needs are met at school.
Smallest denominators
Authors: Marklof Jens
Published: March 2024

We establish higher dimensional versions of a recent theorem by Chen and Haynes [Int. J. Number Theory 19 (2023), 1405–1413] on the expected value of the smallest denominator of rational points in a randomly shifted interval of small length, and of the closely related 1977 Kruyswijk–Meijer conjecture recently proved by Balazard and Martin [Bull. Sci. Math. 187 (2023), Paper No. 103305]. We express the distribution of smallest denominators in terms of the void statistics of multidimensional Farey fractions and prove convergence of the distribution function and certain finite moments. The latter was previously unknown even in the one‐dimensional setting. We furthermore obtain a higher dimensional extension of Kargaev and Zhigljavsky's work on moments of the distance function for the Farey sequence [J. Number Theory 65 (1997), 130–149] as well as new results on pigeonhole statistics.
A narrative review of periodic breathing during sleep at high altitude: From acclimatizing lowlanders to adapted highlanders
Authors: Patrician Alexander , Anholm James D. , Ainslie Philip N.
Published: March 2024

Periodic breathing during sleep at high altitude is almost universal among sojourners. Here, in the context of acclimatization and adaptation, we provide a contemporary review on periodic breathing at high altitude, and explore whether this is an adaptive or maladaptive process. The mechanism(s), prevalence and role of periodic breathing in acclimatized lowlanders at high altitude are contrasted with the available data from adapted indigenous populations (e.g. Andean and Tibetan highlanders). It is concluded that (1) periodic breathing persists with acclimatization in lowlanders and the severity is proportional to sleeping altitude; (2) periodic breathing does not seem to coalesce with poor sleep quality such that, with acclimatization, there appears to be a lengthening of cycle length and minimal impact on the average sleeping oxygen saturation; and (3) high altitude adapted highlanders appear to demonstrate a blunting of periodic breathing, compared to lowlanders, comprising a feature that withstands the negative influences of chronic mountain sickness. These observations indicate that periodic breathing persists with high altitude acclimatization with no obvious negative consequences; however, periodic breathing is attenuated with high altitude adaptation and therefore potentially reflects an adaptive trait to this environment.

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Ultrasound-guided thrombin injection in the management of brachial artery pseudoaneurysm with median nerve compression
Authors: Wang Guoyun , Liu Jie , Cao Xiaoli
Published: March 2024

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Prenatal sonographic findings in a case with bilateral Tessier number 7 cleft in first trimester
Authors: Zhu Zheng Feng , Li Jie , Wang Zhao Yu
Published: March 2024

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Incorporating cognitive load theory into curriculum design for the teaching of novel clinical skills in Australian osteopathy students
Authors: McLaughlin Patrick , Vaughan Brett , Tripodi Nicholas , Kelly Kate
Published: March 2024

Introduction: Cognitive load theory provides a theoretical framework through which the teaching of skills to health students can be optimised. The aim of this study was to evaluate the intrinsic and extraneous cognitive load of first-year osteopathy students as they learn a psychomotor-based clinical skill (neurological examination of the upper limb).
Methods: First-year osteopathy students (n = 78) at an Australian university completed an 8-item cognitive load survey at the end of the session where they were taught, and conducted, their first hands-on assessment task (neurological examination of the upper limb). The task was completed in a learning environment designed with low-medium complexity, medium fidelity and high levels of instructional support for learners.
Results: Intrinsic and extraneous load data indicate varied levels of cognitive demand of the task across the cohort. On average, intrinsic load made up three quarters of the total cognitive load associated with this task.
Conclusion: Understanding and utilising cognitive load theory in the design of lesson plans may provide improved opportunity to optimise student learning of novel clinical skills. Extraneous load was much lower than intrinsic load, suggesting the learning environment was fit for purpose for these learners.
Designing for justice: How universal design theory could bolster health professional education research
Authors: Jain Neera , Varpio Lara
Published: March 2024

Universal design theory (UDT), emerging from the field of architecture and infused with the politics of the disability rights movement, refers to a way of planning for and responding to diversity that can be harnessed for research design. We argue that UDT is a critical tool for researchers in health professional education (HPE) to realise their obligations for social accountability, justice, equity, diversity and inclusion in HPE. This paper introduces researchers to UDT and demonstrates how it could inform research design in HPE. We provide an in-depth, socio-political explanation of the theory and why it is important for HPE research, and we elucidate ways it can inform HPE research design and process—including the tensions that may arise in activating these principles alongside some research paradigms and conditions of the field. We seek to highlight the potential of universal design to transform research practice to advance justice.
CuO-ZnO nanocomposite for photocatalytic application
Authors: Rymarczyk Joanna , Stępińska Izabela
Published: March 2024

The rising levels of water pollution and climate change contribute to water shortages. These factors influence the loss of the environment’s biodiversity and threaten human health. Toxic dye pigments from industries are a significant source of pollution. In this article, we present the synthesis method, characteristics, and photocatalytic properties of the CuO-ZnO nanocomposite, which may affect the degree of decomposition of dyes found in water. The nanocomposite consisting of copper oxide nanowires with zinc oxide nanostructures (CuO-ZnO nanocomposite) was prepared by physical vapor deposition and thermal oxidation methods. The crystalline structure, surface topographies and morphologies, elemental composition, and optical properties of the obtained samples were studied with various techniques such as x-ray diffraction analysis, high-resolution transmission electron microscopy, field emission scanning electron microscopy, energy dispersive x-ray analysis, and UV-vis spectroscopy. The photocatalytic activity of the nanocomposite was measured by testing the degradation of methylene blue under visible irradiation. An increase in the photocatalytic activity of the nanocomposite was observed compared to pure CuO and ZnO. The CuO-ZnO nanocomposite demonstrated a high dye degradation of about 94% during 120 min.
Understanding Well-Being in High-Performance Coaches: A Constructivist Grounded Theory Approach
Authors: Simova Marketa , Olusoga Peter , Brown Christopher J. , Chroni Stiliani “Ani”
Published: March 2024

Objectives: The purpose of the study was to explore, in depth, well-being within the unique context of high-performance sports coaching. The aim was to capture the process of well-being while considering the contextual nuances and influences of high-performance coaching environments in a mid-range theory of coaches’ well-being. Design: Constructivist grounded theory served as a guiding approach for data collection and analysis. Method: Individual interviews (n = 20) were conducted with methodological rigour enhanced by originality, usefulness, resonance, and credibility. Aligned with the methodology, we utilised theoretical sampling to aid the development of individual categories. Results: Findings suggest that well-being is an integrating process between coaches’ personal values (identity) and culturally prescribed values (identity), with a degree of harmony as the overall goal. Conclusion: The mid-range theory presents a contextually bound process of coaches’ well-being. It provides a more practical insight into the area and highlights the importance of cultural considerations and competencies.
Tracing Gender Allyship and the Role of Awareness in Addressing the Gender Leadership Gap in Sport Organizations
Authors: Heffernan Caroline , Kihl Lisa A.
Published: March 2024

An extensive literature base has investigated women’s underrepresentation in decision-making positions with sport organizations, yet women’s access to these positions remains limited. Diversification strategies, based on distributive justice, have failed to create further opportunities. A new approach is needed to address this latent issue. The concept of gender allyship is presented to address the limitations of distributive justice paradigms that involves men and women to work as members of a coalition to improve gender equity in sport organizations. Utilizing grounded theory, this paper presents the core category of awareness and related subcategories self-awareness, organizational awareness, and industry awareness, as a means of informing the performance of gender allyship. The findings provide interesting theoretical and empirical implications for understanding the development of awareness, its subcategories, and how it contributes to change.
Sensitive detection of multiple blood biomarkers via immunomagnetic exosomal PCR for the diagnosis of Alzheimer’s disease
Authors: Hu Shun , Zhang Liding , Su Ying , Liang Xiaohan , Yang Jie , Luo Qingming , Luo Haiming
Published: March 2024

Blood exosomes are emerging as potential biomarkers for diagnosing brain diseases such as Alzheimer’s disease (AD). There is currently a lack of an ultrasensitive technology for identifying core AD biomarkers in blood exosomes to optimize the utility of biomarkers in clinical practice. Here, an immunomagnetic exosomal polymerase chain reaction (iMEP) platform was developed using DNA-conjugated antibodies for the rapid detection of amyloid-β (Aβ
1–40
and Aβ
1–42
) and phosphorylated tau (p-tau
396,404
and p-tau
181
) in clinical blood exosomes. The toehold shift–mediated DNA affinity pulldown eliminates the high detection background, which allows the detection of biomarkers at concentrations down to 10 femtograms per milliliter. With the iMEP assay, exosomal Aβ
1–42
was more accurate in differentiating patients with AD from healthy individuals compared with exosomal p-tau
181
and p-tau
396,404
, with a sensitivity of 95.0% and a specificity of 95.0%. The iMEP technique is also adept at quantifying the levels of different exosomal biomarkers associated with disease pathogenesis.
Lupus susceptibility gene
Pbx1
controls the development, stability, and function of regulatory T cells via
Rtkn2
expression
Authors: Choi Seung-Chul , Park Yuk Pheel , Roach Tracoyia , Jimenez Damian , Fisher Amanda , Zadeh Mojgan , Ma Longhuan , Sobel Eric S. , Ge Yong , Mohamadzadeh Mansour , Morel Laurence
Published: March 2024

The maintenance of regulatory T (T
reg
) cells critically prevents autoimmunity. Pre–B cell leukemia transcription factor 1 (
Pbx1
) variants are associated with lupus susceptibility, particularly through the expression of a dominant negative isoform
Pbx1-d
in CD4
+
T cells.
Pbx1-d
overexpression impaired T
reg
cell homeostasis and promoted inflammatory CD4
+
T cells. Here, we showed a high expression of
Pbx1
in human and murine T
reg
cells, which is decreased in lupus patients and mice.
Pbx1
deficiency or
Pbx1-d
overexpression reduced the number, stability, and suppressive activity of T
reg
cells, which increased murine responses to immunization and autoimmune induction. Mechanistically,
Pbx1
deficiency altered the expression of genes implicated in cell cycle and apoptosis in T
reg
cells. Intriguingly,
Rtkn2
, a Rho-GTPase previously associated with T
reg
homeostasis, was directly transactivated by Pbx1. Our results suggest that the maintenance of T
reg
cell homeostasis and stability by
Pbx1
through cell cycle progression prevent the expansion of inflammatory T cells that otherwise exacerbates lupus progression in the hosts.
Iterative assay for transposase-accessible chromatin by sequencing to isolate functionally relevant neuronal subtypes
Authors: Merrill Collin B. , Titos Iris , Pabon Miguel A. , Montgomery Austin B. , Rodan Aylin R. , Rothenfluh Adrian
Published: March 2024

The
Drosophila
brain contains tens of thousands of distinct cell types. Thousands of different transgenic lines reproducibly target specific neuron subsets, yet most still express in several cell types. Furthermore, most lines were developed without a priori knowledge of where the transgenes would be expressed. To aid in the development of cell type–specific tools for neuronal identification and manipulation, we developed an iterative assay for transposase-accessible chromatin (ATAC) approach. Open chromatin regions (OCRs) enriched in neurons, compared to whole bodies, drove transgene expression preferentially in subsets of neurons. A second round of ATAC-seq from these specific neuron subsets revealed additional enriched OCR2s that further restricted transgene expression within the chosen neuron subset. This approach allows for continued refinement of transgene expression, and we used it to identify neurons relevant for sleep behavior. Furthermore, this approach is widely applicable to other cell types and to other organisms.
Food matters: Dietary shifts increase the feasibility of 1.5°C pathways in line with the Paris Agreement
Authors: Humpenöder Florian , Popp Alexander , Merfort Leon , Luderer Gunnar , Weindl Isabelle , Bodirsky Benjamin Leon , Stevanović Miodrag , Klein David , Rodrigues Renato , Bauer Nico , Dietrich Jan Philipp , Lotze-Campen Hermann , Rockström Johan
Published: March 2024

A transition to healthy diets such as the EAT-Lancet Planetary Health Diet could considerably reduce greenhouse gas (GHG) emissions. However, the specific contributions of dietary shifts for the feasibility of 1.5°C pathways remain unclear. Here, we use the open-source integrated assessment modeling (IAM) framework REMIND-MAgPIE to compare 1.5°C pathways with and without dietary shifts. We find that a flexitarian diet increases the feasibility of the Paris Agreement climate goals in different ways: The reduction of GHG emissions related to dietary shifts, especially methane from ruminant enteric fermentation, increases the 1.5°C compatible carbon budget. Therefore, dietary shifts allow to achieve the same climate outcome with less carbon dioxide removal (CDR) and less stringent CO
2
emission reductions in the energy system, which reduces pressure on GHG prices, energy prices, and food expenditures.
Activation of endogenous retroviruses and induction of viral mimicry by MEK1/2 inhibition in pancreatic cancer
Authors: Cortesi Alice , Gandolfi Francesco , Arco Fabiana , Di Chiaro Pierluigi , Valli Emanuele , Polletti Sara , Noberini Roberta , Gualdrini Francesco , Attanasio Sergio , Citron Francesca , Ho I-lin , Shah Rutvi , Yen Er-Yen , Spinella Mara Cetty , Ronzoni Simona , Rodighiero Simona , Mitro Nico , Bonaldi Tiziana , Ghisletti Serena , Monticelli Silvia , Viale Andrea , Diaferia Giuseppe Riccardo , Natoli Gioacchino
Published: March 2024

While pancreatic ductal adenocarcinomas (PDACs) are addicted to KRAS-activating mutations, inhibitors of downstream KRAS effectors, such as the MEK1/2 kinase inhibitor trametinib, are devoid of therapeutic effects. However, the extensive rewiring of regulatory circuits driven by the attenuation of the KRAS pathway may induce vulnerabilities of therapeutic relevance. An in-depth molecular analysis of the transcriptional and epigenomic alterations occurring in PDAC cells in the initial hours after MEK1/2 inhibition by trametinib unveiled the induction of endogenous retroviruses (ERVs) escaping epigenetic silencing, leading to the production of double-stranded RNAs and the increased expression of interferon (IFN) genes. We tracked ERV activation to the early induction of the transcription factor ELF3, which extensively bound and activated nonsilenced retroelements and synergized with IRF1 (interferon regulatory factor 1) in the activation of IFNs and IFN-stimulated genes. Trametinib-induced viral mimicry in PDAC may be exploited in the rational design of combination therapies in immuno-oncology.
Multiple parallel cell lineages in the developing mammalian cerebral cortex
Authors: Del-Valle-Anton Lucia , Amin Salma , Cimino Daniela , Neuhaus Florian , Dvoretskova Elena , Fernández Virginia , Babal Yigit K. , Garcia-Frigola Cristina , Prieto-Colomina Anna , Murcia-Ramón Raquel , Nomura Yuki , Cárdenas Adrián , Feng Chao , Moreno-Bravo Juan Antonio , Götz Magdalena , Mayer Christian , Borrell Víctor
Published: March 2024

Cortical neurogenesis follows a simple lineage: apical radial glia cells (RGCs) generate basal progenitors, and these produce neurons. How this occurs in species with expanded germinal zones and a folded cortex, such as human, remains unclear. We used single-cell RNA sequencing from individual cortical germinal zones in ferret and barcoded lineage tracking to determine the molecular diversity of progenitor cells and their lineages. We identified multiple RGC classes that initiate parallel lineages, converging onto a common class of newborn neuron. Parallel RGC classes and transcriptomic trajectories were repeated across germinal zones and conserved in ferret and human, but not in mouse. Neurons followed parallel differentiation trajectories in the gyrus and sulcus, with different expressions of human cortical malformation genes. Progenitor cell lineage multiplicity is conserved in the folded mammalian cerebral cortex.
The gut microbiota posttranslationally modifies IgA1 in autoimmune glomerulonephritis
Authors: Gleeson Patrick J. , Benech Nicolas , Chemouny Jonathan , Metallinou Eleftheria , Berthelot Laureline , da Silva Jennifer , Bex-Coudrat Julie , Boedec Erwan , Canesi Fanny , Bounaix Carine , Morelle Willy , Moya-Nilges Maryse , Kenny John , O’Mahony Liam , Saveanu Loredana , Arnulf Bertrand , Sannier Aurélie , Daugas Eric , Vrtovsnik François , Lepage Patricia , Sokol Harry , Monteiro Renato C.
Published: March 2024

Mechanisms underlying the disruption of self-tolerance in acquired autoimmunity remain unclear. Immunoglobulin A (IgA) nephropathy is an acquired autoimmune disease where deglycosylated IgA1 (IgA subclass 1) auto-antigens are recognized by IgG auto-antibodies, forming immune complexes that are deposited in the kidneys, leading to glomerulonephritis. In the intestinal microbiota of patients with IgA nephropathy, there was increased relative abundance of mucin-degrading bacteria, including
Akkermansia muciniphila
. IgA1 was deglycosylated by
A. muciniphila
both in vitro and in the intestinal lumen of mice. This generated neo-epitopes that were recognized by autoreactive IgG from the sera of patients with IgA nephropathy. Mice expressing human IgA1 and the human Fc α receptor I (α1
KI
-CD89
tg
) that underwent intestinal colonization by
A. muciniphila
developed an aggravated IgA nephropathy phenotype. After deglycosylation of IgA1 by
A. muciniphila
in the mouse gut lumen, IgA1 crossed the intestinal epithelium into the circulation by retrotranscytosis and became deposited in the glomeruli of mouse kidneys. Human α-defensins—a risk locus for IgA nephropathy—inhibited growth of
A. muciniphila in
vitro. A negative correlation observed between stool concentration of α-defensin 6 and quantity of
A. muciniphila
in the guts of control participants was lost in patients with IgA nephropathy. This study demonstrates that gut microbiota dysbiosis contributes to generation of auto-antigens in patients with IgA nephropathy and in a mouse model of this disease.
Sensitivity and specificity of the new Bio-Rad HIV screening test, Access HIV combo V2
Authors: Guiraud Vincent , Ciczora Yann , Cardona Muriel , Defer Christine , Gréaume Sandrine , Nogues David , Gautheret-Dejean Agnès
Published: March 2024

Diagnosing of human immunodeficiency virus (HIV) types 1 and 2 requires a screening with a highly sensitive and specific enzyme immunoassay and a low detection limit for the HIV-1 p24 antigen to minimize the diagnostic window. The objective of the study was to determine the sensitivity, specificity, and p24 limit of detection of the Access HIV combo V2 assay. Retrospective part of sensitivity: 452 HIV-1 positive samples from 403 chronic (9 different HIV-1 group M subtypes, 22 different HIV-1 group M CRFs, and 3 HIV-1 group O), 49 primary HIV-1 infections, 103 HIV-2 positive samples assessed at Pitié-Salpêtrière Hospital, 600 untyped HIV-1, 10 subtype-D, and 159 untyped HIV-2 samples assessed in Bio-Rad Laboratories. Prospective part of clinical specificity: all consecutive samples in two blood donor facilities and Pitié-Salpêtrière (6,570 patients) tested with Access HIV combo V2 and respectively Prism HIV O Plus (Abbott) or Architect HIV Ag/Ab Combo (Abbott) for Ag/Ab screening, and Procleix Ultrio (Gen Probe) for HIV RNA screening. Limit of detection for p24 antigen was assessed on recombinant virus-like particles (10 HIV-1 group M subtypes/CRFs, HIV-1 group O). Sensitivity [95% confidence interval (CI)] of Access HIV combo V2 was 100% (99.63–100) for HIV-1 chronic infection, 100% (98.55–100) for HIV-2 chronic infection, and 100% (93.00–100) for HIV-1 primary infection. Specificity (95% CI) was 99.98 (99.91–100). Limit of detection for p24 antigen was around 0.43 IU/mL [interquartile range (0.38–0.56)], and consistent across the 11 analyzed subtypes/CRFs. Hence, with both high sensitivity and specificity, Access HIV combo V2 is a suitable screening assay for HIV-1/2 infection.

IMPORTANCE

Bio-Rad is one of the leading human immunodeficiency virus (HIV) screening test manufacturers. This laboratory released in 2021 their new version of the Access combo HIV test. However, to date, there have been no studies regarding its performance, especially its limit of detection of the diverse p24 antigen. We present the sensitivity (chronic and primary HIV-1 infection and HIV-2 chronic infection), specificity (blood donors and hospitalized patients), and raw data for the p24/seroconversion panels the manufacturer gave to the European agencies.
Bordetella
filamentous hemagglutinin and adenylate cyclase toxin interactions on the bacterial surface are consistent with FhaB-mediated delivery of ACT to phagocytic cells
Authors: Nash Zachary M. , Inatsuka Carol S. , Cotter Peggy A. , Johnson Richard M.
Published: March 2024

Bordetella
species that cause respiratory infections in mammals include
B. pertussis
, which causes human whooping cough, and
B. bronchiseptica
, which infects nearly all mammals. Both bacterial species produce filamentous hemagglutinin (FhaB) and adenylate cyclase toxin (ACT), prominent surface-associated and secreted virulence factors that contribute to persistence in the lower respiratory tract by inhibiting clearance by phagocytic cells. FhaB and ACT proteins interact with themselves, each other, and host cells. Using immunoblot analyses, we showed that ACT binds to FhaB on the bacterial surface before it can be detected in culture supernatants. We determined that SphB1, a surface protease identified based on its requirement for FhaB cleavage, is also required for ACT cleavage, and we determined that the presence of ACT blocks SphB1-dependent and -independent cleavage of FhaB, but the presence of FhaB does not affect SphB1-dependent cleavage of ACT. The primary SphB1-dependent cleavage site on ACT is proximal to ACT’s active site, in a region that is critical for ACT activity. We also determined that FhaB-bound ACT on the bacterial surface can intoxicate host cells producing CR3, the receptor for ACT. In addition to increasing our understanding of FhaB, ACT, and FhaB-ACT interactions on the
Bordetella
surface, our data are consistent with a model in which FhaB functions as a novel toxin delivery system by binding to ACT and allowing its release upon binding of ACT to its receptor, CR3, on phagocytic cells.

IMPORTANCE

Bacteria need to control the variety, abundance, and conformation of proteins on their surface to survive. Members of the Gram-negative bacterial genus
Bordetella
include
B. pertussis
, which causes whooping cough in humans, and
B. bronchiseptica
, which causes respiratory infections in a broad range of mammals. These species produce two prominent virulence factors, the two-partner secretion (TPS) effector FhaB and adenylate cyclase toxin (ACT), that interact with themselves, each other, and host cells. Here, we determined that ACT binds FhaB on the bacterial surface before being detected in culture supernatants and that ACT bound to FhaB can be delivered to eukaryotic cells. Our data are consistent with a model in which FhaB delivers ACT specifically to phagocytic cells. This is the first report of a TPS system facilitating the delivery of a separate polypeptide toxin to target cells and expands our understanding of how TPS systems contribute to bacterial pathogenesis.
Complete genome sequence of
Chlamydia psittaci
АМК-16, isolated from a small ruminant in the Middle Volga Region, Russia
Authors: Zaitsev Sergey , Khizhnyakova Mariya , Saltykov Yury , Evstifeev Vitaliy , Khusainov Fidail , Ivanova Svetlana , Morozova Daria , Yakovlev Sergey , Larionova Olga , Feodorova Valentina
Published: March 2024

We report the complete genome sequence of the
Chlamydia psittaci
АМК-16, recovered from the aborted caprine fetus during a case of chlamydia infection. This 1,152,497-bp genome with 7,552-bp cryptic plasmid provides novel insights into the genetic diversity of chlamydia agent strains particularly those causing the infection in small ruminants.
Use of the 23S rRNA gene as a target template in the universal loop-mediated isothermal amplification (LAMP) of genomic DNA from phytoplasmas
Authors: Akahori Mako , Miyazaki Akio , Koinuma Hiroaki , Tokuda Ryosuke , Iwabuchi Nozomu , Kitazawa Yugo , Maejima Kensaku , Namba Shigetou , Yamaji Yasuyuki
Published: March 2024

Plant-pathogenic bacteria cause numerous diseases in host plants and can result in serious damage. Timely and accurate diagnostic techniques are, therefore, crucial. While advances in molecular techniques have led to diagnostic systems able to distinguish known plant pathogens at the species or strain level, systems covering larger categories are mostly lacking. In this study, a specific and universal LAMP-based diagnostic system was developed for phytoplasmas, a large group of insect-borne plant-pathogenic bacteria that cause significant agricultural losses worldwide. Targeting the 23S rRNA gene of phytoplasma, the newly designed primer set CaPU23S-4 detected 31 ‘
Candidatus
Phytoplasma’ tested within 30 min. This primer set also showed high specificity, without false-positive results for other bacteria (including close relatives of phytoplasmas) or healthy plants. The detection sensitivity was ~10,000 times higher than that of PCR methods for phytoplasma detection. A simple, rapid method of DNA extraction, by boiling phytoplasma-infected tissues, was developed as well. When used together with the universal LAMP assay, it enabled the prompt and accurate detection of phytoplasmas from plants and insects. The results demonstrate the potential of the 23S rRNA gene as a versatile target for the LAMP-based universal detection of bacteria at the genus level and provide a novel avenue for exploring this gene as molecular marker for phytoplasma presence detection.

IMPORTANCE

Phytoplasmas are associated with economically important diseases in crops worldwide, including lethal yellowing of coconut palm, “flavescence dorée” and “bois noir” of grapevine, X-disease in stone fruits, and white leaf and grassy shoot in sugarcane. Numerous LAMP-based diagnostic assays, mostly targeting the 16S rRNA gene, have been reported for phytoplasmas. However, these assays can only detect a limited number of ‘
Candidatus
Phytoplasma’ species, whereas the genus includes at least 50 of these species. In this study, a universal, specific, and rapid diagnostic system was developed that can detect all provisionally classified phytoplasmas within 1 h by combining the LAMP technique targeting the 23S rRNA gene with a simple method for DNA extraction. This diagnostic system will facilitate the on-site detection of phytoplasmas and may aid in the discovery of new phytoplasma-associated diseases and putative insect vectors, irrespective of the availability of infrastructure and experimental resources.
Functional versatility of Zur in metal homeostasis, motility, biofilm formation, and stress resistance in
Yersinia pseudotuberculosis
Authors: Gu Yanchao , Liu Yongde , Mao Wei , Peng Ying , Han Xiaoru , Jin Han , Xu Jingling , Chang Liyang , Hou Yixin , Shen Xihui , Liu Xingyu , Yang Yantao
Published: March 2024

Zur (zinc uptake regulator) is a significant member of the Fur (ferric uptake regulator) superfamily, which is widely distributed in bacteria. Zur plays crucial roles in zinc homeostasis and influences cell development and environmental adaptation in various species.
Yersinia pseudotuberculosis
is a Gram-negative enteric that pathogen usually serves as a model organism in pathogenicity studies. The regulatory effects of Zur on the zinc transporter ZnuABC and the protein secretion system T6SS have been documented in
Y. pseudotuberculosis
. In this study, a comparative transcriptomics analysis between a ∆
zur
mutant and the wild-type (WT) strain of
Y. pseudotuberculosis
was conducted using RNA-seq. This analysis revealed global regulation by Zur across multiple functional categories, including membrane transport, cell motility, and molecular and energy metabolism. Additionally, Zur mediates the homeostasis not only of zinc but also ferric and magnesium
in vivo
. There was a notable decrease in 35 flagellar biosynthesis and assembly-related genes, leading to reduced swimming motility in the ∆
zur
mutant strain. Furthermore, Zur upregulated multiple simple sugar and oligopeptide transport system genes by directly binding to their promoters. The absence of Zur inhibited biofilm formation as well as reduced resistance to chloramphenicol and acidic stress. This study illustrates the comprehensive regulatory functions of Zur, emphasizing its importance in stress resistance and pathogenicity in
Y. pseudotuberculosis
.

IMPORTANCE

Bacteria encounter diverse stresses in the environment and possess essential regulators to modulate the expression of genes in responding to the stresses for better fitness and survival. Zur (zinc uptake regulator) plays a vital role in zinc homeostasis. Studies of Zur from multiple species reviewed that it influences cell development, stress resistance, and virulence of bacteria.
Y. pseudotuberculosis
is an enteric pathogen that serves a model organism in the study of pathogenicity, virulence factors, and mechanism of environmental adaptation. In this study, transcriptomics analysis of Zur’s regulons was conducted in
Y. pseudotuberculosis
. The functions of Zur as a global regulator in metal homeostasis, motility, nutrient acquisition, glycan metabolism, and nucleotide metabolism, in turn, increasing the biofilm formation, stress resistance, and virulence were reviewed. The importance of Zur in environmental adaptation and pathogenicity of
Y. pseudotuberculosis
was emphasized.
Antibiotic resistance begets more resistance: chromosomal resistance mutations mitigate fitness costs conferred by multi-resistant clinical plasmids
Authors: Nair Ramith R. , Andersson Dan I. , Warsi Omar M.
Published: March 2024

Plasmids are the primary vectors of horizontal transfer of antibiotic resistance genes among bacteria. Previous studies have shown that the spread and maintenance of plasmids among bacterial populations depend on the genetic makeup of both the plasmid and the host bacterium. Antibiotic resistance can also be acquired through mutations in the bacterial chromosome, which not only confer resistance but also result in changes in bacterial physiology and typically a reduction in fitness. However, it is unclear whether chromosomal resistance mutations affect the interaction between plasmids and the host bacteria. To address this question, we introduced 13 clinical plasmids into a susceptible
Escherichia coli
strain and three different congenic mutants that were resistant to nitrofurantoin (Δ
nfsAB
), ciprofloxacin (
gyrA,
S83L), and streptomycin (
rpsL,
K42N) and determined how the plasmids affected the exponential growth rates of the host in glucose minimal media. We find that though plasmids confer costs on the susceptible strains, those costs are fully mitigated in the three resistant mutants. In several cases, this results in a competitive advantage of the resistant strains over the susceptible strain when both carry the same plasmid and are grown in the absence of antibiotics. Our results suggest that bacteria carrying chromosomal mutations for antibiotic resistance could be a better reservoir for resistance plasmids, thereby driving the evolution of multi-drug resistance.

IMPORTANCE

Plasmids have led to the rampant spread of antibiotic resistance genes globally. Plasmids often carry antibiotic resistance genes and other genes needed for its maintenance and spread, which typically confer a fitness cost on the host cell observed as a reduced growth rate. Resistance is also acquired
via
chromosomal mutations, and similar to plasmids they also reduce bacterial fitness. However, we do not know whether resistance mutations affect the bacterial ability to carry plasmids. Here, we introduced 13 multi-resistant clinical plasmids into a susceptible and three different resistant
E. coli
strains and found that most of these plasmids do confer fitness cost on susceptible cells, but these costs disappear in the resistant strains which often lead to fitness advantage for the resistant strains in the absence of antibiotic selection. Our results imply that already resistant bacteria are a more favorable reservoir for multi-resistant plasmids, promoting the ascendance of multi-resistant bacteria.
Timescales of mafic magmatic fractionation documented by paleosecular variation in basaltic drill core, Snake River Plain volcanic province, Idaho, USA
Authors: Shervais John W. , Potter Katherine E.
Published: March 2024

The timescales over which fractional crystallization and recharge work in mafic volcano-plutonic provinces is subject to great uncertainty. Currently modeled processes are subject to the scale of measurement: monogenetic basaltic fields accumulate over hundreds of thousands of years, consistent with U-Th-Ra isotopic variations that imply 50% crystallization of basic magmas on timescales of 100,000 years or more, whereas crystal diffusion modeling implies phenocryst residence times of ~1–1000 years.

Monogenetic basalts of the Snake River Plain in southern Idaho, USA, are up to 2 km thick and postdate passage over the Yellowstone–Snake River Plain hotspot. Detailed lithologic and geophysical logging of core from deep drill holes, along with chemical stratigraphy and high-resolution paleomagnetic inclination measurements, document individual eruptive units, compound lava flows, and basaltic flow groups that accumulated over 1–6 m.y. Hiatuses are commonly marked by loess or fluvial interbeds that vary from ~0.1 m thick to 20 m thick. Radiometric (40Ar-39Ar, detrital zircon U-Pb) and paleomagnetic timescale ages show that the deepest hole (Kimama drill hole, 1912 m total depth) accumulated over ~6 m.y. Cycles of fractional crystallization and recharge are recognized in the chemical stratigraphy as up-section shifts in major and trace elements; these fractionation cycles commonly represent 40%–50% fractionation. Individual fractionation cycles may comprise 20–40 eruptive units (8–17 lava flows) with little to no change in paleomagnetic inclination (0°–1°), whereas adjacent cycles may differ by several degrees from one another or reflect changes in polarity.

Rates of paleosecular variation in Holocene lavas and sediments dated using 14C document significant shifts in magnetic inclination over short timescales, ranging from ~0.05° to 2°/decade, with an average of ~0.5°/decade and a minimum rate of 0.05°/decade. This implies that fractionation cycles with ≤1° variation in magnetic inclination formed on timescales of a few decades up to a few centuries (20–200 years). Thus, the lavas collectively represent only a few thousand years of eruptive activity, with major flow groups separated in time by tens to hundreds of thousands of years. We suggest that the rates defined by paleosecular variation capture the timescales of magmatic chamber evolution (fractionation/recharge) in the seismically imaged mid-crustal sill complex; in contrast, we suggest that crystal diffusion modeling captures the residence times in shallow subvolcanic magmatic chambers that underlie individual monogenetic volcanoes.