bluuebunny/crossref_metadata_2025 huggingface dataset:
Etioplasts are more susceptible to salinity stress than chloroplasts and photosynthetically active etio‐chloroplasts of wheat (Triticum aestivum L.)
Authors: Ounoki Roumaissa , Sóti Adél , Ünnep Renáta , Sipka Gábor , Sárvári Éva , Garab Győző , Solymosi Katalin
Published: December 2023

High soil salinity is a global problem in agriculture that directly affects seed germination and the development of the seedlings sown deep in the soil. To study how salinity affected plastid ultrastructure, leaf segments of 11‐day‐old light‐ and dark‐grown (etiolated) wheat (Triticum aestivum L. cv. Mv Béres) seedlings were floated on Hoagland solution, 600 mM KCl:NaCl (1:1) salt or isosmotic polyethylene glycol solution for 4 h in the dark. Light‐grown seedlings were also treated in the light. The same treatments were also performed on etio‐chloroplasts of etiolated seedlings greened for different time periods. Salt stress induced slight to strong changes in the relative chlorophyll content, photosynthetic activity, and organization of thylakoid complexes. Measurements of malondialdehyde contents and high‐temperature thermoluminescence indicated significantly increased oxidative stress and lipid peroxidation under salt treatment, except for light‐grown leaves treated in the dark. In chloroplasts of leaf segments treated in the light, slight shrinkage of grana (determined by transmission electron microscopy and small‐angle neutron scattering) was observed, while a swelling of the (pro)thylakoid lumen was observed in etioplasts. Salt‐induced swelling disappeared after the onset of photosynthesis after 4 h of greening. Osmotic stress caused no significant alterations in plastid structure and only mild changes in their activities, indicating that the swelling of the (pro)thylakoid lumen and the physiological effects of salinity are rather associated with the ionic component of salt stress. Our data indicate that etioplasts of dark‐germinated wheat seedlings are the most sensitive to salt stress, especially at the early stages of their greening.
Genomic and Transcriptomic Analyses Illuminates Unique Traits of Elusive Night Flowering Jasmine Parijat (Nyctanthes arbor‐tristis)
Authors: Patil Ajinkya Bharatraj , Kar Debojyoti , Datta Sourav , Vijay Nagarjun
Published: December 2023

The night‐flowering Jasmine, Nyctanthes arbor‐tristis also known as Parijat, is a perennial woody shrub belonging to the family of Oleaceae. It is popular for its fragrant flowers that bloom in the night and is a potent source of secondary metabolites. However, knowledge about its genome and the expression of genes regulating flowering or secondary metabolite accumulation is lacking. In this study, we generated whole genome sequencing data to assemble the first de novo assembly of Parijat and use it for comparative genomics and demographic history reconstruction. The temporal dynamics of effective population size (Ne) experienced a positive influence of colder climates suggesting the switch to night flowering may have provided an evolutionary advantage. We employed multi‐tissue transcriptome sequencing of floral stages/parts to obtain insights into the transcriptional regulation of nocturnal flower development and the production of volatiles/metabolites. Tissue‐specific transcripts for mature flowers revealed key players in circadian regulation and flower development, including the auxin pathway and cell wall modifying genes. Furthermore, we identified tissue‐specific transcripts responsible for producing numerous secondary metabolites, mainly terpenoids and carotenoids. The diversity and specificity of Terpene Synthase (TPS) and CCDs (Carotenoid Cleavage Deoxygenases) mediate the bio‐synthesis of specialised metabolites in Parijat. Our study establishes Parijat as a novel non‐model species to understand the molecular mechanisms of nocturnal blooming and secondary metabolite production.
The impact of CO2 emissions and climate on economic growth and productivity: International evidence
Authors: Rigas Nikos , Kounetas Konstantinos Elias
Published: December 2023

In this study, we apply a detailed country level data in the 1961–2015 period to investigate the relationship between weather variables, CO2, share of renewable energy sources, gross domestic product, and total factor productivity in a standard Cobb–Douglas production function by using an instrumental variable approach. Our findings suggest that economic growth has been positively affected by temperature and CO2 emissions, while climate vulnerability varies significantly between rich‐poor countries. Furthermore, the negative nexus between renewable sources and CO2 emissions demonstrates its importance for optimal environmental policies design while an inverted U‐shaped relationship for temperature and emissions.
Network effect and international currency
Authors: Liu Tao , Wang Xiaosong , Woo Wing Thye
Published: December 2023

The network effect is an important factor for the inertia and path dependence in the international monetary system. In this paper, we explore its influence, both theoretically and empirically: (a) by extending the standard monetary search model to a three‐country three‐currency model with multiple transitions to clarify the network effect on currency choices; (b) by showing empirically that the network effect is positive, statistically significant, and quantitatively comparable with other factors, such as trade share. The empirical results hold both for major international currencies and emerging currencies, such as RMB, and for various estimation specifications and subsamples.
Island effects and amelioration by resumption in Jordanian Arabic: An auditory acceptability‐judgment study
Authors: Al‐Aqarbeh Rania , Sprouse Jon
Published: December 2023

This study brings evidence from Jordanian Arabic, a primarily spoken grammatical‐resumption language, into the (formal‐experimental) empirical base of both theories of island effects and theories of island amelioration by resumption. We report four auditory judgment studies exploring two dependency types and four island types with a gap or resumption in the tail of the dependency, yielding 16 distinct quantified effects. Our experiments identified two notable sources of variation: variation across dependency types in the sets of island effects that occur with gaps and variation across island types in amelioration by resumption. We discuss the challenges these results raise for four major classes of theories of island effects, and we point to paths forward for each. We also discuss the consequences of the variation in amelioration for theories of the source of resumption, concluding that both base generation and movement must be available options to learners of Jordanian Arabic. We also observe some evidence of individual variation in the availability of resumption across dependency types that could be explored in future studies.
Reporting and analysis of process-of-care time measures in clinical trials for hyperacute stroke interventions: a scoping review protocol
Authors: Italiano Dominic , Johns Hannah , Campbell Bruce , Turc Guillaume , Churilov Leonid
Published: December 2023

Objective:

The objective of this scoping review is to investigate the reporting and comparison of process-of-care time measures in hyperacute stroke trials and systematic reviews of trials (subsequently referred to as “studies”).

Introduction:

Stroke is a leading cause of death and disability worldwide. A crucial factor in determining the effectiveness of stroke care in improving patient outcomes is time; therefore, time measures are frequently reported in studies of hyperacute stroke interventions. However, there is inconsistency in how these measures are reported and compared. Furthermore, there is a lack of clarity in how compatible the reporting methods are with the statistical analysis methods.

Inclusion criteria:

This scoping review will include studies that report and/or compare time measures between key events of interest in the delivery of hyperacute stroke care. Studies of thrombolytic therapy and/or thrombectomy, as well as controlled trials of mobile stroke unit interventions, will be included.

Methods:

The scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) and the JBI methodology for scoping reviews. The search will be executed in MEDLINE (PubMed), Embase (Ovid), and clinical trial registries ANZCTR, ISRCTN, and ClinicalTrials.gov. Title and abstract screening will be followed by full-text screening and subsequent data extraction from eligible studies. The results from this scoping review will be presented in tables and narratively summarized.

Review registration:

Open Science Framework https://osf.io/y98wz
Network‐based systematic dissection of exercise‐induced inhibition of myosteatosis in older individuals
Authors: Iijima Hirotaka , Ambrosio Fabrisia , Matsui Yusuke
Published: December 2023

Accumulated fat in skeletal muscle (i.e. myosteatosis), common in sedentary older individuals, compromises skeletal muscle health and function. A mechanistic understanding of how physical activity levels dictate fat accumulation represents a critical step towards establishment of therapies that promote healthy ageing. Using a network medicine paradigm that characterized the transcriptomic response of aged muscle to exercise versus immobilization protocols, this study explored the shared molecular cascade that regulates the fate of fibro‐adipogenic progenitors (FAPs), the cell population primarily responsible for fat accumulation. Specifically, gene set enrichment analyses with network propagation revealed Pgc‐1α as a functional hub of a large gene regulatory network underlying the regulation of FAPs by physical activity in aged muscle, but not in young counterparts. Integrated in silico and in situ approaches to induce Pgc‐1α overexpression in aged muscle promoted mitochondrial fatty acid oxidation and inhibited FAP adipogenesis. These findings suggest that the Pgc‐1α–mitochondrial fatty acid oxidation axis is a shared mechanism by which physical activity regulates age‐related myosteatosis. The network medicine paradigm introduced provides mechanistic insight into exercise adaptation in elderly skeletal muscle and offers translational opportunities to advance exercise prescription for older populations.

image

Key points

Fat accumulation is a quintessential feature of aged skeletal muscle.

While increasing physical activity levels has been proposed as an effective strategy to reduce the fat in skeletal muscle (i.e. myosteatosis), the molecular cascade underlying these benefits has been poorly defined.

This study implemented a series of network medicine approaches and uncovered Pgc‐1α as a mechanistic driver of the regulation of fibro‐adipogenic progenitors (FAPs) by physical activity.

Integrated in silico and in situ approaches to induce Pgc‐1α overexpression promoted mitochondrial fatty acid oxidation and inhibited FAP adipogenesis.

Together, the findings of the current study suggest a novel hypothesis that physical activity reduces myosteatosis via upregulation of Pgc‐1α‐mediated mitochondrial fatty acid oxidation and subsequent inhibition of FAP adipogenesis.
The Organization and Conduct of an Industrial Laboratory
Authors: Little A. D. , Howe H. E.
Published: December 2023

During the war industrial research in the United States was naturally stimulated, and as a result there now exists a deeper interest than heretofore in the applications of science to manufacturing processes. New laboratories will undoubtedly be built and many old ones reorganized in order to render more efficient service. It is the purpose of this paper to point out the organization and conduct of such a research laboratory.

The authors first outline the aims of a research organization, following which the divisions of the laboratory are enumerated and discussed, the laboratories of Arthur D. Little, Inc., being taken as a type. The methods of management, writing of reports and the commercial organization of the laboratory are also discussed at some length, and the paper concludes with a description of the building and equipment best suited to carry on this type of work.
Pulverized Coal as a Fuel
Authors: Harrison N. C.
Published: December 2023

The author first reviews some of the uses of pulverized coal in the industries — such as the cement, steel and copper industries, after which he gives a technical definition of pulverized coal, describes the process by which it is prepared for use and furnishes tables of costs of preparation. The pulverized-coal-burning open-hearth steel plant of the American Iron & Steel Manufacturing Co., Lebanon, Pa., is described and the advantages observed in the plant of pulverized coal, compared with producer gas as a fuel for open-hearth furnaces, are listed.

The use of pulverized coal in stationary boiler plants is discussed, five determining factors in the successful operation of such a plant being taken up in detail. As compared with mechanical-stoker plants the advantages of the pulverized-coal plant are enumerated and certain precautions to be observed with the latter type of plant are brought out.

A report of a test of a 468-hp. Edge Moor boiler with pulverized-coal equipment is included in the paper and the efficiency obtained is compared with the efficiency of a stoker-fed boiler in the same plant, a greater net efficiency being found in the pulverized-coal plant.

The paper concludes with a statement of some advantages obtained in the pulverized-coal plant.
Economy of Certain Arizona Steam-Electric Power Plants Using Oil Fuel
Authors: Weymouth C. R.
Published: December 2023

In certain steam-electric power plants the combination of load factor and high fuel cost not only necessitates but also makes possible the attainment of high economies in operation. These particular conditions exist in three Arizona plants known and located as follows: Inspiration Consolidated Copper Company, Inspiration, Ariz.; New Cornelia Copper Company, Ajo, Ariz. and Arizona Power Company, Clarkdale, Ariz. All of these plants embody many similar features and in this paper the author discusses the economy of operation of each. Tables and curves of operating characteristics are also given and these show that the best economy per bbl. of oil obtained at the Inspiration Plant was 294.5 kw-hr., at the New Cornelia Plant 326.2 kw-hr., and at the Arizona plant 333.3 kw-hr. All these values were obtained during the winter months when conditions were most favorable. The paper concludes with a section dealing with the personnel responsible for the installations.
Steam Use in Textile Processes
Authors: Perkins George H.
Published: December 2023

The following paper, presents tables of comparative figures showing the importance of the use of steam for the manufacturing processes in the textile industry. Analyses are given of the various uses to which steam is put and suggestions are made for research and improvement of economy.
Reliability of Materials and Mechanism of Fractures
Authors: de Freminville Charles
Published: December 2023

It is a common experience that the behavior of materials in practice does not always agree with their behavior under test; designs worked out from data secured from test pieces have not always proved satisfactory, and actual machines have had to be modified from the experience of practice. The differences between test predictions and actual results are set forth in the following paper, and it is shown that the reasons for the discrepancy between test and actual conditions can be determined by an analysis of the mechanism of fractures of the test pieces and of actual specimens. Such an analysis reveals the fact that the mechanism of the fracture follows certain laws which can be formulated. The paper also deals with methods of designing members so that stresses in them do not conflict with the laws of mechanism of fracture. Pieces can be so designed and so assembled that the stresses in them largely avoid the conditions of fracture, and it is significant that when such design and assembling is carried out, the behavior of the actual machines is much more similar to the behavior of the test pieces themselves.
Scientific Development of the Steam Locomotive
Authors: Muhlfeld John E.
Published: December 2023

The future of the steam locomotive has been a topic for frequent discussion, particularly since the electrification of the main line of the Baltimore and Ohio Railroad through the city of Baltimore in 1895.

Little attention was given to improving its efficiency until the tunnel, bridge and track-clearance and weight limitations and the rising costs for fuel and labor made it necessary to find means to increase capacity and economy, since which time the compound, Mallet articulated, and superheated-steam types of locomotives have been generally adopted, although the working steam pressures, due to the continuation of the existing locomotive type of boiler, have remained relatively low, with a few extreme cases of from 225 to 250 lb.

In this paper the author discusses at length the scientific factors that have been considered in the design and development of a new, high-powered freight locomotive for the purpose of substantially increasing the average thermal efficiency, as well as the maximum and sustained drawbar pull and horsepower per unit of weight, all of which are now limited by the capacity of the generally adopted boiler superheater.
Development of a Novel Compact Robotic Exoskeleton Glove With Reinforcement Learning Control
Authors: Xu Wenda , Guo Yunfei , Liu Yujiong , Ben-Tzvi Pinhas
Published: December 2023

This paper presents the design, optimization, control, and experimental evaluation of a novel compact exoskeleton glove aiming to assist patients with brachial plexus injuries in grasping daily used objects. The finger mechanism is based on a rigid coupling hybrid mechanism concept, which utilizes a serially connected rack-and-pinion mechanism and an offset slider-crank mechanism to couple the motions of different finger joints. The glove dimensions are synthesized based on the natural grasping motion of human hands. To better control the glove and enhance the grasping capabilities, a simulation environment was developed and reinforcement learning techniques were applied. This learning-based control trained an agent to perform different grasp types with appropriate force. The trained agent was then applied in real-world experiments with the developed exoskeleton glove. The results validated the effectiveness of the mechanical design and the real-time self-adjustable control policy, which demonstrated the glove’s functionality and capability to grasp various objects relevant to activities of daily living.
Data and Knowledge for Overtaking Scenarios in Autonomous Driving
Authors: Pinto Mariana , Dutra Inês , Fonseca Joaquim
Published: December 2023

Autonomous driving has become one of the most popular research topics within artificial intelligence. An autonomous vehicle is understood as a system that combines perception, decision-making, planning, and control. All of those tasks require that the vehicle collects surrounding data in order to make a good decision and action. In particular, the overtaking manoeuvre is one of the most critical actions of driving. The process involves lane changes, acceleration and deceleration actions, and estimation of the speed and distance of the vehicle in front or in the lane in which it is moving. Despite the amount of work available in the literature, just a few handle overtaking manoeuvres and, because overtaking can be risky, no real-world dataset is available. This work contributes in this area by presenting a new synthetic dataset whose focus is the overtaking manoeuvre. We start by performing a review of the state of the art in autonomous driving and then explore the main datasets found in the literature (public and private, synthetic and real), highlighting their limitations, and suggesting a new set of features whose focus is the overtaking manoeuvre.
Practical utility of a head-mounted gaze-directed beamforming system
Authors: Culling John F. , D'Olne Emilie F. C. , Davies Bryn D. , Powell Niamh , Naylor Patrick A.
Published: December 2023

Assistive auditory devices that enhance signal-to-noise ratio must follow the user's changing attention; errors could lead to the desired source being suppressed as noise. A method for measuring the practical benefit of attention-following speech enhancement is described and used to show a benefit for gaze-directed beamforming over natural binaural hearing. First, participants watched a recorded video conference call between two people with six additional interfering voices in different directions. The directions of the target voices corresponded to the spatial layout of their video streams. A simulated beamformer was yoked to the participant's gaze direction using an eye tracker. For the control condition, all eight voices were spatially distributed in a simulation of unaided binaural hearing. Participants completed questionnaires on the content of the conversation, scoring twice as high in the questionnaires for the beamforming condition. Sentence-by-sentence intelligibility was then measured using new participants who viewed the same audiovisual stimulus for each isolated sentence. Participants recognized twice as many words in the beamforming condition. The results demonstrate the potential practical benefit of gaze-directed beamforming for hearing aids and illustrate how detailed intelligibility data can be retrieved from an experiment that involves behavioral engagement in an ongoing listening task.
A nested generalized sidelobe canceller for source counting, localization, and signal separation in reverberant fields
Authors: Kung Fan-Jie , Bai Mingsian R.
Published: December 2023

This paper proposes a nested generalized sidelobe canceller (NGSC) for typical array signal processing tasks, including source counting, localization, and signal separation. Multiple blocking matrices are arranged in a nested structure to successively eliminate dominant sources until the remaining signal is predominantly incoherent noise. The microphone signals are dereverberated using a multichannel weighted prediction error algorithm. In source counting, the number of sound sources is determined by tracking the average power of the blocked signal. In source localization, the direction-of-arrival (DOA) is estimated via cosine similarity in conjunction with the golden section search. In signal separation, the estimated DOA enables speech separation in a linearly constrained minimum variance beamformer with postfiltering (LCMV-PF). Monte Carlo simulations are performed to compare the proposed NGSC approach with four baselines, minimum description length, second order statistic of the eigenvalue, multistage Wiener filtering, and multiple signal classification. The results show that NGSC achieves at least 28.80% higher source counting accuracy with a 1.04° lower root mean square degree error than the baselines. The signal-to-distortion ratio achieved by LCMV-PF is 1.52 dB higher than that achieved by the linearly constrained minimum power beamformer and the multichannel Wiener filter.
Lithospheric thickness records tectonic evolution by controlling metamorphic conditions
Authors: Zhang Zhen-Jie , Chen Guo-Xiong , Kusky Timothy , Yang Jie , Cheng Qiu-Ming
Published: December 2023

The lithosphere, as the outermost solid layer of our planet, preserves a progressively more fragmentary record of geological events and processes from Earth’s history the further back in time one looks. Thus, the evolution of lithospheric thickness and its cascading impacts in Earth’s tectonic system are presently unknown. Here, we track the lithospheric thickness history using machine learning based on global lithogeochemical data of basalt. Our results demonstrate that four marked lithospheric thinning events occurred during the Paleoarchean, early Paleoproterozoic, Neoproterozoic, and Phanerozoic with intermediate thickening scenarios. These events respectively correspond to supercontinent/supercraton breakup and assembly periods. Causality investigation further indicates that crustal metamorphic and deformation styles are the feedback of lithospheric thickness. Cross-correlation between lithospheric thickness and metamorphic thermal gradients records the transition from intraoceanic subduction systems to continental margin and intraoceanic in the Paleoarchean and Mesoarchean and a progressive emergence of large thick continents that allow supercontinent growth, which promoted assembly of the first supercontinent during the Neoarchean.
Modularized microrobot with lock-and-detachable modules for targeted cell delivery in bile duct
Authors: Su Lin , Jin Dongdong , Wang Yuqiong , Wang Qinglong , Pan Chengfeng , Jiang Shuai , Yang Haojin , Yang Zhengxin , Wang Xin , Xia Neng , Chan Kai Fung , Chiu Philip Wai Yan , Sung Joseph Jao-Yiu , Zhang Li
Published: December 2023

The magnetic microrobots promise benefits in minimally invasive cell-based therapy. However, they generally suffer from an inevitable compromise between their magnetic responsiveness and biomedical functions. Herein, we report a modularized microrobot consisting of magnetic actuation (MA) and cell scaffold (CS) modules. The MA module with strong magnetism and pH-responsive deformability and the CS module with cell loading-release capabilities were fabricated by three-dimensional printing technique. Subsequently, assembly of modules was performed by designing a shaft-hole structure and customizing their relative dimensions, which enabled magnetic navigation in complex environments, while not deteriorating the cellular functionalities. On-demand disassembly at targeted lesion was then realized to facilitate CS module delivery and retrieval of the MA module. Furthermore, the feasibility of proposed system was validated in an in vivo rabbit bile duct. Therefore, this work presents a modular design–based strategy that enables uncompromised fabrication of multifunctional microrobots and stimulates their development for future cell-based therapy.
Correlated x-ray fluorescence and ptychographic nano-tomography on Rembrandt’s
The Night Watch
reveals unknown lead “layer”
Authors: Broers Fréderique T.H. , Verslype Ige , Bossers Koen W. , Vanmeert Frederik , Gonzalez Victor , Garrevoet Jan , van Loon Annelies , van Duijn Esther , Krekeler Anna , De Keyser Nouchka , Steeman Ilse , Noble Petria , Janssens Koen , Meirer Florian , Keune Katrien
Published: December 2023

The Night Watch
, one of the most famous masterpieces by Rembrandt, is the subject of a large research and conservation project. For the conservation treatment, it is of great importance to understand its current condition. Correlated nano-tomography using x-ray fluorescence and ptychography revealed a—so far unknown—lead-containing “layer”, which likely acts as a protective impregnation layer applied on the canvas before the quartz-clay ground was applied. This layer might explain the presence of lead soap protrusions in areas where no other lead components are present. In addition to the three-dimensional elemental mapping, ptychography visualizes and quantifies components not detectable by hard x-ray fluorescence such as the organic fraction and quartz. The first-time use of this combination of synchrotron-based techniques on a historic paint micro-sample shows it to be an important tool to better interpret the results of noninvasive imaging techniques operating on the macroscale.
Early human lung immune cell development and its role in epithelial cell fate
Authors: Barnes Josephine L. , Yoshida Masahiro , He Peng , Worlock Kaylee B. , Lindeboom Rik G.H. , Suo Chenqu , Pett J. Patrick , Wilbrey-Clark Anna , Dann Emma , Mamanova Lira , Richardson Laura , Polanski Krzysztof , Pennycuick Adam , Allen-Hyttinen Jessica , Herczeg Iván T. , Arzili Romina , Hynds Robert E. , Teixeira Vitor H. , Haniffa Muzlifah , Lim Kyungtae , Sun Dawei , Rawlins Emma L. , Oliver Amanda J. , Lyons Paul A. , Marioni John C. , Ruhrberg Christiana , Tuong Zewen Kelvin , Clatworthy Menna R. , Reading James L. , Janes Sam M. , Teichmann Sarah A. , Meyer Kerstin B. , Nikolić Marko Z.
Published: December 2023

Studies of human lung development have focused on epithelial and mesenchymal cell types and function, but much less is known about the developing lung immune cells, even though the airways are a major site of mucosal immunity after birth. An unanswered question is whether tissue-resident immune cells play a role in shaping the tissue as it develops in utero. Here, we profiled human embryonic and fetal lung immune cells using scRNA-seq, smFISH, and immunohistochemistry. At the embryonic stage, we observed an early wave of innate immune cells, including innate lymphoid cells, natural killer cells, myeloid cells, and lineage progenitors. By the canalicular stage, we detected naive T lymphocytes expressing high levels of cytotoxicity genes and the presence of mature B lymphocytes, including B-1 cells. Our analysis suggests that fetal lungs provide a niche for full B cell maturation. Given the presence and diversity of immune cells during development, we also investigated their possible effect on epithelial maturation. We found that IL-1β drives epithelial progenitor exit from self-renewal and differentiation to basal cells in vitro. In vivo, IL-1β–producing myeloid cells were found throughout the lung and adjacent to epithelial tips, suggesting that immune cells may direct human lung epithelial development.
Distribution characteristics of the
Legionella
CRISPR-Cas system and its regulatory mechanism underpinning phenotypic function
Authors: Xu Pei-Xing , Ren Hong-Yu , Zhao Na , Jin Xiao-Jing , Wen Bo-Hai , Qin Tian
Published: December 2023

Legionella
is a common intracellular parasitic bacterium that infects humans via the respiratory tract, causing Legionnaires’ disease, with fever and pneumonia as the main symptoms. The emergence of highly virulent and azithromycin-resistant
Legionella pneumophila
is a major challenge in clinical anti-infective therapy. The CRISPR-Cas acquired immune system provides immune defense against foreign nucleic acids and regulates strain biological functions. However, the distribution of the CRISPR-Cas system in
Legionella
and how it regulates gene expression in
L. pneumophila
remain unclear. Herein, we assessed 915
Legionella
whole-genome sequences to determine the distribution characteristics of the CRISPR-Cas system and constructed gene deletion mutants to explore the regulation of the system based on growth ability
in vitro
, antibiotic sensitivity, and intracellular proliferation of
L. pneumophila
. The CRISPR-Cas system in
Legionella
was predominantly Type II-B and was mainly concentrated in the genome of
L. pneumophila
ST1 strains. The Type II-B CRISPR-Cas system showed no effect on the strain’s growth ability
in vitro
but significantly reduced resistance to azithromycin and decreased proliferation ability due to regulation of the
lpeAB
efflux pump and the Dot/Icm type IV secretion system. Thus, the Type II-B CRISPR-Cas system plays a crucial role in regulating the virulence of
L. pneumophila
. This expands our understanding of drug resistance and pathogenicity in
Legionella
, provides a scientific basis for the prevention of Legionnaires’ disease outbreaks and the rational use of clinical drugs, and facilitates effective treatment of Legionnaires’ disease.
Rapid turnover and short-term blooms of
Escherichia coli
in the human gut
Authors: Han Na , Peng Xianhui , Zhang Tingting , Qiang Yujun , Li Xiuwen , Zhang Wen
Published: December 2023

Escherichia coli (E. coli
) is a common microorganism that is widely present in the environment and closely related to human health. The extent of
E. coli
presence in the human gut has been a subject of ongoing debate. Through whole-genome shotgun metagenomic sequencing, our study revealed that
E. coli
exists in the human body at a low abundance (average abundance 1.21%), with occasional short-term bursts leading to temporary increases in abundance, with the highest recorded at 50.91%. Further investigations into the factors contributing to these short-term blooms of
E. coli
showed significant variations in strain types and genomes within fecal samples collected from the same individuals at different time points. Evolutionary tree analysis indicated that samples from different individuals crossed, suggesting a change in the dominant
E. coli
strains within the human gut. Therefore, it can be inferred that
E. coli
in the human body are more likely to be transient bacteria rather than permanent residents in the gut. The rapid rate of turnover among months (87.5% within a month) and short-term blooms of
E. coli
in the human body can establish "latent infections" of nonpathogenic strains in healthy individuals while also posing a potential risk of introducing pathogenic strains, thereby impacting human health. In summary, our study revealed the variation in
E. coli
abundance and strains within the human gut, influenced by geographic area and temporal factors. These findings contribute to a better understanding of the relationship between
E. coli
, the gut microbiota, and human health.

IMPORTANCE

Escherichia coli (E. coli
) is a microorganism closely linked to human health, and its presence in the human gut has been a topic of debate. Our study, using whole-genome shotgun metagenomic sequencing, revealed that
E. coli
exists at a low abundance in the human body, with occasional short-term bursts leading to temporary increases. Strain and genome variations were observed within fecal samples from the same individuals at different time points, suggesting transient rather than permanent residence of
E. coli
in the gut. The rapid turnover rate and short-term blooms of
E. coli
can establish latent infections while also posing a risk of introducing pathogenic strains. These findings enhance our understanding of the relationship between
E. coli
, the gut microbiota, and human health.
Detection of
Histoplasma capsulatum
and
Blastomyces dermatitidis
antigens in serum using a single quantitative enzyme immunoassay
Authors: Granger Dane , Streck Nicholas T. , Theel Elitza S.
Published: December 2023

Histoplasma
and
Blastomyces
antigen detection assays are commonly used diagnostic tools. However, a high level of cross-reactivity between these antigens prevents definitive pathogen identification by these assays alone. Retrospective analysis of 3,529 patients with
Histoplasma
and
Blastomyces
antigen testing performed on the same serum sample yielded an overall percent agreement of 99.3% (3,506 of 3,529; kappa: 0.859) between the two assays, suggesting that use of a single assay to detect both antigens may be an alternative diagnostic approach. We assessed performance of the Gotham BioTech
Blastomyces
antigen (GBA) enzyme immunoassay (EIA) (Portland, Maine) for detection of
Blastomyces
and
Histoplasma
antigens in serum. Comparison to the MiraVista Diagnostics
Blastomyces
(MVB) EIA showed 100% positive (24 of 24), negative (57 of 57), and overall (81 of 81) percent agreement. Additionally, 171 sera were used to compare the GBA EIA to the MiraVista Diagnostics
Histoplasma
(MVH) EIA, which showed 91.3% (63 of 69), 98% (100 of 102), and 95.3% (163 of 171) positive, negative, and overall percent agreement, respectively. Among eight patients with discordant GBA/MVH EIA results, seven had additional fungal testing performed, and results suggested that the MVH and GBA results were inaccurate for two and five samples, respectively. Overall, this study suggests that the GBA EIA has a high level of agreement with both of the commonly used, individual
Blastomyces
and
Histoplasma
antigen EIAs. By taking advantage of the high level of cross-reactivity between
Blastomyces
and
Histoplasma
antigen EIAs, utilization of a single antigen detection assay for these fungi provides an opportunity to optimize test utilization and decrease patient cost while maintaining a high level of diagnostic accuracy.
The inaugural
mBio
Junior Editorial Board—lessons learned and the path forward toward improving the peer review process
Authors: Adinortey Cynthia Ayefoumi , Dolan Stephen K. , Doore Sarah , Lijek Rebeccah , Pires Diana Priscila , Yu Wenqi , Draganova Elizabeth B. , Schada von Borzyskowski Lennart
Published: December 2023

The inaugural Junior Editorial Board (JEB) of
mBio
consisted of 64 early-career researchers active from 2022 to 2023. The goal of the JEB was to train early-career researchers in the art of peer review under the guidance of experienced editors. JEB members gained hands-on experience in peer review by participating in modules detailing the publishing process through the lenses of the journal, editor, and reviewer. Ultimately, JEB members applied this new knowledge by reviewing
mBio
manuscripts. Here, we summarize the background, the mission, and the achievements of the first
mBio
JEB. We also include possible trajectories for the future editions of this important program.
Filtration effect of
Cordyceps chanhua
mycoderm on bacteria and its transport function on nitrogen
Authors: Hu Gongping , Zhou Yeming , Mou Dan , Qu Jiaojiao , Luo Li , Duan Lin , Xu Zhongshun , Zou Xiao
Published: December 2023

Cordyceps chanhua
is a kind of entomopathogenic fungus that has a long medicinal history in traditional Chinese medicine. In this study, we aimed to explore the role of
C. chanhua
mycoderm. Our results showed that
C. chanhua
mycoderm has a certain ability to transfer nitrogen, which can transfer nitrogen from the insect body to the external environment and transfer nitrogen from the environment to
C. chanhua
. By studying the filtration of bacterial mycoderm, it was found that the mycoderm of
C. chanhua
was able to filter out most of the bacteria in the environment. Using the high-throughput sequencing methods, we found that the abundance of bacterial community first increased and then decreased during the growth and development of
C. chanhua
. The bacterial richness and diversity of mycoderm of
C. chanhua
cultivated in sterile glass bottles were significantly lower than those cultivated in soil mulching. In addition, this study also found that the mycoderm of
C. chanhua
formed under both soil mulching cultivation and sterile glass bottle cultivation was hydrophobic. The mycoderm of
C. chanhua
, which occurred under sterile glass bottle cultivation, was closely and orderly arranged, while the mycoderm of
C. chanhua
cultivated in soil was quite the opposite. The density and thickness of the
C. chanhua
membrane in aseptic glass bottle culture were higher than those in soil-covered culture, but the dry/fresh weight was lower than those in soil-covered culture.

IMPORTANCE

During the natural growth of
Cordyceps chanhua
, it will form a mycoderm structure specialized from hyphae. We found that the bacterial membrane of
C. chanhua
not only filters environmental bacteria but also absorbs and transports nitrogen elements inside and outside the body of
C. chanhua
. These findings are of great significance for understanding the stable mechanism of the internal microbial community maintained by
C. chanhua
and how
C. chanhua
maintains its own nutritional balance. In addition, this study also enriched our understanding of the differences in bacterial community composition and related bacterial community functions of
C. chanhua
at different growth stages, which is of great value for understanding the environmental adaptation mechanism, the element distribution network, and the changing process of symbiotic microbial system after
Cordyceps
fungi infected the host. At the same time, it can also provide a theoretical basis for some important ecological imitation cultivation technology of
Cordyceps
fungi.
Detecting horizontal gene transfer among microbiota: an innovative pipeline for identifying co-shared genes within the mobilome through advanced comparative analysis
Authors: Schwarzerova Jana , Zeman Michal , Babak Vladimir , Jureckova Katerina , Nykrynova Marketa , Varga Margaret , Weckwerth Wolfram , Dolejska Monika , Provaznik Valentine , Rychlik Ivan , Cejkova Darina
Published: December 2023

The study presents an innovative pipeline for detecting horizontal gene transfer (HGT) among a collection of sequenced genomes from gut microbiota. Herein, chicken and porcine gut microbiota were analyzed. Based on statistical analysis, we propose that nearly identical genes co-shared between distinct genera can be evidence for a previous event of mobilization of that gene from genome to genome
via
HGT. Data mining, computational analysis, and network analysis were used to investigate genomes of 452 isolates of chicken or porcine origin to detect genes involved in HGT. The proposed pipeline is user-friendly and includes network visualization. The study highlights that different species and strains of the same genera typically carry different cargo of mobilized genes. The pipeline is capable of identifying not yet characterized genes, as well as genes that are usually co-transferred with genes involved in resistance, virulence, and/or mobilization. Among the analyzed genome collection, the main reservoirs of the HGT genes were found in
Phocaeicola
spp. (
Bacteroidaceae
) and UBA9475 spp. (early
Pseudoflavonifractor
,
Oscillospiraceae
). Altogether, over 6,000 genes suspected of HGT were identified. Genes associated with intracellular trafficking and secretion and DNA repair were enriched, while genes of unknown and general functions were dominant but not enriched. Only 15 genes were co-shared between Gram-positive and Gram-negative bacteria, mostly genes directly associated with mobilome or antibiotic resistance. However, most HGTs were identified among different genera of the same phylum. Therefore, we suggest that a significant selection pressure exists on gene variants at the phylum level.

IMPORTANCE

Horizontal gene transfer (HGT) is a key driver in the evolution of bacterial genomes. The acquisition of genes mediated by HGT may enable bacteria to adapt to ever-changing environmental conditions. Long-term application of antibiotics in intensive agriculture is associated with the dissemination of antibiotic resistance genes among bacteria with the consequences causing public health concern. Commensal farm-animal-associated gut microbiota are considered the reservoir of the resistance genes. Therefore, in this study, we identified known and not-yet characterized mobilized genes originating from chicken and porcine fecal samples using our innovative pipeline followed by network analysis to provide appropriate visualization to support proper interpretation.
Supplemental Material: High-precision U-Pb geochronology links magmatism in the Southwestern Laurentia large igneous province and Midcontinent Rift
Authors: Mohr Michael T. , al. et
Published: December 2023

Full U-Pb geochronology data and additional analytical methods.  
Trend, regional variation and socioeconomic inequality in cardiovascular disease among the elderly population in China: evidence from a nationwide longitudinal study during 2011–2018
Authors: Wu Qiong , Zhao Yang , Liu Lihua , Liu Yuehui , Liu Jianchao
Published: December 2023

Introduction

Cardiovascular disease (CVD) continues to pose a significant burden among the elderly population in China. There is a knowledge gap in the temporal trends, regional variations and socioeconomic inequalities among this vulnerable population.

Methods

This study conducted cross-sectional and cohort analyses based on four survey waves of the China Health and Retirement Longitudinal Study among adults aged ≥60 years spanning 2011–2018 across 28 provinces. Cross-sectional analyses examined temporal trends, regional variations and socioeconomic inequalities in CVD prevalence. Cohort analyses identified individuals without CVD in 2011 and followed them up until 2018 to calculate CVD incidence. Generalised estimating equations (GEE) were employed to identify associated factors.

Results

A total of 5451, 7258, 8820 and 11 393 participants were eligible for cross-sectional analyses, and 4392 and 5396 participants were included in cohort analyses of CVD and comorbid CVD. In 2018, the age-adjusted and sex-adjusted prevalence of CVD and comorbid CVD was 31.21% (95% CI 27.25% to 35.17%) and 3.83% (95% CI 2.85% to 4.81%), respectively. Trend analyses revealed a significant increase in the adjusted prevalence from 2011 to 2018 (p for trend <0.001). There were substantial provincial variations in the adjusted prevalence of CVD and comorbid CVD. Higher socioeconomic status (SES) participants exhibited higher prevalence, and the concentration curves and concentration indices suggested persistent but narrowing inequalities in CVD and comorbid CVD across survey waves. Cohort analyses from 2011 to 2018 yielded overall CVD and comorbid CVD incidence densities of 17.96 and 2.65 per 1000 person-years, respectively. GEE results indicated increased CVD risks among older individuals, women, higher SES participants and northern residents.

Conclusion

More efforts should be taken to optimise strategies for high-quality CVD prevention and management in China’s elderly population. Future interventions and policies should address age-specific and gender-specific, geographical, and socioeconomic disparities to ensure equitable access and outcomes for all.
Immune microenvironment of basal cell carcinoma and tumor regression following combined PD-1/LAG-3 blockade
Authors: Deutsch Julie Stein , Lai Jonathan , Schenk Kara M , Soni Abha , Will Elizabeth M , Engle Logan L , Xu Haiying , Ogurtsova Alexandra , Madan Vrinda , Chong Jennifer K , Wang Daphne , Green Benjamin F , Nguyen Peter , Schollenberger Megan D , Lipson Evan J , Taube Janis M
Published: December 2023

Systemic treatment options for patients with locally advanced or metastatic basal cell carcinoma (BCC) are limited, particularly when tumors are refractory to anti-programmed cell death protein-1 (PD-1). A better understanding of immune checkpoint expression within the BCC tumor microenvironment may inform combinatorial treatment strategies to optimize response rates. CD3, PD-1, programmed death ligand-1 (PD-L1), lymphocyte activation gene 3 (LAG-3), and T-cell immunoglobulin domain and mucin domain 3 (TIM-3)+ cell densities within the tumor microenvironment of 34 archival, histologically aggressive BCCs were assessed. Tumor infiltrating lymphocyte (TIL) expression of PD-1, PD-L1, and LAG-3, and to a lesser degree TIM-3, correlated with increasing CD3+ T-cell densities (Pearson’sr=0.89, 0.72, 0.87, and 0.63, respectively). 100% of BCCs (34/34) demonstrated LAG-3 and PD-1 expression in >1% TIL; and the correlation between PD-1 and LAG-3 densities was high (Pearson’s r=0.89). LAG-3 was expressed at ~50% of the level of PD-1. Additionally, we present a patient with locally-advanced BCC who experienced stable disease during and after 45 weeks of first-line anti-PD-1 (nivolumab), followed by a partial response after the addition of anti-LAG-3 (relatlimab). Longitudinal biopsies throughout the treatment course showed a graduated increase in LAG-3 expression after anti-PD-1 therapy, lending support for coordinated immunosuppression and suggesting LAG-3 as a co-target for combination therapy to augment the clinical impact of anti-PD-(L)1.