bluuebunny/crossref_metadata_2025 huggingface dataset:
MdMYB54 reduces disease severity caused by Fusarium solani in apple by modulating cell wall cellulose and pectate lyase‐dependent defense
Authors: Liu Qianwei , Chen Xiao , Li Sujuan , Wang Qian , Liu Yusong , Zhang Zhijun , Yang Chao , Xu Shuo , Mao Ke , Ma Fengwang , Li Chao
Published: December 2024

The plant cell wall is the first barrier against pathogen invasion. Fusarium solani is the primary pathogen responsible for apple replant disease. In this study, we identified an MYB protein, MdMYB54, which interacts with the positive regulator of F. solani resistance, MdERF114, and confers apple‐increased tolerance against F. solani. The cellulose synthetase (CESA) gene MdCesA6 and pectin lyase‐like (PLL) genes MdPLL8 and MdPLL12 were screened as three potential downstream target genes of MdMYB54 using DAP‐seq. The results of electrophoretic mobility shift and yeast one‐hybrid assays showed that MdMYB54 directly binds to the promoters of MdCesA6, MdPLL8, and MdPLL12 in vivo and in vitro. Dual‐luciferase and β‐glucuronidase assays showed that MdMYB54 activates the expression of these genes. The cellulose content and pectin lyase activity of MdMYB54‐overexpressed roots were significantly higher than those of wild‐type plants under F. solani treatment but were the opposite in MdMYB54‐RNAi roots. The deposition of cellulose enhanced the physical barrier of the plant cell wall, whereas the activation of pectin lyase promoted the formation of oligogalacturonides and the production of reactive oxygen species. Overexpression of MdCesA6, MdPLL8, and MdPLL12 in the root system enhanced the tolerance of apple to F. solani. The direct interaction of MdERF114 with MdMYB54 enhanced MdMYB54‐mediated cell wall defense response. These results suggest that modifying these candidate genes may provide a strategy for improving the resistance of apple to F. solani.
Recurrencias en lectura literaria escolar: análisis desde (y para) la justicia social
Authors: Sánchez-Lara Ricardo Antonio
Published: December 2024

El propósito de este artículo es caracterizar la lectura literaria escolar desde una perspectiva de justicia, puntualizando en las participaciones recurrentes del estudiantado. Para estos fines, se examinan 26 incidentes críticos y 13 entrevistas semiestructuradas, reportadas por estudiantes del sistema educativo chileno, de entre 15 y 17 años. En específico, se analiza la literacidad escolar relacionando algunas textualidades del corpus con premisas de la justicia socioeducativa y de la educación literaria. Entre las principales conclusiones, es posible destacar que la lectura literaria es un evento de literacidad donde no es habitual la interacción entre pares, la reflexión ni la creación, cuando se asocia con la medición. Por el contrario, es frecuente concebirla como un fenómeno de decodificación universal, siendo recurrente la limitación de espacios expresivos, la anulación emocional y la evaluación de comprensiones lectoras posteriores a la experiencia estética.
Integrating Graph Retrieval-Augmented Generation With Large Language Models for Supplier Discovery
Authors: Li Yunqing , Ko Hyunwoong , Ameri Farhad
Published: December 2024

As supply chain complexity and dynamism challenge traditional management approaches, integrating large language models (LLMs) and knowledge graphs (KGs) emerges as a promising method for advancing supply chain analytics. This article presents a methodology crafted to harness the synergies between LLMs and KGs, with a particular focus on enhancing supplier discovery practices. The primary goal is to transform and integrate a vast body of unstructured supplier capability data into a harmonized KG, thus improving the supplier discovery process and enhancing the accessibility and findability of manufacturing suppliers. Through an ontology-driven graph construction process, the presented methodology integrates KGs and retrieval-augmented generation with advanced LLM-based natural language processing techniques. With the aid of a detailed case study, we showcase how this integrated approach not only enhances the quality of answers and increases visibility for small- and medium-sized manufacturers but also amplifies agility and provides strategic insights into supply chain management.
An Educational Review on Machine Learning: A SWOT Analysis for Implementing Machine Learning Techniques in Football
Authors: Beato Marco , Jaward Mohamed Hisham , Nassis George P. , Figueiredo Pedro , Clemente Filipe Manuel , Krustrup Peter
Published: December 2024

Purpose: The abundance of data in football presents both opportunities and challenges for decision making. Consequently, this review has 2 primary objectives: first, to provide practitioners with a concise overview of the characteristics of machine-learning (ML) analysis, and, second, to conduct a strengths, weaknesses, opportunities, and threats (SWOT) analysis regarding the implementation of ML techniques in professional football clubs. This review explains the difference between artificial intelligence and ML and the difference between ML and statistical analysis. Moreover, we summarize and explain the characteristics of ML learning approaches, such as supervised learning, unsupervised learning, and reinforcement learning. Finally, we present an example of a SWOT analysis that suggests some actions to be considered in applying ML techniques by medical and sport science staff working in football. Specifically, 4 dimensions are presented: the use of strengths to create opportunities and make the most of them, the use of strengths to avoid threats, working on weaknesses to take advantage of opportunities, and upgrading weaknesses to avoid threats. Conclusion: ML analysis can be an invaluable tool for football clubs and sport-science and medical departments due to its ability to analyze vast amounts of data and extract meaningful insights. Moreover, ML can enhance performance by assessing the risk of injury, physiological parameters, and physical fitness, as well as optimizing training, recommending strategies based on opponent analysis, and identifying talent and assessing player suitability.
Smartphone Google Location History: A Novel Approach to Outdoor Physical Activity Research
Authors: Amram Ofer , Oje Olufunso , Larkin Andrew , Boakye Kwadwo , Avery Ally , Gebremedhin Assefaw , Williams Bethany , Duncan Glen E. , Hystad Perry
Published: December 2024

Background: Outdoor physical activity (PA) is an important component of overall health; however, it is difficult to measure. Passively collected smartphone location data like Google Location History (GLH) present an opportunity to address this issue. Objectives: To evaluate the use of GLH data for measuring outdoor PA. Methods: We collected GLH data for 357 individuals from the Washington State Twin Registry. We first summarized GLH measurements relevant to outdoor PA. Next, we compared accelerometer measurements to GLH classified PA for a subset of 25 participants who completed 2 weeks of global positioning system and accelerometer monitoring. Finally, we examined the association between GLH measured walking and obesity. Results: Participants provided a mean (SD) average 52 (18.8) months of GLH time-activity data, which included a mean (SD) average of 2421 (1632) trips per participant. GLH measurements were classified as the following: 79,994 unique walking trips (11.6% of all trips), 564,558 (81.8%) trips in a passenger vehicle, 11,974 cycling trips (1.7%), and 890 running trips (0.1%). Sixty-two percent of these trips had location accuracy >80%. In the accelerometry evaluation, GLH walking trips had a corresponding mean vector magnitude of 3150 counts per minute, compared with 489 counts per minute for vehicle trips. In adjusted cross-sectional analyses, we observed an inverse association between both walking minutes and trips per month and the odds of being obese (odds ratio = 0.78; 95% CI, 0.60–0.96, and odds ratio = 0.91; 95% CI, 0.82–0.98, respectively). Conclusions: GLH data provide a novel method for measuring long-term, retrospective outdoor PA that can provide new opportunities for PA research.
Highly multiplexed fluorescence microscopy with spectrally tunable semiconducting polymer dots
Authors: Guo Ziyu , Poudel Chetan , Sarfatis Margaret C. , Yu Jiangbo , Wong Madeline , Chiu Daniel T. , Vaughan Joshua C.
Published: December 2024

Current studies of biological tissues require visualizing diverse cell types and molecular interactions, creating a growing need for versatile techniques to simultaneously probe numerous targets. Traditional multiplexed imaging is limited to around five targets at once. Emerging methods using sequential rounds of staining, imaging, and signal removal can probe tens of targets but require specialized hardware and time-consuming workflows and face challenges with sample distortion and artifacts. We present a highly multiplexed fluorescence microscopy method using semiconducting polymer dots (Pdots) in a single round of staining and imaging. Pdots are small, bright, and photostable fluorescent probes with a wide range of tunable Stokes shifts (20 to 450 nanometers). Multiple series of Pdots with varying excitation wavelengths allow for fast (<1 minute) and single-round imaging of up to 21 targets in the brain and kidney. This method is based on a simple immunofluorescence workflow, efficient use of spectral space, standard hardware, and straightforward analysis, making it widely applicable for bioimaging laboratories.
MLL/WDR5 complex recruits centriolar satellite protein Cep72 to regulate microtubule nucleation and spindle formation
Authors: Chodisetty Swathi , Arora Aditi , Malik Kausika Kumar , Goel Himanshu , Tyagi Shweta
Published: December 2024

Dysfunction of the centrosome, the major microtubule-organizing center of the cell, is implicated in microcephaly. Haploinsufficiency of mixed-lineage leukemia (MLL/KMT2A) protein causes Wiedemann-Steiner syndrome (WSS), a neurodevelopmental disorder associated with microcephaly. However, whether MLL has a function at the centrosome is not clear. Here, we show that loss of the MLL/WDR5 complex affects microtubule nucleation and regrowth. MLL/WDR5 localize to the pericentriolar material and interact with centriolar satellite protein Cep72 and γ-tubulin ring complex proteins (γ-TuRCs). MLL/WDR5 promote the localization of γ-TuRCs and structural proteins like AKAP9 to the centrosome during interphase and mitosis, a phenotype also observed in cells derived from patients with WSS. During mitosis, loss of MLL, WDR5, and Cep72 affects spindle formation and leads to misaligned chromosomes. Last, we show that MLL and WDR5 recruit Cep72 to the centrosome. Our studies provide insight into an undiscovered role of MLL at the centrosome and elucidate how centriolar satellite proteins like Cep72 can be recruited to the centrosome.
Perceptual constancy for an odor is acquired through changes in primary sensory neurons
Authors: Conway Mark , Oncul Merve , Allen Kate , Zhang Zongqian , Johnston Jamie
Published: December 2024

The ability to consistently recognize an object despite variable sensory input is termed perceptual constancy. This ability is not innate; rather, it develops with experience early in life. We show that, when mice are naïve to an odor object, perceptual constancy is absent across increasing concentrations. The perceptual change coincides with a rapid reduction in activity from a single olfactory receptor channel that is most sensitive to the odor. This drop in activity is not a property of circuit interactions within the olfactory bulb; instead, it is due to a sensitivity mismatch of olfactory receptor neurons within the nose. We show that, after forming an association of this odor with food, the sensitivity of the receptor channel is matched to the odor object, preventing transmission failure and promoting perceptual stability. These data show that plasticity of the primary sensory organ enables learning of perceptual constancy.
Noninvasive identification of carbon-based black pigments with pump-probe microscopy
Authors: Kastenholz Heidi V. , Topper Michael I. , Warren Warren S. , Fischer Martin C. , Grass David
Published: December 2024

Carbon-based black pigments, a widely used class of pigments, are difficult to differentiate with the noninvasive techniques currently used in cultural heritage science. We use pump-probe microscopy, coupled with a support vector machine, to distinguish common carbon-based black pigments as pure pigments, as two-component black pigment mixtures, and as a mixture of a black and a colorful pigment. This work showcases the potential of pump-probe microscopy to spatially differentiate carbon-based black pigments, which would have interesting applications to works of art.
Framework nucleic acid strategy enables closer microbial contact for programming short-range interaction
Authors: Chen Na , Xi Jing , Du Na , Shen Ruichen , Zhao Rui , He Wei , Peng Tianhuang , Yang Yanbing , Zhang Yun , Yu Lilei , Tan Weihong , Yuan Quan
Published: December 2024

Programming precise and specific microbial intraspecies or interspecies interaction would be powerful for microbial metabolic regulation, signal pathway mechanism understanding, and therapeutic application. However, it is still of great challenge to develop a simple and universal method to artificially encode the microbial interactions without interfering with the intrinsic cell metabolism. Here, we proposed an extensible and flexible framework nucleic acid strategy for encoding the specific and precise microbial interactions upon self-assembly. With this spatial manipulation tool, we propose the microbial spatial heterogeneity and short-range interaction mechanism that the microbial assembly facilitates the gene expressions of the surface sensors including flagella and pili in
Pseudomonas aeruginosa
, leading to a more sensitive response to quorum sensing. The microbial interaction programming strategy proposed in this work is expected to provide a powerful and designable nanoplatform for better understanding of distance-dependent bacterial communication networks.
The BfmRS stress response protects
Acinetobacter baumannii
against defects in outer membrane lipoprotein biogenesis
Authors: Marotta Julianna , Zhao Alan , Rather Philip N. , Grabowicz Marcin
Published: December 2024

The outer membrane (OM) of Gram-negative bacteria is the outermost layer of the cell and serves as permeability barrier against environmental toxins, including antibiotics. The OM is built by several pathways that transport and assemble lipids and proteins into the OM. Since the OM is an essential organelle for the cell, envelope stress responses (ESRs) continuously monitor its assembly to preserve viability if defects arise. While ESRs have been extensively characterized in
Escherichia coli
, they are generally narrowly conserved. Lipoprotein trafficking to the OM via the “Lol” pathway is a linchpin for all OM assembly pathways. In
E. coli
, defects in this essential process are sensed when the sensor OM lipoprotein NlpE activates the CpxAR two-component system. Distantly related
Acinetobacter baumannii
encodes an NlpE homolog but lacks any Cpx homolog; how OM lipoprotein stress might be sensed and mitigated in these bacteria is therefore unclear. Here, we used CRISPRi to transiently induce defects in OM lipoprotein synthesis (targeting
lgt
and
lnt
) or trafficking (targeting
lolA
) in
A. baumannii
. We defined the transcriptional response to blocks in OM lipoprotein biogenesis. After scrutinizing candidate ESRs, we identified the BfmRS two-component systems as specifically critical for preserving
A. baumannii
viability during stress in OM lipoprotein biogenesis. Surprisingly,
A. baumannii
NlpE played no role in combatting OM lipoprotein stress. Our study identifies an
A. baumannii
ESR for OM lipoprotein biogenesis defects that acts in a distinct mechanism, not involving the NlpE sensor lipoprotein.

IMPORTANCE

As the cell’s surface, the outer membrane (OM) of bacteria, such as
Acinetobacter baumannii
, is continuously under assault from the environment or host. OM integrity is needed for cell survival, and envelope stress responses (ESRs) act to detect and repair any defects. ESRs are well-defined in
Escherichia coli
but are poorly conserved. We sought to identify an ESR for the essential process of OM lipoprotein biogenesis in
A. baumannii
. We found that the BfmRS two-component system performs this function and does so without relying on its NlpE sensor homolog, suggesting a novel mechanism of stress sensing is involved in
A. baumannii
. Our work identifies a key cellular role for BfmRS.
Exploring aggregation genes in a
P. aeruginosa
chronic infection model
Authors: Gannon Alexa D. , Matlack Jenet , Darch Sophie E.
Published: December 2024

Bacterial aggregates are observed in both natural and artificial environments. In the context of disease, aggregates have been isolated from chronic and acute infections.
Pseudomonas aeruginosa
(
Pa
) aggregates contribute significantly to chronic infections, particularly in the lungs of people with cystic fibrosis (CF). Unlike the large biofilm structures observed
in vitro
,
Pa
in CF sputum forms smaller aggregates (~10–1,000 cells), and the mechanisms behind their formation remain underexplored. This study aims to identify genes essential and unique
to
Pa aggregate formation in a synthetic CF sputum media (SCFM2). We cultured
Pa
strain PAO1 in SCFM2 and LB, both with and without mucin, and used RNA sequencing (RNA-seq) to identify differentially expressed genes. The presence of mucin revealed 13 significantly differentially expressed (DE) genes, predominantly downregulated, with 40% encoding hypothetical proteins unique to aggregates. Using high-resolution microscopy, we assessed the ability of mutants to form aggregates. Notably, no mutant exhibited a completely planktonic phenotype. Instead, we identified multiple spatial phenotypes described as “normal,” “entropic,” or “impaired.” Entropic mutants displayed tightly packed, raft-like structures, while impaired mutants had loosely packed cells. Predictive modeling linked the prioritized genes to metabolic shifts, iron acquisition, surface modification, and quorum sensing. Co-culture experiments with wild-type PAO1 revealed further spatial heterogeneity and the ability to “rescue” some mutant phenotypes, suggesting cooperative interactions during growth. This study enhances our understanding of
Pa
aggregate biology, specifically the genes and pathways unique to aggregation in CF-like environments. Importantly, it provides insights for developing therapeutic strategies targeting aggregate-specific pathways.

IMPORTANCE

This study identifies genes essential for the formation of
Pseudomonas aeruginosa
(Pa) aggregates in cystic fibrosis (CF) sputum, filling a critical gap in understanding their specific biology. Using a synthetic CF sputum model (SCFM2) and RNA sequencing, 13 key genes were identified, whose disruption led to distinct spatial phenotypes observed through high-resolution microscopy. The addition of wild-type cells either rescued the mutant phenotype or increased spatial heterogeneity, suggesting cooperative interactions are involved in aggregate formation. This research advances our knowledge of
Pa
aggregate biology, particularly the unique genes and pathways involved in CF-like environments, offering valuable insights for developing targeted therapeutic strategies against aggregate-specific pathways.
Construction and characterization of an infectious cDNA clone of turtle grass virus X from a naturally infected
Thalassia testudinum
plant
Authors: Alvarado-Marchena Luis , Furman Bradley T. , Breitbart Mya
Published: December 2024

Seagrasses are a polyphyletic group of marine flowering plants that play crucial roles in nearshore ecology, yet their interactions with viruses remain largely unexplored. This study presents the construction and characterization of an infectious cDNA clone of the potexvirus turtle grass virus X (TGVX). The complete genome of this positive-sense single-stranded RNA virus was amplified from field samples of
Thalassia testudinum
and assembled into a pLX-based mini binary vector using a multi-fragment directional cloning strategy, resulting in the infectious clone pLX-TGVX. Agroinfection assays of potexvirus-free
T. testudinum
plants resulted in systemic infections by TGVX, as confirmed by multiplex RT-PCR experiments and phenotypic changes reflecting virus-induced symptoms. Ultrastructural studies also demonstrated significant cytopathological changes resulting from TGVX infection, including chloroplast swelling, reduced thylakoid grana, and the presence of viral replication organelles and filamentous virus-like particles. The development of the TGVX infectious clone offers a novel tool for investigating the impact of this virus on seagrass health and productivity. This study demonstrates the first successful agroinfection of a marine plant with an infectious clone, creating a new avenue for studying viruses identified through sequence-based surveys and paving the way for exploring the ecological significance of viral infection in these critical marine ecosystems.

IMPORTANCE

This study pioneers the construction of an infectious clone of turtle grass virus X and describes its application in the natural marine plant host,
Thalassia testudinum
. The creation of this infectious clone not only provides a valuable tool for marine plant virology research but also opens new avenues for exploring the influence of viral infections on the health and productivity of seagrass meadows. Given that seagrasses play a crucial role in sediment stabilization, nutrient cycling, and habitat provisioning, understanding the impact of viruses on these ecosystems is essential for their effective conservation and management. This methodological advance enables detailed studies of viral replication, virus-host interactions, and the broader ecological implications of viral infections in marine plants.
Catabolic pathway acquisition by rhizosphere bacteria readily enables growth with a root exudate component but does not affect root colonization
Authors: Christel Stephan , Carrell Alyssa A. , Hochanadel Leah H. , Villalobos Solis Manuel I. , Abraham Paul E. , Jawdy Sara S. , Chaves Julie E. , Engle Nancy L. , Berhane Timkhite-Kulu , Yao Tao , Chen Jin-Gui , Muchero Wellington , Tschaplinski Timothy J. , Cregger Melissa A. , Michener Joshua K.
Published: December 2024

Horizontal gene transfer (HGT) is a fundamental evolutionary process that plays a key role in bacterial evolution. The likelihood of a successful transfer event is expected to depend on the precise balance of costs and benefits resulting from pathway acquisition. Most experimental analyses of HGT have focused on phenotypes that have large fitness benefits under appropriate selective conditions, such as antibiotic resistance. However, many examples of HGT involve phenotypes that are predicted to provide smaller benefits, such as the ability to catabolize additional carbon sources. We have experimentally simulated the consequences of one such HGT event in the laboratory, studying the effects of transferring a pathway for catabolism of the plant-derived aromatic compound salicyl alcohol between rhizosphere isolates from the
Pseudomonas
genus. We find that pathway acquisition enables rapid catabolism of salicyl alcohol with only minor disruptions to the existing metabolic and regulatory networks of the new host. However, this new catabolic potential does not confer a measurable fitness advantage during competitive growth in the rhizosphere. We conclude that the phenotype of salicyl alcohol catabolism is readily transferable but is selectively neutral under environmentally relevant conditions. We propose that this condition is common and that HGT of many pathways will be self-limiting because the selective benefits are small.

IMPORTANCE

Horizontal gene transfer (HGT) is a key process in microbial evolution, but the factors limiting HGT are poorly understood. Aside from the rather unique scenario of antibiotic resistance, the evolutionary benefits of pathway acquisition are still unclear. To experimentally test the effects of pathway acquisition, we transferred a pathway for catabolism of a plant-derived aromatic compound between soil bacteria isolated from the roots of poplar trees and determined the resulting phenotypic and fitness effects. We found that pathway acquisition allowed bacteria to grow using the plant-derived compound in the laboratory, but that this new phenotype did not provide an advantage when the bacteria were reinoculated onto plant roots. These results suggest that the benefits of pathway acquisition may be small when measured under ecologically-relevant conditions. From an engineering perspective, efforts to alter microbial community composition
in situ
by manipulating catabolic pathways or nutrient availability will be challenging when gaining access to a new niche does not provide a benefit.
Vibrio alginolyticus
is the pathogen of “Baotou” disease causing serious damage to
Gracilariopsis lemaneiformis
cultivation in China
Authors: Pang Tong , Wang Feng , Guo Qunqun , Zhang Mengjie , Sun Yuanyuan , Liu Jianguo
Published: December 2024

In recent years, a disease called “Baotou” has been causing large-scale yield reductions of
Gracilariopsis lemaneiformis
in China. Interestingly,
Vibrio alginolyticus
, which once reported to be a probiotic or pathogen for multiple marine organisms, was strongly proved to be the pathogen causing “Baotou” disease in this study. Analysis of 16S rRNA gene profiling revealed that
V. alginolyticus
was the most abundant and dominant bacterium on the algal thalli suffering from “Baotou” disease, whereas its presence was scarcely detected on healthy thalli. Scanning electron microscope (SEM) analysis revealed that a large number of
V. alginolyticus
cells were found to be attached to the algal thalli with “Baotou” disease and the rotten thalli acquired by the lab infection treatment.
V. alginolyticus
could cause the rotten symptoms which were consistent with those of “Baotou” disease. According to Koch’s postulates,
V. alginolyticus
was identified as the pathogen causing “Baotou” disease.

IMPORTANCE

A highly contagious disease known as “Baotou” disease has persistently triggered significant yield reductions in
G. lemaneiformis
throughout China. The pathogen of “Baotou” disease was isolated and identified as
V. alginolyticus
in this study. Interestingly,
V. alginolyticus
was once reported to be a probiotic to
Saccharina japonica
, and pathogen to
Haliotis diversicolor
,
Paleopneustes cristatus
,
Ruditapes decussatus,
and
Litopenaeus vannamei
. The study indicates that
V. alginolyticus
play a significant role in the competition or co-existence between
G. lemaneiformis
,
S. japonica
, abalone, sea urchin, bivalve, and shrimp.
Geographically widespread and novel hemotropic mycoplasmas and bartonellae in Mexican free-tailed bats and sympatric North American bat species
Authors: Becker Daniel J. , Dyer Kristin E. , Lock Lauren R. , Olbrys Beckett L. , Pladas Shawn A. , Sukhadia Anushka A. , Demory Bret , Nunes Batista Juliana Maria , Pineda Micaela , Simmons Nancy B. , Adams Amanda M. , Frick Winifred F. , O'Mara M. Teague , Volokhov Dmitriy V.
Published: December 2024

Bacterial pathogens remain poorly characterized in bats, especially in North America. We describe novel (and in some cases panmictic) hemoplasmas (10.1% positivity) and bartonellae (25.6% positivity) across three colonies of Mexican free-tailed bats (
Tadarida brasiliensis
), a partially migratory species that can seasonally travel hundreds of kilometers. Molecular analyses identified three novel
Candidatus
hemoplasma species most similar to another novel
Candidatus
species in Neotropical molossid bats. We also detected novel hemoplasmas in sympatric cave myotis (
Myotis velifer
) and pallid bats (
Antrozous pallidus
), with sequences in the latter 96.5% related to
Candidatus
Mycoplasma haematohominis. We identified nine
Bartonella
genogroups, including those in cave myotis with 96.1% similarity to
Candidatus
Bartonella mayotimonensis. We also detected
Bartonella rochalimae
in migratory Mexican free-tailed bats, representing the first report of this human pathogen in the Chiroptera. Monthly sampling of migratory Mexican free-tailed bats during their North American occupancy period also revealed significant seasonality in infection for both bacterial pathogens, with prevalence increasing following spring migration, peaking in the maternity season, and declining into fall migration. The substantial diversity and seasonality of hemoplasmas and bartonellae observed here suggest that additional longitudinal, genomic, and immunological studies in bats are warranted to inform One Health approaches.

IMPORTANCE

Bats have been intensively sampled for viruses but remain mostly understudied for bacterial pathogens. However, bacterial pathogens can have significant impacts on both human health and bat morbidity and even mortality. Hemoplasmas and bartonellae are facultative intracellular bacteria of special interest in bats, given their high prevalence and substantial genetic diversity. Surveys have also supported plausible zoonotic transmission of these bacteria from bats to humans, including
Candidatus
Mycoplasma haematohominis and
Candidatus
Bartonella mayotimonensis. Greater characterization of these bacteria across global bat diversity (over 1,480 species) is therefore warranted to inform infection risks for both bats and humans, although little surveillance has thus far been conducted in North American bats. We here describe novel (and in some cases panmictic) hemoplasmas and bartonellae across three colonies of Mexican free-tailed bats and sympatric bat species. We find high genetic diversity and seasonality of these pathogens, including lineages closely related to human pathogens, such as
Bartonella rochalimae
.
Advancing dental biofilm models: the integral role of pH in predicting
S. mutans
colonization
Authors: Sangha Jay S. , Gogulancea Valentina , Curtis Thomas P. , Jakubovics Nicholas S. , Barrett Paul , Metris Aline , Ofiţeru Irina D.
Published: December 2024

Mathematical models can provide insights into complex interactions and dynamics within microbial communities to complement and extend experimental laboratory approaches. For dental biofilms, they can give a basis for evaluating biofilm growth or the transition from health to disease. We have developed mathematical models to simulate the transition toward a cariogenic microbial biofilm, modeled as the overgrowth of
Streptococcus mutans
within a five-species dental community. This work builds on experimental data from a continuous flow reactor with hydroxyapatite coupons for biofilm growth, in a chemically defined medium with varying concentrations of glucose and lactic acid. The biofilms formed on the coupons were simulated using individual-based models (IbMs), with bacterial growth modeled using experimentally measured kinetic parameters. The IbM assumes that the maximum theoretical growth yield for biomass is dependent on the local concentration of reactants and products, while the growth rates were described using traditional Monod equations. We have simulated all the conditions studied experimentally, considering different initial relative abundance of the five species, and also different initial clustering in the biofilm. The simulation results only reproduced the experimental dominance of
S. mutans
at high glucose concentration after we considered the species-specific effect of pH on growth rates. This highlights the significance of the aciduric property of
S. mutans
in the development of caries. Our study demonstrates the potential of combining
in vitro
and
in silico
studies to gain a new understanding of the factors that influence dental biofilm dynamics.

IMPORTANCE

We have developed
in silico
models able to reproduce the relative abundance measured
in vitro
in the synthetic dental biofilm communities growing in a chemically defined medium. The advantage of this combination of
in vitro
and
in silico
models is that we can study the influence of one parameter at a time and aim for direct validation. Our work demonstrates the utility of individual-based models for simulating diverse conditions affecting dental biofilm scenarios, such as the frequency of glucose intake, sucrose pulsing, or integration of pathogenic or probiotic species. Although
in silico
models are reductionist approaches, they have the advantage of not being limited in the scenarios they can test by the ethical consideration of an
in vivo
system, thus significantly contributing to dental biofilm research.
PhoU homologs from
Staphylococcus aureus
dimerization and protein interactions
Authors: Matthews Clayton T. , Mahmud Sakib , Gardner Stewart G.
Published: December 2024

PhoU proteins are negative regulators of the phosphate response, regulate virulence, and contribute to antibiotic resistance.
Staphylococcus aureus
has multiple genes encoding PhoU homologs that regulate persister formation and potentially virulence, but the molecular mechanisms of this regulation are not fully understood. We used a bacterial adenylate cyclase two-hybrid system to assess interactions between PhoU homologs and other proteins known to interact with PhoU from
Escherichia coli. S. aureus
PhoU (also referred to as PhoU1) interacted with PhoU itself; PitR (also referred to as PhoU2) interacted with PitR itself. We identified potential structural and dimerization models for
S. aureus
PhoU homologs. Dimerization was confirmed using size exclusion chromatography of purified proteins. These results highlight the complex nature of PhoU proteins. Further analysis may elucidate the potential mechanisms for regulating gene expression, persister formation, and virulence in
S. aureus
.

IMPORTANCE

PhoU proteins affect pathogenesis and persister formation in many bacterial species. This protein is essential for signaling environmental phosphate levels in
Escherichia coli
but is still not well characterized in many other pathogenic bacterial strains. This work identifies some similarities and key differences in
Staphylococcus aureus
PhoU homologs compared to
E. coli
PhoU, specifically, PhoU and PitR from
S. aureus
form homodimers but do not appear to interact with PhoR or phosphate transporter proteins.
Gut mycobiome alterations and network interactions with the bacteriome in patients with atherosclerotic cardiovascular disease
Authors: Su Guangming , Huang Ping , Liu Dan , Xing Guorui , Guo Ruochun , Li Shenghui , Fan Shao , Cheng Lin , Yan Qiulong , Yang Wei
Published: December 2024

The connection between the gut mycobiome and atherosclerotic cardiovascular disease (ACVD) is largely uncharted. In our study, we compared the gut fungal communities of 214 ACVD patients with those of 171 healthy controls using shotgun metagenomic sequencing and examined their interactions with gut bacterial communities and network key taxa. The gut mycobiome composition in ACVD patients is significantly different, showing a rise in opportunistic pathogens like
Candida albicans
,
Exophiala spinifera
, and
Malassezia restricta
, with
Exophiala
and
Malassezia
showing the most significant changes (Wilcoxon rank-sum test,
P
< 0.001, fold change >10). Network analysis revealed a less interconnected and more uneven gut microbial network in ACVD patients. Network key taxa identified in the ACVD gut microbiome network include
Malassezia globosa
c182,
Nakaseomyces glabratus
c88,
Malassezia arunalokei
c192, and
Penicillium sumatraense
c22. Predictive models that integrated both bacterial and fungal taxa enhanced prediction accuracy, underscoring the critical role of gut fungi in ACVD. Our findings offer a thorough understanding of the link between the gut mycobiome and ACVD progression, which is vital for directing future therapeutic research.

IMPORTANCE

ACVD is a leading cause of death and morbidity worldwide. While the role of the gut microbiome in ACVD development is recognized, the contribution of the gut mycobiome remains largely unexplored. Our study reveals significant alterations in the gut mycobiome of ACVD patients and identifies key fungal taxa associated with the disease. These findings underscore the importance of the gut mycobiome in the pathogenesis of ACVD and offer new avenues for developing preventive and therapeutic strategies targeting the gut fungal community. Our results provide valuable insights into the complex interplay between gut fungi and bacteria in ACVD, paving the way for novel therapeutic approaches.
Cardiorespiratory fitness is associated with cognitive function in late adulthood: baseline findings from the IGNITE study
Authors: Oberlin Lauren E , Wan Lu , Kang Chaeryon , Romano Allison , Aghjayan Sarah , Lesnovskaya Alina , Ripperger Hayley S , Drake Jermon , Harrison Rae , Collins Audrey M , Molina-Hidalgo Cristina , Grove George , Huang Haiqing , Kramer Arthur , Hillman Charles H , Burns Jeffrey M , Vidoni Eric D , McAuley Edward , Kamboh M Ilyas , Jakicic John M , Erickson Kirk I
Published: December 2024

Objectives

To evaluate the association between cardiorespiratory fitness (CRF) and cognition in a large sample of older adults, and to examine clinical and demographic factors that might moderate these associations.

Methods

CRF was measured with a graded exercise test performed on a motorised treadmill. A confirmatory factor analysis was conducted using data from a comprehensive neuropsychological battery to obtain latent factors reflecting core cognitive domains. Linear regression models evaluated the association between CRF and each of the cognitive composites, and potential moderators including demographic factors (age, sex, education), apolipoprotein E ε4 (APOE4) carriage, beta-blocker use and components of maximal effort criteria during CRF testing.

Results

The sample consisted of 648 adults (mean (SD) age 69.88 (3.75)), including 461 women (71.1%). The highest oxygen consumption obtained during testing (VO2max) was mean (SD) = 21.68 (5.06) mL/kg/min. We derived a five-factor model composed of episodic memory, processing speed, working memory, executive function/attentional control and visuospatial function. Higher CRF was associated with better performance across all five cognitive domains after controlling for covariates. Age andAPOE4carriage did not moderate observed associations. The relationship between CRF and cognitive performance was greater in women, those with fewer years of education and those taking beta-blockers in the domains of processing speed (sex: β=−0.447; p=0.015; education: β=−0.863; p=0.018) and executive function/attentional control (sex: β=−0.417; p=0.022; education β=−0.759; p=0.034; beta-blocker use: β=0.305; p=0.047).

Conclusion

Higher CRF in older adulthood is associated with better cognitive performance across multiple domains susceptible to age-related cognitive decline. Sex, education and use of beta-blockers moderated observed associations within select cognitive domains.
Efficacy of combining aspirin with hydroxychloroquine in pregnancies at high risk for pre-eclampsia: a prospective, multicentre, open-label, single-arm clinical trial, investigator-initiated study (HUGS study)
Authors: Kim Yoo-Min , Seong Jisu , Kim Ji Hoi , Nam Gina , Kim Gwang jun , Cha Hyun-Hwa , Seong Won Joon , Sung Ji-Hee , Choi Suk-Joo , Oh Soo-Young , Roh Cheong-Rae
Published: December 2024

Introduction

The use of hydroxychloroquine (HCQ) during pregnancies complicated by systemic lupus erythematosus or refractory antiphospholipid antibody syndrome has demonstrated a significant ability to prevent pre-eclampsia (PE). As such, the potential for the administration of HCQ to prevent PE in other high-risk pregnancies is an important clinical research agenda among maternal and fetal medicine specialists. Mechanistically, the anti-inflammatory and immunomodulatory effects of HCQ can offer vascular protection and inhibit the placental dysfunction-associated thrombotic changes underlying the pathophysiology of PE, fetal growth restriction (FGR) and fetal death in utero (FDIU). Placenta-mediated complications exhibit a distinctive overlapping syndrome between pregnancies, and low-dose aspirin is the only prevention method currently in use. This study investigated the effects of improvements in outcomes with HCQ administration in high-risk pregnancies complicated by a previous experience of PE, FGR or FDIU.

Methods and analysis

This multicentre, open-label, single-arm trial commenced on 31 May 2022, in three tertiary hospitals in Korea. Pregnant women with a prior history of PE, FGR or FDIU are eligible to participate. This single-arm study set the previous study with the most similar inclusion criteria, aspirin dose and drug administration period as the comparison group. The required sample size was determined to be 58, with an expected dropout rate of 10%.

Ethics and dissemination

This study protocol was approved by the following institutions and committees: Institutional Review Boards of Chung-Ang University Gwangmyeong Hospital (2304-082-056), Samsung Medical Center (2021-11-087-003) and Kyungpook National University Chilgok Hospital (2021-06-005-006) and the Ministry of Food and Drug Safety. The results will be disseminated to the general public, grant funder, maternal–fetal medicine specialists and other researchers.

Trial registration number

NCT05287321.
Different doses of epidural morphine combined with multimodal analgesia strategies for postpartum pain management: study protocol for a single-centre, double-blind randomised, pragmatic clinical trial
Authors: Yu Rou , Lin Xuemei
Published: December 2024

Introduction

The neuraxial morphine has been regarded as the gold standard for postpartum analgesia. However, the recent advancements in patient-controlled analgesia and various regional nerve blocks have led to the implementation of multimodal analgesia strategies, which aim to reduce opioid usage and associated complications while ensuring satisfactory pain relief. The objective of this research is to investigate the optimal dosage of epidural morphine for alleviating moderate and severe pain after caesarean sections in healthy parturients, as well as reducing unnecessary burden of respiratory monitoring resources.

Methods and analysis

The present single-centre randomised controlled pragmatic clinical trial aims to enrol a total of 310 healthy parturients with American Society of Anesthesiologists grade I/II, who are scheduled for caesarean section under combined spinal and epidural anaesthesia at West China Second University Hospital of Sichuan University. The recruitment process has not yet commenced and is anticipated to commence in March 2024, concluding in September 2024. Enrolled patients will be evenly distributed into five groups, namely morphine groups (M1–M4) and the control group (M0). The primary outcome measure is the incidence rate of postoperative use Numerical Rating Scale (NRS) pain score ≥4 points within 24 hours, which will be primarily assessed through bedside follow-up conducted by investigators and patient self-assessment at 2, 4, 6, 8, 12 and 24 hours postoperatively. The secondary outcomes encompass the following: incidence of postoperative NRS score ≥4 within 48 hours, occurrence of SpO2 <90% (during air inhalation)/ SpO2 <95% (during nasal cannula oxygen inhalation) and respiratory rate (RR)＜10 breaths/min recorded on the bedside monitoring, Ramsay sedation score, administration of rescue analgesics and total usage of patient-controlled intravenous analgesia pump, time to first flatus and food intake, maternal and neonatal urinary morphine concentrations, and any other maternal adverse reactions such as nausea, vomiting, pruritus, urinary retention and neonatal depression. The administration of local anaesthetics, surgical procedures and the timing for administering rescue analgesics will not be subject to any restrictions.

Ethics and dissemination

Ethical approval has been obtained from the Ethics Committee of West China Second University Hospital, Sichuan University (2022(269)).

Trial registration number

ChiCTR2400080350.
Exploring patients’ views regarding the support and rehabilitation needs of people living with myocardial ischaemia and no obstructive coronary arteries: a qualitative interview study
Authors: Humphreys Helen , Paddock Danielle , Brown Sarah , Cowie Aynsley , Berry Colin , Dawkes Susan , Nichols Simon
Published: December 2024

Objectives

This study aimed to generate new qualitative insights to understand the rehabilitation needs of people living with a confirmed or presumed diagnosis of ischaemia with no obstructive coronary arteries (INOCA), explore which aspects of current cardiovascular prevention and rehabilitation programmes could meet the needs of people with INOCA and where adjustments (if any) may be appropriate.

Design

Semistructured qualitative interview study.

Participants

Interviews were undertaken (n=17; 88% female, age range 31–69 years) with people with a confirmed or presumed diagnosis of INOCA.

Results

Findings highlighted concerns around a lack of evidence-based guidance for cardiovascular prevention and rehabilitation programmes for patients with INOCA. Participants expressed a desire for modular cardiovascular prevention and rehabilitation programmes that could be accessed flexibly to accommodate episodic fluctuations in symptoms. Participants suggested that existing cardiovascular prevention and rehabilitation programme content needed adjustment including enhanced psychosocial support, supervised low-impact physical activity and specialist dietary advice and medication reviews. Additional elements specific to INOCA should be made available as appropriate including acute care planning and a module to provide information and support for female-specific issues. The importance of involving INOCA patients in the codesign of future programmes and associated training was emphasised.

Conclusions

People with INOCA are willing to engage with cardiovascular prevention and rehabilitation programmes and express a desire for more support. This patient group shares some barriers to rehabilitation programme attendance with other cardiac patient groups, but they also have specific concerns about the need for improved professional knowledge and evidence-based guidance regarding the management of INOCA. Cardiovascular rehabilitation programmes need to be delivered flexibly and individually tailored to ensure the relapsing and remitting nature of INOCA and associated support needs are addressed.