bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulatory and retrograde signaling networks in the chlorophyll biosynthetic pathway
Authors: Li Yuhong , Cao Tianjun , Guo Yunling , Grimm Bernhard , Li Xiaobo , Duanmu Deqiang , Lin Rongcheng
Published: January 2025

Plants, algae and photosynthetic bacteria convert light into chemical energy by means of photosynthesis, thus providing food and energy for most organisms on Earth. Photosynthetic pigments, including chlorophylls (Chls) and carotenoids, are essential components that absorb the light energy necessary to drive electron transport in photosynthesis. The biosynthesis of Chl shares several steps in common with the biosynthesis of other tetrapyrroles, including siroheme, heme and phycobilins. Given that many tetrapyrrole precursors possess photo‐oxidative properties that are deleterious to macromolecules and can lead to cell death, tetrapyrrole biosynthesis (TBS) requires stringent regulation under various developmental and environmental conditions. Thanks to decades of research on model plants and algae, we now have a deeper understanding of the regulatory mechanisms that underlie Chl synthesis, including (i) the many factors that control the activity and stability of TBS enzymes, (ii) the transcriptional and post‐translational regulation of the TBS pathway, and (iii) the complex roles of tetrapyrrole‐mediated retrograde signaling from chloroplasts to the cytoplasm and the nucleus. Based on these new findings, Chls and their derivatives will find broad applications in synthetic biology and agriculture in the future.
Relationships for Social Change: The Value of the Promotora Framework in Navigating Systems of Employment
Authors: Abraham Danna , Distelberg Brian , Ewing Jan , Lister Zephon , Lopez‐Bradley Lena , Ochoa Sandra
Published: January 2025

In the United States, socioeconomic disparities are a reality that shapes the challenges many communities of color experience. Throughout the globe, community‐based initiatives have been explored as a way to reduce several barriers that contribute to social inequalities. One in particular, the Promotora framework, has been widely used to improve health outcomes. However, it has yet to be explored to maximize socioeconomic opportunities. The Launch Program, a pre‐COVID‐19 pilot study, aimed to investigate the experiences of LatinX people in one of the first community programs designed to offer a Promotora‐led intervention supporting socioeconomic goals. Researchers collected qualitative data via focus groups from 25 LatinX participants who completed the program. Using narrative thematic analysis, the study explored the potential of a liberatory framework to address employment barriers. Results from this study highlight the benefits of adopting a culturally responsive intervention as a valuable tool in reducing socioeconomic disparities within LatinX populations.
Automation of Ultrasonographic Optic Nerve Sheath Diameter Measurement: A Scoping Review
Authors: Escamilla‐Ocañas César E. , Morales‐Cardona Noelia C. , Sagreiya Hersh , Akhbardeh Alireza , Hirzallah Mohammad I.
Published: January 2025

Intracranial pressure (ICP) monitoring is a cornerstone of neurocritical care in managing severe brain injury. However, current invasive ICP monitoring methods carry significant risks, including infection and intracranial hemorrhage, and are contraindicated in certain clinical situations. Additionally, these methods are not universally available. Optic nerve sheath diameter (ONSD) measurement presents a promising noninvasive alternative for ICP monitoring, though its clinical adoption has been limited due to its operator dependence and inconsistencies in imaging acquisition and measurement techniques. Automating both ONSD image acquisition and measurement could enhance accuracy and reliability, thereby improving its utility as a noninvasive ICP estimation tool. A range of image analysis and machine learning (ML) techniques have been applied to address these challenges. In this paper, we provide a narrative review of the current literature on ONSD automation, examining the strengths and limitations of classical image analysis and ML models in improving ONSD‐based ICP assessment.
Asynchronous shifts in the demographics of two wave‐swept kelp species (Laminariales) after nearly four decades
Authors: Starko Samuel , Allchurch Alyssa , Neufeld Christopher
Published: January 2025

Kelp forests are among the most abundant and productive marine ecosystems but are under threat from climate change and other anthropogenic stressors. Although knowledge is growing about how the abundance and distribution of kelp forests are changing, much less is known about the “non‐lethal” effects that global change is having on the performance and health of kelp populations in areas where they persist. Here we assessed the age distribution of two common stipitate kelp species, Laminaria setchelli and Pterygophora californica, at Wizard Islet in Barkley Sound, British Columbia, Canada, and compared these data to historical demographic data collected by De Wreede (1984) and Klinger and DeWreede (1988) from the same site between 1981 and 1983. We observed that L. setchelli populations in 2020 were younger and less evenly aged than the same populations sampled nearly four decades prior, while the P. californica population was composed of older individuals on average than at the historical time point. Although the drivers of these demographic changes remain unclear, Barkley Sound has experienced substantial changes in the physical and biological environment over the past decade that could be responsible for these patterns. Given that the size of an individual and its probability of reproduction increases with age, shifting demographics may impact the reproductive output of each population, potentially altering the competitive relationships between co‐occurring species. Changes in size distribution may also influence ecosystem‐level processes such as habitat complexity or productivity.
Drug‐Induced Liver Injury Associated With Emerging Cancer Therapies
Authors: Chodup Piotr , Samodelov Sophia L. , Visentin Michele , Kullak‐Ublick Gerd A.
Published: January 2025

Targeted therapies and immunotherapies have shown great promise as best‐in‐class treatments for several cancers with respect to efficacy and safety. While liver test abnormalities are rather common in patients treated with kinase inhibitors or immunotherapy, events of severe hepatotoxicity in these patients are rare in comparison with those associated with chemotherapeutics. The underlying mechanisms and risk factors for severe hepatotoxicity with novel oncology therapies are not well understood, complicating the drug‐induced liver injury (DILI) risk assessment in the preclinical and clinical phases of drug development. The epidemiological and clinical characteristics, as well as mechanisms of liver toxicity, are described here to the current state of knowledge. Tools to study and assess the risk of DILI during drug development are concisely summarised, focusing on caveats thereof for novel oncology treatments. Emerging tools to optimise safety assessments and gather additional mechanistic insights into DILI are introduced. Particularly in oncology, where standard liver signals during drug development are tolerated to a marginally higher degree than in other indications due to the life‐saving, life‐extending and quality‐of‐life improvements for patients with severe or advanced cancers versus previous standard‐of‐care therapeutics, safety assessments must be tailored to the drug and indication. Trends in patient safety‐centred drug development programmes and regulatory approval processes must continually be revisited and streamlined via obtaining an overall greater understanding of DILI and the tools available to assess mechanisms of injury, frequency, severity and prognosis.
Dynamic Outlier Slicing Allows Broader Exploration of Adaptive Divergence: A Comparison of Individual Genome and Pool‐Seq Data Linked to Humic Adaptation in Perch
Authors: López María‐Eugenia , Ozerov Mikhail , Pukk Lilian , Noreikiene Kristina , Gross Riho , Vasemägi Anti
Published: January 2025

How genetic variation contributes to adaptation at different environments is a central focus in evolutionary biology. However, most free‐living species still lack a comprehensive understanding of the primary molecular mechanisms of adaptation. Here, we characterised the targets of selection associated with drastically different aquatic environments—humic and clear water—in the common freshwater fish, Eurasian perch (Perca fluviatilis). By using whole‐genome sequencing (WGS) on a large population dataset (n = 42 populations) and analysing 873,788 SNPs, our primary aim was to uncover novel and confirm known footprints of selection. We compared individual and pooled WGS, and developed a novel approach, termed dynamic outlier slicing, to assess how the choice of outlier‐calling stringency influences functional and Gene Ontology (GO) enrichment. By integrating genome‐environment association (GEA) analysis with allele frequency‐based approaches, we estimated composite selection signals (CSS) and identified 2679 outlier SNPs distributed across 324 genomic regions, involving 468 genes. Dynamic outlier slicing identified robust enrichment signals in five annotation categories (upstream, downstream, synonymous, 5′UTR and 3′UTR) highlighting the crucial role of regulatory elements in adaptive evolution. Furthermore, GO analyses revealed strong enrichment of molecular functions associated with gated channel activity, transmembrane transporter activity and ion channel activity, emphasising the importance of osmoregulation and ion balance maintenance. Our findings demonstrate that despite substantial random drift and divergence, WGS of high number of population pools enabled the identification of strong selection signals associated with adaptation to both humic and clear water environments, providing robust evidence of widespread adaptation. We anticipate that the dynamic outlier slicing method we developed will enable a more thorough exploration of adaptive divergence across a diverse range of species.
Enhanced three‐dimensional instance segmentation using multi‐feature extracting point cloud neural network
Authors: Wang Hongxu , Liu Jiepeng , Li Dongsheng , Chen Tianze , Liu Pengkun , Yan Han , Wu Yadong
Published: January 2025

Precise three‐dimensional (3D) instance segmentation of indoor scenes plays a critical role in civil engineering, including reverse engineering, size detection, and advanced structural analysis. However, existing methods often fall short in accurately segmenting complex indoor environments due to challenges of diverse material textures, irregular object shapes, and inadequate datasets. To address these limitations, this paper introduces StructNet3D, a point cloud neural network specifically designed for instance segmentation in indoor components including ceilings, floors, and walls. StructNet3D employs a novel multi‐scale 3D U‐Net backbone integrated with ArchExtract, which designed to capture both global context and local structural details, enabling precise segmentation of diverse indoor environments. Compared to other methods, StructNet3D achieved an AP50 of 87.7 on the proprietary dataset and 68.6 on the S3DIS dataset, demonstrating its effectiveness in accurately segmenting and classifying major structural components within diverse indoor environments.
Decoding Plant–Pathogen Interactions: A Comprehensive Exploration of Effector–Plant Transcription Factor Dynamics
Authors: Xiang Hui , Stojilkovic Boris , Gheysen Godelieve
Published: January 2025

In the coevolutionary process between plant pathogens and hosts, pathogen effectors, primarily proteinaceous, engage in interactions with host proteins, such as plant transcription factors (TFs), during the infection process. This review delves into the intricate interplay between TFs and effectors, a key aspect in the prolonged and complex battle between plants and pathogens. Effectors strategically manipulate TFs using diverse tactics. These include modulating activity of TFs, influencing their incorporation into multimeric complexes, directly changing TF expression levels, promoting their degradation via the ubiquitin‐proteasome system, and inducing their subcellular relocalization. The review systematically presents documented interactions, elucidating key mechanisms and their profound impact on host–pathogen dynamics. It emphasises the central role of TFs in plant defence and investigates the convergent evolution of effectors targeting TFs. By providing this overview, we offer valuable insights into this dynamic interaction landscape and suggest potential directions for future research.
The Progression of College Student Romantic Relationship Development: Stability and Change Over 10 Years
Authors: Ogolsky Brian G. , Dobson Kiersten , Rivas‐Koehl Matthew , Kawas Ghada , Hardesty Jennifer L.
Published: January 2025

Romantic relationships play an important role in mental and physical health. The initiation and progression of these relationships may be particularly relevant to college students, as they experience a period of personal and social growth while presumably away from parental supervision for the first time. However, some of the more prominent models of relationship initiation and progression have not been updated to reflect recent social changes, including technological advances and more general societal trends. In the current research, we use a qualitative approach to examine how college students describe the initiation and progression of romantic relationships. Additionally, we present data from two studies collected a decade apart to examine changes in perceived relationship progression over time. Results revealed four stages of relationship progression (i.e., flirtationship, relationship potential, in a relationship, and commitment or bust) that were consistent across decades, with some minor differences. The contributions of these findings to current theoretical and empirical knowledge on relationship development are discussed, and promising directions for future inquiry are identified.
Lancang‐Mekong Cooperation and policy actors' coalition behavior around hydropower development in the Mekong countries: Testing the impact of coalition opportunity structures
Authors: He Linlang , Wills Kate , Benson Claire , Flaim Amanda
Published: January 2025

The Advocacy Coalition Framework (ACF) literature has long discussed coalition opportunity structures' (COSs) ability to shape the composition, resources, and strategies of coalitions. Yet, more empirical work is needed to understand how COSs explain coalition behavior across political systems. Guided by the ACF, this study uses English newspaper articles from the lower Mekong countries to analyze the composition of coalitions and policy actors' coalition behavior in these countries' hydropower policy subsystem around the establishment of the Lancang‐Mekong Cooperation (LMC), a China‐led initiative for regional governance. Our results reveal significant variations in COSs across the countries we studied. These variations in COSs help explain some of the observed differences in the composition of coalitions and non‐state actors' coalition strategies across these countries. Moreover, despite operating within authoritarian regimes with generally restrictive COSs, members of various advocacy coalitions actively adjust their short‐term coordination networks following LMC's establishment. Our study contributes to the thin literature on COSs' utility in explaining coalition behavior and enriches ACF's application in non‐democratic political systems. Our study also helps understand the influence of subregional collaborative frameworks on hydropower development in the Mekong region.
On a Sampling-Based Method for Multi-Objective Robust Optimization
Authors: Jordan Elizabeth , Chatterjee Arko , Yang Ruochen , Groth Katrina , Azarm Shapour
Published: January 2025

Many engineering design optimization problems are multi-objective, constrained, and contain uncertain parameters. For these problems, it is desirable to obtain solutions that are robustly optimum. A robust optimal solution is one which remains feasible and optimal despite perturbations in the uncertainty parameters. This article presents a scenario-generation-based method for solving multi-objective robust optimization (MORO) problems. The approach follows a sequential, single-level optimization problem workflow, with the uncertainty handled by a fixed sampling method. The proposed approach is applied to an unmanned surface vessel (USV) case study problem. The results obtained and subsequent performance analysis show that the proposed approach generally performs well.
Dynamic Modeling, Uncertainty Analysis, and Experimental Study of a New Cable-Driven Parallel Robot With Interval Variables
Authors: Zhou Bin , Li Sipan , Wang Zhiyuan , Chen Bing , Zi Bin
Published: January 2025

Based on the Chebyshev polynomial method (CPM) and interval theory, this article establishes the relationship between uncertain parameters and the dynamic response of a new cable-driven parallel robot (CDPR). Meanwhile, the time-varying characteristic of uncertain parameters in the dynamic uncertainty analysis of the model is considered in this article, effectively enhancing the accuracy of the dynamic response. The mechanical design and kinematic modeling are conducted, and the dynamic model is established based on the Lagrangian method. Thus, uncertain parameters including the length of the lifting arm L, the angle of the lifting arm rotation on the support plate α, and the length of the payload l are defined as interval variables, and the dynamic equilibrium equation with interval variables is derived. Numerical examples show that the CPM has a higher accuracy than the first-order interval perturbation method (FOIPM), and a higher efficiency than the Monte Carlo method (MCM) when it comes to solve the dynamic response of the CDPR with uncertain parameters. Experimental results demonstrate the effectiveness of dynamic modeling and the CPM in achieving efficient dynamic response and show that the largest relative error between the theoretical and experimental values for the dynamic response of the CDPR with uncertain parameter L is 1.466%; the largest relative error with uncertain parameter α is 0.783%; the largest relative error with uncertain parameter l is 0.857%; and the largest relative error with multiple uncertain parameters is 1.513%.
Large Language Models for Computer-Aided Design Fine Tuned: Dataset and Experiments
Authors: Sun Yuewan , Li Xingang , Sha Zhenghui
Published: January 2025

Despite the power of large language models (LLMs) in various cross-modal generation tasks, their ability to generate 3D computer-aided design (CAD) models from text remains underexplored due to the scarcity of suitable datasets. Additionally, there is a lack of multimodal CAD datasets that include both reconstruction parameters and text descriptions, which are essential for the quantitative evaluation of the CAD generation capabilities of multimodal LLMs. To address these challenges, we developed a dataset of CAD models, sketches, and image data for representative mechanical components such as gears, shafts, and springs, along with natural language descriptions collected via Amazon Mechanical Turk. By using CAD programs as a bridge, we facilitate the conversion of textual output from LLMs into precise 3D CAD designs. To enhance the text-to-CAD generation capabilities of GPT models and demonstrate the utility of our dataset, we developed a pipeline to generate fine-tuning training data for GPT-3.5. We fine-tuned four GPT-3.5 models with various data sampling strategies based on the length of a CAD program. We evaluated these models using parsing rate and intersection over union (IoU) metrics, comparing their performance to that of GPT-4 without fine-tuning. The new knowledge gained from the comparative study on the four different fine-tuned models provided us with guidance on the selection of sampling strategies to build training datasets in fine-tuning practices of LLMs for text-to-CAD generation, considering the trade-off between part complexity, model performance, and cost.
Inverse Design of Three-Dimensional Variable Curvature Pneumatic Soft Actuators
Authors: Liu Tong , Wang Xiaojie
Published: January 2025

The inverse design of soft actuators refers to a design methodology that derives the actuator's geometric and material parameters based on the desired target shape. This approach offers an efficient solution for developing soft actuators with complex geometries, enabling the precise matching of intricate deformation targets. Furthermore, it facilitates personalized customization and design optimization for complex application scenarios. In this article, we present a novel inverse design method for three-dimensional (3D) variable curvature pneumatic soft actuators and incorporate buckling deformation to improve shape matching. By analyzing variable cross-sectional actuators, we demonstrate that cross-sectional curvature is determined solely by its shape, enabling specific curvatures to be achieved by adjusting the cross-sectional geometry. To process input 3D point coordinates and calculate curve curvatures, we introduce cubic spline interpolation and the three-point circle method. Additionally, a minimum discretization method is proposed to identify the helical axis for helical curves. Finally, based on the actuator's deformation model, we develop an inverse design program to achieve the desired actuator shape. Finite element simulations and experimental validation confirm the effectiveness of this approach, demonstrating that the fabricated actuators can precisely match complex 3D variable curvature shapes. The proposed approach has broad potential applications in situations that require specific, repetitive use, such as specific object grasping and customized medical rehabilitation devices.
Design and Performance Experiment of a Combined Cold Storage Plate Refrigerated Container Based on Phase Change Material
Authors: Chen Junwen , Kang Na , Wang Yu , Asfandyar Khan Dawar
Published: January 2025

The cold chain is a critical component in the transportation of food and pharmaceuticals, with refrigerated transportation equipment representing a significant sector within this domain. This article presents a design scheme aimed at achieving uniform temperature and extended cold storage duration to enhance the performance of combined cold storage plate refrigerated containers. Utilizing the principles of combined cold storage, we designed the combined cold storage plates and the refrigerated container. We compared the performance of various phase change materials (PCMs)—specifically 2-octanone, n-undecane, n-tetradecane, and water—from the perspectives of equal mass combination schemes and equal phase change latent heat value schemes. Our findings indicate that the equal mass combination scheme, which employs n-tetradecane as the inner layer and water as the outer layer, exhibits superior performance. Additionally, we evaluated the effective cold preservation time, melting time, minimum temperature, uniformity coefficient, and cold power consumption of the combined cold storage plates in different placement configurations (side placement and diagonal placement) within the refrigerated container. The results demonstrate that the refrigerated container utilizing the equal mass combination scheme with n-tetradecane and water in a diagonal placement configuration performs optimally. This experimental conclusion serves as a reference for advancing the application of combined cold storage plate refrigerated containers in ultra-low-temperature control.
Numerical Study on Unsteady Flow of a Supersonic Partial Admission Impulse Turbine
Authors: Li Tongxi , Wang Jiakang , Wang Zhiheng , Xi Guang
Published: January 2025

Partial admission is an essential method to ensure the effective operation of turbines in various operating conditions. The transition section of partial admission turbines is pivotal in governing the unsteadiness and nonuniformity, yet its flow dynamics remain elusive. To enhance the comprehension within supersonic partial admission impulse (SPAI) turbines, this study uses 3D unsteady simulations on a single-stage SPAI turbine with four nozzles to understand its dynamics and compares the performance of centralized and symmetrical nozzle arrangements. The findings reveal that shock waves are produced in the admission area, followed by two flow separations, while the turbulent, stagnant fluid exists in the nonadmission area. A strong shock wave is formed at the entrance of the transition section channel leaving the admission area. High- and low-energy gases mix in the subsequent channel and undergo an emptying process, resulting in significant energy loss. Furthermore, blades undergo fluctuating aerodynamic forces, and phenomena of under- and over-shoot are observed as the blades enter or exit the admission area, impeding turbine rotation or providing an additional torque. When adopting symmetrical nozzle arrangements, the mixing process is strengthened, resulting in a 0.29% decrease in the isentropic efficiency with the spacing of 40 deg and a 1.30% decrease with the spacing of 60 deg compared to the centralized arrangement. However, the lateral force and overturning moment on the rotor are mitigated. Consequently, in practical engineering, adopting a symmetrical arrangement is a feasible solution to ensure the stability and safety of SPAI turbine operation.
Monte Carlo, blocking, and inference: How to measure the renormalization group flow
Authors: Di Carlo Luca
Published: January 2025

Renormalization group theory is a powerful and intriguing technique with a wide range of applications. One of the main successes of renormalization group theory is the description of continuous phase transitions and the development of scaling theory. Most courses on phase transitions focus on scaling and critical exponents, while less attention is paid to universality, renormalization group flow, and the existence of a unique fixed point, which are the ultimate reasons why scaling theory is so effective in describing continuous phase transitions. We use a combination of Monte Carlo simulations and real space renormalization group theory to determine the renormalization group flow and to show the existence of a universal fixed point in the context of the ferromagnetic Ising model.
Advanced undergraduate lab on quantum beats
Authors: Wright M. J. , Beban R. , Chierchio O. , McCluney L. , Peña T. , St. John J. P.
Published: January 2025

Spontaneous emission has been studied by physicists for decades and continues to reveal exciting physics. We describe an experiment to study the spontaneous emission of a monoatomic vapor at room temperature as a fundamental experiment for upper-level physics undergraduates. The experiment begins by exciting a population of Rb atoms in a room temperature vapor cell with a laser pulse shorter than the average lifetime of the excited states. The resulting fluorescence signal is recorded as a function of time, and the excited state lifetime can be determined by measuring the decay rate. By analyzing the Fourier transform of the time-dependent polarized fluorescence signal, quantum interference (i.e., quantum beating) is observed among the hyperfine energy levels. This experiment can be completed by upper-level undergraduates in physics to demonstrate and connect hands-on experiments with concepts in atomic and quantum physics classes.
Examining Factors Shaping the Consumption of Televised Ladies Professional Golf Association Events: Attitudes, Subjective Norms, Perceived Behavioral Control, and Intergroup Dynamics in a Multicultural Context
Authors: Kim Euisoo , Zhao Troy T. , Zhang James J.
Published: January 2025

This study aimed to identify the factors influencing the viewing behavior of current Ladies Professional Golf Association (LPGA) audiences, especially whether the growing dominance of golfers from Asian countries plays a role in shaping such behavior. The research investigates the reasons for which existing LPGA viewers watch these tournaments by examining key factors such as attitudes toward watching, subjective norms, perceived behavioral control, and intergroup attitudes. A quantitative survey was distributed to 536 LPGA event viewers in the United States. The survey measured constructs such as watching and intergroup attitudes, subjective norms, perceived behavioral control, and intention to watch. Structural equation modeling was used to analyze the data and test the hypothesized relationships among the variables. The findings indicate that salient beliefs directly and positively affect predictor variables, which in turn positively influence the intention to watch LPGA events. Watching attitudes, subjective norms, and perceived behavioral control significantly enhance the intention to watch. However, intergroup attitudes toward golfers from Asia negatively affected the intention to watch, highlighting a potential barrier to audience engagement. This study highlights the dynamics of psychological and social factors in shaping LPGA viewership and offers insights for strategies to better engage diverse audience segments.
Scientists as advocates
Citizen Scholar: Public Engagement for Social Scientists
Philip N. Cohen
Columbia University Press, 2025. 312 pp.
Authors: Wai Jonathan
Published: January 2025

A sociologist rejects the notion that science is inherently apolitical, urging scholars to join the public square
Mpox drug wins approval in Japan—but it doesn’t work
Authors: Cohen Jon
Published: January 2025

Europe previously approved tecovirimat for mpox, based on animal data; the U.S. has stockpiled it for smallpox
A novel FadL family outer membrane transporter is involved in the uptake of polycyclic aromatic hydrocarbons
Authors: Meng Qiu , Liang Yuxuan , Xu Yinming , Li Saiyue , Huang Haiyan , Xu Yuanyou , Cao Feifei , Yin Jianhua , Zhu Tingheng , Gao Haichun , Yu Zhiliang
Published: January 2025

Gram-negative bacteria play a pivotal role in the bioremediation of persistent organic pollutants, such as polycyclic aromatic hydrocarbons (PAHs). Because the outer membrane (OM) of these bacteria hinders the direct permeation of hydrophobic substances into the cells, trans-OM proteins are required for the uptake of PAHs. However, neither the characteristics of PAH transporters nor the specific transport mechanism has been well interpreted. In this study, we revealed the participation of a novel FadL family transporter, PadL, in the biodegradation of the representative PAH phenanthrene in
Novosphingobium pentaromativorans
US6-1, an efficient PAH-degrading bacterium. PadL facilitates the cross-OM transport of phenanthrene, thus upregulating the expression of the gene
ahdA1e
that is critical to the PAH catabolism. We then showed that hydrophobic amino acid residues in the substrate binding pockets of PadL are essential for the binding of PAHs, such as phenanthrene and benzo[
a
]pyrene. PadL homologs commonly exist in most of the PAH-degrading species from
Sphingomonas
and
Novosphingobium
. The characterization of PadL provided in this study holds significant potential for improving the PAH biodegradation efficiency.

IMPORTANCE

Persistent organic pollutants, including polycyclic aromatic hydrocarbons (PAHs), pose serious threats to human health, and biodegradation has been applied as an efficient strategy for PAH removal. However, due to the high hydrophobicity of PAHs, their uptake is hindered by the bacterial outer membrane, restraining degradation efficiency. The present study reveals the critical roles of a novel FadL family protein (PadL) in the biodegradation of PAHs. PadL specifically transports PAHs such as phenanthrene and benzo[a]pyrene and PadL homologs generally exist in PAH-degrading bacteria of Sphingomonas and Novosphingobium. Our findings fill the knowledge gap in the bacterial trans-membrane uptake process of PAHs and provide a future direction for enhancing the bacterial PAH bioremediation capacity.
Development of a conditional plasmid for gene deletion in non-model
Fusobacterium nucleatum
strains
Authors: Zhou Peng , G C Bibek , Wu Chenggang
Published: January 2025

Fusobacterium nucleatum
is an opportunistic pathogen with four subspecies:
nucleatum
(FNN),
vincentii
(FNV),
polymorphum
(FNP), and
animalis
(FNA), each with distinct disease potentials. Research on fusobacterial pathogenesis has mainly focused on the model strain ATCC 23726 from FNN. However, this narrow focus may overlook significant behaviors of other FNN strains and those from other subspecies, given the genetic and phenotypic diversity within
F. nucleatum
. While ATCC 23726 is highly transformable, most other
Fusobacterium
strains exhibit low transformation efficiency, complicating traditional gene deletion methods that rely on non-replicating plasmids. To address this, we developed a conditional plasmid system in which the RepA protein, essential for replication of a pCWU6-based shuttle plasmid, is controlled by an inducible system combining an
fdx
promoter with a theophylline-responsive riboswitch. This system allows plasmid replication in host cells upon induction and plasmid loss when the inducer is removed, forcing chromosomal integration via homologous recombination in the presence of the antibiotic thiamphenicol. We validated this approach by targeting the
galK
gene, successfully generating mutants in FNN (ATCC 23726, CTI-2), FNP (ATCC 10953), FNA (21_1A), and the closely related species
Fusobacterium periodonticum
. Incorporating a
sacB
counterselection marker in this conditional plasmid enabled the deletion of the
radD
gene in non-model strains. Interestingly, while
radD
deletion in 23726, 10953, and 21_1A abolished coaggregation with
Actinomyces oris
, the CTI-2 mutant retained this ability, suggesting the involvement of other unknown adhesins. This work significantly advances gene deletion in genetically recalcitrant
F. nucleatum
strains, enhancing our understanding of this pathogen.

IMPORTANCE

Fusobacterium nucleatum
is implicated in various human diseases, including periodontal disease, preterm birth, and colorectal cancer, often linked to specific strains and reflecting the species’ genetic and phenotypic diversity. Despite this diversity, most genetic research has centered on the model strain ATCC 23726, potentially missing key aspects of other strains’ pathogenic potential. This study addresses a critical gap by developing a novel conditional plasmid system that enables gene deletion in genetically recalcitrant strains of
F. nucleatum
. We successfully deleted genes in the FNN clinical strain CTI-2, the FNA strain 21_1A, and
F. periodonticum
for the first time. Our findings, particularly the varying behavior of the
radD
gene production in coaggregation across strains, underscore the complexity of
F. nucleatum
and the need for broader genetic studies. This work advances our understanding of
F. nucleatum
virulence at the strain level and provides a valuable tool for future bacterial genetics research.
The GacS/GacA two-component system strongly regulates antimicrobial competition mechanisms of
Pseudomonas fluorescens
MFE01 strain
Authors: Dupont Charly A. , Bourigault Yvann , Biziere-Maco Héloïse , Boukerb Amine M. , Latour Xavier , Barbey Corinne , Verdon Julien , Merieau Annabelle
Published: January 2025

Pseudomonas fluorescens
MFE01 is an environmental bacterium characterized by an hyperactive type 6 secretion system (T6SS) and a strong emission of volatile organic compounds (VOCs). In a previous study, a transposition mutant, 3H5, exhibited an inactive T6SS and altered VOC emission. In 3H5, the interruption of
trpE
gene by the transposon was insufficient to explain these phenotypes. To determine the actual impact of this insertion, a comparative transcriptomic analysis was performed on the two-component system GacS/GacA, known to influence numerous phenotypes in
Pseudomonas
. The results demonstrated that the
gacS
gene is less expressed in 3H5 than in MFE01. Phenotypic analysis of a
gacS
deletion mutant, Δ
gacS
, confirmed many similarities between Δ
gacS
and 3H5. Indeed, Δ
gacS
exhibited an inactive T6SS and an altered VOC emission profile. In-depth analysis of volatilomes and phenotypes correlated with the decrease in
gacS
transcription, highlighting that the emission of 1-undecene is under the strict control of GacS/GacA. This study confirms that 1-undecene is not the sole volatile molecule responsible for MFE01’s inhibition of
Legionella
. Moreover, MFE01 has antimicrobial activity against the phytopathogenic oomycetes
Phytophthora infestans
via hydrogen cyanide (HCN) emission, which is also controlled by GacS. In MFE01, GacS/GacA is also a partial positive regulator of other VOC emission, whose reduced emission in 3H5 coincides with the decrease in
gacS
transcription.

IMPORTANCE

Our model strain
Pseudomonas fluorescens
MFE01 uses an active type VI secretion system (T6SS) and volatile compounds (VCs) to outcompete other microorganisms in the natural environment. By investigating the cellular mechanism regulating the production of these weapons, we identified the two-component system GacS/GacA. Indeed, GacS cellular membrane sensor plays a crucial role in regulating T6SS activity and VC emission. Among the latter, 1-undecene and hydrogen cyanide are strong aerial inhibitors of the
Legionella
human pathogen and the
Phytophtora infestans
major plant pest, respectively. The aim is to improve the understanding of the regulation of these volatile molecule emission and the critical role of a global regulator in both plant and human health.
Immunological findings of West Caucasian bat virus in an accidental host
Authors: Castellan Martina , Zamperin Gianpiero , Foiani Greta , Zorzan Maira , Priore Maria Francesca , Drzewnioková Petra , Melchiotti Erica , Vascellari Marta , Monne Isabella , Crovella Sergio , Leopardi Stefania , De Benedictis Paola
Published: January 2025

The
Lyssavirus
genus includes seventeen viral species able to cause rabies, an acute and almost invariably fatal encephalomyelitis of mammals. Rabies virus (RABV), which represents the type species of the genus, is a multi-host pathogen that over the years has undergone multiple events of host-switching, thus occupying several geographical and ecological niches. In contrast, non-RABV lyssaviruses are mainly confined within a single natural host with rare spillover events. In this scenario, unveiling the mechanisms underlying the host immune response against a virus is crucial to understand the dynamics of infection and to predict the probability of colonization/adaptation to a new target species. Presently, the host response to lyssaviruses has only been partially explored, with the majority of data extrapolated from RABV infection. West Caucasian bat virus (WCBV), a divergent lyssavirus, has recently been associated with a spillover event to a domestic cat, raising concern about the risks to public health due to the circulation of the virus in its natural host. Through this study we have investigated the immune response determined by the WCBV versus two widely known lyssaviruses. We selected the Syrian hamster as representative of an accidental host, and chose the intramuscular route in order to mimic the natural infection. In hamsters, WCBV was highly pathogenic, determining 100% lethality and mild encephalitis. In comparison with Duvenhage virus (DUVV) and RABV, we found that WCBV displayed an intermediate ability to promote cellular antiviral response, produce pro-inflammatory cytokines, and recruit and activate lymphocytes in the hamsters’ central nervous system.

IMPORTANCE

Although all lyssaviruses cause fatal encephalomyelitis in mammals, they display a different host tropism and pathogenicity, with the ecology of Rabies virus (RABV) continually evolving and adapting to new host species. In 2020, West Caucasian bat virus (WCBV) was identified as the causative agent of rabies in a domestic cat in Italy. This event raised concerns about its public health consequences, due to the absence of biologicals against the infection. Our study investigates the host immune response triggered by WCBV in comparison with a pathogenic strain of RABV and the low pathogenic Duvenhage lyssavirus (DUVV), as a proxy to understand the mechanisms leading to lyssavirus spillover and pathogenicity. We overall confirm that previous evidence indicating an inverse relationship between lyssavirus pathogenicity and immune response is applicable for WCBV as well. Importantly, this work represents the first transcriptomic analysis of the WCBV interaction in the central nervous system with an accidental host.
Kalamari: a representative set of genomes of public health concern
Authors: Katz Lee S. , Griswold Taylor , Lindsey Rebecca L. , Lauer A. C. , Im Monica S. , Williams Grant , Halpin Jessica L. , Gómez Gerardo A. , Kucerova Zuzana , Morrison Shatavia , Page Andrew , Den Bakker Henk C. , Carleton Heather A.
Published: January 2025

Kalamari is a resource that supports genomic epidemiology and pathogen surveillance. It consists of representative genomes and common contaminants. Kalamari also contains a custom taxonomy and software for downloading and formatting the data.
Predictive signatures of immune response to vaccination and implications of the immune setpoint remodeling
Authors: Ramos Irene
Published: January 2025

In 2020, I featured two articles in the “mSphere of Influence” commentary series that had profound implications for the field of immunology and helped shape my research perspective. These articles were “Global Analyses of Human Immune Variation Reveal Baseline Predictors of Postvaccination Responses” by Tsang et al. (Cell 157:499–513, 2014,
https://doi.org/10.1016/j.cell.2014.03.031
) and “A crowdsourced analysis to identify ab initio molecular signatures predictive of susceptibility to viral infection” by Fourati et al. (Nat Commun 9:4418, 2018,
https://doi.org/10.1038/s41467-018-06735-8
). From these topics, the identification of signatures predictive of immune responses to vaccination has greatly advanced and pivoted our understanding of how the immune state at the time of vaccination predicts (and potentially determines) vaccination outcomes. While most of this work has been done using influenza vaccination as a model, pan-vaccine signatures have been also identified. The key implications are their potential use to predict who will respond to vaccinations and to inform strategies for fine-tuning the immune setpoint to enhance immune responses. In addition, investigations in this area led us to understand that immune perturbations, such as acute infections and vaccinations, can remodel the baseline immune state and alter immune responses to future exposures, expanding this exciting field of research. These processes are likely epigenetically encoded, and some examples have already been identified and are discussed in this minireview. Therefore, further research is essential to gain a deeper understanding of how immune exposures modify the epigenome and transcriptome, influence the immune setpoint in response to vaccination, and define its exposure-specific characteristics.
Minimal change disease following autologous stem cell transplant for Hodgkin lymphoma
Authors: Leung Patrick , Pianta Timothy , Langsford David , Tay Hui Sien , Cooke Rachel
Published: January 2025

Nephrotic syndrome is characterised by heavy proteinuria secondary to glomerular injury. It is an uncommon but serious complication of allogeneic haematopoietic stem cell transplant (HSCT), but rarely reported after autologous HSCT. Here, we report the case of a man in his mid-20s who presented with significant peripheral oedema 2 months after autologous HSCT for Hodgkin lymphoma. Investigations demonstrated nephrotic range proteinuria and hypoalbuminaemia. Renal biopsy demonstrated minimal change disease. Initial treatment with glucocorticoids was complicated by toxicity without remission. However, the clinical and biochemical resolution of his nephrotic syndrome promptly followed administration of rituximab. This case highlights nephrotic syndrome as a complication after autologous HSCT and suggests potential effectiveness of rituximab in minimal change disease in the presence of steroid toxicity or other contraindications.
Pretreatment attrition after rifampicin-resistant tuberculosis diagnosis with Xpert MTB/RIF or ultra in high TB burden countries: a systematic review and meta-analysis
Authors: Jouego Christelle Geneviève , Decroo Tom , Netongo Palmer Masumbe , Gils Tinne
Published: January 2025

Introduction

The WHO endorsed the Xpert MTB/RIF (Xpert) technique since 2011 as initial test to diagnose rifampicin-resistant tuberculosis (RR-TB). No systematic review has quantified the proportion of pretreatment attrition in RR-TB patients diagnosed with Xpert in high TB burden countries.

Pretreatment attrition for RR-TB represents the gap between patients diagnosed and those who effectively started anti-TB treatment regardless of the reasons (which include pretreatment mortality (death of a diagnosed RR-TB patient before starting adequate treatment) and/or pretreatment loss to follow-up (PTLFU) (drop-out of a diagnosed RR-TB patient before initiation of anti-TB treatment).

Methods

In this systematic review and meta-analysis, we queried EMBASE, PubMed and Web of science to retrieve studies published between 2011 and 22 July 2024, that described pretreatment attrition for RR-TB using Xpert in high TB burden countries. Data on RR-TB patients who did not start treatment after diagnosis and reasons for not starting were extracted in an Excel table. A modified version of the Newcastle-Ottawa scale was used to evaluate the risk of bias among all included studies. The pooled proportion of pretreatment attrition and reasons were assessed using random-effects meta-analysis. Forest plots were generated using R software.

Results

Thirty eligible studies from 21 countries were identified after full-text screening and included in the meta-analysis. Most studies used routine programme data. The pooled proportion of pretreatment attrition in included studies was 18% (95% CI: 12 to 25). PTLFU and pretreatment mortality were, respectively, reported in 10 and nine studies and explained 78% (95% CI: 51% to 92%) and 30% (95% CI: 15% to 52%) of attrition.

Conclusion

Pretreatment attrition was widespread, with significant heterogeneity between included studies. National TB programmes should ensure accurate data collection and reporting of pretreatment attrition to enable reliable overall control strategies.

PROSPERO registration number

CRD42022321509.