bluuebunny/crossref_metadata_2025 huggingface dataset:
Vacuolar H+‐ATPase Is Required for Efficient Vacuolar Phosphate Storage and Systemic Pi Homeostasis in Arabidopsis
Authors: Sun Guangfang , Luan Mingda , Xue Shuting , Yan Jun , Lan Wenzhi
Published: September 2024

The vacuolar H+‐ATPase (V‐ATPase) plays a crucial role in facilitating nutrient ions storage in vacuoles, whereas its direct impact on vacuolar phosphate (Pi) accumulation has not been fully elucidated. Previous research revealed that the absence of VPT1 and VPT3, two major vacuolar Pi influx transporters, significantly affected vacuolar Pi storage. This study shows that disrupting V‐ATPase function could mimic the vpt1 vpt3 mutant phenotypes. The vha‐a2 a3 mutant, lacking V‐ATPase activity, had lower vacuolar Pi levels, higher cytoplasmic Pi and increased resistance to As(V) toxicity under sufficient Pi conditions. Complementation assays in Pi transport‐deficient yeast confirmed that high pH suppressed VPT1 activity, while overexpressing VPT1 couldn't overload Pi in vacuoles of vha‐a2 a3 mutants. These data illustrate the reliance of VPT1's activity on V‐ATPase‐generated proton gradients. Furthermore, we find V‐ATPase activity correlates positively with Pi availability, and varying across developmental stages. During flowering, V‐ATPase activity decreases to enhance Pi allocation in xylem sap for long‐distance transport when external Pi is replete, akin to the vpt1 vpt3 mutant. Thus, V‐ATPase could cooperate with VPT proteins to regulate Pi homeostasis at both subcellular and systemic levels.
Association of benzodiazepine and Z‐hypnotic use with cardiovascular disease risk: insights from a prospective study of 10 million people in China
Authors: Yang Ruotong , Yu Huan , Wu Junhui , Wang Siyue , Chen Hongbo , Wang Mengying , Qin Xueying , Wu Tao , Wu Yiqun , Hu Yonghua
Published: September 2024

Aim

To assess the association between Benzodiazepines (BZDs) or Z‐hypnotic use and cardiovascular diseases (CVD) incidence in residents in Beijing, China.

Methods

We included 2,415,573 individuals with a prescription record for BZDs or Z‐hypnotics in the Beijing Medical Claim Data for Employees database during 2010–2017, and 8,794,356 non‐users with other prescriptions for the same period. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional risk models for 712,850 exposed and 712,850 unexposed participants who were matched 1:1 by propensity score.

Results

BZDs or Z‐hypnotics users had a higher risk of CVD than non‐users, with an HR of 1.11 (95% CI: 1.10, 1.13). Compared with non‐users, those who used them for less than 3 months had the lowest risk of CVD, and those for more than 5 years had the highest risk, with HRs of 0.50 (0.48, 0.51) and 1.78 (1.72, 1.83), respectively. The risk of CVD was relatively low in those who used only one of the long‐acting BZDs, short‐acting BZDs, or Z‐hypnotics compared to unexposed individuals. Individuals exposed to all three types of drugs had the highest risk, 2.33 (2.22, 2.44) times that of non‐users. Users below the median dose had a lower risk of CVD compared to non‐users, whereas users exceeding the median dose had an increased risk.

Conclusion

BZD or Z‐hypnotic use in general was nominally associated with an elevated risk of CVD. However, for short‐term, single‐type, and low‐to‐moderate‐dose users, not only did this elevated risk disappear, but drug use also demonstrated a protective effect.
Development of an emergency science popularization capacity index system for nurses in China—A Delphi study
Authors: Lu Minghui , Chai Qianwen , Wei Li , Wang Yanmei , Cao Cancan
Published: September 2024

Aim

To construct a popularization of an emergency science capacity index system for nurses based on the iceberg model.

Design

A mixed‐method research design incorporating quantitative and qualitative components was used.

Methods

In this study, the first draft of the questionnaire was developed through literature analysis and semi‐structured interviews. According to the Delphi expert inclusion criteria, 20 experts with rich experience in the field of science popularization were selected, and the system of emergency science popularization ability of nurses was ultimately developed through two rounds of consultation according to the Delphi method. The weights of various indicators were determined through hierarchical analysis.

Results

Following two rounds of Delphi surveys, a total of 3 primary, 6 secondary, and 26 tertiary indicators were identified. The indicators were found to be highly significant, with variation coefficients ranging from 0.063 to 0.140. The Kendall's harmonization coefficients for the primary, secondary, and tertiary indicators were 0.350, 0.341, and 0.146, respectively. The popularization of the emergency science capacity system has a certain scientific and practical significance, which is of guidance to the competency of nurses in public health emergencies.

Patient or public contribution

No patient or public contribution. This study did not involve patients, service users, caregivers, or members of the public.
Glycine betaine: A multifaceted protectant against salt stress in Indian mustard through ionic homeostasis, ROS scavenging and osmotic regulation
Authors: Islam Shaistul , Mohammad Firoz , Shakeel Adnan , Corpas Francisco J.
Published: September 2024

Salt stress is a prevalent environmental issue that disrupts the redox balance and metabolic processes in plants, leading to reduced crop growth and productivity. Currently, over 6.74 million hectares in India are salt‐affected, and about 75% of this land lies in states that are the major cultivators of edible oilseed crops (rapeseed‐mustard). Therefore, this study focused on the efficacy of glycine betaine (GB) supplementation in mitigating the detrimental effects of salt stress in Brassica juncea L. (Indian mustard) plants. Indian mustard plants were subjected to salt stress [0, 50, 100, and 150 mM sodium chloride] 20 days after sowing (DAS), while a foliar spray of 20 mM GB was applied to the foliage at 50 and 70 DAS. The data showed that salt stress substantially reduced growth, photosynthetic rate, membrane stability, and yield by significantly increasing lipid peroxidation, ion toxicity, cell death, electrolyte leakage, and reactive oxygen species accumulation that triggered oxidative stress. Supplementation with 20 mM GB provided tolerance to plants against salt‐induced toxicity since it substantially increased growth, biomass, water content, nutrient uptake, and photosynthetic efficiency. Additionally, GB enhances the accumulation of osmolytes, enhances the antioxidant defence system, improves ionic balance, and enhances cell viability. Taken together, the obtained data provides deeper insights into the beneficial effect of the exogenous GB application that could have biotechnological uses to enhance crop stress tolerance in challenging environments.
Case study: The downside of using a worst‐case approach in occupational safety policy as an interpretation of the precautionary principle: Putting the uncertain UXO occupational safety risk into probabilistic perspective
Authors: Helsloot Marijn , Snip Wino , Helsloot Ira
Published: September 2024

Unexploded ordnance (UXO) from the World Wars on the North Sea floor pose an uncertain occupational safety risk for dredging and cable installation. At present mitigation strategies are based on an interpretation of the precautionary principle that uses a worst‐case approach, that is, assuming that UXO will be encountered, will explode, and will harm people onboard. We propose a probabilistic framework to estimate the UXO risk. Using this probabilistic framework, we conclude that the UXO risk during cable installation meets the prevailing safety standard in the Netherlands. Furthermore, we demonstrate that the UXO risk is lower than the general maritime risk, that is, the occupational health risk caused by the mitigation is higher than the UXO risk itself. We conclude that even for uncertain occupational risks, such as the UXO risk in the North Sea, a probabilistic analysis can be more instrumental in the decision‐making process on accepting and mitigating risks than using worst‐case scenario thinking.
Hearing Heat: An Anthropocene acoustemology
Authors: Feld Steven
Published: September 2024

‘Hearing Heat: An Anthropocene acoustemology’ is an intermedia composition that meditates on the climate of history, listening to histories of listening from the Papua New Guinea rainforest to nuclear Japan to ancient and contemporary Greece. It proceeds through continual recombinations of visual and sonic media, with photographs, graphics, animation, and cinema dialoguing with ethnographic field recording of Indigenous song, ambient environmental sound, cinema soundtracks, electroacoustic and radio composition, and vocally performed text.
ESBL Producing E. coli in Chickens and Poultry Farms Environment in Selangor, Malaysia: A Cross‐Sectional Study on Their Occurrence and Associated Risk Factors With Environment and Public Health Importance
Authors: Aliyu Abdulrasheed Bello , Jalila Abu , Saleha Abdul Aziz , Zunita Zakaria
Published: September 2024

Introduction

Extended‐spectrum β‐lactamase‐producing Escherichia coli (ESBL‐EC) are widespread multidrug‐resistant zoonotic bacteria that threaten animal production, food safety and antimicrobial therapy worldwide including Malaysia. Poultry has been reported as one of the pathways for human exposure to ESBL‐EC. There has been little research on the occurrence of ESBL‐EC within the Malaysian poultry food chain. Hence, the objectives of the study were to determine the occurrence of ESBL‐EC in chickens and to identify the potential risk factors associated with their occurrence in poultry farms.

Methods

A cross‐sectional study was conducted on 400 samples, consisting of 240 cloacal swabs from chickens and 160 from poultry farms environments in eight districts in Selangor, Malaysia using culture and disk combination methods and multiple polymerase chain reaction assays. In the determination of possible factors associated with the presence of ESBL‐EC at poultry farms, a questionnaire was used to obtain the information and data.

Results

The findings demonstrated the wide distribution of ESBL‐EC in all the farms with an overall occurrence of 37.2%. Farms in Gombak, Klang and Hulu Selangor had the highest occurrence rates at 62%, 50% and 50%, respectively, followed by farms in Petaling 38%, Sepang at 34%, Kuala Langat at 26% and Kuala Selangor at 24%, and the lowest was in Hulu Langat 14%. Among the study samples, chickens had the highest occurrence rate at 45.4%, followed by chicken house floors at 40% and flies at 30%, while feed and water samples at 17.5% and 12.5%, respectively. The present study indicated the high occurrence and wide dissemination of ESBL‐EC in chickens and poultry farms environment. The ESBL‐EC occurrence was associated with several factors including imprudent use of antibiotics, poor husbandry, management and biosecurity practices at the farms.

Conclusions

Our study showed the presence and spread of ESBL EC among chickens in the farms and their environment; this may lead to being spread to outside of farm environment by flies, vermins, flying birds, litter and farm wastes and possibly to humans upon contact with the contaminated environment and by poultry meat. Thus, the findings of the study can assist to serve as a piece of useful information to veterinary authority in designing evidence‐based mitigation strategies for the control of ESBL‐EC in poultry farms.
A Multi-Sized Unit Cell Method for the Design of LPBF Lattice Support Structures Concerning Complex Geometries
Authors: White Lisha , Zhang Guanglu , Seo Junwon , Lamprinakos Nicholas , Rollett Anthony , Cagan Jonathan , Zhang Yongjie Jessica
Published: September 2024

Composed of individual unit cells strategically arranged to achieve a desired function, lattices are a promising solution for laser powder bed fusion support structure design in additive manufacturing. Despite their many advantages (e.g., multifunctionality and reduced material cost), prior work in lattice support structure design primarily focuses on horizontal support domains that are not translatable to support domains for complex geometries, thereby limiting their application. This work introduces a multi-sized unit cell design optimization (MSO) method to create lattice support structures (LSS) for parts with complex geometries. The proposed method utilizes voxelization to generate LSS using box-like unit cells of different sizes. It also allows for efficient, high-dimensional design optimization for the types and locations of user-specified unit cells through a modified simulated annealing-based optimization algorithm. The effectiveness and efficiency of the MSO method are demonstrated through the case study of an adapter pipe for a high-temperature heat exchanger. For this demonstration, LSS using multi-sized unit cells is designed to increase heat transfer rate while satisfying structural integrity and material cost constraints. The case study results indicate that the design of the LSS derived from the MSO method fulfills all constraints, including the design constraint of 50% material cost reduction, compared to the solid support structure. In contrast, the lattice support structure designs derived from equal-sized unit cell methods either cannot satisfy all design constraints or have a lower heat transfer rate than the design of the MSO method.
Impact of the Wall-Parallel Length Scale of Roughness on the Development of Turbulent Boundary Layers in Turbines
Authors: Berhane Abigail M. , Longley John P.
Published: September 2024

The detrimental effects of surface roughness on the growth of turbulent boundary layers in turbines, and compressors, are well known. However, robust prediction of these effects can be problematic, especially for surfaces which are not similar to sand grains. Several publications have proposed that additional parameters such as effective slope, skew, etc. can be used to augment a wall-normal measure such as Sa to correlate surface roughness. Here, we introduce a new roughness parameter, the mean feature separation, which explicitly measures the average separation between each local minima and its closest local maxima. Scans of turbine blade surfaces showed that they can have mean separations which are up to six times that of the sand grain surface which has the same wall-normal length scale. The availability of high resolution, typically < 0.1 µm, area scanning tools, and 3D printing techniques have enabled the development of a “Scan-Scale-Print-Measure” methodology. A surface scan is scaled-up, 3D printed, applied to a flat-plate, and then the turbulent boundary layer is measured. The surface roughness-loss is the additional momentum thickness, above that of the datum smooth surface. The Scan-Scale-Print-Measure methodology has enabled parametric studies to be undertaken where the mean separation was increased while keeping either the Sa value or the feature size constant. Both studies demonstrated a surface roughness-loss that was strongly dependent on the mean separation and different to a Schlichting-based sand grain correlation. It also showed that for large mean separations, the roughness-loss decreased to zero. A parametric study into pits-and-peaks surface features showed that, at the same wall-normal length scale, peaks generated a surface roughness-loss twice that of pits. An engine representative surface produced only half the roughness-loss that would be attributed to a sand grain surface. The measured surface roughness-loss could be estimated within 5% using the aforementioned parametric studies.
A method for calculating the grand average of a set of auditory brain-stem responses
Authors: Kristensen Sinnet G. B. , Elberling Claus
Published: September 2024

To calculate a grand average waveform for a set of auditory brain-stem responses (ABRs), no generally accepted method exists. Here, we evaluate a new method using temporal adjustment of the underlying ABRs. Compared to a method without temporal adjustment, the new method results in higher amplitudes of the individual waves in the grand average. The grand average produced by the method better represents the group mean wave-amplitudes because it reduces smearing of the individual waves caused by inter-subject latency variability.
Global prediction and analysis for helicopter noise footprint based on acoustic modes
Authors: Shao Mengxue , Lu Yang , Xu Xice , Lu Jiaxin
Published: September 2024

Aiming to address the significant external noise produced by helicopter rotors, an integrated process based on acoustic modes has been developed for predicting the global noise footprint. The proposed method has the advantages of global prediction, analysis, and low computational costs. The key steps involve constructing an acoustic modal database and efficient prediction of noise footprint. First, the global noise model is utilized to map the time-domain sound pressure to amplitudes and coefficients in the acoustic modal domain. Acoustic mode coefficients representing various flight states are systematically cataloged in the database. Subsequently, the coefficients are extracted based on the characteristic parameters of trajectory elements, allowing for the evaluation of noise radiation in the acoustic modal domain. To investigate the impact of descent angle and advance ratio on the noise footprint, a simulation study is conducted in the forward and approach flight with an AS350 helicopter. Results indicated that, for a region with 1800 observers, the computational time of the developed approach requires only one-fifth of the time compared to the traditional Rotorcraft Noise Model method. This remarkable reduction in computation time, along with the global predictive capability, supports the practicality of efficient noise footprint assessment in both military and civilian contexts.
The ESCAPE Trial for Older People With Chronic Low Back Pain: A Feasibility Study of a Clinical Trial of Group-Based Exercise in Primary Health Care
Authors: Silva Hytalo de Jesus , Miranda Júlio Pascoal de , Melo Camila Silva de , Fonseca Leticia Soares , Mascarenhas Rodrigo de Oliveira , Veloso Nathalia Soares , Silva Whesley Tanor , Bastone Alessandra de Carvalho , Oliveira Vinícius Cunha
Published: September 2024

Low back pain is a highly disabling health condition that generates high costs for patients and healthcare systems. For this reason, it is considered a serious public health problem worldwide. This pilot study aimed to assess the feasibility of a future randomized controlled trial (RCT) by evaluating adherence to treatment, contamination between groups, satisfaction with treatment, and understanding of the exercise instructions provided by the physiotherapist. Additionally, we sought to identify and implement necessary modifications to the exercise protocol for better suitability in older people. We conducted a prospective, registered pilot RCT comparing an 8-week group-based exercise program with a waiting list in older people (≥60 years old) with chronic low back pain. Sixty participants were recruited through social media, pamphlets, and invitations at community referral centers. The study demonstrated the feasibility of a full RCT. Participants reported high satisfaction with the treatment (i.e., 100% indicated willingness to return for future services) and a high understanding of the exercise instructions (i.e., 81.8% reported “very easy” comprehension). Adherence to the exercise program exceeded the average reported for group exercise interventions in older adults (i.e., 82.58%). Dropout was associated solely with preexisting physical activity levels. The exercise protocol was successfully adapted to better suit the needs of the older adult population. This pilot RCT demonstrates the feasibility of a full-scale RCT to evaluate the effectiveness of group exercise in improving pain intensity and disability in older adults with chronic low back pain. The implemented adjustments to the exercise protocol and overall study approach strengthen the methodological foundation and expected accuracy of the future RCT.
Translation, Cross-Cultural Adaptation, and Validation of the Italian Version of the Shoulder Instability—Return to Sport After Injury (SI-RSI) Scale
Authors: Segat Francesco , Buscemi Claudia Benedetta , Guido Federico , Hardy Alexandre , Pellicciari Leonardo , Brindisino Fabrizio , Vascellari Alberto , Visonà Enrico , Poser Antonio , Venturin Davide
Published: September 2024

Objective: To culturally adapt and validate the Italian version of the Shoulder Instability—Return to Sport after Injury (SI-RSI-I) scale. Methods: The SI-RSI-I was developed by adapting the Anterior Cruciate Ligament—Return to Sport Index—Italian version and replacing the term “knee” with “shoulder.” Subsequently, it underwent validation following COSMIN recommendations. The study involved athletic participants who experienced SI. They completed the SI-RSI-I together with other measurement instruments: Western Ontario Shoulder Instability Index, Kerlan-Jobe Orthopedic Clinic Score, EuroQol-5D-5L, and Numeric Pain Rating Scale. The following psychometric properties were investigated: structural validity, internal consistency, test–retest reliability, measurement error, and construct validity. Results: The study included 101 participants (age mean [SD] 28.5 [7.4] y; 83 males, 18 females). The SI-RSI-I showed a single-factor structure, excellent internal consistency (α = .935), and excellent test–retest reliability (ICC = .926; 95% CI, .853–.964). The standard error of measurement was 6.1 points, and the minimal detectable change was 17.0 points. Furthermore, SI-RSI-I demonstrated moderate to strong correlations with all reference scales, confirming 8 out of 9 (88.0%) hypotheses, thus establishing satisfactory construct validity. Conclusion: The SI-RSI-I has demonstrated robust internal consistency, reliability, validity, and feasibility as a valuable scale for assessing psychological readiness to return to sport in Italian athletes with SI.
Critical assessment of water enthalpy characterization through dark environment evaporation
Authors: Caratenuto Andrew , Zheng Yi
Published: September 2024

Comparative evaporation rate testing in a dark environment, commonly used to characterize a reduced vaporization enthalpy in interfacial solar evaporators, requires the assumption of equal energy input between cases. However, this assumption is not generally valid, leading to misleading characterization results. Interfacial evaporators yield larger evaporation rates in dark conditions due to enlarged liquid-vapor surface areas, resulting in increased evaporative cooling and larger environmental temperature differentials. Theoretical and experimental evidence is provided, which shows that these temperature differences invalidate the equal energy input assumption. The results indicate that differences in evaporation rates correspond to energy input variations, without requiring enthalpy to be reduced below theoretical values. These findings offer alternative explanations for previous claims of reduced vaporization enthalpy and contradict enthalpy-related conclusions drawn from differential scanning calorimetry. We conclude that postulating a reduced vaporization enthalpy using the dark environment method is inaccurate and that re-evaluation of vaporization enthalpy reduction is required.
ACSL6-activated IL-18R1–NF-κB promotes IL-18–mediated tumor immune evasion and tumor progression
Authors: Di Yuqin , Wang Ziyang , Xiao Jing , Zhang Xiang , Ye Lvlan , Wen Xiangqiong , Qin Jiale , Lu Ligong , Wang Xiongjun , He Weiling
Published: September 2024

Aberrant activation of IL-18 signaling regulates tumor immune evasion and progression. However, the underlying mechanism remains unclear. Here, we report that long-chain acyl-CoA synthase 6 (ACSL6) is highly expressed in liver cancer and correlated with poor prognosis. ACSL6 promotes tumor growth, metastasis, and immune evasion mediated by IL-18, independent of its metabolic enzyme activity. Mechanistically, upon IL-18 stimulation, ACSL6 is phosphorylated by ERK2 at S674 and recruits IL-18RAP to interact with IL-18R1, thereby reinforcing the IL-18R1–IL-18RAP heterodimer and triggering NF-κB–dependent gene expression to facilitate tumor development. Furthermore, the up-regulation of CXCL1 and CXCL5 by ACSL6 promotes tumor-associated neutrophil and tumor-associated macrophage recruitment, thereby inhibiting cytotoxic CD8
+
T cell infiltration. Ablation or S674A mutation of ACSL6 potentiated anti–PD-1 therapeutic efficacy by increasing the effector activity of intertumoral CD8
+
T cells. We revealed that ACSL6 is a potential adaptor that activates IL-18–NF-κB axis–mediated tumor immune evasion and provides valuable insights for developing effective immunotherapy strategies for cancer.
Deep humoral profiling coupled to interpretable machine learning unveils diagnostic markers and pathophysiology of schistosomiasis
Authors: Saha Anushka , Chakraborty Trirupa , Rahimikollu Javad , Xiao Hanxi , de Oliveira Lorena B. Pereira , Hand Timothy W. , Handali Sukwan , Secor W. Evan , A. O. Fraga Lucia , Fairley Jessica K. , Das Jishnu , Sarkar Aniruddh
Published: September 2024

Schistosomiasis, a highly prevalent parasitic disease, affects more than 200 million people worldwide. Current diagnostics based on parasite egg detection in stool detect infection only at a late stage, and current antibody-based tests cannot distinguish past from current infection. Here, we developed and used a multiplexed antibody profiling platform to obtain a comprehensive repertoire of antihelminth humoral profiles including isotype, subclass, Fc receptor (FcR) binding, and glycosylation profiles of antigen-specific antibodies. Using Essential Regression (ER) and SLIDE, interpretable machine learning methods, we identified latent factors (context-specific groups) that move beyond biomarkers and provide insights into the pathophysiology of different stages of schistosome infection. By comparing profiles of infected and healthy individuals, we identified modules with unique humoral signatures of active disease, including hallmark signatures of parasitic infection such as elevated immunoglobulin G4 (IgG4). However, we also captured previously uncharacterized humoral responses including elevated FcR binding and specific antibody glycoforms in patients with active infection, helping distinguish them from those without active infection but with equivalent antibody titers. This signature was validated in an independent cohort. Our approach also uncovered two distinct endotypes, nonpatent infection and prior infection, in those who were not actively infected. Higher amounts of IgG1 and FcR1/FcR3A binding were also found to be likely protective of the transition from nonpatent to active infection. Overall, we unveiled markers for antibody-based diagnostics and latent factors underlying the pathogenesis of schistosome infection. Our results suggest that selective antigen targeting could be useful in early detection, thus controlling infection severity.
ARGX-119 is an agonist antibody for human MuSK that reverses disease relapse in a mouse model of congenital myasthenic syndrome
Authors: Vanhauwaert Roeland , Oury Julien , Vankerckhoven Bernhardt , Steyaert Christophe , Jensen Stine Marie , Vergoossen Dana L. E. , Kneip Christa , Santana Leah , Lim Jamie L. , Plomp Jaap J. , Augustinus Roy , Koide Shohei , Blanchetot Christophe , Ulrichts Peter , Huijbers Maartje G. , Silence Karen , Burden Steven J.
Published: September 2024

Muscle-specific kinase (MuSK) is essential for the formation, function, and preservation of neuromuscular synapses. Activation of MuSK by a MuSK agonist antibody may stabilize or improve the function of the neuromuscular junction (NMJ) in patients with disorders of the NMJ, such as congenital myasthenia (CM). Here, we generated and characterized ARGX-119, a first-in-class humanized agonist monoclonal antibody specific for MuSK, that is being developed for treatment of patients with neuromuscular diseases. We performed in vitro ligand-binding assays to show that ARGX-119 binds with high affinity to the Frizzled-like domain of human, nonhuman primate, rat, and mouse MuSK, without off-target binding, making it suitable for clinical development. Within the Fc region, ARGX-119 harbors L234A and L235A mutations to diminish potential immune-activating effector functions. Its mode of action is to activate MuSK, without interfering with its natural ligand neural Agrin, and cluster acetylcholine receptors in a dose-dependent manner, thereby stabilizing neuromuscular function. In a mouse model of
DOK7
CM, ARGX-119 prevented early postnatal lethality and reversed disease relapse in adult
Dok7
CM mice by restoring neuromuscular function and reducing muscle weakness and fatigability in a dose-dependent manner. Pharmacokinetic studies in nonhuman primates, rats, and mice revealed a nonlinear PK behavior of ARGX-119, indicative of target-mediated drug disposition and in vivo target engagement. On the basis of this proof-of-concept study, ARGX-119 has the potential to alleviate neuromuscular diseases hallmarked by impaired neuromuscular synaptic function, warranting further clinical development.
Downregulation of APN1 and
ABCC2
mutation in Bt Cry1Ac-resistant
Trichoplusia ni
are genetically independent
Authors: Cotto-Rivera Rey O. , Joya Noelia , Hernández-Martínez Patricia , Ferré Juan , Wang Ping
Published: September 2024

The resistance to the insecticidal protein Cry1Ac from the bacterium
Bacillus thuringiensis
(Bt) in the cabbage looper,
Trichoplusia ni
, has previously been identified to be associated with a frameshift mutation in the ABC transporter ABCC2 gene and with altered expression of the aminopeptidase N (APN) genes
APN1
and
APN6
, shown as missing of the 110-kDa APN1 (phenotype APN1¯) in larval midgut brush border membrane vesicles (BBMV). In this study, genetic linkage analysis identified that the APN1¯ phenotype and the
ABCC2
mutation in Cry1Ac-resistant
T. ni
segregated independently, although they were always associated under Cry1Ac selection. The
ABCC2
mutation and APN1¯ phenotype were separated into two
T. ni
strains respectively. Bioassays of the
T. ni
strains with Cry1Ac determined that the
T. ni
with the APN1¯ phenotype showed a low level resistance to Cry1Ac (3.5-fold), and the associated resistance is incompletely dominant in the background of the
ABCC2
mutation. Whereas the
ABCC2
mutation-associated resistance to Cry1Ac is at a moderate level, and the resistance is incompletely recessive in the genetic background of downregulated APN1. Analysis of Cry1Ac binding to larval midgut BBMV indicated that the midgut in larvae with the APN1¯ phenotype had reduced binding affinity for Cry1Ac, but the number of binding sites remained unchanged, and the midgut in larvae with the
ABCC2
mutation had both reduced binding affinity and reduced number of binding sites for Cry1Ac. The reduced Cry1Ac binding to BBMV from larvae with the
ABCC2
mutation or APN1¯ phenotype correlated with the lower levels of resistance.

IMPORTANCE

The soil bacterium
Bacillus thuringiensis
(Bt) is an important insect pathogen used as a bioinsecticide for pest control. Bt genes coding for insecticidal proteins are the primary transgenes engineered into transgenic crops (Bt crops) to confer insect resistance. However, the evolution of resistance to Bt proteins in insect populations in response to exposure to Bt threatens the sustainable application of Bt biotechnology. Cry1Ac is a major insecticidal toxin utilized for insect control. Genetic mechanisms of insect resistance to Cry1Ac are complex and require to be better understood. The resistance to Cry1Ac in
Trichoplusia ni
is associated with a mutation in the
ABCC2
gene and also associated with the APN expression phenotype APN1¯. This study identified the genetic independence of the APN1¯ phenotype from the
ABCC2
mutation and isolated and analyzed the
ABCC2
mutation-associated and APN1¯ phenotype-associated resistance traits in
T. ni
to provide new insights into the genetic mechanisms of Cry1Ac resistance in insects.
A strong priority effect in the assembly of a specialized insect-microbe symbiosis
Authors: Chen Jason Z. , Junker Anthony , Zheng Iris , Gerardo Nicole M. , Vega Nic M.
Published: September 2024

Specialized host-microbe symbioses are ecological communities, whose composition is shaped by various processes. Microbial community assembly in these symbioses is determined in part by interactions between taxa that colonize ecological niches available within habitat patches. The outcomes of these interactions, and by extension the trajectory of community assembly, can display priority effects—dependency on the order in which taxa first occupy these niches. The underlying mechanisms of these phenomena vary from system to system and are often not well resolved. Here, we characterize priority effects in colonization of the squash bug (
Anasa tristis
) by bacterial symbionts from the genus
Caballeronia
, using pairs of strains that are known to strongly compete during host colonization, as well as strains that are isogenic and thus functionally identical. By introducing symbiont strains into individual bugs in a sequential manner, we show that within-host populations established by the first colonist are extremely resistant to invasion, regardless of strain identity and competitive interactions. By knocking down the population of an initial colonist with antibiotics, we further show that colonization success by the second symbiont is still diminished even when space in the symbiotic organ is available and ostensibly accessible for colonization. We speculate that resident symbionts exclude subsequent infections by manipulating the host environment, partially but not exclusively by eliciting tissue remodeling of the symbiont organ.

IMPORTANCE

Host-associated microbial communities underpin critical ecosystem processes and human health, and their ability to do so is determined in turn by the various processes that shape their composition. While selection deterministically acts on competing genotypes and species during community assembly, the manner by which selection determines the trajectory of community assembly can differ depending on the sequence by which taxa are established within that community. We document this phenomenon, known as a priority effect, during experimental colonization of a North American insect pest, the squash bug
Anasa tristis
, by its betaproteobacterial symbionts in the genus Caballeronia. Our study demonstrates how stark, strain-level variation can emerge in specialized host-microbe symbioses simply through differences in the order by which strains colonize the host. Understanding the mechanistic drivers of community structure in host-associated microbiomes can highlight both pitfalls and opportunities for the engineering of these communities and their constituent taxa for societal benefit.
Unraveling the mystery of Tacaribe virus
Authors: Schountz Tony
Published: September 2024

Tacaribe virus (TCRV) was first isolated in the mid-1950s from several
Artibeus
species bats in and around Port of Spain, Trinidad and Tobago. Since that time, debate has persisted whether artibeus bats serve as reservoir hosts of the virus or whether infection of the bats was an incidental spillover event from another, unidentified reservoir host. Complicating the issue is that the only TCRV isolate routinely used, TRVL-11573, had been passaged in suckling mice and likely accumulated mutations that altered its biology. Recent fieldwork has now identified two distinct genomes of TCRV in apparently healthy artibeus bats sampled in Brazil and the Dominican Republic (C. Fischer, M. H. A. Cassiano, W. R. Thomas, L. M. Dávalos, et al., mSphere e00520-24, 2024,
https://doi.org/10.1128/msphere.00520-24
). Together, these works suggest that artibeus bats are natural reservoirs of TCRV and that the virus has a wide geographic distribution in the Americas.
Changes in growth, lanthanide binding, and gene expression in
Pseudomonas alloputida
KT2440 in response to light and heavy lanthanides
Authors: Gorniak Linda , Bucka Sarah Luise , Nasr Bayan , Cao Jialan , Hellmann Steffen , Schäfer Thorsten , Westermann Martin , Bechwar Julia , Wegner Carl-Eric
Published: September 2024

Pseudomonas alloputida
KT2440 is a ubiquitous, soil-dwelling bacterium that metabolizes recalcitrant and volatile carbon sources. The latter is utilized by two redundant, Ca- and lanthanide (Ln)-dependent, pyrroloquinoline quinone-dependent alcohol dehydrogenases (PQQ ADH), PedE and PedH, whose expression is regulated by Ln availability.
P. alloputida
KT2440 is the best-studied non-methylotroph in the context of Ln-utilization. Combined with microfluidic cultivation and single-cell elemental analysis, we studied the impact of light and heavy Ln on transcriptome-wide gene expression when growing
P. alloputida
KT2440 with 2-phenylethanol as the carbon and energy source. Light Ln (La, Ce, and Nd) and a mixture of light and heavy Ln (La, Ce, Nd, Dy, Ho, Er, and Yb) had a positive effect on growth, whereas supplementation with heavy Ln (Dy, Ho, Er, and Yb) exerted fitness costs. These were likely a consequence of mismetallation and non-utilizable Ln interfering with Ln sensing and signaling. The measured amounts of cell-associated Ln varied between elements. Gene expression analysis suggested that the Ln sensing and signaling machinery, the two-component system PedS2R2 and PedH, responds differently to (non-)utilizable Ln. We expanded our understanding of the lanthanide (Ln) switch in
P. alloputida
KT2440, demonstrating that it adjusts the levels of
pedE
and
pedH
transcripts based on the availability of Ln. We propose that the usability of Ln influences the bacterium’s response to different Ln elements.

IMPORTANCE

The Ln switch, the inverse regulation of Ca- and Ln-dependent PQQ ADH in response to Ln availability in organisms featuring both, is central to our understanding of Ln utilization. Although the preference of bacteria for light Ln is well known, the effect of different Ln, light and heavy, on growth and gene expression has rarely been studied. We provide evidence for a fine-tuning mechanism of Ca- and Ln-dependent PQQ ADH in
P. alloputida
KT2440 on the transcriptome level. The response to (non-)utilizable Ln differs depending on the element. Ln commonly co-occur in nature. Our findings underline that Ln-utilizing microbes must be able to discriminate between Ln to use them effectively. Considering the prevalence of Ln-dependent proteins in many microbial taxa, more work addressing Ln sensing and signaling is needed. Ln availability likely necessitates different adaptations regarding Ln utilization.
Proteomic insights into extracellular matrix dynamics in the intestine of
Labeo rohita
during
Aeromonas hydrophila
infection
Authors: Nissa Mehar Un , Pinto Nevil , Ghosh Biplab , Banerjee Anwesha , Singh Urvi , Goswami Mukunda , Srivastava Sanjeeva
Published: September 2024

In the aquaculture sector, one of the challenges includes disease outbreaks such as bacterial infections, particularly from
Aeromonas hydrophila
(
Ah
), impacting both wild and farmed fish. In this study, we conducted a proteomic analysis of the intestinal tissue in
Labeo rohita
following
Ah
infection to elucidate the protein alterations and its implications for immune response. Our findings indicate significant dysregulation in extracellular matrix (ECM)-associated proteins during
Ah
infection, with increased abundance of elastin and collagen alpha-3(VI). Pathway and enrichment analysis of differentially expressed proteins highlights the involvement of ECM-related pathways, including focal adhesions, integrin cell surface interactions, and actin cytoskeleton organization. Focal adhesions, crucial for connecting intracellular actin bundles to the ECM, play a pivotal role in immune response during infections. Increased abundance of integrin alpha 1, integrin beta 1, and tetraspanin suggests their involvement in the host’s response to
Ah
infection. Proteins associated with actin cytoskeleton reorganization, such as myosin, tropomyosin, and phosphoglucomutase, exhibit increased abundance, influencing changes in cell behavior. Additionally, upregulated proteins like LTBP1 and fibrillin-2 contribute to TGF-β signaling and focal adhesion, indicating their potential role in immune regulation. The study also identifies elevated levels of laminin, galectin 3, and tenascin-C, which interact with integrins and other ECM components, potentially influencing immune cell migration and function. These proteins, along with decorin and lumican, may act as immunomodulators, coordinating pro- and anti-inflammatory responses. ECM fragments released during pathogen invasion could serve as “danger signals,” initiating pathogen clearance and tissue repair through Toll-like receptor signaling.

IMPORTANCE

The study underscores the critical role of the extracellular matrix (ECM) and its associated proteins in the immune response of aquatic organisms during bacterial infections like
Aeromonas hydrophila
. Understanding the intricate interplay between ECM alterations and immune response pathways provides crucial insights for developing effective disease control strategies in aquaculture. By identifying key proteins and pathways involved in host defense mechanisms, this research lays the groundwork for targeted interventions to mitigate the impact of bacterial infections on fish health and aquaculture production.
Effects of antibiotic and disinfectant exposure on the mouse gut microbiome and immune function
Authors: Xu Wen-Bo , Wang Yun-Fan , Meng Si-Yu , Zhang Xiao-Tong , Wang Yi-Rong , Liu Zhao-Ying
Published: September 2024

This study explores the effects of disinfectant and antibiotic exposure on gut health, focusing on gut microbiota balance and gut immune function. Our analysis indicates that disinfectants increase the proportion of Gram-positive bacteria, particularly increasing
Staphylococcus
levels, while antibiotics increase the proportion of Gram-negative bacteria, especially
Bacteroides
levels. These changes disrupt microbial harmony and affect the gut microbiome’s functional capacity. Additionally, our research reveals that both disinfectants and antibiotics reduce colon length and cause mucosal damage. A significant finding is the downregulation of
NLRC4
, a key immune system regulator in the gut, accompanied by changes in immune factor expression. This interaction between chemical exposure and immune system dysfunction increases susceptibility to inflammatory bowel disease and other gut conditions. Given the importance of disinfectants in disease prevention, this study advocates for a balanced approach to their use, aiming to protect public health while minimizing adverse effects on the gut microbiome and immune function.

IMPORTANCE

Disinfectants are extensively employed across various sectors, such as the food sector. Disinfectants are widely used in various sectors, including the food processing industry, animal husbandry, households, and pharmaceuticals. Their extensive application risks environmental contamination, impacting water and soil quality. However, the effect of disinfectant exposure on the gut microbiome and the immune function of animals remains a significant, unresolved issue with profound public health implications. This highlights the need for increased scrutiny and more regulated use of disinfectants to mitigate unintended consequences on gut health and maintain immune system integrity.
A bacteriophage cocktail targeting
Yersinia pestis
provides strong post-exposure protection in a rat pneumonic plague model
Authors: Kilgore Paul B. , Sha Jian , Hendrix Emily K. , Neil Blake H. , Lawrence William S. , Peel Jennifer E. , Hittle Lauren , Woolston Joelle , Sulakvelidze Alexander , Schwartz Jennifer A. , Chopra Ashok K.
Published: September 2024

Yersinia pestis,
one of the deadliest bacterial pathogens ever known, is responsible for three plague pandemics and several epidemics, with over 200 million deaths during recorded history. Due to high genomic plasticity,
Y. pestis
is amenable to genetic mutations as well as genetic engineering that can lead to the emergence or intentional development of pan-drug-resistant strains. Indeed, antibiotic-resistant strains (e.g., strains carrying multidrug-resistant or MDR plasmids) have been isolated in various countries and endemic areas. Thus, there is an urgent need to develop novel, safe, and effective treatment approaches for managing
Y. pestis
infections. This includes infections by antigenically distinct strains for which vaccines (none FDA approved yet) may not be effective and those that cannot be managed by currently available antibiotics. Lytic bacteriophages provide one such alternative approach. In this study, we examined post-exposure efficacy of a bacteriophage cocktail, YPP-401, to combat pneumonic plague caused by
Y. pestis
CO92. YPP-401 is a four-phage preparation effective against a panel of at least 68 genetically diverse
Y. pestis
strains. Using a pneumonic plague aerosol challenge model in gender-balanced Brown Norway rats, YPP-401 demonstrated ~88% protection when delivered 18 h post-exposure for each of two administration routes (i.e., intraperitoneal and intranasal) in a dose-dependent manner. Our studies provide proof-of-concept that YPP-401 could be an innovative, safe, and effective approach for managing
Y. pestis
infections, including those caused by naturally occurring or intentionally developed multidrug-resistant strains.

IMPORTANCE

Currently, there are no FDA-approved plague vaccines. Since antibiotic-resistant strains of
Y. pestis
have emerged or are being intentionally developed to be used as a biothreat agent, new treatment modalities are direly needed. Phage therapy provides a viable option against potentially antibiotic-resistant strains. Additionally, phages are nontoxic and have been approved by the FDA for use in the food industry. Our study provides the first evidence of the protective effect of a cocktail of four phages against pneumonic plague, the most severe form of disease. When treatment was initiated 18 h post infection by either the intranasal or intraperitoneal route in Brown Norway rats, up to 87.5% protection was observed. The phage cocktail had a minimal impact on a representative human microbiome panel, unlike antibiotics. This study provides strong proof-of-concept data for the further development of phage-based therapy to treat plague.
Inverse Faraday Effect in Ferrite–Garnet Films in the Near-Infrared Range
Authors: Gribova N. I. , Berzhansky V. N. , Polulyakh S. N. , Belotelov V. I.
Published: September 2024

The magneto-optical Faraday effect is determined by the electric dipole and magnetic dipole transitions in a transparent magnetic material. At the same time, the inverse Faraday effect is still described by an expression that includes only electric dipole transitions. The magnetic dipole contribution to the inverse Faraday effect is considered theoretically, and the dependence of the inverse Faraday effect on the wavelength in the near-infrared range (where the magnetic dipole contribution becomes significant) is obtained by the example of a ferrite–garnet film. It is shown that, although both contributions to the inverse Faraday effect always take place for homogeneous films, only the magnetic-dipole inverse Faraday effect manifests itself for films with a periodic nanostructure upon excitation by a TE waveguide mode, which may be useful for its experimental observation.