bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Patellar Health Condition Through Wearable Devices: A combination of new material and machine-learning classifier
Authors: Jiang Zilin , Zhan Wenchao , Zhang Wenxi , Gao Chenjun , Fang Ziwei , He Jingjing , Sun Wei , Wen Chang , Lin Jing
Published: October 2023

Knee diseases such as osteoarthritis and patellofemoral disorder can cause abnormal patellar motion and lead to the reduction of a person’s activity ability. In this work, a new kind of flexible sensors combining graphene particles, lead magnesium niobate-lead titanate (PMN-PT) and polyvinylidene fluoride (PVDF) to form a flexible ternary composite is developed. A wearable device with six flexible sensors is specifically constructed to monitor the movement of patella. The position of sensors is designed based on medical mechanism of the patella movements. Testing data of patella movement is acquired from volunteers with and without knee injury. The raw signals are filtered to reduce high-frequency noises. Several features are extracted to characterize the motion of patella, including the number of change points and auto-correlation coefficient. The extracted features and the data are labeled according to Lysholm Knee Scoring Scale. Because the number of unhealthy data is much smaller than that of the healthy data, an oversampling strategy is applied to introduce new artificial data for subsequent machine learning classifier. Three classification methods including the Tree BAGGER, the k-nearest neighbors and the support vector machine are employed. Results show that the best performance is achieved by the support vector machine method with 96% accuracy.
Lamb Waves in a Double-Layer Plate with Nonlinear Spring Interface
Authors: Wang Junzhen , Qu Jianmin
Published: October 2023

This paper investigates the conditions under which resonant second-harmonic guided waves can be generated by the adhesive bond between two sublayers in a composite plate. It is assumed that the adhesive bond can be modeled as a nonlinear spring interface. As such, it can be further assumed that the interfacial traction is continuous across the interface, while the displacement has a jump across the interface. The jump is related to the interfacial traction nonlinearly. To illustrate the solution methodology without invoking complicated algebras, the two sublayers are assumed to share the same material and thickness. The modified normal mode expansion (mNME) method is adopted to solve the corresponding boundary value problem. It is found that a resonant second harmonic guided wave can be generated in such a composite plate when the frequency of the incident propagating Lamb mode coincides with that of a propagating Lamb mode in the plate whose frequency, when doubled, happens to be the frequency of another propagating Lamb mode.
Self-Sensing Piezoelectric Composite Structures using Disperse Electro-Mechanical Impedance Measurements
Authors: Zhou Shulong , Shen Yanfeng , Tian Yuan , Wang Bao , Wang Chunquan
Published: October 2023

This paper proposes a novel family of intelligent piezoelectric composite structures for the purpose of establishing structural self-awareness via disperse measurements of Electro-mechanical Impedance Spectroscopy (EMIS) methodology. The target of the current study aims at developing a functional composite material that embraces both load bearing and self-sensing capabilities at the same time. This is achieved by incorporating active material components, such as piezoelectric ingredients, in the structural component, forming a disperse and dense sensing grid, combined with active sensing methodologies. To develop a deep insight into the mechanism of the intelligent structure, coupled-field finite element models are constructed for verifying the feasibility of the EMIS for damage detection. In particular, the model employs the Equivalent Average Parameter (EAP) method, utilizing overall and nominal parameters, in order to simulate the self-sensing composites. A Root Mean Square Deviation (RMSD) damage metric is subsequently applied to determine the position of the structural damage. Furthermore, the manufacturing process of a piezoelectric composite beam structure is introduced in detail. meticulously crafted through a continuous process of material ratio optimization and process step refinement. Careful manufacturing parameters are explored to ensure the highest extent of sensitivity and reliability. Finally, experimental validation of the EMIS method is performed, showcasing the feasibility and accuracy of the impedance spectra for the damage location and quantification. The paper finished with summary, concluding remarks, and suggestions for future work.
Machine Learning-Based Digital Twin Framework for Realistic Guided Wave Signal Generation, Applied to Reliability Assessment and Global Sensitivity Analysis in SHM
Authors: Nerlikar Vivek , Miorelli Roberto , Recoquillay Arnaud , D’Almeida Oscar
Published: October 2023

An ultrasonic guided wave-based structural health monitoring system has potential applications in mainy domains such as, the oil and gas industry, civil engineering, and aerospace. However, there are some inherent challenges, such as the sensitivity of the Guided Waves (GW) to environmental and operational conditions (EOCs), defect(s) size and location, and sensor(s) placement. Therefore, the reliability of detection systems based on GW requires validation. Simulation tools are often used to study the impact of the above-mentioned factors. However, the computational burden associated to extensive simulation campaigns is excessive. To increase the computational efficiency, this work proposes a machine learning-based Digital Twin (DT) framework. More specifically, the DT framework employed in this paper comprises a linear dimensionality reduction algorithm and fully connected neural networks that work as a metamodel. The performance of the DT is evaluated on a simulation configuration of Aluminum with uncertainties in instrumentation and damage size. The simulation data required for training are obtained from CIVA simulation platform. The predicted signals from the DT are quantified using misfit-based criteria targeting amplitude and phase aspects based on time-frequency transformation. The assessment of the results suggests that DT has captured all the dynamics of the signals, and the predicted signals are in good agreement with the simulated ones. Furthermore, the developed DT has been employed to efficiently carry out the probability of detection study for reliability assessment and sensitivity analysis based on the propagation of uncertainties.
Chemical significance of x-ray photoelectron spectroscopy binding energy shifts: A Perspective
Authors: Bagus Paul S. , Nelin Connie J. , Brundle C. R.
Published: October 2023

The principal intent of this Perspective is to review the mechanisms that are responsible for the shifts of binding energies, ΔBE, observed in x-ray photoelectron spectroscopy (XPS) measurements and so to relate the shifts to the electronic structure and the chemical bonding in the systems studied. To achieve this goal, several theoretical considerations are necessary beyond just the calculation of XPS BEs. Though briefly discussed here, we are not primarily interested in absolute values of BE or quantitation using relative intensities. Within the molecular orbital (MO) theory framework, it is shown that the analysis of orbital properties is critical for the correct interpretation of XPS. In particular, rigorous definitions are given for the initial state and final state contributions to BEs and to BE shifts, ΔBE. It is first shown how the BEs of core levels are related to the electronic structure by consideration of the BEs for a model atomic system to establish the origins and magnitudes of BE shifts. The mechanisms established for the model system are then applied to a review of XPS measurements and MO theory on a set of real examples. An important focus of the paper is to demonstrate that, in many cases, initial state mechanisms allow for a definitive interpretation of the XPS BE shifts and that an important role of theory is to provide qualitative explanations rather than quantitative agreement with XPS measurements. The mechanisms established are a guide to the interpretation of XPS measurements and consideration of these mechanisms may suggest additional calculations that would be useful. It is concluded that there is still a bright future for the coupling of ab initio MO theory with XPS measurements.
Relationship Between Nordic Hamstring Strength and Single Leg Bridge Test in University Soccer Players
Authors: Murakami Yuta , Nishida Satoru , Yoshida Riku , Kasahara Kazuki , Kumazaki Akira , Sakuma Hirokazu , Fujimoto Hirosi , Kaneko Yuki , Abe Otoka , Nakamura Masatoshi
Published: October 2023

Context: Nordic hamstring strength (NH strength) and single leg bridge test (SLBT) scores are used to predict the risk of hamstring strain injury. Although NH strength and SLBT scores may be related, the relationship between NH strength and SLBT score remains unknown. Objectives: This study investigated the relationship between NH strength and SLBT scores in university soccer players. Design: Cross-sectional study. Setting: Research laboratory. Participants: 38 male university soccer players. Main Outcome Measures: NH strength and SLBT scores. Interventions: A participant was instructed to lean forward gradually at the slowest possible speed from a kneeling posture with the knee joint flexed 90° for the NH strength measurement. Participants in the SLBT crossed their arms over their chests, pushed down from their heels, and lifted their hips off the ground as many times as they could until they failed. We investigated the relationship between NH strength and SLBT scores in the left and right sides using Spearman rank correlation coefficient. Additionally, we calculated the percentage of left–right asymmetry in NH strength and SLBT scores and investigated the relationship between these variables using Pearson correlation coefficient. Results: There were no significant correlations between NH strength and SLBT scores in the right (rs = .239, P = .16) and left (rs = .311, P = .065) legs. Furthermore, there was no significant relationship between NH strength and SLBT between-limb asymmetry (r = .073, P = .671). Conclusions: NH strength and SLBT scores could be different indexes, indicating either maximal muscle strength or muscle endurance. Thus, the findings suggested that when assessing risk factors for hamstring strain injury, both NH strength and SLBT scores should be measured.
“I Realized It Was a Different Kind of Culture to Other Sports”: An Exploration of Sport Psychology Service Provision and Delivery in Gaelic Games
Authors: Jackman Patricia C. , Lane Aoife , Tod David , Bird Matthew D.
Published: October 2023

In this article, we present two studies that provide the first evidence on sport psychology services in Gaelic games. In Study 1, 36 participants providing support for mental aspects of performance in Gaelic games completed a survey that ascertained an initial insight into practitioners and the services they provided in this context. Findings of Study 1 suggested considerable engagement with psychology support in Gaelic games but also highlighted a range of challenges with service delivery. In Study 2, we interviewed 11 sport psychology consultants to understand the active ingredients that contribute to context-driven sport psychology in Gaelic games and the role of contextual intelligence. Findings from Study 2 offered insights into how participants shaped their services to the context and how the active ingredients for effective service delivery, including working alliances, buy-in, and engagement with individuals within the performance environment, could be enabled or constrained in this context.
Integrome signatures of lentiviral gene therapy for SCID-X1 patients
Authors: Yan Koon-Kiu , Condori Jose , Ma Zhijun , Metais Jean-Yves , Ju Bensheng , Ding Liang , Dhungana Yogesh , Palmer Lance E. , Langfitt Deanna M. , Ferrara Francesca , Throm Robert , Shi Hao , Risch Isabel , Bhatara Sheetal , Shaner Bridget , Lockey Timothy D. , Talleur Aimee C. , Easton John , Meagher Michael M. , Puck Jennifer M. , Cowan Morton J. , Zhou Sheng , Mamcarz Ewelina , Gottschalk Stephen , Yu Jiyang
Published: October 2023

Lentiviral vector (LV)–based gene therapy holds promise for a broad range of diseases. Analyzing more than 280,000 vector integration sites (VISs) in 273 samples from 10 patients with X-linked severe combined immunodeficiency (SCID-X1), we discovered shared LV integrome signatures in 9 of 10 patients in relation to the genomics, epigenomics, and 3D structure of the human genome. VISs were enriched in the nuclear subcompartment A1 and integrated into super-enhancers close to nuclear pore complexes. These signatures were validated in T cells transduced with an LV encoding a CD19-specific chimeric antigen receptor. Intriguingly, the one patient whose VISs deviated from the identified integrome signatures had a distinct clinical course. Comparison of LV and gamma retrovirus integromes regarding their 3D genome signatures identified differences that might explain the lower risk of insertional mutagenesis in LV-based gene therapy. Our findings suggest that LV integrome signatures, shaped by common features such as genome organization, may affect the efficacy of LV-based cellular therapies.
How genomic insights into the evolutionary history of clouded leopards inform their conservation
Authors: Yuan Jiaqing , Wang Guiqiang , Zhao Le , Kitchener Andrew C. , Sun Ting , Chen Wu , Huang Chen , Wang Chen , Xu Xiao , Wang Jinhong , Lu Huimeng , Xu Lulu , Jiangzuo Qigao , Murphy William J. , Wu Dongdong , Li Gang
Published: October 2023

Clouded leopards (Neofelisspp.), a morphologically and ecologically distinct lineage of big cats, are severely threatened by habitat loss and fragmentation, targeted hunting, and other human activities. The long-held poor understanding of their genetics and evolution has undermined the effectiveness of conservation actions. Here, we report a comprehensive investigation of the whole genomes, population genetics, and adaptive evolution ofNeofelis. Our results indicate the genusNeofelisarose during the Pleistocene, coinciding with glacial-induced climate changes to the distributions of savannas and rainforests, and signatures of natural selection associated with genes functioning in tooth, pigmentation, and tail development, associated with clouded leopards’ unique adaptations. Our study highlights high-altitude adaptation as the main factor driving nontaxonomic population differentiation inNeofelis nebulosa. Population declines and inbreeding have led to reduced genetic diversity and the accumulation of deleterious variation that likely affect reproduction of clouded leopards, highlighting the urgent need for effective conservation efforts.
Occurrence-based diversity estimation reveals macroecological and conservation knowledge gaps for global woody plants
Authors: Kusumoto Buntarou , Chao Anne , Eiserhardt Wolf L. , Svenning Jens-Christian , Shiono Takayuki , Kubota Yasuhiro
Published: October 2023

Incomplete sampling of species’ geographic distributions has challenged biogeographers for many years to precisely quantify global-scale biodiversity patterns. After correcting for the spatial inequality of sample completeness, we generated a global species diversity map for woody angiosperms (82,974 species, 13,959,780 occurrence records). The standardized diversity estimated more pronounced latitudinal and longitudinal diversity gradients than the raw data and improved the spatial prediction of diversity based on environmental factors. We identified areas with potentially high species richness and rarity that are poorly explored, unprotected, and threatened by increasing human pressure: They are distributed mostly at low latitudes across central South America, Central Africa, subtropical China, and Indomalayan islands. These priority areas for botanical exploration can help to efficiently fill spatial knowledge gaps for better describing the status of biodiversity and improve the effectiveness of the protected area network for global woody plant conservation.
Direct isolation of small extracellular vesicles from human blood using viscoelastic microfluidics
Authors: Meng Yingchao , Zhang Yanan , Bühler Marcel , Wang Shuchen , Asghari Mohammad , Stürchler Alessandra , Mateescu Bogdan , Weiss Tobias , Stavrakis Stavros , deMello Andrew J.
Published: October 2023

Small extracellular vesicles (sEVs; <200 nm) that contain lipids, nucleic acids, and proteins are considered promising biomarkers for a wide variety of diseases. Conventional methods for sEV isolation from blood are incompatible with routine clinical workflows, significantly hampering the utilization of blood-derived sEVs in clinical settings. Here, we present a simple, viscoelastic-based microfluidic platform for label-free isolation of sEVs from human blood. The separation performance of the device is assessed by isolating fluorescent sEVs from whole blood, demonstrating purities and recovery rates of over 97 and 87%, respectively. Significantly, our viscoelastic-based microfluidic method also provides for a remarkable increase in sEV yield compared to gold-standard ultracentrifugation, with proteomic profiles of blood-derived sEVs purified by both methods showing similar protein compositions. To demonstrate the clinical utility of the approach, we isolate sEVs from blood samples of 20 patients with cancer and 20 healthy donors, demonstrating that elevated sEV concentrations can be observed in blood derived from patients with cancer.
Turicibacterales protect mice from severe
Citrobacter rodentium
infection
Authors: Hoek Kristen L. , McClanahan Kathleen G. , Latour Yvonne L. , Shealy Nicolas , Piazuelo M. Blanca , Vallance Bruce A. , Byndloss Mariana X. , Wilson Keith T. , Olivares-Villagómez Danyvid
Published: October 2023

One of the major contributors to child mortality in the world is diarrheal diseases, with an estimated 800,000 deaths per year. Many pathogens are causative agents of these illnesses, including the enteropathogenic or enterohemorrhagic forms of
Escherichia coli
. These bacteria are characterized by their ability to cause attaching and effacing lesions in the gut mucosa. Although much has been learned about the pathogenicity of these organisms and the immune response against them, the role of the intestinal microbiota during these infections is not well characterized. Infection of mice with
E. coli
requires pre-treatment with antibiotics in most mouse models, which hinders the study of the microbiota in an undisturbed environment. Using
Citrobacter rodentium
as a murine model for attaching and effacing bacteria, we show that C57BL/6 mice deficient in granzyme B expression are highly susceptible to severe disease caused by
C. rodentium
infection. Although a previous publication from our group shows that granzyme B-deficient CD4
+
T cells are partially responsible for this phenotype, in this report, we present data demonstrating that the microbiota, in particular members of the order Turicibacterales, have an important role in conferring resistance. Mice deficient in
Turicibacter sanguinis
have increased susceptibility to severe disease. However, when these mice are co-housed with resistant mice or colonized with
T. sanguinis
, susceptibility to severe infection is reduced. These results clearly suggest a critical role for this commensal in the protection against enteropathogens.
Immunity induced by vaccination with recombinant influenza B virus neuraminidase protein breaks viral transmission chains in guinea pigs in an exposure intensity-dependent manner
Authors: McMahon Meagan , Tan Jessica , O'Dell George , Kirkpatrick Roubidoux Ericka , Strohmeier Shirin , Krammer Florian
Published: October 2023

Mucosal vaccines and vaccines that block pathogen transmission are under-appreciated in vaccine development. However, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has shown that blocking viral transmission is an important attribute of efficient vaccines. Here, we investigated if recombinant influenza virus neuraminidase (NA) vaccines delivered at a mucosal site could protect from onward transmission of influenza B viruses in the guinea pig model. We tested four different scenarios in which sequential transmission was investigated in chains of three to four guinea pigs. The variables tested included a low and a high viral inoculum (10
4
vs 10
5
plaque-forming units) in the initial donor guinea pig and variation of exposure/cohousing time (1 day vs 6 days). In three out of four scenarios—low inoculum-long exposure, low inoculum-short exposure, and high inoculum-short exposure—transmission chains were efficiently blocked. Based on this data, we believe an intranasal recombinant NA vaccine could be used to efficiently curtail influenza virus spread in the human population during influenza epidemics.

IMPORTANCE

Vaccines that can slow respiratory virus transmission in the population are urgently needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus. Here, we describe how a recombinant neuraminidase-based influenza virus vaccine reduces transmission in vaccinated guinea pigs in an exposure intensity-based manner.
An integrated nationwide genomics study reveals transmission modes of typhoid fever in China
Authors: Feng Ye , Pan Hang , Zheng Beiwen , Li Fang , Teng Lin , Jiang Zhijie , Feng Mengyao , Zhou Xiao , Peng Xianqi , Xu Xuebin , Wang Haoqiu , Wu Beibei , Xiao Yonghong , Baker Stephen , Zhao Guoping , Yue Min
Published: October 2023

Typhoid fever, caused by
Salmonella
Typhi (
S
. Typhi), is a life-threatening disease, usually food-borne and commonly associated with international travel. The disease transmission remains endemic in many low- and middle-income countries, representing further hotspots for seeding new global outbreaks. China has historically been affected by typhoid fever, but the respective roles of local transmission and importation remain unknown. Here, we generated a nationwide map of the typhoid burden in China and investigated the associations between typhoid disease, climate and various socioeconomic parameters. To assess transmission dynamics, we sub-sampled
S
. Typhi isolated within China over five decades and sequenced their genomes. The resulting 705 new genomes, placed in context with 5,190 global isolates from 87 countries on six continents, led to the discovery of several predominant inland Chinese clones belonging to the clades 2.1/2.3/3.2/4.3. These clones were associated with multiple introductions from overseas, followed by local expansion. Notably, 4.3.1 isolates from eastern China were not genetically close to those from northwestern China but to the international isolates, indicating their association with international travel. Additional
in vitro
assays showed that 4.3.1 elaborated better intracellular survival, acid tolerance, and desiccation tolerance than other lineages, partially explaining its success. For the first time, we have probed typhoid transmission in China, finding local transmission and importation, which could guide the policy for typhoid control.

IMPORTANCE

Typhoid fever is a life-threatening disease caused by
Salmonella enterica
serovar Typhi, resulting in a significant disease burden across developing countries. Historically, China was very much close to the global epicenter of typhoid, but the role of typhoid transmission within China and among epicenter remains overlooked in previous investigations. By using newly produced genomics on a national scale, we clarify the complex local and global transmission history of such a notorious disease agent in China spanning the most recent five decades, which largely undermines the global public health network.
Inbred SJL mice recapitulate human resistance to
Cryptococcus
infection due to differential immune activation
Authors: Davis M. J. , Martin R. E. , Pinheiro G. M. , Hoke E. S. , Moyer S. , Ueno K. , Rodriguez-Gil J. L. , Mallett M. A. , Khillan J. S. , Pavan W. J. , Chang Y. C. , Kwon-Chung K. J.
Published: October 2023

Cryptococcosis remains a significant threat to human health. While the popular C57BL/6J mouse model of cryptococcosis has some advantages, there are some serious shortcomings that limit the ability of researchers to address the disease. Since humans are resistant to environmental cryptococcal infection until rendered immunodeficient while C57BL/6J mice are innately susceptible, we screened 15 inbred mouse strains for resistance to
Cryptococcus
infection. The SJL/J mouse strain was unusually resistant to several virulent strains of
Cryptococcus
while the closely related FVB/J strain was susceptible. The infection pathobiology in SJL/J mice and susceptible mice was similar for the first 7–10 days then markedly diverged toward pathogen clearance. Interferon-gamma (IFN-γ) expression was critical for SJL/J resistance while tumor necrosis factor-alpha was also important. Both CD4 and CD8 T cells produced IFN-γ and were collectively critical. While IL-17 and associated cytokines were expressed in SJL/J mice, IL-17 inhibition did not affect the outcome of infection. Unlike the C57BL/6J, infected SJL/J mice failed to express Th2/atopy-type cytokines even when rendered susceptible by IFN-γ blockade or infection with an alternative fatal cryptococcal strain virulent in SJL/J. These data suggest that the atopic-type response typically associated with the C57BL/6J model is not critical for susceptibility. The productive immune response in SJL/J mice resulted in immune memory that protected mice from reinfection. The SJL/J cryptococcal resistance phenotype was associated with a strong genetic linkage from regions located in chromosomes 2 and 11 suggesting strain-specific modifiers contribute to disease severity. Thus, SJL/J mice are an exciting alternative animal model for cryptococcal pathobiology.

IMPORTANCE

Cryptococcosis studies often utilize the common C57BL/6J mouse model. Unfortunately, infection in these mice fails to replicate the basic course of human disease, particularly hampering immunological studies. This work demonstrates that SJL/J mice can recapitulate human infection better than other mouse strains. The immunological response to
Cryptococcus
infection in SJL/J mice was markedly different from C57BL/6J and much more productive in combating this infection. Characterization of infected mice demonstrated strain-specific genetic linkage and differential regulation of multiple important immune-relevant genes in response to
Cryptococcus
infection. While our results validate many of the previously identified immunological features of cryptococcosis, we also demonstrate limitations from previous mouse models as they may be less translatable to human disease. We concluded that SJL/J mice more faithfully recapitulate human cryptococcosis serving as an exciting new animal model for immunological and genetic studies.
Gene editing of
SAMHD1
in macrophage-like cells reveals complex relationships between SAMHD1 phospho-regulation, HIV-1 restriction, and cellular dNTP levels
Authors: Schüssler Moritz , Schott Kerstin , Fuchs Nina Verena , Oo Adrian , Zahadi Morssal , Rauch Paula , Kim Baek , König Renate
Published: October 2023

Sterile α motif and HD domain-containing protein 1 (SAMHD1) is a dNTP triphosphate triphosphohydrolase (dNTPase) and a potent restriction factor for immunodeficiency virus 1 (HIV-1), active in myeloid and resting CD4
+
T cells. The anti-viral activity of SAMHD1 is regulated by dephosphorylation of the residue T592. However, the impact of T592 phosphorylation on dNTPase activity is still under debate. Whether additional cellular functions of SAMHD1 impact anti-viral restriction is not completely understood. We report BLaER1 cells as a novel human macrophage HIV-1 infection model combined with CRISPR/Cas9 knock-in (KI) introducing specific mutations into the
SAMHD1
locus to study mutations in a physiological context. Transdifferentiated BLaER1 cells harbor active dephosphorylated SAMHD1 that blocks HIV-1 reporter virus infection. As expected, homozygous T592E mutation, but not T592A, relieved a block to HIV-1 reverse transcription. Co-delivery of VLP-Vpx to SAMHD1 T592E KI mutant cells did not further enhance HIV-1 infection indicating the absence of additional SAMHD1-mediated anti-viral activity independent of T592 dephosphorylation. T592E KI cells retained dNTP levels similar to WT cells indicating uncoupling of anti-viral and dNTPase activity of SAMHD1. The integrity of the catalytic site in SAMHD1 was critical for anti-viral activity, yet a poor correlation between HIV-1 restriction and global cellular dNTP levels was observed in cells harboring catalytic core mutations. Together, we emphasize the complexity of the relationship between HIV-1 restriction, SAMHD1 enzymatic function, and T592 phospho-regulation and provide novel tools for investigation in an endogenous and physiological context.

IMPORTANCE

We introduce BLaER1 cells as an alternative myeloid cell model in combination with CRISPR/Cas9-mediated gene editing to study the influence of sterile α motif and HD domain-containing protein 1 (SAMHD1) T592 phosphorylation on anti-viral restriction and the control of cellular dNTP levels in an endogenous, physiologically relevant context. A proper understanding of the mechanism of the anti-viral function of SAMHD1 will provide attractive strategies aiming at selectively manipulating SAMHD1 without affecting other cellular functions. Even more, our toolkit may inspire further genetic analysis and investigation of restriction factors inhibiting retroviruses and their cellular function and regulation, leading to a deeper understanding of intrinsic anti-viral immunity.
Whole-genome sequence of
Staphylococcus epidermidis
strain AH3, isolated from Nile tilapia (
Oreochromis niloticus
)
Authors: Al-Harbi Ahmed H.
Published: October 2023

The whole-genome sequence of
Staphylococcus epidermidis
strain AH3 isolated from moribund farmed Nile tilapia (
Oreochromis niloticus
) was performed using a combination of the Illumina and Pacific Biosciences (PacBio) sequencing platforms. The genome sequence is composed of a single chromosome of 2,464,380 bp with a GC content of 32.2% and 2,220 predicted protein-coding genes.
Geographical survey of the mycobiome and microbiome of Southern California glassy-winged sharpshooters
Authors: Ettinger Cassandra L. , Wu-Woods Jessica , Kurbessoian Tania , Brown Dylan J. , Souza Pacheco Inaiara de , Vindiola Beatriz G. , Walling Linda L. , Atkinson Peter W. , Byrne Frank J. , Redak Richard , Stajich Jason E.
Published: October 2023

The glassy-winged sharpshooter,
Homalodisca vitripennis
Germar, is an invasive xylem-feeding leafhopper with a devastating economic impact on California agriculture through transmission of the plant pathogen,
Xylella fastidiosa
. While studies have focused on
X. fastidiosa
or known symbionts of
H. vitripennis
, little work has been done at the scale of the microbiome (the bacterial community) or mycobiome (the fungal community). Here, we characterize the mycobiome and the microbiome of
H. vitripennis
across Southern California and explore correlations with captivity and host insecticide resistance status. Using high-throughput sequencing of the ribosomal internal transcribed spacer 1 region and the 16S rRNA gene to profile the mycobiome and microbiome, respectively, we found that while the
H. vitripennis
mycobiome significantly varied across Southern California, the microbiome did not. We also observed a significant difference in both the mycobiome and microbiome between captive and wild
H. vitripennis
. Finally, we found that the mycobiome, but not the microbiome, was correlated with insecticide resistance status in wild
H. vitripennis
. This study serves as a foundational look at the
H. vitripennis
mycobiome and microbiome across Southern California. Future work should explore the putative link between microbes and insecticide resistance status and investigate whether microbial communities should be considered in
H. vitripennis
management practices.

IMPORTANCE

The glassy-winged sharpshooter is an invasive leafhopper that feeds on the xylem of plants and transmits the devastating pathogen,
Xylella fastidiosa
, resulting in significant economic damage to California’s agricultural system. While studies have focused on this pathogen or obligate symbionts of the glassy-winged sharpshooter, there is limited knowledge of the bacterial and fungal communities that make up its microbiome and mycobiome. To address this knowledge gap, we explored the composition of the mycobiome and the microbiome of the glassy-winged sharpshooter across Southern California and identified differences associated with geography, captivity, and host insecticide resistance status. Understanding sources of variation in the microbial communities associated with the glassy-winged sharpshooter is an important consideration for developing management strategies to control this invasive insect. This study is a first step toward understanding the role microbes may play in the glassy-winged sharpshooter’s resistance to insecticides.
Identification of chronic wasting disease prions in decaying tongue tissues from exhumed white-tailed deer
Authors: Soto Paulina , Bravo-Risi Francisca , Benavente Rebeca , Lichtenberg Stuart , Lockwood Mitch , Reed J. Hunter , Morales Rodrigo
Published: October 2023

Chronic wasting disease (CWD) prions cause fatal neuropathies in farmed and free-ranging cervids. The deposition of prions in natural and humanmade environmental components has been implicated as a major mechanism mediating CWD spread in wild and captive populations. Prions can be deposited in the environment through excreta, tissues, and carcasses from pre-clinical and clinical animals. Furthermore, burial of CWD-positive animals may reduce but not completely mitigate prion spread from carcasses into the surrounding environment. Here, we analyzed exhumed, decaying deer carcasses for the presence of CWD prions. By analyzing tongue tissues through the protein misfolding cyclic amplification (PMCA) technique, we were able to identify seven out of 95 exhumed white-tailed deer carcasses as CWD prions carriers. Confirmatory analyses were performed using the real-time quaking-induced conversion (RT-QuIC) technique. In addition, we evaluated the potential contamination of the pens that housed these animals by swabbing feeders and waterers. PMCA analyses of swabs confirmed CWD contamination on farming equipment. This work demonstrates the usefulness of PMCA to detect CWD prions in a variety of contexts, including exhumed/decaying tissues. In addition, this is the first report demonstrating swabbing coupled with PMCA as a method for the detection of prion seeding activity on naturally exposed surfaces. Considering that this study was focused on a single site, further studies should confirm whether prion amplification assays are useful to identify CWD prions not only in animals but also in the environment that contains them.

IMPORTANCE

Environmental contamination is thought to be a major player in the spread of chronic wasting disease (CWD), a fatal prion disease affecting a wide variety of cervid species. At present, there are no officially approved methods allowing for the detection of prion infectivity in environmental components. Importantly, animal as well as anthropogenic activities are thought to contribute to prion environmental contamination. Here, we detected CWD prions in exhumed white-tailed deer carcasses by using the protein misfolding cyclic amplification (PMCA) assay. In addition, we identified CWD prions in feeders used within the infected facility. These results highlight the potential role of PMCA in identifying prion infectivity in a variety of scenarios, ranging from decaying tissues to farming equipment.
SarS and Rot are necessary for the repression of
lukED
and
lukSF-PV
in
Staphylococcus aureus
Authors: Anderson Exene E. , Ilmain Juliana K. , Torres Victor J.
Published: October 2023

Staphylococcus aureus
is an opportunistic pathogen that employs an array of different virulence factors to evade the immune system. The bi-component pore-forming leukocidins are of particular importance for their ability to target and kill phagocytes. The operon of two of these toxins,
lukED
and
lukSF-PV
, are repressed by two proteins, SarS and Rot. However, how these repressors work together to repress these toxins is not completely understood. Here, we determine that repression of leukocidins by SarS and Rot is not additive and that SarS and Rot are able to bind concurrently to the leukocidin promoters. In addition, in a tissue culture model using primary human neutrophils, the deletion of both repressors did not result in increased virulence compared to the single deletions of
sarS
and
rot
. Further experiments revealed that in an
in vivo
mouse infection model, virulence was similar in strains lacking one versus both repressors. Overall, these data show that while the repression of leukocidins by SarS and Rot is not additive, both proteins are critical for the repression of these toxins.

IMPORTANCE

The leukocidins play an important role in disarming the host immune system and promoting infection. While both SarS and Rot have been established as repressors of leukocidins, the importance of each repressor in infection is unclear. Here, we demonstrate that repression by SarS and Rot is not additive and show that in addition to upregulating expression of each other, they are also able to bind concurrently to the leukocidin promoters. These findings suggest that both repressors are necessary for maximal repression of
lukED
and
lukSF-PV
and illuminate another complex relationship among
Staphylococcus aureus
virulence regulators.
Bee wisdom: exploring bee control strategies for food microflora by comparing the physicochemical characteristics and microbial composition of beebread
Authors: Wang Ying , Ma Lanting , Xu Baohua
Published: October 2023

Beebread serves not only as a vital food source for bees but also as a significant reservoir of microbes for their intestinal tracts. The distribution of beebread in honeycomb cells is characterized by distinct vertical patterns; however, the vertical distribution patterns of the physicochemical characteristics and microbial composition of beebread remain unclear. In this study, we collected beebread samples from nine colonies in three representative ecosystems (forest, forest-urban, and urban-farmland ecosystems) and systematically assessed the physicochemical characteristics and bacterial diversity in three beebread layers (lower, middle, and upper). We found that upper beebread samples had lower pH; higher proportions of fructose and sucrose; and lower proportions of total solids, crude protein, and ash compared to lower samples. Moreover, 16S rDNA sequencing showed that the dominant bacterial phyla and genera were relatively simple and highly conserved across the three ecosystems. Overall, the microbial community richness of upper beebread was significantly higher than that of lower beebread, and Bacteroidetes and Acidobacteria were significantly decreased in lower compared to upper beebread. Meanwhile, the relative abundance of dominant taxa in the same beebread layer differed by ecosystem types. These findings suggest that bees employ fermentation processes to selectively enrich microbes present in flower pollen, leading to homogenous and relatively stable microbial diversity in beebread. Our study expands on the current understanding of beebread and highlights the significance of fermentation in its production. Furthermore, our findings provide a useful reference for further in-depth exploration of the interactions between food, food microbes, and bee gut microbes.

IMPORTANCE

Bees are a valuable model for investigating the relationship between environmental factors, gut microbiota, and organismal health. Beebread, produced from collected pollen, is a natural food source and a primary reservoir of gut microorganisms. Although pollen typically has diverse bacterial species, beebread has low species richness and bacterial abundance. Consequently, considerable attention has been paid to the adaptive strategies employed by honey bees to cope with the microorganisms within their food environment during co-evolution with plants. This study identified the distribution patterns of beebread's physicochemical characteristics, showing how bees use fermentation to enrich specific microbes. These findings help understand the relationship between environmental and food-associated microbes and bee intestinal microbiota. They also bridge gaps in the literature and provide a valuable reference for studying the complex interplay between these factors.
Salmonella
Derby adaptation to swine and simultaneous attenuation for humans go through decay of
Salmonella
Pathogenicity Island I
Authors: Berni Melissa , Bolzoni Luca , Menozzi Ilaria , Dodi Alessandra , Bracchi Chiara , Morganti Marina , Scaltriti Erika , Pongolini Stefano , Tambassi Martina
Published: October 2023

We report the identification, within the global population of
Salmonella
Derby, of a lineage highly diffused and expanding in swine while being significantly under-represented in humans which carries stop mutations in the Salmonella Pathogenicity Island 1 (SPI-1) genes
sipA
and
hilC
. Single-cell analysis of invasion, vacuolar load, and cytosolic hyper-replication show that these mutations attenuate
S
. Derby virulence in human intestinal cells. Identification of this lineage follows the previous detection of another lineage over-represented in swine compared with humans which carries a loss-of-function mutation in
hilD
, the major SPI-1 regulator, responsible for reduced infection of human cells. Notably, this
hilD
-mutated lineage represents a sub-population of the wider
sipA
and
hilC-
mutated lineages identified in this study, indicating that SPI-1 is subjected to genetic decay in this part of the
Salmonella
Derby population adapted to swine. Virulence assessment on swine intestinal cells showed drastically lower levels for both wild-type and mutant
S
. Derby compared with human cells. Still,
S
. Derby with impaired
sipA
and
hilC
showed further attenuation also in swine cells compared with the wild type. These data suggest that invasion of swine intestinal epithelium is not needed by
S
. Derby to circulate in pigs, leading to the decay of SPI-1, which in turn determines attenuation for humans. Accordingly, a further
S
. Derby lineage under-represented in humans compared with pigs was found carrying truncated or missing SPI-1 genes, indicating that the
S
. Derby population is undergoing converging evolution in its adaptation to swine while attenuating for humans through loss of SPI-1 function.

IMPORTANCE

This study integrated population data with
in vitro
assessment of virulence phenotypes to unveil that a considerable part of the global population of
Salmonella
Derby is evolving to enhance its host adaptation to the swine host and that this evolution is simultaneously increasing its attenuation for humans. The study shows that the fixation of deleterious mutations in SPI-1 has a role in this process. This evidence indicates that SPI-1 has a key role for
S
. Derby virulence in humans but not for its circulation in swine. The results show that genes generally considered essential for
Salmonella
pathogenesis do not play the same key role for all
Salmonella
serovars or lineages and/or all hosts. The study helps in understanding the molecular mechanisms underlying the ecology and host adaptation of
Salmonella
showing that the adaptation process can vary for different types of
Salmonella
and hosts.
Mycobacteriophage D29 Lysin B exhibits promising anti-mycobacterial activity against drug-resistant
Mycobacterium tuberculosis
Authors: Singh Amit Kumar , Gangakhedkar Rutuja , Thakur Hemant Singh , Raman Sunil Kumar , Patil Shripad A. , Jain Vikas
Published: October 2023

The emergence of antibiotic resistance in
Mycobacterium tuberculosis
has been the culprit behind the inefficient treatment of tuberculosis (TB). Mycobacteriophages being rapid and specific in their activity against mycobacteria including
M. tuberculosis
are an emerging alternative solution to the antibiotic resistance problem. D29 mycobacteriophage is known as an efficient lytic phage. Its lytic cassette encodes for two lytic proteins, Lysin A (LysA) and Lysin B (LysB), and a holin protein responsible for the translocation of the former two. LysB is a mycolyl-arabinogalactan esterase, which has shown a promising lytic effect on
M. tuberculosis
. In this study, we explored the lytic efficiency of D29 mycobacteriophage LysB protein on drug-resistant strains of
M. tuberculosis
. We demonstrate that LysB effectively lyses multi-drug-resistant
M. tuberculosis
both alone and along with anti-TB drugs. We also report that the surfactant Tween-80, although not vital, potentiates LysB activity. We are able to demonstrate that LysB can eliminate
M. tuberculosis
residing in mouse macrophages. Thus, by combining our
in vitro
and
ex vivo
data, we are able to claim that LysB is a potential phage-derived therapeutic which should undergo pre-clinical and clinical trials.

IMPORTANCE

To combat the rapidly emerging drug-resistant
M. tuberculosis
, it is now essential to look for alternative therapeutics. Mycobacteriophages can be considered as efficient therapeutics due to their natural ability to infect and kill mycobacteria including
M. tuberculosis
. Here, we have exploited the mycolyl-arabinogalactan esterase property of LysB encoded from mycobacteriophage D29. This study is novel in terms of targeting a multi-drug-resistant pathogenic strain of
M. tuberculosis
with LysB and also examining the combination of anti-TB drugs and LysB. All the experiments include external administration of LysB. Therefore, the remarkable lytic activity of LysB overcomes the difficulty to enter the complex cell envelope of mycobacteria. Targeting the intracellularly located
M. tuberculosis
by LysB and non-toxicity to macrophages take the process of the development of LysB as a drug one step ahead, and also, the interaction studies with rifampicin and isoniazid will help to form a new treatment regimen against tuberculosis.
Developing an Interferometric Method for Measuring the Transverse Dimensions of a Particle Beam in Cyclic Accelerators
Authors: Dorokhov V. L. , Meshkov O. I. , Styrin A. I. , Smygachev A. S.
Published: October 2023

This work is devoted to the development of a method for measuring beam sizes in cyclic charged particle accelerators using an interferometer based on the Young scheme with a double-slit diaphragm. We have carried out an experimental verification of the original spectral method for scanning the interference pattern. The results of measurements of the spectrum of low-frequency oscillations of the beam of the storage ring of the Kurchatov Synchrotron Radiation Source (KSRS) obtained by means of the Optical Observation Station (OOS) of the storage ring are presented.
Possible evidence for the production of Ar$$_2^{*-}$$ metastable negative molecular ions in gaseous argon of two-phase detectors for dark matter searches
Authors: Buzulutskov A. , Frolov E. , Borisova E. , Nosov V. , Oleynikov V. , Sokolov A.
Published: October 2023

Our recent studies of electroluminescence (EL) properties in two-phase argon detectors for dark matter searches have revealed the presence of unusual delayed pulses in the EL signal in the form of two slow components with time constants of about 5 and 50 $$\upmu \text {s}$$

μ
s

. These components were shown to be present in the charge signal itself, which clearly indicates that drifting electrons are temporarily trapped on two states of metastable negative argon ions which have never been observed before. In this work, using the pressure dependence of the ratio of slow component contributions measured in experiment, it is deduced that these states are those of two types of metastable negative molecular ions, $${{\textrm{Ar}}}_2^{*-}(b \ ^4\varSigma _u^-)$$

Ar
2

∗
-

(
b

4

Σ
u
-

)

and $${{\textrm{Ar}}}_2^{*-}(a \ ^4\varSigma _g^+)$$

Ar
2

∗
-

(
a

4

Σ
g
+

)

for the higher and lower energy level respectively.