bluuebunny/crossref_metadata_2025 huggingface dataset:
GFAP serves as a structural element of tunneling nanotubes between glioblastoma cells and could play a role in the intercellular transfer of mitochondria
Authors: Simone L. , Capobianco D. L. , Di Palma F. , Binda E. , Legnani F. G. , Vescovi A. L. , Svelto M. , Pisani F.
Published: October 2023

Tunneling nanotubes (TNTs) are long F-actin-positive plasma membrane bridges connecting distant cells, allowing the intercellular transfer of cellular cargoes, and are found to be involved in glioblastoma (GBM) intercellular crosstalk. Glial fibrillary acid protein (GFAP) is a key intermediate filament protein of glial cells involved in cytoskeleton remodeling and linked to GBM progression. Whether GFAP plays a role in TNT structure and function in GBM is unknown. Here, analyzing F-actin and GFAP localization by laser-scan confocal microscopy followed by 3D reconstruction (3D-LSCM) and mitochondria dynamic by live-cell time-lapse fluorescence microscopy, we show the presence of GFAP in TNTs containing functional mitochondria connecting distant human GBM cells. Taking advantage of super-resolution 3D-LSCM, we show the presence of GFAP-positive TNT-like structures in resected human GBM as well. Using H2O2 or the pro-apoptotic toxin staurosporine (STS), we show that GFAP-positive TNTs strongly increase during oxidative stress and apoptosis in the GBM cell line. Culturing GBM cells with STS-treated GBM cells, we show that STS triggers the formation of GFAP-positive TNTs between them. Finally, we provide evidence that mitochondria co-localize with GFAP at the tip of close-ended GFAP-positive TNTs and inside receiving STS-GBM cells. Summarizing, here we found that GFAP is a structural component of TNTs generated by GBM cells, that GFAP-positive TNTs are upregulated in response to oxidative stress and pro-apoptotic stress, and that GFAP interacts with mitochondria during the intercellular transfer. These findings contribute to elucidate the molecular structure of TNTs generated by GBM cells, highlighting the structural role of GFAP in TNTs and suggesting a functional role of this intermediate filament component in the intercellular mitochondria transfer between GBM cells in response to pro-apoptotic stimuli.
Dendritic cells in liver transplantation immune response
Authors: Du Xiaodong , Li Mingqian , Huan Chen , Lv Guoyue
Published: October 2023

Dendritic cells (DCs) are the most powerful antigen presenting cells (APCs), they are considered one of the key regulatory factors in the liver immune system. There is currently much interest in modulating DC function to improve transplant immune response. In liver transplantation, DCs participate in both the promotion and inhibition of the alloreponse by adopting different phenotypes and function. Thus, in this review, we discussed the origin, maturation, migration and pathological effects of several DC subsets, including the conventional DC (cDC), plasmacytoid DC (pDC) and monocyte-derived DC (Mo-DC) in liver transplantation, and we summarized the roles of these DC subsets in liver transplant rejection and tolerance. In addition, we also outlined the latest progress in DC-based related treatment regimens. Overall, our discussion provides a beneficial resource for better understanding the biology of DCs and their manipulation to improve the immune adaptability of patients in transplant status.
Occurrence and characterization of plasmids carrying tmexCD1-toprJ1, blaDHA-1, and blaCTX-M-127, in clinical Klebsiella pneumoniae strains
Authors: Qu Ying , Wang Wenji , Lu Qinhong , Qiu Jihai , Wang Dongguo , Ma Liman
Published: October 2023

Objective

Today, the emergence of Klebsiella pneumoniae with the tmexCD1-toprJ1 gene cassette in patients has presented a significant clinical challenge.

Methods

To present the detailed genetic features of the tmexCD1-toprJ1 gene cassette of K. pneumoniae strain F4_plasmid pA, the whole bacterial genome was sequenced by Illumina and nanopore platforms, and mobile genetic elements related to antibiotic resistance genes were analyzed with a series of bioinformatics methods.

Results

K. pneumoniae strain F4 was determined to be a class A+C beta-lactamase, and was resistant to routinely used antibiotics, especially tigecycline, because of the oqxAB gene localized on the F4_chromosome and tmexCD1-toprJ1 on F4_plasmid A. After plasmid transfer assays, the F4_plasmid pA or F4_plasmid pB could be recovered with an average conjugation frequencies of 3.42×10-4 or 4.19×10-4. F4_plasmid pA carried tmexCD1-toprJ1 and blaDHA-1 accompanied by genetic intermixing of TnAs1, Tn5393, TnAs3, and In641, while F4_plasmid pB, bearing blaCTX-M-174, had structural overlap of TnAs3 and In641.

Conclusions

We suggested that plasmids carrying tmexCD1- toprJ1 might be strongly related to IS26-integrated loop intermediates. This study showed that due to the structural evolution of F4 and related strains, their resistances were so strong that effective antibiotics were virtually unavailable, therefore their spread and prevalence should be strictly controlled.
Analysis of the gut microbiota in children with gastroesophageal reflux disease using metagenomics and metabolomics
Authors: Ye Xiaolin , Yu Feihong , Zhou Jin , Zhao Chunna , Wu Jie , Ni Xin
Published: October 2023

Background

There is no direct evidence of gut microbiota disturbance in children with gastroesophageal reflux disease (GERD). This study aimed to provide direct evidence and a comprehensive understanding of gut microbiota disturbance in children with GERD through combined metagenomic and metabolomic analysis.

Methods

30 children with GERD and 30 healthy controls (HCs) were continuously enrolled, and the demographic and clinical characteristics of the subjects were collected. First, 16S rRNA sequencing was used to evaluate differences in the gut microbiota between children with GERD and HC group, and 10 children with GERD and 10 children in the HC group were selected for metagenomic analysis. Nontargeted metabolomic analysis was performed using liquid chromatography/mass spectrometry (LC/MS), and metagenomic and metabolomic data were analyzed together.

Results

There were significant differences in the gut microbiota diversity and composition between children with GERD and HCs. The dominant bacteria in children with GERD were Proteobacteria and Bacteroidota. At the species level, the top three core bacterial groups were Bacteroides stercoris, Bacteroides vulgatus and Alistipes putredinis. The main differential pathways were identified to be related to energy, amino acid, vitamin, carbohydrate and lipid metabolism. LC/MS detected 288 different metabolites in the positive and negative ion modes between children with GERD and HCs, which were mainly involved in arachidonic acid (AA), tyrosine, glutathione and caffeine metabolism.

Conclusion

This study provides new evidence of the pathogenesis of GERD. There are significant differences in the gut microbiota, metabolites and metabolic pathways between HCs and children with GERD, and the differences in metabolites are related to specific changes in bacterial abundance. In the future, GERD may be treated by targeting specific bacteria related to AA metabolism.
Uneven transmission of traditional knowledge and skills in a changing wildmeat system: Yangambi, Democratic Republic of Congo
Authors: Shephard Samuel , Muhindo Jonas , Nyumu Jonas , Mbangale Emmanuela , Nziavake Sagesse , Cerutti Paolo , van Vliet Nathalie
Published: October 2023

Introduction

Indigenous communities typically hold diverse traditional ecological knowledge (TEK) of their social-ecological system. Much of this knowledge is embodied as skills related to subsistence practices within a specific landscape and is associated with community values and norms. Ways of knowing often reflect the different activities traditionally undertaken by men and women. The incursion of external forces, including urbanization, the cash economy and migration tends to diminish transmission of traditional embodied skills. Knowledge can be lost as culturally significant environments degrade or species become extirpated. Lack of opportunity to develop traditional knowledge and skills can diminish feelings of place and identity, and thus capacity for local environmental stewardship.

Methods

The Yangambi region, Democratic Republic of Congo is a hunting territory of the Turumbu ethnic group. We used questionnaires to explore how levels of wildmeat knowledge and skill may have changed over time among the Turumbu.

Results

The responses showed lower levels of self-reported skill among women who started to participate in the last 10-15 years. This pattern partly reflects the period of ‘apprenticeship’ but may also suggest diminished learning opportunity in recent years. Skills in cooking, smoking, and selling wildmeat persisted at a higher level than skills in curing disease and gathering wild produce. There was a much more marked pattern for men, with diminishing levels of wildmeat skill reported for around 35-40 years, and even earlier for knowledge of traditional medicine and wildmeat taboos. Questions about mentoring suggested that women have maintained knowledge pathways between mother and daughter, while men showed a shift toward increased learning from uncles.

Discussion

Gender differences in sharing and learning TEK may be linked to the type of skills that remain valuable in a changing social, ecological, and economic context. Men traditionally undertake the capture elements of hunting, while women deal with wildmeat processing, marketing, and cooking. The Yangambi wildmeat system has evolved from subsistence to a strongly market-driven economy during the lifetime of our study participants. This shift may partly explain why market-based kills such as food smoking and selling have endured longer than hunter’s nature-based knowledge.
Automated segmentation of 3D cine cardiovascular magnetic resonance imaging
Authors: Tayebi Arasteh Soroosh , Romanowicz Jennifer , Pace Danielle F. , Golland Polina , Powell Andrew J. , Maier Andreas K. , Truhn Daniel , Brosch Tom , Weese Juergen , Lotfinia Mahshad , van der Geest Rob J. , Moghari Mehdi H.
Published: October 2023

Introduction

As the life expectancy of children with congenital heart disease (CHD) is rapidly increasing and the adult population with CHD is growing, there is an unmet need to improve clinical workflow and efficiency of analysis. Cardiovascular magnetic resonance (CMR) is a noninvasive imaging modality for monitoring patients with CHD. CMR exam is based on multiple breath-hold 2-dimensional (2D) cine acquisitions that should be precisely prescribed and is expert and institution dependent. Moreover, 2D cine images have relatively thick slices, which does not allow for isotropic delineation of ventricular structures. Thus, development of an isotropic 3D cine acquisition and automatic segmentation method is worthwhile to make CMR workflow straightforward and efficient, as the present work aims to establish.

Methods

Ninety-nine patients with many types of CHD were imaged using a non-angulated 3D cine CMR sequence covering the whole-heart and great vessels. Automatic supervised and semi-supervised deep-learning-based methods were developed for whole-heart segmentation of 3D cine images to separately delineate the cardiac structures, including both atria, both ventricles, aorta, pulmonary arteries, and superior and inferior vena cavae. The segmentation results derived from the two methods were compared with the manual segmentation in terms of Dice score, a degree of overlap agreement, and atrial and ventricular volume measurements.

Results

The semi-supervised method resulted in a better overlap agreement with the manual segmentation than the supervised method for all 8 structures (Dice score 83.23 ± 16.76% vs. 77.98 ± 19.64%; P-value ≤0.001). The mean difference error in atrial and ventricular volumetric measurements between manual segmentation and semi-supervised method was lower (bias ≤ 5.2 ml) than the supervised method (bias ≤ 10.1 ml).

Discussion

The proposed semi-supervised method is capable of cardiac segmentation and chamber volume quantification in a CHD population with wide anatomical variability. It accurately delineates the heart chambers and great vessels and can be used to accurately calculate ventricular and atrial volumes throughout the cardiac cycle. Such a segmentation method can reduce inter- and intra- observer variability and make CMR exams more standardized and efficient.
Ensemble learning of myocardial displacements for myocardial infarction detection in echocardiography
Authors: Nguyen Tuan , Nguyen Phi , Tran Dai , Pham Hung , Nguyen Quang , Le Thanh , Van Hanh , Do Bach , Tran Phuong , Le Vinh , Nguyen Thuy , Tran Long , Pham Hieu
Published: October 2023

Background

Early detection and localization of myocardial infarction (MI) can reduce the severity of cardiac damage through timely treatment interventions. In recent years, deep learning techniques have shown promise for detecting MI in echocardiographic images. Existing attempts typically formulate this task as classification and rely on a single segmentation model to estimate myocardial segment displacements. However, there has been no examination of how segmentation accuracy affects MI classification performance or the potential benefits of using ensemble learning approaches. Our study investigates this relationship and introduces a robust method that combines features from multiple segmentation models to improve MI classification performance by leveraging ensemble learning.

Materials and Methods

Our method combines myocardial segment displacement features from multiple segmentation models, which are then input into a typical classifier to estimate the risk of MI. We validated the proposed approach on two datasets: the public HMC-QU dataset (109 echocardiograms) for training and validation, and an E-Hospital dataset (60 echocardiograms) from a local clinical site in Vietnam for independent testing. Model performance was evaluated based on accuracy, sensitivity, and specificity.

Results

The proposed approach demonstrated excellent performance in detecting MI. It achieved an F1 score of 0.942, corresponding to an accuracy of 91.4%, a sensitivity of 94.1%, and a specificity of 88.3%. The results showed that the proposed approach outperformed the state-of-the-art feature-based method, which had a precision of 85.2%, a specificity of 70.1%, a sensitivity of 85.9%, an accuracy of 85.5%, and an accuracy of 80.2% on the HMC-QU dataset. On the external validation set, the proposed model still performed well, with an F1 score of 0.8, an accuracy of 76.7%, a sensitivity of 77.8%, and a specificity of 75.0%.

Conclusions

Our study demonstrated the ability to accurately predict MI in echocardiograms by combining information from several segmentation models. Further research is necessary to determine its potential use in clinical settings as a tool to assist cardiologists and technicians with objective assessments and reduce dependence on operator subjectivity. Our research codes are available on GitHub at https://github.com/vinuni-vishc/mi-detection-echo.
A blind convolutional deep autoencoder for spectral unmixing of hyperspectral images over waterbodies
Authors: Alfaro-Mejía Estefanía , Manian Vidya , Ortiz Joseph D. , Tokars Roger P.
Published: October 2023

Harmful algal blooms have dangerous repercussions for biodiversity, the ecosystem, and public health. Automatic identification based on remote sensing hyperspectral image analysis provides a valuable mechanism for extracting the spectral signatures of harmful algal blooms and their respective percentage in a region of interest. This paper proposes a new model called a non-symmetrical autoencoder for spectral unmixing to perform endmember extraction and fractional abundance estimation. The model is assessed in benchmark datasets, such as Jasper Ridge and Samson. Additionally, a case study of the HSI2 image acquired by NASA over Lake Erie in 2017 is conducted for extracting optical water types. The results using the proposed model for the benchmark datasets improve unmixing performance, as indicated by the spectral angle distance compared to five baseline algorithms. Improved results were obtained for various metrics. In the Samson dataset, the proposed model outperformed other methods for water (0.060) and soil (0.025) endmember extraction. Moreover, the proposed method exhibited superior performance in terms of mean spectral angle distance compared to the other five baseline algorithms. The non-symmetrical autoencoder for the spectral unmixing approach achieved better results for abundance map estimation, with a root mean square error of 0.091 for water and 0.187 for soil, compared to the ground truth. For the Jasper Ridge dataset, the non-symmetrical autoencoder for the spectral unmixing model excelled in the tree (0.039) and road (0.068) endmember extraction and also demonstrated improved results for water abundance maps (0.1121). The proposed model can identify the presence of chlorophyll-a in waterbodies. Chlorophyll-a is an essential indicator of the presence of the different concentrations of macrophytes and cyanobacteria. The non-symmetrical autoencoder for spectral unmixing achieves a value of 0.307 for the spectral angle distance metric compared to a reference ground truth spectral signature of chlorophyll-a. The source code for the proposed model, as implemented in this manuscript, can be found at https://github.com/EstefaniaAlfaro/autoencoder_owt_spectral.git.
The Fourth Industrial Revolution in South Africa’s basic education: a search for cogent curriculum justice
Authors: Sehlako Nothando , Chibambo Mackenzie Ishmael , Divala Joseph Jinja
Published: October 2023

This study sought to examine how the Fourth Industrial Revolution (4IR) has promulgated curriculum (in) justices within basic education contexts in South Africa. Utilizing qualitative methods, we interviewed fifteen students and three teachers from three selected schools and one ICT district manager representing the Gauteng Education Zone in Johannesburg. We also deployed critical interpretivism to analyze the documents and the responses from the research subjects in order to explain how the ideologies related to use of 4IR and its roles in education had helped create and sustain curriculum (in) justices in South Africa. We mainly used Ideal Utilitarianism by George Moore, Justice as Fairness by John Rawls, and the Technology Acceptance Model by Fred Davis as key theoretical frameworks for analyzing 4IR within educational contexts. Key findings showed that 4IR has hugely sorted, stratified and unequalized rural-poor students more than it has done with the rich students especially at the basic education level. Essentially, the benefits highlighted by some respondents, particularly teachers, could not help offset the injustices and damages 4IR had unleashed upon the marginalized groups of students at this level. While acknowledging that 4IR was irreversible at this point – since it was now part of human life – we recommended that DBE should judiciously revisit the 4IR policy governing the Operation Phakisa Initiative (OPI), by instituting different support systems that will ensure provision of an equitable and just 4IR aided education for everybody. One such supports, but not limited to that, was provision of consistent capacity building trainings for the schools and society.
Association between sarcopenia-related traits and cardiovascular diseases: a bi-directional Mendelian randomization study
Authors: Liu Xu , Wang Yunjie , Wang Zhaojun , Li Lingzhi , Yang Haibo , Liu Juncai , Li Zhong
Published: October 2023

Background

The two geriatric diseases, sarcopenia and cardiovascular disease (CVD), often coexist, yet the causal relationship is unclear. However, few studies focus on the effect of muscle mass on CVD. This comprehensive study is dedicated to unearthing the potential connection between sarcopenia-related traits and CVD at the genetic level.

Method

A two-sample bi-directional Mendelian randomization (MR) study was conducted. In the first stage, we performed MR analysis regarding coronary heart disease (CHD), stroke, and myocardial infarction (MI) as exposure factors to reveal their effect on appendicular lean mass (ALM) and hand grip strength. In the second stage, we reverse the position of exposures and outcomes. The inverse variance weighted (IVW) method was used as the primary approach to reveal the potential causation between the exposure and outcome.

Results

The results of the IVW method revealed a negative causal effect of ALM on CHD (OR = 0.848, 95% CI = 0.804 to 0.894, p = 8.200E-10), stroke (OR = 0.931, 95% CI = 0.890 to 0.975, p = 2.220E-03), and MI (OR = 0.810, 95% CI = 0.694 to 0.901, p = 1.266E-13). Additionally, the left-hand grip strength is a significant protective factor for CHD (OR = 0.737, 95% CI = 0.601 to 0.904, p = 3.353E-03) and MI (OR = 0.631, 95% CI = 0.515 to 0.765, p = 2.575E-06), but is not causally linked to the stroke (OR = 0.971, 95% CI =0.829 to 1.139, p = 0.720). Meanwhile, the same conclusion about the effect of right-hand grip strength on CHD (OR = 0.681, 95% CI = 0.558 to 0.832, p = 1.702E-05), MI (OR = 0.634, 95% CI = 0.518 to 0.776, p = 9.069E-06), and stroke (OR = 1.041, 95% CI = 0.896 to 1.209, p = 0.604) was obtained. However, no significant causal effect of CVD (CHD, stroke, MI) on sarcopenia-related traits (ALM, handgrip strength) was found.

Conclusion

There is a unidirectional causal relationship between sarcopenia and CVD. The loss of muscle mass and strength has a significant causal role in promoting the occurrence and development of CVD, providing a reference for the prevention and treatment of comorbidities in older people.
Advances in mitochondria-centered mechanism behind the roles of androgens and androgen receptor in the regulation of glucose and lipid metabolism
Authors: Yin Lijun , Qi Shuo , Zhu Zhiqiang
Published: October 2023

An increasing number of studies have reported that androgens and androgen receptors (AR) play important roles in the regulation of glucose and lipid metabolism. Impaired glucose and lipid metabolism and the development of obesity-related diseases have been found in either hypogonadal men or male rodents with androgen deficiency. Exogenous androgens supplementation can effectively improve these disorders, but the mechanism by which androgens regulate glucose and lipid metabolism has not been fully elucidated. Mitochondria, as powerhouses within cells, are key organelles influencing glucose and lipid metabolism. Evidence from both pre-clinical and clinical studies has reported that the regulation of glucose and lipid metabolism by androgens/AR is strongly associated with the impact on the content and function of mitochondria, but few studies have systematically reported the regulatory effect and the molecular mechanism. In this paper, we review the effect of androgens/AR on mitochondrial content, morphology, quality control system, and function, with emphases on molecular mechanisms. Additionally, we discuss the sex-dimorphic effect of androgens on mitochondria. This paper provides a theoretical basis for shedding light on the influence and mechanism of androgens on glucose and lipid metabolism and highlights the mitochondria-based explanation for the sex-dimorphic effect of androgens on glucose and lipid metabolism.
Natural disasters and energy innovation: unveiling the linkage from an environmental sustainability perspective
Authors: Ahmed Nihal , Ore Areche Franklin , Saenz Arenas Esther Rosa , Cosio Borda Ricardo Fernando , Javier-Vidalón Jorge L. , Silvera-Arcos Susan , Ober Józef , Kochmańska Anna
Published: October 2023

Natural disasters, characterized by their escalating frequency and intensification, fueled relentlessly by the inexorable forces of climate change, unambiguously underscore the urgent need to reassess our built environments and meticulously revise infrastructure design to withstand the unforgiving onslaught of these extreme events, thereby demanding concerted attention and unwavering dedication from policymakers and academic researchers to navigate this formidable predicament. The current study delves into the exploration of how natural disaster impact the course of energy technology evolution. To achieve this, This investigation uses panel data from 1990–2020 and sophisticated econometric analyses to model the effect of calamities on energy technology advancement across BRICS countries. Rigorous empirical methodologies lend credibility regarding the observed detrimental impact of disasters on innovation. The preliminary findings of the investigation suggest that natural disasters potentially exert a markedly detrimental effect on energy technology innovation. This influence is not merely confined to the year of the disaster occurrence but persistently lingers for the subsequent 4-year period. Moreover, the adverse impacts of such environmental upheavals on energy evolution seem to be mitigated by various factors. These include robust economic growth, government stability, interpersonal globalization, financial openness, trade openness, and the expansion of social globalisation. Adding further dimension to this research is the understanding that epidemics have the most pronounced negative implications on energy innovation. Concluding on a nuanced note, the study underscores a significant inverse relationship between natural disasters and low-carbon energy innovation. Interestingly, however, there is no discernible correlation when it comes to non-low carbon energy innovation. In a nutshell, this research presents a potential reference guide for policymakers, illuminating pathways to enhance the degree of energy innovation while tackling natural disasters and ensuring environmental sustainability.
Optimizing direct power control of DFIG-based WECS using super-twisting algorithm under real wind profile
Authors: Hadoune Aziz , Mouradi Abderrahman , Mimet Abdelaziz , Chojaa Hamid , Dardabi Chaimae , Gulzar Muhammad Majid , Alqahtani Mohammed , Khalid Muhammad
Published: October 2023

In this study, we address the optimization of the direct power control of a doubly fed induction generator within a wind conversion system under actual wind conditions. The primary objective is to enhance the dynamic response of the wind energy conversion system (WECS) while minimizing the impact of wind fluctuations on power generation. To achieve this goal, we introduce a novel control methodology based on the super-twisting algorithm (STA). This approach allows for effective regulation of both reactive and active power output in the WECS. We employ comprehensive simulations using a detailed model of the WECS and real wind profiles to evaluate the efficacy of the STA-based control strategy. Our simulations demonstrate that the adopted STA-based control strategy successfully tracks the desired power set-point and effectively mitigates the adverse effects of wind power fluctuations and uncertainties on the WECS power output. Specifically, it exhibits superior performance in managing transients and rejecting disturbances compared to a conventional approach employing a switching table and hysteresis controller. These results suggest the practical viability and potential applications of the STA-based control strategy in real-world wind energy systems.
Supply chain control tower and the adoption of intelligent dock booking for improving efficiency
Authors: Wyciślak Sławomir , Pourhejazy Pourya
Published: October 2023

Poor coordination at distribution centers is a prime source of supply chain delays and energy waste that can be avoided through real-time planning and enhanced visibility. As a modern logistics topic with implications for supply chain transformation, Intelligent Dock Booking (IDB) coordinates the incoming and outgoing shipments at distribution centers. The research on IDB is at the early development stage. This study contributes to the Supply Chain Control Tower (SCCT) by developing a conceptual model of IDB, identifying its implementation requirements, and exploring its impacts on the supply chain performance. The causal loops and stock/flow diagrams are used to investigate how several efficiency indicators like the number of cancellations, planning time, utilization of space for loading and unloading, and the duration of processing trucks at distribution centers can be improved. Further, real-time data integration, operational preconditions, automated scheduling, dynamic responsiveness, and interdepartmental integration are identified as the key implementation requirements. The findings provide a foundation for implementing IDB systems in SCCTs.
Use and effectiveness of wildlife exits designed for ocelots and other mesocarnivores on a south Texas highway
Authors: Sheikh Zarina N. , Langbein Jamie E. , Ryer Kevin , Rahman Md Saydur , Gabler Christopher A. , Young John H. , Kline Richard J.
Published: October 2023

Movement is a key component of survival and reproduction, often causing wildlife to cross heavily trafficked highways, resulting in road mortalities by oncoming vehicles. Fencing and crossing structures are commonly regarded as effective mitigation structures to reduce these mortalities. In south Texas, ten wildlife exits (WE) were installed along State Highway 100 in conjunction with existing mitigation structures to provide the US endangered ocelot (Leopardus pardalis), a medium-sized spotted wild cat, a safe option to escape the right of way (ROW). The objectives of this study were to determine the effectiveness and species usage and to estimate the percentage of wildlife that crossed back into the habitat via a WE. Camera traps were used for monitoring with one on the roadside and one on the habitat side of each WE and ten at adjacent right-of-way (ROW) sites. Entry and exit rates through WE were calculated to determine where wildlife was entering and exiting the roadway. The total number of individuals for each target species was counted for all entries (H-R) and exits (R-H) at any mitigation structure within 200 m of an exit and was compared to those using a WE. Results showed that ten species – jackrabbit (Lepus californicus), bobcat (Lynx rufus), coyote (Canis latrans), domestic cat (Felis catus), cottontail (Sylvilagus floridanus), skunk (Mephitis mephitis), raccoon (Procyon lotor), opossum (Didelphis virginiana), armadillo (Dasypus novemcinctus), and weasel (Mustela frenata) – used a WE to return to the habitat. Coyote and bobcat usage at WE increased over time, with bobcats first exhibiting usage within 30 days while coyotes first used WE at 180 days. PERMANOVA showed significantly different assemblages of nine target species between the habitat side and all other groups along the roadside. The species assemblage using WE to escape the roadway was also significantly different from those using the WE to enter the roadway. Approximately 43% of bobcats, a surrogate species for the ocelot, used a WE to escape the ROW. Information on the effectiveness of these novel structures will be useful in the development of future WE to optimize placement and design.
Numerical study on compressive mechanical characteristics of filled jointed rock under confining pressure based on PFC
Authors: Song Lang , Chai Shaobo , Li Jing , Song Boyang , Chai Lianzeng
Published: October 2023

Confining pressure is an important factor affecting the strength and deformation characteristics of rock mass, it is of great significance to study the mechanical and deformation characteristics of jointed rock mass under confining pressure for the construction of deep underground engineering and the prevention of geological disasters. In order to study the mechanical and deformation characteristics of filled jointed rock under confining pressure, based on the laboratory experiment results of static uniaxial compression of filled jointed rock samples, the Particle Flow Code is used to conduct the numerical simulation. The strength characteristics, failure characteristics and micro-cracks development characteristics of filled jointed rock under different confining pressure levels, different joint inclination angles and different sample sizes are analyzed. The results show that the peak stress and peak strain increase with the increase of confining pressure level, and there is a strong linear relationship between peak stress and confining pressure level. The peak stress and initiation stress decrease first and then increase with the increase of joint inclination angle. With the increase of confining pressure level, the change law of initiation stress of filled jointed rock under different joint inclination angles is different. The confining pressure will prolong the development process of micro-cracks in filled jointed rock, which will make the distribution of micro-cracks more dispersed and the total number of micro-cracks increase. The failure mode changes from splitting failure to shear failure with the increase of confining pressure level. The change of joint inclination angle will seriously affect the failure mode and micro-cracks development characteristics of filled jointed rock.
WTAP gene variants and susceptibility to ovarian endometriosis in a Chinese population
Authors: Wan Zixian , Ye Lu , Chen Guange , Xiong Chaoyi , OuYang Zhenbo , Wu Liangzhi , He Jing , Duan Ping , Jie Youkun , Zhang Qiushi , Hua Wenfeng
Published: October 2023

Background: Endometriosis is a common chronic gynecologic disorder with a significant negative impact on women’s health. Wilms tumor 1-associated protein (WTAP) is a vital component of the RNA methyltransferase complex for N6-methyladenosine modification and plays a critical role in various human diseases. However, whether single nucleotide polymorphisms (SNPs) of the WTAP gene predispose to endometriosis risk remains to be investigated.

Methods: We genotyped three WTAP polymorphisms in 473 ovarian endometriosis patients and 459 control participants using the Agena Bioscience MassArray iPLEX platform. The logistic regression models were utilized to assess the associations between WTAP SNPs and the risk of ovarian endometriosis.

Results: In the single-locus analyses, we found that the rs1853259 G variant genotypes significantly increased, while the rs7766006 T variant genotypes significantly decreased the association with ovarian endometriosis risk. Combined analysis indicated that individuals with two unfavorable genotypes showed significantly higher ovarian endometriosis risk (adjusted OR = 1.71 [1.23–2.37], p = 0.001) than those with zero risk genotypes. In the stratified analysis, the risk effect of the rs1853259 AG/GG and rs7766006 GG genotypes was evident in subgroups of age ≤30, gravidity≤1, parity≤1, rASRM stage I, and the rs7766006 GG genotype was associated with worse risk (adjusted OR = 1.64 [1.08–2.48], p = 0.021) in the patients with rASRM stage II + III + IV. The haplotype analysis indicated that individuals with GGG haplotypes had a higher risk of ovarian endometriosis than wild-type AGG haplotype carriers. Moreover, false positive report probability and Bayesian false discovery probability analysis validated the reliability of the significant results. The quantitative expression trait loci analysis revealed that rs1853259 and rs7766006 were correlated with the expression levels of WTAP.

Conclusion: Our findings demonstrated that WTAP polymorphisms were associated with susceptibility to ovarian endometriosis among Chinese women.
Rational design of the genetic code expansion toolkit for in vivo encoding of D-amino acids
Authors: Jiang Han-Kai , Weng Jui-Hung , Wang Yi-Hui , Tsou Jo-Chu , Chen Pei-Jung , Ko An-Li Andrea , Söll Dieter , Tsai Ming-Daw , Wang Yane-Shih
Published: October 2023

Once thought to be non-naturally occurring, D-amino acids (DAAs) have in recent years been revealed to play a wide range of physiological roles across the tree of life, including in human systems. Synthetic biologists have since exploited DAAs’ unique biophysical properties to generate peptides and proteins with novel or enhanced functions. However, while peptides and small proteins containing DAAs can be efficiently prepared in vitro, producing large-sized heterochiral proteins poses as a major challenge mainly due to absence of pre-existing DAA translational machinery and presence of endogenous chiral discriminators. Based on our previous work demonstrating pyrrolysyl-tRNA synthetase’s (PylRS’) remarkable substrate polyspecificity, this work attempts to increase PylRS’ ability in directly charging tRNAPyl with D-phenylalanine analogs (DFAs). We here report a novel, polyspecific Methanosarcina mazei PylRS mutant, DFRS2, capable of incorporating DFAs into proteins via ribosomal synthesis in vivo. To validate its utility, in vivo translational DAA substitution were performed in superfolder green fluorescent protein and human heavy chain ferritin, successfully altering both proteins’ physiochemical properties. Furthermore, aminoacylation kinetic assays further demonstrated aminoacylation of DFAs by DFRS2 in vitro.
Novel alleles in the era of next-generation sequencing-based HLA typing calls for standardization and policy
Authors: Tran Jenny N. , Sherwood Karen R. , Mostafa Ahmed , Benedicto Rey Vincent , ElaAlim Allaa , Greenshields Anna , Keown Paul , Liwski Robert , Lan James H.
Published: October 2023

Next-Generation Sequencing (NGS) has transformed clinical histocompatibility laboratories through its capacity to provide accurate, high-throughput, high-resolution typing of Human Leukocyte Antigen (HLA) genes, which is critical for transplant safety and success. As this technology becomes widely used for clinical genotyping, histocompatibility laboratories now have an increased capability to identify novel HLA alleles that previously would not be detected using traditional genotyping methods. Standard guidelines for the clinical verification and reporting of novelties in the era of NGS are greatly needed. Here, we describe the experience of a clinical histocompatibility laboratory’s use of NGS for HLA genotyping and its management of novel alleles detected in an ethnically-diverse population of British Columbia, Canada. Over a period of 18 months, 3,450 clinical samples collected for the purpose of solid organ or hematopoietic stem cell transplantation were sequenced using NGS. Overall, 29 unique novel alleles were identified at a rate of ∼1.6 per month. The majority of novelties (52%) were detected in the alpha chains of class II (HLA-DQA1 and -DPA1). Novelties were found in all 11 HLA classical genes except for HLA-DRB3, -DRB4, and -DQB1. All novelties were single nucleotide polymorphisms, where more than half led to an amino acid change, and one resulted in a premature stop codon. Missense mutations were evaluated for changes in their amino acid properties to assess the potential effect on the novel HLA protein. All novelties identified were confirmed independently at another accredited HLA laboratory using a different NGS assay and platform to ensure validity in the reporting of novelties. The novel alleles were submitted to the Immuno Polymorphism Database-Immunogenetics/HLA (IPD-IMGT/HLA) for official allele name designation and inclusion in future database releases. A nationwide survey involving all Canadian HLA laboratories confirmed the common occurrence of novel allele detection but identified a wide variability in the assessment and reporting of novelties. In summary, a considerable proportion of novel alleles were identified in routine clinical testing. We propose a framework for the standardization of policies on the clinical management of novel alleles and inclusion in proficiency testing programs in the era of NGS-based HLA genotyping.
Enterosorbents in complex therapy of food allergies: a focus on digestive disorders and systemic toxicity in children
Authors: Shichkin Valentin P. , Kurchenko Oleg V. , Okhotnikova Elena N. , Chopyak Valentyna V. , Delfino Domenico V.
Published: October 2023

The review analyzes mechanisms and concomitant factors in developing IgE-associated allergic diseases provoked by food allergens and discusses clinical symptoms and current approaches for the treatment of food allergies. The expediency of using enterosorbents in complex therapy of food allergies and skin and respiratory manifestations associated with gastroenterological disorders is substantiated. The review summarizes the experience of using enterosorbents in post-Soviet countries to detoxify the human body. In this regard, special attention is paid to the enterosorbent White Coal (Carbowhite) based on silicon dioxide produced by the Ukrainian company OmniFarma.
Multi-faceted roles of C1q/TNF-related proteins family in atherosclerosis
Authors: Guo Shuren , Mao Xiaohuan , Liu Jun
Published: October 2023

Purpose of review

C1q/TNF-related proteins (CTRPs) are involved in the modulation of the development and prognosis of atherosclerosis (AS). Here, we summarizes the pathophysiological roles of individual members of the CTRP superfamily in the development of AS. Currently, there is no specific efficacious treatment for AS-related diseases, therefore it is urgent to develop novel therapeutic strategies aiming to target key molecules involved in AS.

Recent findings

Recently, mounting studies verified the critical roles of the CTRP family, including CTRP1-7, CTRP9 and CTRP11-15, in the development and progression of AS by influencing inflammatory response, modulating glucose and lipid metabolism, regulating endothelial functions and the proliferation of vascular smooth muscle cells (VSMCs).

Conclusions

CTRP family regulate different pathophysiology stages of AS. CTRP3, CTRP9, CTRP12, CTRP13 and CTRP15 play a clear protective role in AS, while CTRP5 and CTRP7 play a pro-atherosclerotic role in AS. The remarkable progress in our understanding of CTRPs’ role in AS will provide an attractive therapeutic target for AS.
Regulatory T cell adoptive transfer alters uterine immune populations, increasing a novel MHC-IIlow macrophage associated with healthy pregnancy
Authors: Lewis Emma L. , Reichenberger Erin R. , Anton Lauren , Gonzalez Michael V. , Taylor Deanne M. , Porrett Paige M. , Elovitz Michal A.
Published: October 2023

Intrauterine fetal demise (IUFD) – fetal loss after 20 weeks – affects 6 pregnancies per 1,000 live births in the United States, and the majority are of unknown etiology. Maternal systemic regulatory T cell (Treg) deficits have been implicated in fetal loss, but whether mucosal immune cells at the maternal-fetal interface contribute to fetal loss is under-explored. We hypothesized that the immune cell composition and function of the uterine mucosa would contribute to the pathogenesis of IUFD. To investigate local immune mechanisms of IUFD, we used the CBA mouse strain, which naturally has mid-late gestation fetal loss. We performed a Treg adoptive transfer and interrogated both pregnancy outcomes and the impact of systemic maternal Tregs on mucosal immune populations at the maternal-fetal interface. Treg transfer prevented fetal loss and increased an MHC-IIlow population of uterine macrophages. Single-cell RNA-sequencing was utilized to precisely evaluate the impact of systemic Tregs on uterine myeloid populations. A population of C1q+, Trem2+, MHC-IIlow uterine macrophages were increased in Treg-recipient mice. The transcriptional signature of this novel uterine macrophage subtype is enriched in multiple studies of human healthy decidual macrophages, suggesting a conserved role for these macrophages in preventing fetal loss.
Immunotherapy with STING and TLR9 agonists promotes synergistic therapeutic efficacy with suppressed cancer-associated fibroblasts in colon carcinoma
Authors: Hajiabadi Sare , Alidadi Soodeh , Montakhab Farahi Zohreh , Ghahramani Seno Mohammad M. , Farzin Hamidreza , Haghparast Alireza
Published: October 2023

The innate immune sensing of nucleic acids using effective immunoadjuvants is critical for increasing protective immune responses against cancer. Stimulators of interferon genes (STING) and toll-like receptor 9 (TLR9) agonists are considered promising candidates in several preclinical tumor models with the potential to be used in clinical settings. However, the effects of such treatment on tumor stroma are currently unknown. In this study, we investigated the immunotherapeutic effects of ADU-S100 as a STING agonist and CpG ODN1826 as a TLR9 agonist in a preclinical model of colon carcinoma. Tumor-bearing mice were treated intratumorally on days 10 and 16 post-tumor inoculation with ADU-S100 and CpG ODN1826. Cytokine profiles in the tumor and spleen, tumor cell apoptosis, the infiltration of immune cells, and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) were evaluated to identify the immunological mechanisms after treatment. The powerful antitumor activity of single and combination treatments, the upregulation of the expression of pro-inflammatory cytokines in the tumor and spleen, and the recruitment and infiltration of the TME by immune cells revealed the synergism of immunoadjuvants in the eradication of the colon carcinoma model. Remarkably, the significant downregulation of CAFs in the TME indicated that suppression of tumorigenesis occurred after immunoadjuvant therapy. The results illustrate the potential of targeting the STING and TLR9 pathways as powerful immunoadjuvants in the treatment of preclinical colon carcinoma and the possibility of harnessing these pathways in future therapeutic approaches.
T cells, more than antibodies, may prevent symptoms developing from respiratory syncytial virus infections in older adults
Authors: Salaun Bruno , De Smedt Jonathan , Vernhes Charlotte , Moureau Annick , Öner Deniz , Bastian Arangassery Rosemary , Janssens Michel , Balla-Jhagjhoorsingh Sunita , Aerssens Jeroen , Lambert Christophe , Coenen Samuel , Butler Christopher C. , Drysdale Simon B. , Wildenbeest Joanne G. , Pollard Andrew J. , Openshaw Peter J. M. , Bont Louis
Published: October 2023

Introduction

The immune mechanisms supporting partial protection from reinfection and disease by the respiratory syncytial virus (RSV) have not been fully characterized. In older adults, symptoms are typically mild but can be serious in patients with comorbidities when the infection extends to the lower respiratory tract.

Methods

This study formed part of the RESCEU older-adults prospective-cohort study in Northern Europe (2017–2019; NCT03621930) in which a thousand participants were followed over an RSV season. Peripheral-blood samples (taken pre-season, post-season, during illness and convalescence) were analyzed from participants who (i) had a symptomatic acute respiratory tract infection by RSV (RSV-ARTI; N=35) or (ii) asymptomatic RSV infection (RSV-Asymptomatic; N=16). These analyses included evaluations of antibody (Fc-mediated–) functional features and cell-mediated immunity, in which univariate and machine-learning (ML) models were used to explore differences between groups.

Results

Pre–RSV-season peripheral-blood biomarkers were predictive of symptomatic RSV infection. T-cell data were more predictive than functional antibody data (area under receiver operating characteristic curve [AUROC] for the models were 99% and 76%, respectively). The pre-RSV season T-cell phenotypes which were selected by the ML modelling and which were more frequent in RSV-Asymptomatic group than in the RSV-ARTI group, coincided with prominent phenotypes identified during convalescence from RSV-ARTI (e.g., IFN-γ+, TNF-α+ and CD40L+ for CD4+, and IFN-γ+ and 4-1BB+ for CD8+).

Conclusion

The evaluation and statistical modelling of numerous immunological parameters over the RSV season suggests a primary role of cellular immunity in preventing symptomatic RSV infections in older adults.