bluuebunny/crossref_metadata_2025 huggingface dataset:
The Reaction Specificity of Mammalian ALOX15 Orthologs is Changed During Late Primate Evolution and These Alterations Might Offer Evolutionary Advantages for Hominidae
Authors: Heydeck Dagmar , Reisch Florian , Schäfer Marjann , Kakularam Kumar R. , Roigas Sophie A. , Stehling Sabine , Püschel Gerhard P. , Kuhn Hartmut
Published: April 2022

Arachidonic acid lipoxygenases (ALOXs) have been implicated in the immune response of mammals. The reaction specificity of these enzymes is decisive for their biological functions and ALOX classification is based on this enzyme property. Comparing the amino acid sequences and the functional properties of selected mammalian ALOX15 orthologs we previously hypothesized that the reaction specificity of these enzymes can be predicted based on their amino acid sequences (Triad Concept) and that mammals, which are ranked in evolution below gibbons, express arachidonic acid 12-lipoxygenating ALOX15 orthologs. In contrast, Hominidae involving the great apes and humans possess 15-lipoxygenating enzymes (Evolutionary Hypothesis). These two hypotheses were based on sequence data of some 60 mammalian ALOX15 orthologs and about half of them were functionally characterized. Here, we compared the ALOX15 sequences of 152 mammals representing all major mammalian subclades expressed 44 novel ALOX15 orthologs and performed extensive mutagenesis studies of their triad determinants. We found that ALOX15 genes are absent in extant Prototheria but that corresponding enzymes frequently occur in Metatheria and Eutheria. More than 90% of them catalyze arachidonic acid 12-lipoxygenation and the Triad Concept is applicable to all of them. Mammals ranked in evolution above gibbons express arachidonic acid 15-lipoxygenating ALOX15 orthologs but enzymes with similar specificity are only present in less than 5% of mammals ranked below gibbons. This data suggests that ALOX15 orthologs have been introduced during Prototheria-Metatheria transition and put the Triad Concept and the Evolutionary Hypothesis on a much broader and more reliable experimental basis.
Superhalogen Anions Supported by the Systems Comprising Alternately Aligned Boron and Nitrogen Central Atoms
Authors: Cyraniak Adrianna , Faron Dawid , Freza Sylwia , Anusiewicz Iwona , Skurski Piotr
Published: April 2022

Using DFT/(B3LYP/wB97XD/B2PLYPD) and OVGF electronic structure methods with flexible atomic orbital basis sets, we examined the series of polynuclear superhalogen anions matching the (BF3(BN)nF4n+1)– formula (for n = 1-10,13,18-20) containing alternately aligned boron and nitrogen central atoms decorated with fluorine ligands. It was found that the equilibrium structures of these anions correspond to fully extended chains (with each B and N central atom surrounded by four substituents arranged in a tetrahedral manner) and thus mimic the globally stable fully extended (all-trans) conformations of higher n-alkanes. The vertical electron detachment energies of the (BF3(BN)nF4n+1)– anions were found to exceed 8 eV in all cases and gradually increase with the increasing number of n. The approximate limiting value of vertical electron binding energy that could be achieved for such polynuclear superhalogen anions was estimated as equal to ca. 10.7 eV.
Novel Insights Into Leishmania (Viannia) braziliensis In Vitro Fitness Guided by Temperature Changes Along With Its Subtilisins and Oligopeptidase B
Authors: Zabala-Peñafiel Anabel , Cysne-Finkelstein Lea , Conceição-Silva Fatima , Fagundes Aline , Miranda Luciana de Freitas Campos , Souza-Silva Franklin , Brandt Artur A. M. L. , Dias-Lopes Geovane , Alves Carlos Roberto
Published: April 2022

Proteases are virulence factors with a recognized impact on the Leishmania spp. life cycle. This study considers a set of analyses measuring phenotypic factors of L. (V.) braziliensis clinical isolates as promastigotes growth curves, murine peritoneal macrophages infection, inflammatory mediators production, and serine proteases gene expression (subtilisin 13: S13, subtilisin 28: S28, oligopeptidase B: OPB) assessing these isolates’ fitness on in vitro conditions. Parasites had different behavior during the early growth phase from day zero to day three, and all isolates reached the stationary growth phase between days four and seven. Macrophages infection showed two tendencies, one of decreased infection rate and number of parasites per macrophage (Infection Index <1000) and another with a constant infection index (≥1400). TNF-α (≥10 pg/mL) detected in infections by 75% of isolates, IL-6 (≥80 pg/mL) by 30% of isolates and low levels of NO (≥0.01µM) in almost all infections. Gene expression showed higher values of S13 (≥2RQ) in the intracellular amastigotes of all the isolates evaluated. On the contrary, S28 expression was low (≤1RQ) in all isolates. OPB expression was different between promastigotes and intracellular amastigotes, being significantly higher (≥2RQ) in the latter form of 58% of the isolates. Predictive structural assays of S13 and OPB were performed to explore temperature influence on gene expression and the encoded proteases. Gene expression data is discussed based on in silico predictions of regulatory regions that show plasticity in the linearity index of secondary structures of S13 and OPB 3’-untranslated regions of mRNA, dependent on temperature changes. While hairpin structures suggest an active region of mRNA for both genes above 26°C, pseudoknot structure found in S13 is an indication of a particular profile of this gene at mammalian host temperatures (37°C). Furthermore, the predicted 3D structures are in accordance with the influence of these temperatures on the catalytic site stability of both enzymes, favoring their action over peptide substrates. Data gathered here suggest that L. (V.) braziliensis serine proteases can be influenced by the temperature conditions affecting parasite fitness throughout its life cycle.
Anti-Viral Activities of Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Against Human Respiratory Viruses
Authors: Oh Soo-Jin , Lee Eun-Na , Park Joo-Hoo , Lee Jae Kyung , Cho Geum Joon , Park Il-Ho , Shin Ok Sarah
Published: April 2022

The endemic and pandemic caused by respiratory virus infection are a major cause of mortality and morbidity globally. Thus, broadly effective antiviral drugs are needed to treat respiratory viral diseases. Small extracellular vesicles derived from human umbilical cord mesenchymal stem cells (U-exo) have recently gained attention as a cell-free therapeutic strategy due to their potential for safety and efficacy. Anti-viral activities of U-exo to countermeasure respiratory virus-associated diseases are currently unknown. Here, we tested the antiviral activities of U-exo following influenza A/B virus (IFV) and human seasonal coronavirus (HCoV) infections in vitro. Cells were subject to IFV or HCoV infection followed by U-exo treatment. U-exo treatment significantly reduced IFV or HCoV replication and combined treatment with recombinant human interferon-alpha protein (IFN-α) exerted synergistically enhanced antiviral effects against IFV or HCoV. Interestingly, microRNA (miR)-125b, which is one of the most abundantly expressed small RNAs in U-exo, was found to suppress IFV replication possibly via the induction of IFN-stimulated genes (ISGs). Furthermore, U-exo markedly enhanced RNA virus-triggered IFN signaling and ISGs production. Similarly, human nasal epithelial cells cultured at the air-liquid interface (ALI) studies broadly effective anti-viral and anti-inflammatory activities of U-exo against IFV and HCoV, suggesting the potential role of U-exo as a promising intervention for respiratory virus-associated diseases.
Failure Mechanism and Dynamic Response Characteristics of Loess Slopes Under the Effects of Earthquake and Groundwater
Authors: Chai Shaofeng , Wang Lanmin , Wang Ping , Pu Xiaowu , Xu Shiyang , Guo Haitao , Wang Huijuan
Published: April 2022

A large-scale shaking table test was conducted with simulated earthquakes and groundwater to study the dynamic response and instability mechanism of a loess slope with a saturated bottom. By examining the acceleration, dynamic pore water pressure, corresponding soil pressure and observed macroscopic failure behaviour of the slope under different shaking intensities, the dynamic responses of acceleration and pore water pressure of the loess slope were analysed. By comparing the time history curve of acceleration with the time history curves of pore water pressure and surrounding soil pressure, we found that the instability failure of the slope was first due to the continuous vibration that caused the local structure of the slope soil to be damaged, forming locally saturated soil and the rise in the groundwater table during shaking. Then, the saturated soil liquefied under the action of strong vibration, and the liquefied soil mass slid under the action of a high-intensity earthquake force. Finally, the acceleration and spectral characteristics of the pore water pressure changed sharply with a shift in the predominant frequency at the liquefied locations under a high shaking intensity. The significant changes in dynamic pore water pressure mainly occurred when the shaking components in the low-frequency bands below 1 Hz. This implied that the shift in the frequency mainly resulted from the damage in the structure of the loess slope after high-intensity shaking. These results help us better understand the triggering mechanism and failure mechanism of saturated loess slopes during the Minxian-Zhangxian earthquake.
Trabecular Bone Score and Osteoprotegerin as Useful Tools in the Assessment of Bone Deterioration in Acromegaly
Authors: Jawiarczyk-Przybyłowska Aleksandra , Halupczok-Żyła Jowita , Syrycka Joanna , Zembska Agnieszka , Kuliczkowska-Płaksej Justyna , Bolanowski Marek
Published: April 2022

Purpose

This study aimed to assess bone mineral density (BMD) and trabecular bone score (TBS) in 61 patients from the acromegaly group (AG) with regard to the activity of the disease in comparison to 42 patients—control group (CG). We also analyzed selected bone markers and their association with BMD and TBS.

Materials and Methods

Lumbar spine and femoral neck BMD measurements were performed. TBS values were obtained. Serum concentrations of selected bone markers, including osteoprotegerin (OPG), were measured.

Results

We revealed a difference in TBS values between the AG and CG as well as between the TCA (treatment-controlled acromegaly) vs. CG and TCA+CA (cured acromegaly) vs. CG. We did not observe any statistically significant difference in BMD. OPG had a lower concentration in the CG compared to the AG. TBS correlated negatively with OPG in the AG (r = −0.31, p = 0.01) and in the TCA+ CA group (r = −0.3, p = 0.01).

Conclusions

The acromegalic patients have altered bone microstructure as indicated by the decreased TBS regardless of the activity of the disease and BMD. OPG could be a marker of the destruction of the bone microstructure, but further studies are needed.
Mapping Highway Mobile Carbon Source Emissions Using Traffic Flow Big Data: A Case Study of Guangdong Province, China
Authors: Li Yuanjun , Wu Qitao , Zhang Yuling , Huang Guangqing , Jin Shuangquan , Fang Shun
Published: April 2022

The continuously growing transportation sector has become the second largest, yet increasing, industrial emissions source of CO2, posing serious challenges to global environmental security. Among the various transport modes, road transportation yields the highest cumulative level of CO2 emissions. However, these emissions have not been sufficiently investigated in previous studies, especially with respect to analyses from the perspective of vehicle emission sources. This can make source management and emissions reduction difficult. To address these methodological issues, this study aims to build a highway traffic carbon emissions monitoring and spatial analysis system, employing the mobile carbon sources concept, and establish a carbon emissions model encompassing all types of passenger and freight vehicles based on interstation O-D traffic flow data recorded by the toll collection network, to calculate vehicle carbon emissions and create a mobile carbon source emissions map. Empirical analyses in Guangdong Province revealed that, compared with conventional studies, the mobile carbon source emission mapping approach can accurately identify vehicle types with higher emissions while assisting with source management. Of the average total daily carbon emissions from all types of vehicles that use highways (15,311 t), 57.10% originated from freight vehicles (8,743 t) while passenger vehicles contributed 42.90%. By specific vehicle type, emissions mainly originated from small and medium-sized vehicles, including Class I passenger vehicles (i.e., cars) and Class I and III freight vehicles. Further, the proposed method could locate road sections characterized by high carbon emissions. High-emission sections in Guangdong Province were mainly spatially autocorrelated, with peak aggregations on national highways; near economically developed and densely populated areas; and adjacent to surrounding airports, ports, and overpass roads. This study improves the scientific and spatial analytical accuracy for carbon emissions measurements of highway vehicles, thus informing source management and sustainable development, as well as providing technical support for attaining carbon neutrality in China.
The Influence of Coalescent Microbiotic Particles From Water and Soil on the Evolution and Spread of Antimicrobial Resistance
Authors: Baquero F. , Coque T.M. , Guerra-Pinto N. , Galán J.C. , Jiménez-Lalana D. , Tamames J. , Pedrós-Alió C.
Published: April 2022

Water and soil contain a multiplicity of particulate material coated with bacterial populations and communities. Microbiotic particles are any type of small particle (measuring less than 2 mm) to which bacteria and other microbes attach, resulting in medium to long-term colonization. This study reviews the interactions of ecologically distant bacterial organisms on microbiotic particles in soil and water as a method for explaining the evolution and spread of antibiotic resistance traits. These particles include bacteria-bacteria aggregates, which can merge with particles from fungi, protozoa, phytoplankton, zooplankton, and biodetritus resulting from animal and vegetal decomposition, humus, mineral particles (clay, carbonates, silicates), and anthropogenic particles (including wastewater particles and microplastics). In turn, these complex particles can interact and coalesce. Natural phenomena (waterflow, tides, tsunamis, currents, and strong winds) and anthropogenic activity (agriculture, waste-water management, mining, excavation/construction) favor the interaction and merging of microbiotic particles in soil and water, resulting in enhanced recombinant communities capable of exchanging genetic material, including antimicrobial resistance genes, particularly in antimicrobial-polluted environments. In this review, we propose that the worldwide spread of antimicrobial resistance might be related to the environmental dynamics of microbiotic particles, and we discuss possible methods for reducing this problem that threatens One Health and Planetary Health.
Insights on the Early Pleistocene Hominin Population of the Guadix-Baza Depression (SE Spain) and a Review on the Ecology of the First Peopling of Europe
Authors: Palmqvist Paul , Rodríguez-Gómez Guillermo , Bermúdez de Castro José María , García-Aguilar José Manuel , Espigares M. Patrocinio , Figueirido Borja , Ros-Montoya Sergio , Granados Alejandro , Serrano Francisco J. , Martínez-Navarro Bienvenido , Guerra-Merchán Antonio
Published: April 2022

The chronology and environmental context of the first hominin dispersal in Europe have been subject to debate and controversy. The oldest settlements in Eurasia (e.g., Dmanisi, ∼1.8 Ma) suggest a scenario in which the Caucasus and southern Asia were occupied ∼0.4 Ma before the first peopling of Europe. Barranco León (BL) and Fuente Nueva 3 (FN3), two Early Pleistocene archeological localities dated to ∼1.4 Ma in Orce (Guadix-Baza Depression, SE Spain), provide the oldest evidence of hominin presence in Western Europe. At these sites, huge assemblages of large mammals with evidence of butchery and marrow processing have been unearthed associated to abundant Oldowan tools and a deciduous tooth ofHomosp. in the case of BL. Here, we: (i) review the Early Pleistocene archeological sites of Europe; (ii) discuss on the subsistence strategies of these hominins, including new estimates of resource abundance for the populations of Atapuerca and Orce; (iii) use cartographic data of the sedimentary deposits for reconstructing the landscape habitable in Guadix-Baza; and (iv) calculate the size of the hominin population using an estimate of population density based on resource abundance. Our results indicate that Guadix-Baza could be home for a small hominin population of 350–280 individuals. This basin is surrounded by the highest mountainous reliefs of the Alpine-Betic orogen and shows a limited number of connecting corridors with the surrounding areas, which could have limited gene flow with other hominin populations. Isolation would eventually lead to bottlenecks, genetic drift and inbreeding depression, conditions documented in the wild dog population of the basin, which probably compromised the viability of the hominin population in the medium to long term. This explains the discontinuous nature of the archeological record in Guadix-Baza, a situation that can also be extrapolated to the scarcity of hominin settlements for these ancient chronologies in Europe.
Identifying Key MicroRNA Signatures for Neurodegenerative Diseases With Machine Learning Methods
Authors: Li ZhanDong , Guo Wei , Ding ShiJian , Chen Lei , Feng KaiYan , Huang Tao , Cai Yu-Dong
Published: April 2022

Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease, and many other disease types, cause cognitive dysfunctions such as dementia via the progressive loss of structure or function of the body’s neurons. However, the etiology of these diseases remains unknown, and diagnosing less common cognitive disorders such as vascular dementia (VaD) remains a challenge. In this work, we developed a machine-leaning-based technique to distinguish between normal control (NC), AD, VaD, dementia with Lewy bodies, and mild cognitive impairment at the microRNA (miRNA) expression level. First, unnecessary miRNA features in the miRNA expression profiles were removed using the Boruta feature selection method, and the retained feature sets were sorted using minimum redundancy maximum relevance and Monte Carlo feature selection to provide two ranking feature lists. The incremental feature selection method was used to construct a series of feature subsets from these feature lists, and the random forest and PART classifiers were trained on the sample data consisting of these feature subsets. On the basis of the model performance of these classifiers with different number of features, the best feature subsets and classifiers were identified, and the classification rules were retrieved from the optimal PART classifiers. Finally, the link between candidate miRNA features, including hsa-miR-3184-5p, has-miR-6088, and has-miR-4649, and neurodegenerative diseases was confirmed using recently published research, laying the groundwork for more research on miRNAs in neurodegenerative diseases for the diagnosis of cognitive impairment and the understanding of potential pathogenic mechanisms.
The Role of Purinergic Signaling in Heart Transplantation
Authors: Jiang Yanzhi , Lin Jianxin , Zheng Haiyun , Zhu Ping
Published: April 2022

Heart transplantation remains the optimal treatment option for patients with end-stage heart disease. Growing evidence demonstrates that purinergic signals mediated by purine nucleotides and nucleosides play vital roles in heart transplantation, especially in the era of ischemia-reperfusion injury (IRI) and allograft rejection. Purinergic signaling consists of extracellular nucleotides and nucleosides, ecto-enzymes, and cell surface receptors; it participates in the regulation of many physiological and pathological processes. During transplantation, excess adenosine triphosphate (ATP) levels are released from damaged cells, and driver detrimental inflammatory responses largelyviapurinergic P2 receptors. Ecto-nucleosidases sequentially dephosphorylate extracellular ATP to ADP, AMP, and finally adenosine. Adenosine exerts a cardioprotective effect by its anti-inflammatory, antiplatelet, and vasodilation properties. This review focused on the role of purinergic signaling in IRI and rejection after heart transplantation, as well as the clinical applications and prospects of purinergic signaling.
The Potential Role of Ferroptosis in Systemic Lupus Erythematosus
Authors: Chen Qian , Wang Jie , Xiang Mengmeng , Wang Yilun , Zhang Zhixiong , Liang Jun , Xu Jinhua
Published: April 2022

Systemic lupus erythematosus (SLE) is an autoimmune disease that is accompanied with autoantibody production and inflammation. Other features of SLE pathogenesis include iron accumulation, oxidative stress, and lipid peroxidation, which are also major biochemical characteristics of ferroptosis, a novel non-apoptotic regulated form of cell death. To date, ferroptosis has been demonstrated to be an important driver of lupus progression, and several ferroptosis inhibitors have therapeutic effect in lupus-prone mice. Given the emerging link between ferroptosis and SLE, it can be postulated that ferroptosis is an integral component in the vicious cycle of immune dysfunction, inflammation, and tissue damage in SLE pathogenesis. In this review, we summarize the potential links between ferroptosis and SLE, with the aim of elucidating the underlying pathogenic mechanism of ferroptosis in lupus, and providing a new promising therapeutic strategy for SLE.
IL-27 Improves Prophylactic Protection Provided by a Dead Tumor Cell Vaccine in a Mouse Melanoma Model
Authors: Seaver Kyle , Kourko Olena , Gee Katrina , Greer Peter A. , Basta Sameh
Published: April 2022

The protocol used to induce cell death for generating vaccines from whole tumor cells is a critical consideration that impacts vaccine efficacy. Here we compared how different protocols used to induce cell death impacted protection provided by a prophylactic whole tumor cell vaccine in a mouse melanoma model. We found that melanoma cells exposed to γ-irradiation or lysis combined with UV-irradiation (LyUV) provided better protection against tumor challenge than lysis only or cells exposed to UV-irradiation. Furthermore, we found that the immunoregulatory cytokine, IL-27 enhanced protection against tumor growth in a dose-dependent manner when combined with either LyUV or γ-irradiated whole tumor cell vaccine preparations. Taken together, this data supports the use of LyUV as a potential protocol for developing whole tumor cell prophylactic cancer vaccines. We also showed that IL-27 can be used at low doses as a potent adjuvant in combination with LyUV or γ-irradiation treated cancer cells to improve the protection provided by a prophylactic cancer vaccine in a mouse melanoma model.
Tracking Jellyfish Swarm Origins Using a Combined Oceanographic-Genetic-Citizen Science Approach
Authors: Edelist Dor , Knutsen Øyvind , Ellingsen Ingrid , Majaneva Sanna , Aberle Nicole , Dror Hila , Angel Dror L.
Published: April 2022

Biological invasions of jellyfish may critically affect ecosystems and ecosystem services, yet their complex life cycle makes tracking their origins and dispersal vectors a challenging task. Here we combine citizen science observations, oceanographic modeling, and population genetics to track swarms of the invasive nomad jellyfish,Rhopilema nomadica, across the Eastern Mediterranean Sea. Jellyfish observations were recorded by citizens from two Israeli beaches in two consecutive years. A Lagrangian model coupled with a high-resolution 3D hydrodynamic model (SINMOD) was then used to simulate drift of ephyrae from probable polyp bed locations. Finally, mitochondrial DNA (mtDNA) sequence was constructed to examine swarm connectivity. Temporal (both seasonal and interannual) variation in observed swarms generally exceeded spatial differences between the two surveyed beaches. Early detection of swarms by citizens in offshore waters and the higher offshore particle distribution shown by the drift model, point to considerable offshore transport of the swarms. However, a higher probability was found for a nearshore location of the polyp beds, as nearshore origins were more closely correlated to hits on target beaches.R. nomadicareleased as ephyrae in early spring were likely to reach target beaches 200-300 km down current within two to three months as swarms of young adults in the early summer bathing season.R. nomadicapopulations exhibited little temporal or spatial genetic differentiation, a typical feature of a species that has recently undergone rapid population expansion. The offshore transport, the lack of genetic structure, and the interannual differences in both hydrodynamics and citizen scientist observations, all indicate decentralized swarm origins. This type of interdisciplinary approach can thus provide viable tools to track bloom formations. Understanding the complexity of jellyfish swarm dynamics supports future management strategies such as forecasting, preparedness and public education.
Influence of Quartz Fiber on Electromagnetic Wave Transmission Properties of High-Alumina Cement Paste
Authors: Yang Bin , Li Yue , Liu Jianglin , Li YiNuo , Jin Caiyun , Li Hongwen
Published: April 2022

In this paper, the effects of quartz fibers on the resistivity, complex permittivity, complex permeability, and S-parameters of high-alumina cement pastes are investigated. Meanwhile, the change of microstructure after adding quartz fibers were analyzed by mercury intrusion porosimetry (MIP) and scanning electron microscope (SEM). The results show that with the increase the content of quartz fiber, the real part of complex permittivity decreases, while the imaginary part of complex permittivity, dielectric loss tangent, and resistivity increased. At the same time, there are more small pores, and the interface situation is more complicated after adding quartz fiber. Therefore, the reflectivity decreases and the absorptivity increases, but the scope of increase in the absorptivity is smaller than the decrease in the reflectivity, resulting in an increase in the transmittivity. When the content of quartz fiber is 0.15, 0.30, 0.45, and 0.60%, the average transmittance of high-alumina cement paste is increased by 3.69, 6.18, 15.51, and 21.03% respectively. It is indicated that the quartz fibers can improve the wave transmission properties of the high-alumina cement paste.
Early COPD Risk Decision for Adults Aged From 40 to 79 Years Based on Lung Radiomics Features
Authors: Yang Yingjian , Li Wei , Guo Yingwei , Liu Yang , Li Qiang , Yang Kai , Wang Shicong , Zeng Nanrong , Duan Wenxin , Chen Ziran , Chen Huai , Li Xian , Zhao Wei , Chen Rongchang , Kang Yan
Published: April 2022

Background

Chronic obstructive pulmonary disease (COPD), a preventable lung disease, has the highest prevalence in the elderly and deserves special consideration regarding earlier warnings in this fragile population. The impact of age on COPD is well known, but the COPD risk of the aging process in the lungs remains unclear. Therefore, it is necessary to understand the COPD risk of the aging process in the lungs, providing an early COPD risk decision for adults.

Methods

COPD risk is evaluated for adults to make an early COPD risk decision from the perspective of lung radiomics features. First, the subjects are divided into four groups according to the COPD stages. Their ages are divided into eight equal age intervals in each group. Second, four survival Cox models are established based on the lung radiomics features to evaluate the risk probability from COPD stage 0 to suffering COPD and COPD stages. Finally, four risk ranks are defined by equally dividing the COPD risk probability from 0 to 1. Subsequently, the COPD risk at different stages is evaluated with varying age intervals to provide an early COPD risk decision.

Results

The evaluation metrics area under the curve (AUC)/C index of four survival Cox models are 0.87/0.94, 0.84/0.83, 0.94/0.89, and 0.97/0.86, respectively, showing the effectiveness of the models. The risk rank levels up every 5 years for the subjects who had suffered COPD after 60. For the subjects with COPD stage 0, the risk rank of suffering COPD stage I levels up every 5 years after the age of 65 years, and the risk rank of suffering COPD stages II and III & IV levels up every 5 years after the age of 70 years.

Conclusion

Once the age is above 60 years, the patients with COPD need to take action to prevent the progress and deterioration of COPD. Once the age is above 65 years, the patients with COPD stage 0 need to take precautions against COPD.
The Perception of the Anesthesiologist Among the Medical, Paramedical and Administrative Staff
Authors: Selim Jean , Selim Marc , Demailly Zoé , Wable Thierry , Clavier Thomas , Besnier Emmanuel , Dureuil Bertrand , Veber Benoît , Djerada Zoubir , Compere Vincent
Published: April 2022

Introduction

Anesthesia remains a young medical discipline still relatively unknown by the general public and probably by some health professionals. The objective of the study was to evaluate the perception of anesthesiologist by health professionals working with this specialty.

Methods

We distributed a computerized survey to physicians, residents, paramedical, midwives, and administrative staff in different hospitals between April and July 2018 in Normandy, France. The survey included 38 questions on 6 different topics: communicated image, skills and knowledge, communication, place in patient care, workload, and initial anesthesiologist formation. The survey was validated by a semi-directive interview methodology. A Likert scale from ×2 to +2 (“completely disagree” to “completely agree”) was used for each item.

Results

Six hundred and twenty five out of 2,000 surveys sent were analyzed. The anesthesiologist conveys an image of serenity (+0.94 ± 0.79), has a high degree of responsibility (+1.72 ± 0.59) with important decision-making power (+1.39 ± 0.82). He guarantees patient safety and comfort (+1.07 ± 0.88) with his/her dual competence in anesthesia and intensive care (+1.36 ± 0.82). Anesthesiology requires teamwork (+1.68 ± 0.58) and good communication skills (+1.48 ± 0.73). The anesthesiologist is not perceived as a service provider (−0.33 ± 1.15) but is the physician responsible for perioperative care (+1.69 ± 1.00). His/her workload is moderately perceived as high (+0.71 ± 1.17) but is confronted with potentially conflictual relationships with colleagues from other specialties (+1.40 ± 0.68) and stressful situations (+1.44 ± 0.80).

Conclusion

The overall perception of the anesthesiologist in our study appears to be good.
Quantification of Motility in Bacillus subtilis at Temperatures Up to 84°C Using a Submersible Volumetric Microscope and Automated Tracking
Authors: Dubay Megan M. , Johnston Nikki , Wronkiewicz Mark , Lee Jake , Lindensmith Christian A. , Nadeau Jay L.
Published: April 2022

We describe a system for high-temperature investigations of bacterial motility using a digital holographic microscope completely submerged in heated water. Temperatures above 90°C could be achieved, with a constant 5°C offset between the sample temperature and the surrounding water bath. Using this system, we observed active motility in Bacillus subtilis up to 66°C. As temperatures rose, most cells became immobilized on the surface, but a fraction of cells remained highly motile at distances of >100 μm above the surface. Suspended non-motile cells showed Brownian motion that scaled consistently with temperature and viscosity. A novel open-source automated tracking package was used to obtain 2D tracks of motile cells and quantify motility parameters, showing that swimming speed increased with temperature until ∼40°C, then plateaued. These findings are consistent with the observed heterogeneity of B. subtilis populations, and represent the highest reported temperature for swimming in this species. This technique is a simple, low-cost method for quantifying motility at high temperatures and could be useful for investigation of many different cell types, including thermophilic archaea.
Deletion of Non-histidine Domains of Histidine Kinase CHK1 Diminishes the Infectivity of Candida albicans in an Oral Mucosal Model
Authors: Feng Yahui , Bian Shaodong , Pang Zhiping , Wen Yiyang , Calderone Richard , Li Dongmei , Shi Dongmei
Published: April 2022

Objectives

The histidine kinase (HK) CHK1 and other protein kinases in Candida albicans are key players in the development of hyphae. This study is designed to determine the functional roles of the S_Tkc domain (protein kinase) and the GAF domain of C. albicans CHK1 in hyphal formation and mucosal invasion.

Methods

The domain mutants CHK25 (ΔS_TkcCHK1/Δchk1) and CHK26 (ΔS_TkcΔgafCHK1/Δchk1) were first constructed by the his1-URA3-his1 method and confirmed by sequencing and Southern blots. A mouse tongue infection model was used to evaluate the hyphal invasion and fungal loads in each domain mutant, full-gene deletion mutant CHK21 (chk1Δ/chk1Δ), re-constituted strain CHK23 (chk1Δ/CHK1), and wild type (WT) from day 1 to day 5. The degree of invasion and damage to the oral mucosa of mice in each strain-infected group was evaluated in vivo and compared with germ tube rate and hyphal formation in vitro.

Result

When compared with severe mucosal damage and massive hyphal formation in WT- or CHK23-infected mouse tongues, the deletion of S_Tkc domain (CHK25) caused mild mucosal damage, and fungal invasion was eliminated as we observed in full-gene mutant CHK21. However, the deletion of S_Tkc and GAF (CHK26) partially restored the hyphal invasion and mucosal tissue damage that were exhibited in WT and CHK23. Regardless of the in vivo results, the decreased hyphal formation and germ tube in vitro were less apparent and quite similar between CHK25 and CHK26, especially at the late stage of the log phase where CHK26 was closer to WT and CHK23. However, growth defect and hyphal impairment of both domain mutants were similar to CHK21 in the early stages.

Conclusion

Our data suggest that both protein kinase (S_Tkc) and GAF domains in C. albicans CHK1 are required for hyphal invasiveness in mucosal tissue. The appropriate initiation of cell growth and hyphal formation at the lag phase is likely mediated by these two functional domains of CHK1 to maintain in vivo infectivity of C. albicans.
Novel Viral DNA Polymerases From Metagenomes Suggest Genomic Sources of Strand-Displacing Biochemical Phenotypes
Authors: Keown Rachel A. , Dums Jacob T. , Brumm Phillip J. , MacDonald Joyanne , Mead David A. , Ferrell Barbra D. , Moore Ryan M. , Harrison Amelia O. , Polson Shawn W. , Wommack K. Eric
Published: April 2022

Viruses are the most abundant and diverse biological entities on the planet and constitute a significant proportion of Earth’s genetic diversity. Most of this diversity is not represented by isolated viral-host systems and has only been observed through sequencing of viral metagenomes (viromes) from environmental samples. Viromes provide snapshots of viral genetic potential, and a wealth of information on viral community ecology. These data also provide opportunities for exploring the biochemistry of novel viral enzymes. The in vitro biochemical characteristics of novel viral DNA polymerases were explored, testing hypothesized differences in polymerase biochemistry according to protein sequence phylogeny. Forty-eight viral DNA Polymerase I (PolA) proteins from estuarine viromes, hot spring metagenomes, and reference viruses, encompassing a broad representation of currently known diversity, were synthesized, expressed, and purified. Novel functionality was shown in multiple PolAs. Intriguingly, some of the estuarine viral polymerases demonstrated moderate to strong innate DNA strand displacement activity at high enzyme concentration. Strand-displacing polymerases have important technological applications where isothermal reactions are desirable. Bioinformatic investigation of genes neighboring these strand displacing polymerases found associations with SNF2 helicase-associated proteins. The specific function of SNF2 family enzymes is unknown for prokaryotes and viruses. In eukaryotes, SNF2 enzymes have chromatin remodeling functions but do not separate nucleic acid strands. This suggests the strand separation function may be fulfilled by the DNA polymerase for viruses carrying SNF2 helicase-associated proteins. Biochemical data elucidated from this study expands understanding of the biology and ecological behavior of unknown viruses. Moreover, given the numerous biotechnological applications of viral DNA polymerases, novel viral polymerases discovered within viromes may be a rich source of biological material for further in vitro DNA amplification advancements.
Molecular and Biological Characterization of the First Mymonavirus Identified in Fusarium oxysporum
Authors: Wang Jing , Li Chengjun , Song Pengyu , Qiu Rui , Song Ruifang , Li Xiaojie , Ni Yunxia , Zhao Hui , Liu Hongyan , Li Shujun
Published: April 2022

We characterized a negative sense single-stranded RNA mycovirus, Fusarium oxysporum mymonavirus 1 (FoMyV1), isolated from the phytopathogenic fungus Fusarium oxysporum. The genome of FoMyV1 is 10,114 nt, including five open reading frames (ORFs1–5) that are non-overlapping and linearly arranged. The largest, ORF5, encodes a large polypeptide L containing a conserved regions corresponding to Mononegavirales RNA-dependent RNA polymerase and mRNA-capping enzyme region V; the putative functions of the remaining four ORFs are unknown. The L protein encoded by ORF5 shared a high amino acid identity of 65% with that of Hubei rhabdo-like virus 4, a mymonavirus that associated with arthropods. However, the L protein of FoMyV1 also showed amino acid similarity (27–36%) with proteins of mynonaviruses that infect the phytopathogenic fungi Sclerotinia sclerotiorum and Botrytis cineaea. Phylogenetic analysis based on L protein showed that FoMyV1 is clustered with the members of the genus Hubramonavirus in the family Mymonaviridae. Moreover, we found that FoMyV1 could successfully transfer by hyphal anastomosis to a virus-free strain. FoMyV1 reduced the vegetative growth and conidium production of its fungal host but did not alter its virulence. To the best of our knowledge, this is not only the first mymonavirus described in the species F. oxysporum, but also the first Hubramonavirus species found to infect a fungus. However, the incidence of FoMyV1 infections in the tested F. oxysporum strains was only 1%.
Intelligent Healthcare System Using Patients Confidential Data Communication in Electrocardiogram Signals
Authors: Zhao Ming , Chen Shuo-Tsung , Chen Tzu-Li , Tu Shu-Yi , Yeh Cheng-Ta , Lin Fang-Yu , Lu Hao-Chun
Published: April 2022

With the advent of the aging era, healthcare and elderly care have become the focus of medical care, especially the care of the elderly with dementia. Patients’ confidential data hiding is a useful technology for healthcare and patient information privacy. In this study, we implement an intelligent healthcare system using the multiple-coefficient quantization technology in transform domain to hide patients’ confidential data into electrocardiogram (ECG) signals obtained by ECG sensor module. In embedding patients’ confidential data, we first consider a non-linear model for optimizing the quality of the embedded ECG signals. Next, we apply simulated annealing (SA) to solve the non-linear model so as to have good signal-to-noise ratio (SNR), root mean square error (RMSE), and relative RMSE (rRMSE). Accordingly, the distortion of the PQRST complexes and the ECG amplitude is very small so that the embedded confidential data can satisfy the requirements of physiological diagnostics. In end devices, one can receive the ECG signals with the embedded confidential data and without the original ECG signals. Experimental results confirm the effectiveness of our method, which remains high quality for each ECG signal with the embedded confidential data no matter how the quantization size Q is increased.
Association Between Aneurysmal Hemodynamics and Rupture Risk of Unruptured Intracranial Aneurysms
Authors: Tian Zhongbin , Li Xifeng , Wang Chao , Feng Xin , Sun Kaijian , Tu Yi , Su Hengxian , Yang Xinjian , Duan Chuanzhi
Published: April 2022

Background

Assessing rupture risk in patients with unruptured intracranial aneurysms (UIAs) remains challenging. Hemodynamics plays an important role in the natural history of intracranial aneurysms. This study aimed to compare aneurysmal hemodynamic features between patients with different rupture risk as determined by PHASES score.

Methods

We retrospectively examined 238 patients who harbored a solitary saccular UIA. Patients were stratified by rupture risk into low-, intermediate-, and high-risk groups according to PHASES score. Flow simulations were performed to compare differences in hemodynamics among the groups.

Results

Aneurysmal time-averaged wall shear stress (WSSa) and normalized WSS (WSSn) decreased progressively as PHASES score increased. WSSa and WSSn significantly differed among the low-, intermediate-, and high-risk groups (p < 0.001). WSSa was significantly lower in the high-risk group than the low-risk group (p < 0.001) and the intermediate-risk group (p = 0.004). WSSn was also significantly lower in the high-risk group than the low-risk group (p < 0.001) and the intermediate-risk group (p = 0.001).

Conclusions

Low WSS was significantly associated with higher risk of intracranial aneurysm rupture as determined by PHASES score, indicating that hemodynamics may play an important role in aneurysmal rupture. In the future, a multidimensional rupture risk prediction model that includes hemodynamic parameters should be investigated.
A Translational Model to Improve Early Detection of Epithelial Ovarian Cancers
Authors: Gockley Allison , Pagacz Konrad , Fiascone Stephen , Stawiski Konrad , Holub Nicole , Hasselblatt Kathleen , Cramer Daniel W. , Fendler Wojciech , Chowdhury Dipanjan , Elias Kevin M.
Published: April 2022

Neural network analyses of circulating miRNAs have shown potential as non-invasive screening tests for ovarian cancer. A clinically useful test would detect occult disease when complete cytoreduction is most feasible. Here we used murine xenografts to sensitize a neural network model to detect low volume disease and applied the model to sera from 75 early-stage ovarian cancer cases age-matched to 200 benign adnexal masses or healthy controls. The 14-miRNA model efficiently discriminated tumor bearing animals from controls with 100% sensitivity down to tumor inoculums of 50,000 cells. Among early-stage patient samples, the model performed well with 73% sensitivity at 91% specificity. Applied to a population with 1% disease prevalence, we hypothesize the model would detect most early-stage ovarian cancers while maintaining a negative predictive value of 99.97% (95% CI 99.95%-99.98%). Overall, this supports the concept that miRNAs may be useful as screening markers for early-stage disease.
Glioblastoma Relapses Show Increased Markers of Vulnerability to Ferroptosis
Authors: Kram Helena , Prokop Georg , Haller Bernhard , Gempt Jens , Wu Yang , Schmidt-Graf Friederike , Schlegel Jürgen , Conrad Marcus , Liesche-Starnecker Friederike
Published: April 2022

Background

Despite the availability of various therapy options and being a widely focused research area, the prognosis of glioblastoma (GBM) still remains very poor due to therapy resistance, genetic heterogeneity and a diffuse infiltration pattern. The recently described non-apoptotic form of cell death ferroptosis may, however, offer novel opportunities for targeted therapies. Hence, the aim of this study was to investigate the potential role of ferroptosis in GBM, including the impact of treatment on the expression of the two ferroptosis-associated players glutathione-peroxidase 4 (GPX4) and acyl-CoA-synthetase long-chain family number 4 (ACSL4). Furthermore, the change in expression of the recently identified ferroptosis suppressor protein 1 (FSP1) and aldehyde dehydrogenase (ALDH) 1A3 was investigated.

Methods

Immunohistochemistry was performed on sample pairs of primary and relapse GBM of 24 patients who had received standard adjuvant treatment with radiochemotherapy. To identify cell types generally prone to undergo ferroptosis, co-stainings of ferroptosis susceptibility genes in combination with cell-type specific markers including glial fibrillary acidic protein (GFAP) for tumor cells and astrocytes, as well as the ionized calcium-binding adapter molecule 1 (Iba1) for microglial cells were performed, supplemented by double stains combining GPX4 and ACSL4.

Results

While the expression of GPX4 decreased significantly during tumor relapse, ACSL4 showed a significant increase. These results were confirmed by analyses of data sets of the Cancer Genome Atlas. These profound changes indicate an increased susceptibility of relapsed tumors towards oxidative stress and associated ferroptosis, a cell death modality characterized by unrestrained lipid peroxidation. Moreover, ALDH1A3 and FSP1 expression also increased in the relapses with significant results for ALDH1A3, whereas for FSP1, statistical significance was not reached. Results obtained from double staining imply that ferroptosis occurs more likely in GBM tumor cells than in microglial cells.

Conclusion

Our study implies that ferroptosis takes place in GBM tumor cells. Moreover, we show that recurrent tumors have a higher vulnerability to ferroptosis. These results affirm that utilizing ferroptosis processes might be a possible novel therapy option, especially in the situation of recurrent GBM.
Tip110/SART3-Mediated Regulation of NF-κB Activity by Targeting IκBα Stability Through USP15
Authors: Timani Khalid Amine , Rezaei Sahar , Whitmill Amanda , Liu Ying , He Johnny J.
Published: April 2022

To date, there are a small number of nuclear-restricted proteins that have been reported to play a role in NF-κB signaling. However, the exact molecular mechanisms are not fully understood. Tip110 is a nuclear protein that has been implicated in multiple biological processes. In a previous study, we have shown that Tip110 interacts with oncogenic ubiquitin specific peptidase 15 (USP15) and that ectopic expression of Tip110 leads to re-distribution of USP15 from the cytoplasm to the nucleus. USP15 is known to regulate NF-κB activity through several mechanisms including modulation of IκBα ubiquitination. These findings prompted us to investigate the role of Tip110 in the NF-κB signaling pathway. We showed that Tip110 regulates NF-κB activity. The expression of Tip110 potentiated TNF-α-induced NF-κB activity and deletion of the nuclear localization domain in Tip110 abrogated this potentiation activity. We then demonstrated that Tip110 altered IκBα phosphorylation and stability in the presence of TNF-α. Moreover, we found that Tip110 and USP15 opposingly regulated NF-κB activity by targeting IκBα protein stability. We further showed that Tip110 altered the expression of NF-κB-dependent proinflammatory cytokines. Lastly, by using whole-transcriptome analysis of Tip110 knockout mouse embryonic stem cells, we found several NF-κB and NF-κB-related pathways were dysregulated. Taken together, these findings add to the nuclear regulation of NF-κB activity by Tip110 through IκBα stabilization and provide new evidence to support the role of Tip110 in controlling cellular processes such as cancers that involve proinflammatory responses.