bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of the flow diversion technique on nucleotide levels in intra-cranial aneurysms: A feasibility study providing new research perspectives
Authors: Eker Omer F. , Lubicz Boris , Cortese Melissa , Delporte Cedric , Berhouma Moncef , Chopard Bastien , Costalat Vincent , Bonafé Alain , Alix-Panabières Catherine , Van Anwterpen Pierre , Zouaoui Boudjeltia Karim
Published: September 2022

Introduction

The flow diverter stent (FDS) has become a first-line treatment for numerous intra-cranial aneurysms (IAs) by promoting aneurysm thrombosis. However, the biological phenomena underlying its efficacy remain unknown. We proposed a method to collect in situ blood samples to explore the flow diversion effect within the aneurysm sac. In this feasibility study, we assessed the plasma levels of nucleotides within the aneurysm sac before and after flow diversion treatment.

Materials and methods

In total, 14 patients with unruptured IAs who were selected for FDS implantation were prospectively recruited from February 2015 to November 2015. Two catheters dedicated to (1) FDS deployment and (2) the aneurysm sac were used to collect blood samples within the parent artery (P1) and the aneurysm sac before (P2) and after (P3) flow diversion treatment. The plasma levels of adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP) at each collection point were quantified with liquid chromatography and tandem mass spectrometry.

Results

The aneurysms were extradural in nine (64.3%) patients and intra-dural in five (35.7%) patients. They presented an average diameter of 15.5 ± 7.1 mm, height of 15.8 ± 4.6 mm, and volume of 2,549 ± 2,794 ml. In all patients (100%), 16 FDS implantations and 42 in situ blood collections were performed successfully without any complications associated with the procedure. The ATP, ADP, and AMP concentrations within the aneurysm sac were decreased after flow diversion (p = 0.005, p = 0.03, and p = 0.12, respectively). Only the ATP levels within the aneurysm sac after flow diversion were significantly correlated with aneurysm volume (adjusted R2 = 0.43; p = 0.01).

Conclusion

In situ blood collection within unruptured IAs during a flow diversion procedure is feasible and safe. Our results suggest that the flow diversion technique is associated with changes in the nucleotide plasma levels within the aneurysm sac.
The role of post-translational modifications in driving abnormal cardiovascular complications at high altitude
Authors: Hou Jun , Wen Xudong , Long Pan , Xiong Shiqiang , Liu Hanxiong , Cai Lin , Deng Haoyu , Zhang Zhen
Published: September 2022

The high-altitude environment is characterized by hypobaric hypoxia, low temperatures, low humidity, and high radiation, which is a natural challenge for lowland residents entering. Previous studies have confirmed the acute and chronic effects of high altitude on the cardiovascular systems of lowlanders. Abnormal cardiovascular complications, including pulmonary edema, cardiac hypertrophy and pulmonary arterial hypertension were commonly explored. Effective evaluation of cardiovascular adaptive response in high altitude can provide a basis for early warning, prevention, diagnosis, and treatment of altitude diseases. At present, post-translational modifications (PTMs) of proteins are a key step to regulate their biological functions and dynamic interactions with other molecules. This process is regulated by countless enzymes called “writer, reader, and eraser,” and the performance is precisely controlled. Mutations and abnormal expression of these enzymes or their substrates have been implicated in the pathogenesis of cardiovascular diseases associated with high altitude. Although PTMs play an important regulatory role in key processes such as oxidative stress, apoptosis, proliferation, and hypoxia response, little attention has been paid to abnormal cardiovascular response at high altitude. Here, we reviewed the roles of PTMs in driving abnormal cardiovascular complications at high altitude.
Functional components of Chinese rice wine can ameliorate diabetic cardiomyopathy through the modulation of autophagy, apoptosis, gut microbiota, and metabolites
Authors: Yang Jinjin , Song Jiaoying , Zhou Jiedong , Lin Hui , Wu Zhuonan , Liu Nan , Xie Wenqing , Guo Hangyuan , Chi Jufang
Published: September 2022

Background

Dietary polyphenols, polypeptides, and oligosaccharides modulate inflammation and immunity by altering the composition of gut microbiota. The polyphenols and polypeptides in Chinese rice wine have protective effects against cardiovascular disease. In this study, we hypothesized that the polyphenols, polypeptides, and oligosaccharides in Chinese rice wine can ameliorate diabetic cardiomyopathy (DCM) by altering gut microbiota and metabolites.

Methods

Mice with DCM and high glucose cells were treated with rice wine polyphenols (RWPH), rice wine polypeptides (RWPE), and rice wine oligosaccharides. Cardiac function was evaluated by echocardiography and detection of myocardial injury markers. We observed the pathological structures using hematoxylin and eosin staining, Masson's trichrome staining, and transmission electron microscopy. The expression levels of autophagy-related proteins and stubRFP-sensGFP-LC3 fluorescence were measured to evaluate autophagy. We performed TUNEL staining and measured the levels of Bax, Bcl-2, and p53 to assess apoptosis. To analyze the effects of the rice wine functional components on the gut microbiota and metabolites of DCM mice, we performed fecal 16S-rDNA gene sequencing and serum untargeted metabolomics.

Results

Our results showed an increase in cardiac and mitochondrial function, promotion of autophagy, and inhibition of cardiomyocyte apoptosis, which indicates that RWPH and RWPE can ameliorate DCM. The abundance of Akkermansia and Desulfovibrio were reduced by the presence of RWPH and RWPE. The growth of the Lachnospiraceae_NK4A136_group and Clostridiales-unclassified were promoted by the presence of RWPH. Tryptophan metabolism-associated metabolites were increased and phenylalanine levels were reduced by the presence of RWPH and RWPE. The biosynthesis of primary bile acids was enhanced by the presence of RWPH.

Conclusion

Both RWPH and RWPE provided a protective effect against DCM by promoting autophagy, inhibiting apoptosis, and reversing both gut microbiota dysbiosis and metabolic dysregulation.
Long-term triggered seismicity on the Mosha fault by Damavand volcano, Iran: Implications on the seismic hazard of Tehran metropolis
Authors: Momeni Seyyedmaalek , Madariaga Raul
Published: September 2022

The seismic history of the Mosha fault, the largest and most active fault of Eastern Tehran metropolis, and its relation to the Damavand active volcano, the highest mountain in the Middle East, is investigated. We deduce that the central Mosha, near the Damavand, has a higher seismicity than either its western or eastern segments. On 7 May 2020, an Mw 5.1 earthquake occurred on the central Mosha, about 40 km east of Tehran and 10 km southwest of the Damavand crest, and it was felt intensely in Tehran. Its rupture is imaged and located in a region that presented a relative seismic quiescence compared to its eastern and western parts, during the last 14 years, suggesting its partial locking and heterogeneous distribution of fault frictional strength on this segment of Mosha. Its significant directivity to the west is confirmed by the mainshock rupture model, its PGA distribution, and distribution of early aftershocks. The rupture model suggests a relatively small stress drop of 2.6 bar, which is consistent with the comparatively high rupture dimension of 9 km for a Mw 5.1 earthquake, and indicates the easy rupture expansion on the central Mosha near the Damavand Volcano. The central Mosha experienced earthquakes in 1930, 1955, and 1983, as well as high microseismic activity and the 2020 seismic sequence, all of which strongly point to a possible influence of the Damavand Volcano on the seismicity of the central Mosha. This is corroborated by the observation of hydrothermal zones on the Mosha fault and the extension of a sill-like Damavand young magma chamber until central Mosha in tomography studies. We propose that the existing heat may increase the pore pressure on the fault, which lowers the effective normal stress, facilitates the nucleation-expansion of the rupture, and unclamps the fault. Damavand could act as a fuse and nucleate earthquakes, and if the rupture extends toward the west, it could have a significant directivity effect on low-frequency seismic waves that reach Tehran without attenuation and affect tall structures. In addition, high site amplification for frequencies up to 16 Hz due to the deep sedimentary basin, mainly in the mid-city of Tehran, will be remarkable for short buildings.
Modification of the CSIRO method in the long-term monitoring of slope-induced stress
Authors: Jin Zhihao , Li Yuan , Li Qingwen , Liu Zibin , Wu Shibing , Wang Zhuo
Published: September 2022

The in situ stress measurement technique can be used in long-term monitoring of induced stress to obtain three-dimensional stress states in slope engineering. In the monitoring, the ambient temperature fluctuation, “zero” drift of the logging data, and stable power supply should be considered. A dual temperature compensation circuit and experimental calibration techniques are proposed to increase accuracy based on the principle of the CSIRO method and considering the effect of a long-term disturbance of temperature in slope engineering. In view of the characteristics of the stress field distribution of the slope rock, the strain gauge layout scheme for induced stress monitoring of slope rock is modified to achieve the acquisition of three parallel measurements at one measurement and a stress–strain relationship equation for multilayer elastic layers is derived. An in situ stress logging system with the function of transient logging and data-connection in power cut condition is introduced to achieve a continuous correlation of measurement data under power cut conditions. An online cloud platform is established for the slope engineering of Au Mountain Iron Mine in Maanshan City. The results show that the data deviation of logging system is ±14 με with 24 days’ power off, and errors with amount of 15% were corrected by the dual temperature compensation method. The remotely transmitted data reflect the effect of temperature changes and the evolution of strain (induced stress) in real time to satisfy the demand of long-term monitoring of slope engineering.
Required jacking force for deviation rectification of inclined structures supported with rigid piles
Authors: Chai Shupeng , Fan Liujun , Liang Hui
Published: September 2022

Light poles or transmission towers may become tilted over the design life, which needs rectifying considering safety and continued use. The jacking pushing method is an efficient way to rectify deviations of these inclined structures supported with rigid piles, but there is a lack of relevant engineering standards and research in this aspect. In this study, a numerical method using FLAC3Dis proposed to estimate the required jacking force at the pile top to plumb inclined piles in cohesive soils. Good agreements between the results obtained from the present numerical models and those taken from published experimental and numerical results suggest the reliability of the conclusion. Besides, elaborate parameter analyses including pile geometry, soil properties, and properties of the soil-pile interface are conducted to investigate their influences on the required jacking force. The results can contribute to a safer and more cost-efficient design for rectifying deviations of rigid inclined piles, especially in terms of the required jacking force.
Evaluation of research performed on energy efficiency in energy-intensive manufacturing companies
Authors: Knayer Tobias , Kryvinska Natalia
Published: September 2022

The implementation of climate protection cannot succeed without increasing energy efficiency in companies. Increasing energy efficiency is an important success factor for the energy transition, but unfortunately, the energy saving potentials are only insufficiently exploited. The aim of this study is, therefore, to highlight the current state of research on energy efficiency potentials in companies at the technology level. For this purpose, an extensive literature search was conducted with more than 30 keywords. After screening and cleaning, 101 articles were selected and reviewed in detail. The literature search was performed using eight evaluation criteria: origin and year of publication, type of company, type of industry, type of data, survey method, number of participants, data collection method, and analysis method. In order to evaluate the statements and results of the considered works, a SWOT analysis was used. Our analysis revealed that: 1) studies explicitly addressing energy efficiency measures and potentials at the technology level are scarce. Even fewer studies address the relationships and interactions (positive or negative) between individual measures; 2) most studies focus on large and manufacturing companies, most of which are energy intensive. SMEs in the non-manufacturing sector, such as trade, commerce, and services, are far less represented; and 3) the chosen research focus and content are often barriers, drivers, and theory models for energy efficiency, and secondary data are mostly used. Of the studies that considered primary data, 71% used a questionnaire survey. Research into the interactions between individual measures enables policymakers to target business support programs.
Effect of compound lean blades on separation structures in high loaded compressor cascades under high subsonic condition
Authors: Tao Chuansijia , Du Xin , Zhou Xun , Luo Yizhou , Xu Wenjuan , Wang Songtao , Wang Zhongqi
Published: September 2022

Three-dimensional separation is an inherent flow feature in the blade-end corner of compressors passage, which is a primary source of entropy generation and loss. This paper researches the effect of key geometrical parameters (camber angle, solidity, dihedral angle of compound lean blade) and incoming condition (Mach number) on the evolution of corner separation in a low aspect ratio linear cascade. The underlying flow mechanism is explored in detail. The evolution of typical flow characteristics with the variation of inlet Mach number, camber angle and solidity is interpreted. For different blade loading levels, there are different corner separation forms and vortex structures. The influence of dihedral angle on the flow field structure and flow loss is analyzed, thus the effect mechanism of the compound lean blade in different flow environment is explored. Without the trailing edge shedding vortex, positive dihedral angle alleviates the low momentum fluid accumulation and corner separation at the incidence angle about 0°, but exacerbates the deteriorating corner separation at large positive incidence angle. When the trailing edge shedding vortex and the suction surface separating vortex exist together, positive dihedral angle promotes the upstream migration of the trailing edge shedding vortex, which helps to truncate the suction surface separating vortex. This variation of vortex structures is conducive to weaken the development of corner separation and delay corner stall.
Remaining useful life prediction of lithium-ion batteries using CEEMDAN and WOA-SVR model
Authors: Meng Xianmeng , Cai Cuicui , Wang Yueqin , Wang Qijian , Tan Linglong
Published: September 2022

The remaining useful life (RUL) prediction of Lithium-ion batteries (LIBs) is a crucial element of battery health management. The accurate prediction of RUL enables the maintenance and replacement of batteries with potential safety hazards, which ensures safe and stable battery operation. This paper develops a new method for the RUL prediction of LIBs, which is combined with complete ensemble empirical mode decomposition with adaptive noise (CEEDMAN), whale optimization algorithm (WOA), and support vector regression (SVR). Firstly, the CEEMDAN is employed to perform noise reduction in battery capacity data for prediction accuracy improvement. Then, an SVR model optimized by the WOA is proposed to predict the RUL. Finally, the public battery datasets are selected to validate the performance of the CEEMDAN-WOA-SVR method. The RUL prediction accuracy of the CEEMDAN-WOA-SVR method is better than the WOA-SVR method. In addition, a comparison is made between the proposed method and the existing methods (artificial bee colony algorithm-SVR method, ensemble empirical mode decomposition-gray wolf optimization-SVR method). The results show that the accurate prediction of the proposed method is superior to the two methods.
Soot formation characteristics in hybrid pyrolysis of zero-carbon fuel ammonia and ethylene mixtures
Authors: He Jiaying , Ying Yaoyao , Chen Mingxiao , Liu Dong
Published: September 2022

As soot particles from incomplete combustion of fossil fuels pose a great threat to human health, the development of low-carbon or zero-carbon alternative fuels is essential to mitigate climate change. An experimental and numerical study on the pyrolysis properties of ammonia and ethylene mixtures is conducted, focusing on the properties of soot generated by pyrolysis under different conditions and the coupling relationship between soot properties and soot precursors. The results show that the graphitization degree of soot particles generated at higher pyrolysis temperatures is enhanced, but the oxidation reactivity is decreased. When ammonia is blended, the graphitization of soot decreases and the oxidation reactivity increases. The peak mole fractions of soot precursors are negatively correlated with the graphitization degree of soot particles as the temperature increases.
Spatiotemporal variation and ecological risk assessment of sediment heavy metals in two hydrologically connected lakes
Authors: Jiang Mengyu , Wang Qichen , Tian Xue , Zhu Xiaoyan , Dong Xiangqian , Wu Zhong , Yuan Yuxiang
Published: September 2022

Excessive accumulation of heavy metals in global lake sediments poses a serious threat to lake water quality and ecosystem security. However, there is still a knowledge gap in comparison of heavy metal variation and pollution in hydrologically connected lakes. In this study, concentrations of As, Cd, Cr, Cu, Hg, Pb, and Zn in sediments of two hydrologically connected lakes, Xingkai Lake and Xiaoxingkai Lake, were determined during the hydrologically connected periods (May and September) and disconnected period (January and July) in 2021. We found the range of As was 2.58∼14.35 mg/kg, Cd was 0.050∼0.21 mg/kg, Cr was 28.58∼262.3 mg/kg, Cu was 3.12∼28.05 mg/kg, Hg was 0.0030∼0.14 mg/kg, Pb was 10.87∼58.86 mg/kg, and Zn was 18.21∼90.73 mg/kg. Heavy metal concentrations were lower than grade I level in Chinese soil quality standards with significant spatial and temporal differences in the basin. Overall, most of the sampling sites in Xingkai Lake and Xiaoxingkai Lake were at the uncontaminated level and moderate ecological risk during the sampling period. Two lakes showed different heavy metal compositions, accompanied by higher contamination level and higher potential ecological risk in the small lake than those in the large lake based on analysis of the geo-accumulation index and potential ecological risk index. Besides, the contamination level and potential ecological risk in May and September were higher than those in January and July, mainly due to human activities and hydrological connectivity. The ecological risks were moderate for Cd and Hg, and low for As, Cr, Cu, Pb, and Zn. Correlation and PCA analyses showed that Cd mainly originated from anthropogenic sources, while other metals mainly came from natural sources. These findings elucidate the effects of agriculture and hydrological connectivity on heavy metals in sediments, and provide scientific basis for the reasonable management of lake ecosystem.
Producing non-steady-state gaits (starting, stopping, and turning) in a biologically realistic quadrupedal simulation
Authors: Sellers William Irvin , Cross Charlotte Francesca , Fukuhara Akira , Ishiguro Akio , Hirasaki Eishi
Published: September 2022

Multibody dynamic analysis (MDA) has become part of the standard toolkit used to reconstruct the biomechanics of extinct animals. However, its use is currently almost exclusively limited to steady state activities such as walking and running at constant velocity. If we want to reconstruct the full range of activities that a given morphology can achieve then we must be able to reconstruct non-steady-state activities such as starting, stopping, and turning. In this paper we demonstrate how we can borrow techniques from the robotics literature to produce gait controllers that allow us to generate non-steady-state gaits in a biologically realistic quadrupedal simulation of a chimpanzee. We use a novel proportional-derivative (PD) reach controller that can accommodate both the non-linear contraction dynamics of Hill-type muscles and the large numbers of both single-joint and two-joint muscles to allow us to define the trajectory of the distal limb segment. With defined autopodial trajectories we can then use tegotae style locomotor controllers that use decentralized reaction force feedback to control the trajectory speed in order to produce quadrupedal gait. This combination of controllers can generate starting, stopping, and turning kinematics, something that we believe has never before been achieved in a simulation that uses both physiologically realistic muscles and a high level of anatomical fidelity. The gait quality is currently relatively low compared to the more commonly used feedforward control methods, but this can almost certainly be improved in future by using more biologically based foot trajectories and increasing the complexity of the underlying model and controllers. Understanding these more complex gaits is essential, particularly in fields such as paleoanthropology where the transition from an ancestral hominoid with a diversified repertoire to a bipedal hominin is of such fundamental importance, and this approach illustrates one possible avenue for further research in this area.
Successional trajectories of seed dispersal mode and seed size of canopy tree species in wet tropical forests
Authors: Wendt Amanda L. , Chazdon Robin L. , Vargas Ramirez Orlando
Published: September 2022

Despite the critical role of seed dispersal for tree colonization during forest succession in wet tropical forests, successional trajectories of seed dispersal modes are poorly documented at the community level. Overall successional trends in wet tropical forests indicate that, over time, animal-dispersed and large-seeded species increase in relative abundance in woody vegetation, whereas wind-dispersed and small-seeded species decline. Increased abundance of animal-dispersed trees during succession may be attributed to higher rates of seed deposition by animals and higher survival rates of animal-dispersed species with larger seeds (diaspores) compared to wind-dispersed species. We compiled categorical information on seed size (maximum seed length) and dispersal mode (anemochory, autochory, or zoochory) for 240 canopy tree species in six naturally regenerating forests (11–45 years since the abandonment of pasture) and two old-growth forests in lowland wet forests in northeastern Costa Rica. We evaluated dispersal mode and seed size among tree species classified as second growth and old growth specialists, and generalists based on relative abundance data in these plots. Further, we compared long-term trajectories in the dispersal and seed-size profile for 240 species of canopy tree species for seedlings, saplings, and trees ≥5 cm dbh using annual vegetation survey data from 1997 to 2013. Seed size was significantly associated with dispersal mode, which was driven by anemochorous species with intermediate seeds 6 mm to 15 mm and autochorous seeds with large seeds >15 mm. Dispersal modes of canopy tree species exhibited clear directional trajectories, with decreasing relative abundance of anemochory and increasing relative abundance of zoochory. Zoochorous seedlings showed higher survival rates than anemochorous seedlings. Species with seeds ≤ 6 mm decreased in relative abundance through succession, while species with seeds >15 mm increased within seedling and sapling communities. Seedlings with seeds >15 mm showed higher survival rates than smaller seeds in second-growth forests. The study further demonstrates the importance of seed traits, such as dispersal mode and seed size, for community assembly during forest regrowth, and the importance of frugivorous animals in this process. The abundance of animal-dispersed tree species in different size classes can be a useful indicator of the recovery of biodiversity and species interactions during forest succession in wet tropical regions.
Trichoderma – genomes and genomics as treasure troves for research towards biology, biotechnology and agriculture
Authors: Schalamun Miriam , Schmoll Monika
Published: September 2022

The genusTrichodermais among the best studied groups of filamentous fungi, largely because of its high relevance in applications from agriculture to enzyme biosynthesis to biofuel production. However, the physiological competences of these fungi, that led to these beneficial applications are intriguing also from a scientific and ecological point of view. This review therefore summarizes recent developments in studies of fungal genomes, updates on previously started genome annotation efforts and novel discoveries as well as efforts towards bioprospecting for enzymes and bioactive compounds such as cellulases, enzymes degrading xenobiotics and metabolites with potential pharmaceutical value. Thereby insights are provided into genomes, mitochondrial genomes and genomes of mycoviruses ofTrichodermastrains relevant for enzyme production, biocontrol and mycoremediation. In several cases, production of bioactive compounds could be associated with responsible genes or clusters and bioremediation capabilities could be supported or predicted using genome information. Insights into evolution of the genusTrichodermarevealed large scale horizontal gene transfer, predominantly of CAZyme genes, but also secondary metabolite clusters. Investigation of sexual development showed thatTrichodermaspecies are competent of repeat induced point mutation (RIP) and in some cases, segmental aneuploidy was observed. Some random mutants finally gave away their crucial mutations likeT. reeseiQM9978 and QM9136 and the fertility defect of QM6a was traced back to its gene defect. TheTrichodermacore genome was narrowed down to 7000 genes and gene clustering was investigated in the genomes of multiple species. Finally, recent developments in application of CRISPR/Cas9 inTrichoderma, cloning and expression strategies for the workhorseT. reeseias well as the use genome mining tools for bioprospectingTrichodermaare highlighted. The intriguing new findings on evolution, genomics and physiology highlight emerging trends and illustrate worthwhile perspectives in diverse fields of research withTrichoderma.
PANoptosis-based molecular clustering and prognostic signature predicts patient survival and immune landscape in colon cancer
Authors: Wang Xu , Sun Rui , Chan Shixin , Meng Lei , Xu Yuanmin , Zuo Xiaomin , Wang Zhenglin , Hu Xianyu , Han Qijun , Dai Longfei , Bai Tao , Yu Zhen , Wang Ming , Yang Wenqi , Zhang Huabing , Chen Wei
Published: September 2022

PANoptosis is a newly-discovered cell death pathway that involves crosstalk and co-ordination between pyroptosis, apoptosis, and necroptosis processes. However, the roles of PANoptosis-related genes (PRGs) in prognosis and immune landscape of colon cancer remain widely unknown. Here, we performed a bioinformatics analysis of expression data of nineteen PRGs identified from previous studies and clinical data of colon cancer patients obtained from TCGA and GEO databases. Colon cancer cases were divided into two PRG clusters, and prognosis-related differentially expressed genes (PRDEGs) were identified. The patient data were then separated into two corresponding distinct gene clusters, and the relationship between the risk score, patient prognosis, and immune landscape was analyzed. The identified PRGs and gene clusters correlated with patient survival and immune system and cancer-related biological processes and pathways. A prognosis signature based on seven genes was identified, and patients were divided into high-risk and low-risk groups based on the calculated risk score. A nomogram model for prediction of patient survival was also developed based on the risk score and other clinical features. Accordingly, the high-risk group showed worse prognosis, and the risk score was related to immune cell abundance, cancer stem cell (CSC) index, checkpoint expression, and response to immunotherapy and chemotherapeutic drugs. Results of quantitative real-time polymerase chain reaction (qRT-PCR) showed that LGR5 and VSIG4 were differentially expressed between normal and colon cancer samples. In conclusion, we demonstrated the potential of PANoptosis-based molecular clustering and prognostic signatures for prediction of patient survival and tumor microenvironment (TME) in colon cancer. Our findings may improve our understanding of the role of PANoptosis in colon cancer, and enable the development of more effective treatment strategies.
Development and characterization of type I interferon receptor knockout sheep: A model for viral immunology and reproductive signaling
Authors: Davies Christopher J. , Fan Zhiqiang , Morgado Kira P. , Liu Ying , Regouski Misha , Meng Qinggang , Thomas Aaron J. , Yun Sang-Im , Song Byung-Hak , Frank Jordan C. , Perisse Iuri V. , Van Wettere Arnaud , Lee Young-Min , Polejaeva Irina A.
Published: September 2022

Type I interferons (IFNs) initiate immune responses to viral infections. Their effects are mediated by the type I IFN receptor, IFNAR, comprised of two subunits: IFNAR1 and IFNAR2. One or both chains of the sheep IFNAR were disrupted in fetal fibroblast lines using CRISPR/Cas9 and 12 lambs were produced by somatic cell nuclear transfer (SCNT). Quantitative reverse transcription-polymerase chain reaction for IFN-stimulated gene expression showed that IFNAR deficient sheep fail to respond to IFN-alpha. Furthermore, fibroblast cells from anIFNAR2−/−fetus supported significantly higher levels of Zika virus (ZIKV) replication than wild-type fetal fibroblast cells. Although many lambs have died from SCNT related problems or infections, one fertileIFNAR2−/−ram lived to over 4 years of age, remained healthy, and produced more than 80 offspring. Interestingly, ZIKV infection studies failed to demonstrate a high level of susceptibility. Presumably, these sheep compensated for a lack of type I IFN signaling using the type II, IFN-gamma and type III, IFN-lambda pathways. These sheep constitute a unique model for studying the pathogenesis of viral infection. Historical data supports the concept that ruminants utilize a novel type I IFN, IFN-tau, for pregnancy recognition. Consequently, IFNAR deficient ewes are likely to be infertile, making IFNAR knockout sheep a valuable model for studying pregnancy recognition. A breeding herd of 32IFNAR2+/−ewes, which are fertile, has been developed for production ofIFNAR2−/−sheep for both infection and reproduction studies.
Providers' approaches to contraceptive provision in Cape Town
Authors: Fataar Kulthum , Zweigenthal Virginia , Harries Jane
Published: September 2022

Background

Health care providers can play a significant role in empowering women to make informed decisions when selecting suitable contraceptive methods during contraceptive counseling. This study explores primary care providers' perspectives and approaches to contraceptive service provision for women attending public sector clinics in South Africa, with the intention of ascertaining established practices and training needs.

Methods

Ten in-depth interviews were conducted at five primary health care facilities in urban areas in Cape Town, South Africa. Eligible participants included nurses providing contraceptive services and willing to participate in the study. The qualitative software package NVivo was used to sort and manage data. Data was analyzed using a thematic analysis approach.

Results

Overall, providers emphasized supporting women in contraceptive decision-making. Sexual and reproductive health training increased providers confidence to deliver appropriate contraceptive services. Contraceptive prescribing practices were influenced by women's medical history and preferred bleeding patterns. Providers' concerns about adherence to methods for younger women and suspected adverse events for older women impacted on prescribing. Challenges experienced when providing contraceptive services included: contraceptive stockouts; time constraints of employed women accessing the service; and their work pressure due to providing other health services.

Discussion

Health care providers play a critical role in facilitating women's right to access high quality contraceptive services. Providers saw themselves as negotiators during contraceptive counseling. They considered both women's preferences and their own recommendations for contraception, to provide information that would enable women to make informed contraceptive decisions. By reinforcing this approach to contraceptive counseling and focusing on shared decision-making, should encourage autonomy in method selection and limit the influence of provider's contraceptive method selection.
SARS-CoV-2 neutralizing camelid heavy-chain-only antibodies as powerful tools for diagnostic and therapeutic applications
Authors: Schlör Anja , Hirschberg Stefan , Amor Ghada Ben , Meister Toni Luise , Arora Prerna , Pöhlmann Stefan , Hoffmann Markus , Pfaender Stephanie , Eddin Omar Kamal , Kamhieh-Milz Julian , Hanack Katja
Published: September 2022

Introduction

The ongoing COVID-19 pandemic situation caused by SARS-CoV-2 and variants of concern such as B.1.617.2 (Delta) and recently, B.1.1.529 (Omicron) is posing multiple challenges to humanity. The rapid evolution of the virus requires adaptation of diagnostic and therapeutic applications.

Objectives

In this study, we describe camelid heavy-chain-only antibodies (hcAb) as useful tools for novel in vitro diagnostic assays and for therapeutic applications due to their neutralizing capacity.

Methods

Five antibody candidates were selected out of a naïve camelid library by phage display and expressed as full length IgG2 antibodies. The antibodies were characterized by Western blot, enzyme-linked immunosorbent assays, surface plasmon resonance with regard to their specificity to the recombinant SARS-CoV-2 Spike protein and to SARS-CoV-2 virus-like particles. Neutralization assays were performed with authentic SARS-CoV-2 and pseudotyped viruses (wildtype and Omicron).

Results

All antibodies efficiently detect recombinant SARS-CoV-2 Spike protein and SARS-CoV-2 virus-like particles in different ELISA setups. The best combination was shown with hcAb B10 as catcher antibody and HRP-conjugated hcAb A7.2 as the detection antibody. Further, four out of five antibodies potently neutralized authentic wildtype SARS-CoV-2 and particles pseudotyped with the SARS-CoV-2 Spike proteins of the wildtype and Omicron variant, sublineage BA.1 at concentrations between 0.1 and 0.35 ng/mL (ND50).

Conclusion

Collectively, we report novel camelid hcAbs suitable for diagnostics and potential therapy.
The multifaceted roles of common gut microbiota in immune checkpoint inhibitor-mediated colitis: From mechanism to clinical application
Authors: Han Xu , Zang Dan , Liu Dan , Chen Jun
Published: September 2022

With the arrival of the era of tumor immunotherapy, Immune Checkpoint Inhibitors have benefited countless tumor patients. However, the emergence of Immune-Related Adverse Events, especially Immune Checkpoint Inhibitor-Mediated Colitis (IMC), has become an important obstacle to immunotherapy. Therefore, it is very important to clarify the mechanism and influencing factors of IMC. The effect of gut microbiota on IMC is gradually becoming a research hotspot. Gut microbiota from different phyla can affect IMC by regulating innate and acquired immunity of tumor patients in various ways. In this review, we make a systematic and comprehensive introduction of the effect of gut microbiota on IMC. Through understanding the specific effects of gut microbiota on IMC, and then exploring the possibility of reducing IMC by regulating gut microbiota.
Deep anthropogenic impacts on benthic marine diversity of the Humboldt Current Marine Ecosystem: Insights from a Quaternary fossil baseline
Authors: Rivadeneira Marcelo M. , Nielsen Sven N.
Published: September 2022

The Humboldt Current Marine Ecosystem (HCE) is one of the most productive areas in the global ocean, but current anthropogenic stressors, particularly overfishing, pose a significant threat to marine biodiversity. Moreover, the limited time scale of modern assessments may underestimate the magnitude of human alterations to marine biodiversity. Here we use the rich Quaternary fossil record present along the HCE coast, encompassing the last ca. 500 kyr, to build a baseline to evaluate the impact of human activities on the diversity of mollusk assemblages. We compiled an extensive database of >13,000 occurrences and ca. 370,000 individuals of 164 species of gastropods and bivalves from modern and fossiliferous outcrops from southern Peru to northern Chile (15-30°S). We tested for changes in coverage-based species richness, species dominance, species composition (Chao dissimilarity, unweighted and weighted by abundance), and the relative abundance (i.e., the proportion of individuals) of species exploited by the artisanal fisheries. Comparisons between fossil and modern assemblages were carried out at different scales of spatial aggregation to buffer against inherent differences in spatial and temporal averaging. Species composition shows remarkable stability in fossil assemblages, from Middle Pleistocene to Holocene, at most scales of spatial aggregation. Modern assemblages showed drastic alterations compared to fossil counterparts when analyses considered spatial aggregation scales, i.e., significant changes in species composition, and a 3 to 6-fold reduction in the relative abundance of exploited species, but not changes in species richness and dominance. Results suggest that contemporaneous anthropogenic activities disrupted a long-term stability in the species composition. The diversity of modern mollusk assemblages is unseen in the past 500 kyr and seems deeply perturbated by overfishing. Our synthesis sets the foundations for a conservation paleobiology approach to robustly understand the impacts of anthropogenic stressors at the HCE.
Method for predicting dynamic loads for a health monitoring system for subway tracks
Authors: Jauregui-Correa Juan Carlos , Morales-Velazquez Luis , Otremba Frank , Hurtado-Hurtado Gerardo
Published: September 2022

This paper presents a method for processing acceleration data registered on a train and determining the health condition of a subway’s substructure. The acceleration data was converted into a dynamic deformation by applying a transfer function defined using the Empirical Mode Decomposition Method. The transfer function was constructed using data produced on an experimental rig, and it was scaled to an existing subway system. The equivalent deformation improved the analysis of the dynamic loads that affect the substructure of the subway tracks because it is considered the primary load that acts on the track and substructure. The acceleration data and the estimated deformations were analyzed with the Continues Wavelet Transform. The equivalent deformation data facilitated the application of a health monitoring system and simplified the development of predictive maintenance programs for the subway or railroad operators. This method better identified cracks in the substructure than using the acceleration data.
Opti-4TB: A protocol for a prospective cohort study evaluating the performance of new biomarkers for active tuberculosis outcome prediction
Authors: Bahuaud Olivier , Genestet Charlotte , Hoffmann Jonathan , Dumitrescu Oana , Ader Florence
Published: September 2022

Introduction

Tuberculosis (TB) treatment requires the combination of multiple anti-TB drugs during 6 months or more depending on strain drug susceptibility profile. Optimizing the monitoring of anti-TB therapy efficacy is required to provide adequate care and prevent drug resistance emergence. Moreover, accurate monitoring tools are needed for the development of strategies aiming at reducing treatment duration. Opti-4TB is a “proof of concept” study aiming at developing a blood-based monitoring of TB outcome by deciphering host immune signatures associated with latency or disease activity through the combination of “omic” methods. The primary objective is to assess the performances of new biomarkers for TB outcome prediction and to determine specific profiles associated with the outcome of treated TB patients.

Methods and analysis

Opti-4TB is a prospective, single center study including adult patients hospitalized for pulmonary TB. A workflow will be set up to study the immune status of 40 TB patients and 20 controls with latent TB infection. Blood samples will be collected at four timepoints: before treatment initiation (V1), at day 15 (V2), at 2 months (V3) and at 6 months (V4). Mtb-specific immune responses will be assessed at each timepoint with three different assays: (1) A whole blood transcriptomic signature assessing the “RISK-6” score; (2) A proteomic signature based on 27 cytokines and chemokines measured in plasma; (3) An immunophenotypic monitoring of circulating T-cell subpopulations using spectral flow cytometry. This in depth characterization of Mtb-specific immune response throughout the treatment, correlated with clinical outcomes, will lay the basis for the elaboration of the most basic and universal stage-specific immune signatures associated with latency, active disease and cure.

Ethics and dissemination

Ethical approval has been obtained from the institutional review board (n°69HCL18_0757). Results will be communicated at scientific meetings and submitted for publication in peer-reviewed journals.

Trial registration number

NCT04271397.
Unraveling key interactions and the mechanism of demethylation during hAGT-mediated DNA repair via simulations
Authors: T. G. Shruti , Siddiqui Shakir Ali , Dubey Kshatresh Dutta
Published: September 2022

Alkylating agents pose the biggest threat to the genomic integrity of cells by damaging DNA bases through regular alkylation. Such damages are repaired by several automated types of machinery inside the cell. O6-alkylguanine-DNA alkyltransferase (AGT) is an enzyme that performs the direct repair of an alkylated guanine base by transferring the alkyl group to a cysteine residue. In the present study, using extensive MD simulations and hybrid QM/MM calculations, we have investigated the key interactions between the DNA lesion and the hAGT enzyme and elucidated the mechanisms of the demethylation of the guanine base. Our simulation shows that the DNA lesion is electrostatically stabilized by the enzyme and the Arg135 of hAGT enzyme provides the main driving force to flip the damaged base into the enzyme. The QM/MM calculations show demethylation of the damaged base as a three-step process in a thermodynamically feasible and irreversible manner. Our calculations show that the final product forms via Tyr114 in a facile way in contrast to the previously proposed Lys-mediated route.
Role of USP13 in physiology and diseases
Authors: Wang Qian , Sun Zhenzhen , Xia Weiwei , Sun Le , Du Yang , Zhang Yue , Jia Zhanjun
Published: September 2022

Ubiquitin specific protease (USP)-13 is a deubiquitinase that removes ubiquitin from substrates to prevent protein degradation by the proteasome. Currently, the roles of USP13 in physiology and pathology have been reported. In physiology, USP13 is highly associated with cell cycle regulation, DNA damage repair, myoblast differentiation, quality control of the endoplasmic reticulum, and autophagy. In pathology, it has been reported that USP13 is important in the pathogenesis of infection, inflammation, idiopathic pulmonary fibrosis (IPF), neurodegenerative diseases, and cancers. This mini-review summarizes the most recent advances in USP13 studies involving its pathophysiological roles in different conditions and provides new insights into the prevention and treatment of relevant diseases, as well as further research on USP13.
Oxytocin in Huntington’s disease and the spectrum of amyotrophic lateral sclerosis-frontotemporal dementia
Authors: Bergh Sofia , Cheong Rachel Y. , Petersén Åsa , Gabery Sanaz
Published: September 2022

Neurodegenerative disorders (NDDs) such as Huntington’s disease (HD) and the spectrum of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are characterized by progressive loss of selectively vulnerable populations of neurons. Although often associated with motor impairments, these NDDs share several commonalities in early symptoms and signs that extend beyond motor dysfunction. These include impairments in social cognition and psychiatric symptoms. Oxytocin (OXT) is a neuropeptide known to play a pivotal role in the regulation of social cognition as well as in emotional behaviors such as anxiety and depression. Here, we present an overview of key results implicating OXT in the pathology of HD, ALS and FTD and seek to identify commonalities across these NDDs. OXT is produced in the hypothalamus, a region in the brain that during the past decade has been shown to be affected in HD, ALS, and FTD. Several studies using human post-mortem neuropathological analyses, measurements of cerebrospinal fluid, experimental treatments with OXT as well as genetic animal models have collectively implicated an important role of central OXT in the development of altered social cognition and psychiatric features across these diseases. Understanding central OXT signaling may unveil the underlying mechanisms of early signs of the social cognitive impairment and the psychiatric features in NDDs. It is therefore possible that OXT might have potential therapeutic value for early disease intervention and better symptomatic treatment in NDDs.
Improved localization of radioactivity with a normalized sinc transform
Authors: Tsitsimpelis Ioannis , Alton Tilly L. , West Andrew , Taylor C. James , Livens Francis R. , Lennox Barry , Joyce Malcolm J.
Published: September 2022

A technique for the in-situ localization of radioactivity is described in which the influence of γ-radiation impinging on a high-Z collimator, by which the angular response of a scintillation detector is constrained in order to identify the corresponding angular position of the radiation source, is expressed mathematically by way of a normalized sinc transform. We test this approach by examining the utility of the sinc transform to express the angular responses derived from a slot-collimated cerium bromide detector, across a variety of energy regions. Individual spectra have been acquired as a function of angle to explore how the shape of the response of the collimator-detector arrangement changes for X-rays and γ rays. A 90% improvement in localization is observed when this is defined in terms of the area described by the variance between the known location and that indicated by the response of the collimated system. This approach has the potential to improve source location accuracy and to further optimize autonomous robot exploration routines used to characterize contaminated environments associated with nuclear legacies and radiological emergencies.