bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical Simulation of Deep-Sea Sediment Transport Induced by a Dredge Experiment in the Northeastern Pacific Ocean
Authors: Purkiani Kaveh , Gillard Benjamin , Paul André , Haeckel Matthias , Haalboom Sabine , Greinert Jens , de Stigter Henko , Hollstein Martina , Baeye Matthias , Vink Annemiek , Thomsen Laurenz , Schulz Michael
Published: September 2021

Predictability of the dispersion of sediment plumes induced by potential deep-sea mining activities is still very limited due to operational limitations on in-situ observations required for a thorough validation and calibration of numerical models. Here we report on a plume dispersion experiment carried out in the German license area for the exploration of polymetallic nodules in the northeastern tropical Pacific Ocean in 4,200 m water depth. The dispersion of a sediment plume induced by a small-scale dredge experiment in April 2019 was investigated numerically by employing a sediment transport module coupled to a high-resolution hydrodynamic regional ocean model. Various aspects including sediment characteristics and ocean hydrodynamics were examined to obtain the best statistical agreement between sensor-based observations and model results. Results show that the model is capable of reproducing suspended sediment concentration and redeposition patterns observed during the dredge experiment. Due to a strong southward current during the dredging, the model predicts no sediment deposition and plume dispersion north of the dredging tracks. The sediment redeposition thickness reaches up to 9 mm directly next to the dredging tracks and 0.07 mm in about 320 m away from the dredging center. The model results suggest that seabed topography and variable sediment release heights above the seafloor cause significant changes especially for the low sedimentation pattern in the far-field area. Near-bottom mixing is expected to strongly influence vertical transport of suspended sediment.
Stock Assessment of 19 Perciformes in the Beibu Gulf, China, Using a Length-Based Bayesian Biomass Method
Authors: Hou Gang , Zhang Hui , Wang Jinrun , Chen Yanying , Lin Jianbin
Published: September 2021

The Beibu Gulf in China is rich in fish resources. However, only a small number of commercially developed fish stocks have been specifically assessed owing to limited data and expertise. In this study, 19 perciform fish populations in the Beibu Gulf were assessed using a length-based Bayesian biomass (LBB) estimator method, which is a new approach to evaluate a fishery’s status using length frequency (LF) data. The results showed that only 21% of the evaluated stocks were healthy and 79% were overfished. In particular, 26 and 21% of the assessed species had collapsed and were grossly overfished, respectively. Only 11 and 21% of the assessed species were slightly overfished and overfished, respectively. The ratios between the mean and optimum length (Lmean/Lopt) and between the mean length at first capture and the mean length, which maximizes catch and biomass (Lc/Lc_opt), were below one in 14 out of the 19 stocks, suggesting a truncated length structure and fishing of undersized individuals. The ratio of the 95th percentile length to asymptotic length L95th/Linf was close to one (>0.9) in 10 of 19 stocks, suggesting that at least some large fish were still present. Our research confirmed that the fishery resources in the Beibu Gulf were seriously overfished and provided evidence that LBB was an efficient method to evaluate the fishery resources. Fishery managers need to take specific measures to restore fishery resources.
Rules of Engagement: Epithelial-Microbe Interactions and Inflammatory Bowel Disease
Authors: Jergens Albert E. , Parvinroo Shadi , Kopper Jamie , Wannemuehler Michael J.
Published: September 2021

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex, multifactorial disorders that lead to chronic and relapsing intestinal inflammation. The exact etiology remains unknown, however multiple factors including the environment, genetic, dietary, mucosal immunity, and altered microbiome structure and function play important roles in disease onset and progression. Supporting this notion that the gut microbiota plays a pivotal role in IBD pathogenesis, studies in gnotobiotic mice have shown that mouse models of intestinal inflammation require a microbial community to develop colitis. Additionally, antimicrobial therapy in some IBD patients will temporarily induce remission further demonstrating an association between gut microbes and intestinal inflammation. Finally, a dysfunctional intestinal epithelial barrier is also recognized as a key pathogenic factor in IBD. The intestinal epithelium serves as a barrier between the luminal environment and the mucosal immune system and guards against harmful molecules and microorganisms while being permeable to essential nutrients and solutes. Beneficial (i.e., mutualists) bacteria promote mucosal health by strengthening barrier integrity, increasing local defenses (mucin and IgA production) and inhibiting pro-inflammatory immune responses and apoptosis to promote mucosal homeostasis. In contrast, pathogenic bacteria and pathobionts suppress expression and localization of tight junction proteins, cause dysregulation of apoptosis/proliferation and increase pro-inflammatory signaling that directly damages the intestinal mucosa. This review article will focus on the role of intestinal epithelial cells (IECs) and the luminal environment acting as mediators of barrier function in IBD. We will also share some of our translational observations of interactions between IECs, immune cells, and environmental factors contributing to maintenance of mucosal homeostasis, as it relates to GI inflammation and IBD in different animal models.
Clinical Risk Factors for Mortality Among Critically Ill Mexican Patients With COVID-19
Authors: Hernández-Cárdenas Carmen M. , Choreño-Parra José Alberto , Torruco-Sotelo Carlos , Jurado Felipe , Serna-Secundino Héctor , Aguilar Cristina , García-Olazarán José G. , Hernández-García Diana , Choreño-Parra Eduardo M. , Zúñiga Joaquín , Lugo-Goytia Gustavo
Published: September 2021

Little literature exists about critically ill patients with coronavirus disease 2019 (COVID-19) from Latin America. Here, we aimed to describe the clinical characteristics and mortality risk factors in mechanically ventilated COVID-19 patients from Mexico. For this purpose, we recruited 67 consecutive mechanically ventilated COVID-19 patients which were grouped according to their clinical outcome (survival vs. death). Clinical risk factors for mortality were identified by machine-learning and logistic regression models. The median age of participants was 42 years and 65% were men. The most common comorbidity observed was obesity (49.2%). Fever was the most frequent symptom of illness (88%), followed by dyspnea (84%). Multilobe ground-glass opacities were observed in 76% of patients by thoracic computed tomography (CT) scan. Fifty-two percent of study participants were ventilated in prone position, and 59% required cardiovascular support with norepinephrine. Furthermore, 49% of participants were coinfected with a second pathogen. Two-thirds of COVID-19 patients developed acute kidney injury (AKIN). The mortality of our cohort was 44.7%. AKIN, uric acid, lactate dehydrogenase (LDH), and a longitudinal increase in the ventilatory ratio were associated with mortality. Baseline PaO2/FiO2 values and a longitudinal recovery of lymphocytes were protective factors against mortality. Our study provides reference data about the clinical phenotype and risk factors for mortality in mechanically ventilated Mexican patients with COVID-19.
Radiation Therapy Planning of Thoracic Tumors: A Review of Challenges Associated With Lung Toxicities and Potential Perspectives of Gallium-68 Lung PET/CT Imaging
Authors: Lucia François , Rehn Martin , Blanc-Béguin Frédérique , Le Roux Pierre-Yves
Published: September 2021

Despite the introduction of new radiotherapy techniques, such as intensity modulated radiation therapy or stereotactic body radiation therapy, radiation induced lung injury remains a significant treatment related adverse event of thoracic radiation therapy. Functional lung avoidance radiation therapy is an emerging concept in the treatment of lung disease to better preserve lung function and to reduce pulmonary toxicity. While conventional ventilation/perfusion (V/Q) lung scintigraphy is limited by a relatively low spatial and temporal resolution, the recent advent of 68Gallium V/Q lung PET/CT imaging offers a potential to increase the accuracy of lung functional mapping and to better tailor lung radiation therapy plans to the individual's lung function. Lung PET/CT imaging may also improve our understanding of radiation induced lung injury compared to the current anatomical based dose–volume constraints. In this review, recent advances in radiation therapy for the management of primary and secondary lung tumors and in V/Q PET/CT imaging for the assessment of functional lung volumes are reviewed. The new opportunities and challenges arising from the integration of V/Q PET/CT imaging in radiation therapy planning are also discussed.
Artificial Intelligence in Obstetric Ultrasound: An Update and Future Applications
Authors: Chen Zhiyi , Liu Zhenyu , Du Meng , Wang Ziyao
Published: September 2021

Artificial intelligence (AI) can support clinical decisions and provide quality assurance for images. Although ultrasonography is commonly used in the field of obstetrics and gynecology, the use of AI is still in a stage of infancy. Nevertheless, in repetitive ultrasound examinations, such as those involving automatic positioning and identification of fetal structures, prediction of gestational age (GA), and real-time image quality assurance, AI has great potential. To realize its application, it is necessary to promote interdisciplinary communication between AI developers and sonographers. In this review, we outlined the benefits of AI technology in obstetric ultrasound diagnosis by optimizing image acquisition, quantification, segmentation, and location identification, which can be helpful for obstetric ultrasound diagnosis in different periods of pregnancy.
The Role of IL-37 and IL-38 in Obstetrics Abnormalities
Authors: Wang Mei
Published: September 2021

There are two fairly common complications during pregnancy, i.e., gestational diabetes mellitus (GDM) and pre-eclampsia, which are independent, but are also closely linked in prevalence in pregnant women, with potential serious adverse consequences. IL-37 and IL-38, which belong to the IL-1 superfamily, participate in anti-inflammatory responses. Dysregulation of IL-37 and IL-38 has been observed in many auto-immune diseases. IL-37 is substantially reduced in the umbilical cords and placentas of GDM subjects, but IL-37 is significantly induced in the placentas of pre-eclampsia patients, suggesting there are differential regulatory roles of IL-37 in obstetrics, despite IL-37 being an anti-inflammatory mediator. Furthermore, IL-38 is substantially increased in the umbilical cords and placentas of GDM subjects, but minimal difference is observed in the placentas from pre-eclampsia patients. These data imply that IL-38 is also regulated independently within the diseased placentas. This review provides some insight for both basic scientists and medical practitioners to manage these patients effectively.
Dialyzer Classification and Mortality in Hemodialysis Patients: A 3-Year Nationwide Cohort Study
Authors: Abe Masanori , Masakane Ikuto , Wada Atsushi , Nakai Shigeru , Nitta Kosaku , Nakamoto Hidetomo
Published: September 2021

Background: Dialyzers are classified as low-flux, high-flux, and protein-leaking membrane dialyzers internationally and as types I, II, III, IV, and V based on β2-microglobulin clearance rate in Japan. Type I dialyzers correspond to low-flux membrane dialyzers, types II and III to high-flux membrane dialyzers, and types IV and V to protein-leaking membrane dialyzers. Here we aimed to clarify the association of dialyzer type with mortality.

Methods: This nationwide retrospective cohort study analyzed data from the Japanese Society for Dialysis Therapy Renal Data Registry from 2010 to 2013. We enrolled 238,321 patients on hemodialysis who were divided into low-flux, high-flux, and protein-leaking groups in the international classification and into type I to V groups in the Japanese classification. We assessed the associations of each group with 3-year all-cause mortality using Cox proportional hazards models and performed propensity score matching analysis.

Results: By the end of 2013, 55,308 prevalent dialysis patients (23.2%) had died. In the international classification subgroup analysis, the hazard ratio (95% confidence interval) was significantly higher in the low-flux group [1.12 (1.03–1.22), P = 0.009] and significantly lower in the protein-leaking group [0.95 (0.92–0.98), P = 0.006] compared with the high-flux group after adjustment for all confounders. In the Japanese classification subgroup analysis, the hazard ratios were significantly higher for types I [1.10 (1.02–1.19), P = 0.015] and II [1.10 (1.02–1.39), P = 0.014] but significantly lower for type V [0.91 (0.88–0.94), P < 0.0001] compared with type IV after adjustment for all confounders. These significant findings persisted after propensity score matching under both classifications.

Conclusions: Hemodialysis using protein-leaking dialyzers might reduce mortality rates. Furthermore, type V dialyzers are superior to type IV dialyzers in hemodialysis patients.
Evaluation of the Good Review Practices of Countries Participating in the Southern African Development Community: Alignment and Strategies for Moving Forward
Authors: Sithole Tariro , Mahlangu Gugu , Capote Velma , Sitoie Tania , Shifotoka Saren , Gaeseb Johannes , Padayachee Silverani , Sehloho Tohlang , Khea Akida , Fimbo Adam , Munkombwe Zuma , Mwale Bernice , Salek Sam , Walker Stuart
Published: September 2021

Introduction: National medicines regulatory agencies are faced with challenges including limited resources and technical capacity, resulting in countries collaborating and sharing resources to improve efficiency of the review process to facilitate access to quality-assured medicines by their populations. One such collaboration is the Southern African Development Community (SADC) medicines registration collaborative initiative, ZaZiBoNa. Countries participate in the initiative by contributing to regulatory reviews and good manufacturing practices inspections. The aim of this study was to review and compare the registration processes of regulatory authorities of Mozambique, Namibia, South Africa, Tanzania, Zambia, and Zimbabwe to identify strategies for better alignment.

Methods: A senior member of the division responsible for issuing marketing authorisations completed an established and validated questionnaire, which standardises the review process, allowing key milestones, activities and practices of the six regulatory authorities to be identified and compared. The completed questionnaires were validated by the heads of the respective agencies.

Results: The six countries vary in population and in the size of their respective regulatory agency and the resources allocated to regulatory reviews. The review processes of the six agencies were similar; however, differences were noted in the milestones recorded; for example, two of the countries did not record the start of the scientific assessment. Additionally, decisions for marketing authorisation were made by an expert committee in four of the countries and by the head of the agency and the Minister of Health in two countries. All six agencies implemented the majority of good review practices; however, the need for improvement in the areas of transparency and communication and quality decision making practices was a common finding for all six countries.

Conclusions: Participation in the ZaZiBoNa initiative has improved the way in which the six agencies perform regulatory reviews in their countries, highlighting the realisation of one of the key objectives of the initiative, which was building the expert capacity of member countries. Other agencies in the SADC region and beyond can use the results of this study to identify best practices, which in turn, could improve their regulatory performance.
Discerning the Antimicrobial Resistance, Virulence, and Phylogenetic Relatedness of Salmonella Isolates Across the Human, Poultry, and Food Materials Sources in Malaysia
Authors: Zakaria Zunita , Hassan Latiffah , Ahmad Norazah , Husin Suraya Amir , Ali Rohaya Mohd , Sharif Zawiyah , Sohaimi Norfitriah Mohamed , Garba Bashiru
Published: September 2021

Salmonella entericasubspeciesentericaserovar Enteritidis is one of the major foodborne zoonotic pathogens globally. It has significantly impacted human health and global trade. In this investigation, whole-genome sequencing was employed to determine the antimicrobial resistance (AMR) pattern of a collection ofSalmonellaEnteritidis isolated from humans, poultry, and food sources. The study also investigated the virulence genes profile of the isolates as well as the phylogenetic relationships among strains. Illumina NextSeq technology was used to sequence the genome of 82SalmonellaEnteritidis strains isolated over 3 years (2016–2018) in Peninsular Malaysia. The pattern of resistance showed that tetracycline had the highest frequency (37/82, 45.12%), and isolates from food samples showed the highest rate of 9/18 (50.00%), followed by human 17/35 (48.57%) and then poultry 11/29 (37.93%). The second drug with the highest resistance rate is ampicillin with 5/29 (17.24%) for poultry, 4/35 (11.43%) for human, and 0/18 (0.00%) for food isolates respectively. Similarly, a total of 19 antimicrobial resistance (AMR) genes corresponding to the nine drugs used in the disc diffusion assay were evaluated from the whole genome sequence data. The aminoglycoside resistance geneaac(6′)-lywas detected in 79 of the 82 isolates (96.34%). While the phylogenetic analysis revealed distinct lineages isolated, the three sources indicating possible cross-contamination. In conclusion, the results showed that the genomic profile ofSalmonellaEnteritidis isolated from humans, poultry, and food samples share genetic traits, hence the need to institute measures at controlling the continuous spread of these resistant pathogens.
Effects of Biogas Slurry Combined With Chemical Fertilizer on Soil Bacterial and Fungal Community Composition in a Paddy Field
Authors: Zhang Hanlin , Li Shuangxi , Zheng Xianqing , Zhang Juanqin , Bai Naling , Zhang Haiyun , Lv Weiguang
Published: September 2021

The application of biogas slurry and chemical fertilizer in paddy fields can be a practical method to reduce the environmental risk and utilize the nutrients of biogas slurry. The responses of bacterial and fungal communities to the application of biogas slurry and chemical fertilizer are important reflections of the quality of the ecological environment. In this study, based on a 3-year field experiment with different ratios of biogas slurry and chemical fertilizer (applying the same pure nitrogen amount), the Illumina MiSeq platform was used to investigate the bacterial and fungal community diversity and composition in paddy soil. Our results revealed that compared with the observations under regular chemical fertilization, on the basis of stable paddy yield, the application of biogas slurry combined with chemical fertilizer significantly enhanced the soil nutrient availability and bacterial community diversity and reduced the fungal community diversity. Dissolved organic carbon (DOC), DOC/SOC (soil organic carbon), available nitrogen (AN) and available phosphorus (AP) were positively correlated with the bacterial community diversity, but no soil property was significantly associated with the fungal community. The bacterial community was primarily driven by the application of biogas slurry combined with chemical fertilizer (40.78%), while the fungal community was almost equally affected by the addition of pure biogas slurry, chemical fertilizer and biogas slurry combined with chemical fertilizer (25.65–28.72%). Biogas slurry combined with chemical fertilizer significantly enriched Proteobacteria, Acidobacteria, Planctomycetes, Rokubacteria, and Ascomycota and depleted Chloroflexi, Bacteroidetes, Crenarchaeota, Basidiomycota, and Glomeromycota. The observation of the alteration of some bacteria- and fungus-specific taxa provides insights for the proper application of biogas slurry combined with chemical fertilizer, which has the potential to promote crop growth and inhibit pathogens.
Synergies of Systems Biology and Synthetic Biology in Human Microbiome Studies
Authors: Ezzamouri Bouchra , Shoaie Saeed , Ledesma-Amaro Rodrigo
Published: September 2021

A number of studies have shown that the microbial communities of the human body are integral for the maintenance of human health. Advances in next-generation sequencing have enabled rapid and large-scale quantification of the composition of microbial communities in health and disease. Microorganisms mediate diverse host responses including metabolic pathways and immune responses. Using a system biology approach to further understand the underlying alterations of the microbiota in physiological and pathological states can help reveal potential novel therapeutic and diagnostic interventions within the field of synthetic biology. Tools such as biosensors, memory arrays, and engineered bacteria can rewire the microbiome environment. In this article, we review the computational tools used to study microbiome communities and the current limitations of these methods. We evaluate how genome-scale metabolic models (GEMs) can advance our understanding of the microbe–microbe and microbe–host interactions. Moreover, we present how synergies between these system biology approaches and synthetic biology can be harnessed in human microbiome studies to improve future therapeutics and diagnostics and highlight important knowledge gaps for future research in these rapidly evolving fields.
RNA-Based Analysis Reveals High Diversity of Plant-Associated Active Fungi in the Atmosphere
Authors: Chen Yan , Zhu Xishen , Hou Ziqiong , Wang Yi , Zhou Yunying , Wang Ling , Liu Lin , Duan Jingrong , Jibril Sauban Musa , Li Chengyun
Published: September 2021

Fungi are ubiquitous in nature; that is, they are present everywhere on the planet; understanding the active state and functional capacity of airborne microbes associated with health of human, animal, and plant is critical for biosafety management. Here, we firstly and directly proved that there were about 40% active fungi in the airviarRNA amplicon sequencing and imaging flow cytometry simultaneously. Amplicon sequencing analysis showed differences between structures of active and total fungal community; Ascomycota were dominant in the active community, while Basidiomycota have low transcriptional activity across all samples. Notably, plant pathogenic fungi were predominant in the air, and more than 50% were active, including not only several common plant pathogens but also biotrophic fungi (Erysiphesp. andMicrobotryumsp.) and host-specific pathogens, which were generally considered to be inactive after leaving the host. Putative plant pathogens of eight genera were found active across the sampling season, indicating their superior ability to obtain nutrients even in barren nutrient environments. Interestingly, we detected several potentially active unrecorded fungi in China (Diatrype prominens,Septofusidium herbarum,Pseudomicrostroma glucosiphilum, andUromycladium tepperianum), which suggested that they spread over a long distance by air and may cause diseases under favorable conditions. Our results suggested that maintaining transmission in air is an essential feature of many fungi including plant pathogens regardless of being a biotrophic, hemibiotrophic, or necrotrophic group. Moreover, two potentially active human pathogens and one animal pathogen were captured, which indicated their potential risks. This study provided a new perspective for more comprehensive understanding of airborne fungi, including their multidimensional lifestyle, state, functioning, and potential pathogenic risk. It also laid the foundation for further prediction and management of airborne microbial communities, which would be of interest for public health and agriculture.
Comparative Analysis of Machine Learning Algorithms on Surface Enhanced Raman Spectra of Clinical Staphylococcus Species
Authors: Tang Jia-Wei , Liu Qing-Hua , Yin Xiao-Cong , Pan Ya-Cheng , Wen Peng-Bo , Liu Xin , Kang Xing-Xing , Gu Bing , Zhu Zuo-Bin , Wang Liang
Published: September 2021

Raman spectroscopy (RS) is a widely used analytical technique based on the detection of molecular vibrations in a defined system, which generates Raman spectra that contain unique and highly resolved fingerprints of the system. However, the low intensity of normal Raman scattering effect greatly hinders its application. Recently, the newly emerged surface enhanced Raman spectroscopy (SERS) technique overcomes the problem by mixing metal nanoparticles such as gold and silver with samples, which greatly enhances signal intensity of Raman effects by orders of magnitudes when compared with regular RS. In clinical and research laboratories, SERS provides a great potential for fast, sensitive, label-free, and non-destructive microbial detection and identification with the assistance of appropriate machine learning (ML) algorithms. However, choosing an appropriate algorithm for a specific group of bacterial species remains challenging, because with the large volumes of data generated during SERS analysis not all algorithms could achieve a relatively high accuracy. In this study, we compared three unsupervised machine learning methods and 10 supervised machine learning methods, respectively, on 2,752 SERS spectra from 117 Staphylococcus strains belonging to nine clinically important Staphylococcus species in order to test the capacity of different machine learning methods for bacterial rapid differentiation and accurate prediction. According to the results, density-based spatial clustering of applications with noise (DBSCAN) showed the best clustering capacity (Rand index 0.9733) while convolutional neural network (CNN) topped all other supervised machine learning methods as the best model for predicting Staphylococcus species via SERS spectra (ACC 98.21%, AUC 99.93%). Taken together, this study shows that machine learning methods are capable of distinguishing closely related Staphylococcus species and therefore have great application potentials for bacterial pathogen diagnosis in clinical settings.
Effects of Simulated Microgravity on the Physiology of Stenotrophomonas maltophilia and Multiomic Analysis
Authors: Su Xiaolei , Guo Yinghua , Fang Tingzheng , Jiang Xuege , Wang Dapeng , Li Diangeng , Bai Po , Zhang Bin , Wang Junfeng , Liu Changting
Published: September 2021

Many studies have shown that the space environment plays a pivotal role in changing the characteristics of conditional pathogens, especially their pathogenicity and virulence. However, Stenotrophomonas maltophilia, a type of conditional pathogen that has shown to a gradual increase in clinical morbidity in recent years, has rarely been reported for its impact in space. In this study, S. maltophilia was exposed to a simulated microgravity (SMG) environment in high-aspect ratio rotating-wall vessel bioreactors for 14days, while the control group was exposed to the same bioreactors in a normal gravity (NG) environment. Then, combined phenotypic, genomic, transcriptomic, and proteomic analyses were conducted to compare the influence of the SMG and NG on S. maltophilia. The results showed that S. maltophilia in simulated microgravity displayed an increased growth rate, enhanced biofilm formation ability, increased swimming motility, and metabolic alterations compared with those of S. maltophilia in normal gravity and the original strain of S. maltophilia. Clusters of Orthologous Groups (COG) annotation analysis indicated that the increased growth rate might be related to the upregulation of differentially expressed genes (DEGs) involved in energy metabolism and conversion, secondary metabolite biosynthesis, transport and catabolism, intracellular trafficking, secretion, and vesicular transport. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the increased motility might be associated the upregulation of differentially expressed proteins (DEPs) involved in locomotion, localization, biological adhesion, and binding, in accordance with the upregulated DEGs in cell motility according to COG classification, including pilP, pilM, flgE, flgG, and ronN. Additionally, the increased biofilm formation ability might be associated with the upregulation of DEPs involved in biofilm formation, the bacterial secretion system, biological adhesion, and cell adhesion, which were shown to be regulated by the differentially expressed genes (chpB, chpC, rpoN, pilA, pilG, pilH, and pilJ) through the integration of transcriptomic and proteomic analyses. These results suggested that simulated microgravity might increase the level of corresponding functional proteins by upregulating related genes to alter physiological characteristics and modulate growth rate, motility, biofilm formation, and metabolism. In conclusion, this study is the first general analysis of the phenotypic, genomic, transcriptomic, and proteomic changes in S. maltophilia under simulated microgravity and provides some suggestions for future studies of space microbiology.
Respiratory Microbiota Profiles Associated With the Progression From Airway Inflammation to Remodeling in Mice With OVA-Induced Asthma
Authors: Zheng Jun , Wu Qian , Zou Ya , Wang Meifen , He Li , Guo Sheng
Published: September 2021

Background

The dysbiosis of respiratory microbiota plays an important role in asthma development. However, there is limited information on the changes in the respiratory microbiota and how these affect the host during the progression from acute allergic inflammation to airway remodeling in asthma.

Objective

An ovalbumin (OVA)-induced mouse model of chronic asthma was established to explore the dynamic changes in the respiratory microbiota in the different stages of asthma and their association with chronic asthma progression.

Methods

Hematoxylin and eosin (H&E), periodic acid-schiff (PAS), and Masson staining were performed to observe the pathological changes in the lung tissues of asthmatic mice. The respiratory microbiota was analyzed using 16S rRNA gene sequencing followed by taxonomical analysis. The cytokine levels in bronchoalveolar lavage fluid (BALF) specimens were measured. The matrix metallopeptidase 9 (MMP-9) and vascular endothelial growth factor (VEGF-A) expression levels in lung tissues were measured to detect airway remodeling in OVA-challenged mice.

Results

Acute allergic inflammation was the major manifestation at weeks 1 and 2 after OVA atomization stimulation, whereas at week 6 after the stimulation, airway remodeling was the most prominent observation. In the acute inflammatory stage, Pseudomonas was more abundant, whereas Staphylococcus and Cupriavidus were more abundant at the airway remodeling stage. The microbial compositions of the upper and lower respiratory tracts were similar. However, the dominant respiratory microbiota in the acute inflammatory and airway remodeling phases were different. Metagenomic functional prediction showed that the pathways significantly upregulated in the acute inflammatory phase and airway remodeling phase were different. The cytokine levels in BALF and the expression patterns of proteins associated with airway remodeling in the lung tissue were consistent with the metagenomic function results.

Conclusion

The dynamic changes in respiratory microbiota are closely associated with the progression of chronic asthma. Metagenomic functional prediction indicated the changes associated with acute allergic inflammation and airway remodeling.
Detection of Colistin Resistance in Pseudomonas aeruginosa Using the MALDIxin Test on the Routine MALDI Biotyper Sirius Mass Spectrometer
Authors: Jeannot Katy , Hagart Katheryn , Dortet Laurent , Kostrzewa Markus , Filloux Alain , Plesiat Patrick , Larrouy-Maumus Gerald
Published: September 2021

Colistin is frequently a last resort treatment for Pseudomonas aeruginosa infections caused by multidrug-resistant (MDR) and extensively drug resistant (XDR) strains, and detection of colistin resistance is essential for the management of infected patients. Therefore, we evaluated the recently developed MALDIxin test for the detection of colistin resistance in P. aeruginosa clinical strains using the routine matrix-assisted laser desorption ionization (MALDI) Biotyper Sirius system. The test is based on the detection by mass spectrometry of modified lipid A by the addition of 4-amino-l-arabinose (l-ara4N) molecules on one or two phosphate groups, in strains resistant to colistin. Overproduction of l-Ara4N molecules is mainly due to the constitutive activation of the histidine kinase (PmrB) or the response regulator (PmrA) following an amino-acid substitution in clinical strains. The performance of the test was determined on a panel of 14 colistin-susceptible and 14 colistin-resistant P. aeruginosa clinical strains, the reference strain PAO1 and positive control mutants PmrB (V28G), PmrB (D172), PhoQ (D240–247), and ParR (M59I). In comparison with the broth microdilution (BMD) method, all the susceptible strains (n=14) and 8/14 colistin-resistant strains were detected in less than 1h, directly on whole bacteria. The remaining resistant strains (n=6) were all detected after a short pre-exposure (4h) to colistin before sample preparation. Validation of the method on a larger panel of strains will be the next step before its use in diagnostics laboratories. Our data showed that the MALDIxin test offers rapid and efficient detection of colistin resistant P. aeruginosa and is thus a valuable diagnostics tool to control the spread of these emerging resistant strains.
Wiring Up Along Electrodes for Biofilm Formation
Authors: Prados María Belén , Lescano Mariela , Porzionato Natalia , Curutchet Gustavo
Published: September 2021

Millimeter-length cables of bacteria were discovered growing along a graphite-rod electrode serving as an anode of a microbial electrolysis cell (MEC). The MEC had been inoculated with a culture of Fe-reducing microorganisms enriched from a polluted river sediment (Reconquista river, Argentina) and was operated at laboratory controlled conditions for 18 days at an anode poised potential of 240 mV (vs. Ag/AgCl), followed by 23 days at 480 mV (vs. Ag/AgCl). Anode samples were collected for scanning electron microscopy, phylogenetic and electrochemical analyses. The cables were composed of a succession of bacteria covered by a membranous sheath and were distinct from the known “cable-bacteria” (family Desulfobulbaceae). Apparently, the formation of the cables began with the interaction of the cells via nanotubes mostly located at the cell poles. The cables seemed to be further widened by the fusion between them. 16S rRNA gene sequence analysis confirmed the presence of a microbial community composed of six genera, including Shewanella, a well-characterized electrogenic bacteria. The formation of the cables might be a way of colonizing a polarized surface, as determined by the observation of electrodes extracted at different times of MEC operation. Since the cables of bacteria were distinct from any previously described, the results suggest that bacteria capable of forming cables are more diverse in nature than already thought. This diversity might render different electrical properties that could be exploited for various applications.
Differential Early in vivo Dynamics and Functionality of Recruited Polymorphonuclear Neutrophils After Infection by Planktonic or Biofilm Staphylococcus aureus
Authors: Abdul Hamid Aizat Iman , Cara Andréa , Diot Alan , Laurent Frédéric , Josse Jérôme , Gueirard Pascale
Published: September 2021

Staphylococcus aureus is a human pathogen known for its capacity to shift between the planktonic and biofilm lifestyles. In vivo, the antimicrobial immune response is characterized by the recruitment of inflammatory phagocytes, namely polymorphonuclear neutrophils (PMNs) and monocytes/macrophages. Immune responses to planktonic bacteria have been extensively studied, but many questions remain about how biofilms can modulate inflammatory responses and cause recurrent infections in live vertebrates. Thus, the use of biologically sound experimental models is essential to study the specific immune signatures elicited by biofilms. Here, a mouse ear pinna model of infection was used to compare early innate immune responses toward S. aureus planktonic or biofilm bacteria. Flow cytometry and cytokine assays were carried out to study the inflammatory responses in infected tissues. These data were complemented with intravital confocal imaging analyses, allowing the real-time observation of the dynamic interactions between EGFP + phagocytes and bacteria in the ear pinna tissue of LysM-EGFP transgenic mice. Both bacterial forms induced an early and considerable recruitment of phagocytes in the ear tissue, associated with a predominantly pro-inflammatory cytokine profile. The inflammatory response was mostly composed of PMNs in the skin and the auricular lymph node. However, the kinetics of PMN recruitment were different between the 2 forms in the first 2 days post-infection (pi). Two hours pi, biofilm inocula recruited more PMNs than planktonic bacteria, but with decreased motility parameters and capacity to emit pseudopods. Inversely, biofilm inocula recruited less PMNs 2 days pi, but with an “over-activated” status, illustrated by an increased phagocytic activity, CD11b level of expression and ROS production. Thus, the mouse ear pinna model allowed us to reveal specific differences in the dynamics of recruitment and functional properties of phagocytes against biofilms. These differences would influence the specific adaptive immune responses to biofilms elicited in the lymphoid tissues.
Responses of Marine Diatom-Dinoflagellate Competition to Multiple Environmental Drivers: Abundance, Elemental, and Biochemical Aspects
Authors: Bi Rong , Cao Zhong , Ismar-Rebitz Stefanie M. H. , Sommer Ulrich , Zhang Hailong , Ding Yang , Zhao Meixun
Published: September 2021

Ocean-related global change has strongly affected the competition between key marine phytoplankton groups, such as diatoms and dinoflagellates, especially with the deleterious consequency of the increasing occurrence of harmful algal blooms. The dominance of diatoms generally shifts toward that of dinoflagellates in response to increasing temperature and reduced nutrient availability; however, contradictory findings have also been observed in certain sea areas. A key challenge in ecology and biogeochemistry is to quantitatively determine the effects of multiple environmental factors on the diatom-dinoflagellate community and the related changes in elemental and biochemical composition. Here, we test the interplay between temperature, nutrient concentrations and their ratios on marine diatom-dinoflagellate competition and chemical composition using bi-algal competition experiments. The ubiquitous diatom Phaeodactylum tricornutum and dinoflagellate Prorocentrum minimum were cultivated semi-continuously, provided with different N and P concentrations (three different levels) and ratios (10:1, 24:1, and 63:1 molar ratios) under three temperatures (12, 18, and 24°C). The responses of diatom-dinoflagellate competition were analyzed by a Lotka-Volterra model and quantified by generalized linear mixed models (GLMMs) and generalized additive models (GAMs). The changes in nutrient concentrations significantly affected diatom-dinoflagellate competition, causing a competitive superiority of the diatoms at high nutrient concentrations, independent of temperature and N:P supply ratios. Interestingly, the effect amplitude of nutrient concentrations varied with different temperatures, showing a switch back toward a competitive superiority of the dinoflagellates at the highest temperature and at very high nutrient concentrations. The ratios of particulate organic nitrogen to phosphorus showed significant negative correlations with increasing diatoms/dinoflagellates ratios, while lipid biomarkers (fatty acids and sterols) correlated positively with increasing diatoms/dinoflagellates ratios over the entire ranges of temperature, N and P concentrations and N:P ratios. Our results indicate that the integration of phytoplankton community structure and chemical composition provides an important step forward to quantitatively understand and predict how phytoplankton community changes affect ecosystem functions and biogeochemical cycles in the ocean.
Repair of Hypoxanthine in DNA Revealed by DNA Glycosylases and Endonucleases From Hyperthermophilic Archaea
Authors: Lin Tan , Zhang Likui , Wu Mai , Jiang Donghao , Li Zheng , Yang Zhihui
Published: September 2021

Since hyperthermophilic Archaea (HA) thrive in high-temperature environments, which accelerate the rates of deamination of base in DNA, their genomic stability is facing a severe challenge. Hypoxanthine (Hx) is one of the common deaminated bases in DNA. Generally, replication of Hx in DNA before repaired causes AT → GC mutation. Biochemical data have demonstrated that 3-methyladenine DNA glycosylase II (AlkA) and Family V uracil DNA glycosylase (UDG) from HA could excise Hx from DNA, thus triggering a base excision repair (BER) process for Hx repair. Besides, three endonucleases have been reported from HA: Endonuclease V (EndoV), Endonuclease Q (EndoQ), and Endonuclease NucS (EndoNucS), capable of cleaving Hx-containing DNA, thereby providing alternative pathways for Hx repair. Both EndoV and EndoQ could cleave one DNA strand with Hx, thus forming a nick and further initiating an alternative excision repair (AER) process for the follow-up repair. By comparison, EndoNucS cleaves both strands of Hx-containing DNA in a restriction endonuclease manner, thus producing a double-stranded break (DSB). This created DSB might be repaired by homologous recombination (HR) or by a combination activity of DNA polymerase (DNA pol), flap endonuclease 1 (FEN1), and DNA ligase (DNA lig). Herein, we reviewed the most recent advances in repair of Hx in DNA triggered by DNA glycosylases and endonucleases from HA, and proposed future research directions.
Prognostic Immunity and Therapeutic Sensitivity Analyses Based on Differential Genomic Instability-Associated LncRNAs in Left- and Right-Sided Colon Adenocarcinoma
Authors: Guo Jun-Nan , Xia Tian-Yi , Deng Shen-Hui , Xue Wei-Nan , Cui Bin-Bin , Liu Yan-Long
Published: September 2021

Background: The purpose of our study was to develop a prognostic risk model based on differential genomic instability-associated (DGIA) long non-coding RNAs (lncRNAs) of left-sided and right-sided colon cancers (LCCs and RCCs); therefore, the prognostic key lncRNAs could be identified.

Methods: We adopted two independent gene datasets, corresponding somatic mutation and clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Identification of differential DGIA lncRNAs from LCCs and RCCs was conducted with the appliance of “Limma” analysis. Then, we screened out key lncRNAs based on univariate and multivariate Cox proportional hazard regression analysis. Meanwhile, DGIA lncRNAs related prognostic model (DRPM) was established. We employed the DRPM in the model group and internal verification group from TCGA for the purpose of risk grouping and accuracy verification of DRPM. We also verified the accuracy of key lncRNAs with GEO data. Finally, the differences of immune infiltration, functional pathways, and therapeutic sensitivities were analyzed within different risk groups.

Results: A total of 123 DGIA lncRNAs were screened out by differential expression analysis. We obtained six DGIA lncRNAs by the construction of DRPM, including AC004009.1, AP003555.2, BOLA3-AS1, NKILA, LINC00543, and UCA1. After the risk grouping by these DGIA lncRNAs, we found the prognosis of the high-risk group (HRG) was significantly worse than that in the low-risk group (LRG) (all p < 0.05). In all TCGA samples and model group, the expression of CD8+ T cells in HRG was lower than that in LRG (all p < 0.05). The functional analysis indicated that there was significant upregulation with regard to pathways related to both genetic instability and immunity in LRG, including cytosolic DNA sensing pathway, response to double-strand RNA, RIG-Ⅰ like receptor signaling pathway, and Toll-like receptor signaling pathway. Finally, we analyzed the difference and significance of key DGIA lncRNAs and risk groups in multiple therapeutic sensitivities.

Conclusion: Through the analysis of the DGIA lncRNAs between LCCs and RCCs, we identified six key DGIA lncRNAs. They can not only predict the prognostic risk of patients but also serve as biomarkers for evaluating the differences of genetic instability, immune infiltration, and therapeutic sensitivity.
Shedding Light on the Molecular Recognition of Sub-Kilodalton Macrocyclic Peptides on Thrombin by Supervised Molecular Dynamics
Authors: Hassankalhori Mahdi , Bolcato Giovanni , Bissaro Maicol , Sturlese Mattia , Moro Stefano
Published: September 2021

Macrocycles are attractive structures for drug development due to their favorable structural features, potential in binding to targets with flat featureless surfaces, and their ability to disrupt protein–protein interactions. Moreover, large novel highly diverse libraries of low-molecular-weight macrocycles with therapeutically favorable characteristics have been recently established. Considering the mentioned facts, having a validated, fast, and accurate computational protocol for studying the molecular recognition and binding mode of this interesting new class of macrocyclic peptides deemed to be helpful as well as insightful in the quest of accelerating drug discovery. To that end, the ability of the in-house supervised molecular dynamics protocol called SuMD in the reproduction of the X-ray crystallography final binding state of a macrocyclic non-canonical tetrapeptide—from a novel library of 8,988 sub-kilodalton macrocyclic peptides—in the thrombin active site was successfully validated. A comparable binding mode with the minimum root-mean-square deviation (RMSD) of 1.4 Å at simulation time point 71.6 ns was achieved. This method validation study extended the application domain of the SuMD sampling method for computationally cheap, fast but accurate, and insightful macrocycle–protein molecular recognition studies.