bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbonic Anhydrases: An Ancient Tool in Calcareous Sponge Biomineralization
Authors: Voigt Oliver , Fradusco Benedetta , Gut Carolin , Kevrekidis Charalampos , Vargas Sergio , Wörheide Gert
Published: April 2021

Enzymes of the α-carbonic anhydrase gene family (CAs) are essential for the deposition of calcium carbonate biominerals. In calcareous sponges (phylum Porifera, class Calcarea), specific CAs are involved in the formation of calcite spicules, a unique trait and synapomorphy of this class. However, detailed studies on the CA repertoire of calcareous sponges exist for only two species of one of the two Calcarea subclasses, the Calcaronea. The CA repertoire of the second subclass, the Calcinea, has not been investigated so far, leaving a considerable gap in our knowledge about this gene family in Calcarea. Here, using transcriptomic analysis, phylogenetics, and in situ hybridization, we study the CA repertoire of four additional species of calcareous sponges, including three from the previously unsampled subclass Calcinea. Our data indicate that the last common ancestor of Calcarea had four ancestral CAs with defined subcellular localizations and functions (mitochondrial/cytosolic, membrane-bound, and secreted non-catalytic). The evolution of membrane-bound and secreted CAs involved gene duplications and losses, whereas mitochondrial/cytosolic and non-catalytic CAs are evidently orthologous genes. Mitochondrial/cytosolic CAs are biomineralization-specific genes recruited for biomineralization in the last common ancestor of calcareous sponges. The spatial–temporal expression of these CAs differs between species, which may reflect differences between subclasses or be related to the secondary thickening of spicules during biomineralization that does not occur in all species. With this study, we extend the understanding of the role and the evolution of a key biomineralization gene in calcareous sponges.
Human ALKBH6 Is Required for Maintenance of Genomic Stability and Promoting Cell Survival During Exposure of Alkylating Agents in Pancreatic Cancer
Authors: Zhao Shengyuan , Devega Rodan , Francois Aaliyah , Kidane Dawit
Published: April 2021

Alpha-ketoglutarate-dependent dioxygenase (ALKBH) is a DNA repair gene involved in the repair of alkylating DNA damage. There are nine types of ALKBH (ALKBH1-8 and FTO) identified in humans. In particular, certain types of ALKBH enzymes are dioxygenases that directly reverse DNA methylation damage via transfer of a methyl group from the DNA adduct onto α-ketoglutarate and release of metabolic products including succinate and formaldehyde. Here, we tested whether ALKBH6 plays a significant role in preventing alkylating DNA damage and decreasing genomic instability in pancreatic cancer cells. Using anE. colistrain deficient with ALKB, we found that ALKBH6 complements ALKB deficiency and increases resistance after alkylating agent treatment. In particular, the loss of ALKBH6 in human pancreatic cancer cells increases alkylating agent-induced DNA damage and significantly decreases cell survival. Furthermore,in silicoanalysis from The Cancer Genome Atlas (TCGA) database suggests that overexpression of ALKBH6 provides better survival outcomes in patients with pancreatic cancer. Overall, our data suggest that ALKBH6 is required to maintain the integrity of the genome and promote cell survival of pancreatic cancer cells.
Proteome and Phosphoproteome Analyses Reveal the Kinase Regulatory Network Involved in Glycogen Synthesis Kinase 3β
Authors: Hu Mingyang , Fang Jiuyuan , Wang Huijuan , Zhou Sijie
Published: April 2021

Diabetic nephropathy is the most common chronic kidney disease in the world and the main cause of end-stage renal disease (ESRD). The structural integrity of podocytes is fundamental to the normal function of the glomerulus, and the role of glycogen synthase kinase 3β (GSK-3β) in podocytes is complicated. A thorough understanding of GSK-3β is crucial to understand the mechanism of diabetic nephropathy. To analyze the roles of GSK-3β in podocytes, GSK-3β knockdown lentivirus by clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated protein (Cas)9 was applied to establish stable cell lines. Mass spectrometry was utilized to search for differentially expressed proteins. Consequently, we found 34 proteins with higher levels and 115 proteins with lower levels in GSk-3β knockdown cells than in control cells and identified 581 phosphosites with higher phosphorylation levels and 288 phosphosites with lower phosphorylation levels. We performed functional enrichment analysis of these proteins and phosphorylated proteins based on public databases. Enrichment analysis revealed that GSK-3β participates in the spliceosome, Hippo signaling pathway, actin binding, structural molecule activity, and other pathways. Then, we used motif analysis of phosphate sites to determine 89 conserved motifs based on 1,068 phosphoserine (pS) sites and 15 conserved motifs in view of 104 phosphothreonine (pT) sites. Additionally, protein–protein interaction network analysis was carried out using the STRING database. Cytoscape’s add-on Molecular Complex Detection (MCODE) was used to analyze key and core protein groups. In quantitative differential protein analysis, four MCODEs were obtained, and 22 MCODEs were obtained in the analysis of the phosphoproteome of differentially expressed proteins. Finally, we analyzed the kinase regulatory network in podocytes after GSK-3β knockdown and identified 299 protein kinases and 3,460 significantly changed phosphorylation modification sites on 1,574 proteins. These results will be valuable for further research on GSK-3β.
Membrane Particles Derived From Adipose Tissue Mesenchymal Stromal Cells Improve Endothelial Cell Barrier Integrity
Authors: Merino Ana , Sablik Marta , Korevaar Sander S. , López-Iglesias Carmen , Ortiz-Virumbrales Maitane , Baan Carla C. , Lombardo Eleuterio , Hoogduijn Martin J.
Published: April 2021

Proinflammatory stimuli lead to endothelial injury, which results in pathologies such as cardiovascular diseases, autoimmune diseases, and contributes to alloimmune responses after organ transplantation. Both mesenchymal stromal cells (MSC) and the extracellular vesicles (EV) released by them are widely studied as regenerative therapy for the endothelium. However, for therapeutic application, the manipulation of living MSC and large-scale production of EV are major challenges. Membrane particles (MP) generated from MSC may be an alternative to the use of whole MSC or EV. MP are nanovesicles artificially generated from the membranes of MSC and possess some of the therapeutic properties of MSC. In the present study we investigated whether MP conserve the beneficial MSC effects on endothelial cell repair processes under inflammatory conditions. MP were generated by hypotonic shock and extrusion of MSC membranes. The average size of MP was 120 nm, and they showed a spherical shape. The effects of two ratios of MP (50,000; 100,000 MP per target cell) on human umbilical vein endothelial cells (HUVEC) were tested in a model of inflammation induced by TNFα. Confocal microscopy and flow cytometry showed that within 24 hours >90% of HUVEC had taken up MP. Moreover, MP ended up in the lysosomes of the HUVEC. In a co-culture system of monocytes and TNFα activated HUVEC, MP did not affect monocyte adherence to HUVEC, but reduced the transmigration of monocytes across the endothelial layer from 138 ± 61 monocytes per microscopic field in TNFα activated HUVEC to 61 ± 45 monocytes. TNFα stimulation induced a 2-fold increase in the permeability of the HUVEC monolayer measured by the translocation of FITC-dextran to the lower compartment of a transwell system. At a dose of 1:100,000 MP significantly decreased endothelial permeability (1.5-fold) respect to TNFα Stimulated HUVEC. Finally, MP enhanced the angiogenic potential of HUVEC in an in vitro Matrigel assay by stimulating the formation of angiogenic structures, such as percentage of covered area, total tube length, total branching points, total loops. In conclusion, MP show regenerative effects on endothelial cells, opening a new avenue for treatment of vascular diseases where inflammatory processes damage the endothelium.
Identification of Prognostic Genes in the Tumor Microenvironment of Hepatocellular Carcinoma
Authors: Xiang Shixin , Li Jing , Shen Jing , Zhao Yueshui , Wu Xu , Li Mingxing , Yang Xiao , Kaboli Parham Jabbarzadeh , Du Fukuan , Zheng Yuan , Wen Qinglian , Cho Chi Hin , Yi Tao , Xiao Zhangang
Published: April 2021

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. The efficacy of immunotherapy usually depends on the interaction of immunomodulation in the tumor microenvironment (TME). This study aimed to explore the potential stromal-immune score-based prognostic genes related to immunotherapy in HCC through bioinformatics analysis.

Methods: ESTIMATE algorithm was applied to calculate the immune/stromal/Estimate scores and tumor purity of HCC using the Cancer Genome Atlas (TCGA) transcriptome data. Functional enrichment analysis of differentially expressed genes (DEGs) was analyzed by the Database for Annotation, Visualization, and Integrated Discovery database (DAVID). Univariate and multivariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were performed for prognostic gene screening. The expression and prognostic value of these genes were further verified by KM-plotter database and the Human Protein Atlas (HPA) database. The correlation of the selected genes and the immune cell infiltration were analyzed by single sample gene set enrichment analysis (ssGSEA) algorithm and Tumor Immune Estimation Resource (TIMER).

Results: Data analysis revealed that higher immune/stromal/Estimate scores were significantly associated with better survival benefits in HCC within 7 years, while the tumor purity showed a reverse trend. DEGs based on both immune and stromal scores primarily affected the cytokine–cytokine receptor interaction signaling pathway. Among the DEGs, three genes (CASKIN1, EMR3, and GBP5) were found most significantly associated with survival. Moreover, the expression levels of CASKIN1, EMR3, and GBP5 genes were significantly correlated with immune/stromal/Estimate scores or tumor purity and multiple immune cell infiltration. Among them, GBP5 genes were highly related to immune infiltration.

Conclusion: This study identified three key genes which were related to the TME and had prognostic significance in HCC, which may be promising markers for predicting immunotherapy outcomes.
Interactions Between Commensal Microbiota and Mucosal Immunity in Teleost Fish During Viral Infection With SVCV
Authors: Meng Kai-Feng , Ding Li-Guo , Wu Sha , Wu Zheng-Ben , Cheng Gao-Feng , Zhai Xue , Sun Ru-Han , Xu Zhen
Published: April 2021

The mucosa of vertebrates is a particularly complex but dynamic environment in which the host constantly interacts with trillions of commensal microorganisms and pathogens. Although the internal and external mucosal microbiomes with immune defense of mammals have been well investigated, the relationship between mucosal microbes and their host’s immune responses has not been systematically understood in the early vertebrates. In this study, we compared the composition and distribution of mucosal microbiota in common carp (Cyprinus carpio), and found that there were significant differences of microbiota between in the internal (gut) and external mucosal (buccal mucosa, gills and skin) tissues. Next, we successfully constructed an infection model with spring viremia of carp virus (SVCV). Specifically, following viral infection, the immune and antiviral related genes showed different up-regulation in all selected mucosal tissues while significant morphological changes were only found in external tissues including buccal mucosa, gills and skin. Using 16S rRNA gene sequence, we revealed that the abundance of Proteobacteria in mucosal tissues including buccal mucosa, gills and gut showed increased trend after viral infection, whereas the abundance of Fusobacteria significantly decreased in gut. In addition, the loss of dominant commensal microorganisms and increased colonization of opportunistic bacteria were discovered in the mucosal surfaces indicating that a secondary bacterial infection might occur in these mucosal tissues after viral infection. Overall, our results firstly point out the distribution of internal and external mucosal microbiota and analyze the changes of mucosal microbiota in common carp after SVCV infection, which may indicated that the potential role of mucosal microbiota in the antiviral process in early vertebrates.
Determinants of Serum Immunoglobulin Levels: A Systematic Review and Meta-Analysis
Authors: Khan Samer R. , van der Burgh Anna C. , Peeters Robin P. , van Hagen P. Martin , Dalm Virgil A. S. H. , Chaker Layal
Published: April 2021

Background

An up-to-date overview of determinants of serum immunoglobulins in adults is pivotal for clinical practice and research, but currently lacking. We therefore performed a systematic review and meta-analysis to identify determinants of serum immunoglobulin levels.

Methods

Embase, Web of Science, Medline, Cochrane, and Google Scholar were searched from inception to July 11th, 2019 for articles reporting on determinants of serum immunoglobulin A, G or M (IgA, IgG or IgM) in adult humans. Random and fixed effect models were applied to obtain pooled mean differences (MDs) and 95% confidence intervals (CIs) for the association of age and sex with serum immunoglobulins.

Results

We retrieved 117 articles reporting on determinants of serum immunoglobulins, of which 28 could be meta-analyzed. Older compared to younger individuals had higher IgA (MD: 0.38; CI: 0.18 – 0.58), but lower IgM levels (MD: -0.40; 95%: -0.66 – -0.14). Men had higher IgA (MD: 0.22; CI: 0.03 – 0.42), but lower IgM levels (MD: -0.21; CI: -0.32 – -0.10) than women. Age and sex did not influence IgG. Caucasian ethnicity was associated with lower IgA, IgG, and IgM. Smoking and corticosteroid use were associated with lower IgG. Positive associations were reported of probiotics with IgG, alcohol with IgA, hypertension with IgA and IgG, and acute psychological stress with IgA, IgG, and IgM.

Conclusions

Older age and male sex are associated with higher IgA, but lower IgM, and urge investigation of age- and sex-specific reference ranges of immunoglobulins. Other identified determinants were ethnicity, diet, lifestyle and cardio-metabolic factors.
Macrophage-Mediated Tissue Vascularization: Similarities and Differences Between Cornea and Skin
Authors: Hadrian Karina , Willenborg Sebastian , Bock Felix , Cursiefen Claus , Eming Sabine A. , Hos Deniz
Published: April 2021

Macrophages are critical mediators of tissue vascularization both in health and disease. In multiple tissues, macrophages have been identified as important regulators of both blood and lymphatic vessel growth, specifically following tissue injury and in pathological inflammatory responses. In development, macrophages have also been implicated in limiting vascular growth. Hence, macrophages provide an important therapeutic target to modulate tissue vascularization in the clinic. However, the molecular mechanisms how macrophages mediate tissue vascularization are still not entirely resolved. Furthermore, mechanisms might also vary among different tissues. Here we review the role of macrophages in tissue vascularization with a focus on their role in blood and lymphatic vessel formation in the barrier tissues cornea and skin. Comparing mechanisms of macrophage-mediated hem- and lymphangiogenesis in the angiogenically privileged cornea and the physiologically vascularized skin provides an opportunity to highlight similarities but also tissue-specific differences, and to understand how macrophage-mediated hem- and lymphangiogenesis can be exploited for the treatment of disease, including corneal wound healing after injury, graft rejection after corneal transplantation or pathological vascularization of the skin.
Beyond Post-release Mortality: Inferences on Recovery Periods and Natural Mortality From Electronic Tagging Data for Discarded Lamnid Sharks
Authors: Bowlby Heather D. , Benoît Hugues P. , Joyce Warren , Sulikowski James , Coelho Rui , Domingo Andrés , Cortés Enric , Hazin Fabio , Macias David , Biais Gérard , Santos Catarina , Anderson Brooke
Published: April 2021

Accurately characterizing the biology of a pelagic shark species is critical when assessing its status and resilience to fishing pressure. Natural mortality (M) is well known to be a key parameter determining productivity and resilience, but also one for which estimates are most uncertain. WhileMcan be inferred from life history, validated direct estimates are extremely rare for sharks. Porbeagle (Lamna nasus) and shortfin mako (Isurus oxyrinchus) are presently overfished in the North Atlantic, but there are no directed fisheries and successful live release of bycatch is believed to have increased. UnderstandingM, post-release mortality (PRM), and variables that affect mortality are necessary for management and effective bycatch mitigation. From 177 deployments of archival satellite tags, we inferred mortality events, characterized physiological recovery periods following release, and applied survival mixture models to assessMand PRM. We also evaluated covariate effects on the duration of any recovery period and PRM to inform mitigation. Although large sample sizes involving extended monitoring periods (>90 days) would be optimal to directly estimateMfrom survival data, it was possible to constrain estimates and infer probable values for both species. Furthermore, the consistency ofMestimates with values derived from longevity information suggests that age determination is relatively accurate for these species. Regarding bycatch mitigation, our analyses suggest that juvenile porbeagle are more susceptible to harm during capture and handling, that keeping lamnid sharks in the water during release is optimal, and that circle hooks are associated with longer recovery periods for shortfin mako.
Challenges of Whale Watching and Swim With Dolphins in Mexico
Authors: Jorge Urbán R. , Viloria-Gómora Lorena
Published: April 2021

Mexico is one of the top 10 whale-watching destinations in the world. The target species for “whale watching” (WW) are the gray whale, blue whale, humpback whale, and fin whale; the target species for “swim with dolphins” (SWD) are the bottlenose dolphin, spotted dolphin, spinner dolphin, and killer whale. WW has an increment of 666% income, 94% of trips, and 51% in the jobs generated in the last 11 years. Although Mexican legislation to regulate WW appears to be well designed, the great challenge is applying this normative in the field. In particular, it has been observed that surveillance and enforcement of normative differ significantly whether WW has carried out within a Marine Protected Area (MPA) or area without such designation. WW of gray and blue whales in El Vizcaíno Biosphere Reserve and Bahía de Loreto National Park, respectively, is developed within the MPAs. They are considered examples of acceptable WW practices. In contrast, in places without protected status as Puerto Vallarta, Jal., and Los Cabos, Baja California Sur (BCS), the WW practices have different problems related to boats’ presence without permission as sport fishing boats, private boats, and jet skis that do not respect WW guidelines. On the other hand, creating normativity or policies to regulate SWD in Mexico represents a current challenge. It is also a challenge to promote that local communities are involved in carrying out WW and SWD and are included in granting permits and the jobs and benefits of the economic spillover that these tourist activities generate.
Identify the Characteristics of Metabolic Syndrome and Non-obese Phenotype: Data Visualization and a Machine Learning Approach
Authors: Yu Cheng-Sheng , Chang Shy-Shin , Lin Chang-Hsien , Lin Yu-Jiun , Wu Jenny L. , Chen Ray-Jade
Published: April 2021

Introduction: A third of the world's population is classified as having Metabolic Syndrome (MetS). Traditional diagnostic criteria for MetS are based on three or more of five components. However, the outcomes of patients with different combinations of specific metabolic components are undefined. It is challenging to be discovered and introduce treatment in advance for intervention, since the related research is still insufficient.

Methods: This retrospective cohort study attempted to establish a method of visualizing metabolic components by using unsupervised machine learning and treemap technology to discover the relations between predicting factors and different metabolic components. Several supervised machine-learning models were used to explore significant predictors of MetS and to construct a powerful prediction model for preventive medicine.

Results: The random forest had the best performance with accuracy and c-statistic of 0.947 and 0.921, respectively, and found that body mass index, glycated hemoglobin, and controlled attenuation parameter (CAP) score were the optimal primary predictors of MetS. In treemap, high triglyceride level plus high fasting blood glucose or large waist circumference group had higher CAP scores (>260) than other groups. Moreover, 32.2% of patients with high CAP scores during 3 years of follow-up had metabolic diseases are observed. This reveals that the CAP score may be used for detecting MetS, especially for the non-obese MetS phenotype.

Conclusions: Machine learning and data visualization can illustrate the complicated relationships between metabolic components and potential risk factors for MetS.
Efficacy of Teprenone for Prevention of NSAID-Induced Gastrointestinal Injury: A Systematic Review and Meta-Analysis
Authors: Zhao Chongxiang , Wang Jingwu , Xiao Qiang
Published: April 2021

Background: The study aimed to conduct a systematic review and meta-analysis comparing the efficacy of teprenone with control or other drugs for reducing the incidence of gastrointestinal (GI) adverse events in patients receiving long-term non-steroidal anti-inflammatory drugs (NSAIDs).

Methods: Databases of PubMed, Embase, BioMed Central, CENTRAL, and Google Scholar were searched up to November 10th, 2020 for randomized controlled trials (RCTs) comparing teprenone with control or other drugs. A random-effects model was used for the meta-analysis. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used for assessing the certainty of evidence.

Results: Seven RCTs were included. Six compared teprenone with control and one with famotidine. Meta-analysis indicated a statistically significant reduced risk of GI ulcers in patients receiving teprenone as compared to control after 12 weeks/3months (RR 0.37 95% CI 0.17, 0.18 I2 = 0% p = 0.01). Pooled data of three open-label studies indicated statistically significant reduction of GI symptoms in patients on teprenone as compared to control at 6 months and 12 months, but not at 3 months. Comparing teprenone with control, our analysis indicated non-significant but a tendency of better reduction in Modified Lanza Score (MLS) with teprenone. The RCT comparing teprenone to famotidine demonstrated better reduction of MLS with famotidine. The certainty of evidence-based on GRADE was deemed to be low.

Conclusion: Low-quality evidence indicates a beneficial role of teprenone in preventing GI injuries in patients receiving long-term NSAIDs. Further high-quality RCTs comparing teprenone with placebo as well as other gastroprotective drugs are needed to strengthen current evidence.
Vulvar Pruritus: A Review of Clinical Associations, Pathophysiology and Therapeutic Management
Authors: Raef Haya S. , Elmariah Sarina B.
Published: April 2021

Vulvar pruritus is an unpleasant sensation and frequent symptom associated with many dermatologic conditions, including infectious, inflammatory and neoplastic dermatoses affecting the female genitalia. It can lead to serious impairment of quality of life, impacting sexual function, relationships, sleep and self-esteem. In this review, common conditions associated with vulvar itch are discussed including atopic and contact dermatitis, lichen sclerosus, psoriasis and infectious vulvovaginitis. We review the potential physiologic, environmental and infectious factors that contribute to the development of vulvar itch and emphasize the importance of addressing their complex interplay when managing this disruptive and challenging symptom.
Phenotypic and Genomic Variability of Serial Peri-Lung Transplantation Pseudomonas aeruginosa Isolates From Cystic Fibrosis Patients
Authors: Datar Rucha , Coello Pelegrin Andreu , Orenga Sylvain , Chalansonnet Valérie , Mirande Caroline , Dombrecht Jill , Perry John D. , Perry Audrey , Goossens Herman , van Belkum Alex
Published: April 2021

Cystic fibrosis (CF) represents one of the major genetic and chronic lung diseases affecting Caucasians of European descent. Patients with CF suffer from recurring infections that lead to further damage of the lungs. Pulmonary infection due to Pseudomonas aeruginosa is most prevalent, further increasing CF-related mortality. The present study describes the phenotypic and genotypic variations among 36 P. aeruginosa isolates obtained serially from a non-CF and five CF patients before, during and after lung transplantation (LTx). The classical and genomic investigation of these isolates revealed a common mucoid phenotype and only subtle differences in the genomes. Isolates originating from an individual patient shared ≥98.7% average nucleotide identity (ANI). However, when considering isolates from different patients, substantial variations in terms of sequence type (ST), virulence factors and antimicrobial resistance (AMR) genes were observed. Whole genome multi-locus sequence typing (MLST) confirmed the presence of unique STs per patient regardless of the time from LTx. It was supported by the monophyletic clustering found in the genome-wide phylogeny. The antibiogram shows that ≥91.6% of the isolates were susceptible to amikacin, colistin and tobramycin. For other antibiotics from the panel, isolates frequently showed resistance. Alternatively, a comparative analysis of the 36 P. aeruginosa isolates with 672 strains isolated from diverse ecologies demonstrated clustering of the CF isolates according to the LTx patients from whom they were isolated. We observed that despite LTx and associated measures, all patients remained persistently colonized with similar isolates. The present study shows how whole genome sequencing (WGS) along with phenotypic analysis can help us understand the evolution of P. aeruginosa over time especially its antibiotic resistance.
Colonization of Supplemented Bifidobacterium breve M-16V in Low Birth Weight Infants and Its Effects on Their Gut Microbiota Weeks Post-administration
Authors: Horigome Ayako , Hisata Ken , Odamaki Toshitaka , Iwabuchi Noriyuki , Xiao Jin-zhong , Shimizu Toshiaki
Published: April 2021

The colonization and persistence of probiotics introduced into the adult human gut appears to be limited. It is uncertain, however, whether probiotics can successfully colonize the intestinal tracts of full-term and premature infants. In this study, we investigated the colonization and the effect of oral supplementation with Bifidobacterium breve M-16V on the gut microbiota of low birth weight (LBW) infants. A total of 22 LBW infants (12 infants in the M-16V group and 10 infants in the control group) were enrolled. B. breve M-16V was administrated to LBW infants in the M-16V group from birth until hospital discharge. Fecal samples were collected from each subject at weeks (3.7–9.3 weeks in the M-16V group and 2.1–6.1 weeks in the control group) after discharge. qPCR analysis showed that the administrated strain was detected in 83.3% of fecal samples in the M-16V group (at log10 8.33 ± 0.99 cell numbers per gram of wet feces), suggesting that this strain colonized most of the infants beyond several weeks post-administration. Fecal microbiota analysis by 16S rRNA gene sequencing showed that the abundance of Actinobacteria was significantly higher (P < 0.01), whereas that of Proteobacteria was significantly lower (P < 0.001) in the M-16V group as compared with the control group. Notably, the levels of the administrated strain and indigenous Bifidobacterium bacteria were both significantly higher in the M-16V group than in the control group. Our findings suggest that oral administration of B. breve M-16V led to engraftment for at least several weeks post-administration and we observed a potential overall improvement in microbiota formation in the LBW infants’ guts.
Understanding the Transcriptional Changes During Infection of Meloidogyne incognita Eggs by the Egg-Parasitic Fungus Purpureocillium lilacinum
Authors: Xu Wen-Feng , Yang Jia-Lin , Meng Xiang-Kun , Gu Zhi-Guang , Zhang Qi-Lin , Lin Lian-Bing
Published: April 2021

The egg-pathogenic fungus Purpureocillium lilacinum parasitizes on nematode eggs, and thus, it is used as a good biocontrol agent against plant root-knot nematodes. However, little is known about the transcriptional response of P. lilacinum while infecting nematode eggs. This study presents the whole transcriptome sequencing of P. lilacinum and transcriptome-wide gene expression analysis of P. lilacinum upon infecting the eggs of Meloidogyne incognita compared to non-infecting controls. A transcriptomic library of P. lilacinum was used as reference gene set and six transcriptomic libraries of the non-infecting control and P. lilacinum infecting M. incognita eggs were constructed, respectively, comprising three biological replicates of each. A total of 1,011 differently expressed genes (DEGs) were identified in the infecting samples, including 553 up-regulated and 458 down-regulated genes compared to the non-infecting control samples. Furthermore, functional enrichment analysis exhibited that these DEGs were primarily involved in oxidative phosphorylation, oxidoreductase activity, and metabolic processes. Fifteen DEGs were randomly selected to verify the RNA sequencing results through quantitative real-time polymerase chain reaction (qPCR). The study focused on P. lilacinum genes that were strongly expressed upon infecting M. incognita eggs. These DEGs were primarily involved in detoxification, parasitic behavior, and nutritional utilization. This study contributes significantly to the understanding of the molecular mechanisms underlying the parasitic action of P. lilacinum on nematode eggs and provides a valuable genetic resource for further research on parasitic behavior of P. lilacinum. Notably, this study examined the transcriptomics of P. lilacinum infecting M. incognita eggs at only one time point. Since there were fungi at different stages of the infection process at that time point, the transcriptional profiles are not precisely examining one specific stage in this process.
Evolutionary Significance of the Neuroendocrine Stress Axis on Vertebrate Immunity and the Influence of the Microbiome on Early-Life Stress Regulation and Health Outcomes
Authors: Ortega Van A. , Mercer Emily M. , Giesbrecht Gerald F. , Arrieta Marie-Claire
Published: April 2021

Stress is broadly defined as the non-specific biological response to changes in homeostatic demands and is mediated by the evolutionarily conserved neuroendocrine networks of the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system. Activation of these networks results in transient release of glucocorticoids (cortisol) and catecholamines (epinephrine) into circulation, as well as activation of sympathetic fibers innervating end organs. These interventions thus regulate numerous physiological processes, including energy metabolism, cardiovascular physiology, and immunity, thereby adapting to cope with the perceived stressors. The developmental trajectory of the stress-axis is influenced by a number of factors, including the gut microbiome, which is the community of microbes that colonizes the gastrointestinal tract immediately following birth. The gut microbiome communicates with the brain through the production of metabolites and microbially derived signals, which are essential to human stress response network development. Ecological perturbations to the gut microbiome during early life may result in the alteration of signals implicated in developmental programming during this critical window, predisposing individuals to numerous diseases later in life. The vulnerability of stress response networks to maladaptive development has been exemplified through animal models determining a causal role for gut microbial ecosystems in HPA axis activity, stress reactivity, and brain development. In this review, we explore the evolutionary significance of the stress-axis system for health maintenance and review recent findings that connect early-life microbiome disturbances to alterations in the development of stress response networks.
Blastocystis Colonization Alters the Gut Microbiome and, in Some Cases, Promotes Faster Recovery From Induced Colitis
Authors: Billy Vincent , Lhotská Zuzana , Jirků Milan , Kadlecová Oldřiška , Frgelecová Lucia , Parfrey Laura Wegener , Pomajbíková Kateřina Jirků
Published: April 2021

Protists are a normal component of mammalian intestinal ecosystems that live alongside, and interact with, bacterial microbiota.Blastocystis, one of the most common intestinal eukaryotes, is reported as a pathogen that causes inflammation and disease, though health consequences likely vary depending on host health, the gut ecosystem, and genetic diversity. Accumulating evidence suggests thatBlastocystisis by and large commensal.Blastocystisis more common in healthy individuals than those with immune mediated diseases such as Inflammatory Bowel Diseases (IBD).Blastocystispresence is also associated with altered composition and higher richness of the bacterial gut microbiota. It is not clear whetherBlastocystisdirectly promotes a healthy gut and microbiome or is more likely to colonize and persist in a healthy gut environment. We test this hypothesis by measuring the effect ofBlastocystisST3 colonization on the health and microbiota in a rat experimental model of intestinal inflammation using the haptenizing agent dinitrobenzene sulfonic acid (DNBS). We experimentally colonized rats withBlastocystisST3 obtained from a healthy, asymptomatic human donor and then induced colitis after 3 weeks (short term exposure experiment) or after 13 weeks (long term exposure experiment) and compared these colonized rats to a colitis-only control group. Across experimentsBlastocystisST3 colonization alters microbiome composition, but not richness, and induces only mild gut inflammation but no clinical symptoms. Our results showed no effect of short-term exposure toBlastocystisST3 on gut inflammation following colitis induction. In contrast, long-termBlastocystisexposure appears to promote a faster recovery from colitis. There was a significant reduction in inflammatory markers, pathology 2 days after colitis induction in the colonized group, and clinical scores also improved in this group.Blastocystiscolonization resulted in a significant reduction in tumor necrosis factor alpha (TNFα) and IL-1β relative gene expression, while expression of IFNγ and IL17re/17C were elevated. We obtained similar results in a previous pilot study. We further found that bacterial richness rebounded in rats colonized byBlastocystisST3. These results suggest thatBlastocystissp. may alter the gut ecosystem in a protective manner and promote faster recovery from disturbance.
Understanding the Shift in the Microbiome of Composts That Are Optimized for a Better Fit-for-Purpose in Growing Media
Authors: Pot Steffi , De Tender Caroline , Ommeslag Sarah , Delcour Ilse , Ceusters Johan , Gorrens Ellen , Debode Jane , Vandecasteele Bart , Vancampenhout Karen
Published: April 2021

Three characteristics are considered key for optimal use of composts in growing media: maturity, pH and organic matter content. Maturation is a critical step in the processing of composts contributing to compost quality. Blending of composts with chopped heath biomass, sieving out the larger fraction of composts and acidification of composts by adding elemental sulfur may be used either to increase organic matter content or to reduce pH for a better fit in growing media. While several studies have shown the effectiveness of these treatments to improve the use of composts in growing media, the effect of these treatments on the compost microbiome has merely been assessed before. In the present study, five immature composts were allowed to mature, and were subsequently acidified, blended or sieved. Bacterial and fungal communities of the composts were characterized and quantified using 16S rRNA and ITS2 gene metabarcoding and phospholipid fatty acid analysis. Metabolic biodiversity and activity were analyzed using Biolog EcoPlates. Compost batch was shown to be more important than maturation or optimization treatments to determine the compost microbiome. Compost maturation increased microbial diversity and favored beneficial microorganisms, which may be positive for the use of composts in growing media. Blending of composts increased microbial diversity, metabolic diversity, and metabolic activity, which may have a positive effect in growing media. Blending may be used to modify the microbiome to a certain degree in order to optimize microbiological characteristics. Acidification caused a decrease in bacterial diversity and microbial activity, which may be negative for the use in growing media, although the changes are limited. Sieving had limited effect on the microbiome of composts. Because of the limited effect on the microbiome, sieving of composts may be used flexible to improve (bio)chemical characteristics. This is the first study to assess the effects of maturation and optimization treatments to either increase organic matter content or lower pH in composts on the compost microbiome.
Deciphering the Relationship Between Cycloheximides Structures and Their Different Biological Activities
Authors: Nguyen Hang Thi Thu , Kim Jae Deok , Raj Vinit , Hwang In Min , Yu Nan Hee , Park Ae Ran , Choi Jung Seob , Lee Jintae , Kim Jin-Cheol
Published: April 2021

Streptomyces species are the most important sources of antibacterial, antifungal, and phytotoxic metabolites. In this study, cycloheximide (CH) and acetoxycycloheximide (ACH) were isolated from the fermentation broth of Streptomyces sp. JCK-6092. The antifungal and phytotoxic activities of the two compounds (CH and ACH) and a cycloheximide derivative, hydroxycycloheximide (HCH), were compared. CH exhibited the strongest antagonistic activity against all the true fungi tested, followed by ACH and HCH. However, both CH and ACH displayed similar mycelial growth inhibitory activities against several phytopathogenic oomycetes, and both were more active than that of HCH. Disparate to antifungal ability, ACH showed the strongest phytotoxic activity against weeds and crops, followed by HCH and CH. ACH caused chlorophyll content loss, leaf electrolytic leakage, and lipid peroxidation in a dose-dependent manner. Its phytotoxicity was stronger than that of glufosinate-ammonium but weaker than that of paraquat in the in vitro experiments. CH and its derivatives are well-known protein synthesis inhibitors; however, the precise differences between their mechanism of action remain undiscovered. A computational study revealed effects of CHs on the protein synthesis of Pythium ultimum (oomycetes), Magnaporthe oryzae (true fungus), and Capsicum annum (plant) and deciphered the differences in their biological activities on different targets. The binding energies and conformation stabilities of each chemical molecule correlated with their biological activities. Thus, molecular docking study supported the experimental results. This is the first comparative study to suggest the ribosomal protein alteration mechanisms of CHs in plants and fungi and to thus show how the protein inhibitory activities of the different derivatives are altered using molecular docking. The correlation of structures features of CHs in respect to bond formation with desired protein was revealed by density functional theory. Overall collective results suggested that CHs can be used as lead molecules in the development of more potent fungicides and herbicides molecules.
Soil Microsite Outweighs Cultivar Genotype Contribution to Brassica Rhizobacterial Community Structure
Authors: Klasek Scott A. , Brock Marcus T. , Morrison Hilary G. , Weinig Cynthia , Maignien Loïs
Published: April 2021

Microorganisms residing on root surfaces play a central role in plant development and performance and may promote growth in agricultural settings. Studies have started to uncover the environmental parameters and host interactions governing their assembly. However, soil microbial communities are extremely diverse and heterogeneous, showing strong variations over short spatial scales. Here, we quantify the relative effect of meter-scale variation in soil bacterial community composition among adjacent field microsites, to better understand how microbial communities vary by host plant genotype as well as soil microsite heterogeneity. We used bacterial 16S rDNA amplicon sequencing to compare rhizosphere communities from four Brassica rapa cultivars grown in three contiguous field plots (blocks) and evaluated the relative contribution of resident soil communities and host genotypes in determining rhizosphere community structure. We characterize concomitant meter-scale variation in bacterial community structure among soils and rhizospheres and show that this block-scale variability surpasses the influence of host genotype in shaping rhizosphere communities. We identified biomarker amplicon sequence variants (ASVs) associated with bulk soil and rhizosphere habitats, each block, and three of four cultivars. Numbers and percent abundances of block-specific biomarkers in rhizosphere communities far surpassed those from bulk soils. These results highlight the importance of fine-scale variation in the pool of colonizing microorganisms during rhizosphere assembly and demonstrate that microsite variation may constitute a confounding effect while testing biotic and abiotic factors governing rhizosphere community structure.
Aerobic Vaginitis Induced by Escherichia coli Infection During Pregnancy Can Result in Adverse Pregnancy Outcomes Through the IL-4/JAK-1/STAT-6 Pathway
Authors: Fan Chong , Dai Youjin , Zhang Lei , Rui Can , Wang Xinyan , Luan Ting , Fan Yuru , Dong Zhiyong , Hou Wenwen , Li Ping , Liao Qinping , Zeng Xin
Published: April 2021

Aerobic vaginitis (AV) can occur if normal vaginal microflora are dominated by aerobic bacteria, seriously affects not only female health, but also fetal health while they are pregnant. Besides, pregnant status also aggravates the symptoms and consequences of the infection. Here, we infected pregnant BALB/c mice with Escherichia coli on embryonic day 4.5 (E4.5) (study group), and administered an equivalent volume of phosphate-buffered saline in another cohort of pregnant mice (control group). We recorded the weight of pregnant mice and their fetuses. The maternal and fetal weight of the study group decreased in comparison with that of the control group, whereas the weight of placenta increased in the study group. Then, five genes with significant upregulation and 15 genes with downregulation were screened. Expression of interleukin 4 (IL-4) mRNA in the study group decreased to 18.5%. Enzyme-linked immunosorbent assay results showed IL-4 expression in mouse plasma declined in the study group at E11.5 and E18.5. mRNA expression of chemokine (c-c motif) ligand (CCL)-17, CCL-22, CCL-24, IL-4, Janus Kinase (JAK)-1, signal transducer and activator of transcription (STAT)-6, and GATA-3 showed significant downregulation in placental and uterine tissues. Flow cytometry of primary decidual macrophages (DMs) revealed more M1-like macrophages in the study group. And after addition of IL-4 to DMs, more M1 macrophages polarized to M2 type macrophages. We did not discover bacteria existed in mouse placentas. Our study affords a feasible method for exploring and managing AV during pregnancy.
Illumina Sequencing and Metabolomics Analysis Reveal Thiamine Modulation of Ruminal Microbiota and Metabolome Characteristics in Goats Fed a High-Concentrate Diet
Authors: Ma Yi , Wang Chao , Zhang Hao , Yu Lihuai , Dong Li , Gong Daoqing , Yao Junhu , Wang Hongrong
Published: April 2021

Long-term supplementation of a high-concentrate diet enhances the accumulation of lactate and decrease in pH in goat rumen, thereby disrupting the composition of microbial community. Studies have shown that incorporation of thiamine in high-concentrate diet increases ruminal pH and decreases rumen lactate concentration. To explore the effects of thiamine supplementation with a high-concentrate diet on alteration of the whole ruminal microbiota and their metabolites, 18 mid-lactating Saanen goats were randomly fed with one of three diets: (1) control diet (CON; n = 6; concentrate:forage 30:70), (2) high-concentrate diet (HG; n = 6; concentrate:forage 70:30), and (3) high-concentrate diet with 200 mg of thiamine/kg of DMI (HGT; n = 6; concentrate:forage 70:30). The goats received experimental diets for 8 weeks. Ruminal samples were collected on the last day of the 8 weeks for 16S rRNA gene sequencing and the liquid chromatograph–mass spectrometer (LC-MS) analysis. The results revealed significant alterations of the ruminal bacterial community structure and diversity in HGT groups compared to HG groups, with an overall dominance of Bacteroidetes at the phylum level and Oribacterium (P < 0.05), Anaerobiospirillum (P < 0.01), and Fibrobacter (P < 0.01) at genus level in the HGT group. The LC-MS analysis revealed that thiamine supplementation resulted in lower levels of propionate (P < 0.05), pyruvate (P < 0.01), lactate (P < 0.05), putrescine (P < 0.05), tyramine (P < 0.05), and histamine (P < 0.01) and higher levels of acetate (P < 0.05), succinates (P < 0.01), oxaloacetic acid (P < 0.01), leucine (P < 0.01), valine (P < 0.05), linoleic acid (P < 0.05), docosahexaenoic acid (P < 0.05), and 4-phenylbutyric acid (P < 0.05) in the HGT group than in the HG group. The decrease in these compounds enhanced homeostasis in the rumen environment and suppressed epithelial inflammation. Correlation analysis revealed the potential relationships between ruminal metabolites and microbial community. These findings demonstrate that thiamine supplementation can alleviate subacute ruminal acidosis (SARA) by stabilizing the microbial community and reducing toxic unnatural compounds.