scholarly journals Effect of a Flaxseed Lignan Intervention on Circulating Bile Acids in a Placebo-Controlled Randomized, Crossover Trial

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1837
Author(s):  
Sandi L. Navarro ◽  
Lisa Levy ◽  
Keith R. Curtis ◽  
Isaac Elkon ◽  
Orsalem J. Kahsai ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bacterial Metabolism ◽  
Cross Sectional ◽  
Bacterial Gene ◽  
Bacterial Gene Expression ◽  
Randomized Crossover Trial ◽  
Sectional Analysis ◽  
Plant Lignans ◽  
Inducible Gene

Plant lignans and their microbial metabolites, e.g., enterolactone (ENL), may affect bile acid (BA) metabolism through interaction with hepatic receptors. We evaluated the effects of a flaxseed lignan extract (50 mg/day secoisolariciresinol diglucoside) compared to a placebo for 60 days each on plasma BA concentrations in 46 healthy men and women (20–45 years) using samples from a completed randomized, crossover intervention. Twenty BA species were measured in fasting plasma using LC-MS. ENL was measured in 24-h urines by GC-MS. We tested for (a) effects of the intervention on BA concentrations overall and stratified by ENL excretion; and (b) cross-sectional associations between plasma BA and ENL. We also explored the overlap in bacterial metabolism at the genus level and conducted in vitro anaerobic incubations of stool with lignan substrate to identify genes that are enriched in response to lignan metabolism. There were no intervention effects, overall or stratified by ENL at FDR < 0.05. In the cross-sectional analysis, irrespective of treatment, five secondary BAs were associated with ENL excretion (FDR < 0.05). In vitro analyses showed positive associations between ENL production and bacterial gene expression of the bile acid-inducible gene cluster and hydroxysteroid dehydrogenases. These data suggest overlap in community bacterial metabolism of secondary BA and ENL.

scholarly journals Fetal Echocardiography:Short Term Profile from Shahid Gangalal National Heart Centre, Kathmandu, Nepal

2016 ◽  
Vol 13 (1) ◽  
pp. 9-12
Author(s):  
Sudhir Regmi ◽  
Deewakar Sharma
Keyword(s):  
Pregnant Women ◽  
Congenital Heart ◽  
Fetal Echocardiography ◽  
Tertiary Care ◽  
Outcome Data ◽  
Cross Sectional ◽  
Vitro Fertilization ◽  
History Of ◽  
Sectional Analysis

Background and Aims: Fetal echocardiography is helpful in early detection of Congenital Heart Disease. Our study was conducted to evaluate the most common indications of referral and outcome in a tertiary-care fetal echocardiography practice.Methods: A Cross-sectional analysis of all pregnant women referred by obstetricians to cardiology unit for fetal echocardiography over a 1-year period (July 2014 and July 2015) was performed. The primary indications for referral for fetal echocardiography were obtained from the obstetric referral forms. Outcome data were extracted from performa containing client’s demographic, physical examination and the fetal echocardiograhic data. Postnatal Echocardiography was advised to all cases having positive echocardiographic finding.Results: A series of 251 fetal cardiac studies were reviewed. Average gestational age was 25.6 weeks (range, 18 to 38 weeks). Thirty-eight (15.1%) pregnant women had abnormal fetal cardiac findings. The most common referral for fetal cardiac scan was related to maternal indications (48.6%). Other indications were abnormal prenatal fetal findings in ultrasonography (23.1%), family history of CHD (12%), general screening (15.5%), and follow up of IVF (In-vitro fertilization) (0.8%). The highest yield of significant abnormal findings was there among patients referred with abnormal prenatal fetal finding in ultrasonography (47%).Conclusion: Majority of referral were for abnormal prenatal ultrasonographic findings. So, fetal Echocardiography is an important part of overall management of the pregnancy at risk for producing an infant with congenital heart disease.Nepalese Heart Journal 2016; 13(1): 9-12

scholarly journals Evaluation of Live Bacterial Prophylactics to Decrease IncF Plasmid Transfer and Association With Intestinal Small RNAs

2021 ◽  
Vol 11 ◽  
Author(s):  
Graham A. J. Redweik ◽  
Mary Kate Horak ◽  
Ryley Hoven ◽  
Logan Ott ◽  
Melha Mellata
Keyword(s):  
Virulence Genes ◽  
Positive Association ◽  
Multidrug Resistant ◽  
Plasmid Transfer ◽  
Siderophore Production ◽  
Causal Mechanism ◽  
Bacterial Gene ◽  
E Coli ◽  
Bacterial Gene Expression

Chicken intestinal Escherichia coli are a reservoir for virulence and antimicrobial resistance (AMR) genes that are often carried on incompatibility group F (IncF) plasmids. The rapid transfer of these plasmids between bacteria in the gut contributes to the emergence of new multidrug-resistant and virulent bacteria that threaten animal agriculture and human health. Thus, the aim of the present study was to determine whether live bacterial prophylactics could affect the distribution of large virulence plasmids and AMR in the intestinal tract and the potential role of smRNA in this process. In this study, we tested ∼100 randomly selected E. coli from pullet feces (n = 3 per group) given no treatment (CON), probiotics (PRO), a live Salmonella vaccine (VAX), or both (P + V). E. coli isolates were evaluated via plasmid profiles and several phenotypic (siderophore production and AMR), and genotypic (PCR for virulence genes and plasmid typing) screens. P + V isolates exhibited markedly attenuated siderophore production, lack of AMR and virulence genes, which are all related to the loss of IncF and ColV plasmids (P &lt; 0.0001). To identify a causal mechanism, we evaluated smRNA levels in the ceca mucus and found a positive association between smRNA concentrations and plasmid content, with both being significantly reduced in P + V birds compared to other groups (P &lt; 0.01). To test this positive association between IncF plasmid transfer and host smRNA concentration, we evenly pooled smRNA per group and treated E. coli mating pairs with serial concentrations of smRNA in vitro. Higher smRNA concentrations resulted in greater rates of IncF plasmid transfer between E. coli donors (APEC O2 or VAX isolate IA-EC-001) and recipient (HS-4) (all groups; P &lt; 0.05). Finally, RNAHybrid predictive analyses detected several chicken miRNAs that hybridize with pilus assembly and plasmid transfer genes on the IncF plasmid pAPEC-O2-R. Overall, we demonstrated P + V treatment reduced smRNA levels in the chicken ceca, which was associated with a reduction in potentially virulent E. coli. Furthermore, we propose a novel mechanism in which intestinal smRNAs signal plasmid exchange between E. coli. Investigations to understand the changes in bacterial gene expression as well as smRNAs responsible for this phenomenon are currently underway.

scholarly journals Role of Hfq in Genome Evolution: Instability of G-Quadruplex Sequences in E. coli

2019 ◽  
Vol 8 (1) ◽  
pp. 28 ◽  
Author(s):  
Virali J. Parekh ◽  
Brittany A. Niccum ◽  
Rachna Shah ◽  
Marisa A. Rivera ◽  
Mark J. Novak ◽  
...  
Keyword(s):  
Genomic Instability ◽  
Dna Repeats ◽  
Loop Formation ◽  
Bacterial Gene ◽  
Quadruplex Dna ◽  
E Coli ◽  
Alternative Structures ◽  
Bacterial Gene Expression ◽  
G Quadruplex

Certain G-rich DNA repeats can form quadruplex in bacterial chromatin that can present blocks to DNA replication and, if not properly resolved, may lead to mutations. To understand the participation of quadruplex DNA in genomic instability in Escherichia coli (E. coli), mutation rates were measured for quadruplex-forming DNA repeats, including (G3T)4, (G3T)8, and a RET oncogene sequence, cloned as the template or nontemplate strand. We evidence that these alternative structures strongly influence mutagenesis rates. Precisely, our results suggest that G-quadruplexes form in E. coli cells, especially during transcription when the G-rich strand can be displaced by R-loop formation. Structure formation may then facilitate replication misalignment, presumably associated with replication fork blockage, promoting genomic instability. Furthermore, our results also evidence that the nucleoid-associated protein Hfq is involved in the genetic instability associated with these sequences. Hfq binds and stabilizes G-quadruplex structure in vitro and likely in cells. Collectively, our results thus implicate quadruplexes structures and Hfq nucleoid protein in the potential for genetic change that may drive evolution or alterations of bacterial gene expression.

Spatiotemporal control of the bacteria to express interferon-γ by focused ultrasound for tumor immunotherapy

2021 ◽  
Author(s):  
Yuhao Chen ◽  
Meng Du ◽  
Zhen Yuan ◽  
Fei Yan ◽  
Zhiyi Chen
Keyword(s):  
Focused Ultrasound ◽  
Tumor Therapy ◽  
Tumor Immunotherapy ◽  
Interferon Γ ◽  
Genetic Switch ◽  
Bacterial Gene ◽  
Bacterial Gene Expression ◽  
Ifn Γ

Abstract Bacteria-based tumor therapy has recently attracted wide attentions due to its unique capability in targeting tumors and preferentially colonizing the core area of the tumor. Various therapeutic genes were also harbored into these engineering bacteria to enhance their anti-tumor efficacy. However, it is difficult to spatiotemporally control the expression of these inserted genes in the tumor site. Here, we engineered an ultrasound-responsive bacterium (URB) which can induce the expression of exogenous genes in an ultrasound-controllable manner. Owing to the advantage of ultrasound in the tissue penetration, energy focusing into heating, an acoustic remote control of bacterial gene expression can be realized by designing a temperature-actuated genetic switch. Cytokine interferon-γ (IFN-γ), an important immune regulatory molecule that plays a significant role in tumor immunotherapy, was used to test the system. Our results showed a brief hyperthermia by focused ultrasound successfully induced the expression of IFN-γ gene, significantly improving anti-tumor efficacy of URB in vitro and in vivo. Our study provided a novel strategy for bacteria-mediated tumor immunotherapy.

scholarly journals Measurement of bacterial gene expression in vivo

2000 ◽  
Vol 355 (1397) ◽  
pp. 601-611 ◽  
Author(s):  
Isabelle Hautefort ◽  
Jay C. D. Hinton
Keyword(s):  
Gene Expression ◽  
Dynamic Environment ◽  
Subtractive Hybridization ◽  
Fluorescence Induction ◽  
Infection Process ◽  
Bacterial Gene ◽  
Technology System ◽  
Bacterial Gene Expression

The complexities of bacterial gene expression during mammalian infection cannot be addressed by in vitro experiments. We know that the infected host represents a complex and dynamic environment, which is modified during the infection process, presenting a variety of stimuli to which the pathogen must respond if it is to be successful. This response involves hundreds of ivi (in vivo– induced) genes which have recently been identified in animal and cell culture models using a variety of technologies including in vivo expression technology, differential fluorescence induction, subtractive hybridization and differential display. Proteomic analysis is beginning to be used to identify IVI proteins, and has benefited from the availability of genome sequences for increasing numbers of bacterial pathogens. The patterns of bacterial gene expression during infection remain to be investigated. Are ivi genes expressed in an organ–specific or cell–type–specific fashion ? New approaches are required to answer these questions. The uses of the immunologically based in vivo antigen technology system, in situ PCR and DNA microarray analysis are considered. This review considers existing methods for examining bacterial gene expression in vivo, and describes emerging approaches that should further our understanding in the future.

USE OF DNA-DIRECTED IN VITRO SYSTEMS TO STUDY BACTERIAL GENE EXPRESSION

1981 ◽  
pp. 215-243
Author(s):  
Herbert Weissbach ◽  
Tanya Zarucki-Schulz ◽  
Hsiang-fu Kung ◽  
Carlos Spears ◽  
Betty Redfield ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bacterial Gene ◽  
Bacterial Gene Expression ◽  
In Vitro Systems

scholarly journals Biotic Factors Affecting Expression of the 2,4-Diacetylphloroglucinol Biosynthesis Gene phlA in Pseudomonas fluorescens Biocontrol Strain CHA0 in the Rhizosphere

2001 ◽  
Vol 91 (9) ◽  
pp. 873-881 ◽  
Author(s):  
R. Notz ◽  
M. Maurhofer ◽  
U. Schnider-Keel ◽  
B. Duffy ◽  
D. Haas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pseudomonas Fluorescens ◽  
Reporter Gene ◽  
Pythium Ultimum ◽  
Disease Suppression ◽  
Biotic Factors ◽  
Host Genotype ◽  
Bacterial Gene ◽  
Bacterial Gene Expression

Production of the polyketide antimicrobial metabolite 2,4-diacetyl-phloroglucinol (DAPG) is a key factor in the biocontrol activity of Pseudomonas fluorescens CHA0. Strain CHA0 carrying a translational phlA′-′lacZ fusion was used to monitor expression of the phl biosynthetic genes in vitro and in the rhizosphere. Expression of the reporter gene accurately reflected actual production of DAPG in vitro and in planta as determined by direct extraction of the antimicrobial compound. In a gnotobiotic system containing a clay and sand-based artificial soil, reporter gene expression was significantly greater in the rhizospheres of two monocots (maize and wheat) compared with gene expression in the rhizospheres of two dicots (bean and cucumber). We observed this host genotype effect on bacterial gene expression also at the level of cultivars. Significant differences were found among six additional maize cultivars tested under gnotobiotic conditions. There was no difference between transgenic maize expressing the Bacillus thuringiensis insecticidal gene cry1Ab and the near-isogenic parent line. Plant age had a significant impact on gene expression. Using maize as a model, expression of the phlA′-′lacZ reporter gene peaked at 24 h after planting of pregerminated seedlings, and dropped to a fourth of that value within 48 h, remaining at that level throughout 22 days of plant growth. Root infection by Pythium ultimum stimulated bacterial gene expression on both cucumber and maize, and this was independent of differences in rhizosphere colonization on these host plants. To our knowledge, this is the first comprehensive evaluation of how biotic factors that commonly confront bacterial inoculants in agricultural systems (host genotype, host age, and pathogen infection) modulate the expression of key biocontrol genes for disease suppression.

scholarly journals Novel Riboswitch-Binding Flavin Analog That Protects Mice against Clostridium difficile Infection without Inhibiting Cecal Flora

2015 ◽  
Vol 59 (9) ◽  
pp. 5736-5746 ◽  
Author(s):  
Kenneth F. Blount ◽  
Cynthia Megyola ◽  
Mark Plummer ◽  
David Osterman ◽  
Tim O'Connell ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
High Rate ◽  
Flavin Mononucleotide ◽  
Antibacterial Drug ◽  
Bacterial Gene ◽  
Content Type ◽  
Bacterial Gene Expression ◽  
Time Kill

ABSTRACTNovel mechanisms of action and new chemical scaffolds are needed to rejuvenate antibacterial drug discovery, and riboswitch regulators of bacterial gene expression are a promising class of targets for the discovery of new leads. Herein, we report the characterization of 5-(3-(4-fluorophenyl)butyl)-7,8-dimethylpyrido[3,4-b]quinoxaline-1,3(2H,5H)-dione (5FDQD)—an analog of riboflavin that was designed to bind riboswitches that naturally recognize the essential coenzyme flavin mononucleotide (FMN) and regulate FMN and riboflavin homeostasis.In vitro, 5FDQD and FMN bind to and trigger the function of an FMN riboswitch with equipotent activity. MIC and time-kill studies demonstrated that 5FDQD has potent and rapidly bactericidal activity againstClostridium difficile. In C57BL/6 mice, 5FDQD completely prevented the onset of lethal antibiotic-inducedC. difficileinfection (CDI). Against a panel of bacteria representative of healthy bowel flora, the antibacterial selectivity of 5FDQD was superior to currently marketed CDI therapeutics, with very little activity against representative strains from theBacteroides,Lactobacillus,Bifidobacterium,Actinomyces, andPrevotellagenera. Accordingly, a single oral dose of 5FDQD caused less alteration of culturable cecal flora in mice than the comparators. Collectively, these data suggest that 5FDQD or closely related analogs could potentially provide a high rate of CDI cure with a low likelihood of infection recurrence. Future studies will seek to assess the role of FMN riboswitch binding to the mechanism of 5FDQD antibacterial action. In aggregate, our results indicate that riboswitch-binding antibacterial compounds can be discovered and optimized to exhibit activity profiles that merit preclinical and clinical development as potential antibacterial therapeutic agents.

scholarly journals Effect of a Flaxseed Lignan Intervention on Circulating Bile Acids in a Randomized, Crossover Trial

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1576-1576
Author(s):  
Sandi Navarro ◽  
Lisa Levy ◽  
Timothy Randolph ◽  
Natalie Hong ◽  
Fausto Neto ◽  
...  
Keyword(s):  
Dietary Fat ◽  
Mixed Models ◽  
Serum Lipids ◽  
Crossover Trial ◽  
Microbial Metabolites ◽  
Cross Sectional ◽  
High Fiber ◽  
Funding Sources ◽  
Randomized Crossover Trial ◽  
Sectional Analysis

Abstract Objectives Health benefits of high-fiber foods may be attributed, in part, to microbial metabolites of plant compounds. Lignans and their microbial metabolites, the enterolignans [enterolactone (ENL) and enterodiol (END)], reduce serum lipids through a variety of mechanisms, including regulation of bile acid (BA) synthesis. BA, released into the gut lumen in response to dietary fat, undergo microbial metabolism to secondary (2°) BA, which have been positively associated with chronic disease, e.g., liver disease and colorectal cancer. Our aims were to evaluate the effects of a flaxseed lignan supplement on circulating BA and examine associations between enterolignans and 2° BA. Methods We conducted a randomized, crossover trial of a flaxseed lignan supplement (50 mg/d secoisolariciresinol diglucoside) compared to placebo in 46 healthy men and women (20-45 y). Each period lasted 60 days, separated by a 60-day washout period. Six primary and fourteen 2° BA species were measured in fasting plasma using LC-MS. ENL and END were measured in 24-h urines by GC-MS. Low- and high-ENL excreters were defined as below and above the median 24-h ENL excretion at the end of the flaxseed lignan intervention (23.4 µmol/24 h). Linear mixed models were used to a) test the effects of the intervention on individual BA concentrations, overall and stratified by low and high ENL excreters; and b) to cross-sectionally determine the association between plasma 2o BA and ENL and END. Results There was no significant effect of the flaxseed lignan intervention compared to placebo on BA concentrations overall, or by ENL-excreter status, after FDR adjustment. In the cross-sectional analysis, irrespective of treatment, six 2° BA were statistically significantly associated with ENL (FDR &lt; 0.05), with two positive associations (isolithocholic and lithocholic acids), and four inverse associations (glycoursodeoxycholic, glycohyodeoxycholic, hyodeoxycholic, and muricholic acids). Conclusions The flaxseed lignan intervention and subsequent ENL production had no effect on plasma BA concentrations. However, the strong associations between ENL excretion and certain 2° BA concentrations suggests that the gut microbial communities capable of producing ENL may also play a role in 2° BA metabolism. Funding Sources NIH.

scholarly journals A bacteriophage mimic of the bacterial nucleoid-associated protein Fis

2020 ◽  
Vol 477 (7) ◽  
pp. 1345-1362
Author(s):  
Soumyananda Chakraborti ◽  
Dhanasekaran Balakrishnan ◽  
Alexander J. Trotter ◽  
William H. Gittens ◽  
Ally W.H. Yang ◽  
...  
Keyword(s):  
Structural Studies ◽  
Bacterial Gene ◽  
Site Specific ◽  
Bacterial Gene Expression ◽  
Double Stranded Dna ◽  
Bacterial Nucleoid ◽  
Signature Sequence ◽  
Identification And Characterization

We report the identification and characterization of a bacteriophage λ-encoded protein, NinH. Sequence homology suggests similarity between NinH and Fis, a bacterial nucleoid-associated protein (NAP) involved in numerous DNA topology manipulations, including chromosome condensation, transcriptional regulation and phage site-specific recombination. We find that NinH functions as a homodimer and is able to bind and bend double-stranded DNA in vitro. Furthermore, NinH shows a preference for a 15 bp signature sequence related to the degenerate consensus favored by Fis. Structural studies reinforced the proposed similarity to Fis and supported the identification of residues involved in DNA binding which were demonstrated experimentally. Overexpression of NinH proved toxic and this correlated with its capacity to associate with DNA. NinH is the first example of a phage-encoded Fis-like NAP that likely influences phage excision-integration reactions or bacterial gene expression.

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