Alterations in Metabolome and Microbiome Associated with an Early Stress Stage in Male Wistar Rats: A Multi-Omics Approach

Stress disorders have dramatically increased in recent decades becoming the most prevalent psychiatric disorder in the United States and Europe. However, the diagnosis of stress disorders is currently based on symptom checklist and psychological questionnaires, thus making the identification of candidate biomarkers necessary to gain better insights into this pathology and its related metabolic alterations. Regarding the identification of potential biomarkers, omic profiling and metabolic footprint arise as promising approaches to recognize early biochemical changes in such disease and provide opportunities for the development of integrative candidate biomarkers. Here, we studied plasma and urine metabolites together with metagenomics in a 3 days Chronic Unpredictable Mild Stress (3d CUMS) animal approach that aims to focus on the early stress period of a well-established depression model. The multi-omics integration showed a profile composed by a signature of eight plasma metabolites, six urine metabolites and five microbes. Specifically, threonic acid, malic acid, alpha-ketoglutarate, succinic acid and cholesterol were proposed as key metabolites that could serve as key potential biomarkers in plasma metabolome of early stages of stress. Such findings targeted the threonic acid metabolism and the tricarboxylic acid (TCA) cycle as important pathways in early stress. Additionally, an increase in opportunistic microbes as virus of the Herpesvirales was observed in the microbiota as an effect of the primary stress stages. Our results provide an experimental biochemical characterization of the early stage of CUMS accompanied by a subsequent omic profiling and a metabolic footprinting that provide potential candidate biomarkers.

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Characterization of a Viral Phosphoprotein Binding Site on the Surface of the Respiratory Syncytial Nucleoprotein

Journal of Virology ◽

10.1128/jvi.00058-12 ◽

2012 ◽

Vol 86 (16) ◽

pp. 8375-8387 ◽

Cited By ~ 28

Author(s):

Marie Galloux ◽

Bogdan Tarus ◽

Ilfad Blazevic ◽

Jenna Fix ◽

Stéphane Duquerroy ◽

...

Keyword(s):

Biochemical Characterization ◽

Specific Interaction ◽

Viral Rna ◽

Site Directed Mutagenesis ◽

Luciferase Reporter ◽

Potential Candidate ◽

Luciferase Reporter Gene ◽

Interaction Domain ◽

Rna Complex

The human respiratory syncytial virus (HRSV) genome is composed of a negative-sense single-stranded RNA that is tightly associated with the nucleoprotein (N). This ribonucleoprotein (RNP) complex is the template for replication and transcription by the viral RNA-dependent RNA polymerase. RNP recognition by the viral polymerase involves a specific interaction between the C-terminal domain of the phosphoprotein (P) (PCTD) and N. However, the P binding region on N remains to be identified. In this study, glutathioneS-transferase (GST) pulldown assays were used to identify the N-terminal core domain of HRSV N (NNTD) as a P binding domain. A biochemical characterization of the PCTDand molecular modeling of the NNTDallowed us to define four potential candidate pockets on N (pocket I [PI] to PIV) as hydrophobic sites surrounded by positively charged regions, which could constitute sites complementary to the PCTDinteraction domain. The role of selected amino acids in the recognition of the N-RNA complex by P was first screened for by site-directed mutagenesis using a polymerase activity assay, based on an HRSV minigenome containing a luciferase reporter gene. When changed to Ala, most of the residues of PI were found to be critical for viral RNA synthesis, with the R132A mutant having the strongest effect. These mutations also reduced or abolishedin vitroandin vivoP-N interactions, as determined by GST pulldown and immunoprecipitation experiments. The pocket formed by these residues is critical for P binding to the N-RNA complex, is specific for pneumovirus N proteins, and is clearly distinct from the P binding sites identified so far for other nonsegmented negative-strand viruses.

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Effects of intramammary infection on whey proteinograms of sheep during lactation

Pesquisa Veterinária Brasileira ◽

10.1590/s0100-736x2015000300004 ◽

2015 ◽

Vol 35 (3) ◽

pp. 230-236 ◽

Cited By ~ 1

Author(s):

Vânia F. Lemos ◽

Eduardo L.S. Guaraná ◽

José A.B. Afonso ◽

José J. Fagliari ◽

Paulo C. Silva ◽

...

Keyword(s):

Mammary Gland ◽

Biochemical Characterization ◽

Production Systems ◽

Polyacrylamide Gel Electrophoresis ◽

Whey Proteins ◽

Sodium Dodecyl ◽

Acid Glycoprotein ◽

Milk Samples ◽

Lactation Stage ◽

Potential Biomarkers

The study aimed to identify potential biomarkers of mammary gland infection in Santa Inês sheep. Commercial flocks of sheep provided the same hygiene, sanitary, and nutritional management under semi-intensive production systems were monitored during the lactation stage-and assessed 15, 30, 60, and 90 days after delivery (through the end of lactation and weaning). The California Mastitis Test (CMT) was performed on the mammary glands. Milk was collected for bacterial examination and protein analysis. Bacterial culture and biochemical characterization of the samples were performed. Forty-two milk samples from healthy glands (negative CMT and bacterial testing) and 43 milk samples from infected glands (positive CMT and bacterial testing) taken at the predefined time points were assessed. A rennin solution was used to obtain the whey. The proteins analysis was performed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), which allowed for the quantification of nine whey proteins produced in healthy glands: serum albumin, lactoferrin, IgA, IgG heavy-chain (IgG HC), IgG light-chain (IgG LC), total IgG (IgG HC + IgG LC), α-lactalbumin, β-lactoglobulin, protein with MW 15.000 Da, protein with MW 29.000 Da and eleven whey proteins secreted by infected glands, including haptoglobin and α-1-acid glycoprotein. A comparison of whey proteins between healthy and infected glands showed increases (P<0.05) in the secreted and total contents of all proteins, except for IgG LC and α-lactoalbumin. The most significant changes were observed in α-1-acid glycoprotein, lactoferrin and haptoglobin, which showed three-, five-, and seven-fold increases in secretion, respectively. This study showed that haptoglobin, α-1-acid glycoprotein, lactoferrin, albumin, and the IgA and IgG immunoglobulins may serve as potential biomarkers for mammary gland infection in sheep.

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Transcranial magnetic stimulation and transcranial direct current stimulation appear to be safe neuromodulatory techniques useful in the treatment of anxiety disorders and other neuropsychiatric disorders

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20160115 ◽

2016 ◽

Vol 74 (10) ◽

pp. 829-835 ◽

Cited By ~ 9

Author(s):

Aline Iannone ◽

Antonio Pedro de Mello Cruz ◽

Joaquim Pereira Brasil-Neto ◽

Raphael Boechat-Barros

Keyword(s):

Transcranial Magnetic Stimulation ◽

Anxiety Disorders ◽

Direct Current ◽

Transcranial Direct Current Stimulation ◽

Magnetic Stimulation ◽

Neuropsychiatric Disorders ◽

The United States ◽

Stress Disorders ◽

Off Label ◽

Direct Current Stimulation

ABSTRACT Transcranial magnetic stimulation (TMS) has recently been investigated as a possible adjuvant treatment for many neuropsychiatric disorders, and has already been approved for the treatment of drug-resistant depression in the United States and in Brazil, among other countries. Although its use in other neuropsychiatric disorders is still largely experimental, many physicians have been using it as an off-label add-on therapy for various disorders. More recently, another technique, transcranial direct current stimulation (tDCS), has also become available as a much cheaper and portable alternative to TMS, although its mechanisms of action are different from those of TMS. The use of off-label therapeutic TMS or tDCS tends to occur in the setting of diseases that are notoriously resistant to other treatment modalities. Here we discuss the case of anxiety disorders, namely panic and post-traumatic stress disorders, highlighting the uncertainties and potential problems and benefits of the clinical use of these neuromodulatory techniques at the current stage of knowledge.

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Plasma metabolites in treatment-requiring retinopathy of prematurity: Potential biomarkers identified by metabolomics

Experimental Eye Research ◽

10.1016/j.exer.2020.108198 ◽

2020 ◽

Vol 199 ◽

pp. 108198

Author(s):

Yedi Zhou ◽

Yu Xu ◽

Xiang Zhang ◽

Peiquan Zhao ◽

Xiaoyun Gong ◽

...

Keyword(s):

Retinopathy Of Prematurity ◽

Plasma Metabolites ◽

Potential Biomarkers

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Identification and confirmation of greenbug resistance loci in an advanced mapping population of sorghum

The Journal of Agricultural Science ◽

10.1017/s0021859617000685 ◽

2017 ◽

Vol 155 (10) ◽

pp. 1610-1622 ◽

Cited By ~ 1

Author(s):

SOMASHEKHAR PUNNURI ◽

YINGHUA HUANG

Keyword(s):

Great Plains ◽

Qtl Analysis ◽

Mapping Population ◽

Molecular Genetic ◽

The United States ◽

Chromosome 9 ◽

Potential Candidate ◽

Resistant Parent ◽

Molecular Genetic Map ◽

Greenbug Resistance

SUMMARYGreenbug infestations to sorghum can cause severe and above economic threshold damage in the Great Plains of the United States. The current study was conducted to identify quantitative trait loci (QTLs) and potential candidate genes residing within the QTL region responsible for greenbug resistance in an advanced mapping population. Inter-crossed populations are useful in detecting QTLs tightly linked to genetic markers with high resolution. In the current study, QTLs responsible for greenbug resistance in sorghum were mapped using an inter-cross population derived from two parents, BTx623 (greenbug-susceptible line) and PI 607900 (greenbug-resistant line). Molecular markers for 115 loci were used to construct a linkage map which eventually facilitated tagging portions of the sorghum genome regions responsible for greenbug resistance. The molecular genetic map covered all the chromosomes of sorghum with a total genome length of 963·0 cM. The advanced mapping population revealed and confirmed the location of greenbug resistance loci, which explained a high phenotypic variation from 72·9 to 80·9% of greenbug resistance. The loci for greenbug resistance were mapped to the region flanked by markers Starssbnm 93 and Starssbnm 102 on chromosome 9 with an increased allelic effect from the resistant parent. The locations of these loci were compared with a previous study on QTL analysis using an F2 mapping population. The results from the present study were in agreement with the findings in the F2 QTL analysis and identified QTLs had a better confidence interval. The markers/QTLs identified from the current study can be effectively utilized in marker-assisted selection and map-based cloning experiments.

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Polyphenol-Based Microencapsulated Extracts as Novel Green Insecticides for Sustainable Management of Polyphagous Brown Marmorated Stink Bug (Halyomorpha halys Stål, 1855)

Sustainability ◽

10.3390/su122310079 ◽

2020 ◽

Vol 12 (23) ◽

pp. 10079

Author(s):

Ivana Pajač Živković ◽

Slaven Jurić ◽

Marko Vinceković ◽

Marija Andrijana Galešić ◽

Marijan Marijan ◽

...

Keyword(s):

Bioactive Compounds ◽

Encapsulation Efficiency ◽

The United States ◽

Fickian Diffusion ◽

Growth Stages ◽

Halyomorpha Halys ◽

Potential Candidate ◽

Brown Marmorated Stink Bug ◽

Stink Bug ◽

Fruit Growing

The brown marmorated stink bug (Halyomorpha halys Stål, 1855) is an invasive polyphagous species that threatens fruit growing both in the United States and Europe. Many pesticide active ingredients have been studied in H. halys management, but for sustainable fruit growing, which implies the reduction of chemical harm to the environment, new safe insecticides should be implemented into the practice. For this purpose, novel green insecticide based on natural polyphenols of species Stevia rebaudiana (Bertoni) Bertoni and Aronia melanocarpa (Michx.) Elliott 1821 was developed. Stevia leaves (SLE) and Aronia pomace (APE) aqueous extracts were prepared using the ultrasound-assisted extraction method. Optimal extraction conditions for bioactive compounds (total polyphenols, flavonoids, anthocyanins, and flavan-3-ols, respectively) and antioxidant activity were determined using response surface methodology. Bioactive compounds rich SLE and APE were encapsulated in calcium alginate microparticles by the ionic gelation method. Physicochemical characteristics (morphology, size, encapsulation efficiency, loading capacity, and swelling) of microparticles showed very good properties with especially high encapsulation efficiency. Fitting to simple Korsmeyer–Peppa’s empirical model revealed that the underlying release mechanism of polyphenols is Fickian diffusion. SLE loaded microparticles showed very good pesticidal efficiency against Halyomorpha halys, especially on younger larval stages after both contact and digestive treatment. Microparticles loaded with APE did not achieve satisfactory digestive efficiency, but a certain toxic impact has been observed at contact application on all H. halys growth stages. Microparticles loaded with SLS exhibited prolonged insecticidal action against H. halys and could be a potential candidate as a green insecticide whose application could increase fruit growing safety.

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Identification of Potential Biomarkers for Early Prediction of Gestational Diabetes

Current Developments in Nutrition ◽

10.1093/cdn/nzaa049_038 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 645-645

Author(s):

Lauren McMichael ◽

Catherine Johnson ◽

Rob Fanter ◽

Alex Brito ◽

Noemi Alarcon ◽

...

Keyword(s):

Gestational Diabetes ◽

Dietary Intervention ◽

Post Partum ◽

Intervention Group ◽

First Trimester ◽

The United States ◽

Plasma Samples ◽

Third Trimester ◽

Purine Derivative ◽

Potential Biomarkers

Abstract Objectives Gestational Diabetes Mellitus (GDM) is present in up to 10% of pregnancies in the United States. The occurrence of GDM causes severe short- and long-term complications for the mother and offspring. baby pre- and post-partum. Identification of the metabolites and potential biomarkers involved in GDM could improve the prediction of its occurence. The integration of food data with metabolite results could provide innovative diet intervention strategies. The objective of this study is to identify metabolites that differed in the first and third trimesters of GDM versus Non-GDM pregnancies. Methods Participants were 68 OW/OB pregnant women enrolled in the Healthy Beginnings Trial and completed blood draws at first (10–16 weeks) and third trimester (28–35 weeks). Participants from the control and dietary intervention group who developed GDM (n = 34; GDM group) were matched on age, BMI, ethnicity, and treatment group with those who did not develop GDM (n = 34; Non-GDM group). Plasma samples were analyzed by ultra-high-performance liquid chromatography-hybrid triple-quadrupole linear ion trap mass spectrometry (UPLC-QTRAP) using three targeted metabolomics assays for primary metabolomics, aminomics and lipdomics. Dietary intake was estimated using 24 hour recalls in order to assess potential dietary differences between groups. Results A total of 243 metabolites were identified in the plasma samples. At first trimester, several complex lipids, including cholestryl esters and phospholipids, were higher in the GDM group (P < 0.05). Furthermore, the purine derivative hypoxanthine was also higher in GDM subjects (P < 0.05). At third trimester, multiple acylcarnitines, associated with utilization of fat for energy, were lower in the GDM group (P < 0.05). Conclusions Metabolite differences between GDM and Non-GDM groups in plasma samples collected during first trimester may predict the development of GDM. Further research is required to identify the roles these metabolite changes play in the development of this disease. Funding Sources NIH National Heart, Lung, and Blood Institute (NHLBI; HL114377), ARI #58,875, Cal Poly CAFES SURP.

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Genetic Context and Biochemical Characterization of the IMP-18 Metallo-β-Lactamase Identified in aPseudomonas aeruginosaIsolate from the United States

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00858-10 ◽

2010 ◽

Vol 55 (1) ◽

pp. 140-145 ◽

Cited By ~ 15

Author(s):

Luisa Borgianni ◽

Silvia Prandi ◽

Laurie Salden ◽

Gisela Santella ◽

Nancy D. Hanson ◽

...

Keyword(s):

United States ◽

Biochemical Characterization ◽

Gene Cassette ◽

The United States ◽

Turnover Rates ◽

Reading Frame ◽

Class 1 ◽

Original Array ◽

Genetic Context

ABSTRACTThe production of metallo-β-lactamase (MBL) is an important mechanism of resistance to β-lactam antibiotics, including carbapenems. Despite the discovery and emergence of many acquired metallo-β-lactamases, IMP-type determinants (now counting at least 27 variants) remain the most prevalent in some geographical areas. In Asian countries, and notably Japan, IMP-1 and its closely related variants are most widespread. Some other variants have been detected in other countries and show either an endemic (e.g., IMP-13 in Italy) or sporadic (e.g., IMP-12 in Italy or IMP-18 in the United States) occurrence. The IMP-18-producingPseudomonas aeruginosastrain PS 297 from the southwestern United States carried at least two class 1 integrons. One was identical to In51, while the other, named In133and carrying theblaIMP-18gene cassette in the third position, showed an original array of five gene cassettes, includingaacA7,qacF,aadA1, and an unknown open reading frame (ORF). Interestingly. In133differed significantly from In96, theblaIMP-18-carrying integron identified in aP. aeruginosaisolate from Mexico. The meropenem and ertapenem MIC values were much lower forEscherichia colistrains producing IMP-18 (0.06 and 0.12 μg/ml, respectively) than for strains producing IMP-1 (2 μg/ml for each). Kinetic data obtained with the purified enzyme revealed lower turnover rates of IMP-18 than of other IMP-type enzymes with most substrates.

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First Report of Anthracnose of Salsola tragus Caused by Colletotrichum gloeosporioides in Greece

Plant Disease ◽

10.1094/pd-90-0971b ◽

2006 ◽

Vol 90 (7) ◽

pp. 971-971 ◽

Cited By ~ 4

Author(s):

D. K. Berner ◽

C. A. Cavin ◽

M. B. McMahon ◽

I. Loumbourdis

Keyword(s):

Biological Control ◽

Colletotrichum Gloeosporioides ◽

Type A ◽

The United States ◽

Ionic Surfactant ◽

Potential Candidate ◽

Conidial Suspension ◽

Type B ◽

First Report ◽

Stems And Leaves

In early October of 2005, dying Salsola tragus L. (Russian thistle, tumbleweed), family Chenopodiaceae, plants were found along the Aegean Sea at Kryopigi Beach, Greece (40°02′29″N, 23°29′02″E, elevation 0 m). All of the 30 to 40 plants in the area were diseased and approximately 80% were dead or dying. All plants were relatively large (approximately 1 m tall × 0.5 m diameter), and living portions of diseased plants were flowering. Dying plants had irregular, necrotic lesions extending the length of the stems. Leaves of these plants were also necrotic. Lesions on stems and leaves were dark brown and usually coalesced. Diseased stem pieces were taken to the European Biological Control Laboratory, USDA, ARS at the American Farm School in Thessaloniki, Greece. There, diseased stem pieces were surface disinfested for 15 min with 0.5% NaOCl and placed on moist filter paper in petri dishes. Numerous, waxy subepidermal acervuli with black setae were observed in all lesions after 2 to 3 days. Conidiophores were simple, short, and erect. Conidia were one-celled, hyaline, ovoid to oblong, falcate to straight, 12.9 to 18.0 × 2.8 to 5.5 μm (mode 16.1 × 4.5 μm). These characters conformed to the description of Colletotrichum gloeosporioides (Penz.) Penz. & Sacc. in Penz. (2). Conidia were placed on modified potato carrot agar and axenic cultures from these isolations were sent to the quarantine facility of the Foreign Disease-Weed Science Research Unit, USDA, ARS, Fort Detrick, MD for testing. On the basis of DNA sequences, two variants within S. tragus have been described in California and named “Type A” and “Type B” (1). Conidia were harvested from 14-day-old cultures grown on 20% V8 juice agar, and healthy stems and leaves of 18 30-day-old plants of S. tragus Type A and 10 Type B plants were spray inoculated with an aqueous conidial suspension (1.0 × 106 conidia/ml plus 0.1% non-ionic surfactant). Three control plants of each type were sprayed with water and surfactant only. Plants were placed in an environmental chamber (18 h of dew in darkness at 25°C). After 1 day, all plants were transferred to a greenhouse (20 to 25°C, 30 to 50% relative humidity, and natural light augmented with 12-h light periods with 500-W sodium vapor lights). Lesions developed on stems of inoculated Type A plants after 5 days. After 14 days, all inoculated Type A plants were dead. Lesions on Type B plants were small and localized; all plants were diseased but no plants died. No symptoms occurred on control plants. C. gloeosporioides was reisolated 14 to 21 days after inoculation from stem pieces of all inoculated plants of both types of S. tragus. This isolate of C. gloeosporioides is a destructive pathogen on S. tragus Type A and is a potential candidate for biological control of this weed in the United States. To our knowledge, this is the first report of anthracnose caused by C. gloeosporioides on S. tragus in Greece. A voucher specimen has been deposited with the U.S. National Fungus Collections, Beltsville, MD (BPI 871126). Nucleotide sequences for the internal transcribed spacers (ITS 1 and 2) were deposited in GenBank (Accession No. DQ344621) and exactly matched sequences of the teleomorph, Glomerella cingulata. References: (1) F. Ryan and D. Ayres. Can. J. Bot. 78:59, 2000. (2) B. C. Sutton. Page 15 in: Colletotrichum Biology, Pathology and Control. J. A. Bailey and M. J. Jeger, eds. CAB International Mycological Institute, Wallingford, UK, 1992.

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Involuntary Competence in United States Criminal Law

10.1093/oso/9780198788478.003.0010 ◽

2018 ◽

Author(s):

Stephen J Morse

Keyword(s):

Mental Health ◽

United States ◽

Mental Health Professionals ◽

Criminal Law ◽

The United States ◽

Potential Candidate ◽

Competence To Stand Trial ◽

Involuntary Treatment ◽

Justice Process ◽

Trial Competence

This chapter explores all the stages in the United States criminal justice process in which a defendant or prisoner may become incompetent and a potential candidate for involuntary treatment to restore the subject’s competence, including competence to stand trial, competence to plead guilty and to waive trial rights, competence to represent himself, and competence to be sentenced. Other legal systems may treat this as primarily a mental health law question addressed best by mental health laws, but in the United States, it is a criminal law question, although some courts are very deferential to the judgement of mental health professionals. The chapter then surveys the law and offers a normative set of recommendations for when involuntary treatment is justified, as well as recommendations for the disposition of the subject if involuntary treatment is not justified or is unsuccessful.

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