Bioanalytical Detection of Steroid Abuse in Sports Based on the Androgenic Activity Measurement

The anabolic androgenic steroids (AAS) are the most frequently consumed performance enhancing drugs (PED) in sports. In the anti-doping field, the detection of AAS is carried out by the analysis of the athlete’s urine using methodologies based on liquid/gas chromatography-mass spectrometry. Unfortunately, the detection of unknown compounds is not possible. BDS’s AR CALUX® bio detection technology was studied as an indirect method to detect the administration of a single dose of testosterone (T). Twelve T and placebo single dose administered men volunteers underwent a triple-blind crossover clinical trial. The UGT2B17 deletion was present among the volunteers and evenly distributed in heterozygous (ins/del), wild-type homozygous (ins/ins), and mutated homozygous (del/del) groups. A significant statistical difference in terms of bioluminescence was observed after the testosterone (T) administration for the three types of polymorphic groups. The ratio of means between the pre- and post-T administration periods, depending on the type of polymorphism, was in group ins/ins 3.31 (CI. 95%: 2.07–5.29), group ins/del 4.15 (CI 95%: 3.05–5.67), and group del/del 2.89 (CI 95%: 2.42–3.46). The results of the study are very promising, as they may offer us the possibility of designing a detection approach that, based on intra-individual monitoring of androgenic values, in the UGT2B17 deletion type.

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Characterization of the Volatile Profile of Cultivated and Wild-Type Italian Celery (Apium graveolens L.) Varieties by HS-SPME/GC-MS

Applied Sciences ◽

10.3390/app11135855 ◽

2021 ◽

Vol 11 (13) ◽

pp. 5855

Author(s):

Samantha Reale ◽

Valter Di Cecco ◽

Francesca Di Donato ◽

Luciano Di Martino ◽

Aurelio Manzi ◽

...

Keyword(s):

Solid Phase ◽

Principal Component ◽

Apium Graveolens ◽

Gas Chromatography Mass Spectrometry ◽

Bioactive Metabolites ◽

Chemical Components ◽

Volatile Profile ◽

Wild Type ◽

Multivariate Statistical ◽

Clear Differentiation

Celery (Apium graveolens L.) is a vegetable belonging to the Apiaceae family that is widely used for its distinct flavor and contains a variety of bioactive metabolites with healthy properties. Some celery ecotypes cultivated in specific territories of Italy have recently attracted the attention of consumers and scientists because of their peculiar sensorial and nutritional properties. In this work, the volatile profiles of white celery “Sedano Bianco di Sperlonga” Protected Geographical Indication (PGI) ecotype, black celery “Sedano Nero di Torricella Peligna” and wild-type celery were investigated using head-space solid-phase microextraction combined with gas-chromatography/mass spectrometry (HS-SPME/GC-MS) and compared to that of the common ribbed celery. Exploratory multivariate statistical analyses were conducted using principal component analysis (PCA) on HS-SPME/GC-MS patterns, separately collected from celery leaves and petioles, to assess similarity/dissimilarity in the flavor composition of the investigated varieties. PCA revealed a clear differentiation of wild-type celery from the cultivated varieties. Among the cultivated varieties, black celery “Sedano Nero di Torricella Peligna” exhibited a significantly different composition in volatile profile in both leaves and petioles compared to the white celery and the prevalent commercial variety. The chemical components of aroma, potentially useful for the classification of celery according to the variety/origin, were identified.

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A Single Dose of a Hybrid hAdV5-Based Anti-COVID-19 Vaccine Induces a Long-Lasting Immune Response and Broad Coverage against VOC

Vaccines ◽

10.3390/vaccines9101106 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1106

Author(s):

M. Verónica López ◽

Sabrina E. Vinzón ◽

Eduardo G. A. Cafferata ◽

Felipe J. Núñez ◽

Ariadna Soto ◽

...

Keyword(s):

Dendritic Cells ◽

Single Dose ◽

Neutralizing Antibodies ◽

Human Adenovirus ◽

Human Muscle ◽

T Cell Immunity ◽

Wild Type ◽

Cell Immunity ◽

Human Muscle Cells ◽

Adenovirus 5

Most approved vaccines against COVID-19 have to be administered in a prime/boost regimen. We engineered a novel vaccine based on a chimeric human adenovirus 5 (hAdV5) vector. The vaccine (named CoroVaxG.3) is based on three pillars: (i) high expression of Spike to enhance its immunodominance by using a potent promoter and an mRNA stabilizer; (ii) enhanced infection of muscle and dendritic cells by replacing the fiber knob domain of hAdV5 by hAdV3; (iii) use of Spike stabilized in a prefusion conformation. The transduction with CoroVaxG.3-expressing Spike (D614G) dramatically enhanced the Spike expression in human muscle cells, monocytes and dendritic cells compared to CoroVaxG.5 that expressed the native fiber knob domain. A single dose of CoroVaxG.3 induced a potent humoral immunity with a balanced Th1/Th2 ratio and potent T-cell immunity, both lasting for at least 5 months. Sera from CoroVaxG.3-vaccinated mice was able to neutralize pseudoviruses expressing B.1 (wild type D614G), B.1.117 (alpha), P.1 (gamma) and B.1.617.2 (delta) Spikes, as well as an authentic P.1 SARS-CoV-2 isolate. Neutralizing antibodies did not wane even after 5 months, making this kind of vaccine a likely candidate to enter clinical trials.

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Contribution of epoxyeicosatrienoic acids to flow-induced dilation in arteries of male ERα knockout mice: role of aromatase

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00185.2007 ◽

2007 ◽

Vol 293 (3) ◽

pp. R1239-R1246 ◽

Cited By ~ 14

Author(s):

Dong Sun ◽

Changdong Yan ◽

Azita Jacobson ◽

Houli Jiang ◽

Mairead A. Carroll ◽

...

Keyword(s):

Gas Chromatography Mass Spectrometry ◽

Epoxyeicosatrienoic Acids ◽

Epoxyeicosatrienoic Acid ◽

Wild Type ◽

Electrophysiological Technique ◽

Isolated Arteries ◽

Oxide Synthase ◽

Interfering Rna ◽

Endothelial Nitric Oxide

We studied the roles of estrogen receptors (ER) and aromatase in the mediation of flow-induced dilation (FID) in isolated arteries of male ERα-knockout (ERα-KO) and wild-type (WT) mice. FID was comparable between gracilis arteries of WT and ERα-KO mice. In WT arteries, inhibition of NO and prostaglandins eliminated FID. In ERα-KO arteries, Nω-nitro-l-arginine methyl ester (l-NAME) inhibited FID by ∼26%, whereas indomethacin inhibited dilations by ∼50%. The remaining portion of the dilation was abolished by additional administration of 6-(2-proparglyoxyphenyl)hexanoic acid (PPOH) or iberiotoxin, inhibitors of epoxyeicosatrienoic acid (EET) synthesis and large-conductance potassium channels, respectively. By using an electrophysiological technique, we found that, in the presence of 10 dyne/cm2 shear stress, perfusate passing through donor vessels isolated from gracilis muscle of ERα-KO mice subjected to l-NAME and indomethacin elicited smooth muscle hyperpolarization and a dilator response of endothelium-denuded detector vessels. These responses were prevented by the presence of iberiotoxin in detector or PPOH in donor vessels. Gas chromatography-mass spectrometry (GC-MS) analysis indicated a significant increase in arterial production of EETs in ERα-KO compared with WT mice. Western blot analysis showed a significantly reduced endothelial nitric oxide synthase expression but enhanced expressions of aromatase and ERβ in ERα-KO arteries. Treatment of ERα-KO arteries with specific aromatase short-interfering RNA for 72 h, knocked down the aromatase mRNA and protein associated with elimination of EET-mediation of FID. Thus, FID in male ERα-KO arteries is maintained via an endothelium-derived hyperpolarizing factor/EET-mediated mechanism compensating for reduced NO mediation due, at least in part, to estrogen aromatized from testosterone.

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Abstract 450: The Role of CD38 as a Therapeutic Target for Protection Against Doxorubicin-induced Cardiotoxicity Through Nad+ Boosting

Circulation Research ◽

10.1161/res.127.suppl_1.450 ◽

2020 ◽

Vol 127 (Suppl_1) ◽

Author(s):

Thais R Peclat ◽

Guillermo Agorrody ◽

Lilian S Gomez ◽

Eduardo N Chini

Keyword(s):

Single Dose ◽

Therapeutic Target ◽

Potential Role ◽

Damage Mechanism ◽

Treated Group ◽

Wild Type ◽

Chemotherapeutic Treatment ◽

Positive Effect ◽

Dose Injection

Background: Doxorubicin is a chemotherapy medication used to treat several types of cancer. Its major adverse effect is cardiotoxicity, which may limit its use. Doxorubicin-induced cardiotoxicity (DIC), once developed, carries a poor prognosis. Therefore strategies to prevent or treat DIC are of paramount importance but have not yet been fully developed. Being NAD + a critical nucleotide which is involved in oxy-reduction reactions and CD38 the main NAD + -consuming enzyme responsible for NAD levels regulation and homeostasis, we aim to investigate the link of CD38 and NAD + metabolism in DIC and its potential role as a therapeutic target. Methods: We compared Wild-type (WT) control mice with WT mice treated with a single dose injection of 15 mg/kg of doxorubicin who received vehicle or an antibody that blocksCD38 ecto-enzymatic activity. We also compared genetically CD38 catalytic inactive (CI) mice treated or not with the same single dose injection. Results: Doxorubicin caused a decrease in Ejection Fraction (EF) in WT mice. We also observed that CD38 CI mice treated with doxorubicin did not have changes in EF compared to their control. When compared to WT receiving just doxorubicin, WT mice treated also with the antibody had a trend to improve EF. As for exercise performance, our results show a decrease in exercise capacity induced by doxorubicin that was reversed in the antibody group and did not happen in the CD38 CI mice treated with doxorubicin. Doxorubicin caused a decrease in heart rate variability (HRV) which was improved in the antibody treated group. Moreover, our results show a survival rate that is similar to what has been previously shown, with 50% mortality associated with doxorubicin. Blockage of CD38 activity with antibody reduced mortality in this model to approximately 20%. Mechanistically, we did not observe decreases in NAD+ levels induced by Doxorubicin. However, boost of NAD induced by blocking CD38 was related to protection against DIC. Conclusion: Our results indicate that the damage mechanism of DIC may not be related directly with NAD decrease, but NAD boosting induced by CD38 blockage seems to have a positive effect in protection against cardiac dysfunction related to this chemotherapeutic treatment.

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Identification and Sequencing of β-Myrcene Catabolism Genes from Pseudomonas sp. Strain M1

Applied and Environmental Microbiology ◽

10.1128/aem.65.7.2871-2876.1999 ◽

1999 ◽

Vol 65 (7) ◽

pp. 2871-2876 ◽

Cited By ~ 26

Author(s):

Sandra Iurescia ◽

Andrea M. Marconi ◽

Daniela Tofani ◽

Augusto Gambacorta ◽

Annalisa Paternò ◽

...

Keyword(s):

Genomic Library ◽

Enrichment Culture ◽

Open Reading Frames ◽

Gas Chromatography Mass Spectrometry ◽

Complete Agreement ◽

Wild Type ◽

Genomic Insert ◽

The One ◽

Acyl Coenzyme A ◽

Reading Frames

ABSTRACT The M1 strain, able to grow on β-myrcene as the sole carbon and energy source, was isolated by an enrichment culture and identified as a Pseudomonas sp. One β-myrcene-negative mutant, called N22, obtained by transposon mutagenesis, accumulated (E)-2-methyl-6-methylen-2,7-octadien-1-ol (or myrcen-8-ol) as a unique β-myrcene biotransformation product. This compound was identified by gas chromatography-mass spectrometry. We cloned and sequenced the DNA regions flanking the transposon and used these fragments to identify the M1 genomic library clones containing the wild-type copy of the interrupted gene. One of the selected cosmids, containing a 22-kb genomic insert, was able to complement the N22 mutant for growth on β-myrcene. A 5,370-bp-long sequence spanning the region interrupted by the transposon in the mutant was determined. We identified four open reading frames, named myrA,myrB, myrC, and myrD, which can potentially code for an aldehyde dehydrogenase, an alcohol dehydrogenase, an acyl-coenzyme A (CoA) synthetase, and an enoyl-CoA hydratase, respectively. myrA, myrB, andmyrC are likely organized in an operon, since they are separated by only 19 and 36 nucleotides (nt), respectively, and no promoter-like sequences have been found in these regions. ThemyrD gene starts 224 nt upstream of myrA and is divergently transcribed. The myrB sequence was found to be completely identical to the one flanking the transposon in the mutant. Therefore, we could ascertain that the transposon had been inserted inside the myrB gene, in complete agreement with the accumulation of (E)-2-methyl-6-methylen-2,7-octadien-1-ol by the mutant. Based on sequence and biotransformation data, we propose a pathway for β-myrcene catabolism in Pseudomonas sp. strain M1.

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Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1 Activity in Vivo Limits Glucocorticoid Exposure to Human Adipose Tissue and Decreases Lipolysis

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-2325 ◽

2007 ◽

Vol 92 (3) ◽

pp. 857-864 ◽

Cited By ~ 71

Author(s):

Jeremy W. Tomlinson ◽

Mark Sherlock ◽

Beverley Hughes ◽

Susan V. Hughes ◽

Fiona Kilvington ◽

...

Keyword(s):

Adipose Tissue ◽

Single Dose ◽

Interstitial Fluid ◽

Human Adipose Tissue ◽

Serum Cortisol ◽

Hydroxysteroid Dehydrogenase ◽

Continuous Treatment ◽

Gas Chromatography Mass Spectrometry ◽

Glycerol Release

Abstract Context: The pathophysiological importance of glucocorticoids (GCs) is exemplified by patients with Cushing’s syndrome who develop hypertension, obesity, and insulin resistance. At a cellular level, availability of GCs to the glucocorticoid and mineralocorticoid receptors is controlled by the isoforms of 11β-hydroxysteroid dehydrogenase (11β-HSD). In liver and adipose tissue, 11β-HSD1 converts endogenous, inactive cortisone to active cortisol but also catalyzes the bioactivation of the synthetic prednisone to prednisolone. Objective: The objective of the study was to compare markers of 11β-HSD1 activity and demonstrate that inhibition of 11β-HSD1 activity limits glucocorticoid availability to adipose tissue. Design and Setting: This was a clinical study. Patients: Seven healthy male volunteers participated in the study. Intervention: Intervention included carbenoxolone (CBX) single dose (100 mg) and 72 hr of continuous treatment (300 mg/d). Main Outcome Measures: Inhibition of 11β-HSD1 was monitored using five different mechanistic biomarkers (serum cortisol and prednisolone generation, urinary corticosteroid metabolite analysis by gas chromatography/mass spectrometry, and adipose tissue microdialysis examining cortisol generation and glucocorticoid-mediated glycerol release). Results: Each biomarker demonstrated reduced 11β-HSD1 activity after CBX administration. After both a single dose and 72 hr of treatment with CBX, cortisol and prednisolone generation decreased as did the urinary tetrahydrocortisol+5α-tetrahydrocortisol to tetrahydrocortisone ratio. Using adipose tissue microdialysis, we observed decreased interstitial fluid cortisol availability with CBX treatment. Furthermore, a functional consequence of 11β-HSD1 inhibition was observed, namely decreased prednisone-induced glycerol release into adipose tissue interstitial fluid indicative of inhibition of GC-mediated lipolysis. Conclusion: CBX is able to inhibit rapidly the generation of active GC in human adipose tissue. Importantly, limiting GC availability in vivo has functional consequences including decreased glycerol release.

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Alterations In the Bone Marrow Microenvironment Contribute to Oxidative Stress and DNA Damage In Hematopoietic Stem/Progenitors Carrying a Csf3r Truncation Mutation

Blood ◽

10.1182/blood.v116.21.387.387 ◽

2010 ◽

Vol 116 (21) ◽

pp. 387-387

Author(s):

Ghada M Kunter ◽

Jill Woloszynek ◽

Daniel C. Link

Keyword(s):

Oxidative Stress ◽

Bone Marrow ◽

Dna Damage ◽

Single Dose ◽

Bone Marrow Failure ◽

Bone Marrow Microenvironment ◽

Wild Type ◽

Leukemic Transformation ◽

Hematopoietic Stem ◽

Increased Risk

Abstract Abstract 387 A shared feature of many bone marrow failure syndromes is their propensity to develop myelodysplasia (MDS) or acute myeloid leukemia (AML). The molecular mechanisms that underlie this susceptibility are largely unknown. Severe congenital neutropenia (SCN) is an inherited disorder of granulopoiesis that is associated with a marked increased risk of developing MDS/AML. Somatic mutations of CSF3R, encoding the G-CSF receptor (G-CSFR), that truncate the carboxy-terminal tail are associated with the development of MDS/AML in SCN. Transgenic mice carrying a ‘knock-in’ mutation of their Csf3r (termed d715 G-CSFR) reproducing a mutation found in a patient with SCN have normal basal granulopoiesis but an exaggerated neutrophil response to G-CSF treatment. We previously reported that the d715 G-CSFR is able to cooperate with the PML-RARƒÑ oncogene to induce AML in mice. Herein, we summarize data supporting the hypothesis that alterations in the bone marrow microenvironment induced by G-CSF contribute to oxidative DNA damage in hematopoietic stem/progenitors cells (HSPCs) and possibly leukemic transformation. We previously showed that G-CSF treatment is associated with a marked loss of osteoblasts in the bone marrow, thereby potentially disrupting the osteoblast stem cell niche (Semerad, Blood 2005). Of note, patients with SCN chronically treated with G-CSF are prone to develop osteopenia, suggesting that osteoblast suppression by G-CSF also may occur in humans. We first asked whether the d715 G-CSFR was able to mediate this response. Wild-type or d715 G-CSFR were treated with G-CSF for 1–7 days and osteoblast activity in the bone marrow measured by expression of CXCL12 and osteocalcin. Consistent with previous reports, a decrease in osteocalcin and CXCL12 was not apparent until after 3 days of G-CSF treatment and reached a maximum after 7 days. Surprisingly, the magnitude of osteoblast suppression was greater in d715 G-CSFR compared with wild-type mice. The fold-decrease in osteocalcin mRNA from baseline in wild-type mice was 147 ± 70.1 versus 1,513 ± 1091 in d715 G-CSFR mice (p < 0.001). Likewise, a greater fold-decrease in CXCL12 mRNA was observed. We next assessed oxidative stress in c-KIT+ Sca+ lineage− (KSL) progenitors after G-CSF treatment. In both wild-type and d715 G-CSFR KSL cells no increase in reactive oxygen species (ROS) was observed at baseline or 12 hours after a single dose of G-CSF. However, after 7 days of G-CSF, a significant increase (3.4 ± 0.1 fold; p = 0.009) in ROS was observed in d715 G-CSFR but not wild-type KSL cells. To determine whether oxidative stress contributed to DNA damage, histone H2AX phosphorylation (pH2AX) was measured by flow cytometry. No increase in pH2AX was observed after short-term (less than 24 hour) G-CSF treatment. However, a modest but significant (1.9 ± 0.1 fold; p = 0.0007) increase in pH2AX was observed in d715 G-CSFR but not wild-type KSL cells after 7 days of G-CSF. To determine whether increased oxidative stress was casually linked to DNA damage, we co-administered the antioxidant N-acetyl cysteine (NAC) during G-CSF treatment. As expected, induction of ROS in KSL cells was markedly suppressed by NAC administration. Importantly, the increase in pH2AX levels in d715 G-CSFR KSL cells induced by G-CSF was completely blocked by NAC administration. Finally, to determine whether alterations in the bone marrow microenvironment, specifically decreased CXCL12 expression, contributed to DNA damage, we treated mice with AMD3100, a specific antagonist of CXCR4 (the major receptor for CXCL12). Treatment of wild-type or d715 G-CSFR mice with a single dose of G-CSF (3 hour time point) or with AMD3100 alone did not induce H2AXp. However, co-administration of AMD3100 with a single dose of G-CSF induced modest but significant H2AXp in d715 G-CSFR KSL cells (5.74 ± 1.06 fold; P<0.001). Collectively, these data suggest a model in which alterations in the bone marrow microenvironment induced by G-CSF may contribute to genetic instability in HSPCs and ultimately leukemic transformation. The mutant CSF3R may contribute to leukemogenesis through both increased ROS production in HSPCs and increased suppression of osteoblasts. Disclosures: No relevant conflicts of interest to declare.

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Facultative Sterol Uptake in an Ergosterol-Deficient Clinical Isolate of Candida glabrata Harboring a Missense Mutation inERG11and Exhibiting Cross-Resistance to Azoles and Amphotericin B

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.06253-11 ◽

2012 ◽

Vol 56 (8) ◽

pp. 4223-4232 ◽

Cited By ~ 56

Author(s):

Claire M. Hull ◽

Josie E. Parker ◽

Oliver Bader ◽

Michael Weig ◽

Uwe Gross ◽

...

Keyword(s):

Amphotericin B ◽

Clinical Isolate ◽

Candida Glabrata ◽

Sterol Composition ◽

Single Amino Acid ◽

Gas Chromatography Mass Spectrometry ◽

Cross Resistance ◽

Wild Type ◽

Content Type ◽

Sterol Uptake

ABSTRACTWe identified a clinical isolate ofCandida glabrata(CG156) exhibiting flocculent growth and cross-resistance to fluconazole (FLC), voriconazole (VRC), and amphotericin B (AMB), with MICs of >256, >256, and 32 μg ml−1, respectively. Sterol analysis using gas chromatography-mass spectrometry (GC-MS) revealed that CG156 was a sterol 14α-demethylase (Erg11p) mutant, wherein 14α-methylated intermediates (lanosterol was >80% of the total) were the only detectable sterols.ERG11sequencing indicated that CG156 harbored a single-amino-acid substitution (G315D) which nullified the function of native Erg11p. In heterologous expression studies using a doxycycline-regulatableSaccharomyces cerevisiae erg11strain, wild-typeC. glabrataErg11p fully complemented the function ofS. cerevisiaesterol 14α-demethylase, restoring growth and ergosterol synthesis in recombinant yeast; mutated CG156 Erg11p did not. CG156 was culturable using sterol-free, glucose-containing yeast minimal medium (glcYM). However, when grown on sterol-supplementedglcYM (with ergosta 7,22-dienol, ergosterol, cholestanol, cholesterol, Δ7-cholestenol, or desmosterol), CG156 cultures exhibited shorter lag phases, reached higher cell densities, and showed alterations in cellular sterol composition. Unlike comparator isolates (harboring wild-typeERG11) that became less sensitive to FLC and VRC when cultured on sterol-supplementedglcYM, facultative sterol uptake by CG156 did not affect its azole-resistant phenotype. Conversely, CG156 grown usingglcYM with ergosterol (or with ergosta 7,22-dienol) showed increased sensitivity to AMB; CG156 grown usingglcYM with cholesterol (or with cholestanol) became more resistant (MICs of 2 and >64 μg AMB ml−1, respectively). Our results provide insights into the consequences of sterol uptake and metabolism on growth and antifungal resistance inC. glabrata.

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Zap1 Control of Cell-Cell Signaling in Candida albicans Biofilms

Eukaryotic Cell ◽

10.1128/ec.05196-11 ◽

2011 ◽

Vol 10 (11) ◽

pp. 1448-1454 ◽

Cited By ~ 42

Author(s):

Shantanu Ganguly ◽

Andrew C. Bishop ◽

Wenjie Xu ◽

Suman Ghosh ◽

Kenneth W. Nickerson ◽

...

Keyword(s):

Candida Albicans ◽

Yeast Cells ◽

Gas Chromatography Mass Spectrometry ◽

Wild Type ◽

Content Type ◽

Reverse Transcription Pcr ◽

Hypha Formation ◽

Dependent Signal ◽

Reporter Strains ◽

Biosensor Strain

ABSTRACTBiofilms ofCandida albicansinclude both yeast cells and hyphae. Prior studies indicated that azap1Δ/Δ mutant, defective in zinc regulator Zap1, has increased accumulation of yeast cells in biofilms. This altered yeast-hypha balance may arise from internal regulatory alterations or from an effect on the production of diffusible quorum-sensing (QS) molecules. Here, we develop biosensor reporter strains that express yeast-specificYWP1-RFPor hypha-specificHWP1-RFP, along with a constitutiveTDH3-GFPnormalization standard. Seeding these biosensor strains into biofilms allows a biological activity assay of the surrounding biofilm milieu. Azap1Δ/Δ biofilm induces the yeast-specificYWP1-RFPreporter in a wild-type biosensor strain, as determined by both quantitative reverse transcription-PCR (qRT-PCR) gene expression measurements and confocal microscopy. Remediation of thezap1Δ/Δ zinc uptake defect through zinc transporter geneZRT2overexpression reverses induction of the yeast-specificYWP1-RFPreporter. Gas chromatography-mass spectrometry (GC-MS) measurements of known organic QS molecules show that thezap1Δ/Δ mutant accumulates significantly less farnesol than wild-type or complemented strains and thatZRT2overexpression does not affect farnesol accumulation. Farnesol is a well-characterized inhibitor of hypha formation; hence, a reduction in farnesol levels inzap1Δ/Δ biofilms is unexpected. Our findings argue that a Zap1- and zinc-dependent signal affects the yeast-hypha balance and that it is operative in the low-farnesol environment of thezap1Δ/Δ biofilm. In addition, our results indicate that Zap1 is a positive regulator of farnesol accumulation.

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Social Psychobiologic Dysfunction Associated with Anabolic Steroid Abuse: A Review

The Sport Psychologist ◽

10.1123/tsp.4.3.275 ◽

1990 ◽

Vol 4 (3) ◽

pp. 275-284 ◽

Cited By ~ 4

Author(s):

Edward Gregg ◽

W. Jack Rejeski

Keyword(s):

Nonhuman Primate ◽

Social Withdrawal ◽

Primate Research ◽

Primate Model ◽

Psychological States ◽

Steroid Abuse ◽

Overt Behavior ◽

Descriptive Research ◽

The Social ◽

Androgenic Steroids

This article reviews both human and nonhuman primate research dealing with the social psychobiologic effects of anabolic/androgenic steroids (AS). Descriptive research and anecdotal reports within the realm of sport suggest that AS may have a variety of psychological and behavioral effects including psychotic episodes and increased aggression. Recent investigations with a nonhuman primate model confirm that the effects of AS on psychological states and overt behavior can be quite varied, ranging from those that can be characterized as active (e.g., mania and aggression) to more passive states (e.g., depression and social withdrawal). There are also profound physiological effects of a biobehavioral origin that constitute a risk for cardiovascular disease. The most striking aspect of AS is that the effects of this drug are due to an interaction between its pharmacologic properties and the social milieu.

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