978 research outputs found
Pathophysiology of primary aldosteronism: adrenal immunohistochemistry and molecular profiling studies
Angiotensin II Type 1 Receptor Autoantibodies in Primary Aldosteronism
Primary aldosteronism (PA) is the most common form of endocrine hypertension. Agonistic autoantibodies against the angiotensin II type 1 receptor (AT1R-Abs) have been described in transplantation medicine and women with pre-eclampsia and more recently in patients with PA. Any functional role of AT1R-Abs in either of the two main subtypes of PA (aldosterone-producing adenoma or bilateral adrenal hyperplasia) requires clarification. In this review, we discuss the studies performed to date on AT1R-Abs in PA
Angiotensin II Type 1 Receptor Autoantibodies in Primary Aldosteronism
Primary aldosteronism (PA) is the most common form of endocrine hypertension. Agonistic autoantibodies against the angiotensin II type 1 receptor (AT(1)R-Abs) have been described in transplantation medicine and women with pre-eclampsia and more recently in patients with PA. Any functional role of AT(1)R-Abs in either of the two main subtypes of PA (aldosterone-producing adenoma or bilateral adrenal hyperplasia) requires clarification. In this review, we discuss the studies performed to date on AT(1)R-Abs in PA
Making the Most of Qualitative Evidence for Energy Poverty Mitigation:A Research Agenda and Call for Action
Female melon fruit flies, Zeugodacus cucurbitae, are attracted to a synthetic chemical blend based on male epicuticular components
The melon fly, Zeugodacus cucurbitae (Coquillett) (Diptera: Tephritidae), is considered to be the most destructive pest of melons and other related cucurbit crops worldwide. Despite the potential of behaviour-based control strategies, little is known about the mechanisms involved in female mate choice. Herein, we investigated the production and chemoreception of cuticular hydrocarbons in both sexes of Z. cucurbitae, and the behavioural responses they induce. We studied the epicuticular composition of virgin males and females, using two-dimensional gas chromatography coupled with mass spectrometric detection. Data were interpreted using multivariate factorial analysis. The differentiation of chemical profiles was consistently observed over time. In young individuals, the chemical profiles did not differ between sexes, while sex-specific differences were noted in mature flies. The fly olfactory sensitivity to these compounds was explored using gas chromatography combined with chopped triple electroantennography and electropalpography detectors. This extensive exploration of the pest olfactory sensitivity highlighted three compounds produced by the male. When blended, they induced a robust positive response in unmated naive females in a six-choice olfactometer. The responsiveness of other Tephritidae species (a polyphagous species Bactrocera dorsalis (Hendel) and the cucurbit specialist Dacus demmerezi (Bezzi)) to whole body extracts of Z. cucurbitae was also investigated. Our findings showed that Z. cucurbitae uses species-specific olfactory receptors to detect male produced compounds. In addition, the palps were sensitive to a female-specific component, 1,7-dioxaspiro[5.5]undecane, which the males produce in minute quantities. Overall, this study provides a starting point for a pheromone-based tephritid lure that targets unmated females. The potential implications for pest management are discussed
Primary Aldosteronism: KCNJ5 Mutations and Adrenocortical Cell Growth
Aldosterone-producing adenomas with somatic mutations in the KCNJ5 G-protein-coupled inwardly rectifying potassium channel are a cause of primary aldosteronism. These mutations drive aldosterone excess, but their role in cell growth is undefined. Our objective was to determine the role of KCNJ5 mutations in adrenal cell proliferation and apoptosis. The Ki67 proliferative index was positively correlated with adenoma diameter in aldosterone-producing adenomas with a KCNJ5 mutation (r=0.435, P=0.007), a negative correlation was noted in adenomas with no mutation detected (r=-0.548, P=0.023). Human adrenocortical cell lines were established with stable expression of cumate-inducible wild-type or mutated KCNJ5. Increased cell proliferation was induced by low-level induction of KCNJ5-T158A expression compared with control cells (P=0.009), but increased induction ablated this difference. KCNJ5-G151R displayed no apparent proliferative effect, but KCNJ5-G151E and L168R mutations each resulted in decreased cell proliferation (difference P<0.0001 from control cells, both comparisons). Under conditions tested, T158A had no effect on apoptosis, but apoptosis increased with expression of G151R (P<0.0001), G151E (P=0.008), and L168R (P<0.0001). We generated a specific KCNJ5 monoclonal antibody which was used in immunohistochemistry to demonstrate strong KCNJ5 expression in adenomas without a KCNJ5 mutation and in the zona glomerulosa adjacent to adenomas irrespective of genotype as well as in aldosterone-producing cell clusters. Double immunofluorescence staining for KCNJ5 and CYP11B2 (aldosterone synthase) showed markedly decreased KCNJ5 immunostaining in CYP11B2-positive cells compared with CYP11B2-negative cells in aldosterone-producing adenomas with a KCNJ5 mutation. Together, these findings support the concept that cell growth effects of KCNJ5 mutations are determined by the expression level of the mutated channel
Selective crystallization of indigo B by a modified sublimation method and its redetermined structure
Good-quality single crystals of the title compound, indigo B [systematic name: 2-(3-oxoindolin-2-ylÂidene)indolin-3-one], C16H10N2O2, have been prepared with high selectivity by a sublimation process. The previous structure of indigo B [SĂŒsse & Wolf (1980 â¶). Naturwissenschaften, 67, 453], which showed that the complete molÂecule is generated by crystallographic inversion symmetry has been confirmed, but the present study reports more realistic geometrical parameters and modern standards of precision (e.g. Ï for CâC bonds = 0.002â0.003â
Ă
). Each molÂecule features two intraÂmolecular NâHâŻO hydrogen bonds. In the crystal, molÂecules are linked by strong face-to-face ÏâÏ stacking interÂactions involving both the six- and five-membered rings [centroidâcentroid separations = 3.6290â
(14) and 3.6506â
(14)â
Ă
] and interÂmolecular NâHâŻO hydrogen bonds
Single-Center Prospective Cohort Study on the Histopathology, Genotype, and Postsurgical Outcomes of Patients With Primary Aldosteronism
Unilateral forms of primary aldosteronism are usually surgically treated to remove the source of aldosterone excess. After adrenalectomy, aldosteronism persists in some patients indicating abnormal aldosterone production from the unresected gland. Our objective was to investigate histopathology, genotype, and postsurgical outcomes in a 3-year prospective cohort of surgically treated patients for primary aldosteronism (from 2016 to 2018). The cohort comprised 60 consecutively operated patients categorized with classical or nonclassical histopathologic findings of unilateral primary aldosteronism. In the classical group were 45 solitary aldosterone-producing adenomas or dominant aldosterone-producing nodules; in the nonclassical group were 15 cases of multiple aldosterone-producing micronodules or nodules (12 cases) or aldosterone-producing diffuse hyperplasia (3 cases). The classical group displayed higher baseline plasma aldosterone concentrations (262 versus 155 pg/mL, P=0.008) and an increased aldosterone-to-renin ratio (81 versus 42, P=0.002). A high proportion of the classical group achieved complete biochemical success (97.6% versus 66.7% in the nonclassical group, P=0.002). The nonclassical versus classical group displayed an increased ratio of absolute aldosterone concentration in the contralateral adrenal vein to peripheral vein at adrenal venous sampling (3.8 versus 2.0, P=0.004). Variants in aldosterone-driver genes were identified in 85% of 41 aldosterone-producing adenomas and were excluded in the remaining 15% by CYP11B2 guided next-generation sequencing. There were no differences in clinical or biochemical outcomes in patients with a solitary aldosterone-producing adenoma categorized by KCNJ5 mutation status. In conclusion, adrenals with a nonclassical histopathology of unilateral primary aldosteronism are associated with a higher incidence of postsurgical disease persistence and increased aldosterone production from the unresected adrenal
Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity
Currently available COVID-19 vaccines include inactivated virus, live attenuated virus, mRNA-based, viral vectored and adjuvanted protein-subunit-based vaccines. All of them contain the spike glycoprotein as the main immunogen and result in reduced disease severity upon SARS-CoV-2 infection. While we and others have shown that mRNA-based vaccination reactivates pre-existing, cross-reactive immunity, the effect of vector vaccines in this regard is unknown. Here, we studied cellular and humoral responses in heterologous adenovirus-vector-based ChAdOx1 nCOV-19 (AZ; Vaxzeria, AstraZeneca) and mRNA-based BNT162b2 (BNT; Comirnaty, BioNTech/Pfizer) vaccination and compared it to a homologous BNT vaccination regimen. AZ primary vaccination did not lead to measurable reactivation of cross-reactive cellular and humoral immunity compared to BNT primary vaccination. Moreover, humoral immunity induced by primary vaccination with AZ displayed differences in linear spike peptide epitope coverage and a lack of anti-S2 IgG antibodies. Contrary to primary AZ vaccination, secondary vaccination with BNT reactivated pre-existing, cross-reactive immunity, comparable to homologous primary and secondary mRNA vaccination. While induced anti-S1 IgG antibody titers were higher after heterologous vaccination, induced CD4(+) T cell responses were highest in homologous vaccinated. However, the overall TCR repertoire breadth was comparable between heterologous AZ-BNT-vaccinated and homologous BNT-BNT-vaccinated individuals, matching TCR repertoire breadths after SARS-CoV-2 infection, too. The reasons why AZ and BNT primary vaccination elicits different immune response patterns to essentially the same antigen, and the associated benefits and risks, need further investigation to inform vaccine and vaccination schedule development
Tracking des transferts des bactéries porteuses de résistances entre animal, homme et environnement
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