Choleratoxin ADP-ribosylates transducin only when it is bound to photoexcited rhodopsin and depleted of its nucleotide

AbstractThe sensitivity of transducin (T) to choleratoxin (CT) in retinal cells depends on illumination and on the presence of GTP or analogs. Low concentrations of GPP-NH-P or GPP-CH2-P increase ADP-ribosylation while GTPγS inhibits it. We show that GTP analogs permanently activate an ADP-ribosylating factor (ARF) which mediates CT action on retinal cell membranes: when transducin-depleted membranes were pre-activated by GTP analogs, re-added transducin became sensitive to CT in the absence of nucleotide, and presence of photoexcited rhodopsin (R*). Any subsequent G-nucleotide addition (even GDP) decreased ADP-ribosylation. Thus nucleotide-free transducin molecule in R*—Tempty complex is the CT substrate

Etienne Verrier, ingénieur du roi en Nouvelle-France : contraintes et gestion du chantier de Louisbourg (1724-1745)

Les hommes de la famille Veyrier ont bien souvent eu un destin extraordinaire. Fils du sculpteur tretsois Christophe Veyrier, élève du grand Puget, Etienne ne déroge pas à la règle. Né à Aix-en-Provence en 1683, il succombe très tôt à l’appel de la mer. A La Rochelle, il va apprendre l’ingénierie militaire et l’art des fortifications à la manière de Vauban. Après avoir navigué sur les mers de Chine, c’est en Nouvelle-France, dans les lointaines colonies d’Amérique, à Louisbourg, qu’il laissera sa marque dans l’Histoire.The male members of the Veyrier family have had an extraordinary destiny. The son of Christophe Veyrier, a famous sculptor from Trets and a student of the great Puget, Etienne followed the same path. Born in Aix-en-Provence in 1683, the young Veryrier succumbed very early to the call of the sea. In La Rochelle, he studied military engineering and the new art of fortification as practised by Monsieur de Vauban. After first sailing across the Chinese seas, it is in New France, particularly in Louisbourg, that he left his mark in history

Incorporation of cobalt into ZnO nanoclusters

The structural, optical and magnetic properties of nanostructured ZnO films co-doped with cobalt and aluminium have been studied. The nanocrystalline films, with cluster sizes in range 50 - 100 nm, were deposited by pulsed laser ablation in a mixed atmosphere of oxygen and helium. The nanocrystallites have the wurtzite structure and are highly oriented with the c-axis perpendicular to the substrate. Both optical and electron spin resonance (ESR) spectroscopy results show the substitutional incorporation of Co$^{2+}$ ions on the Zn site inside the ZnO nanoclusters. The temperature dependence of the ESR spectra follows Curie law corresponding to a paramagnetic material

An X-ray diffraction study on a single rod outer segment from frog retina

X-ray diffraction was recorded from retinal rod outer segments of frog using a microbeam

Prognostic Impact of Paraneoplastic Cushing’s Syndrome in Small-Cell Lung Cancer

Introduction:Paraneoplastic Cushing’s syndrome (CushingPS) in small-cell lung cancer is rare but severe.Methods:We studied 383 patients with small-cell lung cancer diagnosed between 1998 and 2012. Among them, 23 patients had CushingPS, 56 had other paraneoplastic syndrome (OtherPS), and 304 had no paraneoplastic syndrome (NoPS).Results:After comparison of the three groups, we observed that CushingPS patients had more extensive disease: 82.6% versus 67.8% versus 53.3% (p = 0.005), respectively, with more than two metastatic sites: 63.2% versus 15.8% and 24.1% (p ⩽ 0.001), a higher World Health Organization performance status (2–4): 73.9% versus 57.1% versus 43.7% (p = 0.006), greater weight loss (≥10%): 47.8% versus 33.9% versus 16.4% (p ⩽ 0.001), reduced objective response to first-line treatment: 47.6% versus 74.1% versus 71.1% (p = 0.04), and poorer sensitivity to first-line treatment: 19% versus 38.9% versus 48.6% (p = 0.01). NoPS patients, with World Health Organization performance status of 3–4, had extensive disease at diagnosis, with response, sensitivity to first-line treatment, and survival similar to the CushingPS group. At relapse, the CushingPS group had no objective response to second-line treatment versus 25% versus 42.8% in OtherPS and NoPS groups, respectively (p = 0.005). The median survival of CushingPS patients was 6.6 months versus 9.2 months for OtherPS and 13.1 months for NoPS patients (p ⩽ 0.001). CushingPS is a prognostic factor of death (hazard ratio, 2.31; p ⩽ 0.001).Conclusion:CushingPS is the worst form of the paraneoplastic syndromes with particularly extensive tumors. Reduced objective response and sensitivity to first-line treatment and no response to second-line treatment suggest starting palliative care early at first line and exclusively at relapse

Dendritic glycopolymers based on dendritic polyamine scaffolds: view on their synthetic approaches, characteristics and potential for biomedical applications

In this review we highlight the potential for biomedical applications of dendritic glycopolymers based on polyamine scaffolds. The complex interplay of the molecular characteristics of the dendritic architectures and their specific interactions with various (bio)molecules are elucidated with various examples. A special role of the individual sugar units attached to the dendritic scaffolds and their density is identified, which govern ionic and H-bond interactions, and biological targeting, but to a large extent are also responsible for the significantly reduced toxicity of the dendritic glycopolymers compared to their polyamine scaffolds. Thus, the application of dendritic glycopolymers in drug delivery systems for gene transfection but also as therapeutics in neurodegenerative diseases has great promisePublikacja w ramach programu Royal Society of Chemistry "Gold for Gold" 2014 finansowanego przez Uniwersytet Łódzk

Is basal ultrasensitive measurement of calcitonin capable of substituting for the pentagastrin-stimulation test?

OBJECTIVE: To evaluate a second-generation assay for basal serum calcitonin (CT) measurements compared with the pentagastrin-stimulation test for the diagnosis of inherited medullary thyroid carcinoma (MTC) and the follow-up of patients with MTC after surgery. Recent American Thyroid Association recommendations suggest the use of basal CT alone to diagnose and assess follow-up of MTC as the pentagastrin (Pg) test is unavailable in many countries. DESIGN: Multicentric prospective study. PATIENTS: A total of 162 patients with basal CT <10 ng/l were included: 54 asymptomatic patients harboured noncysteine \u27rearranged during transfection\u27 (RET) proto-oncogene mutations and 108 patients had entered follow-up of MTC after surgery. MEASUREMENT: All patients underwent basal and Pg-stimulated CT measurements using a second-generation assay with 5-ng/l functional sensitivity. RESULTS: Ninety-five per cent of patients with basal CT ≥ 5 ng/l and 25% of patients with basal CT <5 ng/l had a positive Pg-stimulation test (Pg CT >10 ng/l). Compared with the reference Pg test, basal CT ≥ 5 ng/l had 99% specificity, a 95%-positive predictive value but only 35% sensitivity (P < 0.0001). Overall, there were 31% less false-negative results using a 5-ng/l threshold for basal CT instead of the previously used 10-ng/l threshold. CONCLUSION: The ultrasensitive CT assay reduces the false-negative rate of basal CT measurements when diagnosing familial MTC and in postoperative follow-up compared with previously used assays. However, its sensitivity to detect C-cell disease remains lower than that of the Pg-stimulation test