Debio-0932, a second generation oral Hsp90 inhibitor,induces apoptosis in MCF-7 and MDA-MB-231 cell lines

Molecular Biology Reports - Heat shock protein 90 (Hsp90) is a key chaperone that is abnormally expressed in cancer cells, and therefore, designing novel compounds to inhibit chaperone activities...     

Taxonomic study of spongy spumellarian Radiolaria with three and four coplanar spines or arms from the middle Carnian (Late Triassic) of the Köseyahya nappe (Elbistan, SE Turkey) and other Triassic localities

The present article is a taxonomic study of all spongy spumellarian radiolarian taxa with three and four coplanar spines or spongy arms occurring in the middle Carnian from the Köseyahya section, near the town of Elbistan, SE Turkey. This fauna is characteristic of the Tetraporobrachia haeckeli radiolarian Zone, and comes from an 8 m thick succession of clayey-cherty limestones occurring at the lower part of the section. In addition, a few species from the Middle and Upper Triassic from other areas have been also included in this study to improve some generic diagnoses, and to better comprehend the diversity and evolutionary trends of some genera, subfamilies and families. The taxonomy at the generic and suprageneric levels is based primarily on the types of microsphere. This new approach allowed new taxonomic arrangements of genera and suprageneric units, and suggested new phylogenetic relationships among these radiolarians and between them and younger radiolarians. The authors discuss and describe 69 species, of which 37 are new, and 14 genera, of which three are new (Paraparonaella, Pseudangulobracchia, and Ropanaella). The genus Triassoastrum and others are reinterpreted. All genera studied are assigned to five subfamilies, of which two are new (Tetrapaurinellinae and Triassocrucellinae), and two families (Tritrabidae and Veghicycliidae). Nine species in open nomenclature are also illustrated.     

Determining immunoassay cutoff value using Western blot results to predict hepatitis C infection in blood donors with low-titer anti-HCV reactivity

Since the 1990s, blood donors have been scanned for anti-hepatitis C virus (anti-HCV) antibodies, which can be defined by enzyme immunoassay as a screening test. In this population, false-reactive ratios have been high. Recently, some authors have aimed to find a cutoff value for anti-HCV different from those established by test manufacturers to predict HCV infection. In this study, 321 patients, after two repeating tests, had reactive results in s/co <10 titers on anti-HCV test. The patients were 29.6 % (n?=?95) in women and 70.4 % (n?=?226) in men. The patients were classified into three groups by Western blot (WB) results (PS, positive; NG, negative; and ID, indeterminate). The average anti-HCV titer of the whole group was 2.61?±?1.96. Anti-HCV titers of subgroups were 2.43?±?1.95 in NG, 4.93?±?2.53 in PS, and 2.50?±?1.65 in ID (p?<?0.001). There was a significant difference between NG and PS and between PS and ID subgroups (p?<?0.001). There was a positive correlation between WB and anti-HCV titers in all patients (r?=?0.298, p?<?0.001), in women (r?=?0.282, p?<?0.001), and in men (r?=?0.337, p?=?0.002). According to receiver operator characteristic curve analysis, the cutoff value of anti-HCV titer to predict hepatitis C infection was >2.61 s/co, with 74.1 % sensitivity and 71.6 % specificity (area under the curve, 0.820; 95 % confidence interval, 0.753 to 0.887). We suggest that an effective cutoff value for anti-HCV other than that established by the manufacturer cannot be assigned to predict hepatitis C infection for blood donors in low-prevalence areas.     

Distinct intracellular signaling mediates C‐MET regulation of dendritic growth and synaptogenesis

Hepatocyte growth factor (HGF) activation of the MET receptor tyrosine kinase influences multiple neurodevelopmental processes. Evidence from human imaging and mouse models shows that, in the forebrain, disruptions in MET signaling alter circuit formation and function. One likely means of modulation is by controlling neuron maturation. Here, we examined the signaling mechanisms through which MET exerts developmental effects in the neocortex. In situ hybridization revealed that hgf is located near MET‐expressing neurons, including deep neocortical layers and periventricular zones. Western blot analyses of neocortical crude membranes demonstrated that HGF‐induced MET autophosphorylation peaks during synaptogenesis, with a striking reduction in activation between P14 and P17 just before pruning. In vitro analysis of postnatal neocortical neurons assessed the roles of intracellular signaling following MET activation. There is rapid, HGF‐induced phosphorylation of MET, ERK1/2, and Akt that is accompanied by two major morphological changes: increases in total dendritic growth and synapse density. Selective inhibition of each signaling pathway altered only one of the two distinct events. MAPK/ERK pathway inhibition significantly reduced the HGF‐induced increase in dendritic length, but had no effect on synapse density. In contrast, inhibition of the PI3K/Akt pathway reduced HGF‐induced increases in synapse density, with no effect on dendritic length. The data reveal a key role for MET activation during the period of neocortical neuron growth and synaptogenesis, with distinct biological outcomes mediated via discrete MET‐linked intracellular signaling pathways in the same neurons. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1160–1181, 2016     

Simple and reliable detection of slime production of <Emphasis Type="Italic">Candida</Emphasis><Emphasis Type="Italic">spp</Emphasis>. directly from blood culture bottles: Comparison of visual tube method and transmission electron microscopy

Early detection of slime production may be useful for clinical decision because of its suggestive property for potential pathogenic capacity of a Candida strain especially in patients with a prosthetic device. In this study we aimed to compare the visual tube method (VTM) with transmission electron microscopy (TEM) in order to confirm the reliability of the former method. In order to demonstrate the reproducibility of the tube method and to determine the correct timing for the test, Candida isolates directly obtained from blood culture (DBC) bottles and their two subsequent subcultures were used. The results of this study showed that VTM is a simple and reliable method which can be used in every clinical mycology laboratory, provided that the test is applied on DBC isolates; as the ability of slime production is decreased or lost even after the first subculturing. We suggest that this simple method can be used and may have some contributions to the ongoing studies on the controversial issue concerning removal of biomaterials in candidemic patients.     

The presence of promatrix metalloproteinase-3 and its relation with different categories of coal workers' pneumoconiosis

Extracellular matrix formation (ECM) and remodeling are critical events related to the pathogenesis of pulmonary fibrosis. Matrix metalloproteinases play an essential role in degrading and remodeling the ECM. In this study, we tried to show the presence and correlation of promatrix metalloproteinase-3 (proMMP-3) (the inactive form of metalloproteinase-3) levels in coal workers' pneumoconiosis (CWP) with different categories. The study population consisted of 44 coal miners with CWP (pos CWP). Coal miners without CWP (neg CWP, n = 24) and non-underground personnel (controls, n = 17) were taken as controls. All coal miners were stable and had no systemic infection or disease. Standard posterio-anterior chest radiographs and pulmonary function tests were performed to exclude any diseases other than CWP. Serum proMMP-3 was analysed using the sandwich enzyme-linked immunosorbent assay according to the manufacturer's instructions (The Binding Site, Birmingham, UK). Mean proMMP-3 values of the all three groups were compared and a significant statistical difference obtained (p < 0.001). In addition, a statistically significant difference was found between categories of the disease and proMMP-3 values (p < 0.05). The effects of age, exposure duration and cigarette smoking on proMMP-3 values in coal miners with CWP were investigated. There were no correlations between age, smoking and proMMP-3 values. However, a positive correlation was found between exposure duration and proMMP-3 values (r = 0.447, p = 0.008). In conclusion, proMMP-3 (prostromelysin 1) may play an essential role in degrading and remodeling the ECM in workers with pneumoconiosis. ProMMP-3 may also reflect the stage of pneumoconiosis disease.     

Evidence that NOS2 acts as a trigger and mediator of late preconditioning induced by acute systemic hypoxia

Chronic systemic hypoxia (SH) enhances myocardial ischemic tolerance in mammals. We studied the delayed cardioprotection caused by acute SH and associated signaling mechanism. Conscious adult male mice were exposed to one or two cycles of hypoxia (H; 10% O(2)) or normoxia (21% O(2)) for various durations (30 min, 2 h, 4 h) followed by 24 h of reoxygenation. Hearts were isolated 24 h later and subjected to ischemia-reperfusion in a Langendorff model. Infarct size was reduced in mice pretreated with one (H4h) or two cycles (H4hx2) of 4 h SH compared with normoxia mice (P < 0.05), which was abolished by an inducible nitric oxide synthase (NOS2) inhibitor (S-methylisothiourea, 3 mg/kg) given before SH or ischemia. H4hx2 also failed to reduce infarct size in NOS2 knockout mice. Cyclooxygenase-2 (COX-2) inhibitor (NS-398, 10 mg/kg) did not block the protection given either before H4hx2 or ischemia. A two- to three fold increase in myocardial NOS2 expression was observed in H4h, H2hx2, and H4hx2 (P < 0.05), whereas endothelial NOS (NOS3) or COX-2 remained unchanged. We conclude that acute SH induces delayed cardioprotection, which is triggered and mediated by NOS2, but not by NOS3 or COX-2.