Live Imaging at the Onset of Cortical Neurogenesis Reveals Differential Appearance of the Neuronal Phenotype in Apical versus Basal Progenitor Progeny

The neurons of the mammalian brain are generated by progenitors dividing either at the apical surface of the ventricular zone (neuroepithelial and radial glial cells, collectively referred to as apical progenitors) or at its basal side (basal progenitors, also called intermediate progenitors). For apical progenitors, the orientation of the cleavage plane relative to their apical-basal axis is thought to be of critical importance for the fate of the daughter cells. For basal progenitors, the relationship between cell polarity, cleavage plane orientation and the fate of daughter cells is unknown. Here, we have investigated these issues at the very onset of cortical neurogenesis. To directly observe the generation of neurons from apical and basal progenitors, we established a novel transgenic mouse line in which membrane GFP is expressed from the beta-III-tubulin promoter, an early pan-neuronal marker, and crossed this line with a previously described knock-in line in which nuclear GFP is expressed from the Tis21 promoter, a pan-neurogenic progenitor marker. Mitotic Tis21-positive basal progenitors nearly always divided symmetrically, generating two neurons, but, in contrast to symmetrically dividing apical progenitors, lacked apical-basal polarity and showed a nearly randomized cleavage plane orientation. Moreover, the appearance of beta-III-tubulin–driven GFP fluorescence in basal progenitor-derived neurons, in contrast to that in apical progenitor-derived neurons, was so rapid that it suggested the initiation of the neuronal phenotype already in the progenitor. Our observations imply that (i) the loss of apical-basal polarity restricts neuronal progenitors to the symmetric mode of cell division, and that (ii) basal progenitors initiate the expression of neuronal phenotype already before mitosis, in contrast to apical progenitors

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Ion distribution in concrete overlay, mapped by laser induced breakdown spectroscopy (LIBS), modified by an embedded zinc anode

Galvanic corrosion protection by embedded zinc anodes is an accepted technique for the corrosion protection of reinforcing steel in concrete. Galvanic currents flow between the zinc anode and the steel reinforcement due to the potential difference that is in the range of a few hundred mV. The ion distribution was studied on two steel reinforced concrete specimens admixed with 3 wt.% chloride/wt. cement and galvanically protected by a surface applied EZ-anode. On both specimens, a zinc anode was embedded and glued to the concrete surface by a geo-polymer-based chloride-free binder. At one specimen, the EZ-anode was operated for 2,5 years, the EZ-anode at the other specimen was not electrically connected to the reinforcement, this specimen serves as a reference. Both specimens have been stored under identical conditions. The ion distribution between the anode (EZ-ANODE) and cathode (steel reinforcement) was studied by laser-induced breakdown spectroscopy (LIBS) after 7 months, 12 months, and 2,5 years. Results of the LIBS studies on the specimen with activated EZ-anode after 7 months, 12 months, and 2,5 years and of the reference specimen after 2,5 years are reported. Results show that diffusion of ions contributes to the changes in the ion distribution but migration, especially of chlorides towards the EZ-anode is significant despite the weak electric field – several hundred millivolts generated by the galvanic current. Results show that chloride ions accumulate near the zinc-anode as in water-insoluble zinc-hydroxy chlorides Simonkolleit

Galvanic chloride extraction by an embedded zinc anode: Ion distribution mapped by laser induced breakdown spectroscopy (LIBS)

An important aspect with regard to the service life of zinc based galvanic anodes and the durability of the corrosion protection of steel in concrete is the “galvanic chloride extraction”. Chloride ions move in the electric field generated by the current, flowing between the galvanic anode and the cathodic steel. Migration leads to an accumulation of anions, e.g. chloride ions, at the anode and depletion of chlorides near the steel rebar surface. The ion migration was studied on steel reinforced concrete specimens admixed with 3 wt.% chloride/wt. cement and galvanically protected by a surface applied embedded zinc anode (EZA). The zinc anode was embedded and glued to the concrete surface by a geo-polymer based chloride free binder. The EZA was operated over a period of 1 year and the ion distribution between anode (EZA) and cathode (steel reinforcement) was studied by laser induced breakdown spectroscopy (LIBS) after 5 months, 7 months and 12 months. The results show that chloride ions efficiently migrate in the direction of the zinc-anode and accumulate there. Chloride distribution in the EZA correlates with the distribution of zinc ions generated by the anodic dissolution of the zinc anode in the binder matrix. The microstructure of the binder matrix and its interface to the zinc-anode are studied by REM/EDX – preliminary results will be reported

The role of α-E-catenin in cerebral cortex development: Radial glia specific effect on neuronal migration.

During brain development, radial glial cells possess an apico-basal polarity and are coupled by adherens junctions (AJs) to an F-actin belt. To elucidate the role of the actin, we conditionally deleted the key component α-E-catenin in the developing cerebral cortex. Deletion at early stages resulted in severe disruption of tissue polarity due to uncoupling of AJs with the intracellular actin fibers leading to the formation of subcortical band heterotopia. Interestingly, this phenotype closely resembled the phenotype obtained by conditional RhoA deletion, both in regard to the macroscopic subcortical band heterotopia and the subcellular increase in G-actin/F-actin ratio. These data therefore together corroborate the role of the actin cytoskeleton and its anchoring to the AJs for neuronal migration disorders