Kinin-B2 Receptor Activity Determines the Differentiation Fate of Neural Stem Cells

Bradykinin is not only important for inflammation and blood pressure regulation, but also involved in neuromodulation and neuroprotection. Here we describe novel functions for bradykinin and the kinin-B2 receptor (B2BkR) in differentiation of neural stem cells. In the presence of the B2BkR antagonist HOE-140 during rat neurosphere differentiation, neuron-specific beta 3-tubulin and enolase expression was reduced together with an increase in glial protein expression, indicating that bradykinin- induced receptor activity contributes to neurogenesis. In agreement, HOE-140 affected in the same way expression levels of neural markers during neural differentiation of murine P19 and human iPS cells. Kinin-B1 receptor agonists and antagonists did not affect expression levels of neural markers, suggesting that bradykinin-mediated effects are exclusively mediated via B2BkR. Neurogenesis was augmented by bradykinin in the middle and late stages of the differentiation process. Chronic treatment with HOE-140 diminished eNOS and nNOS as well as M1-M4 muscarinic receptor expression and also affected purinergic receptor expression and activity. Neurogenesis, gliogenesis, and neural migration were altered during differentiation of neurospheres isolated from B2BkR knock-out mice. Whole mount in situ hybridization revealed the presence of B2BkR mRNA throughout the nervous system in mouse embryos, and less beta 3-tubulin and more glial proteins were expressed in developing and adult B2BkR knock-out mice brains. As a underlying transcriptional mechanism for neural fate determination, HOE-140 induced up-regulation of Notch1 and Stat3 gene expression. Because pharmacological treatments did not affect cell viability and proliferation, we conclude that bradykinin-induced signaling provides a switch for neural fate determination and specification of neurotransmitter receptor expression.

A Simple Method to Evaluate, Correlate and Predict Boiling and Flash Points of Alkynes

Boiling points (T-B) of acyclic alkynes are predicted from their boiling point numbers (Y-BP) with the relationship T-B(K) = -16.802Y(BP)(2/3) + 337.377Y(BP)(1/3) - 437.883. In turn, Y-BP values are calculated from structure using the equation Y-BP = 1.726 + A(i) + 2.779C + 1.716M(3) + 1.564M + 4.204E(3) + 3.905E + 5.007P - 0.329D + 0.241G + 0.479V + 0.967T + 0.574S. Here A(i) depends on the substitution pattern of the alkyne and the remainder of the equation is the same as that reported earlier for alkanes. For a data set consisting of 76 acyclic alkynes, the correlation of predicted and literature T-B values had an average absolute deviation of 1.46 K, and the R-2 of the correlation was 0.999. In addition, the calculated Y-BP values can be used to predict the flash points of alkynes.

Cause-specific mortality and income inequality in Sao Paulo, Brazil

OBJECTIVE: To analyze cause-specifi c mortality rates according to the relative income hypothesis. METHODS: All 96 administrative areas of the city of Sao Paulo, southeastern Brazil, were divided into two groups based on the Gini coefficient of income inequality: high (>= 0.25) and low (<0.25). The propensity score matching method was applied to control for confounders associated with socioeconomic differences among areas. RESULTS: The difference between high and low income inequality areas was statistically significant for homicide (8.57 per 10,000; 95% CI: 2.60; 14.53); ischemic heart disease (5.47 per 10,000 [95% CI 0.76; 10.17]); HIV/AIDS (3.58 per 10,000 [95% CI 0.58; 6.57]); and respiratory diseases (3.56 per 10,000 [95% CI 0.18; 6.94]). The ten most common causes of death accounted for 72.30% of the mortality difference. Infant mortality also had signifi cantly higher age-adjusted rates in high inequality areas (2.80 per 10,000 [95% CI 0.86; 4.74]), as well as among males (27.37 per 10,000 [95% CI 6.19; 48.55]) and females (15.07 per 10,000 [95% CI 3.65; 26.48]). CONCLUSIONS: The study results support the relative income hypothesis. After propensity score matching cause-specifi c mortality rates was higher in more unequal areas. Studies on income inequality in smaller areas should take proper accounting of heterogeneity of social and demographic characteristics.

Interactions between the NO-Citrulline Cycle and Brain-derived Neurotrophic Factor in Differentiation of Neural Stem Cells

The diffusible messenger NO plays multiple roles in neuroprotection, neurodegeneration, and brain plasticity. Argininosuccinate synthase (AS) is a ubiquitous enzyme in mammals and the key enzyme of the NO-citrulline cycle, because it provides the substrate L-arginine for subsequent NO synthesis by inducible, endothelial, and neuronal NO synthase (NOS). Here, we provide evidence for the participation of AS and of the NO-citrulline cycle in the progress of differentiation of neural stem cells (NSC) into neurons, astrocytes, and oligodendrocytes. AS expression and activity and neuronal NOS expression, as well as L-arginine and NOx production, increased along neural differentiation, whereas endothelial NOS expression was augmented in conditions of chronic NOS inhibition during differentiation, indicating that this NOS isoform is amenable to modulation by extracellular cues. AS and NOS inhibition caused a delay in the progress of neural differentiation, as suggested by the decreased percentage of terminally differentiated cells. On the other hand, BDNF reversed the delay of neural differentiation of NSC caused by inhibition of NOx production. Alikely cause is the lack of NO, which up-regulated p75 neurotrophin receptor expression, a receptor required for BDNF-induced differentiation of NSC. We conclude that the NO-citrulline cycle acts together with BDNF for maintaining the progress of neural differentiation.

In-beam spectroscopy of Rn-215(86)

The yrast level structure of Rn-215 has been studied by means of in-beam spectroscopy alpha-gamma-gamma coincidence techniques through the Pb-207(O-18,2 alpha 2n) reaction at 93 MeV bombarding energy, using the 8 pi GASP-ISIS spectrometer at Legnaro. New spectroscopic information has been obtained. The deduced low-lying level scheme of Rn-215 does not exhibit the alternating parity structure observed in the heavier known isotones Fr-216, Ra-217, Ac-218, and Th-219. From this result, the lightest nucleus showing evidence for octupole collectivity is Fr-216, defining the lowest-mass corner for this kind of phenomenon as N >= 129 and Z >= 87.

Propensity score matching approach to test the association of income inequality and mortality in Sao Paulo, Brazil

Background Support for the adverse effect of high income inequality on population health has come from studies that focus on larger areas, such as the US states, while studies at smaller geographical areas (eg, neighbourhoods) have found mixed results. Methods We used propensity score matching to examine the relationship between income inequality and mortality rates across 96 neighbourhoods (distritos) of the municipality of Sao Paulo, Brazil. Results Prior to matching, higher income inequality distritos (Gini >= 0.25) had slightly lower overall mortality rates (2.23 per 10 000, 95% CI -23.92 to 19.46) compared to lower income inequality areas (Gini <0.25). After propensity score matching, higher inequality was associated with a statistically significant higher mortality rate (41.58 per 10 000, 95% CI 8.85 to 73.3). Conclusion In Sao Paulo, the more egalitarian communities are among some of the poorest, with the worst health profiles. Propensity score matching was used to avoid inappropriate comparisons between the health status of unequal (but wealthy) neighbourhoods versus equal (but poor) neighbourhoods. Our methods suggest that, with proper accounting of heterogeneity between areas, income inequality is associated with worse population health in Sao Paulo.

Regional differences in clinical care among patients with type 1 diabetes in Brazil: Brazilian Type 1 Diabetes Study Group

Background To determine the characteristics of clinical care offered to type 1 diabetic patients across the four distinct regions of Brazil, with geographic and contrasting socioeconomic differences. Glycemic control, prevalence of cardiovascular risk factors, screening for chronic complications and the frequency that the recommended treatment goals were met using the American Diabetes Association guidelines were evaluated. Methods This was a cross-sectional, multicenter study conducted from December 2008 to December 2010 in 28 secondary and tertiary care public clinics in 20 Brazilian cities in north/northeast, mid-west, southeast and south regions. The data were obtained from 3,591 patients (56.0% females and 57.1% Caucasians) aged 21.2 ± 11.7 years with a disease duration of 9.6 ± 8.1 years (<1 to 50 years). Results Overall, 18.4% patients had HbA1c levels <7.0%, and 47.5% patients had HbA1c levels ≥ 9%. HbA1c levels were associated with lower economic status, female gender, age and the daily frequency of self-blood glucose monitoring (SBGM) but not with insulin regimen and geographic region. Hypertension was more frequent in the mid-west (32%) and north/northeast (25%) than in the southeast (19%) and south (17%) regions (p<0.001). More patients from the southeast region achieved LDL cholesterol goals and were treated with statins (p<0.001). Fewer patients from the north/northeast and mid-west regions were screened for retinopathy and nephropathy, compared with patients from the south and southeast. Patients from the south/southeast regions had more intensive insulin regimens than patients from the north/northeast and mid-west regions (p<0.001). The most common insulin therapy combination was intermediate-acting with regular human insulin, mainly in the north/northeast region (p<0.001). The combination of insulin glargine with lispro and glulisine was more frequently used in the mid-west region (p<0.001). Patients from the north/northeast region were younger, non-Caucasian, from lower economic status, used less continuous subcutaneous insulin infusion, performed less SBGM and were less overweight/obese (p<0.001). Conclusions A majority of patients, mainly in the north/northeast and mid-west regions, did not meet metabolic control goals and were not screened for diabetes-related chronic complications. These results should guide governmental health policy decisions, specific to each geographic region, to improve diabetes care and decrease the negative impact diabetes has on the public health system.

Cause-specific mortality and income inequality in São Paulo, Brazil

OBJECTIVE: To analyze cause-specific mortality rates according to the relative income hypothesis. METHODS: All 96 administrative areas of the city of São Paulo, southeastern Brazil, were divided into two groups based on the Gini coefficient of income inequality: high (>0.25) and low (<0.25). The propensity score matching method was applied to control for confounders associated with socioeconomic differences among areas. RESULTS: The difference between high and low income inequality areas was statistically significant for homicide (8.57 per 10,000; 95%CI: 2.60;14.53); ischemic heart disease (5.47 per 10,000 [95%CI 0.76;10.17]); HIV/AIDS (3.58 per 10,000 [95%CI 0.58;6.57]); and respiratory diseases (3.56 per 10,000 [95%CI 0.18;6.94]). The ten most common causes of death accounted for 72.30% of the mortality difference. Infant mortality also had significantly higher age-adjusted rates in high inequality areas (2.80 per 10,000 [95%CI 0.86;4.74]), as well as among males (27.37 per 10,000 [95%CI 6.19;48.55]) and females (15.07 per 10,000 [95%CI 3.65;26.48]). CONCLUSIONS: The study results support the relative income hypothesis. After propensity score matching cause-specific mortality rates was higher in more unequal areas. Studies on income inequality in smaller areas should take proper accounting of heterogeneity of social and demographic characteristics.

Neogene and Pleistocene fossil brachiopods of the Eastern Islands. Current appointments.

[EN] Numerous specimens of fossil brachiopods have been found in the different fossiliferous outcrops of the Canary Islands. These fossils have been found in the deposits of Mio-Pliocene age of the eastern Canary Islands, described and illustrated in the work of Meco et ali. 2005 and in the outcrops interpreted as a tsunami deposits  in Piedra Alta, Lanzarote, belonging to the Marine Isotope Stage 11 dated to circa 330 ka. 4 species of fossil brachiopods have been identificated: Terebratula sinuous Brocchi 1814, Lacazella mediterranea Risso 1826 Terebratulina caputserpentis (Zbyszewski, 1957) and Thecidium cf . digitatum (Sowerby 1823). These fossils provides stratigraphic and paleoclimatic taxonomic information. Furthermore, in order to compare the fossil brachiopods with present in the Canary Island, a reference collection is defined with specimens obtained from marine sediment surveys at Gran Canaria, La Palma and El Hierro, identifying 3 species: Argyrotheca barrettiatia (Davidson, 1866), Megerlia truncata (Linaeus 1767 ) and Pajaudina atlantica (Logan 1988).

Einfluß von Topologie und Verscherung auf Dynamik und mechanische Parameter bei Homopolymeren

Die FT-Rheologie wird zur Unterscheidung verschiedener Kamm-Topologien in Polystyrollösungen und –schmelzen angewendet. Die Polystyrole werden in Abhängigkeit der Deborahzahl De unter LAOS-Bedingungen vermessen. Die Meßergebnisse zeigen, daß der Schritt von wohldefinierten Systemen (lineare Ketten, Sterne) zu solchen mit statistischer Verteilung wie in Kämmen zu großen Veränderungen sowohl im linearen als auch im nichtlinearen Bereich der rheologischen Messungen führt. Sowohl die Masterkurven als auch die Intenstiäten I3/1 und Phasen Phi3 der Nichtlinearitäten der einzelnen Proben weisen jeweils deutliche Unterschiede untereinander auf. Diese sind durch die bisherigen Ergebnisse noch nicht vollständig mit topologischen Merkmalen in Verbindung zu bringen. Die Messungen wurden mit dem von McLeish eingeführten Pom-pom Modell und daraus weiterentwickelten double convected-Pom-pom Modell (DCPP) simuliert und lieferten gute Übereinstimmung sowie auch Vorhersagen über den experimentell nicht mehr zugänglichen Bereich. Zur Untersuchung des Einflusses von mechanischer Scherung auf die lokale, molekulare Dynamik wird das LAOS-Experiment in situ mit dielektrischer Spektroskopie kombiniert. Dazu wurde eine Apparatur entwickelt, die das hochsensitive ARES-Rheometer mit dem hochauflösenden dielektrischen ALPHA-Analyzer verbindet. Mit dieser Apparatur wurde das Typ-A Polymer 1,4-cis-Polyisopren, mit einem Dipolmoment entlang des Rückgrats, bei oszillatorischer Scherung unter gleichzeitiger Aufnahme eines dielektrischen Spektrums vermessen. Es konnte gezeigt werden, daß die oszillatorische Verscherung weder die charakteristische Relaxationszeit noch die Form des Normal Mode Peaks beeinflußt, wohl aber die dielektrische Stärke Delta epsilon. Diese entspricht der Fläche unter dem e“-Peak und kann mit einer Debye- und einer Cole/Davidson-Funktion angepasst werden. Die Abnahme der dielektrischen Stärke mit zunehmender Scheramplitude kann mit der Orientierungsverteilung der End-zu-End-Vektoren in der Probe erklärt werden.

Dielectric relaxation in biological materials

The study of dielectric properties concerns storage and dissipation of electric and magnetic energy in materials. Dielectrics are important in order to explain various phenomena in Solid-State Physics and in Physics of Biological Materials. Indeed, during the last two centuries, many scientists have tried to explain and model the dielectric relaxation. Starting from the Kohlrausch model and passing through the ideal Debye one, they arrived at more com- plex models that try to explain the experimentally observed distributions of relaxation times, including the classical (Cole-Cole, Davidson-Cole and Havriliak-Negami) and the more recent ones (Hilfer, Jonscher, Weron, etc.). The purpose of this thesis is to discuss a variety of models carrying out the analysis both in the frequency and in the time domain. Particular attention is devoted to the three classical models, that are studied using a transcendental function known as Mittag-Leffler function. We highlight that one of the most important properties of this function, its complete monotonicity, is an essential property for the physical acceptability and realizability of the models. Lo studio delle proprietà dielettriche riguarda l’immagazzinamento e la dissipazione di energia elettrica e magnetica nei materiali. I dielettrici sono importanti al fine di spiegare vari fenomeni nell’ambito della Fisica dello Stato Solido e della Fisica dei Materiali Biologici. Infatti, durante i due secoli passati, molti scienziati hanno tentato di spiegare e modellizzare il rilassamento dielettrico. A partire dal modello di Kohlrausch e passando attraverso quello ideale di Debye, sono giunti a modelli più complessi che tentano di spiegare la distribuzione osservata sperimentalmente di tempi di rilassamento, tra i quali modelli abbiamo quelli classici (Cole-Cole, Davidson-Cole e Havriliak-Negami) e quelli più recenti (Hilfer, Jonscher, Weron, etc.). L’obiettivo di questa tesi è discutere vari modelli, conducendo l’analisi sia nel dominio delle frequenze sia in quello dei tempi. Particolare attenzione è rivolta ai tre modelli classici, i quali sono studiati utilizzando una funzione trascendente nota come funzione di Mittag-Leffler. Evidenziamo come una delle più importanti proprietà di questa funzione, la sua completa monotonia, è una proprietà essenziale per l’accettabilità fisica e la realizzabilità dei modelli.

Quantum dot cytotoxicity in vitro: An investigation into the cytotoxic effects of a series of different surface chemistries and their core/shell materials

Abstract The aim of this study was to assess the effects of a series of different surface coated quantum dots (QDs) (organic, carboxylated [COOH] and amino [NH(2)] polytethylene glycol [PEG]) on J774.A1 macrophage cell viability and to further determine which part of the QDs cause such toxicity. Cytotoxic examination (MTT assay and LDH release) showed organic QDs to induce significant cytotoxicity up to 48 h, even at a low particle concentration (20 nM), whilst both COOH and NH(2) (PEG) QDs caused reduced cell viability and cell membrane permeability after 24 and 48 h exposure at 80 nM. Subsequent analysis of the elements that constitute the QD core, core/shell and (organic QD) surface coating showed that the surface coating drives QD toxicity. Elemental analysis (ICP-AES) after 48 h, however, also observed a release of Cd from organic QDs. In conclusion, both the specific surface coating and core material can have a significant impact on QD toxicity.