Dynamical mean field modelling and estimation of neuronal oscillations

Oscillations in neural activity are a ubiquitous phenomenon in the brain. They span multiple timescales and correlate with a myriad of physiological and pathological conditions. Given their intrinsic dynamical nature, mathematical and computational modelling tools have proven to be indispensible in order to interpret and formalize the mechanisms through which these oscillations arise. In this Thesis, I developed a new methodological framework that allows the assimilation of experimental data into biophysically plausible models of neural oscillations. Motivated by the fast oscillatory activity (30 ~ 130 Hz) at the onset of focal epileptic seizures, I started by investigating, via means of bifurcation analyses, whether such fast oscillations can be plausibly described by conductance-based neural mass models. Neural mass models have enjoyed success in describing several forms of epileptiform activity (e.g. spike-and-wave seizures and interictal spikes), but I found that, in order to generate such fast oscillations, the parameters of this family of models would have to depart significantly from biophysical plausibility. These results motivated the exploration of full mean-field models of spiking neurons to characterise this type of dynamics. I hence proposed a variant of a mean-field neural population model based on the Fokker-Planck equation of conductance-based, stochastic, leaky integrate-and-fire neurons. This modelling approach was chosen for its capacity to describe arbitrary network configurations and predict firing rates, trans-membrane currents and local field potentials. I introduced a new numerical scheme that makes the computational cost of integrating the ensuing partial differential equations scale linearly with the number of nodes of the networks. These advances are crucial for the practical implementation of model inversion schemes. I then built upon the literature of Dynamic Causal Modelling to develop a Bayesian model inversion algorithm applicable to dynamical systems in limit cycle regimes. I applied the scheme to the mean-field models described above, using experimental data recordings of carbachol-induced gamma oscillations, in the CA1 region of mice hippocampal slice preparations. The estimated model was able to make accurate predictions about independent data features; namely inter-spike-interval distributions. Also, the inverted models were qualitatively compatible with the observation that excitatory pyramidal cells and inhibitory interneurons play equally important roles in the dynamics of these oscillations (as opposed to interneuron-dominated gamma oscillations). I also explored the applicability of this inversion scheme to neural mass models of electroencephalographically recorded spike-and-wave seizures in humans. In conclusion, the work presented in this thesis provides significant new contributions to model based analyses of neuronal oscillatory data, and helps to bridge single-neuron measurements to network-level interactions

Bioprospecting of yeasts for amylase production in solid state fermentation and evaluation of the catalytic properties of enzymatic extracts

Profiling microorganisms with potential for amylase production in low cost culture media has been widely recognized due to its broad applicability. The aim of this study was to select yeast strains with potential to produce amylolytic enzymes by solid state fermentation. Fifty-four (54) strains were assessed and three exhibited ability to produce amylases: Candida parapsilosis with 14.68 U/mL (146.8 U/g substrate); Rhodotorula mucilaginosa with 25.0 U/mL (250 U/g substrate), and Candida glabrata with 25.39 U/mL (253.9 U/g substrate), in solid state fermentation, for 120 h at 28°C, using wheat bran with 70% moisture. The enzymes exhibited maximum activity at a pH of 7.0 and at 60°C. Amylases demonstrated satisfactory structural stability, maintaining their catalytic activity after 1 h at 50°C. All enzymes were ethanol tolerant and retained more than 70% of their original activities in 15% ethanol solution. Corn starch was efficiently hydrolyzed by enzymes and the extracts produced by C. parapsilosis and C. glabrata exhibited dextrinizing activity, while those produced by R. mucilaginosa exhibited saccharifying activity. Key words: Candida parapsilosis, Candida glabrata, Rhodotorula mucilaginosa, dextrinizing and saccharifying activit

Effectiveness Of 2% And 4% Papain Gels In The Healing Of Venous Ulcers

OBJECTIVE To analyze the effectiveness of 2% and 4% papain gels in tissue repair of venous ulcers. METHOD Quasi-experimental study with consecutive sample of 16 patients with 30 venous ulcers treated at the outpatient clinic of a teaching hospital, from April to November in 2011, using a form for clinical assessment of the patient and its lesion. Variables were analyzed by Wilcoxon and McNemar test (p < 0.05). RESULTS Most participants were female; aged between 51 and 59 years; obese; with hypertension. Regarding ulcers, there was an average decrease of 7.9 cm2 (50% of its original size) in 90 days; 20% of the ulcers completely healed within 56.67 days. There was an increase in epithelialization, significant reduction in the slough and edema, improved depth, in the type and amount of exudate (p < 0.0001). CONCLUSION 2% and 4% papain gels were effective in healing venous ulcers

Inhibitors of Bcl-2 protein family deplete ER Ca2+ stores in pancreatic acinar cells

Physiological stimulation of pancreatic acinar cells by cholecystokinin and acetylcholine activate a spatial-temporal pattern of cytosolic [Ca+2] changes that are regulated by a coordinated response of inositol 1,4,5-trisphosphate receptors (IP3Rs), ryanodine receptors (RyRs) and calcium-induced calcium release (CICR). For the present study, we designed experiments to determine the potential role of Bcl-2 proteins in these patterns of cytosolic [Ca+2] responses. We used small molecule inhibitors that disrupt the interactions between prosurvival Bcl-2 proteins (i.e. Bcl-2 and Bcl-xl) and proapoptotic Bcl-2 proteins (i.e. Bax) and fluorescence microfluorimetry techniques to measure both cytosolic [Ca+2] and endoplasmic reticulum [Ca+2]. We found that the inhibitors of Bcl-2 protein interactions caused a slow and complete release of intracellular agonist-sensitive stores of calcium. The release was attenuated by inhibitors of IP3Rs and RyRs and substantially reduced by strong [Ca2+] buffering. Inhibition of IP3Rs and RyRs also dramatically reduced activation of apoptosis by BH3I-2′. CICR induced by different doses of BH3I-2′ in Bcl-2 overexpressing cells was markedly decreased compared with control. The results suggest that Bcl-2 proteins regulate calcium release from the intracellular stores and suggest that the spatial-temporal patterns of agonist-stimulated cytosolic [Ca+2] changes are regulated by differential cellular distribution of interacting pairs of prosurvival and proapoptotic Bcl-2 proteins

Perception of hypertensive patients about their non-adherence to the use of medication

This qualitative study aims to analyze the perception of patients with hypertension on their non-adherence to medication. 13 participants were interviewed, classified as non-adherent.The analysis was performed using the technique of thematic content analysis. Data points to contradictions in the approach of what is being adherent or not, the difficulty of adhering to the use of medication due to lifestyle habits, that forgetting is understood as a justification for non-compliance, and reinforces factors that hinder such practice, such as the use of many drugs, the presence of signs and symptoms and changes in daily routine. With complex conditions that involve non-adherence to treatment and the current context of the predominance of chronic diseases, it is essential to invest in innovative strategies of care for such people

Monitoring Inequalities in the Health Workforce: The Case Study of Brazil 1991–2005

Introduction: Both the quantity and the distribution of health workers in a country are fundamental for assuring equitable access to health services. Using the case of Brazil, we measure changes in inequalities in the distribution of the health workforce and account for the sources of inequalities at sub-national level to identify whether policies have been effectiv

Effects of Ethanol and NAP on Cerebellar Expression of the Neural Cell Adhesion Molecule L1

The neural cell adhesion molecule L1 is critical for brain development and plays a role in learning and memory in the adult. Ethanol inhibits L1-mediated cell adhesion and neurite outgrowth in cerebellar granule neurons (CGNs), and these actions might underlie the cerebellar dysmorphology of fetal alcohol spectrum disorders. The peptide NAP potently blocks ethanol inhibition of L1 adhesion and prevents ethanol teratogenesis. We used quantitative RT-PCR and Western blotting of extracts of cerebellar slices, CGNs, and astrocytes from postnatal day 7 (PD7) rats to investigate whether ethanol and NAP act in part by regulating the expression of L1. Treatment of cerebellar slices with 20 mM ethanol, 10−12 M NAP, or both for 4 hours, 24 hours, and 10 days did not significantly affect L1 mRNA and protein levels. Similar treatment for 4 or 24 hours did not regulate L1 expression in primary cultures of CGNs and astrocytes, the predominant cerebellar cell types. Because ethanol also damages the adult cerebellum, we studied the effects of chronic ethanol exposure in adult rats. One year of binge drinking did not alter L1 gene and protein expression in extracts from whole cerebellum. Thus, ethanol does not alter L1 expression in the developing or adult cerebellum; more likely, ethanol disrupts L1 function by modifying its conformation and signaling. Likewise, NAP antagonizes the actions of ethanol without altering L1 expression