The Role of Leak Channels in Regulating Endocrine Pituitary Cell Excitability

The pituitary gland produces a variety of hormones that regulate other glands and organs throughout the body to control critical bodily functions including growth, metabolism and the stress response. Endocrine pituitary cells are electrically excitable: they generate action potentials to regulate their intracellular calcium level ([Ca2+]i) and eventually hormone secretion. The interplay between hypothalamic neurohormones and feedback signals coming from peripheral endocrine glands controls hormone secretion from pituitary cells by regulating the properties of ion channels and in turn the pattern of electrical activity. Therefore, elucidating the mechanisms underlying hormone secretion involves characterisation of ionic conductances which govern pituitary cell excitability. This PhD thesis explores how sodium and potassium leak channels regulate pituitary cell excitability. Leak channels play an important role in tuning the resting membrane potential, appropriately maintaining it close to the threshold for generating action potentials in all pituitary cells. The dynamic clamp electrophysiology technique was used to virtually vary the conductance of the leak channels, and evaluate their effect on the pattern of electrical activity and intracellular calcium concentration in the GH4 lacto-somatotroph cell line as well as in murine primary pituitary cells. It was found that very small alterations in the conductance of sodium and potassium leak channels result in substantial changes in the patterns of electrical activity and intracellular calcium oscillations in both GH4 and primary pituitary cells. Increasing the conductance of sodium leak channels by only a few fractions of a nanosiemen (nS) enhanced the excitability of pituitary cells significantly. In contrast, increasing the conductance of potassium leak channels by comparable values reduced the excitability and intracellular calcium concentration of the cells. Despite the crucial role of sodium leak conductance in tuning the resting membrane potential at depolarised levels away from the potassium equilibrium potential, the molecular identity of this channel in pituitary cells has remained unknown. One candidate protein channel is the sodium leak channel, non-selective (NALCN). The NALCN channel is widely expressed in the central nervous system, and has been characterised as a key modulator of cell excitability in several neuronal populations. Hence, in the second stage of my PhD, we constructed a lentiviral vector to knock down the NALCN channel in murine primary anterior pituitary cells in culture, and evaluate NALCN’s role in regulating cell excitability and intracellular calcium concentration using electrophysiology and calcium imaging techniques. We discovered that: (1) NALCN encodes for sodium leak channel to acutely adjust the resting membrane potential and sustain intrinsically-regulated spontaneous firing in endocrine pituitary cells; (2) the NALCN channel is crucial for maintaining spontaneous [Ca2+]i oscillations; (3) NALCN mediates the major depolarising inward leak current in pituitary cells; and (4) as in neurons, extracellular calcium inhibits NALCN activity in pituitary cells. These discoveries advance our understanding of how cell excitability and consequently hormone secretion is regulated in endocrine pituitary cells

High Pressure and High Temperature Study of Magnesiochromite and Its Geophysical Implications

Magnesiochromite (MgCr2O4) is commonly found in the Earth’s crust, upper mantle, meteorites, and possibly in lunar crust. Synchrotron X-ray diffraction measurements of MgCr2O4 using double-sided laser heating diamond anvil cell showed the dissociation of MgCr2O4 to Cr2O3+MgO at ~15 GPa and to Mg2Cr2O5+Cr2O3 below and above ~1500 K, respectively. At above 20 GPa, only a single phase CaTi2O4-type structure of MgCr2O4 was observed at 1400-2000 K. Fitting the pressure-volume data of CaTi2O4 type structure of MgCr2O4 with Birch-Murnaghan equation of state yields volume at ambient condition (V0) = 264.4(8) Å3, bulk modulus (K0) = 185.4(4) GPa, and pressure derivative of the bulk modulus (K0’) = 4; and for CaTi2O4 type structure of natural chromite: V0 = 261(1) Å3, K0 = 175.4(2) GPa, K0’ = 4, and mLd-type Mg2Cr2O5 yields: V0 = 338.9(8) Å3, K0 = 186.5(6) GPa, K0’ = 4. Obtained phase diagram and bulk modulus data provide important information to better understand the structure and dynamics of the deep earth

Numerical and Rational Analysis of Shotcrete Lining for Rock Tunnels under Effect of Explosion Loads

Tunnels in rock media are considered one of the most important types of fortified structures that can be used to resist the progressive development of military destructive weapons. The geological formation of tunnel rock mass has a great influence on the degree of protection to human and weapons. This protection degree is based mainly on both the utilized system of tunnel lining and the type and quality of rock mass which reduces the effect of wave propagation generated by explosion. Shotcrete lining is one of the most commonly used support system used in tunnel lining. Understanding the dynamic response and damage characteristics of shotcrete lining for rock tunnels due to explosion loads is essential for safe design. The main aim of this paper is to investigate the stresses and displacements of shotcrete lining under blasting loads and the effect of different of rock mass qualities on the wave propagation associated with the explosion. In order to achieve this aim, numerical analysis technique, commercial software package, AUTODYN version 6.1 is used to perform 90 three-dimensional elasto-plastic dynamic models to analyze rock-shotcrete lining interaction. A parametric study was carried out taking into consideration the effect of Rock Mass Rating (RMR), tunnel radius, charge weight and detonation distance. The numerical simulation of explosion in rock mass is extremely demanding, requiring hydrodynamic computer codes, combined with non-linear dynamic codes based on finite elements which is a very complex approach. Therefore, regression analysis is used for statistics prediction of the behavior of shotcrete lining. A rational analysis is conducted to form non-linear equations to predict stresses and displacements of shotcrete lining at tunnel crown based on the results of the parametric study. The suggested equations were used to form design charts for different values of Rock Mass Rating. A comparison between the results of the numerical simulation and rational analysis for the different models showed a good matching

Reversed flow-injection method for estimation of chlorpromazine in pharmaceuticals and urine samples using charge-transfer complexation

A simple, automated and sensitive reversed flow-injection analysis (rFIA) method for the determination of chlorpromazine hydrochloride (CLP) in pharmaceutical formulations and human urine samples is described. The automated method is based on the formation of charge-transfer complex between CLP (donor) with new reagent (an acceptor) used for the first time namely, 4,4’-tetramethyl-diaminodiphenylmethane (TDM) in the presence of K2S2O8 as an oxidant. An intense blue-colored product, which gave a maximum absorbance at 604 nm, was formed immediately at room temperature. The various chemical and physical conditions that affected the reaction have been studied. The calibration curve was rectilinear within the concentration range 1-45 µg/mL and the detection and quantification limits of 0.72 and 2.40 µg/mL respectively with a sample through put of 80 sample/hour. The proposed procedure was applied successfully for the estimation of CLP and the results obtained were favorably compared with those given by a reference method, and there was no significant difference between the obtained results, regarding accuracy and precision at the 95% confidence level.               KEY WORDS: Chlorpromazine, Flow injection analysis, Charge-transfer complexation Bull. Chem. Soc. Ethiop. 2019, 33(1), 11-20.DOI: https://dx.doi.org/10.4314/bcse.v33i1.

The absence of corporate social responsibility reporting in Bangladesh

This paper aims to broaden the present corporate social responsibility (CSR) reporting literature by extending its focus to the absence of CSR reporting within a developing country, an area which, to date, is relatively under researched in comparison to the more widely studied presence of CSR reporting within developed Western countries. In particular this paper concentrates upon the lack of disclosure on three particular eco-justice issues: child labour, equal opportunities and poverty alleviation. We examine why this is the case and thereby illuminate underlying motives behind corporate unwillingness to address these issues. For this purpose, 23 semi-structured interviews were undertaken with senior corporate managers in Bangladesh. The findings suggest that the main reasons for non-disclosure include lack of resources, the profit imperative, lack of legal requirements, lack of knowledge/awareness, poor performance and the fear of bad publicity. Given these findings the paper raises some serious concerns as to why corporations would ever be expected to voluntarily report on eco-justice issues where performance is poor and negative publicity would be generated and profit impaired. Further research is still required to uncover current injustices and to imagine what changes can be made

Intellectual capital disclosures by South African companies:a longitudinal investigation

Most of the previous studies on intellectual capital disclosures have been conducted from developed countries' context. There is very limited empirical evidence in this area from the context of emerging economies in general and Africa in particular. This paper is one of the early attempts in this regard. The main purpose of this study is to examine the extent and nature of intellectual capitaldisclosures in ‘Top 20’ South African companies over a 5 years period (2002–2006). The study uses content analysis method to scrutinise the patterns of intellectual capital disclosures during the study period. The results show that intellectual capital disclosures in South Africa have increased over the 5 years study period with certain firms reporting considerably more than others. Out of the three broad categories of intellectual capital disclosures human capital appears to be the most popular category. This finding stands in sharp contrast to the previous studies in this area where external capital was found to be most popular category