Comparative in vitro studies on native and recombinant human cationic trypsins - Cathepsin B is a possible pathological activator of trypsinogen in pancreatitis

Hereditary pancreatitis, an autosomal dominant disease is believed to be caused by mutation in the human trypsinogen gene. The role of mutations has been investigated by in vitro studies using recombinant rat and human trypsinogen (TG), In this study we compare the enzymatic properties and inhibition by human pancreatic secretory trypsin inhibitor (hPSTI) of the native, postsynthetically modified and recombinant cationic trypsin, and found these values practically identical, We also determined the autolytic stability of recombinant wild type (Hu1Asn21) and pancreatitis-associated (Hu1Ile21) trypsin, Both forms were equally stable. Similarly, we found no difference in the rate of activation of the two zymogens by human cationic and anionic trypsin. Mesotrypsin did not activate either form. The rate of autocatalytic activation of Hu1Asn21 TG and Hu1Ile21 TG was also identical at pH 8 both in the presence and absence of Ca2+. At pH 5 Hu1Ile21 TG autoactivated about twice as fast as HulAsn21 TG, The presence of physiological amount of hPSTI completely prevented autoactivation of both zymogens at pH 8 and at pH 5 as well. Cathepsin B readily activated both zymogens although Hu1Ile21 TG was activated about 2.5-3 times as fast as Hu1Asn21 TG, The presence of hPSTI did not prevent the activation of zymogens by cathepsin B, Our results underlie the central role of cathepsin B in the development of different forms of pancreatitis

Molecular mechanisms of vaspin action: from adipose tissue to skin and bone, from blood vessels to the brain

Visceral adipose tissue derived serine protease inhibitor (vaspin) or SERPINA12 according to the serpin nomenclature was identified together with other genes and gene products that  were specifically expressed or overexpressed in the intra abdominal or visceral adipose tissue  (AT) of the Otsuka Long-Evans Tokushima fatty rat. These rats spontaneously develop visceral  obesity, insulin resistance, hyperinsulinemia and ‐glycemia, as well as hypertension and thus represent a well suited animal model of obesity and related metabolic disorders such as type  2 diabetes.  The follow-up study reporting the cloning, expression and functional characterization of  vaspin suggested the great and promising potential of this molecule to counteract obesity induced insulin resistance and inflammation and has since initiated over 300 publications, clinical and experimental, that have contributed to uncover the multifaceted functions and molecular mechanisms of vaspin action not only in the adipose, but in many different cells, tissues and organs. This review will give an update on mechanistic and structural aspects of vaspin with a focus on its serpin function, the physiology and regulation of vaspin expression, and will summarize the latest on vaspin function in various tissues such as the different adipose tissue depots as well as the vasculature, skin, bone and the brain

Diverse electrical responses in a network of fractional-order conductance-based excitable Morris-Lecar systems

Abstract The diverse excitabilities of cells often produce various spiking-bursting oscillations that are found in the neural system. We establish the ability of a fractional-order excitable neuron model with Caputo’s fractional derivative to analyze the effects of its dynamics on the spike train features observed in our results. The significance of this generalization relies on a theoretical framework of the model in which memory and hereditary properties are considered. Employing the fractional exponent, we first provide information about the variations in electrical activities. We deal with the 2D class I and class II excitable Morris-Lecar (M-L) neuron models that show the alternation of spiking and bursting features including MMOs & MMBOs of an uncoupled fractional-order neuron. We then extend the study with the 3D slow-fast M-L model in the fractional domain. The considered approach establishes a way to describe various characteristics similarities between fractional-order and classical integer-order dynamics. Using the stability and bifurcation analysis, we discuss different parameter spaces where the quiescent state emerges in uncoupled neurons. We show the characteristics consistent with the analytical results. Next, the Erdös-Rényi network of desynchronized mixed neurons (oscillatory and excitable) is constructed that is coupled through membrane voltage. It can generate complex firing activities where quiescent neurons start to fire. Furthermore, we have shown that increasing coupling can create cluster synchronization, and eventually it can enable the network to fire in unison. Based on cluster synchronization, we develop a reduced-order model which can capture the activities of the entire network. Our results reveal that the effect of fractional-order depends on the synaptic connectivity and the memory trace of the system. Additionally, the dynamics captures spike frequency adaptation and spike latency that occur over multiple timescales as the effects of fractional derivative, which has been observed in neural computation

Core\u2013shell hybrid nanomaterial based on prussian blue and surface active maghemite nanoparticles as stable electrocatalyst

A novel core-shell nanomaterial based on prussian blue (PB) coating on peculiar surface active maghemite nanoparticles (SAMNs), was developed. The synthetic process involves the direct crystallization of Fe(II)(CN)6 4- onto the surface of SAMNs by simple incubation in water at controlled pH, demonstrating the presence of under-coordinated Fe(III) on nanoparticle surface. The coating reaction occurs in a narrow pH range and the synthetic procedure was optimized. The resulting SAMNatPB hybrid nanostructures were characterized by transmission and scanning electron microscopy, M\uf6ssbauer, UV-vis and FTIR spectroscopy and X-ray powder diffraction. The nanomaterial, characterized by high stability in alkaline media, behave as excellent electro-catalyst for hydrogen peroxide reduction. The stability of SAMNatPB hybrid has been investigated as a function of pH, showing excellent stability up to pH 9.0 and demonstrating the feasibility of SAMNs, superficially derivatized with prussian blue, to produce an efficient and extremely stable nanostructured material. This maghemite supported nanostructured prussian blue was applied to develop a sensor, based on a simple carbon paste electrode, which was able to catalyze the electro-reduction of hydrogen peroxide, in aqueous solutions, buffered at pH 7.0, at low applied potentials (0.0V vs. SCE)