Molecular dynamics study of the swelling patterns of Na/Cs-, Na/Mg-montmorillonites and hydration of interlayer cations

Over the last two decades, the swelling properties of montmorillonite (MMT) have been studied in many experimental and simulation works, but less attention has been given to MMT containing a mixture of monovalent/monovalent and monovalent/bivalent cations in the interlayer spaces. We carried out a molecular dynamics simulation of the swelling patterns of Na-, Mg-, Na/Cs-, Na/Mg-MMT in an isobaric isothermal ensemble (NPT) at T = 300 K and p = 1 atm. The simulation reproduced a swelling pattern of Na-, Mg-, Na/Cs-, Na/Mg-MMT and the swelling curves obtained showed the difference between the hydration mechanisms of the type of MMT used in this study. We also found out that the differences in size and hydration energy of Na, Cs and Na, Mg ions have strong implications on the structure of interlayer water. This has led to the difference in the swelling curves of the simulated Na-, Mg-, Na/Cs- and Na/Mg-MMT. For Na/Cs-MMT, the hydration energy of Na cations increased compared to that in Na-MMT, the hydration energy of Cs cations decreased in Na/Cs-MMT compared to that in Cs-MMT and also for Na/Mg-MMT, the hydration energy of Na cations increased compared to that in Na-MMT and that of Mg cations decreased in comparison with that in Mg-MMT. The diffusion coefficient of Cs cations obtained in this simulation was higher than that of Mg and Na cations in Cs-, Mg- and Na-MMT, respectively. Cesium cations have been seen to have a low hydration energy compared to Na and Mg cations and can be used as a good inhibitor of Na-MMT swelling process.     

N-(4-{[4-(1H-Benzoimidazol-2-yl)-arylamino]-methyl}-phenyl)-benzamide derivatives as small molecule heparanase inhibitors

A novel class of N-(4-{[4-(1H-benzoimidazol-2-yl)-arylamino]-methyl}-phenyl)-benzamides are described as inhibitors of the endo-beta-glucuronidase heparanase. Among them are N-(4-{[4-(1H-benzoimidazol-2-yl)-phenylamino]-methyl}-phenyl)-3-bromo-4-methoxy-benzamide (15h), and N-(4-{[5-(1H-benzoimidazol-2-yl)-pyridin-2-ylamino]-methyl}- phenyl)-3-bromo-4-methoxy-benzamide (23) which displayed good heparanase inhibitory activity (IC(50) 0.23-0.29 microM), with the latter showing oral exposure in mice.     

Oxadiazole derivatives as a novel class of antimitotic agents: Synthesis, inhibition of tubulin polymerization, and activity in tumor cell lines

Oxadiazole derivatives were synthesized and evaluated for their ability to inhibit tubulin polymerization and to cause mitotic arrest in tumor cells. The most potent compounds inhibited tubulin polymerization at concentrations below 1 microM. Lead analogs caused mitotic arrest of A431 human epidermoid cells and cells derived from multi-drug resistant tumors (10, EC(50)=7.8 nM). Competition for the colchicine binding site and pharmacokinetic properties of selected potent compounds were also investigated and are reported herein, along with structure-activity relationships for this novel series of antimitotic agents.     

OpenCMISS: A multi-physics & multi-scale computational infrastructure for the VPH/Physiome project

The VPH/Physiome Project is developing the model encoding standards CellML (cellml.org) and FieldML (fieldml.org) as well as web-accessible model repositories based on these standards (models.physiome.org). Freely available open source computational modelling software is also being developed to solve the partial differential equations described by the models and to visualise results. The OpenCMISS code (opencmiss.org), described here, has been developed by the authors over the last six years to replace the CMISS code that has supported a number of organ system Physiome projects.OpenCMISS is designed to encompass multiple sets of physical equations and to link subcellular and tissue-level biophysical processes into organ-level processes. In the Heart Physiome project, for example, the large deformation mechanics of the myocardial wall need to be coupled to both ventricular flow and embedded coronary flow, and the reaction-diffusion equations that govern the propagation of electrical waves through myocardial tissue need to be coupled with equations that describe the ion channel currents that flow through the cardiac cell membranes.In this paper we discuss the design principles and distributed memory architecture behind the OpenCMISS code. We also discuss the design of the interfaces that link the sets of physical equations across common boundaries (such as fluid-structure coupling), or between spatial fields over the same domain (such as coupled electromechanics), and the concepts behind CellML and FieldML that are embodied in the OpenCMISS data structures. We show how all of these provide a flexible infrastructure for combining models developed across the VPH/Physiome community.     

Restoring leptin signaling reduces hyperlipidemia and improves vascular stiffness induced by chronic intermittent hypoxia

Chronic intermittent hypoxia (IH) during sleep can result from obstructive sleep apnea (OSA), a disorder that is particularly prevalent in obesity. OSA is associated with high levels of circulating leptin, cardiovascular dysfunction, and dyslipidemia. Relationships between leptin and cardiovascular function in OSA and chronic IH are poorly understood. We exposed lean wild-type (WT) and obese leptin-deficient ob/ob mice to IH for 4 wk, with and without leptin infusion, and measured cardiovascular indices including aortic vascular stiffness, endothelial function, cardiac myocyte morphology, and contractile properties. At baseline, ob/ob mice had decreased vascular compliance and endothelial function vs. WT mice. We found that 4 wk of IH decreased vascular compliance and endothelial relaxation responses to acetylcholine in both WT and leptin-deficient ob/ob animals. Recombinant leptin infusion in both strains restored IH-induced vascular abnormalities toward normoxic WT levels. Cardiac myocyte morphology and function were unaltered by IH. Serum cholesterol and triglyceride levels were significantly decreased by leptin treatment in IH mice, as was hepatic stearoyl-Coenzyme A desaturase 1 expression. Taken together, these data suggest that restoring normal leptin signaling can reduce vascular stiffness, increase endothelial relaxation, and correct dyslipidemia associated with IH.     

Diversity,dynamic and ecology of freshwater snails related to environmental factors in urban and suburban streams in Douala–Cameroon (Central Africa)

Urban land use has increased dramatically over the past few decades, resulting in high variability in nutrients loading which is likely to alter the biological component of urban streams. Freshwater snails and environmental variables that might structure their diversity and distribution were studied from September 2012 to September 2013 in three contiguous watersheds in Douala. Twelve stations were monitored monthly, two of these are located in a suburban forest area, and the rest situated in urbanized and industrialized zones. Snails were collected using a long-handled net (30 × 30 cm side, 400-µm mesh). Meanwhile, measurements of the environmental variables were taken. Ten species were recorded which are as follows: Melanoides tuberculata (Thiaridae); Gabbiella africana (Bythiniidae); Physa acuta, Aplexa sp. (Physidae); Lymnaea natalensis, Lymnaea stagnalis, Lymnaea columella (Lymnaeidae); Biomphalaria pfeifferi, Bulinus forskalii (Planorbidae) and one undetermined taxon of Bythiniidae. All these snails were identified at nine of the ten urban stations; no species being found in suburban stations. These urban streams have very poor health status with highly polluted waters. Among the species found P. acuta (76.95 %), L. natalensis (19.46 %) and M. tuberculata (2.79 %) were the most abundant. Multiple stepwise regression analysis, Spearman correlation test and redundancy analysis showed that snail occurrences and abundances were probably influenced by water temperature, conductivity, suspended solids, alkalinity, nitrites, nitrates, ammonium, phosphates, oxydability, biochemical oxygen demand, rainfall, encumbrance rate of the riverbed and water width. Moreover, snail dynamics showed a seasonal pattern with peak population abundances and recruitment of young generations during rainy season. This malacological survey spotlighted the impacts of anthropogenic activities on snail’s diversity and distribution, with the proliferation of the invasive pulmonate P. acuta in Douala urban streams.     

Balance between the two kinin receptors in the progression of experimental focal and segmental glomerulosclerosis in mice

Focal and segmental glomerulosclerosis (FSGS) is one of the most important renal diseases related to end-stage renal failure. Bradykinin has been implicated in the pathogenesis of renal inflammation, whereas the role of its receptor 2 (B2RBK; also known as BDKRB2) in FSGS has not been studied. FSGS was induced in wild-type and B2RBK-knockout mice by a single intravenous injection of Adriamycin (ADM). In order to further modulate the kinin receptors, the animals were also treated with the B2RBK antagonist HOE-140 and the B1RBK antagonist DALBK. Here, we show that the blockage of B2RBK with HOE-140 protects mice from the development of FSGS, including podocyte foot process effacement and the re-establishment of slit-diaphragm-related proteins. However, B2RBK-knockout mice were not protected from FSGS. These opposite results were due to B1RBK expression. B1RBK was upregulated after the injection of ADM and this upregulation was exacerbated in B2RBK-knockout animals. Furthermore, treatment with HOE-140 downregulated the B1RBK receptor. The blockage of B1RBK in B2RBK-knockout animals promoted FSGS regression, with a less-inflammatory phenotype. These results indicate a deleterious role of both kinin receptors in an FSGS model and suggest a possible cross-talk between them in the progression of disease.KEY WORDS: Focal and segmental glomerulosclerosis, Bradykinin receptors, Inflammation, Podocyte, Fibrosis     

Long-Term Aerobic Exercise Protects against Cisplatin-Induced Nephrotoxicity by Modulating the Expression of IL-6 and HO-1

Nephrotoxicity is substantial side effect for 30% of patients undergoing cancer therapy with cisplatin and may force them to change or even abandon the treatment. Studies regarding aerobic exercise have shown its efficacy for the treatment of many types of diseases and its capacity to reduce tumors. However, little is known about the impact of physical exercise on cisplatin-induced acute kidney injury (AKI). In the present study, our aim was to investigate the role of physical exercise in AKI induced by cisplatin. We submitted C57Bl6 male mice to seven weeks of chronic exercise on a training treadmill and treated them with single i.p. injection of cisplatin (20 mg/kg) in the last week. Exercise efficacy was confirmed by an increased capillary-to-fiber ratio in the gastrocnemius muscle of exercised groups (EX and CIS-EX). The group submitted to exercise before cisplatin administration (CIS-EX) exhibited less weight loss and decreased serum urea levels compared to the cisplatin group (CIS). Exercise also showed a protective role against cisplatin-induced cell death in the kidney. The CIS-EX group showed a lower inflammatory response, with less TNF and IL-10 expression in the kidney and serum. In the same group, we observed an increase of IL-6 and HO-1 expression in the kidney. Taken together, our results indicate that chronic aerobic exercise is able to attenuate AKI by inducing IL-6 and HO-1 production, which results in lower inflammatory and apoptotic profiles in the kidney.     

Numerical simulation of blood flow in the left ventricle and aortic sinus using magnetic resonance imaging and computational fluid dynamics

Understanding cardiac blood flow patterns has many applications in analysing haemodynamics and for the clinical assessment of heart function. In this study, numerical simulations of blood flow in a patient-specific anatomical model of the left ventricle (LV) and the aortic sinus are presented. The realistic 3D geometry of both LV and aortic sinus is extracted from the processing of magnetic resonance imaging (MRI). Furthermore, motion of inner walls of LV and aortic sinus is obtained from cine-MR image analysis and is used as a constraint to a numerical computational fluid dynamics (CFD) model based on the moving boundary approach. Arbitrary Lagrangian–Eulerian finite element method formulation is used for the numerical solution of the transient dynamic equations of the fluid domain. Simulation results include detailed flow characteristics such as velocity, pressure and wall shear stress for the whole domain. The aortic outflow is compared with data obtained by phase-contrast MRI. Good agreement was found between simulation results and these measurements.     

Exclusion of livestock grazing and wood collection in dryland savannah: an effect on long‐term vegetation succession

Sahelian savannah faces increasing pressure from human activities, leading to its degradation. The aim of this study was to investigate the possibility of restoration of dryland savannah vegetation by the elimination of disturbance factors on the ecosystem. Is degraded dryland savannah vegetation able to be restored by means of natural succession? What is the timescale for its recovery? The study took place in the Bandia Reserve, 65 km south‐east of Dakar (Senegal), a unique site with two successional stages due to the elimination of uncontrolled exploitation. The vegetation structure of 15 years (15YRS) and 5 years (5YRS) after fencing was compared with vegetation exposed to continuous livestock grazing and wood collection outside the fenced area. Calculated by redundancy analysis, a significant effect of selected areas on the cover of all species was revealed and successional stage explained more than 45% of data variability. Perennial forbs, annual forbs and perennial grasses achieved the highest cover in 5YRS, woody species in 15YRS and annual grasses in the area outside of the fenced reserve. The dominant woody species Acacia seyal, A. ataxacantha, A. nilotica subsp. adstringens and Balanites aegyptiaca reconstituted the dense formation of Acacia bushland by means of natural succession in the 15YRS area.