Identification of the Binding Site of Apical Membrane Antigen 1 (AMA1) Inhibitors Using a Paramagnetic Probe

Apical membrane antigen 1 (AMA1) is essential for the invasion of host cells by malaria parasites. Several small-molecule ligands have been shown to bind to a conserved hydrophobic cleft in Plasmodium falciparum AMA1. However, a lack of detailed structural information on the binding pose of these molecules has hindered their further optimisation as inhibitors. We have developed a spin-labelled peptide based on RON2, the native binding partner of AMA1, to probe the binding sites of compounds on PfAMA1. The crystal structure of this peptide bound to PfAMA1 shows that it binds at one end of the hydrophobic groove, leaving much of the binding site unoccupied and allowing fragment hits to bind without interference. In paramagnetic relaxation enhancement (PRE)-based NMR screening, the ¹H relaxation rates of compounds binding close to the probe were enhanced. Compounds experienced different degrees of PRE as a result of their different orientations relative to the spin label while bound to AMA1. Thus, PRE-derived distance constraints can be used to identify binding sites and guide further hit optimisation.     

Livability in dense residential neighbourhoods of Dhaka

Prime cities in developing countries, like Dhaka experience haphazard and intense horizontal densification. The livability of dense neighbourhoods needs to be investigated, particularly, the role of housing and planning in mitigating density problems and capitalizing the advantages of high-density living. This article argues that housing form and planned community facilities giving respect to socio-cultural practices can significantly influence Dhaka’s livability. Also, a wider definition of housing should be adopted to facilitate improvements in livability. As well, an integrated approach of residential planning is important in intensified housing development projects or planning for dense areas, encompassing housing standards, community facilities, public transport, open space provision and socio-cultural habits. This paper recommends the Bangladeshi Government to ensure enforcement of residential plans, to establish density zones in Dhaka’s main urban areas to guide spatial and transport development and neighbourhood facility provision, and to give greater respect for cultural practices in neighbourhood planning.     

Secure architecture to circumvent collision using RSSI measurement in WSN: a cross layer design approach

Multimedia Tools and Applications - ‘Wireless sensor networks’ (WSNs) follow layered architecture for the fruitful and reliable working of distributed WSNs. The region of WSN is...     

Non-parametric Method of Path Loss Estimation for Endoscopic Capsule Localization

Localization of the wireless video capsule endoscope (VCE) is necessary for proper diagnosis and treatment of the lesions in the gastrointestinal tract. In this paper, we propose path loss based VCE localization algorithm using weighted average of the sensors position. The main challenge in path loss based localization in human body is the scattered random deviation of path loss caused by the shadowing and multipath propagation of non-homogeneous medium. To address the randomness issue of the scattered path loss, we propose three non-parametric methods of path loss estimation using moving averaging, local weighted regression and local Gaussian weighted average. Then we use the degree based estimated path loss to calculate the weight of the sensors position. We propose a heuristic method of degree estimation for the estimated path loss. We develop a simulation platform using MATLAB to evaluate the performance of our proposed methods. The results show significant improvement in accuracy without any prior knowledge of distance related channel parameters.     

Waste heat utilization in a ceramic industry

The scope for energy conservation in a ceramic factory was studied. It was found that the sensible heat of the flue gas from kilns could be used to heat the casting shop. A pebble bed waste heat regenerator was chosen to collect the sensible heat of the flue gas. Experiments were performed on a pilot plant scale pebble bed to study its characteristics using a flue gas stream whose temperature and composition were similar to the factory conditions. The results of the heating cycle showed that 14 500 kcal h⁻¹ of heat can be collected from flue gas in a 0·126 m³ bed. This information was used to design a complete retrofit system. Financial analysis of the proposed project showed that it has a pay-back period of 15 months. © 1997 by John Wiley & Sons, Ltd.     

Computational Insights into the Deleterious Impacts of Missense Variants on N-Acetyl-d-glucosamine Kinase Structure and Function

An enzyme of the mammalian amino-sugar metabolism pathway, N-acetylglucosamine kinase (NAGK), that synthesizes N-acetylglucosamine (GlcNAc)-6-phosphate, is reported to promote dynein functions during mitosis, axonal and dendritic growth, cell migration, and selective autophagy, which all are unrelated to its enzyme activity. As non-enzymatic structural functions can be altered by genetic variation, we made an effort in this study aimed at deciphering the pathological effect of nonsynonymous single-nucleotide polymorphisms (nsSNPs) in NAGK gene. An integrated computational approach, including molecular dynamics (MD) simulation and protein–protein docking simulation, was used to identify the damaging nsSNPs and their detailed structural and functional consequences. The analysis revealed the four most damaging variants (G11R, G32R, G120E, and A156D), which are highly conserved and functional, positioned in both small (G11R and G32R) and large (G120E and A156D) domains of NAGK. G11R is located in the ATP binding region, while variants present in the large domain (G120E and A156D) were found to induce substantial alterations in the structural organizations of both domains, including the ATP and substrate binding sites. Furthermore, all variants were found to reduce binding energy between NAGK and dynein subunit DYNLRB1, as revealed by protein–protein docking and MM-GBSA binding energy calculation supporting their deleteriousness on non-canonical function. We hope these findings will direct future studies to gain more insight into the role of these variants in the loss of NAGK function and their role in neurodevelopmental disorders.     

Immunohistochemical characterization of phagocytic immune cell infiltration into different adipose tissue depots of dairy cows during early lactation

The present study aimed to investigate whether phagocytic immune cells infiltrate into bovine adipose tissue (AT) and to study the effects of lactation and conjugated linoleic acid (CLA) supplementation on the invasion of phagocytic immune cells into different s.c. and visceral (v.c.) fat depots of primiparous dairy cows during the first 105 d in milk (DIM). German Holstein-Friesian cows (HF; n = 25) with a mean body condition score of 3.0 were divided into a control (CON) and a CLA group. From 1 DIM until sample collection, CLA cows were fed 100 g of CLA supplement/d (about 6% of c9,t11 and t10,c12 isomers each), whereas the CON cows received 100 g/d of a fatty acid mixture instead of CLA. The CON cows (n = 5 each) were slaughtered at 1, 42, and 105 DIM, and the CLA cows (n = 5 each) were slaughtered at 42 and 105 DIM. Adipose tissues (n = 150) from 3s.c. (tailhead, withers, and sternum) and 3 v.c. (omental, mesenteric, and retroperitoneal) depots were sampled. In addition, s.c. tailhead biopsies were collected by repeated surgical biopsies (3 samplings within 7 wk; n = 36) from 12 nonpregnant, nonlactating Simmental heifers (SM; mean body condition score = 5.0) fed diets of varying energy density to compare the changes in phagocytic immune cell infiltration with early lactating cows. Immunohistochemical analyses of different fat depots revealed a low incidence of phagocytic immune cell infiltration in early lactating cows. The portion of infiltrating macrophages (CD68+) in a few positive AT samples of HF cows was slightly lower in s.c. than v.c. fat and was positively correlated with both empty body weight and adipocyte size. However, no differences with regard to DIM and CLA supplementation were observed in HF cows. Increased accumulation of phagocytic immune cells, albeit at low cell numbers, in nonpregnant, over-conditioned SM heifers might be related to larger adipocytes secreting higher amounts of chemoattractant adipokines compared with the early lactating cows. In conclusion, the extent of fatness in HF cows may not be high enough to stimulate significant infiltration of phagocytic cells in AT and, therefore, these immune cells might have no major role in the immunologic and metabolic adaptations of AT during early lactation.     

Hot Isostatically Pressed (HIPed) fluorite glass-ceramic wasteforms for fluoride molten salt wastes

Molten pyroprocessing salts can be used to dissolve used nuclear fuel from a reactor allowing recovery of the actinides. Previously, ANSTO have demonstrated hot isostatically pressed (HIPed) sodalite glass-ceramic wasteforms for eutectic (Li,K)Cl salts containing fission products, but this system cannot be used for the analogous molten alkali fluoride salts (eg, FLiNaK), which have utility in the application of the next generation of nuclear reactors. In this work, a novel glass-ceramic composite wasteform has been prepared by HIPing, as a candidate for the immobilization of fission product-bearing FLiNaK salts. The wasteform has been tailored to immobilize the high fluoride content of the waste within fluorite, whereas the waste alkali elements are incorporated in a durable sodium aluminoborosilicate glass, with total waste loadings of ~17-21 wt% achieved. It was also demonstrated that the speciation of Mo- and Sb-simulated fission products was altered by adding Ti metal due to a controlled redox environment. The resulting candidate wasteform has been studied by X-ray diffraction and scanning electron microscopy, including the HIP canister-wasteform interaction zone, and its performance assessed via leaching studies using the PCT and ASTM C1220 leaching protocols. Dr Vance very much enjoyed the challenge of wasteform design for problematic nuclear wastes, for which fission product-bearing FLiNaK salts are a clear example. His ability to hone in on a wasteform solution with viable waste loadings that meet performance requirements was testament to his nearly 40 years experience in nuclear waste immobilization. The samples discussed in this work represent the last wasteform materials that he prepared.