A Procedure for the 3D Reconstruction of Biological Organs from 2D Image Sequences

In this work, a procedure is presented for the reconstruction of biological organs from image sequences obtained through CT-scan. Although commercial software, which can accomplish this task, are readily available, the procedure presented here needs only free software. The procedure has been applied to reconstruct a liver from the scan data available in literature. 3D biological organs obtained this way can be used for the finite element analysis of biological organs and this has been demonstrated by carrying out an FE analysis on the reconstructed liver.

Synthesis and biological evaluation of novel 2-aralkyl-5-substituted-6-(4 `-fluorophenyl)-imidazo2,1-b]1,3,4]thiadiazole derivatives as potent anticancer agents

Levamisole, the imidazo2,1-b]thiazole derivative has been reported as a potential antitumor agent. In the present study, we synthesized, characterized and evaluated biological activity of its novel analogues with substitution in the aralkyl group and on imidazothiadiazole molecules with same chemical backbone but different side chains namely 2-aralkyl-6-(4'-fluorophenyl)-imidazo2,1-b]1,3,4]thiadiazoles (SCR1), 2-aralkyl-5-bromo-6-(4'-fluorophenyl)-imidazo2,1-b]1,3,4]-thiadiaz oles (SCR2), 2-aralkyl-5-formyl-6-(4'-fluorophenyl)-imidazo2,1-b]1,3,4]-thiadia zoles (SCR3) and 2-aralkyl-5-thiocyanato-6-(4'-fluorophenyl)-imidazo2,1-b]1,3,4]-th iadiazoles (SCR4) on leukemia cells. The cytotoxic studies showed that 3a, 4a, and 4c exhibited strong cytotoxicity while others had moderate cytotoxicity. Among these we chose 4a (IC50, 8 mu M) for understanding its mechanism of cytotoxicity. FACS analysis in conjunction with mitochondrial membrane potential and DNA fragmentation studies indicated that 4a induced apoptosis without cell cycle arrest suggesting that it could be used as a potential chemotherapeutic agent. (C) 2011 Elsevier Masson SAS. All rights reserved.

Interactions of Antithyroid Drugs and Their Analogues with Halogens and their Biological Implications

The selenium analogue of antithyroid drug methimazole (MSeI) reacts with molecular bromine to produce two different types of novel complexes depending upon the molar ratio of MSeI to Br-2 in the reaction medium: Dicationic diselenide complex with two Br- ions as counterions is produced in the reaction of MSeI with 0.5 equiv of Br-2 (MSeI/Br-2, 1.0:0.5), whereas a stable 10-Se-3 hypervalent ``T-shaped'' complex featuring a linear Br-Se-Br moiety was produced when MSeI was treated with Br-2 in an equimolar ratio (MSeI/Br-2, 1.0:1.0). A substitution at the free N-H group in MSeI alters its reactivity toward iodine/bromine. For example, the N,N-disubstituted selones exclusively produce the corresponding 10-Se-3 hypervalent ``T-shaped'' complexes in the reaction with I-2. In the presence of the lectoperoxidase/H2O2/I- system, N,N-dimethylimidazole-2-selone produces the corresponding dicationic diselenide with two I- counterions as the final metabolite. The formation of ionic species in these reactions is confirmed by single crystal X-ray diffraction studies and in some cases by Fourier transform-Raman spectroscopic investigations.

A perspective of biological supramolecular electron transfer

Electron transfer is an essential activity in biological systems. The migrating electron originates from water-oxygen in photosynthesis and reverts to dioxygen in respiration. In this cycle two metal porphyrin complexes possessing circular conjugated system and macrocyclic pi-clouds, chlorophyll and hems, play a decisive role in mobilising electrons for travel over biological structures as extraneous electrons. Transport of electrons within proteins (as in cytochromes) and within DNA (during oxidative damage and repair) is known to occur. Initial evaluations did not favour formation of semiconducting pathways of delocalized electrons of the peptide bonds in proteins and of the bases in nucleic acids. Direct measurement of conductivity of bulk material and quantum chemical calculations of their polymeric structures also did not support electron transfer in both proteins and nucleic acids. New experimental approaches have revived interest in the process of charge transfer through DNA duplex. The fluorescence on photoexcitation of Ru-complex was found to be quenched by Rh-complex, when both were tethered to DNA and intercalated in the base stack. Similar experiments showed that damage to G-bases and repair of T-T dimers in DNA can occur by possible long range electron transfer through the base stack. The novelty of this phenomenon prompted the apt name, chemistry at a distance. Based on experiments with ruthenium modified proteins, intramolecular electron transfer in proteins is now proposed to use pathways that include C-C sigma-bonds and surprisingly hydrogen bonds which remained out of favour for a long time. In support of this, some experimental evidence is now available showing that hydrogen bond-bridges facilitate transfer of electrons between metal-porphyrin complexes. By molecular orbital calculations over 20 years ago. we found that "delocalization of an extraneous electron is pronounced when it enters low-lying virtual orbitals of the electronic structures of peptide units linked by hydrogen bonds". This review focuses on supramolecular electron transfer pathways that can emerge on interlinking by hydrogen bonds and metal coordination of some unnoticed structures with pi-clouds in proteins and nucleic acids, potentially useful in catalysis and energy missions.

Biological water: Femtosecond dynamics of macromolecular hydration

The unique features of a macromolecule and water as a solvent make the issue of solvation unconventional, with questions about the static versus dynamic nature of hydration and the, physics of orientational and translational diffusion at the boundary. For proteins, the hydration shell that covers the surface is critical to the stability of its structure and function. Dynamically speaking, the residence time of water at the surface is a signature of its mobility and binding. With femtosecond time resolution it is possible to unravel the shortest residence times which are key for the description of the hydration layer, static or dynamic. In this article we review these issues guided by experimental studies, from this laboratory, of polar hydration dynamics at the surfaces of two proteins (Subtilisin Carlsberg (SC) and Monellin). The natural probe tryptophan amino acid was used for the interrogation of the dynamics, and for direct comparison we also studied the behavior in bulk water - a complete hydration in 1 ps. We develop a theoretical description of solvation and relate the theory to the experimental observations. In this - theoretical approach, we consider the dynamical equilibrium in the hydration shell, defining the rate processes for breaking and making the transient hydrogen bonds, and the effective friction in the layer which is defined by the translational and orientational motions of water molecules. The relationship between the residence time of water molecules and the observed slow component in solvation dynamics is a direct one. For the two proteins studied, we observed a "bimodal decay" for the hydration correlation function, with two primary relaxation times: ultrafast, typically 1 ps or less, and longer, typically 15-40 ps, and both are related to the residence time at the protein surface, depending on the binding energies. We end by making extensions to studies of the denatured state of the protein, random coils, and the biomimetic micelles, and conclude with our thoughts on the relevance of the dynamics of native structures to their functions.

Estimation of elasticity map of soft biological tissue mimicking phantom using laser speckle contrast analysis

Scattering of coherent light from scattering particles causes phase shift to the scattered light. The interference of unscattered and scattered light causes the formation of speckles. When the scattering particles, under the influence of an ultrasound (US) pressure wave, vibrate, the phase shift fluctuates, thereby causing fluctuation in speckle intensity. We use the laser speckle contrast analysis (LSCA) to reconstruct a map of the elastic property (Young's modulus) of soft tissue-mimicking phantom. The displacement of the scatters is inversely related to the Young's modulus of the medium. The elastic properties of soft biological tissues vary, many fold with malignancy. The experimental results show that laser speckle contrast (LSC) is very sensitive to the pathological changes in a soft tissue medium. The experiments are carried out on a phantom with two cylindrical inclusions of sizes 6 mm in diameter, separated by 8 mm between them. Three samples are made. One inclusion has Young's modulus E of 40 kPa. The second inclusion has either a Young's modulus E of 20 kPa, or scattering coefficient of mu'(s), = 3.00 mm(-1) or absorption coefficient of mu(a) = 0.03 mm(-1). The optical absorption (mu(a)), reduced scattering (mu'(s)) coefficient, and the Young's modulus of the background are mu(a) = 0.01 mm(-1), mu'(s) = 1.00 mm(-1) and 12kPa, respectively. The experiments are carried out on all three phantoms. On a phantom with two inclusions of Young's modulus of 20 and 40 kPa, the measured relative speckle image contrasts are 36.55% and 63.72%, respectively. Experiments are repeated on phantoms with inclusions of mu(a) = 0.03 mm-1, E = 40 kPa and mu'(s) = 3.00 mm(-1). The results show that it is possible to detect inclusions with contrasts in optical absorption, optical scattering, and Young's modulus. Studies of the variation of laser speckle contrast with ultrasound driving force for various values of mu(a), mu'(s), and Young's modulus of the tissue mimicking medium are also carried out. (C) 2011 American Institute of Physics. doi:10.1063/1.3592352]

Reconstructing Solid Model from 2D Scanned Images of Biological Organs for Finite Element Simulation

This work presents a methodology to reconstruct 3D biological organs from image sequences or other scan data using readily available free softwares with the final goal of using the organs (3D solids) for finite element analysis. The methodology deals with issues such as segmentation, conversion to polygonal surface meshes, and finally conversion of these meshes to 3D solids. The user is able to control the detail or the level of complexity of the solid constructed. The methodology is illustrated using 3D reconstruction of a porcine liver as an example. Finally, the reconstructed liver is imported into the commercial software ANSYS, and together with a cyst inside the liver, a nonlinear analysis performed. The results confirm that the methodology can be used for obtaining 3D geometry of biological organs. The results also demonstrate that the geometry obtained by following this methodology can be used for the nonlinear finite element analysis of organs. The methodology (or the procedure) would be of use in surgery planning and surgery simulation since both of these extensively use finite elements for numerical simulations and it is better if these simulations are carried out on patient specific organ geometries. Instead of following the present methodology, it would cost a lot to buy a commercial software which can reconstruct 3D biological organs from scanned image sequences.

Haptic Feedback for Injecting Biological Cells using Miniature Compliant Mechanisms

We present a real-time haptics-aided injection technique for biological cells using miniature compliant mechanisms. Our system consists of a haptic robot operated by a human hand, an XYZ stage for micro-positioning, a camera for image capture, and a polydimethylsiloxane (PDMS) miniature compliant device that serves the dual purpose of an injecting tool and a force-sensor. In contrast to existing haptics-based micromanipulation techniques where an external force sensor is used, we use visually captured displacements of the compliant mechanism to compute the applied and reaction forces. The human hand can feel the magnified manipulation force through the haptic device in real-time while the motion of the human hand is replicated on the mechanism side. The images are captured using a camera at the rate of 30 frames per second for extracting the displacement data. This is used to compute the forces at the rate of 30 Hz. The force computed in this manner is sent at the rate of 1000 Hz to ensure stable haptic interaction. The haptic cell-manipulation system was tested by injecting into a zebrafish egg cell after validating the technique at a size larger than that of the cell.

Synthesis, biological studies of linear and branched arabinofuranoside-containing glycolipids and their interaction with surfactant protein A

Oligoarabinofuranoside-containing glycolipids relevant to mycobacterial cell wall components were synthesized in order to understand the functional roles of such glycolipids. A series of linear tetra-, hexa-, octa-and a branched heptasaccharide oligoarabinofuranosides, with 1 -> 2 and 1 -> 5 a-linkages between the furanoside residues, were synthesized by chemical methods from readily available monomer building blocks. Upon the synthesis of glycolipids, constituted with a double alkyl chain-substituted sn-glycerol core and oligosaccharide fragments, biological studies were performed to identify the effect of synthetic glycolipids on the biofilm formation and sliding motilities of Mycobacterium smegmatis. Synthetic glycolipids and arabinofuranosides displayed an inhibitory effect on the growth profile, but mostly on the biofilm formation and maturation. Similarly, synthetic compounds also influenced the sliding motility of the bacteria. Further, biophysical studies were undertaken, so as to identify the interactions of the glycolipids with a pulmonary surfactant protein, namely surfactant protein A (SP-A), with the aid of the surface plasmon resonance technique. Specificities of each glycolipid interacting with SP-A were thus evaluated. From this study, glycolipids were found to exhibit higher apparent association constants than the corresponding oligosaccharide portion alone, without the double alkyl group-substituted glycerol core.

The biological and structural characterization of Mycobacterium tuberculosis UvrA provides novel insights into its mechanism of action

Mycobacterium tuberculosis is an extremely well adapted intracellular human pathogen that is exposed to multiple DNA damaging chemical assaults originating from the host defence mechanisms. As a consequence, this bacterium is thought to possess highly efficient DNA repair machineries, the nucleotide excision repair (NER) system amongst these. Although NER is of central importance to DNA repair in M. tuberculosis, our understanding of the processes in this species is limited. The conserved UvrABC endonuclease represents the multi-enzymatic core in bacterial NER, where the UvrA ATPase provides the DNA lesion-sensing function. The herein reported genetic analysis demonstrates that M. tuberculosis UvrA is important for the repair of nitrosative and oxidative DNA damage. Moreover, our biochemical and structural characterization of recombinant M. tuberculosis UvrA contributes new insights into its mechanism of action. In particular, the structural investigation reveals an unprecedented conformation of the UvrB-binding domain that we propose to be of functional relevance. Taken together, our data suggest UvrA as a potential target for the development of novel anti-tubercular agents and provide a biochemical framework for the identification of small-molecule inhibitors interfering with the NER activity in M. tuberculosis.

Biological and materials properties of various cholesterol based systems

Liposomes composed of cationic lipids have become very popular gene delivery vehicles. A great deal of research is being pursued to make efficient vectors by varying their molecular architecture. Cholesterol being ubiquitous component in most of the animal cell membranes is increasingly being used as a hydrophobic segment of synthetic cationic lipids. In this review we describe various cholesterol based cationic lipids and focus on the effect of modifying various structural segments like linker and the head group of the cationic lipids on gene transfection efficiency with a special emphasis on the importance of ether linkage between cholesteryl backbone and the polar head group. Interaction of cationic cholesteryl lipids with dipalmitylphosphatidycholine membranes is also discussed here. Apart from cholesterol being an attractive scaffold in the drug/gene delivery vehicles, certain cholesteryl derivatives have also been shown to be attractive room temperature liquid-crystalline materials.

Injection-molded high-density polyethylene-hydroxyapatite-aluminum oxide hybrid composites for hard-tissue replacement: Mechanical, biological, and protein adsorption behavior

In this article, we report the mechanical and biocompatibility properties of injection-molded high-density polyethylene (HDPE) composites reinforced with 40 wt % ceramic filler [hydroxyapatite (HA) and/or Al2O3] and 2 wt % titanate as a coupling agent. The mechanical property measurements revealed that a combination of a maximum tensile strength of 18.7 MPa and a maximum tensile modulus of about 855 MPa could be achieved with the injection-molded HDPE20 wt % HA20 wt % Al2O3 composites. For the same composite composition, the maximum compression strength was determined to be 71.6 MPa and the compression modulus was about 660 MPa. The fractrography study revealed the uniform distribution of ceramic fillers in the semicrystalline HDPE matrix. The cytocompatibility study with osteoblast-like SaOS2 cells confirmed extensive cell adhesion and proliferation on the injection-molded HDPE20 wt % HA20 wt % Al2O3 composites. The cell viability analysis with the 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay revealed a statistically significant difference between the injection-molded HDPE20 wt % HA20 wt % Al2O3 composites and sintered HA for various culture durations of upto 7 days. The difference in cytocompatibility properties among the biocomposites is explained in terms of the difference in the protein absorption behavior. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

From anomalies in neat liquid to structure, dynamics and function in the biological world

Water brings its remarkable thermodynamic and dynamic anomalies in the pure liquid state to biological world where water molecules face a multitude of additional interactions that frustrate its hydrogen bond network. Yet the water molecules participate and control enormous number of biological processes in manners which are yet to be understood at a molecular level. We discuss thermodynamics, structure, dynamics and properties of water around proteins and DNA, along with those in reverse micelles. We discuss the roles of water in enzyme kinetics, in drug-DNA intercalation and in kinetic-proof reading ( the theory of lack of errors in biosynthesis). We also discuss how water may play an important role in the natural selection of biomolecules. (C) 2011 Elsevier B. V. All rights reserved.