A unique approach for protein secondary structure comparison under TOPS representation.

To unravel the intricate connection between protein function and protein structure, it is imperative to comprehensively evaluate protein secondary structure similarity from various perspectives. While numerous techniques have been suggested for comparing protein secondary structure elements (SSE), there continues to be a substantial need for finding alternative ways of comparing the same. In this paper, Topology of Protein Structure (TOPS) representations of protein secondary structures are considered to offer a new alignment-free method for evaluating similarities/dissimilarities of protein secondary structures. Initially, a two-dimensional numerical representation of the SSE is created, associating each point with a mass reflecting its frequency of occurrence. Then the means of coordinate values are determined by averaging weighted sums, and these mean values are subsequently used to calculate moments-of-inertia. Next, a four-component descriptor is generated out of the eigenvalues of the matrix and the mean values of the represented coordinates. Thereafter, Manhattan distance measure is used to obtain the distance matrix. This is finally applied to obtain the phylogenetic trees under the use of NJ method. SSE considered in the proposed method comprises 36-elements from the Chew-Kedem database giving five different taxa: globin, alpha-beta, tim-barrel, beta, and alpha. Phylogenetic trees were created for these SSE through the application of various methods: Clustal-Omega, LZ-Complexity, SED, TOPS + and TOC, to facilitate comparative analysis. Phylogenetic tree of the proposed method outperformed results of the previous methods when applied to the same SSE. Therefore, the method effectively constructs phylogenetic tree for analyzing protein secondary structure comparison.Communicated by Ramaswamy H. Sarma.

Biochemical Property Based Positional Matrix: A New Approach Towards Genome Sequence Comparison.

The growth of the genome sequence has become one of the emerging areas in the study of bioinformatics. It has led to an excessive demand for researchers to develop advanced methodologies for evolutionary relationships among species. The alignment-free methods have been proved to be more efficient and appropriate related to time and space than existing alignment-based methods for sequence analysis. In this study, a new alignment-free genome sequence comparison technique is proposed based on the biochemical properties of nucleotides. Each genome sequence can be distributed in four parameters to represent a 21-dimensional numerical descriptor using the Positional Matrix. To substantiate the proposed method, phylogenetic trees are constructed on the viral and mammalian datasets by applying the UPGMA/NJ clustering method. Further, the results of this method are compared with the results of the Feature Frequency Profiles method, the Positional Correlation Natural Vector method, the Graph-theoretic method, the Multiple Encoding Vector method, and the Fuzzy Integral Similarity method. In most cases, it is found that the present method produces more accurate results than the prior methods. Also, in the present method, the execution time for computation is comparatively small.

A new graph-theoretic approach to determine the similarity of genome sequences based on nucleotide triplets.

Methods of finding sequence similarity play a significant role in computational biology. Owing to the rapid increase of genome sequences in public databases, the evolutionary relationship of species becomes more challenging. But traditional alignment-based methods are found inappropriate due to their time-consuming nature. Therefore, it is necessary to find a faster method, which applies to species phylogeny. In this paper, a new graph-theory based alignment-free sequence comparison method is proposed. A complete-bipartite graph is used to represent each genome sequence based on its nucleotide triplets. Subsequently, with the help of the weights of edges of the graph, a vector descriptor is formed. Finally, the phylogenetic tree is drawn using the UPGMA algorithm. In the present case, the datasets for comparison are related to mammals, viruses, and bacteria. In most of the cases, the phylogeny in the present case is found to be more satisfactory as compared to earlier methods.

Genome sequence comparison under a new form of tri-nucleotide representation based on bio-chemical properties of nucleotides.

Genetic sequence analysis, classification of genome sequence and evolutionary relationship between species using their biological sequences, are the emerging research domain in Bioinformatics. Several methods have already been applied to DNA sequence comparison under tri-nucleotide representation. In this paper, a new form of tri-nucleotide representation is proposed for sequence comparison. The comparison does not depend on the alignment of the sequences. In this representation, the bio-chemical properties of the nucleotides are considered. The novelty of this method is that the sequences of unequal lengths are represented by vectors of the same length and each of the tri-nucleotide formed out of the given sequence has its unique representation. To validate the proposed method, it is verified on several data sets related to mammalians, viruses and bacteria. The results of this method are further compared with those obtained by methods such as probabilistic method, natural vector method, Fourier power spectrum method, multiple encoding vector method, and feature frequency profiles method. Moreover, this method produces accurate phylogeny in all the cases. It is also proved that the time complexity of the present method is less.

Optimal choice of k-mer in composition vector method for genome sequence comparison.

Several proteins and genes are members of families that share a public evolutionary. In order to outline the evolutionary relationships and to recognize conserved patterns, sequence comparison becomes an emerging process. The current work investigates critically the k-mer role in composition vector method for comparing genome sequences. Generally, composition vector methods using k-mer are applied under choice of different value of k to compare genome sequences. For some values of k, results are satisfactory, but for other values of k, results are unsatisfactory. Standard composition vector method is carried out in the proposed work using 3-mer string length. In addition, special type of information based similarity index is used as a distance measure. It establishes that use of 3-mer and information based similarity index provide satisfactory results especially for comparison of whole genome sequences in all cases. These selections provide a sort of unified approach towards comparison of genome sequences.

Role of latency period in viral infection: a pest control model.

The interrelationship of latency period in viral infection and overall infection process in host community are of critical importance in context of pest control programme. Both of them regulate the overall system stability as they are dynamically linked to predation by natural enemies in the system. The present paper deals with the role of latency period in viral infection through mathematical modeling and analysis. We propose a four dimensional mathematical model with delayed infection in pest community. It is shown that there exists a certain value of delay, say T( *) such that for T>T( *) the system exhibits global stability towards disease-free equilibrium. But for T

The role of viral infection in pest control: a mathematical study.

In this paper, we propose a mathematical model of viral infection in pest control. As the viral infection induces host lysis which releases more virus into the environment, on the average 'kappa' viruses per host, kappa e (1,infinity), so the 'virus replication parameter' is chosen as the main parameter on which the dynamics of the infection depends. There exists a threshold value kappa 0 beyond which the infection persists in the system. Still for increasing the value of kappa, the endemic equilibrium bifurcates towards a periodic solution, which essentially indicates that the viral pesticide has a density-dependent 'numerical response' component to its action. Investigation also includes the dependence of the process on predation of natural enemy into the system. A concluding discussion with numerical simulation of the model is also presented.

A more realistic approach to pest-management problem.

The paper deals with integrated pest management (IPM) of a single density-dependent pest affecting a single crop. The model is basically a prey-predator model, predator being the natural enemy of the pest. In addition, it also contains the growth equation of the affected crop. This dynamic model is subjected to biological control in the form of release of additional predators and chemical control in the form of spraying of pesticides. To consider the natural side effect of pesticide on fish living in the soil water, the model is further improved to accommodate the growth equation of the fishes in the soil water. The paper considers the optimal analysis of the model under two control parameters, one is the spraying of pesticide and other one is the release of predators; such optimal analysis under multi-control parameters is completely new of its kind.

An improved integrated pest management model under 2-control parameters (sterile male and pesticide).

The object of the present paper is to study an integrated pest management (IPM) problem in an agroecosystem (paddy-fish culture) through mathematical modeling and analysis, where release of sterile males and spraying of pesticide have been used as control measures for pest population. Using optimal analysis of the model, we have shown that restricted and proper use of control measures might enhance the crop production of the system in an economically viable way. The paper also considers the vulnerability of the underlined ecosystem due to the effect of temperature on the pest growth. Using Liapunov-like function, we have found out a suitable range of temperature, where this IPM strategy remains effective. Some important remarks have finally been made on the basis of numerical simulation.

Prevalence of anti HCV, HBsAg and HIV antibodies in high risk recipients of blood and blood products.

Along with hepatitis B virus (HBV) and human immunodeficiency virus (HIV), Hepatitis C virus (HCV) is emerging as a major transfusion hazard. 22 cases of haemophilia (A 19, B 3) and 20 cases of thalassaemia (2 16, E(2) 4) constituted the study group. Patients tested for anti HCV (using third generation ELISA), HBsAg and antibodies to HIV I and II. Prevalence of anti HCV was 54.5% in haemophilics and 5% in thalassaemics. HBsAg was detected in 9.09% haemophilics and 5% thalassaemics. No anti HIV was detected in this cohort. Anti HCV seropositivity in haemophilics has increased compare to previous studies.

Pest control through viral disease: mathematical modeling and analysis.

This paper deals with the mathematical modeling of pest management under viral infection (i.e. using viral pesticide) and analysis of its essential mathematical features. As the viral infection induces host lysis which releases more virus into the environment, on the average 'kappa' viruses per host, kappain(1,infinity), the 'virus replication parameter' is chosen as the main parameter on which the dynamics of the infection depends. We prove that there exists a threshold value kappa(0) beyond which the endemic equilibrium bifurcates from the free disease one. Still for increasing kappa values, the endemic equilibrium bifurcates towards a periodic solution. We further analyse the orbital stability of the periodic orbits arising from bifurcation by applying Poor's condition. A concluding discussion with numerical simulation of the model is then presented.

The activity of superoxide dismutase in hydroxyurea-treated E beta thalassemia.

AIM: To study the activity of superoxide dismutase (SOD) and the level of fetal hemoglobin (HbF) in hydroxyurea (HU)-treated E beta thalassaemia. METHODS: We have measured SOD level, HbF, mean corpuscular volume (MCV), packed cell volume (PCV) and hemoglobin (Hb) of E beta thalassaemia treated with HU (dose 30 mg/kg/day) for consecutive 90 days. RESULT: The increase of HbF synthesis without increase of Hb was observed in HU-treated patients. CONCLUSION: The decreased SOD level in long term and low dose of HU therapy in E beta thalassaemia may have some role to inhibit superoxide radical of erythrocyte. HU may act as inhibitor for oxidative damage of red cell in E beta thalassaemia.

Molecular characterization of hereditary persistence of foetal haemoglobin mutation by restriction fragment length polymorphism mapping.

Characterization of hereditary persistence of foetal haemoglobin (HPFH) mutation in a family from West Bengal, India, was carried out by analysing the structure of the 5'-Ggamma-Agamma-psibeta-delta-beta-3' globin gene region by using the restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) technique. The HPFH in this family was due to a deletion in the beta-globin gene cluster spanning at least from the Hin cII/5' psibeta to the Hin fI/3' beta RFLP site. This work indicates the importance of RFLP-PCR technique in characterization of the HPFH mutation.

Splenectomy and splenic slice grafting in the management of thalassemia.

Over the last decade and a half, we performed a splenectomy along with slice grafting of the spleen in 170 (beta28 and Ebeta 142) transfusion-dependent, high-risk thalassemic patients. Of these, 17 were selected for study of the fate of the grafts and their immune status before and after operation. The procedure had equally good advantages of splenectomy and immunoconservation as partial splenectomy, partial splenic embolization, or partial splenic dearterialization, if not better, but none of the disadvantages of the other procedures.

O-acetyl sialic acid specific IgM in childhood acute lymphoblastic leukaemia.

Initial studies have revealed an enhanced surface expression of O-acetylated sialoglycoconjugates (O-AcSGs) on lymphoblasts concomitant with high titres of IgG in childhood Acute Lymphoblastic Leukaemia (ALL) (Mandal C, Chatterjee M, Sinha D, Br J Haematol 110, 801-12, 2000). In our efforts to identify disease specific markers for ALL, we have affinity-purified IgM directed against O-AcSGs that reacts with three disease specific O-AcSGs present on membrane proteins derived from peripheral blood mononuclear cells (PBMC) of ALL patients. Antibody specificity towards O-AcSGs was confirmed by selective binding to erythrocytes bearing surface O-AcSGs, decreased binding with de-O-acetylated BSM and following pretreatment with O-acetyl esterase. Competitive inhibition ELISA demonstrated a higher avidity of IgM for O-AcSG than IgG. Flow cytometry demonstrated the diagnostic potential of purified O-AcSA IgM as binding was specific with ALL patients and minimal with other haematological disorders and normal individuals. It therefore may be adopted as a non-invasive approach for detection of childhood ALL. Taken together, the data indicates that carbohydrate epitopes having terminal O-AcSA alpha2 --> 6 GalNAc determinants induce disease specific IgG and IgM, potentially useful molecular markers for childhood ALL.

Identification and purification of cytolytic antibodies directed against O-acetylated sialic acid in childhood acute lymphoblastic leukemia.

Sialic acids typically present as terminal sugars of oligo-saccharides are reported to be modified by O-acetylation at the C-9 position on lymphoblasts of childhood acute lymphoblastic leukemia (ALL) patients (Sinha et al., 1999a, Leukaemia, 13, 119-125). We now report high titers of IgG antibodies directed against O-acetylated derivatives of sialic acids (O-AcSA) in serum of ALL patients. These antibodies were purified using bovine submaxillary mucin (BSM) and the IgG distribution was confined to IgG(1)and IgG(2)subclasses; their binding was totally abolished with de-O-acetylation confirming their specificity towards O-AcSA determinants. Flow cytometry demonstrated binding of these antibody fractions to peripheral blood mononuclear cells (PBMC) of both T- and B-ALL patients having increased cell surface 9-O-AcSA determinants. Western blotting of membranes derived from PBMC of ALL patients confirmed binding of the antibody to O-acetylated sialoglycoconjugates corresponding to 144, 135, 120, 90, and 36 kDa whereas binding to PBMC from normal individuals corresponded to 144 and 36 kDa. Specificity of the antibody fraction towards 9-O-AcSA was substantiated by hemagglutination and hemagglutination-inhibition assays. The antibody purified from ALL serum selectively mediates complement dependent cytolysis of lymphoblasts expressing O-AcSAs and thereby possibly confers passive protection. The enhanced anti O-AcSA antibody levels allowed for development of a serodiagnostic assay (BSM-ELISA) specific for ALL. Minimal crossreactivity was observed with other hematological disorders like acute myeloid leukemia (n = 16), chronic myeloid leukemia (n = 6), chronic lymphocytic leukemia (n = 7) and non-Hodgkin's lymphoma (n = 3) as well as normal healthy individuals (n = 28). The BSM-ELISA therefore provides a simple, noninvasive alternative diagnostic approach for ALL and merits clinical consideration.

Lipid peroxidation and spectrin of RBC membrane in hydroxyurea treated Eß thalassaemia.

The aim of the present work is to understand the effect of low dose of hydroxyurea (HU) therapy on oxidative damage of RBC membrane in non-transfused Eß thalassaemia. HU was administered at a dose of 30 mg/kg/day for 90 consecutive days. The percentage of spectrin and the level of malondialdehyde (MDA), fetal hemoglobin (HbF), hemoglobin (Hb) and packed cell volume (PCV) were measured. The HbF level was significantly increased after 90 days of HU therapy. MDA level of RBC membrane was decreased. There was no change in PCV, Hb and spectrin content of RBC membrane after HU therapy for 90 days in Eß thalassaemia. Increment of HbF in HU treated Eß patient may have some role on the correction of oxidative damage of RBC membrane by inhibiting further degradation of spectrin and by decreasing lipid peroxidation of red cell membrane.

A colorimetric assay to evaluate the chemotherapeutic response of children with acute lymphoblastic leukemia (ALL) employing achatininH: a 9-O-acetyl sialic acid binding lectin.

Employing a 9-O-acetyl sialic acid binding lectin, Achatinin(H) (ATNH), we have reported a non-invasive, blood based lymphoproliferation assay which measures the maximal lymphoproliferative dose (MLD) of ATN(H) to assess the status of 9-O-acetylated sialoglycoconjugates (9-OAcSGs) in patients with Acute lymphoblastic leukemia (ALL) (Mandal C, Sinha D, Sharma V, Bhattacharya DK. O-acetyl sialic acid binding lectin, as a probe for detection of subtle changes on the cell surface induced during acute lymphoblastic leukemia [ALL] and its clinical application. Ind J Biochem Biophys 1997;34:82; Sinha D, Mandal C, Bhattacharya DK. Development of a simple blood based lymphoproliferation assay to assess the clinical status of patients with acute lymphoblastic leukemia. Leuk Res 1999;13:309-312; Sinha D, Mandal C, Bhattacharya DK. A novel method for prognostic evaluation of childhood acute lymphoblastic leukemia. Leukemia 1999;13[in press]). Although the expression of 9-OAcSGs clearly serves as an index of treatment outcome, the assay has limitations in that it requires radioisotopes, i.e. [3H]-TdR. Therefore a colorimetric assay was developed as an alternative approach. The pre-treatment MLD, as measured by the colorimetric assay, was 0.15 +/- 0.02 microg which progressively increased during consolidation therapy (1.40 +/- 0.39 microg), maintenance therapy (4.20 +/- 1.60 microg) and in followed-up cases (5.20 +/- 0.43 microg) but sharply declined following relapse (0.25 +/- 0.02 microg). The colorimetric assay also showed a good correlation with radiometric assay (r = + 0.93) and their mean coefficient of inter-assay precision were also comparable (15.53% versus 14.86%). We therefore propose that the colorimetric assay is a safe, non-radiometric, user-friendly alternative for assessing individual chemotherapeutic responses in childhood ALL.

Development of a simple, blood based lymphoproliferation assay to assess the clinical status of patients with acute lymphoblastic leukemia.

Although childhood acute lymphoblastic leukemia (ALL) is highly responsive to chemotherapy, reliable techniques are needed to determine treatment outcome and predict relapse. Employing a 9-O-acetyl sialic acid binding lectin, ATN(H), we have identified two 9-O-acetylated sialogycoconjugates (9-OAcSGs) as novel biomarkers expressed selectively on leukemic blasts of ALL patients. Presently, we report a non-invasive, blood based lymphoproliferation assay, which employs the maximal lymphoproliferative dose of ATN(H) (MLD) to assess the status of 9-OAcSGs with progressive therapy. A low MLD (0.18 +/- 0.01 microg) in untreated patients reflects increased expression of 9-OAcSGs which decline following therapy (MLD = 2.10 +/- 0.60 microg), persist during maintenance therapy (MLD = 4.50 +/- 1.60 microg)/follow-up (MLD = 5.50 +/- 0.85 microg) and are re-induced with relapse (MLD = 0.25 +/- 0.01 microg). Since the assay detects lymphoblasts with a sensitivity of 10(-4), shows no cross-reactivity with other hematological disorders (n = 48) and has been tested in 212 patients, it meets clinical consideration.