A systems perspective of host-pathogen interactions: predicting disease outcome in tuberculosis

The complex web of interactions between the host immune system and the pathogen determines the outcome of any infection. A computational model of this interaction network, which encodes complex interplay among host and bacterial components, forms a useful basis for improving the understanding of pathogenesis, in filling knowledge gaps and consequently to identify strategies to counter the disease. We have built an extensive model of the Mycobacterium tuberculosis host-pathogen interactome, consisting of 75 nodes corresponding to host and pathogen molecules, cells, cellular states or processes. Vaccination effects, clearance efficiencies due to drugs and growth rates have also been encoded in the model. The system is modelled as a Boolean network. Virtual deletion experiments, multiple parameter scans and analysis of the system's response to perturbations, indicate that disabling processes such as phagocytosis and phagolysosome fusion or cytokines such as TNF-alpha and IFN-gamma, greatly impaired bacterial clearance, while removing cytokines such as IL-10 alongside bacterial defence proteins such as SapM greatly favour clearance. Simulations indicate a high propensity of the pathogen to persist under different conditions.

Comparative Study of Vocal Communication in Two Asian Leaf Monkeys, Presbytis johnii and Presbytis entellus

This paper presents comparative data on the vocal communication of two Asian leaf monkeys, the Nilgiri langur (Presbytis johnii) and South Indian common langur (Presbytis entellus), based on sound recordings and behavioural observations of free-ranging groups. Spectrographical analyses revealed a repertoire of 18 basic patterns for Nilgiri langurs, and 21 basic patterns for common langurs. The repertoires of the two langur species consist of both discretely structured vocal patterns, in which alterations of the physical parameters are restricted to intra-class variation, and those in which structural variations cause intergradation between different sections of the repertoire. Qualitative assessments of group scans indicate that in both species vocal behaviour is characterized by pronounced sex-differences in the use of the different elements of the vocal repertoire. Comparison of data available from different populations of P. entellus suggests population-specific modifications on both structural and behavioural levels. Moreover, characteristic elements of the vocal systems of the two Asian species demonstrate striking similarities to those described for the African black-and-white colobus.

Characterization of foot-and-mouth disease virus types Ο and Asia 1 RNA

Foot-and-mouth disease is an acute and highly contagious febrile disease affecting cloven-footed animals. Identification of the foot-and-mouth disease virus (FMDV), the causative agent of the disease, posed problems because of the occurrence of many types and subtypes of the virus. A molecular approach based on oligonucleotide mapping of FMDV RNA has been used for the identification and characterization of virus isolates obtained in a disease outbreak (King et al., 1981). One-dimensional oligonucleotide mapping was used for rapid analysis of FMDV RNA (LaTorre et al., 1982). FMDV types Ο and Asia 1 of Indian origin are being routinely used for vaccine production in India. This report presents the differences between FMDV types Ο and Asia 1 at molecular level based on one-dimensional oligonucleotide mapping of virus-induced poly (A) RNA.

Antipyretic and antibacterial activity of Chloranthus erectus (Buch.-Ham.) Verdcourt leaf extract: A popular folk medicine of Arunachal Pradesh

Objective : The main objective of this work was to study the antipyretic and antibacterial activity of C. erectus (Buch.-Ham.) Verdcourt leaf extract in an experimental albino rat model. Materials and Methods : The methanol extract of C. erectus leaf (MECEL) was evaluated for its antipyretic potential on normal body temperature and Brewers yeast-induced pyrexia in albino rats model. While the antibacterial activity of MECEL against five Gram (-) and three Gram () bacterial strains and antimycotic activity was investigated against four fungi using agar disk diffusion and microdilution methods. Result : Yeast suspension (10 mL/kg b.w.) elevated rectal temperature after 19 h of subcutaneous injection. Oral administration of MECEL at 100 and 200 mg/kg b.w. showed significant reduction of normal rectal body temperature and yeast-provoked elevated temperature (38.8 0.2 and 37.6 0.4, respectively, at 2-3 h) in a dose-dependent manner, and the effect was comparable to that of the standard antipyretic drug-paracetamol (150 mg/kg b.w.). MECEL at 2 mg/disk showed broad spectrum of growth inhibition activity against both groups of bacteria. However, MECEL was not effective against the yeast strains tested in this study. Conclusion : This study revealed that the methanol extract of C. erectus exhibited significant antipyretic activity in the tested models and antibacterial activity as well, and may provide the scientific rationale for its popular use as antipyretic agent in Khamptiss folk medicines.

Modelling studies on neurodegenerative disease causing triplet repeat sequences d(CGG/GCC) and d(CAG/CTG): Duplexes vs Quadruplexes

Model building and molecular mechanics studies have been carried out to examine the potential structures for d(GGC/GCC)5 and d(CAG/CTG)5 that might relate to their biological function and association with triplet repeat expansion diseases. Model building studies suggested that hairpin and quadruplex structures could be formed with these repeat sequences. Molecular mechanics studies have demonstrated that the hairpin and hairpin dimmer structures of triplet repeat sequences formed by looping out of the two strands are as favourable as the corresponding B-DNA type hetero duplex structures. Further, at high salt condition, Greek key type quadruplex structures are energetically comparable with hairpin dimer and B-DNA type duplex structures. All tetrads in the quadruplex structures are well stacked and provide favourable stacking energy values. Interestingly, in the energy minimized hairpin dimer and Greek key type quadruplex structures, all the bases even in the non-G tetrads are cyclically hydrogen bonded, even though the A, C and T-tetrads were not hydrogen bonded in the starting structures.

A Genetic Study of Immunoglobulin E and Atopic Disease Based on Families Ascertained through Asthmatic Children

In order to investigate the modes of inheritance of serum immunoglobulin E (IgE) levels and atopic disease, serum IgE levels and data on allergic disease were obtained from 42 families ascertained through asthmatic children visiting an allergy clinic. Although the mean IgE levels were elevated (mean 637 U/ml), the prevalence of atopic disease in this population was surprisingly low. When the data were analyzed using complex segregation analysis, no major locus could be detected. Moreover, the polygenic heritability was unexpectedly small even though the correlation between serum IgE levels and the liability to atopic disease was around 0.4. Given this unusual set of findings, it is postulated that parasitic infections in this population have (in accordance with well-established results of parasitic disease) caused both elevated levels of serum IgE and a decreased prevalence of allergic disease with the possible masking of the various genetic components of serum IgE levels and atopic disease.

Boxicity of Leaf Powers

The boxicity of a graph G, denoted as boxi(G), is defined as the minimum integer t such that G is an intersection graph of axis-parallel t-dimensional boxes. A graph G is a k-leaf power if there exists a tree T such that the leaves of the tree correspond to the vertices of G and two vertices in G are adjacent if and only if their corresponding leaves in T are at a distance of at most k. Leaf powers are used in the construction of phylogenetic trees in evolutionary biology and have been studied in many recent papers. We show that for a k-leaf power G, boxi(G) a parts per thousand currency sign k-1. We also show the tightness of this bound by constructing a k-leaf power with boxicity equal to k-1. This result implies that there exist strongly chordal graphs with arbitrarily high boxicity which is somewhat counterintuitive.

Characterization and immune response of a protein produced by a cDNA clone of foot and mouth disease virus, type Asia 1 63/72

A 0.9 kb double stranded cDNA of foot and mouth disease virus (FMDV) Type Asia 1, 63/72 was cloned in an expression vector, pUR222. A protein of 38 kd was produced by the clone which reacted with the antibodies raised against the virus. A 20 kd protein which may be derived from the 38 kd protein contained the antigenic epitopes of the protein VP1 of the virus. Injection of 10-20 micrograms of the partially purified 38 and 20 kd proteins or a lysate of cells containing 240 micrograms of the proteins elicited high titers of FMDV specific antibodies in guinea pigs and cattle respectively. Also, at these concentrations, the proteins protected 5 of 8 guinea pigs and 3 of 8 cattle when challenged with a virulent virus.

Leaf flushing phenology and herbivory in a tropical dry deciduous forest, southern India

Patterns of leaf-flushing phenology of trees in relation to insect herbivore damage were studied at two sites in a seasonal tropical dry forest in Mudumalai, southern India, from April 1988 to August 1990. At both sites the trees began to flush leaves during the dry season, reaching a peak leaf-flushing phase before the onset of rains. Herbivorous insects emerged with the rains and attained a peak biomass during the wet months. Trees that flushed leaves later in the season suffered significantly higher damage by insects compared to those that flushed early or in synchrony during the peak flushing phase. Species whose leaves were endowed with physical defenses such as waxes suffered less damage than those not possessing such defenses. There was a positive association between the abundance of a species and leaf damage levels. These observations indicate that herbivory may have played a major role in moulding leaf flushing phenology in trees of the seasonal tropics.

Impaired conflict monitoring in Parkinson's disease patients during an oculomotor redirect task

Fallibility is inherent in human cognition and so a system that will monitor performance is indispensable. While behavioral evidence for such a system derives from the finding that subjects slow down after trials that are likely to produce errors, the neural and behavioral characterization that enables such control is incomplete. Here, we report a specific role for dopamine/basal ganglia in response conflict by accessing deficits in performance monitoring in patients with Parkinson's disease. To characterize such a deficit, we used a modification of the oculomotor countermanding task to show that slowing down of responses that generate robust response conflict, and not post-error per se, is deficient in Parkinson's disease patients. Poor performance adjustment could be either due to impaired ability to slow RT subsequent to conflicts or due to impaired response conflict recognition. If the latter hypothesis was true, then PD subjects should show evidence of impaired error detection/correction, which was found to be the case. These results make a strong case for impaired performance monitoring in Parkinson's patients.

Regeneration of plantlets from leaf disc cultures of rosewood: control of leaf abscission and shoot tip necrosis

A method for mass production of rosewood (Dalbergia latifolia Roxb.) trees through leaf disc organogenesis was developed and standardized. Compact callus was initiated from mature leaf discs on Murashige and Skoog (MS) basal medium supplemented with 1.0 mg 1?1 2,4-dichlorophenoxy acetic acid (2,4-D), 5.0 mg 1?1 ?-naphthaleneacetic acid (NAA), 1.0 mg 1?1 6-benzylaminopurine (BAP) and 10% coconut water (CW). High frequency (15�20 shoots/g callus) regeneration of shoot bud differentiation was obtained on MS (3/4 reduced major elements) or Woody Plant Medium (WPM) or modified Woody Plant Medium (mWPM) supplemented with BAP (5.0 mg 1?1) and NAA (0.5 mg 1?1). Leaf abscission and shoot tip necrosis was controlled using mWPM. About 90% of the excised shoots were rooted in the mWPM supplemented with 2.0 mg 1?1 ?-indolebutyric acid (IBA) and 1.0 mg 1?1 caffeic acid. The in vitro-raised rooted plantlets were hardened for successful transplantation to soil. The transplanted plants were exposed to various humidity conditions and 80% transplant success was achieved. The in vitro-raised leaf-regenerated plants grew normally and vigorously in soil.

Ring Resonators and Micro Fluidics: Novel Design for Drug/Disease Detection

MEMS systems are technologically developed from integrated circuit industry to create miniature sensors and actuators. Originally these semiconductor processes and materials were used to build electrical and mechanical systems, but expanded to include biological, optical fluidic magnetic and other systems 12]. Here a novel approach is suggested where in two different fields are integrated via moems, micro fluidics and ring resonators. It is well known at any preliminary stage of disease onset, many physiological changes occur in the body fluids like saliva, blood, urine etc. The drawback till now was that current calibrations are not sensitive enough to detect the minor physiological changes. This is overcome using optical detector techniques 1]. The basic concepts of ring resonators, with slight variations can be used for optical detection of these minute disease markers. A well known fact of ring resonators is that a change in refractive index will trigger a shift in the resonant wavelength 5]. The trigger for the wavelength shift in the case discussed will be the presence of disease agents. To trap the disease agents specific antibody has to be used (e. g. BSA).