Department of Bioscience & Bioengineering

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IIT Jodhpur

Present study reports synthesis and characterization of an enzymatically crosslinked injectable gel (iGel) suitable for cell based bone tissue engineering application. The gel comprises of carboxymethyl-chitosan (CMC)/gelatin/nano-hydroxyapatite (nHAp) susceptible to tyrosinase/p-cresol mediated in situ gelling at physiological temperature. Study revealed that a combination of tyrosinase (60U) and p-cresol (2 mM) as crosslinking agents yield rigid gels at physiological temperature when applied to CMC/gelatin within 35 min in presence or absence of nHAp. Rheological study in conjugation with FT-IR analysis showed that an increase in CMC concentration in the gel leads to higher degree of crosslinking and higher strength. Scanning electron microscopy showed that pore sizes of iGels increased with higher gelatin concentration. In vitro study of osteoblast cell proliferation and differentiation showed that, although all iGels are supportive towards the growth of primary osteoblast cells, GC1:1 supported cellular differentiation to the maximum. Application of iGels in mice revealed that stability of the in situ formed gels depends on the degree of crosslinking and CMC concentration. In conclusion, the iGels may be used in treating irregular small bone defects with minimal clinical invasion as well as for bone cell delivery. © 2011 Elsevier B.V. All rights reserved.

World University root node

Materials Science and Engineering C

Enzymatically crosslinked carboxymethyl-chitosan/gelatin/nano- hydroxyapatite injectable gels for in situ bone tissue engineering application

Identification and study of genetic variation in recently admixed populations not only provides insight into historical population events but also is a powerful approach for mapping disease loci. We studied a population (OG-W-IP) that is of African-Indian origin and has resided in the western part of India for 500 years; members of this population are believed to be descendants of the Bantu-speaking population of Africa. We have carried out this study by using a set of 18,534 autosomal markers common between Indian, CEPH-HGDP, and HapMap populations. Principal-components analysis clearly revealed that the African-Indian population derives its ancestry from Bantu-speaking west-African as well as Indo-European-speaking north and northwest Indian population(s). STRUCTURE and ADMIXTURE analyses show that, overall, the OG-W-IPs derive 58.7% of their genomic ancestry from their African past and have very little inter-individual ancestry variation (8.4%). The extent of linkage disequilibrium also reveals that the admixture event has been recent. Functional annotation of genes encompassing the ancestry-informative markers that are closer in allele frequency to the Indian ancestral population revealed significant enrichment of biological processes, such as ion-channel activity, and cadherins. We briefly examine the implications of determining the genetic diversity of this population, which could provide opportunities for studies involving admixture mapping. © 2011 by The American Society of Human Genetics. All rights reserved.

Fulltext

American Journal of Human Genetics

Recent admixture in an Indian population of african ancestry

Long-term injuries to the dorsal columns of the spinal cord at cervical levels result in large-scale somatotopic reorganization of the somatosensory areas of the cortex and the ventroposterior nucleus of the thalamus. As a result of this reorganization, intact inputs from the face expand into the deafferented hand representations. Dorsal column injuries also result in permanent deficits in the use of digits for precision grip and a loss of fractionated movements of the digits. We determined whether the chronic loss of sensory inputs and the behavioral deficits caused by lesions of the dorsal columns in adult macaque monkeys affect organization of the motor cortex. The results show that, in the primary motor cortex, intracortical microstimulation evokes extension - flexion movements of the thumb at significantly fewer sites compared with the normal monkeys. There is a corresponding increase in the adduction - abduction movements. Furthermore, there is a significant increase in the thresholds of the currents required to evoke movements of the digits. Thus, long-term sensory loss in adult monkeys does not change the overall topography of the movement representation in the motor cortex but results in changes in the details of movement representations. Copyright © 2011 the authors.

Journal of Neuroscience

Reorganization of the primary motor cortex of adult macaque monkeys after sensory loss resulting from partial spinal cord injuries

Long-lived humoral immune responses depend upon the generation of memory B cells and long-lived plasma cells during the germinal center (GC) reaction. These memory compartments, characterized by class-switched IgG and high-affinity Abs, are the basis for successful vaccination. We report that a new member of the plexin family of molecules, plexin-D1, controls the GC reaction and is required for secondary humoral immune responses. Plexin-D1 was not required for B cell maturation, marginal zone precursor development, dark and light zone formation, Igλ+ and Igκ+ B cell skewing, B1/B2 development, and the initial extrafollicular response. Plexin-D1 expression was increased following B cell activation, and PlxnD1-/- mice exhibited defective GC reactions during T-dependent immune activation. PlxnD1-/- B cells showed a defect in migration toward the GC chemokines, CXCL12, CXCL13, and CCL19. Accordingly, PlxnD1-/- mice exhibited defective production of IgG1 and IgG2b, but not IgG3 serum Ab, accompanied by reductions in long-lived bone marrow plasmacytes and recall humoral memory responses. These data show a new role for immune plexins in the GC reaction and generation of immunologic memory. Copyright © 2011 by The American Association of Immunologists, Inc.

Journal of Immunology

Plexin-D1 is a novel regulator of germinal centers and humoral immune responses

Background: Partial Trisomy 11q syndrome (or Duplication 11q) has defined clinical features and is documented as a rare syndrome by National Organization of Rare Disorders (NORD). Deletion 1q44 (or Monosomy 1q44) is a well-defined syndrome, but there is controversy about the genes lying in 1q44 region, responsible for agenesis of the corpus callosum. We report a female child with the rare Partial Trisomy 11q syndrome and Deletion 1q44 syndrome. The genomic imbalance in the proband was used for molecular characterization of the critical genes in 1q44 region for agenesis of corpus callosum. Some genes in 11q14q25 may be responsible for laryngomalacia. Results: We report a female child with dysmorphic features, microcephaly, growth retardation, seizures, acyanotic heart disease, and hand and foot deformities. She had agenesis of corpus callosum, laryngomalacia, anterior ectopic anus, esophageal reflux and respiratory distress. Chromosome analysis revealed a derivative chromosome 1. Her karyotype was 46,XX,der(1)t(1;11)(q44;q14)pat. The mother had a normal karyotype and the karyotype of the father was 46,XY,t(1;11)(q44;q14). SNP array analysis showed that the proband had a 54 Mb duplication of 11q14q25 and a 0.9 Mb deletion of the submicroscopic subtelomeric 1q44 region. Fluorescence Insitu Hybridisation confirmed the duplication of 11qter and deletion of 1qter. Conclusion: Laryngomalacia or obstruction of the upper airway is the outcome of increased dosage of some genes due to Partial Trisomy 11q Syndrome. In association with other phenotypic features, agenesis of corpus callosum appears to be a landmark phenotype for Deletion 1q44 syndrome, the critical genes lying proximal to SMYD3 in 1q44 region. © 2011 Lall et al; licensee BioMed Central Ltd.

Molecular Cytogenetics

A 54 Mb 11qter duplication and 0.9 Mb 1q44 deletion in a child with laryngomalacia and agenesis of corpus callosum

Briefings in Functional Genomics

From 'JUNK' to just unexplored noncoding knowledge: The case of transcribed alus

Clustering is one of the important analysis in functional genomics that discovers groups of co-expressed genes from micro array data. In this paper, the application of rough-fuzzy c-means (RFCM)algorithm is presented to discover co-expressed gene clusters. One of the major issues of the RFCM based micro array data clustering is how to select initial prototypes of different clusters. To overcome this limitation, a method is proposed to select initial cluster centers. It enables the RFCM algorithm to converge to an optimum or near optimum solutions and helps to discover co-expressed gene clusters. A method is also introduced based on Dunn's cluster validity index to identify optimum values of different parameters of the initialization method and the RFCM algorithm. The effectiveness of the RFCM algorithm, along with a comparison with other related methods, is demonstrated on five yeast gene expression time-series data sets using Silhouette index, Davies-Bould in index, and gene ontology based analysis. © 2011 IEEE.

Proceedings - 2011 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2011

Microarray time-series data clustering using rough-fuzzy c-means algorithm

We introduce a stochastic model to study the problem of time evolution and outcome of simple two-party competitions or battles on a lattice where each party randomly deploys its constituents or elements to the lattice. The elements have assigned strength levels that determine how competitive or effective they are against the opponent. In our models, the elements neutralize one another when they are at the same site with a combination of strength levels and numbers determining which one gains control of the site. The competitions last until complete dominance has been established by one side by eliminating the opponents or a draw is achieved (unless the time evolution is terminated via some ad hoc condition). A Markov chain approach is used to describe the time-dependent dynamics of such competitions. The advantage of the approach is that it allows us to develop a theoretical framework for describing competitive systems where a combination of random and correlated events decide the outcome. We use the approach here for studies of highly contentious stochastic battles and for that of a battle with correlated events along with stochastic events. We present the method, a simple illustrative example on how the method works and close by considering two non-trivial cases including one with a combination of stochasticity and correlations. © 2011 Elsevier B.V. All rights reserved.

Physica A: Statistical Mechanics and its Applications

Dynamics of stochastic and nearly stochastic two-party competitions

We modify the formulation of Hertz contact theory between two elastic half-solids with axial symmetry and show that these modifications to Hertz's original framework allow the development of force laws of the form Fzn, 1&lt;n&lt;∞, where F is the force and z is the distance between the centers of the two solids. The study suggests that it may be possible to design physical systems that can realize such force laws. We let the half-solids be characterized by radii of curvatures R1 and R2 and invoke a factor m0 to describe any aspect ratio in the two bodies, all being valid near the contact surface. We let the x-y plane be the contact surface with an averaged pressure across the same as opposed to a pressure profile that depends on the contact area of a nonconformal contact as originally used by Hertz. We let the z axis connect the centers of the masses and define z 1,2=xα/R1,2α-1+yα/(mR1,2)α -1, where z1,2≥0 refers to the compression of bodies 1, 2, α1, m0, x,y≥0. The full cross section can be generated by appropriate reflections using the first quadrant part of the area. We show that the nonlinear repulsive force is F=azn, where n=1+1/α, and z=z 1+z2 is the overlap and we present an expression for a=f(E,σ,m,α,R1,R2) with E and σ as Young's modulus and the Poisson ratio, respectively. For α=2,∞, to similar geometry-dependent constants, we recover Hertz's law and the linear law, describing the repulsion between compressed spheres and disks, respectively. The work provides a connection between the contact geometry and the nonlinear repulsive law via α and m. © 2011 American Physical Society.

Physical Review E - Statistical, Nonlinear, and Soft Matter Physics

Nonlinear repulsive force between two solids with axial symmetry

Improving on organic photosensitizers: The photoexcitation of metal nanoparticles results in the formation of singlet oxygen and its phosphorescence emission (see picture). As the nanoparticles are resistant to both photoinduced and enzymatic degradation and also have impressively high extinction coefficients, these findings may have an impact on techniques for the generation of singlet oxygen in biological settings. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.