42 research outputs found

    Truncated hemoglobin, HbN, is post-translationally modified in Mycobacterium tuberculosis and modulates host-pathogen interactions during intracellular infection

    Get PDF
    Mycobacterium tuberculosis (Mtb) is a phenomenally successful human pathogen having evolved mechanisms that allow it to survive within the hazardous environment of macrophages and establish long term, persistent infection in the host against the control of cell-mediated immunity. One such mechanism is mediated by the truncated hemoglobin, HbN, of Mtb that displays a potent O2-dependent nitric oxide dioxygenase activity and protects its host from the toxicity of macrophage-generated nitric oxide (NO). Here we demonstrate for the first time that HbN is post-translationally modified by glycosylation in Mtb and remains localized on the cell membrane and the cell wall. The glycan linkage in the HbN was identified as mannose. The elevated expression of HbN in Mtb and M. smegmatis facilitated their entry within the macrophages as compared with isogenic control cells, and mutation in the glycan linkage of HbN disrupted this effect. Additionally, HbN-expressing cells exhibited higher survival within the THP-1 and mouse peritoneal macrophages, simultaneously increasing the intracellular level of proinflammatory cytokines IL-6 and TNF-α and suppressing the expression of co-stimulatory surface markers CD80 and CD86. These results, thus, suggest the involvement of HbN in modulating the host-pathogen interactions and immune system of the host apart from protecting the bacilli from nitrosative stress inside the activated macrophages, consequently driving cells toward increased infectivity and intracellular survival

    MetaMesh: A hierarchical computational model for design and fabrication of biomimetic armored surfaces

    Get PDF
    Many exoskeletons exhibit multifunctional performance by combining protection from rigid ceramic components with flexibility through articulated interfaces. Structure-to-function relationships of these natural bioarmors have been studied extensively, and initial development of structural (load-bearing) bioinspired armor materials, most often nacre-mimetic laminated composites, has been conducted. However, the translation of segmented and articulated armor to bioinspired surfaces and applications requires new computational constructs. We propose a novel hierarchical computational model, MetaMesh, that adapts a segmented fish scale armor system to fit complex “host surfaces”. We define a “host” surface as the overall geometrical form on top of which the scale units are computed. MetaMesh operates in three levels of resolution: (i) locally—to construct unit geometries based on shape parameters of scales as identified and characterized in the Polypterus senegalus exoskeleton, (ii) regionally—to encode articulated connection guides that adapt units with their neighbors according to directional schema in the mesh, and (iii) globally—to generatively extend the unit assembly over arbitrarily curved surfaces through global mesh optimization using a functional coefficient gradient. Simulation results provide the basis for further physiological and kinetic development. This study provides a methodology for the generation of biomimetic protective surfaces using segmented, articulated components that maintain mobility alongside full body coverage.Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (Contract No. W911NF-13-D-0001)United States. Army Research Office (Institute for Collaborative Biotechnologies (ICB), contract no. W911NF-09-D-0001)United States. Department of Defense (National Security Science and Engineering Faculty Fellowship Program (Grant No. N00244-09-1-0064)

    Biological and bio-inspired morphometry as a route to tunable and enhanced materials design

    No full text
    Thesis: Ph. D., Massachusetts Institute of Technology, Department of Materials Science and Engineering, 2016.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references.Structural materials in nature integrate classical materials selection rules with morphometry (geometry or shape-based rules) to create high-performance, multi-functional structures that exhibit tunable properties through extraordinary complexity, hierarchy, and precise structural control. This thesis explores the use of morphometry as a materials design parameter through the development of bio-inspired, flexible composite armor based on the articulated exoskeleton of an armored fish, Polypterus senegalus, which achieves uniform coverage and protection from predatory threats without restricting flexibility. First, the functional implications of shape and shape variation are examined as materials design parameters within the biological exoskeleton using a new method that integrates continuum strain analysis with landmark-based geometric morphometric analysis in 2D and 3D. Bioinspired flexible composite prototypes are fabricated using multi-material 3D printing and tested under passive loading (self-weight) and active loading (bending) to examine how the shape of scales contributes to local, interscale mobility mechanisms that generate anisotropic, global mechanical behavior. With one prototype design scheme, a wide array of mechanical behavior is generated with stiffness ranging over several orders of magnitude, including 'mechanical invisibility' of the scales, showing how morphometry can tune flexibility without varying the constituent materials. Finally, finite element models simulating the bending experiments are created to establish a computational framework for analyzing the mechanical response of the prototypes. The finite element models are then extended to examine the effect of different loading conditions, scale morphometry, multi-material architecture, and constituent material properties. The results show how morphometric-enabled materials design, inspired by structural biological materials, can allow for tunable behavior in flexible composites made of segmented scale assemblies to achieve enhanced user mobility, custom fit, and flexibility around joints for a variety of protective applications.by Swati Varshney.Ph. D

    Improved Electromagnetic Shielding Performance of Lightweight Compression Molded Polypyrrole/Ferrite Composite Sheets

    No full text
    An attempt has been made to design lightweight polypyrrole/carbon fibers and polypyrrole/carbon fibers/ferrofluid (Fe3O4 particles) composite sheets using novolac resin via compression molding for electromagnetic shielding applications. The optimized formulation has been achieved to get an excellent combination of thermal, mechanical, and electrical properties of the composite sheet. Structural and morphological studies were carried out by x-ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy. Polypyrrole/carbon fibers composite sheets shows maximum flexural strength and a flexural modulus of 62.4 +/- 1 MPa and 0.60 +/- 0.02 GPa, respectively, with total shielding effectiveness of 22.8 dB in the Ku-band (12.4-18 GHz) but when ferrofluid is added to the polypyrrole/carbon fibers composite system, flexural strength increases to 92.3 +/- 1 MPa and the same trend has been observed for flexural modulus with a value of 0.65 +/- 0.04 GPa. This multiphase lightweight polypyrrole composite sheet having 34 vol.% of carbon fibers and 4 vol.% of Fe3O4 nanoparticles offers total shielding effectiveness of 31.9 dB (> 99.99% attenuation) in the Ku-band (12.4-18 GHz) frequency range with a thickness of similar to 1.25 mm. This is accredited to high dielectric losses and magnetic losses in conducting composite sheets. The observed results suggest that lightweight compression molded polypyrrole composite sheets could be a potential commercial alternative for electromagnetic shielding applications

    OECD-407 Driven 28-day-repeated-dose non-clinical safety evaluation of Tinospora cordifolia (Giloy) stem aqueous extract in Sprague-Dawley rats under GLP compliance

    Get PDF
    Introduction:Tinospora cordifolia (Wild.) Hook.f. & Thomson (Giloy), has been widely used in the Ayurvedic system of medicine. However, some sporadic under-powered case studies have recently reported Tinospora cordifolia associated toxicity. Thus, following OECD 407 guidelines, a 28-day-repeated-dose-14-day-recovery toxicological evaluation of the aqueous extract of T. cordifolia stem (TCWE) was conducted under good laboratory practice (GLP), in Sprague-Dawley (SD) rats.Methods: 100, 300, and 1000 mg/kg/day of TCWE was given orally to designated treatment groups of either sex. Two separate 14-day recovery satellite groups received either vehicle control or 1000 mg/kg/day of TCWE.Results: In this study, TCWE was found safe up to a dose of 1000 mg/kg/day with no mortality or related toxicological manifestation in terms of clinical signs, ocular effects, hematology, urinalysis, clinical chemistry parameters, or macro- or microscopic changes in any organs. The satellite group did not show any adverse effect after 14-day recovery period. Thus, the No-Observed-Adverse-Effect-Level (NOAEL) of TCWE was determined to be 1000 mg/kg/day.Discussion: In conclusion, this study established the non-clinical safety of the aqueous extract of T. cordifolia stem, which confirms the age-old safe medicinal use of this herb, and also paves the path for future clinical research on formulations containing Tinospora cordifolia

    Synthesis of ferrofluid based nanoarchitectured polypyrrole composites and its application for electromagnetic shielding

    Get PDF
    The monodispersion of magnetic nanoparticles in conducting polymer is the prerequisite to make a high quality composite for tunable electromagnetic interference (EMI) shielding. To meet this challenge, we have designed and synthesized ferrofluid based nanoarchitectured polypyrrole composites containing Fe3O4 (8-12 nm) via in situ oxidative polymerization. To tune the microwave signals, polypyrrole composites (PFF) with different monomer/ferrofluid weight ratios have been prepared and characterized in microwave frequency domain. A maximum shielding effectiveness value of SEA(max)) = 20.4 dB (similar to 99% attenuation) due to the absorption of microwave has been observed in the frequency range of 12.4-18 GHz and attenuation level varied with ferrofluid loading. The electrical conductivity of PFF composite is of the order of 10(-2) S cm(-1) order and having superparamagnetic nature with saturation magnetization (M-s) of 5.5 emu g(-1). The lightweight PFF composites with high attenuations can provide full control over the atomic structure and are favorable for the practical EMI shielding application for commercial electronic appliances

    Designing of Multiphase Fly Ash/MWCNT/PU Composite Sheet Against Electromagnetic Environmental Pollution

    No full text
    Fly ash and multiwalled carbon nanotubes (MWCNT) reinforced multiphase polyurethane (PU) composite sheets have been fabricated by using a solution casting technique. Utilization of fly ash was the prime objective in order to reduce environmental pollution and to enhance the shielding properties of PU polymer. Our study proves that fly ash particles with MWCNTs in a PU matrix leads to novel hybrid high performance electromagnetic shielding interference material. Scanning electron microscopy confirms the existence of fly ash particles along with MWCNTs in a PU matrix. This multiphase composite shows total shielding effectiveness of 35.8 dB (> 99.99% attenuation) in the Ku-band (12.4-18 GHz) frequency range. This is attributed to high dielectric losses of reinforcement present in the polymers matrix. The Nicolson-Ross-Weir algorithm has been applied to calculate the electromagnetic attributes and dielectric parameters of the PU samples by using scattering parameters (S (11), S (22), S (12), S (21)). The synthesized multiphase composites were further characterized by using x-ray diffraction, Fourier transform infrared spectroscopy, and thermo gravimetric analysis

    Identification of differentially expressed proteins in vitamin B 12

    No full text
    Background: Vitamin B 12 (cobalamin) is a water-soluble vitamin generally synthesized by microorganisms. Mammals cannot synthesize this vitamin but have evolved processes for absorption, transport and cellular uptake of this vitamin. Only about 30% of vitamin B 12 , which is bound to the protein transcobalamin (TC) (Holo-TC [HoloTC]) enters into the cell and hence is referred to as the biologically active form of vitamin B 12 . Vitamin B 12 deficiency leads to several complex disorders, including neurological disorders and anemia. We had earlier shown that vitamin B 12 deficiency is associated with coronary artery disease (CAD) in Indian population. In the current study, using a proteomics approach we identified proteins that are differentially expressed in the plasma of individuals with low HoloTC levels. Materials and Methods: We used isobaric-tagging method of relative and absolute quantitation to identify proteins that are differently expressed in individuals with low HoloTC levels when compared to those with normal HoloTC level. Results: In two replicate isobaric tags for relative and absolute quantitation experiments several proteins involved in lipid metabolism, blood coagulation, cholesterol metabolic process, and lipoprotein metabolic process were found to be altered in individuals having low HoloTC levels. Conclusions: Our study indicates that low HoloTc levels could be a risk factor in the development of CAD
    corecore