Membrane Bound Monomer of Staphylococcal α-Hemolysin Induces Caspase Activation and Apoptotic Cell Death despite Initiation of Membrane Repair Pathway

BACKGROUND: Wild type Staphylococcal alpha-hemolysin (alpha-HL) assembly on target mammalian cells usually results in necrotic form of cell death; however, caspase activation also occurs. The pathways of caspase activation due to binding/partial assembly by alpha-HL are unknown till date. RESULTS: Cells treated with H35N (a mutant of alpha-HL that remains as membrane bound monomer), have been shown to accumulate hypodiploid nuclei, activate caspases and induce intrinsic mitochondrial apoptotic pathway. We have earlier shown that the binding and assembly of alpha-HL requires functional form of Caveolin-1 which is an integral part of caveolae. In this report, we show that the caveolae of mammalian cells, which undergo a continuous cycle of 'kiss and run' dynamics with the plasma membrane, have become immobile upon the binding of the monomer. The cells treated with H35N were unable to recover despite activation of membrane repair mechanism involving caspase-1 dependent activation of sterol regulatory element binding protein-1. CONCLUSIONS: This is for the first time we show the range of cellular changes and responses that take place immediately after the binding of the monomeric form of staphylococcal alpha-hemolysin

In search of consensus: Terminology for entheseal changes (EC)

This article presents a consensus terminology for entheseal changes that was developed in English by an international team of scholars and then translated into French, Italian, Portuguese, Spanish and German. Use of a standard, neutral terminology to describe entheseal morphology will reduce misunderstandings between researchers, improve the reliability of comparisons between studies, and eliminate unwarranted etiological assumptions inherent in some of the descriptive terms presently used in the literature

Gene-Trap Mutagenesis Identifies Mammalian Genes Contributing to Intoxication by Clostridium perfringens ε-Toxin

The Clostridium perfringens ε-toxin is an extremely potent toxin associated with lethal toxemias in domesticated ruminants and may be toxic to humans. Intoxication results in fluid accumulation in various tissues, most notably in the brain and kidneys. Previous studies suggest that the toxin is a pore-forming toxin, leading to dysregulated ion homeostasis and ultimately cell death. However, mammalian host factors that likely contribute to ε-toxin-induced cytotoxicity are poorly understood. A library of insertional mutant Madin Darby canine kidney (MDCK) cells, which are highly susceptible to the lethal affects of ε-toxin, was used to select clones of cells resistant to ε-toxin-induced cytotoxicity. The genes mutated in 9 surviving resistant cell clones were identified. We focused additional experiments on one of the identified genes as a means of validating the experimental approach. Gene expression microarray analysis revealed that one of the identified genes, hepatitis A virus cellular receptor 1 (HAVCR1, KIM-1, TIM1), is more abundantly expressed in human kidney cell lines than it is expressed in human cells known to be resistant to ε-toxin. One human kidney cell line, ACHN, was found to be sensitive to the toxin and expresses a larger isoform of the HAVCR1 protein than the HAVCR1 protein expressed by other, toxin-resistant human kidney cell lines. RNA interference studies in MDCK and in ACHN cells confirmed that HAVCR1 contributes to ε-toxin-induced cytotoxicity. Additionally, ε-toxin was shown to bind to HAVCR1 in vitro. The results of this study indicate that HAVCR1 and the other genes identified through the use of gene-trap mutagenesis and RNA interference strategies represent important targets for investigation of the process by which ε-toxin induces cell death and new targets for potential therapeutic intervention

Effects on poor readers' comprehension of training in rapid decoding

Includes bibliographical references (p. 24-26)Supported by the National Institute of Education under Contract No. US-NIE-C-400-76-011

Achievement Motivation of College Students in relation to their Gender, Stream and Locale

Achievement motivation of the college students is the matter of great concern in the 21 st century Indian society. Unless the students have high level of achievement motivation it will be difficult on the part of the society to develop and to be at par with other developed society. Therefore right from the lower level up to the higher level there should be proper emphasis on the development of the desire to attain excellence in all walks of life. As such the present study is an attempt to focus the achievement motivation of the college students of Himachal Pradesh with regard to gender, stream and locale variation. The objectives of the study were based on comparison of the achievement motivation of the college students having gender, stream i.e. arts vs. science and locale i.e. urban vs. rural background. The study reported that there exists significant difference in the achievement motivation of male vs. female, arts vs. science and urban vs. rural college students

Vibration analysis of multi-supported curved panel using the periodic structure approach

This papers deals with the radial vibration of a row of cylindrical panels of finite length using the concept of wave propagation in periodic structures. For this study, the structure is considered as an assemblage of a number of identical cylindrically curved panels each of which will be referred to as a periodic element. For a given geometry dispersion curves of the propagation constant versus (non-dimensional) natural frequency have been drawn corresponding to the circumferential wave propagation. New conclusions that have emerged from this study are as follows. It is shown that by a proper choice of the periodic element the bounding frequencies and the corresponding modes in all the propagation bands can be determined. These have been shown to correspond to a single curved panel with all its edges simply supported. It is noted that there are no attenuation gaps in the entire frequency spectrum beyond the lowest bounding frequency. This is a unique feature of circumferential wave propagation around circular cylindrical shells and panels, as opposed to the wave propagation of periodically supported beams and rectangular panels without curvature. The natural frequency corresponding to every circumferential mode of the complete shell has been identified on the propagation constant curve. It has been observed that the natural frequencies of a cylindrically curved panel of a given curvature and length but of different circumferential arc length (corresponding to different angles subtended at the centre of any circular cross-section) may also be identified on the same propagation constant curve. Finally, it is shown that the same propagation constant curve may also be used to determine all the natural frequencies of a finite row of curved panels with the extreme edges simply supported. Wherever possible the numerical results have been compared with those obtained independently from finite element13; analysis and=or results available in the literature. Flutter analysis of multi-span curved panels using a wave13; approach is the ultimate objective of this work

Optimal error estimates for semidiscrete Galerkin approximations to equations of motion described by Kelvin-Voigt viscoelastic fluid flow model

In this paper, a finite element Galerkin method is applied to equations of motion arising in the Kelvin-Voigt viscoelastic fluid flow model, when the forcing function is in L-infinity (L-2). Some a priori estimates for the exact solution, which are valid uniformly in time as t bar right arrow infinity and even uniformly in the retardation time kappa an kappa bar right arrow 0 are derived. It is shown that the semidiscrete method admits a global attractor. Further, with the help of a priori bounds and Sobolev-Stokes projection, optimal error estimates for the velocity in L-infinity (L-2) and L-infinity (H-1) norms and for the pressure in L-infinity (L-2)-norm are established. Since the constants involved in error estimates have an exponential growth in time, therefore, in the last part of the article, under certain uniqueness condition, the error bounds are established which are valid uniformly in time. Finally, some numerical experiments are conducted which confirm our theoretical findings. (C) 2016 Elsevier B.V. All rights reserved