Change in spectrum of Brownian fluctuations of optically trapped red blood cells due to malarial infection

We study the properties of single red blood cells (RBCs) held in an optical-tweezers trap. We observe a change in the spectrum of Brownian fluctuations between RBCs from normal and malaria-infected samples. The change, caused by infection-induced structural changes in the cell, appears as a statistical increase in the mean (by 25%) and standard deviation (by 200%) of the corner frequency measured over similar to 100 cells. The increase is observed even though the ensemble of cells being measured consists mostly of cells that do not actually host the parasite, but are from an infected pool. This bystander effect appears to vindicate other observations that infected cells can affect the biomechanical properties of uninfected cells. The change is also observed to be independent of the stage of infection and its duration, highlighting its potential for disease detection. (C) 2010 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3427142].

Pharmacokinetics and chemotherapeutic efficacy of adriamycin encapsulated in immunoliposomes against avian myeloblastosis virus infection

Immunoliposomes were prepared using rabbit anti-AMV gp80 IgG for the targeted chemotherapy of avian myeloblastosis virus infection. Adriamycin was encapsulated into immunoliposomes and used for in vivo studies. Comparative pharmacokinetics of free drug, drug encapsulated in free liposomes and of drug encapsulated in immunoliposomes in the virus-infected cells revealed that (i) the drug encapsulated in liposomes was cleared from the plasma slowly, and (ii) the drug encapsulated in immunoliposomes accumulated in the target tissue, the bone marrow, 5- and 8.5-fold more than the drug encapsulated in free liposomes and free drug, respectively. The drug encapsulated in immunoliposomes inactivated the virus and exhibited more chemotherapeutic efficacy as compared to controls when injected up to 24 h post-infection. However, when injected 48 h post-infection the drug encapsulated in immunoliposomes did not offer any protection against the virus infection. There is no detectable antibody response against immunoliposomes in the infected animals.

Confirmation of pauling's theory that vitamin C improves immunity to infection

It is pointed out that the complement Clq, associated with the immune response system, has a part containing about 80 residues with a collagen-like sequence, with Gly at every third location and having also a number of Hyp and Hyl residues in locations before Gly, and that it takes the triple-helical conformation characteristic of collagen. As with collagen biosynthesis, ascorbic acid is therefore expected to be required for its production. Also, collagen itself, in the extracellular matrix, is connected with the fibroblast surface protein (FSP), whose absence leads to cell proliferation, and whose addition leads to suppression of malignancy in tissue culture. All these show the great importance of vitamin C for resistance to diseases, and even to cancer, as has been widely advocated by Pauling.

Influence of cross-correlation between dipolar and chemical shift anisotropy relaxation mechanisms upon the transverse relaxation rates of 15N in macromolecules

Heteronuclear multiple-quantum coherence relaxation rate are calculated for the individual transitions of the S spin in an AIS nuclear spin system assuming that the heteronucleus (S spin) has relaxation contributions from both intramolecular dipole-dipole and chemical shift anisotropy relaxation. The individual multiplet components of the heteronuclear zero- and double-quantum coherences are shown to have different transverse relaxation rates. The cross-correlation between the two relaxation mechanisms is shown to be the dominant cause of the calculated differential line broadening. Experimental data are presented using as an example a uniformly 15N labelled sample of human epidermal growth factor.

Visiting the cell biology of Salmonella infection

Salmonella, a Gram-negative facultative intracellular pathogen is capable of infecting vast array of hosts. The striking ability of Salmonella to overcome every hurdle encountered in the host proves that they are true survivors. In the host, Salmonella infects various cell types and needs to survive and replicate by countering the defense mechanism of the specific cell. In this review, we will summarize the recent insights into the cell biology of Salmonella infection. Here, we will focus on the findings that deal with the specific mechanism of various cell types to control Salmonella infection. Further, the survival strategies of the pathogen in response to the host immunity will also be discussed in detail. Better understanding of the mechanisms by which Salmonella evade the host defense system and establish pathogenesis will be critical in disease management. (C) 2010 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

In-Network Computation in Random Wireless Networks: A PAC Approach to Constant Refresh Rates with Lower Energy Costs

We propose a method to compute a probably approximately correct (PAC) normalized histogram of observations with a refresh rate of Theta(1) time units per histogram sample on a random geometric graph with noise-free links. The delay in computation is Theta(root n) time units. We further extend our approach to a network with noisy links. While the refresh rate remains Theta(1) time units per sample, the delay increases to Theta(root n log n). The number of transmissions in both cases is Theta(n) per histogram sample. The achieved Theta(1) refresh rate for PAC histogram computation is a significant improvement over the refresh rate of Theta(1/log n) for histogram computation in noiseless networks. We achieve this by operating in the supercritical thermodynamic regime where large pathways for communication build up, but the network may have more than one component. The largest component however will have an arbitrarily large fraction of nodes in order to enable approximate computation of the histogram to the desired level of accuracy. Operation in the supercritical thermodynamic regime also reduces energy consumption. A key step in the proof of our achievability result is the construction of a connected component having bounded degree and any desired fraction of nodes. This construction may also prove useful in other communication settings on the random geometric graph.

Breast cancer and human papillomavirus infection: No evidence of HPV etiology of breast cancer in Indian women

Background: Two clinically relevant high-risk HPV (HR-HPV) types 16 and 18 are etiologically associated with the development of cervical carcinoma and are also reported to be present in many other carcinomas in extra-genital organ sites. Presence of HPV has been reported in breast carcinoma which is the second most common cancer in India and is showing a fast rising trend in urban population. The two early genes E6 and E7 of HPV type 16 have been shown to immortalize breast epithelial cells in vitro, but the role of HPV infection in breast carcinogenesis is highly controversial. Present study has therefore been undertaken to analyze the prevalence of HPV infection in both breast cancer tissues and blood samples from a large number of Indian women with breast cancer from different geographic regions. Methods: The presence of all mucosal HPVs and the most common high-risk HPV types 16 and 18 DNA was detected by two different PCR methods - (i) conventional PCR assays using consensus primers (MY09/11, or GP5 +/GP6+) or HPV16 E6/E7 primers and (ii) highly sensitive Real-Time PCR. A total of 228 biopsies and corresponding 142 blood samples collected prospectively from 252 patients from four different regions of India with significant socio-cultural, ethnic and demographic variations were tested. Results: All biopsies and blood samples of breast cancer patients tested by PCR methods did not show positivity for HPV DNA sequences in conventional PCRs either by MY09/11 or by GP5+/GP6+/HPV16 E6/E7 primers. Further testing of these samples by real time PCR also failed to detect HPV DNA sequences. Conclusions: Lack of detection of HPV DNA either in the tumor or in the blood DNA of breast cancer patients by both conventional and real time PCR does not support a role of genital HPV in the pathogenesis of breast cancer in Indian women.

Ribavirin-Induced Anemia in Hepatitis C Virus Patients Undergoing Combination Therapy

The current standard of care for hepatitis C virus (HCV) infection - combination therapy with pegylated interferon and ribavirin - elicits sustained responses in only similar to 50% of the patients treated. No alternatives exist for patients who do not respond to combination therapy. Addition of ribavirin substantially improves response rates to interferon and lowers relapse rates following the cessation of therapy, suggesting that increasing ribavirin exposure may further improve treatment response. A key limitation, however, is the toxic side-effect of ribavirin, hemolytic anemia, which often necessitates a reduction of ribavirin dosage and compromises treatment response. Maximizing treatment response thus requires striking a balance between the antiviral and hemolytic activities of ribavirin. Current models of viral kinetics describe the enhancement of treatment response due to ribavirin. Ribavirin-induced anemia, however, remains poorly understood and precludes rational optimization of combination therapy. Here, we develop a new mathematical model of the population dynamics of erythrocytes that quantitatively describes ribavirin-induced anemia in HCV patients. Based on the assumption that ribavirin accumulation decreases erythrocyte lifespan in a dose-dependent manner, model predictions capture several independent experimental observations of the accumulation of ribavirin in erythrocytes and the resulting decline of hemoglobin in HCV patients undergoing combination therapy, estimate the reduced erythrocyte lifespan during therapy, and describe inter-patient variations in the severity of ribavirin-induced anemia. Further, model predictions estimate the threshold ribavirin exposure beyond which anemia becomes intolerable and suggest guidelines for the usage of growth hormones, such as erythropoietin, that stimulate erythrocyte production and avert the reduction of ribavirin dosage, thereby improving treatment response. Our model thus facilitates, in conjunction with models of viral kinetics, the rational identification of treatment protocols that maximize treatment response while curtailing side effects.

Aromatic claisen rearrangements in carbohydrates: stereocontrol of rearrangement rates in unsaturated sugar substrates

A remarkable difference is observed in the rates of [3,3]-sigmatropic rearrangement of aryl 4,6-di-O-acetyl-2,3-dideoxy-D-erythro-hex-2-enopyranosides 1 and 2; the slower reactivity of the alpha-isomers is consistent with AM1 calculated transition state energetics of model systems.

Study of Texture Evolution at High Strain Rates in FCC Materials

Evolution of crystallographic texture during high strain rate deformation in FCC materials with different stacking fault energy (Ni, Cu, and Cu-10Zn alloy) has been studied. The texture evolved in FCC materials at these strain rates show little dependence on the Stacking Fault Energy and the amount of deformation. Copper shows an anomalous behavior that is attributed to the ease of cross slip and continuous Dynamic Recrystallization that are operative under the experimental conditions.

Development of specific DNA probes and their usage in the detection of Plasmodium vivax infection in blood

The application of nucleic acid probes, in the detection of pathogenic micro-organisms, has become an integral part of diagnostic technologies. In this study, Plasmodium vivax-specific DNA probes have been identified by carrying out genomic subtractive hybridization. In this approach, the recombinant clones from a P. vivax genomic library are screened with radiolabelled human and P. falciparum DNA. The colonies which react with labelled P. falciparum and human DNA are eliminated and those which do not produce any autoradiographic signal have been subjected to further screening procedures. Three Fl vivax specific DNA probes have been obtained by these repeated screenings. Further analyses indicate that these probes are specific and sensitive enough to detect P. vivax infection in clinical blood samples when used in a non-radioactive DNA hybridization assay. (C) 1995 Academic Press Limited

Japanese encephalitis virus infection of mouse cell lines: ability to prime mice for generation of virus specific cytotoxic T lymphocytes and differences in CTL recognisable viral determinants

Ten different mouse cell lines were examined for Japanese encephalitis virus (JEV) infection in vitro and then tested for their ability to generate virus specific cytotoxic T lymphocytes (CTL). Among all cell lines examined, Neuro La (a neuroblastoma) was readily infected with JEV as examined by immunofluorescence and viral replication. Among other cells, P388D1, RAW 264.7 (Macrophage origin), Sp2/0 (B-cell Hybridoma), YAC-1 (T-cell lymphoma), and L929 (Fibroblast) were semipermissive to JEV infection. The cytopathic effects caused by progressive JEV infection varied from cell line to cell line. In the case of YAC-1 cells long-term viral antigen expression was observed without significant alterations in cell viability. Intermediate degrees of cytopathicity are seen in RAW 264.7 and L929 cells while infection of PS, Neuro 2a, P388D1 and Sp2/0 caused major viability losses. All infected cell lines were able to prime adult BALB/c (H-2(d)) mice for the generation of secondary JEV specific CTL. In contrast to YAC-1, the permissive neuroblastoma cell line Neuro 2a (H-2K(k)D(d)) was found to be least efficient in its ability to stimulate anti-viral CTL generation. Cold target competition studies demonstrated that both Neuro 2a and YAC-1 (H-2K(k)D(d)) cells expressed similar viral determinants that are recognised by CTL, suggesting that the reason for the lower ability of Neuro 2a to stimulate anti-viral CTL was not due to lack of viral CTL determinants. These findings demonstrate that a variety of mouse cell lines can be infected with Japanese encephalitis virus, and that these infected cells could be utilised to generate virus specific CTL in BALB/c mice.

Deformation behaviour of commercially pure titanium at extreme strain rates

The evolution of microstructure and texture during room temperature compression of commercially pure Ti with four different initial orientations were studied under quasi-static and dynamic loading conditions. At a low strain rate (epsilon)over dot = 3 x 10(-4) s(-1) the different initial textures yielded the same end texture, despite different microstructural evolution in terms of twin boundaries. High strain rate deformation at (epsilon)over dot = 1.5 x 10(3) s(-1) was characterized by extensive twinning and evolution of a texture that was similar to that at low strain rate with minor differences. However, there was a significant difference in the strength of the texture for different orientations that was absent for low strain rate deformed samples at high strain rate. A viscoplastic self-consistent model with a secant approach was used to corroborate the experimental results by simulation. (C) 2011 Published by Elsevier Ltd. on behalf of Acta Materialia Inc.