BioNanoAdhesion: atomic force microscopy study of the electrostatic properties of pyridine-and imidazole-based polycationic surfaces

Self-assembled monolayers of pyridine- and imidazole-based disulfides are currently being produced on low roughness gold surfaces. The electrostatic interaction between these surfaces and an atomic force microscope cantilever, modified with a silica microparticle, will subsequently be investigated as a function of environmental pH. The results can be used towards the development of improved nanoparticulate non-viral gene delivery vectors

PHARMACOKINETICS OF SECOND LINE ANTI-TB DRUG (LEVOFLOXACIN) IN MDR-TB PATIENTS

Tuberculosis, commonly known as TB, is the world’s second deadliest disease caused by the bacterium Mycobacterium tuberculosis (MTB). The treatment for TB started in the year 1944 after the discovery of the antibiotic streptomycin. Over the century, the TB bacteria have evolved into the resistance forms, despite the use of effective drugs. In our study, We analysed the pharmacokinetic profile of Levofloxacin in MDR-TB patients. LFX is a synthetic broad spectrum antibacterial agent. It is the S-Isomer of the race mate. Plasma concentrations of levofloxacin were estimated using the validated methods by HPLC at NIRT. We had analysed the plasma concentrations of individual patients over different time intervals post single dosage. In case of LFX, about 10(40%) patients had their Cmax> 12µg/ml, 3 patients showed sub therapeutic Cmax value i.e. < 8 µg/ml and the remaining 12 patients (48%) had their Cmax value within the range. This study is expected to have important clinical implications.&nbsp

N-acetyldopamine quinone methide/1,2-dehydro-N-acetyl dopamine tautomerase A new enzyme involved in sclerotization of insect cuticle

AbstractThe enzyme system causing the side chain desaturation of the sclerotizing precursor, N-acetyldopamine (NADA), was solubilized from the larval cuticle of Sarcophaga bullata and resolved into three components. The first enzyme, phenoloxidase, catalyzed conversion of NADA to NADA quinone and provided it for the second enzyme (NADA quinone isomerase), which makes the highly unstable NADA quinone methide. Quinone methide was hydrated rapidly and nonenzymatically to form N-acetylnorepinephrine. In addition, it also served as the substrate for the last enzyme, quinone methide tautomerase, which converted it to 1,2-dehydro-NADA. Reconstitution of NADA side chain desaturase activity was achieved by mixing the last enzyme fraction with NADA quinone isomerase, obtained from the hemolymph of the same organism, and mushroom tyrosinase. Therefore, NADA side chain desaturation observed in insects is caused by the combined action of three enzymes rather than the action of a single specific NADA desaturase, as previously thought

Glimpses of Tribal Botanical Knowledge of Tirunelveli Hills, Western Ghats, India

In the present paper, 46 plant species of angiosperms belonging to 19 genera of Euphorbiaceae that occur naturally in the Tirunelveli Hills of western Ghats, India, were chosen for study. It was found that the uses of Euphorbiaceous plants by the inhabitants of this region cover a number of broad categories including food, various kinds of poisons, medicines, sundry types of oils, waxes, rubbers, varnishes, compounds for paints and other industrial products

Suppressive actions of eicosapentaenoic acid on lipid droplet formation in 3T3-L1 adipocytes

Background : Lipid droplet (LD) formation and size regulation reflects both lipid influx and efflux, and is central in the regulation of adipocyte metabolism, including adipokine secretion. The length and degree of dietary fatty acid (FA) unsaturation is implicated in LD formation and regulation in adipocytes. The aims of this study were to establish the impact of eicosapentaenoic acid (EPA; C20:5n-3) in comparison to SFA (STA; stearic acid, C18:0) and MUFA (OLA; oleic acid, C18:1n-9) on 3T3-L1 adipocyte LD formation, regulation of genes central to LD function and adipokine responsiveness. Cells were supplemented with 100 &mu;M FA during 7-day differentiation.Results : EPA markedly reduced LD size and total lipid accumulation, suppressing PPAR&gamma;, Cidea and D9D/SCD1 genes, distinct from other treatments. These changes were independent of alterations of lipolytic genes, as both EPA and STA similarly elevated LPL and HSL gene expressions. In response to acute lipopolysaccharide exposure, EPA-differentiated adipocytes had distinct improvement in inflammatory response shown by reduction in monocyte chemoattractant protein-1 and interleukin-6 and elevation in adiponectin and leptin gene expressions.Conclusions : This study demonstrates that EPA differentially modulates adipogenesis and lipid accumulation to suppress LD formation and size. This may be due to suppressed gene expression of key proteins closely associated with LD function. Further analysis is required to determine if EPA exerts a similar influence on LD formation and regulation in-vivo.<br /

The Saito-Kurokawa lifting and Darmon points

Let E_{/_\Q} be an elliptic curve of conductor $Np$ with $p\nmid N$ and let $f$ be its associated newform of weight 2. Denote by $f_\infty$ the $p$-adic Hida family passing though $f$, and by $F_\infty$ its $\Lambda$-adic Saito-Kurokawa lift. The $p$-adic family $F_\infty$ of Siegel modular forms admits a formal Fourier expansion, from which we can define a family of normalized Fourier coefficients $\{\widetilde A_T(k)\}_T$ indexed by positive definite symmetric half-integral matrices $T$ of size $2\times 2$. We relate explicitly certain global points on $E$ (coming from the theory of Stark-Heegner points) with the values of these Fourier coefficients and of their $p$-adic derivatives, evaluated at weight $k=2$.Comment: 14 pages. Title change

Comprehensive mutational analysis of yeast DEXD/H box RNA helicases involved in large ribosomal subunit biogenesis

DEXD/H box putative RNA helicases are required for pre-rRNA processing in Saccharomyces cerevisiae, although their exact roles and substrates are unknown. To characterize the significance of the conserved motifs for helicase function, a series of five mutations were created in each of the eight essential RNA helicases (Has1, Dbp6, Dbp10, Mak5, Mtr4, Drs1, Spb4, and Dbp9) involved in 60S ribosomal subunit biogenesis. Each mutant helicase was screened for the ability to confer dominant negative growth defects and for functional complementation. Different mutations showed different degrees of growth inhibition among the helicases, suggesting that the conserved regions do not function identically in vivo. Mutations in motif I and motif II (the DEXD/H box) often conferred dominant negative growth defects, indicating that these mutations do not interfere with substrate binding. In addition, mutations in the putative unwinding domains (motif III) demonstrated that conserved amino acids are often not essential for function. Northern analysis of steady-state RNA from strains expressing mutant helicases showed that the dominant negative mutations also altered pre-rRNA processing. Coimmunoprecipitation experiments indicated that some RNA helicases associated with each other. In addition, we found that yeasts disrupted in expression of the two nonessential RNA helicases, Dbp3 and Dbp7, grew worse than when either one alone was disrupted

Characteristics of GDI engine flow structures

The benefits of the gasoline direct injection engine over the more traditional gasoline port-fuel injection engine are well known and include the ability to operate lean of stoichiometric for fuel efficiency improvements, reduced knock propensity and reduced unburned hydrocarbons during cold start and transients. Nevertheless, a number of key challenges still remain including cyclic variability, abnormal combustion phenomena and increased particulate emissions. Our progress in each of these challenges is intrinsically linked to our understanding of the flow field formed within the cylinder. This paper presents the development, validation and subsequent utilisation of a 3D-CFD gasoline direct injection engine model for making predictions of the in-cylinder flow field through the intake and compression strokes. An extensive validation exercise was completed using experimental data from a single cylinder optical research engine to validate both the intake runner, intake valve jet and in-cylinder flow fields. Validation results showed the model to generally compare well against experimental data including indicating data, intake runner velocities and flow momentum, valve jet and in-cylinder flow structures. Differences were identified in the timing of the detachment of the intake valve jet from the cylinder head and a subsequent reduction in effective flow area was hypothesised as contributing to an over prediction of the valve jet and in-cylinder flow velocities. A comparison of the spatial and temporal development of the in-cylinder flow field identified the model to well predict the flow structures through the intake and compression stroke. The model was then exercised with a view to evaluate the impact of solid boundaries on the spatial and temporal development of the in-cylinder flow structure. An analysis on the impact of using a pent-roof optical access window in research engines on the flow structure is also provided, indicating that significant asymmetry and additional recirculation zones in the corners of the access window should be considered when evaluating experimental results from a research engine of this configuration

Evaluation of immune responses to porcine reproductive and respiratory syndrome virus in pigs during early stage of infection under farm conditions

<p>Abstract</p> <p>Background</p> <p>Porcine reproductive and respiratory syndrome virus (PRRSV) causes chronic, economically devastating disease in pigs of all ages. Frequent mutations in the viral genome result in viruses with immune escape mutants. Irrespective of regular vaccination, control of PRRSV remains a challenge to swine farmers. In PRRSV-infected pigs, innate cytokine IFN-α is inhibited and the adaptive arm of the immunity is delayed. To elucidate both cellular and innate cytokine responses at very early stages of PRRSV infection, seven weeks old pigs maintained on a commercial pig farm were infected and analyzed.</p> <p>Results</p> <p>One pig in a pen containing 25 pigs was PRRSV infected and responses from this pig and one penmate were assessed two days later. All the infected and a few of the contact neighbor pigs were viremic. At day 2 post-infection, approximately 50% of viremic pigs had greater than 50% reduction in NK cell-mediated cytotoxicity, and nearly a 1-fold increase in IFN-α production was detected in blood of a few pigs. Enhanced secretion of IL-4 (in ~90%), IL-12 (in ~40%), and IL-10 (in ~20%) (but not IFN-γ) in PRRSV infected pigs was observed. In addition, reduced frequency of myeloid cells, CD4^-CD8⁺T cells, and CD4⁺CD8⁺T cells and upregulated frequency of lymphocytes bearing natural T regulatory cell phenotype were detected in viremic pigs. Interestingly, all viremic contact pigs also had comparable immune cell modulations.</p> <p>Conclusion</p> <p>Replicating PRRSV in both infected and contact pigs was found to be responsible for rapid modulation in NK cell-meditated cytotoxicity and alteration in the production of important immune cytokines. PRRSV-induced immunological changes observed simultaneously at both cellular and cytokine levels early post-infection appear to be responsible for the delay in generation of adaptive immunity. As the study was performed in pigs maintained under commercial environmental conditions, this study has practical implications in design of protective vaccines.</p

Rescue of the MERTK phagocytic defect in a human iPSC disease model using translational read-through inducing drugs.

Inherited retinal dystrophies are an important cause of blindness, for which currently there are no effective treatments. In order to study this heterogeneous group of diseases, adequate disease models are required in order to better understand pathology and to test potential therapies. Induced pluripotent stem cells offer a new way to recapitulate patient specific diseases in vitro, providing an almost limitless amount of material to study. We used fibroblast-derived induced pluripotent stem cells to generate retinal pigment epithelium (RPE) from an individual suffering from retinitis pigmentosa associated with biallelic variants in MERTK. MERTK has an essential role in phagocytosis, one of the major functions of the RPE. The MERTK deficiency in this individual results from a nonsense variant and so the MERTK-RPE cells were subsequently treated with two translational readthrough inducing drugs (G418 &amp; PTC124) to investigate potential restoration of expression of the affected gene and production of a full-length protein. The data show that PTC124 was able to reinstate phagocytosis of labeled photoreceptor outer segments at a reduced, but significant level. These findings represent a confirmation of the usefulness of iPSC derived disease specific models in investigating the pathogenesis and screening potential treatments for these rare blinding disorders