Phosphorylated abacavir analogue (ABC-1) has ameliorative action against Newcastle disease virus induced pathogenesis in chicken.

Newcastle disease virus (NDV) causes huge economic loss to the poultry industry due to high mortality and morbidity. The present study aimed to assess the protective role of novel phosphorylated analogue ABC-1 in vivo in NDV-infected chickens through the inhibition of fusion protein. Both NDV-induced oxidative damage and protective role of novel phosphorylated ABC-1 were evaluated in vital organs such as the liver and lung of chickens. Enzyme linked immunosorbent assay (ELISA) results showed that protein oxidation and nitration levels were significantly raised in NDV-infected tissues compared to healthy controls, whereas these levels were reduced significantly (P < 0.05) in birds treated with phosphorylated compounds compared to the NDV-infected group alone. Additional investigation with double immunofluorescence showed that the large amount of immuno colocalization and Western blot analysis also confirmed this observation through its band pattern in NDV-infected birds compared to healthy birds, whereas these alterations were reduced in treatment with novel phosphorylated ABC-1. The expression of fusion glycoprotein was studied by immuno colocalization, PCR, and flow cytometry, and results demonstrated that the novel phosphorylated analogues reduced the expression of fusion glycoprotein. These results put forth that novel phosphorylated ABC-1 protects chickens from NDV-induced pathogenesis, protein oxidation/nitration, and exerts potent antiviral activity.

Self-assembly and molecular packing in cholesteryl esters at interfaces.

To understand the self-assembly and molecular packing in cholesteryl esters relevant to biological processes, we have studied them at the air-water and air-solid interfaces. Our phase and thickness studies employing imaging ellipsometry and atomic force microscopy along with surface manometry show that the molecular packing of cholesteryl esters at interfaces can be related to Craven's model of packing, given for bulk. At the air-water interface, following Craven's model, cholesteryl nonanoate and cholesteryl laurate exhibit a fluidic bilayer phase. Interestingly, we find the fluidic bilayer phase of cholesteryl laurate to be unstable and it switches to a crystalline bilayer phase. However, according to Craven, only cholesteryl esters with longer chain lengths starting from cholesteryl tridecanoate should show the crystalline bilayer phase. The thickness behavior of different phases was also studied by transferring the films onto a silicon substrate by using the Langmuir-Blodgett technique. Texture studies show that cholesterol, cholesteryl acetate, cholesteryl nonanoate, cholesteryl laurate, and cholesteryl myristate exhibit homogeneous films with large size domains, whereas cholesteryl palmitate and cholesteryl stearate exhibit less homogeneous films with smaller size domains. We suggest that such an assembly of molecules can be related to their molecular structures. Simulation studies may confirm such a relation.

The efficacy of isometric resistance training utilizing handgrip exercise for blood pressure management: A randomized trial.

INTRODUCTION: Hypertension is a major risk factor contributing to cardiovascular disease, which is the number one cause of deaths worldwide. Although antihypertensive medications are effective at controlling blood pressure, current first-line treatment for hypertension is nonpharmacological lifestyle modifications. Recent studies indicate that isometric resistance training (IRT) may also be effective for assisting with blood pressure management. The aim of this study was to determine the efficacy of IRT for blood pressure management and the suitability of a low-intensity working control group. METHODS: Forty hypertensive individuals, aged between 36 and 65 years, conducted IRT for 8 weeks. Participants were randomized into 2 groups, working at an intensity of either 5% or 30% of their maximum voluntary contraction. Participants performed 4 × 2 minute isometric handgrip exercises with their nondominant hand, each separated by a 3-minute rest period, 3 days a week. RESULTS: Blood pressure measurements were conducted at baseline and at the end of the protocol using a Finometer. Eight weeks of isometric resistance training resulted in a 7-mmHg reduction of resting systolic blood pressure (SBP) (136 ±â€Š12 to 129 ±â€Š15; P = 0.04) in the 30% group. Reductions of 4 mmHg were also seen in mean arterial pressure (MAP) (100 ±â€Š8 to 96 ±â€Š11; P = 0.04) in the 30% group. There were no statistically significant reductions in diastolic blood pressure for the 30% group, or any of the data for the 5% group. CONCLUSION: Isometric resistance training conducted using handgrip exercise at 30% of maximum voluntary contraction significantly reduced SBP and MAP. A lack of reduction in blood pressure in the 5% group indicates that a low-intensity group may be suitable as a working control for future studies.

The relationship between positive psychological characteristics and longer telomeres.

OBJECTIVE: Longer telomeres are associated with better health and longevity. This research investigated the relationship between positive psychological dispositional traits and telomere length. Positive traits examined were typical high positive affect, typical low negative affect, life satisfaction, trait mindfulness, trait emotional intelligence, general self-efficacy and optimism. DESIGN AND MEASURES: One hundred and twenty women and men, with a mean age of 40.92, completed measures of positive characteristics and provided samples for telomere length analysis. RESULTS: Together the positive dispositional characteristics explained significant variance in telomere length, R = .40. Among the individual characteristics, greater optimism and higher emotional intelligence were associated with longer telomeres after adjustment for age and gender and the association between optimism and telomere length remained significant after adjusting for age and gender as well as the other positive characteristics, with a partial correlation r of .30. CONCLUSION: These results in conjunction with previous research findings provide a platform for further exploration of biological pathways connecting positive characteristics such as optimism to telomere length and investigation of the impact of increasing a characteristic such as optimism on telomere functioning.

Charge transport in a liquid crystalline triphenylene polymer monolayer at air-solid interface.

We have prepared a monolayer of a novel liquid crystalline polymer derived from 2,6-dihydroxy-3,7,10,11-tetraalkoxy-triphenylene (PHAT) at an air-water interface and transferred it onto freshly cleaved mica as well as gold coated mica substrates by the Langmuir-Blodgett (L-B) technique. The atomic force microscope (AFM) images of these L-B films show a uniform coverage with a thickness of 1.5 nm. Electrical conductivity measurements were carried out on the PHAT monolayer deposited on the gold coated mica substrate using a current sensing AFM (CSAFM). The gold substrate-PHAT monolayer-cantilever tip of CSAFM forms a metal-insulator-metal (M-I-M) junction. The CSAFM yields a non-linear current-voltage (I-V) curve for the M-I-M junction. The analysis of the I-V characteristics of the M-I-M junction indicated that the charge transport in the liquid crystalline polymer monolayer is by the direct tunneling mechanism. The barrier height for the PHAT monolayer was estimated to be 1.22 ± 0.02 eV.

Proteomic and Microscopic Strategies towards the Analysis of the Cytoskeletal Networks in Major Neuropsychiatric Disorders.

Mental health disorders have become worldwide health priorities. It is estimated that in the next 20 years they will account for a 16 trillion United State dollars (US$) loss. Up to now, the underlying pathophysiology of psychiatric disorders remains elusive. Altered cytoskeleton proteins expression that may influence the assembly, organization and maintenance of cytoskeletal integrity has been reported in major depressive disorders, schizophrenia and to some extent bipolar disorders. The use of quantitative proteomics, dynamic microscopy and super-resolution microscopy to investigate disease-specific protein signatures holds great promise to improve our understanding of these disorders. In this review, we present the currently available quantitative proteomic approaches use in neurology, gel-based, stable isotope-labelling and label-free methodologies and evaluate their strengths and limitations. We also reported on enrichment/subfractionation methods that target the cytoskeleton associated proteins and discuss the need of alternative methods for further characterization of the neurocytoskeletal proteome. Finally, we present live cell imaging approaches and emerging dynamic microscopy technology that will provide the tools necessary to investigate protein interactions and their dynamics in the whole cells. While these areas of research are still in their infancy, they offer huge potential towards the understanding of the neuronal network stability and its modification across neuropsychiatric disorders.

An update on the interaction between the serotonin transporter promoter variant (5-HTTLPR), stress and depression, plus an exploration of non-confirming findings.

In the three years since the most recent meta-analysis of the association between the serotonin transported promoter polymorphism (5-HTTLPR), stress and the development of depression, another 27 studies have been published on this issue, which is an increase of 50% more studies than were previously reviewed. In addition, previous findings of inconsistency of results across studies argued for further exploration of this relationship. From the 81 studies identified to June 2013, the significant relationship between the short form of the 5-HTTLPR was confirmed (p=.0000009), which is stronger than the relationship reported in the most recent meta-analysis in 2011. However, nearly 26% of the 81 studies reviewed failed to show any significant association between the 5-HTTLPR, stress and depression, and four studies found opposite results to those expected. Examination of the methodologies of all studies failed to indicate any flaws in the opposite or unequivocal studies, and the latter had larger sample sizes than those studies which supported the expected association, arguing that the null results were not an outcome of insufficient statistical power. The need to consider aspects of samples and measures of depression, particularly the presence of subtypes of depression in future research is discussed.

Stress-strain relation in the collapse of Langmuir monolayer of a dimer of disk shaped moiety.

Langmuir monolayer of a novel molecule containing dimer of disk shaped moiety, viz., terephtalic acid bis-[6-(3,6,7,10,11-pentahexyloxy-triphenylen-2-yloxyl)-hexyl] ester (tp-dimer), was studied at air-water interface. The monolayer of the tp-dimer at air-water interface exhibited the coexistence of condensed and gas phases at large area per molecule which on compression transformed to a uniform condensed phase at lower area per molecule (1.80 nm(2)) and then collapsed at 1.67 nm(2). The monolayer film transferred by Langmuir-Blodgett technique onto a hydrophilic silicon substrate was studied using an atomic force microscope. The topography image showed the film to be of height of about 1.5 nm corresponding to the edge-on configuration of the triphenylene moieties. We have studied the collapse of monolayer at air-water interface as a function of compression rate and temperature. We find that the collapse pressure increased with increase in the compression rate. The surface pressure of the monolayer is considered as stress and compression as strain. The strain rate is related to the collapse pressure by a power law similar to that found in the dendrimers. Our studies on the effect of temperature on the collapse pressure of tp-dimer monolayer showed that the collapse pressure decreased with increase in temperature. We have considered the Arrhenius temperature dependence of the strain rate and calculated the activation energy for the collapse of monolayer. Our analysis of the relative area loss as a function of time in the collapse region suggests that the monolayer collapses by the formation of nuclei of three-dimensional crystallites.

Susceptibility of Candida albicans biofilms to azithromycin, tigecycline and vancomycin and the interaction between tigecycline and antifungals.

Despite growing data on antimicrobial lock therapy (ALT) in treating bacterial catheter-related bloodstream infections (CR-BSIs), ALT has not been established as a treatment option for CR-BSI caused by Candida albicans. Based on our finding that high-dose doxycycline exhibited antifungal activity against mature C. albicans biofilms, we evaluated additional antibacterial agents with Gram-positive activity [azithromycin, tigecycline (TIG) and vancomycin]. After screening these antibiotics, it was found that TIG had substantial antifungal activity against mature C. albicans biofilms. Therefore, TIG was assayed alone and in combination with fluconazole (FLC), amphotericin B (AmB) or caspofungin (CAS). TIG at 2048 µg/mL resulted in a >50% reduction in the growth of planktonic C. albicans cells. TIG inhibited the formation of biofilms from 128 µg/mL. Against mature biofilms, 2048 µg/mL TIG reduced metabolic activity by 84.2%. Furthermore, addition of 512 µg/mL TIG to FLC at all concentrations tested provided additional reduction in the metabolic activity of mature biofilms. However, this was not superior to 512 µg/mL TIG alone. TIG at 512 µg/mL increased the antifungal effect of lower concentrations of AmB (0.03125-0.25 µg/mL), but at 0.03125 µg/mL and 0.0625 µg/mL this effect was not superior to 512 µg/mL TIG alone. TIG inhibited the antifungal effect of higher concentrations of AmB (≥ 2 µg/mL). TIG at 512 µg/mL inhibited the antifungal activity of CAS at lower concentrations (0.25-8 µg/mL). These data indicate that high-dose TIG is highly active in vitro against planktonic cells, forming biofilms and mature biofilms of C. albicans.

Deletion of the C-terminus of polynucleotide phosphorylase increases twitching motility, a virulence characteristic of the anaerobic bacterial pathogen Dichelobacter nodosus.

The Gram-negative anaerobe Dichelobacter nodosus is the causative agent of footrot in sheep. Different strains of D. nodosus cause disease of differing severities, ranging from benign to virulent. Virulent strains have greater twitching motility and secrete proteases that are more thermostable than those secreted by benign strains. We have identified polynucleotide phosphorylase (PNPase) as a putative virulence regulator and have proposed that PNPase expression is modulated by the adjacent integration of genetic elements. In this study, we compared PNPase activity in three virulent and four benign strains of D. nodosus and found that PNPase activity is lower in virulent strains. We disrupted the pnpA gene in three benign D. nodosus strains and two virulent strains and showed that deletion of the S1 domain of PNPase reduced catalytic activity. In all but one case, deletion of the PNPase S1 domain had no effect on the thermostability of extracellular proteases. However, this deletion resulted in an increase in twitching motility in benign, but not in virulent strains. Reconstruction of the pnpA gene in two mutant benign strains reduced twitching motility to the parental level. These results support the hypothesis that PNPase is a virulence repressor in benign strains of D. nodosus.

Candida albicans PEP12 is required for biofilm integrity and in vivo virulence.

To investigate the role of the prevacuolar secretion pathway in biofilm formation and virulence in Candida albicans, we cloned and analyzed the C. albicans homolog of the Saccharomyces cerevisiae prevacuolar trafficking gene PEP12. C. albicans PEP12 encodes a deduced t-SNARE that is 28% identical to S. cerevisiae Pep12p, and plasmids bearing C. albicans PEP12 complemented the abnormal vacuolar morphology and temperature-sensitive growth of an S. cerevisiae pep12 null mutant. The C. albicans pep12 Delta null mutant was defective in endocytosis and vacuolar acidification and accumulated 40- to 60-nm cytoplasmic vesicles near the plasma membrane. Secretory defects included increased extracellular proteolytic activity and absent lipolytic activity. The pep12Delta null mutant was more sensitive to cell wall stresses and antifungal agents than the isogenic complemented strain or the control strain DAY185. Notably, the biofilm formed by the pep12Delta mutant was reduced in overall mass and fragmented completely upon the slightest disturbance. The pep12Delta mutant was markedly reduced in virulence in an in vitro macrophage infection model and an in vivo mouse model of disseminated candidiasis. These results suggest that C. albicans PEP12 plays a key role in biofilm integrity and in vivo virulence.

Micro-structural, electrical and spectroscopic investigations of pulsed laser ablated palladium incorporated nanostructured tungsten oxide films.

Pure and Pd incorporated (0.5, 1 and 5 wt%) WO3 films are prepared on quartz substrates using pulsed laser ablation (PLD) technique in an oxygen ambient of 0.12 mbar, at a substrate temperature (Ts) of 873 K. Palladium incorporation effects on the microstructure, optical and electrical properties of tungsten oxide films are systematically investigated using techniques like X-ray diffraction (XRD), Atomic Force Microscopy (AFM), Scanning Electron Microscopy (SEM), Energy dispersive X-ray spectroscopy (EDX), micro-Raman spectroscopy, UV-Vis absorption spectroscopy and temperature dependent electrical resistivity measurements. The micro-structural analysis by XRD and micro-Raman indicates that Pd addition can perturb the tungsten oxide lattice and suppress the grain growth. Optical band gap values of the films increases from 3.17 eV for pure WO3 to 3.29 eV for 5 wt% Pd incorporated WO3 films. All the films present high transparency in the visible spectral range. The electrical resistivity studies of the pure and Pd incorporated films done at room temperature and for the range of temperature; 170-450 K reveal that Pd addition can lower the resistivity of the WO3 thin films. Room temperature resistivity as well as activation energy of the film decreases exponentially with Pd incorporation concentration. Highly transparent, nanocrystalline and semiconducting WO3 films with low resistivity obtained by Pd incorporation can make WO3 suitable for microelectronics industry and for gas sensing applications.

Kinetics of trans-cis isomerization in azobenzene dimers at an air-water interface.

We have studied the kinetics of trans to cis isomerization under the illumination of ultraviolet light, in the Langmuir monolayer of mesogenic azobenzene dimer, bis-[5-( 4' -n-dodecyloxy benzoyloxy)-2-( 4''-methylphenylazo)phenyl] adipate, at an air-water interface. We find that the trans to cis isomerization reaction of the molecules in the monolayer shows deviation from the first-order kinetics unlike those reported on Langmuir monolayers of azobenzene molecules. We attribute the deviation from first-order kinetics to the simultaneous photoisomerization of trans isomers to form cis isomers and the reverse thermal isomerization of cis isomers to form trans isomers. Our analysis of the rate of change of mole fraction of trans isomers to form cis isomers indicates a first-order kinetics for trans to cis photoisomerization reaction and a second-order kinetics for cis to trans thermal isomerization reaction. This second-order kinetics mechanism is similar to the Lindemann-Hinshelwood mechanism for the unimolecular reactions at low concentration of reactants. The formation of the activated cis isomer by collisions is a slow process as compared to the decay of the activated cis isomer to trans isomer in the liquid expanded phase. This results in the second-order kinetics for the thermal isomerization of cis isomers.

Mechanical properties of Langmuir-Blodgett films of a discogen-DNA complex by atomic force microscopy.

We have studied the mechanical properties of films of a novel ionic discogen, pyridinium tethered with hexaalkoxytriphenylene (PyTp) and its complex with DNA (PyTp-DNA) using atomic force microscope (AFM). The PyTp and PyTp-DNA complex monolayer films were first formed at air-water interface and then transferred onto silicon substrates by Langmuir-Blodgett (LB) technique. For the mechanical properties, particularly to obtain elastic modulus, we have carried out nanoindentation measurements on the LB films of PyTp and also PyTp-DNA complex. The load versus indentation curves from the nanoindentation measurements were analyzed quantitatively using Hertz model. Our analysis yields Young's modulus values of 54 and 160 MPa for the PyTp and PyTp-DNA complex films, respectively. In addition, the LB films were imaged in the tapping mode AFM to obtain topography and phase images simultaneously. The energy dissipation maps were constructed from the phase images to determine qualitatively the variation in stiffness on the film surfaces. We find that the complex film exhibits a nonuniform surface with varying stiffness while the pure film exhibits a uniform surface.

Novel mesogenic azobenzene dimer at air-water and air-solid interfaces.

We have synthesized a novel mesogenic azobenzene molecule and studied its monolayer film properties at air-water interface (Langmuir film) and air-solid interface (Langmuir-Blodgett film). The material, H-shaped dimer bis[5-(4'-n-dodecyloxy benzoyloxy)-2-(4''-methylphenylazo)phenyl] adipate (12D1H) exhibits a smectic C phase between 51 and 48 degrees C on cooling. Surface manometry studies showed the formation of a stable monolayer at the air-water interface. Brewster angle microscopy (BAM) showed that liquid domains coexisting with the gas region at large area transformed to a uniform liquid phase with increasing surface density and finally to a collapsed state. We have carried out atomic force microscope (AFM) studies on Langmuir-Blodgett (LB) films transferred onto freshly cleaved hydrophilic mica substrate. The AFM images showed domains of height of about 3.8 nm, which corresponds to the estimated height of the molecule confirming the formation of monomolecular film. On a hydrophobic silicon substrate, the LB transfer yields a bilayer film, which dewets to form uniform nanodroplets of diameter of about 100 nm and height in the range 10-50 nm. Our analysis indicated that the mechanism involved in the formation of nanodroplets can be attributed to spinodal dewetting. The 12D1H molecule containing an azobenzene group undergoes a trans to cis transformation in the presence of ultraviolet light. Our surface manometry studies showed that the monolayer in the presence of ultraviolet light was more stable with a collapse pressure three times that of the monolayer in the dark.

Spatiotemporal patterns in a Langmuir monolayer due to driven molecular precession.

Langmuir monolayers of chiral liquid crystals on the surface of water exhibit orientational waves with complex spatiotemporal patterns. These patterns arise from a collective precession of the mesogenic molecules, driven by the evaporation of water through the monolayer. We investigate the behavior of these orientational waves around topological defects in the molecular orientation. Through Brewster angle microscopy, we find that the waves form a reversing spiral pattern, which rotates about the central vortex. With increasing relative humidity, the rotation slows and then stops. We model the system theoretically, and show that predicted patterns are in good agreement with the experiments.

Conductivity of Langmuir-Blodgett films of a disk-shaped liquid-crystalline molecule-DNA complex studied by current-sensing atomic force microscopy.

We have studied the electrical conductivity in monolayer films of an ionic disk-shaped liquid-crystal molecule, pyridinium tethered with hexaalkoxytriphenylene (PyTp), and its complex with DNA by current-sensing atomic force microscopy (CS-AFM). The pure PyTp and PyTp-DNA complex monolayer films were first formed at the air-water interface and then transferred onto conducting substrates by the Langmuir-Blodgett (LB) technique to study the nanoscale electron transport through these films. The conductive tip of CS-AFM, the LB film, and the metal substrate form a nanoscopic metal-LB film-metal (M-LB-M) junction. We have measured the current-voltage (I-V) characteristics for the M-LB-M junction using CS-AFM and have analyzed the data quantitatively. We find that the I-V curves fit well to the Fowler-Nordheim (FN) model, suggesting electron tunneling to be a possible mechanism for electron transport in our system. Further, analysis of the I-V curves based on the FN model yields the barrier heights of PyTp-DNA complex and pure PyTp films. Electron transport studies of films of ionic disk-shaped liquid-crystal molecules and their complex with DNA are important from the point of view of their applications in organic electronics.

Monolayer of amphiphilic functionalized gold nanoparticles at an air-water interface.

Langmuir films at the air-water interface exhibit a variety of surface phases which arise primarily due to the molecular interaction governed by intermolecular separation. We have studied the thermodynamical aspects of Langmuir monolayers of amphiphilic functionalized gold nanoparticles (AGNs) at the air-water (A-W) interface. Interestingly, the AGN monolayer exhibits phases like gas, a low-ordered liquid (L1) , a high-ordered liquid (L2) , and a collapsed state. We find that the first-order phase transition between L1 and L2 vanishes above a critical temperature of 28.4 degrees C . Surprisingly, for a range of higher temperatures ( > or = 29.4 degrees C and < or = 36.3 degrees C ), the L1 phase undergoes a transition to a bilayer of the L2 phase before entering into the collapsed state.

Discogen-DNA complex films at air-water and air-solid interfaces.

We have studied films of an ionic discogenic (discotic mesogenic) molecule (pyridinium salt tethered with hexaalkoxytriphenylene (PyTp)) and DNA complex at air-water (A-W) and air-solid interfaces. We have formed an PyTp monolayer on an aqueous subphase containing a small amount of DNA to obtain a PyTp-DNA complex at the A-W interface. Compared to the pure PyTp monolayer, the PyTp-DNA complex monolayer exhibits a higher collapse pressure and lower limiting area, indicating condensation and better stability. A Brewster angle microscope was used for in situ observation of the morphology of the film at the A-W interface. The PyTp-DNA complex films on silicon wafers were prepared using the Langmuir-Blodgett (LB) technique. We find that several tens of layers of the PyTp-DNA complex monolayer can be transferred with good efficiency. Fourier transform infrared spectroscopy studies confirm the presence of DNA in the LB films of the PyTp-DNA complex. Nanoindentation measurements using atomic force microscope reveal that the PyTp-DNA complex films are about two times harder as compared to the pure PyTp films.

Films of novel mesogenic molecules at air-water and air-solid interfaces.

Discotic molecules are known to form highly anisotropic structures at the air-water (A-W) interface. We have studied two novel ionic discotic mesogenic molecules, viz., pyridinium tethered with hexaalkoxytriphenylene with bromide counterion (Py-Tp) and imidazolium tethered with hexaalkoxytriphenylene with bromide counterion (Im-Tp) at A-W and air-solid interfaces. The monolayer phases were investigated at the A-W interface employing surface manometry and Brewster angle microscopy techniques. They indicate a uniform monolayer phase which shows negligible hysteresis on expanding and compressing. Also, in both the systems the collapsed state completely reverts to the monolayer state. These monolayer films transferred at different surface pressures by Langmuir-Blodgett technique were studied by employing atomic force microscopy. The topographies of these films transferred at the low and high surface pressure region of the isotherm indicate a transformation of the monolayer from face-on to edge-on structure.