Theoretical calculations on vibrational frequencies and absorption spectra of S-1 and S-2 states of pyridine

Three harmonic potential-energy surfaces of (1)A(1), B-1(1), and B-1(2) singlet states of pyridine have been obtained by using ab initio method. Geometric properties and force fields of these states have been determined with the complete-active-space self-consistent-field (CASSCF) theoretical method. Vibrational frequencies of two excited states have been assigned on the basis of the potential energy distribution from normal mode analysis. The resulting properties are used to simulate the experimental absorption spectrum. From the spectral simulation the totally symmetric vibrations with large Huang-Rhys factors have been identified as nu(12) and nu(6a) modes in the B-1(1) state; nu(1) and nu(12) modes in the B-1(2) state, indicating that these modes have strong vibronic coupling between ground and excited states

Effects of dietary plant-derived phytonutrients on the genome-wide profiles and coccidiosis resistance in the broiler chickens

<p>Abstract</p> <p>Background</p> <p>The present study was conducted to investigate the effects of dietary plant-derived phytonutrients, carvacrol, cinnamaldehyde and Capsicum oleoresin, on the translational regulation of genes associated with immunology, physiology and metabolism using high-throughput microarray analysis and <it>in vivo</it> disease challenge model of avian coccidiosis.</p> <p>Methods</p> <p>In this study, we used nutrigenomics technology to investigate the molecular and genetic mechanisms of dietary modulation of host innate immunity and metabolism by three phytonutrients. To validate their immunomodulatory effects in a disease model, young broiler chickens fed a standard diet supplemented with three phytochemicals (carvacrol, cinnamaldehyde, and Capsicum oleoresin) from one day post-hatch were orally challenged with <it>E. acervulina</it>. The body weight gain and fecal oocyst production were used to evaluate coccidiosis disease parameters.</p> <p>Results</p> <p>Analysis of global gene expression profiles of intestinal tissues from phytonutrient-fed birds indicated that Capsicum oleoresin induced the most gene changes compared to the control group where many of these genes were associated with those of metabolism and immunity. The most reliable network induced by dietary cinnamaldehyde treatment was related with the functions of antigen presentation, humoral immune response, and inflammatory disease. Furthermore, dietary supplementation with these phytonutrients significantly protected broiler chickens against live coccidiosis challenge infection based on body weight and parasite fecundity.</p> <p>Conclusions</p> <p>The results of this study provide clear evidence to support the idea that plant-derived phytochemicals possess immune-enhancing properties in chickens and these new findings create a new possibility to develop effective drug-free alternative strategies for disease control for poultry infectious diseases.</p

Potential conservation of circadian clock proteins in the phylum Nematoda as revealed by bioinformatic searches

Although several circadian rhythms have been described in C. elegans, its molecular clock remains elusive. In this work we employed a novel bioinformatic approach, applying probabilistic methodologies, to search for circadian clock proteins of several of the best studied circadian model organisms of different taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other members of the phylum Nematoda. With this approach we found that the Nematoda contain proteins most related to the core and accessory proteins of the insect and mammalian clocks, which provide new insights into the nematode clock and the evolution of the circadian system.Fil: Romanowski, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Garavaglia, Matías Javier. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goya, María Eugenia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ghiringhelli, Pablo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andres. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Block of NMDA receptor channels by endogenous neurosteroids: implications for the agonist induced conformational states of the channel vestibule

N-methyl-D-aspartate receptors (NMDARs) mediate synaptic plasticity, and their dysfunction is implicated in multiple brain disorders. NMDARs can be allosterically modulated by numerous compounds, including endogenous neurosteroid pregnanolone sulfate. Here, we identify the molecular basis of the use-dependent and voltage-independent inhibitory effect of neurosteroids on NMDAR responses. The site of action is located at the extracellular vestibule of the receptor's ion channel pore and is accessible after receptor activation. Mutations in the extracellular vestibule in the SYTANLAAF motif disrupt the inhibitory effect of negatively charged steroids. In contrast, positively charged steroids inhibit mutated NMDAR responses in a voltage-dependent manner. These results, in combination with molecular modeling, characterize structure details of the open configuration of the NMDAR channel. Our results provide a unique opportunity for the development of new therapeutic neurosteroid-based ligands to treat diseases associated with dysfunction of the glutamate system

New "light" for one-world approach toward safe and effective control of animal diseases and insect vectors from leishmaniac perspectives

Light is known to excite photosensitizers (PS) to produce cytotoxic reactive oxygen species (ROS) in the presence of oxygen. This modality is attractive for designing control measures against animal diseases and pests. Many PS have a proven safety record. Also, the ROS cytotoxicity selects no resistant mutants, unlike other drugs and pesticides. Photodynamic therapy (PDT) refers to the use of PS as light activable tumoricides, microbicides and pesticides in medicine and agriculture.Here we describe "photodynamic vaccination" (PDV) that uses PDT-inactivation of parasites, i.e. Leishmania as whole-cell vaccines against leishmaniasis, and as a universal carrier to deliver transgenic add-on vaccines against other infectious and malignant diseases. The efficacy of Leishmania for vaccine delivery makes use of their inherent attributes to parasitize antigen (vaccine)-presenting cells. Inactivation of Leishmania by PDT provides safety for their use. This is accomplished in two different ways: (i) chemical engineering of PS to enhance their uptake, e.g. Si-phthalocyanines; and (ii) transgenic approach to render Leishmania inducible for porphyrinogenesis. Three different schemes of Leishmania-based PDV are presented diagrammatically to depict the cellular events resulting in cell-mediated immunity, as seen experimentally against leishmaniasis and Leishmania-delivered antigen in vitro and in vivo. Safety versus efficacy evaluations are under way for PDT-inactivated Leishmania, including those further processed to facilitate their storage and transport. Leishmania transfected to express cancer and viral vaccine candidates are being prepared accordingly for experimental trials.We have begun to examine PS-mediated photodynamic insecticides (PDI). Mosquito cells take up rose bengal/cyanosine, rendering them light-sensitive to undergo disintegration in vitro, thereby providing a cellular basis for the larvicidal activity seen by the same treatments. Ineffectiveness of phthalocyanines and porphyrins for PDI underscores its requirement for different PS. Differential uptake of PS by insect versus other cells to account for this difference is under study.The ongoing work is patterned after the one-world approach by enlisting the participation of experts in medicinal chemistry, cell/molecular biology, immunology, parasitology, entomology, cancer research, tropical medicine and veterinary medicine. The availability of multidisciplinary expertise is indispensable for implementation of the necessary studies to move the project toward product development

Development and preliminary evaluation of a quality of life measure targeted at dementia caregivers

<p>Abstract</p> <p>Background</p> <p>Providing care for individuals with a progressive, debilitating condition such as dementia can adversely impact the quality of life (QOL) of informal caregivers. To date, there is no existing caregiver quality of life measure for dementia caregivers with breadth of coverage or that is applicable to caregivers of diverse ethnic backgrounds. The purpose of this study was to develop and evaluate a caregiver-targeted quality-of-life measure (CGQOL) for informal caregivers of persons with dementia that can be used with caregivers from a variety of ethnicities.</p> <p>Methods</p> <p>91 items were field tested by telephone interviews with 179 English-speaking and 21 monolingual Spanish-speaking caregivers of persons with dementia. Repeat interviews were conducted with 71 caregivers. Administration time, scale score distributions, item-scale correlations, reliability, and associations of scales with patient and caregiver demographic and caregiving characteristics were estimated. Structure of associations among scales was examined using exploratory factor analysis.</p> <p>Results</p> <p>Item analysis yielded 80 items distributed across 10 scales, with median administration time of 17 minutes [IQR 13.5–22 minutes] and minimal missing data. There were few floor or ceiling effects in scale score distributions. Internal consistency reliability was ≥ 0.78 for all scales; test-retest reliability (intraclass correlation) estimates exceeded 0.70 for 6 scales. More hours weekly spent in caregiving was uniquely associated with worse quality of life on 8 scales (p's ≤ 0.05). Three higher-order dimensions of caregiving assistance, emotional and social concerns, and spirituality and benefits were identified.</p> <p>Conclusion</p> <p>These preliminary results support subsequent evaluation of test-retest reliability, construct validity, and responsiveness to change of this quality-of-life measure for caregivers from diverse ethnicities.</p

Study on Resistance Switching Properties of Na0.5Bi0.5TiO3Thin Films Using Impedance Spectroscopy

The Na0.5Bi0.5TiO3(NBT) thin films sandwiched between Au electrodes and fluorine-doped tin oxide (FTO) conducting glass were deposited using a sol–gel method. Based on electrochemical workstation measurements, reproducible resistance switching characteristics and negative differential resistances were obtained at room temperature. A local impedance spectroscopy measurement of Au/NBT was performed to reveal the interface-related electrical characteristics. The DC-bias-dependent impedance spectra suggested the occurrence of charge and mass transfer at the interface of the Au/NBT/FTO device. It was proposed that the first and the second ionization of oxygen vacancies are responsible for the conduction in the low- and high-resistance states, respectively. The experimental results showed high potential for nonvolatile memory applications in NBT thin films