Transgenic mouse model for the formation of Hirano bodies

<p>Abstract</p> <p>Background</p> <p>Hirano bodies are actin-rich cytoplasmic inclusions found predominantly in the brain in association with a variety of conditions including aging and Alzheimer's disease. The function of Hirano bodies in normal aging and in progression of disease has not been extensively investigated due to a lack of experimental model systems. We have developed a transgenic mouse model by expression of a gain-of-function actin cross-linking protein mutant.</p> <p>Results</p> <p>We used the Cre/loxP system to permit tissue specific expression of Hirano bodies, and employed the murine Thy 1 promoter to drive expression of Cre recombinase in the brain. Hirano bodies were observed in the cerebral cortex and hippocampus of homozygous double transgenic 6 month old mice containing Cre. The Hirano bodies were eosinophilic rods, and also exhibited the paracrystalline F-actin filament organization that is characteristic of these inclusions. Mice with Hirano bodies appear healthy and fertile, but exhibited some alterations in both short-term and long-term synaptic plasticity, including paired-pulse depression rather than facilitation, and decreased magnitude of early LTP.</p> <p>Conclusions</p> <p>Hirano bodies are not lethal and appear to have little or no effect on histology and tissue organization. Hirano bodies do modulate synaptic plasticity and exert clearly discernable effects on LTP and paired-pulse paradigms. This model system will allow us to investigate the impact of Hirano bodies <it>in vivo</it>, the pathways for formation and degradation of Hirano bodies, and whether Hirano bodies promote or modulate development of pathology and disease progression.</p

Pressure-Dependent Line Intensity and Continuum Absorption for Pure Co2: Experimental Results

Fourier-transform measurements of pure CO2 in the 1.6 µm region covering bands from ground state to 30011, 30012, 30013, and 30014 states at ambient temperature and 212 K with pressures up to 1 bar have been recorded. Line parameters have been retrieved by multispectrum fitting. An intensity depletion parameter quantifying linear intensity dependence on pressure was introduced and fitted. From the fitted baseline polynomials the self continuum was determined for the 30012 and 30013 bands. The depleted intensity was found to be transferred to the continuum for both temperatures, thus the band intensity is conserved. The intensity in the continuum at 1 atm was about 1% of the total band intensities for ambient temperature and about 3% at 212 K. For both temperatures the depleted intensity/continuum area was found in excellent agreement with values calculated from the second virial coefficient. The experimental work is accompanied by rCMDS calculations. The results presented here have significant impact on CO2 retrieval from atmospheric measurements. For OCO/CO2M-type observations it was calculated that in case of the 2 µm band retrieved CO2 columns are too large by about 3% when omitting depletion and continuum. A new spectroscopic database was produced. Systematic line intensity uncertainties are well below 0.1%

Effect of hemicellulose liquid phase on the enzymatic hydrolysis of autohydrolyzed Eucalyptus globulus wood

In this work, Eucalyptus globulus wood was pretreated under non-isothermal autohydrolysis process at 210, 220, and 230 °C, obtaining a pretreated solid with high cellulose content and a hemicellulosic liquid phase (HLP) containing mainly xylose, acetic acid, furfural, xylooligosaccharides, and phenolic compounds. The maximum concentration of xylooligosaccharides (8.97 g/L) and phenolic compounds (2.66 g/L) was obtained at 210 and 230 °C, respectively. To evaluate the effect of HLP addition on the enzymatic hydrolysis using unwashed pretreated solid as substrate, different proportions of HLP were studied. Also, in order to use the whole slurry on enzymatic hydrolysis, the supplementation of xylanases was evaluated. Glucose concentration of 107.49 g/L (corresponding to 74.65 % of conversion) was obtained using pretreated solid at 220 °C liquid/solid ratio (LSR) of 4 g/g and enzyme solid ratio (ESR) of 25 FPU/gwithout the addition of HLP. Thus, it was shown that the unwashed pretreated solids are susceptible to enzymatic hydrolysis contributing to reduce operational cost (water consumption). Additionally, the influence of the inhibitory compounds in the HLP was shown to affect the enzymatic hydrolysis. Results indicated that 82.52 g/L of glucose (59.37 % of conversion) was obtained, using 100 % of HLP at LSR of 4 g/g and ESR of 16 FPU/g at 210 °C of pretreated solid. However, a positive effect was shown on the enzymatic hydrolysis when the xylanases were added using 100 % of HLP, increasing to 35 and 27 % in the glucose production with respect to whole slurry without addition of xylanases.The authors A. Romani and F. B. Pereira thank to the Portuguese Foundation for Science and Technology (FCT, Portugal) for their fellowships (grant number, SFRH/BPD/77995/2011 and SFRH/BD/64776/2009, respectively)

Simvastatin improves the sexual health-related quality of life in men aged 40 years and over with erectile dysfunction : Additional data from the Erectile Dysfunction and Statin trial

© 2014 Trivedi et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background: Erectile dysfunction is prevalent in men over 40 years, affecting their quality of life and that of their partners. The aims of this study were:a)To evaluate the internal reliability of the male erectile dysfunction specific quality of life (MED-QoL) scale and explore its factor structure.b)To evaluate the effect of simvastatin on subscales of the MED-QoL in men over forty years with erectile dysfunction. Methods: This is a double blind randomised controlled trial of 40 mg simvastatin or placebo given once daily for six months to men over forty years with untreated erectile dysfunction, who were not at high cardiovascular risk and were not on anti-hypertensive or lipid-lowering medication. 173 eligible men were recruited from 10 general practices in East of England. Data were collected at two points over 30 weeks. We report on the factor structure of MED-QoL, the internal reliability of the scale and the derived subscales, and the effect of simvastatin on MED-QoL subscales. Results: An initial analysis of the MED-QoL items suggested that a number of items should be removed (MED-QoL-R). Exploratory factor analysis identified three subscales within the MED-QoL-R which accounted for 96% of the variance, related to feelings of Control, initiating Intimacy, and Emotional response to erectile dysfunction. The alpha value for the revised scale (MED-Qol-R) was >0.95 and exceeded .82 for each subscale. Regression analysis showed that patients in the placebo group experienced a significantly reduced feeling of Control over erectile dysfunction than those in the statin group. Those in the placebo group had significantly lower Emotional response than those in the statin group at the close of trial, but there was no significant treatment effect on Intimacy. Conclusions: Our revised MED-QoL-R identified three subscales. Secondary analysis showed a significant improvement in sexual health related quality of life, specifically in relation to perception of control and emotional health in men with untreated erectile dysfunction given 40 mg simvastatin for six months. Trial registration: Current Controlled Trials ISRCTN66772971.Peer reviewe

Centre-of-mass separation in quantum mechanics: Implications for the many-body treatment in quantum chemistry and solid state physics

We address the question to what extent the centre-of-mass (COM) separation can change our view of the many-body problem in quantum chemistry and solid state physics. It was shown that the many-body treatment based on the electron-vibrational Hamiltonian is fundamentally inconsistent with the Born-Handy ansatz so that such a treatment can never respect the COM problem. Born-Oppenheimer (B-O) approximation reveals some secret: it is a limit case where the degrees of freedom can be treated in a classical way. Beyond the B-O approximation they are inseparable in principle. The unique covariant description of all equations with respect to individual degrees of freedom leads to new types of interaction: besides the known vibronic (electron-phonon) one the rotonic (electron-roton) and translonic (electron-translon) interactions arise. We have proved that due to the COM problem only the hypervibrations (hyperphonons, i.e. phonons + rotons + translons) have true physical meaning in molecules and crystals; nevertheless, the use of pure vibrations (phonons) is justified only in the adiabatic systems. This fact calls for the total revision of our contemporary knowledge of all non-adiabatic effects, especially the Jahn-Teller effect and superconductivity. The vibronic coupling is responsible only for removing of electron (quasi)degeneracies but for the explanation of symmetry breaking and forming of structure the rotonic and translonic coupling is necessary.Comment: 39 pages, 11 sections, 3 appendice

The Genetics of Adaptation for Eight Microvirid Bacteriophages

Theories of adaptive molecular evolution have recently experienced significant expansion, and their predictions and assumptions have begun to be subjected to rigorous empirical testing. However, these theories focus largely on predicting the first event in adaptive evolution, the fixation of a single beneficial mutation. To address long-term adaptation it is necessary to include new assumptions, but empirical data are needed for guidance. To empirically characterize the general properties of adaptive walks, eight recently isolated relatives of the single-stranded DNA (ssDNA) bacteriophage φX174 (family Microviridae) were adapted to identical selective conditions. Three of the eight genotypes were adapted in replicate, for a total of 11 adaptive walks. We measured fitness improvement and identified the genetic changes underlying the observed adaptation. Nearly all phages were evolvable; nine of the 11 lineages showed a significant increase in fitness. However, fitness plateaued quickly, and adaptation was achieved through only three substitutions on average. Parallel evolution was rampant, both across replicates of the same genotype as well as across different genotypes, yet adaptation of replicates never proceeded through the exact same set of mutations. Despite this, final fitnesses did not vary significantly among replicates. Final fitnesses did vary significantly across genotypes but not across phylogenetic groupings of genotypes. A positive correlation was found between the number of substitutions in an adaptive walk and the magnitude of fitness improvement, but no correlation was found between starting and ending fitness. These results provide an empirical framework for future adaptation theory

Organizational factors and depression management in community-based primary care settings

Abstract Background Evidence-based quality improvement models for depression have not been fully implemented in routine primary care settings. To date, few studies have examined the organizational factors associated with depression management in real-world primary care practice. To successfully implement quality improvement models for depression, there must be a better understanding of the relevant organizational structure and processes of the primary care setting. The objective of this study is to describe these organizational features of routine primary care practice, and the organization of depression care, using survey questions derived from an evidence-based framework. Methods We used this framework to implement a survey of 27 practices comprised of 49 unique offices within a large primary care practice network in western Pennsylvania. Survey questions addressed practice structure (e.g., human resources, leadership, information technology (IT) infrastructure, and external incentives) and process features (e.g., staff performance, degree of integrated depression care, and IT performance). Results The results of our survey demonstrated substantial variation across the practice network of organizational factors pertinent to implementation of evidence-based depression management. Notably, quality improvement capability and IT infrastructure were widespread, but specific application to depression care differed between practices, as did coordination and communication tasks surrounding depression treatment. Conclusions The primary care practices in the network that we surveyed are at differing stages in their organization and implementation of evidence-based depression management. Practical surveys such as this may serve to better direct implementation of these quality improvement strategies for depression by improving understanding of the organizational barriers and facilitators that exist within both practices and practice networks. In addition, survey information can inform efforts of individual primary care practices in customizing intervention strategies to improve depression management.http://deepblue.lib.umich.edu/bitstream/2027.42/78269/1/1748-5908-4-84.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/2/1748-5908-4-84-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/3/1748-5908-4-84.pdfPeer Reviewe

Synthesis of anthraquinone based electroactive polymers: A critical review

Conducting polymers or synthetic monomers have revolutionized the world and are at the heart of scientific research having a scope of vast diverse applications in many technological fields. The conducting and redox polymers have been investigated as energy storage systems because of their better sustainability, ease of synthesis, and environmental compatibility. Owing to the conducting properties of quinones, they gain too much importance among the researchers. Keeping in view the importance and sustainability of conducting polymers, for the first time, this study compiles a detailed overview of synthetic approaches followed by investigations on electrochemical properties and future directions. This study critically examines the synthetic process of simple monomers, substituted monomers, and polymers of anthraquinone (AQ) under the classification of low- and high-molecular-weight AQ–based derivatives, their working principles, and their electrochemical applications, which enable us to explore their novel possible application in automotive, solar cell devices, aircraft aileron, and biomedical equipment. Irrefutably, we confirm that high-molecular-weight polymeric AQ compounds are best in comparison with low-molecular-weight AQ monomers because they have pre-eminent properties over monomeric systems. Because of the significant properties of AQ, polymeric systems are high demanding and have emerged as a hot topic among the researchers these days. In the current scenario, this study is of immense importance because it identifies and discusses the right and sustainable combination and paves the way to utilize these novel materials in different technologies

Networked buffering: a basic mechanism for distributed robustness in complex adaptive systems

A generic mechanism - networked buffering - is proposed for the generation of robust traits in complex systems. It requires two basic conditions to be satisfied: 1) agents are versatile enough to perform more than one single functional role within a system and 2) agents are degenerate, i.e. there exists partial overlap in the functional capabilities of agents. Given these prerequisites, degenerate systems can readily produce a distributed systemic response to local perturbations. Reciprocally, excess resources related to a single function can indirectly support multiple unrelated functions within a degenerate system. In models of genome:proteome mappings for which localized decision-making and modularity of genetic functions are assumed, we verify that such distributed compensatory effects cause enhanced robustness of system traits. The conditions needed for networked buffering to occur are neither demanding nor rare, supporting the conjecture that degeneracy may fundamentally underpin distributed robustness within several biotic and abiotic systems. For instance, networked buffering offers new insights into systems engineering and planning activities that occur under high uncertainty. It may also help explain recent developments in understanding the origins of resilience within complex ecosystems. \ud \u