Miracle-dz/UniFAR-FTUs huggingface dataset:
Correlation of regenerable opsin with rod ERG signal in Rpe65-/- mice during development and aging.

PURPOSE RPE65 has been shown to be essential for the production of 11-cis retinal by the retinal pigment epithelium. Mutations in RPE65 are known to be associated with severe forms of early-onset retinal dystrophy. This project was designed to determine the amount of regenerable opsin in Rpe65-/- mice during development and aging, and to examine the function of this rhodopsin by electroretinography (ERG). METHODS Young and aged Rpe65-/- and wild-type (WT) mice were dark adapted. Endogenous rhodopsin and regenerable opsin were measured using absorption-difference spectrophotometry. Photoreceptor function was assessed with scotopic single-flash ERGs and photoreceptors were counted in histologic sections. Opsin's primary structure was analyzed by mass-spectrometric mapping. RESULTS Unlike WT mice, amounts of regenerable opsin in Rpe65-/- mice decreased significantly with age, which correlated with a decrease in the number of photoreceptors and a decline in ERG amplitudes. Opsin structure, however, did not change. No endogenous levels of rhodopsin were measurable in the Rpe65-/- mice (detection limit: 0.225 pmol). 11-cis Retinal injections resulted in the regeneration of similar amounts of rhodopsin and improved rod function in a comparable way, irrespective of age. CONCLUSIONS In the aged Rpe65-/- mouse, opsin levels decrease because of the loss of photoreceptors. The remaining opsin is structurally intact, and the components of the phototransduction cascade and the retinal circuitry remain functional, despite the absence of normal photoreceptor activity.
Steroid Androgen Exposure during Development Has No Effect on Reproductive Physiology of Biomphalaria glabrata

Gastropod mollusks have been proposed as alternative models for male reproductive toxicity testing, due to similarities in their reproductive anatomy compared to mammals, together with evidence that endocrine disrupting chemicals can cause effects in some mollusks analogous to those seen in mammals. To test this hypothesis, we used the freshwater pulmonate snail, Biomphalaria glabrata, for which various genetic tools and a draft genome have recently become available, to investigate the effects of two steroid androgens on the development of mollusk secondary sexual organs. Here we present the results of exposures to two potent androgens, the vertebrate steroid; 5α-dihydrotestosterone (DHT) and the pharmaceutical anabolic steroid; 17α-methyltestosterone (MT), under continuous flow-through conditions throughout embryonic development and up to sexual maturity. Secondary sexual gland morphology, histopathology and differential gene expression analysis were used to determine whether steroid androgens stimulated or inhibited organ development. No significant differences between tissues from control and exposed snails were identified, suggesting that these androgens elicited no biologically detectable response normally associated with exposure to androgens in vertebrate model systems. Identifying no effect of androgens in this mollusk is significant, not only in the context of the suitability of mollusks as alternative model organisms for testing vertebrate androgen receptor agonists but also, if applicable to other similar mollusks, in terms of the likely impacts of androgens and anti-androgenic pollutants present in the aquatic environment.
INTERSEXUAL COMPETITION AS AN EXPLANATION FOR SEX‐RATIO AND DISPERSAL BIASES IN POLYGYNOUS SPECIES

Abstract In polygynous mammals, it is commonly observed that both sex ratios at birth and dispersal are male biased. This has been interpreted as resulting from low female dispersal causing high female local resource competition, which would select for male‐biased sex ratios. However, a female‐biased sex ratio can be selected despite lower female than male‐biased dispersal. This will occur if the low female dispersal is close to the optimal dispersal rate, while the male dispersal is not close to the optimal dispersal rate. The actual outcome depends on the joint evolution of sex‐biased dispersal and sex ratio. Earlier analyses of joint evolution imply that there will be no sex‐ratio nor dispersal biases at the joint evolutionarily stable strategy, thus they do not explain the data. However, these earlier analyses assume no intersexual competition for resources. Here, we show that when males and females compete with each other for access to resources, male‐biased dispersal will be associated with male‐biased birth sex ratio, as is commonly observed. A trend toward male‐biased birth sex ratios is also expected if there is intersexual local resource competition and if birth sex ratio is constrained so that it cannot depart from balanced sex ratio.
Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals.

PURPOSE Green tea and green tea polyphenols have been shown to possess cancer preventive activities in preclinical model systems. In preparation for future green tea intervention trials, we have conducted a clinical study to determine the safety and pharmacokinetics of green tea polyphenols after 4 weeks of daily p.o. administration of epigallocatechin gallate (EGCG) or Polyphenon E (a defined, decaffeinated green tea polyphenol mixture). In an exploratory fashion, we have also determined the effect of chronic green tea polyphenol administration on UV-induced erythema response. EXPERIMENTAL DESIGN Healthy participants with Fitzpatric skin type II or III underwent a 2-week run-in period and were randomly assigned to receive one of the five treatments for 4 weeks: 800 mg EGCG once/day, 400 mg EGCG twice/day, 800 mg EGCG as Polyphenon E once/day, 400 mg EGCG as Polyphenon E twice/day, or a placebo once/day (8 subjects/group). Samples were collected and measurements performed before and after the 4-week treatment period for determination of safety, pharmacokinetics, and biological activity of green tea polyphenol treatment. RESULTS Adverse events reported during the 4-week treatment period include excess gas, upset stomach, nausea, heartburn, stomach ache, abdominal pain, dizziness, headache, and muscle pain. All of the reported events were rated as mild events. For most events, the incidence reported in the polyphenol-treated groups was not more than that reported in the placebo group. No significant changes were observed in blood counts and blood chemistry profiles after repeated administration of green tea polyphenol products. There was a >60% increase in the area under the plasma EGCG concentration-time curve after 4 weeks of green tea polyphenol treatment at a dosing schedule of 800 mg once daily. No significant changes were observed in the pharmacokinetics of EGCG after repeated green tea polyphenol treatment at a regimen of 400 mg twice daily. The pharmacokinetics of the conjugated metabolites of epigallocatechin and epicatechin were not affected by repeated green tea polyphenol treatment. Four weeks of green tea polyphenol treatment at the selected dose and dosing schedule did not provide protection against UV-induced erythema. CONCLUSIONS We conclude that it is safe for healthy individuals to take green tea polyphenol products in amounts equivalent to the EGCG content in 8-16 cups of green tea once a day or in divided doses twice a day for 4 weeks. There is a >60% increase in the systemic availability of free EGCG after chronic green tea polyphenol administration at a high daily bolus dose (800 mg EGCG or Polyphenon E once daily).
Inverse Spatially Offset Raman Spectroscopy for Deep Noninvasive Probing of Turbid Media

A new type of highly sensitive spatially offset Raman spectroscopy (SORS) developed for deep noninvasive probing of stratified turbid media is described. The technique, termed inverse SORS, permits much greater depths to be interrogated than those accessible with the conventional SORS approach. This is achieved by enhancing the sensitivity of the technique through the elimination of spectral distortions inherent to the conventional SORS methodology. The method also permits the use of higher laser powers in applications where intensity limits exist, such as when probing human tissue in vivo. In addition, the new approach possesses a much higher degree of flexibility, enabling on-the-spot tailoring of experimental conditions such as the magnitude and number of spatial offsets to individual samples. The scheme uses a reverse SORS geometry whereby Raman light is collected through fibers at the center of the probe and laser radiation is delivered to the sample through a beam in the shape of a ring. The method is demonstrated on a layered powder sample and several practical examples of its uses, presented for the first time, are also given. Potential applications include disease diagnosis, noninvasive probing of pharmaceutical products and chemicals through packaging, probing of polymers, biofilms or paints, and homeland security screening.
In vitro inhibitory effects of farnesol and interactions between farnesol and antifungals against biofilms of Candida albicans resistant strains

Abstract Antifungal resistance is a serious problem in clinical infections. Farnesol, which is a potential antifungal agent against biofilms formed by Candida albicans resistant strains (a fluconazole-resistant isolate derived from SC5314 and two clinical Candida resistant isolates), was investigated in this study. The inhibitory effects of farnesol on biofilms were examined by XTT assay. The morphological changes and biofilm thicknesses were analyzed by scanning electron microscopy and confocal laser scanning microscopy, respectively. Additionally, the checkerboard microdilution method was used to investigate the interactions between farnesol and antifungals (fluconazole, amphotericin B, caspofungin, itraconazole, terbinafine and 5-flurocytosine) against biofilms. The results showed decreased SMICs of farnesol and thinner biofilms in the farnesol-treated groups, indicating that farnesol inhibited the development of biofilms formed by the resistant strain. Furthermore, there were synergistic effects between farnesol and fluconazole/5-flurocytosine, while there were antagonistic effects between farnesol and terbinafine/itraconazole, respectively, on the biofilms formed by the resistant strains.
Unique sequence, ski, in Sloan-Kettering avian retroviruses with properties of a new cell-derived oncogene

The Sloan-Kettering viruses (SKVs) are a group of transforming retroviruses that were isolated from chicken embryo cells which had been infected with the avian leukosis virus transformation-defective Bratislava 77 (tdB77). Each of the SKV isolates was shown to contain multiple genomes of different sizes indicating the presence of several viruses in addition to tdB77. To identify and characterize the putative transforming gene(s) of the SKVs, we used hybridization selection to isolate the fraction of a representative cDNA which was SKV specific. Both solution and blot hybridization studies with viral RNAs showed that the specific probe contained a sequence, ski, that was at least partially held in common by the multiple SKV genomes. This conclusion was confirmed by the observation that a molecularly cloned ski probe also hybridized to each of the multiple SKV genomes. Southern blots of chicken DNA revealed homologs of ski (c-ski) which were not associated with endogenous viral loci. Results showing that c-ski was expressed in polyadenylated cytoplasmic RNA of uninfected chicken cells indicated that it is a functional gene. Other data showed that c-ski was conserved in avian and mammalian evolution, suggesting a functional role for the gene in species other than chickens. Using ski cDNA in solution hybridizations with viral RNAs and in Southern blot hybridization with cloned retroviral oncogenes, we did not detect any relationship between ski and any of 15 previously identified oncogenes.
Detection of drechslera avenae in oat seeds

The fungus Drechslera avenae, the causal agent of Helminthosporium leaf spot on oats (Avena sativa), survives as mycelium in crop residues and in infected seeds. In trials carried out in the laboratory, ten methods were evaluated for their efficiency to detect D. avenae in oat seeds. In each experiment, groups of two or three methods were compared to a standard protocol, in which seeds were placed in Petri dishes containing the Reis selective medium and incubated at 25±2 °C for ten days. Data were submitted to analysis of variation and the means of the methods were compared using the Dunnett test at the 5% significance level. Overall, the highest levels of seed infection by D. avenae were observed on oat seeds plated in the osmotic, the oat-agar and the Reis media, or on seeds subjected to heat treatment previous to incubation in malt-agar. Therefore, these methods should be recommended for detection of D. avenae in oat seed testing.
Neurilemmoma in the Foot as a Cause of Heel Pain: A Report of Two Cases

Two cases of deep-seated neurilemmoma that arose from plantar branches of the posterior tibial nerve and caused chronic heel pain are described. At the initial examination, one case was misdiagnosed as tarsal tunnel syndrome and the other was overlooked as plantar fasciitis; both cases were treated for long periods prior to operation. Deep-seated neurilemmomas in the foot can easily be overlooked and misdiagnosed as tarsal tunnel syndrome or plantar fasciitis because of the rarity, absence of palpable mass, and similarity of symptoms to those of other frequently encountered foot disorders. Magnetic resonance imaging provides the best modality for differential diagnosis. In the present cases, surgical excision of the tumors resulted in immediate and complete relief of chronic heel pain. Surgeons should consider neurilemmoma as a cause of persistent chronic heel pain despite the rarity of the disease.
Privacy as a Tradeoff: Introducing the Notion of Privacy Calculus for Context-Aware Mobile Applications

Evidences collected from smartphones users show a growing desire of personalization offered by services for mobile devices. However, the need to accurately identify users' contexts has important implications for user's privacy and it increases the amount of trust, which users are requested to have in the service providers. In this paper, we introduce a model that describes the role of personalization and control in users' assessment of cost and benefits associated to the disclosure of private information. We present an instantiation of such model, a context-aware application for smartphones based on the Android operating system, in which users' private information are protected. Focus group interviews were conducted to examine users' privacy concerns before and after having used our application. Obtained results confirm the utility of our artifact and provide support to our theoretical model, which extends previous literature on privacy calculus and user's acceptance of context-aware technology.
Preparation of Double-Sided MgO Template for YB2Cu3O7-δ Coated Conductors

Reducing production cost and upgrading current capacity are the key issues for the commercialization of YB<sub>2 </sub>Cu<sub>3</sub>O<italic><sub>7-</sub><sub>δ</sub></italic> (YBCO) high-temperature superconducting coated conductors. In this paper, a novel double-sided ion-beam-assisted deposited (IBAD) MgO template has been proposed and introduced for the deposition of YBCO coated conductors on both sides, which contributes significantly to the performance improvement and production cost cutting. In this template, chemical solution derived amorphous Y<sub>2 </sub>O<sub>3</sub> layer was coated on untreated hastelloy tapes to obtain nanometer-level flatted surface with root-mean-square roughness values of 0.8 and 0.5 nm (5 μm × 5 μm area) for each side, respectively. Based on the smooth surface, double-sided IBAD-MgO and homoepitaxial MgO films were deposited on the Y <sub>2</sub>O<sub>3</sub> coatings by a two-step process. The biaxial textures of meter-long double-sided MgO tape showed <italic>ω</italic>-scans of (200) MgO and <italic>Φ</italic>-scans of (220) MgO yield full width at half maximum values of 2.5°–3° and 4.5°–6°for one side, respectively, as well as 2.6°–3.2° and 5.6°–6.5°for the other side. Finally, the double-sided YBCO films deposited on the LaMnO<sub>3</sub> buffered MgO template achieved a high-transition temperature of 90 K and an overall critical current of 290 A/cm at self-field (110 and 180 A/cm for each side).
Hierarchical Artificial Neural Networks for Recognizing High Similar Large Data Sets

This paper proposes a hierarchical artificial neural network for recognizing high similar large data sets. It is usually required to classify large data sets with high similar characteristics in many applications. Analyzing and identifying those data is a laborious task when the methods adopted are primarily based on visual inspection. In many field applications, data sets are measured and recorded continuously using automatic monitoring equipments. Therefore, a large amount of data can be collected, and manual inspection has become an unsuitable approach to recognizing those data. This proposed hierarchical neural network integrates self-organizing feature map (SOM) networks and learning vector quantization (LVQ) networks. The SOM networks provide an approximate method for computing the input vectors in an unsupervised manner. Then the computation of the SOM may be viewed as the first stage of the proposed hierarchical network. The second stage is provided by the LVQ networks based on a supervised learning technique that uses class information to improve the quality of the classifier from the first stage. The multistage hierarchical network attempts to factorize the overall input vector into a number of small groups, each of which requires very little computation. Consequently, by use of the proposed network, the loss in accuracy can be small.
Reproducibility, sensitivity and compatibility of the ProteoExtract® subcellular fractionation kit with saturation labeling of laser microdissected tissues

Laser microdissection (LMD), a method of isolating specific microscopic regions of interest from a tissue that has been sectioned, is increasingly being applied to study proteomics. LMD generally requires tissues to be fixed and histologically stained, which can interfere with protein recovery and subsequent analysis. We evaluated the compatibility and reproducibility of protein extractions from laser microdissected human colon mucosa using a subcellular fractionation kit (ProteoExtract®, Calbiochem). Four protein fractions corresponding to cytosol (fraction 1), membrane/organelle (fraction 2), nucleus (fraction 3) and cytoskeleton (fraction 4) were extracted, saturation labeled with Cy5 and 5 μg separated by both acidic (pH 4–7) and basic (pH 6–11) 2‐DE. The histological stains and fixation required for LMD did not interfere with the accurate subcellular fractionation of proteins into their predicted fraction. The combination of subcellular fractionation and saturation CyDye labeling produced very well resolved, distinct protein spot maps by 2‐DE for each of the subcellular fractions, and the total number of protein spots consistently resolved between three independent extractions for each fraction was 893, 1128, 1245 and 1577 for fractions 1, 2, 3 and 4, respectively. Although significant carryover of protein did occur between fractions, this carryover was consistent between experiments, and very low inter‐experimental variation was observed. In summary, subcellular fractionation kits are very compatible with saturation labeling DIGE of LMD tissues and provide greater coverage of proteins from very small amounts of microdissected material.
Threonine 393 of β‐catenin regulates interaction with Axin

CK2 is a regulatory kinase implicated in embryonic development and in cancer. Among the CK2 substrates is β‐catenin, a protein with dual function in Wnt signaling and cell adhesion. Previously, we reported that CK2 activity is required for β‐catenin stability and we identified threonine (T) 393 as a major CK2 phosphorylation site in β‐catenin. However, it is not known whether phosphorylation at T393 increases β‐catenin stability and if so, what is the mechanism. In this study we investigate the molecular mechanism of β‐catenin stabilization through phosphorylation at T393. We found that pseudophosphorylation of β‐catenin at T393 resulted in a stable activated form of β‐catenin with decreased affinity for Axin in vitro. This phosphomimetic mutant also displayed decreased regulation by Axin in vivo in a bioassay in Xenopus laevis embryos. In contrast, the binding of T393 pseudophosphorylated β‐catenin to E‐cadherin was unaffected. Further analysis showed that pseudophosphorylation at T393 did not prevent β‐catenin phosphorylation by GSK3β. Interestingly, we found that in the presence of pseudophophorylated β‐catenin and another activated form of β‐catenin, the recruitment of GSK3β to Axin is enhanced. These findings indicate that phosphorylation of T393 by CK2 may affect the stability of β‐catenin through decreased binding to Axin. In addition, the increased recruitment of GSK3β to the destruction complex in the presence of activated β‐catenin mutants could be a feedback mechanism to suppress overactive Wnt signaling. J. Cell. Biochem. 108: 52–63, 2009. © 2009 Wiley‐Liss, Inc.
Helicobacter pylori as a class I carcinogen: Physiopathology and management strategies

The gram‐negative bacterium Helicobacter pylori is known as a persistent colonizer of the human stomach, and probably less known is that it is also involved in extraintestinal diseases. Public awareness of its contribution in the development of gastric cancer is less than 15 years old. The efficacy of the current therapies based on antibiotics against H. pylori has been limited by difficulties such as antibiotic resistance and recurrence. As a consequence, the development of promising vaccines was prompted as the best preventive measure. Unfortunately, so far vaccines failed the transition from animal models to human trials. This keynote presentation is to provide a bird's eye view of H. pylori‐related gastric diseases, including gastric cancer, with a synthesis of the molecular mechanisms involved, and an exhaustive presentation and discussion of the current therapeutic guidelines and future strategies for prevention or therapy. J. Cell. Biochem. 102: 264–273, 2007. © 2007 Wiley‐Liss, Inc.