Miracle-dz/UniFAR-FTUs huggingface dataset:
Sprouty genes prevent excessive FGF signalling in multiple cell types throughout development of the cerebellum

Fibroblast growth factors (FGFs) and regulators of the FGF signalling pathway are expressed in several cell types within the cerebellum throughout its development. Although much is known about the function of this pathway during the establishment of the cerebellar territory during early embryogenesis, the role of this pathway during later developmental stages is still poorly understood. Here, we investigated the function of sprouty genes (Spry1, Spry2 and Spry4), which encode feedback antagonists of FGF signalling, during cerebellar development in the mouse. Simultaneous deletion of more than one of these genes resulted in a number of defects, including mediolateral expansion of the cerebellar vermis, reduced thickness of the granule cell layer and abnormal foliation. Analysis of cerebellar development revealed that the anterior cerebellar neuroepithelium in the early embryonic cerebellum was expanded and that granule cell proliferation during late embryogenesis and early postnatal development was reduced. We show that the granule cell proliferation deficit correlated with reduced sonic hedgehog (SHH) expression and signalling. A reduction in Fgfr1 dosage during development rescued these defects, confirming that the abnormalities are due to excess FGF signalling. Our data indicate that sprouty acts both cell autonomously in granule cell precursors and non-cell autonomously to regulate granule cell number. Taken together, our data demonstrate that FGF signalling levels have to be tightly controlled throughout cerebellar development in order to maintain the normal development of multiple cell types.
Sites of Selective cAMP-dependent Phosphorylation of the L-type Calcium Channel α1 Subunit from Intact Rabbit Skeletal Muscle Myotubes (*)

The principal (α1) subunit of purified skeletal muscle dihydropyridine-sensitive (L-type) calcium channels is present in full-length (212 kDa) and COOH-terminal truncated (190 kDa) forms, which are both phosphorylated by cAMP-dependent protein kinase (cA-PK) in vitro. Immunoprecipitation of the calcium channel from rabbit muscle myotubes in primary cell culture followed by phosphorylation with cA-PK, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and two-dimensional phosphopeptide mapping revealed comparable phosphorylation of three COOH-terminal phosphopeptides found in the purified full-length α1 subunit. Stimulation of muscle myotubes with a permeant cAMP analogue, 8-(4-chlorophenylthio) adenosine 3❘,5❘-cyclic monophosphate, prior to immunoprecipitation of α1 results in a 60-80% reduction of cA-PK catalyzed “back” phosphorylation of each of these sites in vitro in calcium channels purified from the cells, indicating that these sites are phosphorylated in vivo in response to increased intracellular cAMP. Serine 687, the most rapidly phosphorylated site in the truncated 190-kDa α1 subunit, was observed as a minor phosphopeptide whose level of phosphorylation was not significantly affected by stimulation of endogenous cA-PK in the myotubes. The COOH-terminal sites, designated tryptic phosphopeptides 4, 5, and 6, were identified as serine 1757 (phosphopeptides 4 and 6) and 1854 (phosphopeptide 5) by a combination of protease cleavage, phosphorylation of synthetic peptides and fusion proteins, specific immunoprecipitation, and phosphopeptide mapping. Phosphorylation of serines 1757 and 1854 in the COOH-terminal region of the 212-kDa α1 subunit in intact skeletal muscle cells may play a pivotal role in the regulation of calcium channel function by cA-PK.
Paradoxical roles for antioxidants in tumor prevention and eradication

Antioxidants have been shown to provide protection against carcinogens, toxic xenobiotics and oxidative stress. This has led to the hypothesis that the addition of antioxidants to cancer chemotherapeutic regimens could increase their efficacy while reducing the side effects often encountered during treatment. The work described in this study set out to test this hypothesis using two different chemotherapeutics, paclitaxel and FUdR, and three different antioxidants, epigallocatechin gallate, phenethyl isothiocyanate and tert-butylhydroquinone. Experiments were carried out on two different breast carcinoma cell lines, MCF-7 and MDA MB435S. Importantly, we did not observe an enhancement of the efficacy of the chemotherapeutic agents in the twelve combinations tested. In fact, for several combinations, simultaneous treatment with an antioxidant attenuated the efficacy of the chemotherapeutic agent. We also determined that the survival advantage provided by antioxidants is consistent with their ability to induce the expression of genes whose regulatory regions contain antioxidant response elements. Together, these findings suggest that the simultaneous use of antioxidants and chemotherapeutic agents has the potential to attenuate the efficacy of chemotherapy by inducing the expression of enzymes that can detoxify cytotoxic agents. In view of these findings, we suggest that the design of chemotherapeutic regimens that combine antioxidants with chemotherapeutic agents should be considered carefully before being initiated.
Changes of intracellular pH in rat mesenteric vascular smooth muscle with high‐K+ depolarization.

1. In mesenteric vascular smooth muscle cells changes in extracellular pH are rapidly transmitted to the cytoplasm. The mechanism involved is unknown, but it may be due to a high proton permeability of the surface membrane, in which case changes in membrane potential would alter the driving force for proton entry. We have therefore examined the voltage sensitivity of intracellular pH (pHi) in these cells. 2. Strips of mesenteric resistance vessels were loaded with SNARF‐1 to monitor pHi and tension was simultaneously measured. Tissues were superfused with oxygenated solutions at 37 degrees C and pH 7.4. Isosmotic substitution of K+ for Na+ was used to depolarize the preparations. 3. pHi was found to be sensitive to alteration of [K+]. Depolarization of the tissue with K+ caused contraction and produced transient increases in pHi. When pHi regulation was blocked there was no significant change in the size of the alkalinization induced by high K+, thus it is unlikely that the results can be explained by voltage sensitivity of pHi regulating mechanisms. 4. In nominally Ca(2+)‐free solution, the tissue does not contract and the alkalinization with high K+ was significantly greater than that occurring in 3 mM Ca2+. 5. There was a rapid acidification, when pHi regulation was blocked, which is consistent with a high proton permeability. 6. The effects of membrane potential on pHi have been modelled and show that they can be accounted for by effects of voltage on H+ influx through a proton channel. The effects of changing external pH on H+ influx also fit the model. Estimation of the proton permeability gave a high value (0.4 cm s‐1). 7. The results presented demonstrate (i) a voltage sensitivity of pHi in mesenteric vascular smooth muscle cells and (ii) a particularly high permeability of the membrane to protons. The physiological significance of these findings is discussed.
Cognitive humor processing: Different logical mechanisms in nonverbal cartoons—an fMRI study

Abstract Although recent fMRI studies on humor have begun to elucidate cognitive and affective neural correlates, they weren't able to distinguish between different logical mechanisms or steps of humor processing, i.e., the detection of an incongruity and its resolution. This fMRI study aimed to focus in more detail on cognitive humor processing. In order to investigate pure incongruity resolution without preprocessing steps, nonverbal cartoons differing in their logical mechanisms were contrasted with nonhumorous pictures containing an irresolvable incongruity. The logical mechanisms were: (1) visual puns (visual resemblance, PUNs); (2) semantic cartoons (pure semantic relationships, SEMs); and (3) Theory of Mind cartoons (which require additionally mentalizing abilities, TOMs). Thirty cartoons from each condition were presented to 17 healthy subjects while acquiring fMR images. The results reveal a left-sided network involved in pure incongruity resolution: e.g., temporo-parietal junction, inferior frontal gyrus and ventromedian prefrontal cortex. These areas are also involved in processing of SEMs, whereas PUNs show more activation in the extrastriate cortex and TOMs show more activation in so-called mentalizing areas. Processing of pictures containing an irresolvable incongruity evokes activation in the rostral cingulate zone, which might reflect error processing. We conclude that cognitive processing of different logical mechanisms depends on separate neural networks.
Concept map construction from text documents using affinity propagation

Concept maps are playing an increasingly important role in various computing fields. In particular, they have been popularly used for organizing and representing knowledge. However, constructing concept maps manually is a complex and time-consuming task. Therefore, the creation of concept maps automatically or semi-automatically from text documents is a worthwhile research challenge. Recently, various approaches for automatic or semi-automatic construction of concept maps have been proposed. However, these approaches suffer from several limitations. First, only the noun phrases in text documents are included without resolution of the anaphora problems for pronouns. This omission causes important propositions available in the text documents to be missed, resulting in decreased recall. Second, although some approaches label the relationship to form propositions, they do not show the direction of the relationship between the subject and object in the form of Subject–Relationship–Object, leading to ambiguous propositions. In this paper, we present a cluster-based approach to semi-automatically construct concept maps from text documents. First, we extract the candidate terms from documents using typed dependency linguistic rules. Anaphoric resolution for pronouns is introduced to map the pronouns with candidate terms. Second, the similarities are calculated between the pairs of extracted candidate terms of a document and clusters are made through affinity propagation by providing the calculated similarities between the candidate terms. Finally, the extracted relationships are assigned between the candidate terms in each cluster. Our empirical results show that the semi-automatically constructed concept maps conform to the outputs generated manually by domain experts, since the degree of difference between them is proportionally small based on a Likert scale. Furthermore, domain experts verified that the constructed concept maps are in accordance with their knowledge of the information system domain.
Magnetoresistance study in thin zig zag NiFe wires

Thickness dependence on the domain wall resistivity of zig zag thin permalloy wires was studied from 10 to 300 K. The maximum domain wall resistivity was obtained in wire with 100-nm-film thickness. The multidomain state resistivity was 14.29 μΩ cm, while single-domain state resistivity was 14.36 μΩ cm at 10 K. The ratio of domain wall magnetoresistance was measured to be 0.034%, 0.112%, and 0.258%, and the magnetic field where the domain wall started to switch was measured as −70, −40, and +80 Oe for wires with thicknesses of 20, 40, and 100 nm, respectively, at 250 K. Domain wall resistivity was nearly independent of temperature for wire with 40-nm-film thickness but varied significantly with temperature for 100-nm-thick wire between 10 and 300 K.
Is interstitial K+ accumulation a key factor in the fatigue process under physiological conditions?

Muscle fatigue, i.e. the decrease in muscle force in response to prolonged or repeated contractions, can originate from any impairment along the neuromuscular system, from a reduction in central neural drive to impaired contractile protein interaction. At the muscle level, a decrease in the force-generating capacity can result from (i) an impaired force per cross-bridge, (ii) a reduced myofibrillar Ca2+ sensitivity and (iii) a decreased Ca2+ release from the sarcoplasmic reticulum (SR). During prolonged activity, the interstitial K+ increases and concentrations of 10–12 mm have been observed. Therefore, resultant sarcolemmal excitability, leading to a reduction in the amplitude of the action potential, can result in impaired SR Ca2+ release. This last factor was the point of interest in a recent article in The Journal of Physiology by Clausen & Nielsen (2007), that investigated the effect of excitability failure on force production during fatigue of rat soleus muscle exposed to different bath K+ concentrations ([K+]o). Clausen & Nielsen showed that the rate of force decline was greater when muscle was pre-exposed for 10–40 min to a high [K+]o (10 mm) and then electrically stimulated compared with low [K+]o (4 mm). They also showed that this increased fatigability could be counteracted by applying different agents known to directly or indirectly stimulate the Na+–K+ pumps. Thus, the data obtained by Clausen & Nielsen (2007) strongly indicate that these high [K+]o values induce a reduction in sarcolemmal excitability, leading to a decrease in soleus endurance which can be prevented by the stimulation of the Na+–K+ pump. Nevertheless, it is possible that these results are confined to the experimental conditions used to induce fatigue. In their study, Clausen & Nielsen (2007) stimulated soleus muscle continuously at 60 Hz for 1 min; muscle endurance was then assessed by calculating the rate of force decline over the first 20 s of stimulation. In this letter, the possibility that a rise in [K+]o may not be a critical factor of muscle fatigue under physiological conditions is discussed.
Prevalence of glaucoma in a South brazilian population: Projeto Glaucoma.

PURPOSE To assess the prevalence of glaucoma in a South Brazilian population. METHODS Subjects older than 40 years underwent a screening examination that included a medical interview, slit lamp examination, tonometry, and fundoscopy. Those with suspected glaucoma (based on optic disc appearance and/or intraocular pressure) underwent a comprehensive ophthalmic evaluation during the definitive examination. Glaucoma was diagnosed based on the International Society of Geographical and Epidemiologic Ophthalmology classification. RESULTS A total of 1636 subjects were examined (76.5% participation rate); 71% of the study population self-reported their race as white and 24% as nonwhite (most black and mixed-black/white). Glaucoma was found in 56 subjects (crude prevalence of all glaucoma: 3.4%; 95% CI, 2.5-4.3), primary open-angle glaucoma (POAG) was found in 40 (2.4%; 95% CI, 1.7-3.2), and primary angle-closure glaucoma (PACG) in 12 (0.7%; 95% CI, 0.3-1.1). Six (12%) subjects with primary glaucoma had a previous diagnosis of the disease. Nonwhite persons had a higher prevalence rate of POAG than did white participants, although this difference was not significant (3.8% vs. 2.1%, respectively, P = 0.11). Unilateral blindness due to primary glaucoma was observed in seven subjects (five POAG/2 PACG), and nonwhites had a higher rate of unilateral blindness than did whites (five versus two cases, respectively, P = 0.014). CONCLUSIONS Compared to incidence in Hispanic and European populations, PACG was more common among South Brazilians, whereas the POAG rates were similar. The rate of undiagnosed glaucoma was almost 90%. The higher POAG prevalence in the population self-reported as nonwhite may affect the estimation of glaucoma in Brazil, as more than 40% of the population self-report their race as nonwhite.
Evaluation of anti-coccidial vaccines and coccidiostate drugs on growth performance in experimental coccidiosis of broiler chickens.

The present study was designed to compare the effect of coccidiostate drugs and cocccidial vaccines on performance of coccidian-infected broiler chickens. Nine hundred and sixty one-day-old broiler chicks from the Ross strain were randomly divided to eight treatment groups that each group contained 3 replicates. The birds of group 1 as negative control and group 2 as positive control did not receive any medicines or vaccines. Treatments 3 and 4 fed diets supplemented with Salinomycine and Diclazoril respectively, but did not immunize. The chickens of groups 5 to 8 immunized with coccidial vaccines (Livacox Q, Paracox 5, Livacox T and Iracoc respectively) by drinking water on day 5 of age. Chicks in treatments 2 to 8 were inoculated with a suspension containing four Eimeria species of 26 days of age. Surveillances for coccidian oocysts of feces samples were carried out from 7 to 13 days of post-challenged. Body weight and feed conversion ratios were determined weekly. Our data indicated that using coccidial vaccines and coccidiostate drugs decreased OPG of feces. The highest mean of body weight was related to the chickens treated with Salinimycine. The lowest feed conversion ratio was related to negative control groups. It could be indicated that coccidial vaccines and coccidiostate medicines could decline OPG and improve growth performance of broiler chickens.
Metastasis SuppressorGeneRafKinase Inhibitor Protein ( RKIP ) Is aNovel Prognostic Marker in ProstateCancer

BACKGROUND. DiminishedexpressionofRaf kinase inhibitor protein (RKIP), an inhibitor of the Raf signaling cascade, promotes prostate cancer (PCa) metastasis in a murine model, suggesting that it is ametastasis suppressor gene.However, the prognostic significance of RKIP expression and its association with metastasis in PCa patients is unknown. METHODS. To investigate RKIP protein expression is a prognostic marker in PCa we performed immunohistochemical staining for RKIP expression in tissuemicroarrays consisting of 758 non-neoplastic prostate tissues, primary tumors and metastases from 134 PCa patients. TheCox proportional-hazardsmodelwas used to adjust for covariates includingGleason score, tumor volume, tumor weight, clinical stage, digital rectal exam findings, serum PSA level and surgical margins. RESULTS. RKIP expression was low in approximately 5%, 48%, and 89%of non-neoplastic prostate, primary tumors andmetastases, respectively. LowRKIPexpression inprimary tumors was a strong positive predictive factor for PCa recurrence based on PSA levels. In patients whose primary tumors expressed high RKIP levels, the 7-year PSA recurrence rate was <10%; whereas in patients with tumors with low RKIP expression the recurrence rate was 50% (P< 0.001). Multivariate analysis revealed RKIP was an independent prognostic factor (P< 0.001). CONCLUSION. In contrast to increased expression of pro-tumorigenic genes, these results demonstrate decreased protein expression of a gene, for example, RKIP, can serve as a prognostic marker in PCa patients. Prostate 66: 248–256, 2006. # 2005 Wiley-Liss, Inc.
Advances in methods for the determination of biologically relevant lipid peroxidation products

Abstract Lipid peroxidation is recognized to be an important contributor to many chronic diseases, especially those of an inflammatory pathology. In addition to their value as markers of oxidative damage, lipid peroxidation products have also been shown to have a wide variety of biological and cell signalling effects. In view of this, accurate and sensitive methods for the measurement of lipid peroxidation products are essential. Although some assays have been described for many years, improvements in protocols are continually being reported and, with recent advances in instrumentation and technology, highly specialized and informative techniques are increasingly used. This article gives an overview of the most currently used methods and then addresses the recent advances in some specific approaches. The focus is on analysis of oxysterols, F2-isoprostanes and oxidized phospholipids by gas chromatography or liquid chromatography mass spectrometry techniques and immunoassays for the detection of 4-hydroxynonenal.
Measuring participation outcomes following life-saving medical interventions: the Role Checklist Version 2: Quality of Performance

Abstract Purpose: To establish the Role Checklist Version 2: Quality of Performance as a measure of past, present and desired future role incumbency, role value and self-perception of the quality of role performance for 10 roles consistent with the ICF Participation Domains. Methods: Discuss the literature on the measurement of participation; present a conceptually based case for similarities in content between the RC V2: QP; and illustrate through a case example its efficacy as a balanced measure of performance. Results: Despite different origins, the ICF domain areas: Chapters 6–9 correspond to the roles included in the RC V2: QP. The measure is shown sensitive to change in quality of performance through insider self-report serving in the case provided, as an early indicator of deterioration in physical status. Conclusion: A balanced measure of the insider and outsider perspective of participation, the case of one liver transplant recipient illustrates how the RC V2: QP serves to reflect participation outcomes thus, adding an available measure of the ICF construct of participation. Implications for Rehabilitation The Role Checklist Version 2: Quality of Performance is consistent with the ICF performance qualifier of participation. The insider view of participation is strengthened in this Second version of the Role Checklist. The Role Checklist Version 2: Quality of Performance provides a general measure of participation that can be used across populations.
Classical Conditioning of Pupillary Constriction

Previous attempts to condition classically the pupillary response have resulted in mixed outcome. Studies using light as the UCS have generally been unsuccessful while those studies using shock as the UCS have been more successful. In the present study six subjects were visually presented 15 CVC trigrams while their pupil sizes were monitored. Five of the CVCs had been previously presented, five had been previously presented while paired with shock, and five had not been previously presented. Analysis indicated that more pupillary constriction occurred to the five CVCs paired with shock than those presented without shock or those not previously presented. The resulting classically conditioned pupillary constriction is discussed in terms of the development of meaning through classical conditioning.