Miracle-dz/UniFAR-FTUs huggingface dataset:
Glucagon Promotes cAMP-response Element-binding Protein Phosphorylation via Activation of ERK1/2 in MIN6 Cell Line and Isolated Islets of Langerhans*

By using the MIN6 cell line and pancreatic islets, we show that in the presence of a low glucose concentration, corresponding to physiological glucagon release from α cells, glucagon treatment of the β cell caused a rapid, time-dependent phosphorylation and activation of p44/p42 mitogen-activated protein kinase (ERK1/2) independently from extracellular calcium influx. Inhibition of either cAMP-dependent protein kinase (PKA) or MEK completely blocked ERK1/2 activation by glucagon. However, no significant activation of several upstream activators of MEK, including Shc-p21Ras and phosphatidylinositol 3-kinase, was observed in response to glucagon treatment. Chelation of intracellular calcium (intracellular [Ca2+]) reduced glucagon-mediated ERK1/2 activation. In addition, internalization of glucagon receptors through clathrin-coated pits formation is required for ERK1/2 activation. Remarkably, glucagon promotes the nuclear translocation of ERK1/2 and induces the phosphorylation of cAMP-response element-binding protein (CREB). Miniglucagon, produced from glucagon and released together with the mother hormone from the α cells in low glucose situations, blocks the insulinotropic effect of glucagon, whereas it does not inhibit the glucagon-induced PKA/ERK1/2/CREB pathway. We conclude that glucagon-induced ERK1/2 activation is mediated by PKA and that an increase in [Ca2+]i is required for maximal ERK activation. Our results uncover a novel mechanism by which the PKA/ERK1/2 signaling network engaged by glucagon, in situation of low glucose concentration, regulates phosphorylation of CREB, a transcription factor crucial for normal β cell function and survival.
Effects of sources of protein and enzyme supplementation on protein digestibility and chyme characteristics in broilers

1. The purpose of this study was to evaluate the effects of protein source and enzyme supplementation on protein digestibility and chyme characteristics in broilers. 2. One hundred and twenty growing (13 d old) and 60 finishing (34 d old) Arbor Acre strain commercial male broilers were selected and placed into individual metabolic cages. 3. The experiment was a 5 × 2 factorial arrangement with 5 different sources of protein: casein, fish meal, soybean meal (SBM), soy protein concentrate (SPC), maize gluten meal (MGM) and two levels of protease (bromelain), 0 and 65 CDU/kg diets. 4. The diets were iso-nitrogenous and semi-purified, with Cr 2 O 3 as an indicator for determination of ileal digestibility and chyme characteristics. 5. Apparent ileal protein digestibility (AIPD) in both growing and finishing chickens was highest on the casein diet, followed by fish meal, SBM, SPC and MGM. 6. Enzyme inclusion did not improve protein digestibility, but significantly decreased the digesta pH value in the gizzard and increased pH in the ileum in the 3-week-old broilers. 7. The digesta pH values in the gizzard and duodenum were significantly lower in the SBM and fish meal groups compared with the other protein groups. The molecular weight distribution pattern of the soluble protein in the chyme of the gastrointestinal (GI) segments showed a similar trend, regardless of the enzyme inclusion or the stage of growth. 8. The molecular weight profile of soluble protein changed dynamically in the casein fed broilers from the gizzard to ileum and the low molecular weight proteins, <7 kDa, reached maximum levels at the ileum. The molecular weight profile of the soluble protein in the SBM and SPC changed between the jejunum and the ileum and in the intermediate molecular soluble protein weight (7 to 10 kDa) was significantly decreased. This indicated that the hydrolysis process began from the middle to the posterior end of the small intestine. 9. Similar profiles were also shown with fish meal protein. The pattern of distribution, however, did not show any prominent change in the GI segments of the MGM group. 10. The pepsin, trypsin and chymotrypsin protease activity in the gizzard and duodenum were highest in the casein group and lowest in the MGM group as compared with the other protein groups. 11. The rate change in the patterns of molecular weight distribution in soluble protein and the digestive enzyme activity provide indications of the partial digestibility of different protein sources. The exogenous enzyme, bromelain, did not show any beneficial effect on protein digestion.
Direct Visualization of Trans-Synaptic Neurexin–Neuroligin Interactions during Synapse Formation

Neurexins and neuroligins are synaptic cell-adhesion molecules that are essential for normal synapse specification and function and are thought to bind to each other trans-synaptically, but such interactions have not been demonstrated directly. Here, we generated neurexin-1β and neuroligin-1 and neuroligin-2 fusion proteins containing complementary “split” GFP fragments positioned such that binding of neurexin-1β to neuroligin-1 or neuroligin-2 allowed GFP reconstitution without dramatically changing their binding affinities. GFP fluorescence was only reconstituted from split-GFP-modified neurexin-1β and neuroligin-1 if and after neurexin-1β bound to its neuroligin partner; reassociation of the split-GFP components with each other did not mediate binding. Using trans-cellular reconstitution of GFP fluorescence from split-GFP-modified neurexin-1β and neuroligins as an assay, we demonstrate that trans-synaptic neurexin/neuroligin binding indeed occurred when mouse hippocampal neurons formed synapses onto non-neuronal COS-7 cells expressing neuroligins or when mouse hippocampal neurons formed synapses with each other. This visualization of synapses by neurexin/neuroligin binding prompted us to refer to this approach as “SynView. ” Our data demonstrate that neurexin-1β forms a trans-synaptic complex with neuroligin-1 and neuroligin-2 and that this interaction can be used to label synapses in a specific fashion in vivo.
Composition of the panel of reference for concordance tests: Do teaching functions have an impact on examinees’ ranks and absolute scores?

Background: Concordance tests are designed to assess the component of uncertainty of clinical reasoning. Scoring is based on a comparison of examinees’ answers with those of a panel of reference, including their variability. This allows construction of tests that are close to real clinical life, with all its complexity and ambiguity. Aim: This study was carried out to determine the effect of teaching functions of members composing the reference panels on students’ scores and ranking. Methods: A group of 80 residents in family medicine from a French University (Bobigny) completed a 72-item concordance test. The answers of two panels, each made up of 29 family physicians (teaching function versus non-teaching function), were used to generate the correction keys. Results: Correlation between the sets of data obtained with the two panels is high (ICC = 0.98). Concordance scores obtained from the teaching-function panel are higher than scores obtained from the non-teaching-function panel (72.0 versus 76.3; p < 0.001). Ranking provided by the two panels was very similar. Conclusions: This legitimizes the use of non-teaching physicians on panels. Panel composition influenced absolute score values: Residents showed more concordance with their academic trainers than with community-based physicians.
Reciprocal in vivo regulation of myocardial G protein-coupled receptor kinase expression by beta-adrenergic receptor stimulation and blockade.

BACKGROUND Impaired myocardial beta-adrenergic receptor (betaAR) signaling, including desensitization and functional uncoupling, is a characteristic of congestive heart failure. A contributing mechanism for this impairment may involve enhanced myocardial beta-adrenergic receptor kinase (betaARK1) activity because levels of this betaAR-desensitizing G protein-coupled receptor kinase (GRK) are increased in heart failure. An hypothesis has emerged that increased sympathetic nervous system activity associated with heart failure might be the initial stimulus for betaAR signaling alterations, including desensitization. We have chronically treated mice with drugs that either activate or antagonize betaARs to study the dynamic relationship between betaAR activation and myocardial levels of betaARK1. METHODS AND RESULTS Long-term in vivo stimulation of betaARs results in the impairment of cardiac +betaAR signaling and increases the level of expression (mRNA and protein) and activity of +betaARK1 but not that of GRK5, a second GRK abundantly expressed in the myocardium. Long-term beta-blocker treatment, including the use of carvedilol, improves myocardial betaAR signaling and reduces betaARK1 levels in a specific and dose-dependent manner. Identical results were obtained in vitro in cultured cells, demonstrating that the regulation of GRK expression is directly linked to betaAR signaling. CONCLUSIONS This report demonstrates, for the first time, that betaAR stimulation can significantly increase the expression of betaARK1 , whereas beta-blockade decreases expression. This reciprocal regulation of betaARK1 documents a novel mechanism of ligand-induced betaAR regulation and provides important insights into the potential mechanisms responsible for the effectiveness of beta-blockers, such as carvedilol, in the treatment of heart failure.
Characterizing impulsivity profile in patients with obsessive–compulsive disorder

Abstract Objective. Impulsivity represents a key dimension in obsessive–compulsive disorder (OCD), in relation to outcome and course. It can be assessed through the Barratt Impulsiveness Scale (BIS), which explores three main areas: attentional, motor, and nonplanning. Present study was aimed to assess level of impulsivity in a sample of OCD patients, in comparison with healthy controls, using the BIS. Methods. Seventy-five OCD outpatients, 48 of them having psychiatric comorbidities and 70 healthy controls, were assessed through the BIS, and their scores were analyzed using Student's t-test for independent samples, on the basis of demographic and clinical characteristics. Results. BIS total scores were significantly higher (P: 0.01) in patients compared to controls, with no difference between pure and comorbid patients. Attentional impulsivity scores were significantly higher than controls in patients with pure (P < 0.001) and comorbid OCD (P < 0.001), without differences among them. Patients with multiple OC phenotypes showed higher, though statistically non significant, total and attentional scores, compared to single phenotype patients. In addition, patients with comorbid major depressive disorder had higher, though statistically non significant, total and attentional scores, compared to patients with comorbid bipolar disorder, generalized anxiety disorder, and other disorders. Conclusions. Present findings showed higher impulsivity levels in OCD patients versus controls, particularly in the attentional area, and ultimately suggest a potential cognitive implication.
Evaluation of routine prenatal diagnosis by a registry of congenital anomalies

Prenatal diagnosis performed by ultrasound scan is now a routine part of prenatal care in many countries. How many fetal anomalies are actually detected by these procedures? We have used our registry of congenital malformations to answer this question. In a previous study (Prenat. Diagn., 12, 263–270, 1992), considering the period 1979–1988, we have shown that prenatal diagnosis was performed in 23.1 per cent of fetuses with a chromosomal aberration and in 20.1 per cent of fetuses with non‐chromosomal anomalies. In 1991 and 1992, the percentatge of termination for Down syndrome was 44.4 and 41.9 per cent, respectively. From 1989 to 1992, the detection rate and the specificity of prenatal diagnosis by ultrasonographic examination were improved. The detection rate for isolated malformations (fetuses with only one anomaly) and for multiple malformed children was 26.2 and 66.0 per cent, respectively. The detection rate of congenital anomalies by ultrasonography was variable for the different categories of malformation. A high detection rate was observed for anencephaly (100 per cent) and urinary tract malformation. A low detection rate was seen for cleft lip (17.5 per cent) and limb reduction defects (18.2 per cent).
Computer aided plant identification system

Human pressure on the environment has steadily increased throughout the last few decades, especially in Southeast Asia. This part of the world is also particularly rich in biodiversity and an appropriate biological knowledge is in high demand by the civil society which is actually asking for a “greener” life and the questions of quality of life are rising more and more. Unfortunately, plants recognition/identification skills of people in these countries are still limited. However, this skill can be improved with the aid of information technology. Recently, a number of works have been dedicated to plant information collection, plant information management and plant recognition. However, the developed systems are far from user requirement. In this paper, we present our computer aided plant identification system. The developed system contains two main parts: a semi-automatic graphical tool and an automatic plant identification method based on leaf images. Feedbacks from end users for graphical tool show that this tool does not have disadvantage of the classical tools (too technical, not sufficiently precise) while the experimental results of automatic plant identification method based on leaf image analysis are promising.
Effects of Political Connections and Corporate Governance on Tax Aggressiveness in Indonesian Service and Banking Sectors

We investigate whether political connections and corporate governance have any effects on tax aggressiveness in service and banking sector in Indonesia. Corporate governance act as the independent variable on the first model, and as moderating variable on the second model. Tax aggressiveness is measured using effective tax rates. Political connection is measured with the amount of any connection between the company and its board member's political background. While the measurement of corporate governance are among others: board independence, board size, CEO duality, institutional ownership, and external auditor's reputation. We took the samples service companies and banks listed on the Indonesia Stock Exchange for the period 2013-2017. The analysis used in this study is the multiple linear regression analysis. The finding is that political connection does not influence tax aggressiveness in both sectors. In the service sector, corporate governance measured with CEO duality and institutional ownership has a negative effect on tax aggressiveness, while the other measurements have no effect. While in banking sectors, board size has a negative effect, institutional ownership and external auditor's reputation have a positive influence. Corporate governance did not moderate the influence of political connections on tax aggressiveness in both sectors.
A contribution to the fault-based testing of aspect-orientd software

Aspect-Oriented Programming (AOP) is a contemporary software development technique that strongly relies on the Separation of Concerns principle. It aims to tackle software modularisation problems by introducing the aspect as a new implementation unit to encapsulate behaviour required to realise the so-called crosscutting concerns. Despite the benefits that may be achieved with AOP, its implementation mechanisms represent new potential sources of faults that should be handled during the testing phase. In this context, mutation testing is a widely investigated fault-based test selection criterion that can help to demonstrate the absence of prespecified faults in the software. It is believed to be an adequate tool to deal with testing-related specificities of contemporary programming techniques such as AOP. However, to date, the few initiatives for customising the mutation testing for aspect-oriented (AO) programs show either limited coverage with respect to the types of simulated faults, or a need for both adequate tool support and proper evaluation. This thesis tackles these limitations by defining a comprehensive mutation-based testing approach for AO programs written in the AspectJ language. It starts with a fault-proneness investigation in order to define a fault taxonomy for AO software. Such taxonomy encompasses a range of fault types and underlay the definition of a set of mutation operators for AO programs. Automated tool support is also provided. A series of quantitative studies show that the proposed fault taxonomy is able to categorise faults identified from several available AO systems. Moreover, the studies show that the mutation operators are able to simulate faults that may not be revealed by pre-existing, non-mutation-based test suites. Furthermore, the effort required to augment the test suites to provide adequate coverage of mutants does not tend to overwhelm the testers. This provides evidence of the feasibility of the proposed approach and represents a step towards the practical fault-based testing of AO programs.
Activation of purified cardiac ryanodine receptors by dihydropyridine agonists.

Prior observations have raised the possibility that dihydropyridine (DHP) agonists directly affect the sarcoplasmic reticulum (SR) cardiac Ca(2+) release channel [i.e., ryanodine receptor (RyR)]. In single-channel recordings of purified canine cardiac RyR, both DHP agonists (-)-BAY K 8644 and (+)-SDZ202-791 increased the open probability of the RyR when added to the cytoplasmic face of the channel. Importantly, the DHP antagonists nifedipine and (-)-SDZ202-791 had no competitive blocking effects either alone or after channel activation with agonist. Thus there is a stereospecific effect of SDZ202-791, such that the agonist activates the channel, whereas the antagonist has little effect on channel activity. Further experiments showed that DHP agonists changed RyR activation by suppressing Ca(2+)-induced inactivation of the channel. We concluded that DHP agonists can also influence RyR single-channel activity directly at a unique allosteric site located on the cytoplasmic face of the channel. Similar results were obtained in human purified cardiac RyR. An implication of these data is that RyR activation by DHP agonists is likely to cause a loss of Ca(2+) from the SR and to contribute to the negative inotropic effects of these agents reported by other investigators. Our results support this notion that the negative inotropic effects of DHP agonists result in part from direct alteration in the activity of RyRs.
Development of exertainment with interactive floor display

This paper describes new types of amusement and exertainment with an interactive floor display system using infrared radars. The interactive floor display system we have used as a prototype platform consists of a PC, a projector creating large screen image on floor, and infrared radars adding touch detection function on floor. Players can move fast and jump high on the exertainment application screen due to contactless measurement of the touch position by infrared radars. Two production examples of exertainment are introduced and perspectives for further development of the platform are discussed.
Young's modulus, bending strength, and tissue physical properties of human compact bone

The Young's modulus, bending strength, apparent density, and ash content of 155 human compact bone bending specimens were determined. Both Young's modulus (E) and bending strength (S) were strongly correlated to tissue dry apparent density (ρa). Based upon the correlation coefficient (R) and the percent deviation of the data from the regression curve (% dev.), these correlations were best described by power law relationships: E∞ ρa1. 54 (R2 = 0.79, % dev. = 2.4) and S∞ ρa2. 18 (R2 = 0.80, % dev. = 6.4). Bending strength was related to Young's modulus raised to the 1.26 power, implying a nonlinear relationship for these variables. We found a weak correlation between ash content and the mechanical behavior of the compact bone specimens, particularly Young's modulus, but could not statistically justify formulation of a more complex multivariate power model incorporating both density and ash content. Regional variations in strength and stiffness along the femoral shaft and within the cortex were also noted and were attributed primarily to differences in apparent density. The relationships formulated for the mechanical behavior of human compact bone are discussed in terms of the results of previous investigations of the mechanical behavior of nonhuman compact bone and human cancellous bone.
Detection of Staphylococcus aureus andStaphylococcus epidermidis in Clinical Samples by 16S rRNA-Directed In Situ Hybridization

ABSTRACT Staphylococcus epidermidis and Staphylococcus aureus are the most common causes of medical device-associated infections, including septicemic loosenings of orthopedic implants. Frequently, the microbiological diagnosis of these infections remains ambiguous, since at least some staphylococci have the capacity to reduce their growth rate considerably. These strains exhibit a small-colony phenotype, and often they are not detectable by conventional microbiological techniques. Moreover, clinical isolates ofS. aureus and S. epidermidis adhere to polymer and metal surfaces by the generation of thick, multilayered biofilms consisting of bacteria and extracellular polysaccharides. This study reports improved detection and identification of S. aureusand S. epidermidis by an in situ hybridization method with fluorescence-labeled oligonucleotide probes specific for staphylococcal 16S rRNA. The technique has proven to be suitable for the in situ detection of staphylococci, which is illustrated by the identification of S. epidermidis in a connective tissue sample obtained from a patient with septicemic loosening of a hip arthroplasty. We also show that this technique allows the detection of intracellularly persisting bacteria, including small-colony variants of S. aureus, and the differentiation of S. epidermidisfrom other clinically relevant staphylococci even when they are embedded in biofilms. These results suggest that the 16S rRNA in situ hybridization technique could represent a powerful diagnostic tool for the detection and differentiation of many other fastidious microorganisms.
Effects of achievement goals on perceptions of competence in conditions of unfavourable social comparisons: The mastery goal advantage effect

BACKGROUND Previous prospective studies have documented that mastery-approach goals are adaptive because they facilitate less negative psychological responses to unfavourable social comparisons than performance-approach goals. AIMS This study aimed to confirm this so-called 'mastery goal advantage' effect experimentally. METHODS A 2 × 3 design was adopted where achievement goals (mastery vs. performance) and normative information (favourable vs. no-normative information vs. unfavourable) were manipulated as between participant factors. SAMPLE Participants were 201 undergraduates, 57 males and 144 females, ranging in age from 17 to 55 years (Mage = 22.53, SD = 6.51). RESULTS Regression analyses pointed out that experimentally induced mastery-approach goals facilitated higher levels of competence and happiness with task performance than experimentally induced performance-approach goals in conditions of unfavourable social comparisons. In contrast, although performance-approach goals yielded the highest levels of happiness with task performance in conditions of favourable social comparisons, this positive effect of performance-approach goals did not extend to perceptions of competence. CONCLUSION Current findings broaden understanding of the adaptive nature of mastery-approach goals and suggest that it is possible to modulate aversive responses to unfavourable social comparisons by focusing attention on mastery-approach goals.