Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of the endophilins ( SH 3 p 4 y p 8 y p 13 ) as novel binding partners for the b 1-adrenergic receptor

Several G-protein coupled receptors, such as the b1-adrenergic receptor (b1-AR), contain polyproline motifs within their intracellular domains. Such motifs in other proteins are known to mediate protein–protein interactions such as with Src homology (SH)3 domains. Accordingly, we used the proline-rich third intracellular loop of the b1-AR either as a glutathione S-transferase fusion protein in biochemical ‘‘pull-down’’ assays or as bait in the yeast two-hybrid system to search for interacting proteins. Both approaches identified SH3p4yp8yp13 (also referred to as endophilin 1y2y3), a SH3 domain-containing protein family, as binding partners for the b1-AR. In vitro and in human embryonic kidney (HEK) 293 cells, SH3p4 specifically binds to the third intracellular loop of the b1-AR but not to that of the b2-AR. Moreover, this interaction is mediated by the C-terminal SH3 domain of SH3p4. Functionally, overexpression of SH3p4 promotes agonist-induced internalization and modestly decreases the Gs coupling efficacy of b1-ARs in HEK293 cells while having no effect on b2-ARs. Thus, our studies demonstrate a role of the SH3p4yp8yp13 protein family in b1-AR signaling and suggest that interaction between proline-rich motifs and SH3-containing proteins may represent a previously underappreciated aspect of G-protein coupled receptor signaling.
Ca2+-dependent Activation of the 33-kDa Protein Kinase Transmits Thrombin Receptor Signals in Human Platelets

Summary Thrombin stimulation induces a dramatic increase in the activity of the 33-kDa serine/threonine kinase (PK33) in human platelets (10). The Arg-Gly-Asp (RGD) peptide, an inhibitor of the thrombin-mediated aggregation of platelets, did not affect the PK33 activation induced by thrombin suggesting that the activation of this kinase occurs independently from platelet aggregation. To identify a potential role of Ca2+ and calmodulin in the regulation of PK33, the effect of several Ca2+/calmodulin inhibitors on the thrombin-induced activation of PK33 was assessed using denaturation/renaturation method. Pretreatment of platelets with EGTA decreased the maximum PK33 activity induced by thrombin. The chelation of both the extra- and the intracellular Ca2+ by EGTA and by acetoxymethyl ester of 5,5′ -dimethyl-bis-(<9-aminophen-oxy) ethane-N,N,N′,N′-tetraacetic acid (BAPTA-AM) decreased further the PK33 activation by thrombin. Preincubation of platelets with the anticalmodulin agent, N-(4-aminobutyl)-5-chloro-2-naphtha-lenesulfonamide (W13), inhibited markedly the activation of PK33 by thrombin, whereas the inactive structural analog N-(4-aminobutyl)-2-naphthalenesulfonamide (W12) and the myosin light chain kinase inhibitor 1 -(5-chloronaphthalene-1 -sulfonyl)-1 H-hexahydro-1,4-diaze-pine (ML9) showed very weak inhibitory effects. Treatment of resting platelets with the calcium ionophore, A23187, activated PK33 in a dose-dependent manner; phorbol 12-myristate 13-acetate enhanced this effect. However, the two foregoing agents did not induce similar degree of PK33 activities as thrombin. These results indicate that the activation of PK33 is independent of the formation of the GPIIb/IIIa-fibrinogen complex and that it might be regulated by a Ca2+-dependent pathway.
Mouse Models for Investigating the Developmental Basis of Human Birth Defects

Clinicians and basic scientists share an interest in discovering how genetic or environmental factors interact to perturb normal development and cause birth defects and human disease. Given the complexity of such interactions, it is not surprising that 4% of human infants are born with a congenital malformation, and cardiovascular defects occur in nearly 1%. Our research is based on the fundamental hypothesis that an understanding of normal and abnormal development will permit us to generate effective strategies for both prevention and treatment of human birth defects. Animal models are invaluable in these efforts because they allow one to interrogate the genetic, molecular and cellular events that distinguish normal from abnormal development. Several features of the mouse make it a particularly powerful experimental model: it is a mammalian system with similar embryology, anatomy and physiology to humans; genes, proteins and regulatory programs are largely conserved between human and mouse; and finally, gene targeting in murine embryonic stem cells has made the mouse genome amenable to sophisticated genetic manipulation currently unavailable in any other model organism.
GalSOM - Colour-Based Image Browsing and Retrieval with Tree-Structured Self-Organising Maps

This paper describes an image browsing and retrieval application called GalSOM. Bitmap images are described by their colour histograms and sorted using an improved variant of the tree-structured self-organising map (TS-SOM) algorithm. The advantages of using such a system are discussed in detail, and their application to the problem of image theft detection is proposed.
Parameter Estimations of Dynamic Energy Budget (DEB) Model over the Life History of a Key Antarctic Species: The Antarctic Sea Star Odontaster validus Koehler, 1906

Marine organisms in Antarctica are adapted to an extreme ecosystem including extremely stable temperatures and strong seasonality due to changes in day length. It is now largely accepted that Southern Ocean organisms are particularly vulnerable to global warming with some regions already being challenged by a rapid increase of temperature. Climate change affects both the physical and biotic components of marine ecosystems and will have an impact on the distribution and population dynamics of Antarctic marine organisms. To predict and assess the effect of climate change on marine ecosystems a more comprehensive knowledge of the life history and physiology of key species is urgently needed. In this study we estimate the Dynamic Energy Budget (DEB) model parameters for key benthic Antarctic species the sea star Odontaster validus using available information from literature and experiments. The DEB theory is unique in capturing the metabolic processes of an organism through its entire life cycle as a function of temperature and food availability. The DEB model allows for the inclusion of the different life history stages, and thus, becomes a tool that can be used to model lifetime feeding, growth, reproduction, and their responses to changes in biotic and abiotic conditions. The DEB model presented here includes the estimation of reproduction handling rules for the development of simultaneous oocyte cohorts within the gonad. Additionally it links the DEB model reserves to the pyloric caeca an organ whose function has long been ascribed to energy storage. Model parameters described a slowed down metabolism of long living animals that mature slowly. O. validus has a large reserve that—matching low maintenance costs- allow withstanding long periods of starvation. Gonad development is continuous and individual cohorts developed within the gonads grow in biomass following a power function of the age of the cohort. The DEB model developed here for O. validus allowed us to increase our knowledge on the ecophysiology of this species, providing new insights on the role of food availability and temperature on its life cycle and reproduction strategy.
Metastatic dissemination of human malignant oral keratinocyte cell lines following orthotopic transplantation reflects response to TGF‐β 1

This study examined the behaviour of nine human malignant oral keratinocyte cell lines following orthotopic transplantation to the floor of the mouth of athymic mice. Tumourigenesis, local spread, and metastatic dissemination were correlated with known cellular responses to transforming growth factor‐β 1 (TGF‐β 1). Six of nine cell lines were tumourigenic; four of these cell lines showed local spread which was characterized by vascular and bone invasion. Metastatic spread was uncommon, with only 9% of animals with primary tumours developing metastases and these were almost exclusively found in the regional lymph nodes; there was one pulmonary metastasis and no liver deposits. Tumour cell behaviour did not reflect the clinical stage of the original tumours. Cell lines that were resistant to TGF‐β 1‐induced growth inhibition were more likely to form primary tumours, exhibit local spread, and metastasize than cells that were growth‐inhibited by the ligand. The data demonstrate that tumourigenicity and tumour behaviour in this orthotopic mouse model varied between cell lines and that the pattern of local invasion and metastasis was similar to that seen in human oral cancer. Furthermore, cell lines that were refractory to the growth inhibitory effects of TGF‐β 1 behaved more aggressively than cells that underwent ligand‐induced cell‐cycle arrest. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Robust and Global Delay-Dependent Stability for Genetic Regulatory Networks With Parameter Uncertainties

The study of stability is essential for designing or controlling genetic regulatory networks, which can be described by nonlinear differential equations with time delays. Much attention has been paid to the study of delay-independent stability of genetic regulatory networks and as a result, many sufficient conditions have been derived for delay-independent stability. Although it might be more interesting in practice, delay-dependent stability of genetic regulatory networks has been studied insufficiently. Based on the linear matrix inequality (LMI) approach, in this study we will present some delay-dependent stability conditions for genetic regulatory networks. Then we extend these results to genetic regulatory networks with parameter uncertainties. To illustrate the effectiveness of our theoretical results, gene repressilatory networks are analyzed.
Analysis of Behavior and Trafficking of Dendritic Cells within the Brain during Toxoplasmic Encephalitis

Under normal conditions the immune system has limited access to the brain; however, during toxoplasmic encephalitis (TE), large numbers of T cells and APCs accumulate within this site. A combination of real time imaging, transgenic reporter mice, and recombinant parasites allowed a comprehensive analysis of CD11c+ cells during TE. These studies reveal that the CNS CD11c+ cells consist of a mixture of microglia and dendritic cells (DCs) with distinct behavior associated with their ability to interact with parasites or effector T cells. The CNS DCs upregulated several chemokine receptors during TE, but none of these individual receptors tested was required for migration of DCs into the brain. However, this process was pertussis toxin sensitive and dependent on the integrin LFA-1, suggesting that the synergistic effect of signaling through multiple chemokine receptors, possibly leading to changes in the affinity of LFA-1, is involved in the recruitment/retention of DCs to the CNS and thus provides new insights into how the immune system accesses this unique site.
Lipoxin‐induced migration of fish leukocytes

The migration‐inducing abilities of both synthetic lipoxin A4 (LXA4) and leukotriene B4 (LTB4) for rainbow trout neutrophils were examined with an in vitro assay. LXA4 caused enhanced migration of these cells with a three‐ to fourfold greater response than that observed toward LTB4 at most concentrations tested. Checkerboard assays showed that synthetic LXA4 was chemokinetic for trout leukocytes, while LTB4 was chemotactic. The chemokinetic ability of LX synthesized by rainbow trout macrophages maintained in short‐term culture was also determined. These cells produced both 4‐and 5‐series LX, namely LXA4, LXA5, 11‐trans‐LXA4, 11‐trans‐LXA 5 , 7‐cis‐11‐trans‐LXA4 and 6(S)‐LXA4. Although greater migration was found to LXA4 than to most of the other 4‐series positional isomers, at least at some concentrations, this did not exhibit the degree of stereospecificity previously reported in some studies for mammalian leukocytes. Little difference was found between the chemokinetic responses of rainbow trout leukocytes to 4‐ and 5‐series LX. These findings suggest that LXs are important migration‐inducing molecules in trout and have a relatively long evolutionary history.
Exclusion: failed children or systems failure?

Abstract This paper argues that some children ‐‐ particularly certain adolescents ‐‐ are rendered vulnerable as a result of political and systemic failure. Such children become scapegoats of that failure and, by being excluded, have their rights to education and proper attention to their emotional and behavioural needs, at best, compromised, at worst, violated. Recent figures showing steeply increasing exclusion rates are used to illustrate the point. A systemic conceptualisation of the problem is offered and its implications for policy and practice discussed.
Conjugated Linoleic Acid Induces Human Adipocyte Delipidation

Dietary conjugated linoleic acid (CLA) reduces body fat in animals and some humans. Here we show that trans-10, cis-12 CLA, but not cis-9, trans-11 CLA, when added to cultures of stromal vascular cells containing newly differentiated human adipocytes, caused a time-dependent decrease in triglyceride content, insulin-stimulated glucose and fatty acid uptake, incorporation into lipid, and oxidation compared with controls. In parallel, gene expression of peroxisome proliferator-activated receptor-γ and many of its downstream targets were diminished by trans-10, cis-12 CLA, whereas leptin gene expression was increased. Prior to changes in gene expression and metabolism, trans-10, cis-12 CLA caused a robust and sustained activation of mitogen-activated protein kinase kinase/extracellular signal-related kinase (MEK/ERK) signaling. Furthermore, the trans-10, cis-12 CLA-mediated activation of MEK/ERK could be attenuated by pretreatment with U0126 and pertussis toxin. In parallel, pretreatment with U0126 blocked the ability of trans-10, cis-12 CLA to alter gene expression and attenuate glucose and fatty acid uptake of the cultures. Intriguingly, the induction by CLA of MEK/ERK signaling was linked to hypersecretion of adipocytokines interleukin-6 and interleukin-8. Collectively, these data demonstrate for the first time that trans-10, cis-12 CLA decreases the triglyceride content of newly differentiated human adipocytes by inducing MEK/ERK signaling through the autocrine/paracrine actions of interleukins-6 and 8.
Clinical evaluation of root filled teeth restored with or without post-and-core systems in a specialist practice setting.

AIM To assess survival rates and complications of root-filled teeth restored with or without post-and-core systems over a mean observation period of >or=4 years. METHODOLOGY A total of 325 single- and multirooted teeth in 183 subjects treated in a private practice were root filled and restored with either a cast post-and-core or with a prefabricated titanium post and composite core. Root-filled teeth without post-retained restorations served as controls. The restored teeth served as abutments for single unit metal-ceramic or composite crowns or fixed bridges. Teeth supporting cantilever bridges, overdentures or telescopic crowns were excluded. RESULTS Seventeen teeth in 17 subjects were lost to follow-up (17/325: 5.2%). The mean observation period was 5.2 +/- 1.8 (SD) years for restorations with titanium posts, 6.2 +/- 2.0 (SD) years for cast post-and-cores and 4.4 +/- 1.7 (SD) years for teeth without posts. Overall, 54% of build-ups included the incorporation of a titanium post and 26.5% the cementation of a cast post-and-core. The remaining 19.5% of the teeth were restored without intraradicular retention. The adjusted 5-year tooth survival rate amounted to 92.5% for teeth restored with titanium posts, to 97.1% for teeth restored with cast post-and-cores and to 94.3% for teeth without post restorations, respectively. The most frequent complications included root fracture (6.2%), recurrent caries (1.9%), post-treatment periradicular disease (1.6%) and loss of retention (1.3%). CONCLUSION Provided that high-quality root canal treatment and restorative protocols are implemented, high survival and low complication rates of single- and multirooted root-filled teeth used as abutments for fixed restorations can be expected after a mean observation period of >or=4 years.
Placebo Effects in Neurological Diseases

There is an imperious need of redefining placebo effect in contemporary times. The effects of sham medical intervention, combined with a careful observation of the natural evolution of a disease, could reveal the true efficiency and impact of active drugs. This interest is not driven only by a scientific curiosity, but also by the pragmatic fact that the standard process of approving new medicines through supportive clinical trials requires a comparison against placebo. A complete understanding of the placebo effect should include both its psychological mechanisms and the underlying neurobiology. In contrast to other type of conditions, neurological disorders could provide specific clues in understanding the placebo effect, since the pathogenic mechanisms of different diseases might interfere with neuronal circuitry involved in the perception of disease symptoms. However, there are ethical considerations dictating the limits of using placebo. This paper reviews recent articles about placebo effect, with an emphasis on its importance in several neurological conditions (Parkinson's disease, neuropathic pain, headache, multiple sclerosis, epilepsy), and intends to offer new insights on this major topic.
Vascular Imaging Before Intravenous Thrombolysis: Consequences of In‐Hospital Delay in Applying Two Diagnostic Procedures

Vascular imaging is increasingly used for diagnosis of arterial occlusions in acute ischemic stroke (AIS) patients. Our aim was to determine whether computed tomography angiography (CTA) and Doppler/duplex ultrasound (DUS) before intravenous thrombolysis (IVT) is associated with a delay in time‐to‐treatment.
Resource Allocation for Green Cloud Radio Access Networks Powered by Renewable Energy

In this paper, we investigate the sustainable resource allocation for green Cloud Radio Access Networks (C-RAN) powered by renewable energy. Specifically, the Base Station pool (BS pool) in the C-RAN distributes data to a set of remote radio heads (RRHs) with energy harvesting (EH) capability, and allocates sub-carriers to the selected RRHs for downlink transmissions, by jointly considering the user throughput and energy sustainability performance of RRHs. To this end, we formulate a utility optimization problem, characterizing the stochastic process of energy harvesting (EH) and wireless fading channel. Based on Lyapunov optimization techniques, we decompose the formulated problem into three sub-problems, including energy harvesting, data scheduling, and sub-carrier allocation. We then propose an efficient online algorithm to obtain the maximal aggregate user utility while ensuring the stability of the data buffers and sustainability of the energy buffers. Performance analysis demonstrates that the proposed algorithm can achieve a suboptimal performance with guaranteed upper bounds on data queue and energy queue lengths. Extensive simulations validate the effectiveness and efficiency of the proposed algorithm.
Effect of Cement Dust Deposition on Physiological Behaviors of Some Selected Plant Species

Study was carried out to assess the impact of cement dust on some selected plant species around industrial area. Deposition effect of cement dust on pigmentation was studied in Azadirachta indica, Pongamia pinnata, Delonix regia, Polyalthia longifolia and Ficus religiosa. Sampling was done about 500 meter distance difference from the cement industry and measurements were taken for all the plant species spectrophotometrically. All the measured pigments were reduced in dust-exposed plant species compared with control site. This is due to deceleration of the biosynthetic processes rather than degradation of pigments. Changes in chlorophyll and carotenoid content were investigated in selected plant species exposed to alkaline dust emitted by the cement industry. The rate of mortality of young branches was high in the area subjected to the cement dust in all the selected plant species whereas Pongamia pinnata and Azadirachta indica are the most sensitive among them. Unless Polyalthia longifolia and Ficus religiosa is noted that amount of chl a, b and carotenoids in all investigated plants that are far away from cement dust more than that near from the factory. In general, pollution by the cement dust has caused adverse effects on the photosynthetic pigments and the pH of the leaf extract.
Agitation in Dutch Institutionalized Patients with Dementia: Factor Analysis of the Dutch Version of the Cohen-Mansfield Agitation Inventory

Background/Aims: To establish the construct validity of the Dutch version of the Cohen-Mansfield Agitation Inventory (CMAI-D) in institutionalized patients with dementia. Methods: The CMAI-D was administered to a large sample of 1,437 patients with moderate to severe dementia, receiving nursing home or outreaching nursing home care. Exploratory factor analysis was used to examine the behavioral dimensions underlying CMAI-D observations. Results: A restricted 3-factor solution showed 3 factors, i.e. physical aggression, physically nonaggressive behavior and verbally agitated behavior, with prevalences of 62, 67 and 62%, respectively. An unrestricted factor solution revealed 3 additional behavioral dimensions: hiding/hoarding, vocal agitation and a factor of miscellaneous items (i.e. repetitious mannerisms, spitting), which occurred in 30, 28 and 35% of the patients, respectively. Conclusion: The 3-factor solution of physical aggression, physically nonaggressive behavior and verbally agitated behavior corroborates earlier findings in other patient samples and therefore establishes the construct validity in institutionalized patients with severe dementia. The robustness of these findings across different care settings suggests that agitated behaviors have a common basis. In addition, unrestricted factor analysis showed 3 other important independent behavioral symptoms in dementia, but they are in fact too small to be used as a subscale. These findings might add to the taxonomy of agitation and aggression in dementia.
Chronic neonatal NMDA blockade results in long‐term cholinergic increase in the rat spinal cord

Rat pups were treated daily with increasing doses of the competitive N-methyl-D-aspartate (NMDA) antagonist CGP 39551 from postnatal day 1 to 22. Normal rats, as well as rats kept undernourished to the same extent as CGP 39551 -treated animals were raised in parallel. The neonatal treatment resulted in significant increase of choline acetyltransferase (+14%) in the adult spinal cord. High affinity glutamate uptake was increased to a similar magnitude in treated rats, but the same effect was also noticed for neonatally undernourished rats. No alteration of other neurochemical markers was observed. The present results add new evidence to a developmental role mediated by NMDA receptors and extend to the spinal cord the value of models of chronic neonatal block of this receptor.