Miracle-dz/UniFAR-FTUs huggingface dataset:
Leucine Promotes Proliferation and Differentiation of Primary Preterm Rat Satellite Cells in Part through mTORC1 Signaling Pathway

Signaling through the mammalian target of rapamycin (mTOR) in response to leucine modulates many cellular and developmental processes. However, in the context of satellite cell proliferation and differentiation, the role of leucine and mTORC1 is less known. This study investigates the role of leucine in the process of proliferation and differentiation of primary preterm rat satellite cells, and the relationship with mammalian target of rapamycin complex 1 (mTORC1) activation. Dissociation of primary satellite cells occurred with type I collagenase and trypsin, and purification, via different speed adherence methods. Satellite cells with positive expression of Desmin were treated with leucine and rapamycin. We observed that leucine promoted proliferation and differentiation of primary satellite cells and increased the phosphorylation of mTOR. Rapamycin inhibited proliferation and differentiation, as well as decreased the phosphorylation level of mTOR. Furthermore, leucine increased the expression of MyoD and myogenin while the protein level of MyoD decreased due to rapamycin. However, myogenin expressed no affect by rapamycin. In conclusion, leucine may up-regulate the activation of mTORC1 to promote proliferation and differentiation of primary preterm rat satellite cells. We have shown that leucine promoted the differentiation of myotubes in part through the mTORC1-MyoD signal pathway.
An Adaptive Load Balancing Technique for Distributed Virtual Environment Systems

One of the key issues in the design of scalable and costeffective Distributed Virtual Environment (DVE) systems is the partitioning problem. This problem consists of efficiently assigning clients (3-D avatars) to the servers in the system, and some methods have been already proposed for solving it. However, only one of these methods takes into account the non-linear behavior of DVE servers with the number of avatars they support, and this method uses a load balancing technique of local scope. As a result, it only provides good performance if the movement pattern of avatars is uniform. In this paper, we propose an adaptive load balancing technique of global scope for solving the partitioning problem in DVE systems. The global scope of the proposed technique allows to avoid DVE saturation as long as possible. Evaluation results show that the proposed strategy can improve DVE system performance, regardless of both the movement patterns of avatars and also the initial distribution of avatars in the virtual world.
Identification and Characterization of Polycystin-2, the PKD2 Gene Product*

PKD2, the second gene for the autosomal dominant polycystic kidney disease (ADPKD), encodes a protein, polycystin-2, with predicted structural similarity to cation channel subunits. However, the function of polycystin-2 remains unknown. We used polyclonal antisera specific for the intracellular NH2 and COOH termini to identify polycystin-2 as an ∼110-kDa integral membrane glycoprotein. Polycystin-2 from both native tissues and cells in culture is sensitive to Endo H suggesting the continued presence of high-mannose oligosaccharides typical of pre-middle Golgi proteins. Immunofluorescent cell staining of polycystin-2 shows a pattern consistent with localization in the endoplasmic reticulum. This finding is confirmed by co-localization with protein-disulfide isomerase as determined by double indirect immunofluorescence and co-distribution with calnexin in subcellular fractionation studies. Polycystin-2 translation products truncated at or after Gly821 retain their exclusive endoplasmic reticulum localization while products truncated at or before Glu787 additionally traffic to the plasma membrane. Truncation mutants that traffic to the plasma membrane acquire Endo H resistance and can be biotinylated on the cell surface in intact cells. The 34-amino acid region Glu787-Ser820, containing two putative phosphorylation sites, is responsible for the exclusive endoplasmic reticulum localization of polycystin-2 and is the site of specific interaction with an as yet unidentified protein binding partner for polycystin-2. The localization of full-length polycystin-2 to intracellular membranes raises the possibility that the PKD2 gene product is a subunit of intracellular channel complexes.
Genotype-phenotype correlations of 39 patients with Cornelia De Lange syndrome: the Dutch experience

Background: Cornelia de Lange syndrome (CdLS) is a multiple congenital anomaly syndrome characterised by a distinctive facial appearance, prenatal and postnatal growth deficiency, psychomotor delay, behavioural problems, and malformations of the upper extremities. Recently mutations in NIPBL, the human homologue of the Drosophila Nipped-B gene, were found to cause CdLS. Mutations have been found in 39% of reported cases. Methods: Patients were enrolled in the study and classified into one of four groups based on clinical examination: classic, mild, possible, or definitively not CdLS. Three dimensional photography was taken of 20 subjects, and compared between groups. Behaviour was assessed with specific attention to autism. We searched for mutations in NIPBL and correlated genotype with phenotype. Results: : We found mutations in 56% of cases. Conclusions: Truncating mutations were generally found to cause a more severe phenotype but this correlation was not absolute. Three dimensional facial imaging demonstrated the potential for classifying facial features. Behavioural problems were highly correlated with the level of adaptive functioning, and also included autism. No correlation of behaviour with the type of mutation was found
The Murine Cytomegalovirus pp89 Immunodominant H-2Ld Epitope Is Generated and Translocated into the Endoplasmic Reticulum as an 11-Mer Precursor Peptide1

The 20S proteasome is involved in the processing of MHC class I-presented Ags. A number of epitopes is known to be generated as precursor peptides requiring trimming either before or after translocation into the endoplasmic reticulum (ER). In this study, we have followed the proteasomal processing and TAP-dependent ER translocation of the immunodominant epitope of the murine CMV immediate early protein pp89. For the first time, we experimentally linked peptide generation by the proteasome system and TAP-dependent ER translocation. Our experiments show that the proteasome generates both an N-terminally extended 11-mer precursor peptide as well as the correct H2-Ld 9-mer epitope, a process that is accelerated in the presence of PA28. Our direct peptide translocation assays, however, demonstrate that only the 11-mer precursor peptide is transported into the ER by TAPs, whereas the epitope itself is not translocated. In consequence, our combined proteasome/TAP assays show that the 11-mer precursor is the immunorelevant peptide product that requires N-terminal trimming in the ER for MHC class I binding.
Substance P and capsaicin release prostaglandin E2 from rat intrapulmonary bronchi.

We hypothesized that substance P and capsaicin would cause the release of prostaglandin E2(PGE2) from intrapulmonary bronchi isolated from Sprague-Dawley rats. Substance P (1 μM) caused the release of PGE2, measured with enzyme immunoassay, from the isolated airway segments; PGE2 release was inhibited by the neurokinin (NK)1-receptor antagonist, RP-67580, by inhibition of cyclooxygenase with meclofenamate, and by removal of the epithelium. The release of PGE2 caused by capsaicin (1 μM) was similar in magnitude to that caused by substance P. The capsaicin-induced release of PGE2was inhibited by desensitization of sensory nerves with capsaicin and by RP-67580, meclofenamate, and epithelial denudation. We conclude that activation of NK1 receptors on epithelium causes release of PGE2, which most likely represents the ultimate mediator of airway smooth muscle relaxation, produced by exogenous neuropeptides and by activation of the sensory nerve inhibitory system. Epithelial damage, such as that seen in asthmatic airways, would disrupt this protective system in the lungs, which could contribute to the development of airway disease.
Lessons from LambdaMOO: A Social, Text-Based Virtual Environment

The growing use of the Internet to provide a sense of personal connection and community is converging with the development of shared virtual spaces. In particular, the strong popularity of Multi-User Domains (MUDs), text-based networked virtual worlds, suggests the high premium many people place on social interactivity in their virtual environments. The project described in this paper was designed to broadly characterize what life in LambdaMOOa classic, social, text-based MUDis like for many of its members. A comprehensive, data-driven approach was used to explore topics including user and use characteristics, identity and gender role-play, sociality, and spatiality. A rich database of results was gathered. The findings demonstrate a striking and increasingly strong focus on social interaction, even at the expense of spatial navigation. Moreover, contrary to expectations, small, private, even exclusive social interactions were the rule, not the exception. In addition, provocative claims regarding the prevalence of identity and gender role-play were shown not to hold, at least for most people, in this classic social MUD. Finally, some intriguing results regarding the sense of place and space in a purely text-based virtual environment are presented. Taken together, these data shed light on robust psychological and social patterns observed in a large-scale, social virtual world. In doing so, they can help inform the discourse on, and design of, related systems in the future.
Lactobacillus farciminis MD, a newer strain with potential for bacteriocin and antibiotic assay

A native isolate Lactobacillus farciminis MD isolated from fermenting mushroom exhibited a high degree of sensitivity to the majority of the bacteriocins produced by strains of lactobacilli, leuconostoc and pediococci. Also, the efficacy of Lact. farciminis MD as a sensitive strain for antibiotic assay was established against different antibiotics including ampicillin, cefazoline, chloramphenicol and nitrofurantoin at concentrations of 30 μg each, showing an inhibition zone of 30 mm diameter. The high degree of sensitivity towards bacteriocins and antibiotics provide potential for the exploitation of Lact. farciminis MD in establishing very well‐defined bacteriocin producers.
Sex–specific effects of carotenoid intake on the immunological response to allografts in guppies (Poecilia reticulata)

Rarely are the evolutionary origins of mate preferences known, but, recently, the preference of female guppies (Poecilia reticulata) for males with carotenoid‐based sexual coloration has been linked to a sensory bias that may have originally evolved for detecting carotenoid‐rich fruits. If carotenoids enhance the immune systems of these fishes, as has been suggested for other species, this could explain the origin of the attraction to orange fruits as well as the maintenance of the female preference for orange males. We used the classic immunological technique of tissue grafting to assay a component of the immune response of guppies raised on two different dietary levels of carotenoids. Individual scales were transplanted between pairs of unrelated fishes, creating reciprocal allografts. Transplanted scales were scored on a six‐point rejection scale every day for 10 days. Five days later, the same pairs of fishes received a second set of allografts and were scored again. Compared with low‐carotenoid‐diet males, high‐carotenoid‐diet males mounted a significantly stronger rejection response to the second allograft but not to the first allograft. High‐carotenoid‐diet females, however, showed no improvement in graft rejection compared with low‐carotenoid‐diet females. To our knowledge, this is the first experimental evidence for sex‐specific effects of carotenoid consumption on the immune system of a species with carotenoid‐based sexual coloration. These results are consistent with the hypothesis that the mate preference for carotenoid coloration is maintained by the benefits to females of choosing healthy mates, but they cast doubt on the idea that the benefits of carotenoid consumption, per se, could account for the origin of the preference. The sex‐specificity of carotenoid effects on allograft rejection in guppies provides indirect support for the general hypothesis that males pay an immunological cost for sexual ornamentation.
Patients With Glanzmann Thrombasthenia Lacking Platelet Glycoprotein αIIbβ3 (GPIIb/IIIa) and αvβ3 Receptors Are Not Protected From Atherosclerosis

Background— Platelets have been suggested to play a role in the early development of atherosclerosis. As one test of this hypothesis, we assessed whether patients with Glanzmann thrombasthenia who lack platelet glycoprotein αIIbβ3 (GPIIb/IIIa) complexes or both αIIbβ3 and the more ubiquitous αvβ3 cell membrane complexes are protected from development of atherosclerosis. Methods and Results— Seven patients with Glanzmann thrombasthenia, 45 to 66 years of age, underwent bilateral carotid artery ultrasonography and screening for risk factors of atherosclerosis. Findings consistent with early atherosclerosis evaluated by measurement of intima-media thickness and presence of atherosclerotic plaques were observed in 6 of the 7 patients. Intima-media thickness values higher than the 75th and 90th percentiles of age- and sex-matched white control subjects of the Atherosclerosis Risk in Communities (ARIC) study were observed in 30 and 8 of 56 carotid artery measurements, respectively. Five of the 6 patients with s.
INHIBITORY EFFECTS OF IMMUNOSUPPRESSIVE DRUGS ON INSULIN SECRETION FROM HIT-T15 CELLS AND WISTAR RAT ISLETS1

Until recently, islet allotransplantation for type 1 diabetic patients has been largely unsuccessful. Previous pharmacologic studies of single drugs have suggested that one factor contributing to this poor success is toxicity of immunosuppressive drugs on transplanted islets. However, no comprehensive study of agents currently used for islet transplantation has been previously reported. Consequently, we exposed HIT-T15 cells and Wistar rat islets to various concentrations of five immunosuppressive agents for 48 and 24 hr, respectively, and measured glucose-stimulated insulin secretion during subsequent static incubations. Results are expressed as percent reduction of insulin secretion at the lower and upper limits, respectively, of plasma drug concentrations used in clinical transplantation compared with control (no drug exposure). Insulin secretion from HIT-T15 cells was significantly inhibited by 74% and 90% after exposure to methylprednisolone (P <0.05), 11% and 24% after exposure to cyclosporine (P <0.01), 60% and 83% after exposure to mycophenolate (P <0.05), 56% and 63% after exposure to sirolimus (P <0.001), and 10% and 20% after exposure to tacrolimus (P <0.001). Insulin secretion from Wistar rat islets was reduced by 0% and 48% after exposure to mycophenolate (P <0.001) and 20% and 31% after exposure to tacrolimus (P <0.05). No reduction in insulin secretion was observed from either HIT-T15 cells or rat islets after exposure to daclizumab. The results support the hypothesis that toxicity of certain immunosuppressive drugs on &bgr;-cell function plays a role in the poor success of islet allotransplantation. This is especially true of intrahepatically transplanted islets, which are exposed to higher portal concentrations of immunosuppressive agents. These findings support the use of low-dose immunosuppressive drug protocols in clinical islet transplantation.
Signaling by Toll-Like Receptor 2 and 4 Agonists Results in Differential Gene Expression in Murine Macrophages

ABSTRACT Lipopolysaccharide (LPS) derived from the periodontal pathogenPorphyromonas gingivalis has been reported to differ structurally and functionally from enterobacterial LPS. These studies demonstrate that in contrast to protein-free enterobacterial LPS, a similarly purified preparation of P. gingivalis LPS exhibited potent Toll-like receptor 2 (TLR2), rather than TLR4, agonist activity to elicit gene expression and cytokine secretion in murine macrophages and transfectants. More importantly, TLR2 stimulation by this P. gingivalis LPS preparation resulted in differential expression of a panel of genes that are normally induced in murine macrophages by Escherichia coli LPS. These data suggest that (i) P. gingivalis LPS does not signal through TLR4 and (ii) signaling through TLR2 and through TLR4 differs quantitatively and qualitatively. Our data support the hypothesis that the shared signaling pathways elicited by TLR2 and by TLR4 agonists must diverge in order to account for the distinct patterns of inflammatory gene expression.
Valuing health‐related quality of life: An EQ‐5D‐5L value set for England

Abstract A new version of the EQ‐5D, the EQ‐5D‐5L, is available. The aim of this study is to produce a value set to support use of EQ‐5D‐5L data in decision‐making. The study design followed an international research protocol. Randomly selected members of the English general public completed 10 time trade‐off and 7 discrete choice experiment tasks in face‐to‐face interviews. A 20‐parameter hybrid model was used to combine time trade‐off and discrete choice experiment data to generate values for the 3,125 EQ‐5D‐5L health states. Valuation data are available for 996 respondents. Face validity of the data has been demonstrated, with more severe health states generally given lower values. Problems with pain/discomfort and anxiety/depression received the greatest weight. Compared to the existing EQ‐5D‐3L value set, there are considerably fewer “worse than dead” states (5.1%, compared with over one third), and the minimum value is higher. Values range from −0.285 (extreme problems on all dimensions) to 0.950 (for health states 11211 and 21111). Results have important implications for users of the EQ‐5D‐5L both in England and internationally. Quality‐adjusted life year gains from interventions seeking to improve very poor health may be smaller using this value set and may previously have been overestimated.
Perceptions of Nursing Student Clinical Placement Experiences

There is an unprecedented shortage of registered nurses (RNs) in the United States of America. Efforts to educate more RNs have been limited by a shortage of both clinical placements and preceptors for nursing students. The purpose of this study was to examine nursing education issues associated with student clinical placement as experienced by hospital personnel who coordinate the placements with various schools of nursing. A qualitative study involving 15 state-wide participants directly associated with clinical placement of nursing students was conducted. Emergent themes from the data included lack of consistent terminology and definition of student and preceptor roles, preference of clinical scholars, process of site placements, rewards for supervision of students, dis-satisfiers to the supervision of students and suggested strategies for change. Recommendations which developed from the research are summarized and discussed.
Targeted Inhibition of Src Kinase with Dasatinib Blocks Thyroid Cancer Growth and Metastasis

Purpose: There are no effective therapies for patients with poorly differentiated papillary thyroid cancer (PTC) or anaplastic thyroid cancer (ATC), and metastasis to the bone represents a significantly worse prognosis. Src family kinases (SFKs) are overexpressed and activated in numerous tumor types and have emerged as a promising therapeutic target, especially in relation to metastasis. We recently showed that Src is overexpressed and activated in thyroid cancer. We therefore tested whether inhibition of Src with dasatinib (BMS-354825) blocks thyroid cancer growth and metastasis. Experimental Design: The effects of dasatinib on thyroid cancer growth, signaling, cell cycle, and apoptosis were evaluated in vitro. The therapeutic efficacy of dasatinib was further tested in vivo using an orthotopic and a novel experimental metastasis model. Expression and activation of SFKs in thyroid cancer cells was characterized, and selectivity of dasatinib was determined using an Src gatekeeper mutant. Results: Dasatinib treatment inhibited Src signaling, decreased growth, and induced cell-cycle arrest and apoptosis in a subset of thyroid cancer cells. Immunoblotting showed that c-Src and Lyn are expressed in thyroid cancer cells and that c-Src is the predominant SFK activated. Treatment with dasatinib blocked PTC tumor growth in an orthotopic model by more than 90% (P = 0.0014). Adjuvant and posttreatment approaches with dasatinib significantly inhibited metastasis (P = 0.016 and P = 0.004, respectively). Conclusion: These data provide the first evidence that Src is a central mediator of thyroid cancer growth and metastasis, indicating that Src inhibitors may have a higher therapeutic efficacy in thyroid cancer, as both antitumor and antimetastatic agents. Clin Cancer Res; 18(13); 3580–91. ©2012 AACR.
Animal Models of Ischemic Stroke. Part One: Modeling Risk Factors

Ischemic stroke is one of the leading causes of long-term disability and death in developed and developing countries. As emerging disease, stroke related mortality and morbidity is going to step up in the next decades. This is both due to the poor identification of risk factors and persistence of unhealthy habits, as well as to the aging of the population. To counteract the estimated increase in stroke incidence, it is of primary importance to identify risk factors, study their effects, to promote primary and secondary prevention, and to extend the therapeutic repertoire that is currently limited to the very first hours after stroke. While epidemiologic studies in the human population are essential to identify emerging risk factors, adequate animal models represent a fundamental tool to dissect stroke risk factors to their molecular mechanism and to find efficacious therapeutic strategies for this complex multi- factorial disorder. The present review is organized into two parts: the first part deals with the animal models that have been developed to study stroke and its related risk factors and the second part analyzes the specific stroke models. These models represent an indispensable tool to investigate the mechanisms of cerebral injury and to develop novel therapies.
Self-Assessment in Learning: The Relationship Between Active Feedback Strategies And Metacognitive Development

The aim of this action research study was to test the hypothesis that students who take an active part in the feedback process will increase their metacognitive development and raise their achievement. Individuals were given a self-assessment proforma and asked to self-assess their assignments for content and structure, prior to submission. Active engagement with the feedback process was also gained through individuals setting goals for each new assignment based on previous feedback, in an attempt to promote double-loop learning, a strategy purported by Argyris (1982) to increase metacognitive development. As hypothesised, the study found some evidence to support the central premise that actively engaging with the feedback process increases metacognitive development and raises achievement. However, limitations of the study are recognised and recommendations for further research are put forward.